Podcasts about GlaxoSmithKline

After an avalanche of earnings updates, we turn to our annual Income Majors special report and dive into two prominent FTSE 100 dividend stocks. First up is insurer Legal & General; pressure has been mounting on the company as it grapples with a more competitive pensions market. Christopher Akers explains the CEO's buyback plan, its yield and what it means for investors.We then move to GSK, once known as GlaxoSmithKline, which faces a tricky balancing act between dividends and developing new drugs. The pharma giant has been spending heavily on R&D – a staggering £18bn this year alone to build its oncology pipeline. Julian Hofmann has the details.Finally, we cast our ears to Hill & Smith's growth across the pond. The steel products company now generates two-thirds of its revenue from the US and has even switched its currency from sterling to dollars. Michael Fahy discusses what's going on at the growing business.Timestamps: 00:00 Intro03:22 Legal & General10:42 GSK18:57 Hill & Smith Listen to more podcasts from Investors' Chronicle on Apple, Spotify and YouTubeInvestors' Chronicle has supported private investors in the UK for over 160 years by highlighting rewarding investment opportunities. Investors' Chronicle is a service by the Financial Times. Hosted on Acast. See acast.com/privacy for more information.

How can content marketing in a tight niche build the audience that launches your book? And how do you decide whether to hand your self-published bestseller to a traditional publisher. Suzanne Smith shares what she learned in four years of going from blog to book deal. In the intro, how to stand out as a writer in the age of AI [Nathan Barry Show; Interview with Nathan Barry]; thoughts on asset maintenance; Goodreads giveaway on Bones of the Deep (Aug 5-20, 2026) This episode is sponsored by Publisher Rocket, which will help you get your book in front of more Amazon readers so you can spend less time marketing and more time writing. I use Publisher Rocket for researching book titles, categories, and keywords — for new books and for updating my backlist. Check it out at www.PublisherRocket.com This show is also supported by my Patrons. Join my Community at Patreon.com/thecreativepenn Suzanne Smith is the founder of The Independent Landlord, and the bestselling author of The Good Landlord Handbook. You can listen above or on your favorite podcast app or read the notes and links below. Here are the highlights and the full transcript is below. Show Notes How a free blog in a tight niche built the audience for the book Rewriting the book from scratch when the law changed Why speed made self-publishing the only option Building a paid membership after one audience member asked for it Negotiating a Penguin Random House deal with no agent Using AI as a business sidekick, with a control room and an engine room You can find Suzanne at TheIndependentLandlord.com. Transcript of the interview with Suzanne Smith Jo: Suzanne Smith is the founder of The Independent Landlord, and the bestselling author of The Good Landlord Handbook. So welcome to the show, Suzanne. Suzanne: Thank you. Jo: Oh, there's so much to talk about today. But first up— Tell us a bit more about you and your background, and how you got into property and writing after a legal career. Suzanne: Well, I've always loved reading books. In fact, I recently did a French literature degree as a mature student. Being an author was never in the game plan at all. It's not something that I even thought about. I was brought up in New Zealand, so shout out to all the Kiwis and those across the pond in Australia. The thing about it is, Jo, you've lived there yourself. Kiwis are independent, self-reliant and have this great sense of fair play. So that was a very formative experience for me. We moved back to England when I was 16, and I have become thoroughly anglicised since then, but a Kiwi at heart. I always wanted to become a lawyer. New Zealand in some ways on television is quite American, and there was this American programme called The Paper Chase. It was about all of these students at Harvard studying law, and the professor said, “You come here with a skull full of mush and you leave thinking like a lawyer.” I thought, “Oh, I like the sound of that.” I didn't really know what a lawyer was, but everyone seemed to be very happy that I wanted to become one, and then that was it. Jo: So you went into law, and then how did you get into property? Suzanne: So I worked for 25 years as a solicitor. That's like an attorney if you're American. Started off in a law firm, and then I went into pharmaceuticals and I worked for big companies like what is now GSK, GlaxoSmithKline, and small companies as well. When I started out, it was before the internet, before Google. When you're in house, you're very much a generalist. You do a bit of everything. So you help companies grow their business. You're not business prevention, but you're still bound by the code of conduct for solicitors. You've got this role of keeping the company on the right side of the law. Then I had twins, who were born about five years after I became a lawyer, and I decided to work part-time for a while and did an MBA when they were little, part-time through the Open University. I know Jonathan is doing one at the moment. Jo: Yes. He's finished, so that's exciting. Suzanne: That was transformational for me, because I had probably been thinking a bit too much as a lawyer, and it helped me to broaden my view of the world and understand all sorts of things. Sso I continued going up the greasy pole, and then for my last job, in 2015, I joined a biotech company in Cambridge, England, as general counsel and company secretary. It was a long way from home, about two, three hours' drive from home. So I decided to buy a flat, an apartment, and to stay there in the week. I thought to myself, “Well, when I leave this company, I can let it out as a buy-to-let,” but actually as a landlord. So I stayed there for five years, and then when I left, I let out the property. The reason why I decided to leave law after 25 years, I had what I call a sliding doors moment, like in the film. I was 50. I was on holiday with my husband, and we'd probably had one too many rum cocktails. And he said to me, “Well, what do you want to be doing with your life? What would you do if you could do anything?” I was thinking, “Well, I've done law. I want to do something else now.” I didn't really know what that was, and I'd always been thinking about studying French properly, and that's when I left. So I decided, 18 months later, I left to do a French degree at King's College London, full-time. I was the only old person there with lots of 18-year-olds. When I did that, I was able to cash in my share options because I was a good leaver. I retired, and so I started buying properties to let out and became a landlord, without really thinking too much about it, and I used letting agents. They were fine to begin with, but I didn't really have a game plan or anything like that. What I realised is that when I tried to research things online, I couldn't really find anything that was terribly helpful. It was either quite general or it was very legal. So after a while… I became a landlord in 2019. I had the idea, why don't I set up a blog? And this is August 2022, so just four years ago. My husband came up with the idea of the name, The Independent Landlord, because it's that Kiwi spirit, being very independent. I thought, “Right, I'm not going to charge anyone for it. It's a hobby. It's not a business. I'm going to pay it forward and help, use my legal training, practical legal approach, and practical common sense, by doing this blog.” Almost exactly four years ago, I sent my first newsletter to 13 people. Jo: Woo-hoo. Suzanne: And I sent one last week to over 18,000. So it's been quite a journey. Jo: Wow, this is so great. I love this. There's so much in there. The turning 50 and then doing a degree. My master's in death is a little different to your French literature, but I like it. So I love this, and buying properties, starting it on the side, not a business at first, and growing the audience, and obviously you've put so much work in. Then you decide to write a book. So talk about that, because an online blog, although I'm sure your articles and everything were super useful, it's very different to write a blog than a book. So talk about your challenges in writing. Why did you decide to do a book in the first place? Suzanne: Again, I was an accidental landlord, is what they call it when you let a property when you didn't intend to buy it as a buy-to-let, which I did with my Cambridge flat. And I became, in many respects, an accidental author. So I was having a conversation with my husband again and I was saying I'd done this lead magnet to get people to sign up to my newsletter, and a big new law was going through Parliament at the time, called the Renters Reform Bill, that was going to completely transform the way landlords operate. I was saying to my husband, “Oh, I need to update my lead magnet, a little ebook, to explain the new law.” He looked at me and said, “Well, why don't you do a proper book? Write a book.” This was on the 29th of September, 2023. The reason why I mention that is that I thought, “Wow, what a great idea,” and my head was bursting. I went onto Google, and guess what I downloaded on the 1st of October? Jo: My blueprint? Suzanne: Exactly. I found you immediately, the Author Blueprint, and I downloaded it. I checked: on the 1st of October, 2023. Then I listened to almost… well, I think I went back several years on your podcast, just trying to understand. I'm like that. When I try and do something, I just try and learn everything that there is to know about it. So I started writing the book, and I guess the first challenge was I write quickly, and I'm used to writing for people who aren't lawyers, being in-house. So I thought I needed to have a structure. The structure was easy in many respects because, a bit of business at the end, and then you can go through a tenancy. I thought it was important to have a narrative thread all the way through it, just to bring it together. This is the literature degree coming in here. I thought that the mission for everything I do, the reason why I started doing this, is to help landlords, but also to help the experience of renting that people have in England. It's very specific for English law. And to help improve the private rented sector. So that's why I originally set up my blog for free, and I wanted, when people went onto Google, they could find something sensible and very detailed from me. My blog posts were… Well, I've now got over 400,000 words on my blog, so it's a substantial piece of work that is out there free of charge. So what I decided to do was to bring this narrative thread, I call it the good landlord ethos, to the book. Then I wrote very quickly, and I had a pretty good draft by April 2024, because we were all thinking that the law was going to change very soon. But then there was an election, and in the end the government changed and the legislation changed completely, so I had to rewrite the book and start again. So I think that my biggest challenge was that my subject matter, the new law, changed. Because I wanted to publish this book that explained to people practically what they have to do, and make it really straightforward, keeping out of politics, because it is a very politically charged area. I wanted to write it so it's a manual, somebody could literally follow it. So I used an editor, and I did write the book twice. I had a beta reader who is another lawyer, and a landlord as well. Then I got to the get-the-damn-thing-done stage. The really tedious bit of all the typos at the end. Jo: Yes, the finishing energy to get it out there. So at that point, obviously you'd found my blueprint, so you were learning about the indie way of doing things. Did you always decide to self-publish? How did you think about publishing? What were your challenges in publishing? Suzanne: It never occurred to me not to self-publish, because the new law came into effect on the 1st of May, 2026. The law and the details that I needed for the book were finalised in January, and I published on Amazon on the 5th of March, so I had to go so quickly. Even though I'd got a lot of it written, the last bit came in January, and so I needed speed. I knew that for landlords to be able to have something that they can use straightaway to help get them ready for it, and then use as a manual afterwards, I had to be first. Jo: Sorry, just on the year. Was it '24? You said '26. You meant May— Suzanne: 2024? No, no, because I actually published it this year. What happened in 2024, I had the first draft ready, but then I had to do another draft because the law changed when the Labour government came in. Jo: Right. Suzanne: The Renters Reform Bill turned into the Renters' Rights Bill. So I had to rewrite the book. So I finished however many drafts at the end of January 2026. Then it went to an editor, et cetera, et cetera, and I managed to get the book ready for a proof, to get the proof printed, towards the end of February. So it was really quick to go from the law being sufficiently finalised for me to write a book in January, and then having it ready in just over a month. There is no way that I could have done that if I'd gone to a traditional publisher. It didn't even occur to me to go, because I didn't want to be going touting around my book and, “Please publish me,” et cetera. It's just not me. I'm the independent landlord, and that moved very easily to being the independent publisher. So I learnt how to do all the publishing. And a huge thanks: I joined your Patreon and I was a very good student. I went through everything systematically and followed your playbook, and used Vellum and BookFunnel and all the other tools. So I decided to go on Amazon as well as have my own Shopify store, which just about killed me. Jo: I was going to say, you are an excellent student. You really like learning, but you also put this into practice, which is why I also wanted to talk to you. You haven't just talked about all this. You've literally done everything. Suzanne: Sometimes it was like my head was going to burst. Luckily, Claude upped his game earlier this year when we got the Opus 4.5. I didn't use AI really until this year. I decided I need to do exercise all the time, and have that as a have-to-do, because my head was spinning all the time with all these different things. So I would go to the gym, go to a spin class, and then I would walk out with my phone on, with the Claude app, and dictate a stream of consciousness into it. “Oh, I need to do this, or what about that? Oh, I just remembered about this. Oh, I've had this idea, blah.” And then said, “Make sense of it for me, Claude.” So it was very much as a thinking partner, because when you're writing your first book, it's bad enough, but when you're learning how to publish… Even, like, when I got the first proof of the book back from BookVault, I realised that all the footnotes—I have 114 footnotes in my book, and that, again, is the recent degree there—and the formatting had gone skew-whiff. Apparently it was an issue with Vellum, and they were really lovely and they sorted it straight out for me. So it shows: always get a proof of the book. They were able to sort that out very quickly, and BookVault were very quick in getting me another proof, because you can shortcut it and just pay to get a very quick delivery. Amazon, on the other hand, was really slow. It took a week. So I actually published earlier on my Shopify store for my members, of my membership, and I gave them a discount. Then I finally got it onto Amazon on the 5th of March. There are all these different skills you're having to learn. The Shopify store I found very hard, and there was all the tax, because I'm VAT registered. So I think I'm still recovering. Jo: You're still recovering. I wouldn't normally recommend a Shopify store for someone with their first book, doing first of everything. But, as you say, you're someone who learns a lot, puts it into practice, and— I think you were pretty determined to do that because you had a community as well, right? Suzanne: Exactly, yes. The big subscriber list. I think that's why the book did so well. So in the first week, because I met you at the Indie Author Lab put on by— Jo: Yes, London Book Fair, yes. Suzanne: Yes, the Alliance of Independent Authors. I met you there, and it was just my first week, and I had 1,000 sales in the first week. That was because of my audience. I'd been going on about the fact that I'm writing this book for two and a half years, because that's how long it took me to do. So I had a wait list for it, and I had a thing on my website, a landing page on my website, saying how good the book was and why it's the best thing for the Renters' Rights Act. Then I went onto Google, and I think I sent you a screenshot of this at the time. I put into Google, “What's the best book for the Renters' Rights Act for landlords in England?” And it came up with me as a featured snippet, and I hadn't even published it at that time. It was just about there. So the blog really helped, because I'd become an authority on the Renters' Rights Act. Even though I'm not a practising solicitor any more, I spent all my time reading the damn thing, and it is a very complicated bit of legislation. Funnily enough, I have ruffled a lot of feathers. People have even said about me behind my back, “What does she know? She's only got four properties.” But I just took no notice. I thought, “I'm going to try and use my legal brain and my understanding of what it's like being a landlord, there with the rubber gloves cleaning an oven when people have moved out, and try and write something that's not trying to sell anything else, and to help people.” And then it got picked up. Jo: Yes. Wait, let's just slow down. Slow down, because we will get onto that in a minute. But let's just come back to that launch. So as we talked about, you've had a blog for five years— Suzanne: It was three and a half by then. Jo: Three and a half years you've been blogging, but hundreds of thousands of words of useful information. So you've essentially done content marketing. You've attracted people. You had a lead magnet. You got them on your email list. You told them that you were writing a book. You got a sort of pre-sales list up. So that's an email list. You've got a blog. Did you do anything else in terms of marketing? Suzanne: I had YouTube, a big YouTube channel. I'd only set it up at the end of 2024, and I'd had half a million views. And again, just very straightforward advice, and without all the scaremongering and politics. I deliberately keep out of it all. A lot of people joined my newsletter as a result of that. Also a year ago, exactly today, I was running a Facebook group, which was a lot of hard work. There were a few thousand people in it, but there are often a lot of people going in there trying to sell things: insurance, eviction specialists and things. And there was also a lot of people just being unpleasant to other people. I was getting fed up with it. It was taking me a lot of time, and I was doing a lot of speaking events and trying to explain what this new law was doing, and wearing myself out. I'm an extrovert, but even I find speaking events absolutely exhausting, because it's like everything gets sucked out of you. It's strange. Then somebody came up to me in July last year and said, “Suzanne, can you set up a membership?” I said, “Well, landlords aren't going to pay for that.” And they said, “Yes, they will. You build it and they will come.” I asked ChatGPT and thought about it. I asked ChatGPT, who I was dating at the time, now exclusively with Claude, but I know Claude has other people in his life. But I'm very much set with Claude Fable at the moment. So I asked ChatGPT, how can I go about setting up a membership? And I mentioned your one and said, “Should I do it on Patreon?” And then he came back with: go for Circle. So I set up a membership on Circle, exactly a year ago. In fact, it's the anniversary of my first member yesterday. hTe rules I had were, no selling. So I don't sell, no affiliate links, no one else can sell anything, and we have to be supportive. No negativity, no politics. So what it's become, it's like the senior common room of the private rented sector, with landlords, lawyers, letting agents. There's a fantastic forum in there. It's not me doing it, it's peer-to-peer. I have twice-monthly live streams where people can ask me questions. I wonder where I got that from. No, I very much modelled it on your Patreon, but on a different platform. I have courses in there as well. So that has really grown. I launched it in July, and by September, October, I'd gone past the VAT threshold, which has complicated everything, but it means my business now is this membership. I really enjoy doing it, and there hasn't been all the negativity that you have in a Facebook group. So I had them as… talk about your thousand fans. There are about 1,500 in the membership, and their support really helped the launch of my book, as well as the wider people who get my free newsletter. Jo: Yes. Suzanne: So it's all different types of content marketing. Jo: Y, but I do love this. And of course, if people are wondering, I joined Patreon back in 2014, I think it might have even been before that, and there weren't too many places back then to run communities. It wasn't even really a community at the time, it was a sort of, almost a “give me a bit of support for the podcast.” So things have changed a lot in terms of communities, and obviously you went with Circle, which is great. Patreon is slightly different now, and some people are using Substack for something similar. So that's just on the platform, but on the business: early on in our conversation you said, “I wasn't going to have a business. It wasn't a business. It was just putting stuff out there, helping other people,” and then your audience asked for this membership. And so now it is a business, right? Suzanne: Yes, it is. Jo: And you've got a book and all of this. So are you happy with the change to a business? Because obviously you have to treat it quite differently. Suzanne: Yes, I am, because I think to begin with, I was just doing it one or two days a week. I was actually studying a master's in French literature part-time, and I then found that I was enjoying the blog more than the master's, so I dumped the master's after the first year. But after getting 88% for one of my dissertations, which interestingly was on the translation of a Simone de Beauvoir book into English, and the publisher who's got that now is Random House, but that's another thing. Anyway, so I decided to give up my master's and double down and work full-time on the blog. People were paying to help me with all the big fees and things, the big tech stack, Buy Me a Coffee. I was doing a little bit of consulting and things. I was working six, seven days a week. I was treating it like a business in terms of quality and my effort, but it wasn't a business in terms of revenue. Then it just all came together, and this person said, “Set up a membership,” and I thought, “That's what I'm going to do. I'm now going to put it on a business setting.” I've got an MBA, I know how to do it, and people thought I planned it, but I didn't. It just happened. So now I do very much treat it as a business, but I still don't advertise. I don't allow people to advertise with me, because I want to be independent. If I recommend something, I want people to believe it's me recommending it, not just because someone's paying me, which can be a big issue in the landlord area. Jo: Oh, in any industry. I get pitched every day with loads of random things that people are like, “Oh, a dollar a click or whatever, if you send this to your list.” And it's like, seriously? Just stop it already. I did just want to add there: somebody asked you, they said, “You should have a community,” and that sparked that idea. I just wanted to acknowledge that my Patreon came from Jim Kukral. Some of you will remember, who've been around a long time. Jim Kukral came on my blog around sort of 2013. Amanda Palmer had just put out a book called The Art of Asking, and I was doing a lot of unpaid work on the podcast at the time, and I was either going to give it up or I had to fund it somehow. Jim said, “You should do a Patreon.” And I was like, “Oh, no, I hate asking for money.” So at the time I just felt, oh, weird. Then I was like, “No, I do all this work,” as you were saying. Now the Patreon has changed so much in terms of what it is, but it is the backbone of my business, too. So I love that you listened to one of your fans who said what they wanted, and I love that I've listened as well. Sometimes we just have to listen to those urges, don't we, to take things on? Suzanne: Yes, absolutely. In some ways I didn't really back myself before. I thought, “No one's going to pay for this.” Then the more you give, the more they want. Jo: Yes. Suzanne: What I've been really working on now is having boundaries, because there were two big kind of mottos that I picked up when I was working in pharmaceuticals. One was from a head of the business. He was Canadian, and he was always saying, “You've got to skate to where the puck is heading.” Jo: That's Wayne Gretzky, is it? Suzanne: Exactly. Yes. He would always say it, and so that's what I've done with my blog and my book. When I write things, I don't pay for any tools. I don't do keyword searches and all that. I just think, I do one blog post per topic, and I'm going to guess what people are going to be searching for soon, and I build up all this content around it. That's why most of my blog pages are top five. I've had no advertising. I haven't asked for any backlinks. I don't do it. People backlink to it because it's useful. So that was the first thing, is skate to where the puck is heading, and that was my approach with the book. I knew people would need this book from around May, and they'll need it forever, because it is so complicated and regulated, the rules for being a landlord in England. So that was the first one. The second thing was: when you take something on, you've got to let something go. One in, one out. I found that I was taking on so many different things, and I've just been cutting back, because I can't be doing all the speaking, I can't be answering people's emails. So I now don't do emails. If people want my advice on something, they ask me in the hub, at the twice-monthly live streams. Sometimes I answer in the forums, but I don't have time. When there are 2.4 million landlords in the UK, and even with our 18,000 on my newsletter, I could spend, and I did, I used to spend all my time replying to emails. So anyway, there are the things. Oh, and there was a third one, which is: attract, don't chase. One of my friends gave me that advice and that's exactly what my approach has been. I just don't chase for anything. I just put the stuff there and then build it and they will come. Jo: Yes, and I think another thing is the power of the niche. It's so clear that what you write about, the people you are aiming at, you have an extremely tight target market. That is both a strength and obviously a weakness, because they're the only people. But as you say, there's more than enough of those people for a community, for the book you have. From my own perspective, that's the same for me, the power of the niche. That's how I have a successful podcast, for example, because of that reason. I think you're like a poster child of what a non-fiction author should do. What I like is that you didn't go, “Oh, where's a niche where I could make money?” and then jump in. You've gone about this in a kind of slightly accidental way, but now you're leaning in and this uses all your skills. So this really is a great example of the power of the niche and then making the most of it. But let's move on to what then happened, and— What happened with the book deal? Suzanne: Wow. So you and I met each other on whatever day that was in March at the Indie Author Lab, and the following day I got an email, via my website on a contact form, from Penguin Random House saying, “We love the book. We love the mission, its values,” all this kind of thing. And I was thinking, “Oh, it's another one of those. Must be an—” Jo: AI spam bot, right? Suzanne: Yes, and I remember I sent you a screenshot of it, and then I checked her out on LinkedIn and thought, “Okay, there is somebody with that name there.” You're always saying, and Orna Ross and everyone are always saying, “Watch out for scams.” And in fact, Penguin Random House even this weekend on Instagram put out something saying, “There are lots of people impersonating us.” So I didn't take it too seriously, and it was something like, “Oh, would you be interested in us publishing your book?” And I thought, and I laughed. It was like, no, this is too good to be true. So I replied and said… Oh, I said, “Well, thank you so much. The Renters' Rights Act…” And so this is like the second week in March. “The Renters' Rights Act comes into effect on the 1st of May. If you want to publish it, you're going to need to get your skates on.” I literally did say that. Then she arranged a meeting with me the next day, on the Friday. I still was very dubious about it, and I had a think about it. What helped me, and I have the little booklet here: at the Author Lab, we did some work at the beginning, and Orna said, “Put your phones away.” And it was like, “What? Put my phone away?” Then we had to do this definition of success, and our passion, and our mission, and our purpose. I wrote down things like, I want to help landlords, and in so doing, help improve the private rented sector. I get pleasure from helping people. I want to improve standards and use my legal and practical skills, et cetera. So I thought, “Okay, what is my purpose of doing this book?” It isn't really to make money, because going with Penguin, you wouldn't do that for financial reasons, because you'd make very little money. So I thought, what is my why? My why is I want as many people to read this book as possible. And I've managed to sell a few thousand copies, but there are 2.4 million landlords, and they all need to understand this book, and the only way that I can get it out there, apart from doing ads, is to get it out in bookstores. So I thought about it, and then said, “Yes, I will do it, because I want to get the book out there.” So it's distribution. It's going to be published on the 6th of August, which is really quick, bearing in mind they contacted me in the middle of March. It's exactly the same book, it's just got different copyright wording and different blurb, different paper. Same cover, because I managed to find a fantastic cover person to do it. So they've kept everything the same. So we negotiated that book. I have no agent. They came to me. It's the attract, don't chase. I just put my lawyer hat on, and because one licence is very much like another one… I did turn down their first offer. Jo: Well done. Good negotiation. Suzanne: My daughter said to me, who's an adult daughter, she said, “But it's Penguin.” And I said, “Well, no, but it doesn't work for me.” So I had a call with them, and then they came up with something that worked for me a bit more. I did have to concede on a few things, like I can't sell it in my Shopify store. But in some ways, that was a blessing in disguise, because it means I don't get any more “Where's my book?” emails. Jo: Yes, exactly. Pros and cons of everything, basically. Suzanne: I have very clear rights to get it back. If I want it back, I can get it back and I don't have to give a reason. They're lovely. They have been really very wonderful. When I went up there a month or so ago, they gave me this book bag, and it's got on it, “I'm published by Penguin,” and I burst into tears. Jo: Aw. That's nice. Suzanne: I don't know, it just seemed like such a big deal. Because up until then I was just being all very lawyerly and task-orientated. Then I thought, “Oh my goodness,” and then it dawned on me. So I'm now in this interim period where I've taken it off Amazon and off my Shopify store, and I feel very maternalistic towards the book because, you know, it took me two and a half years, which is longer than a pregnancy. Obviously it's not a child, but it's like my book child. I've sent it off with a backpack and a drink and some snacks, and I hope that they look after him, my book. The day I took it off Amazon it was still number one. And a big shout-out to Publisher Rocket, by the way. Jo: Yes. Very, very useful for niche publishing. Suzanne: Very. It helped me choose the right niche categories. So it was number one on at least one category, often six, all the way through. I thought, “Well, it's over to them now.” They're very lovely people. They've given me some marketing assets, as they call it, some swanky graphics and things to use. We'll have to see what we do in terms of marketing. I don't mind doing marketing. I'm on LinkedIn quite a bit, and my whole blog is marketing. What I've been doing is updating my blog to include one of these graphics and to mention the book, and I got Claude to help me draft the code so it looked right. So I've been going through all of my blog posts and sending people to Amazon rather than to my Shopify store. It is mixed feelings, because I care about my book. I put a lot of effort, a lot of love, a lot of tears. No, not tears, but I put a lot of effort into it, and it's out of my control now. Jo: Yes, you said it's over to them, but obviously you will still be creating content around this topic, so you'll probably still be the biggest driver of book sales. Suzanne: Yes. Jo: Are they also suggesting, for example, a podcast tour, like pitching for podcasts? Are they going to assign you some PR? Because, also if people don't know, as we are recording this, we have a new prime minister who wants to do various things. You said no politics, but this is obviously a political thing. So you have the potential to go on a lot of different podcasts, media, talking about this, becoming almost a talking head in this kind of area. So are you angling for all that, and is that in your contract, or is it literally just going to be whatever you want to do? Suzanne: That's not in the contract. What's in the contract is very minimal. I think I've already done what I'm supposed to do. They are pitching for me to go on podcasts and things. I'll tell you a really funny coincidence. So we now have a new Prime Minister, Andy Burnham, and when he was Mayor of Greater Manchester, he set up something called the Good Landlord Charter. I actually talk about it in the book, and I quote him in my book saying that good landlords mean people trying to do the right thing, or something like that. And I coincidentally came up with the same name, The Good Landlord Handbook. I'd already had the book title for a long time. So this idea of good and landlord coming together, the adjective good as opposed to criminal or rogue, and the cover being green. I'm wanting to change the narrative so it's the norm to have a good landlord, and to help people become good landlords. Or if they're good landlords, help them to understand the new rules, because the new rules are very complicated. So what I don't get involved in is this right or wrong. Is it right that landlords can't do this or have to do this? Because as an in-house lawyer, it doesn't really matter what I think about the law. GDPR, goodness me. Jo: Oh, dear. Let's not start on GDPR. Suzanne: No, exactly. Because we've just got to suck it up. I liken it to the grief cycle, that people have been going through so much change and you have the anger, the depression— Jo: Denial. Suzanne: Bargaining, the denial, and then you get to acceptance. For some people, the acceptance means they want to stop doing it. If you want to accept it and stay, you need to understand the rules. So I've deliberately just kept very practical and have kept out of all the politics of it. I have, funnily enough, become involved because I'm now seen as an expert on the Renters' Rights Act. I've worked behind the scenes with the government to help, and give comment on government guidance for landlords. I was even invited to a reception to mark the passing of the Renters' Rights Act at Downing Street with the previous prime minister, all whilst staying apolitical. I won't let anyone make me be a mouthpiece for their political view. It's more, we just have to do this if we want to continue doing it. I've been very clear on that. Jo: It's interesting you mention the grief cycle there, and you've also mentioned Claude and ChatGPT. I wonder if you might also just comment on use of AI for authors and for marketing and all this. Also with legal stuff, because for me now, if I'm looking at a particular legal thing, I tend to ask Claude. I'm like, “Can you just explain this?” or upload a contract or whatever. Although it is not legal advice, it can be quite useful. So give us your thoughts on using AI as a sidekick in your author business and also for wider life. Suzanne: I now struggle to think what life would be like without Claude. I don't use Claude to write, at all, because I have a very particular voice and a turn of phrase, and if ever Claude writes something for me, it doesn't sound like me. It flattens me, and it makes me sound a bit American. So I don't do that. I've used it in the back end of the business. For instance, my blog was down, and there was something called a recursive bot, which I don't even know what it was, and Claude helped me fix it for free. I went through, I did screenshots. When I did an ElevenLabs audiobook and did it all myself, I was literally, for every screenshot, showing it to Claude. Claude said, “Do this, press this, press that.” So I have all these different projects set up. One is the control room, where it's for my strategic thinking. If I have an idea, I want to think about something, I put it in there. I have the engine room, which is for everything techy. Like when I had the recursive bot, or if I'm wanting to have some code on the website to make it look a particular way. Then I have other things for different subjects, and I put all the resources in there, and I use it a lot as a thinking partner. I've noticed that Fable doesn't hallucinate as much, but the Opus used to. There's something called rental discrimination, and it was proofreading and said, “No, it's not rental discrimination, it's rental income discrimination,” and that was just a load of rubbish. So I would never let it go and change things without me looking at it. I went on one of your webinars a month or so ago about MCPs and all the connectors, which is fantastic. It can go into my community and pull out all the questions for one of my live streams and put it into a document in order, by theme, for instance. It can look at my MailerLite, because that's where my newsletter is with, and analyse the different open rates and click rates and things. It's so good for analysing everything, all the book sales. It helped me with my negotiation with Penguin, and it is pretty good on law. It has sometimes hallucinated things, but not so much now. I think with anything, you've always got to go back to the primary source, and this is what we learn in academia: you have to check the primary source yourself. I have a bit of a magpie brain. I'm very much a discovery writer, like you, and things occur to me as I'm doing it. I think that Claude, at the moment, is incredible. I've been quite open about it on social media that I have Claude as a business partner. I'm a solopreneur, or whatever the word is. I have quite a big business now, and lots of different things, and it's just me doing it, because I can ask Claude how to do this, and how to do that. Claude can go and check my emails and tell me, is there somebody I've not replied to, which helps a lot. Jo: Yes. I think it's empowering as a solopreneur as such. You talk there about the fixing the tech stuff. I have my web host come to me and say, “Look, you're getting so much traffic and bot stuff, and we need to put this thing in, and it's going to be $120 extra a month.” I was like, “Can you just give me an hour? I'll get back to you.” And then I just had Claude code up, and I was like, “Analyse this and tell me what we can do.” It was like, “No, you just need to flip this switch and do that.” And I'm like, “Okay, fair enough.” Then the guy said, “Oh, no, okay, actually you don't need it.” Just stuff like that. As a solopreneur, you're either going to pay somebody technically quite a lot of money, or you can get Claude or ChatGPT. We should say, the ChatGPT Sol is very good, like the Claude Fable, for example. So, yes, using it as a sidekick. I love your control room and your engine room projects as well. That's a great way of doing it. Suzanne: I wouldn't be without it now, and I would have published the book a lot later without Claude, because Claude was helping me with the Shopify store and all the many steps of things. It saved me real time. It is just fantastic. I think, like now when I'm updating my blog, I have a connection between Claude and my blog. Claude can go in, I can give it my Google Search Console results for the page: what should I change, are the headings right? All this kind of thing. And it will give me a view on every single page, which is incredible. Jo: And YouTube, and just everything. Just super useful for that business sidekick. That's what I want authors to think. I feel like authors get so obsessed with the creative side with AI, whereas actually, people like you and me, we're using it as that engine room for the solo business, which is what I love. So we're out of time. I did want to ask one more thing, which is, one of the biggest issues with a specific book like yours is when they change the law again. So do you have a plan in place for if, say, a new government changes the law again? Will you just be updating the book over time? Suzanne: I think that there'll need to be a new edition of the book in three years' time, and I've spoken to Penguin about it. Not all of this new law has been implemented, and there's going to be case law and things. So I expect that I will update the book every few years. I have some other ideas for books as well, but for the moment, I'm just taking a bit of a break. You always say we've got to refill our creative well. I really feel like that at the moment. Recently I've just got myself a personal mobile phone so that I can turn off my work one when I'm on holiday and actually take time off. Because for all the time that I was doing the book, basically from Christmas until May, I didn't have one day off. That is not good. So I'm just trying to be a bit more balanced. I had an idea to write another book for summer, but I've just decided not to, and I'm going to leave it until I feel the urge again. Jo: Oh, well done. Suzanne: Which will come. Jo: Yes, well done. Suzanne: I think there's nothing wrong with that. We just need to think what's right for us. I'm 58. So I want to be able to have time to enjoy things and not be working all the time. Jo: No, that's great. It's a sustainable business. So where can people find you and the book and your community online? Suzanne: The easiest way to find me is theindependentlandlord.com. Or if you put Suzanne Smith and landlord into Google, you'll find me as well, and there's a link on there to the book, The Good Landlord Handbook. In the community, there's a link to that on my website as well. Jo: Brilliant. Well, thanks so much for your time, Suzanne. That was great. Suzanne: Thank you.The post From Blog To Community To Book: A Non-Fiction Author's Journey With Suzanne Smith first appeared on The Creative Penn.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a series of events that underscore the dynamic nature of these industries, characterized by scientific advancements, strategic partnerships, and regulatory milestones. Johnson & Johnson has made headlines with its substantial $785 million upfront payment to Sail BioMed for an in vivo CAR-T cell therapy deal. This agreement includes an option for Johnson & Johnson to acquire Sail BioMed for $2.58 billion, underscoring the sustained interest in cell therapies, particularly for autoimmune diseases. In vivo CAR-T therapies represent a significant leap forward by modifying T cells directly within the patient's body. This method offers potential advantages over traditional ex vivo techniques by simplifying the manufacturing process and potentially reducing both costs and time to treatment. Such transactions highlight Johnson & Johnson's commitment to expanding its cell therapy portfolio, which could significantly enhance patient care by making advanced treatments more accessible. Eli Lilly and Resilience have announced a significant $750 million investment aimed at boosting the production of diabetes and obesity medications in the United States. This move comes as a response to the global rise in these conditions, necessitating increased production capacities to meet growing demand. The focus on injectable drug devices emphasizes efforts to improve drug delivery systems, ultimately enhancing patient compliance and therapeutic outcomes. Sanofi's financial outlook for 2026 is promising, driven by robust sales of Dupixent, which exceeded €5 billion in quarterly sales. Dupixent, a monoclonal antibody used for treating atopic dermatitis and other autoimmune conditions, has been a significant revenue driver for Sanofi. The success of Dupixent reflects its effectiveness and strong market adoption, highlighting the potential of monoclonal antibodies as cornerstones of modern pharmacotherapy, particularly for chronic inflammatory diseases. Regeneron and Sanofi's Dupixent continues performing strongly with $6 billion in sales during Q2 2026—marking its largest quarterly revenue since the pandemic began—illustrating robust demand across various indications within both companies' portfolios. On the regulatory front, Alfasigma's Linerixibat (Lynavoy) has received a positive opinion from the CHMP for treating cholestatic pruritus in primary biliary cholangitis following successful Phase 3 trials. As an IBAT inhibitor targeting bile acid metabolism pathways, Lynavoy introduces a novel therapeutic approach for managing symptoms associated with this autoimmune liver disease. Meanwhile, ImmunityBio's Anktiva has gained marketing authorization in the UAE for non-muscle invasive bladder cancer and metastatic non-small cell lung cancer. Anktiva, an IL-15 cytokine-based protein therapy, exemplifies the growing interest in harnessing immune system modulators for cancer treatment. Takeda's recent decision to discontinue its nanoparticle therapy (TAK-101) for celiac disease highlights the inherent challenges in developing new therapies for autoimmune disorders. The disappointing Phase 2 results suggest that achieving immune tolerance to dietary gluten remains a significant scientific hurdle. From a strategic perspective, Sanofi's CEO has emphasized stricter go/no-go decisions during Phase 3 clinical trials amid pipeline cuts and significant impairment losses. This approach could lead to more efficient resource allocation and potentially higher success rates for late-stage drug candidates. The industry is witnessing significant transformations through strategic shifts driven by executives like Sanofi's new CEO Belen Garijo. Her vision includes reversing recent challenges faced by Sanofi by capitalizing on its strengths while addressing setbacks such as discontinuing certain late-stage clinical programs like the joint venture with Regeneron on the IL-33 candidate itepekimab. This strategic pivot mirrors broader industry trends toward optimizing late-stage pipelines to enhance competitive positioning and drive future growth. Advancements in AI-powered drug discovery continue gaining momentum through collaborations like those between GSK and Relation Therapeutics, alongside Causaly and Sage. These partnerships aim to leverage AI and machine learning technologies to accelerate drug discovery processes by integrating vast amounts of scientific literature into data analytics platforms. GlaxoSmithKline's $110 million deal with an AI biotech firm further signals increased integration between artificial intelligence technologies and pharmaceutical research efforts aimed at enhancing dataset quality thereby accelerating innovation throughout drug discovery processes. Bristol Myers Squibb faces further delays regarding its Alzheimer's psychosis treatment Cobenfy—a postponement reflecting ongoing complexities related to neurological drug development which requires overcoming high scientific hurdles alongside regulatory scrutiny. Alnylam Pharmaceuticals recently experienced a 29% drop in stock value following disappointing sales of Amvuttra and a downward revision of its ATTR franchise outlook for 2026. Such fluctuations highlight volatility within biotech investments when market expectations are not met. These collective developments reveal significant trends shaping today's pharmaceutical landscape: strategic pipeline optimization efforts alongside robust investment initiatives targeting high-demand therapeutic areas—all while leveraging technological advancements like AI integration aimed at improving R&D efficiency ultimately impacting patient care worldwide through innovative therapies addressing unmet medical needs globally.Support the show

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we dive into the latest news shaping these dynamic sectors, exploring strategic corporate maneuvers, groundbreaking scientific advances, and pivotal regulatory changes. GlaxoSmithKline (GSK) is embarking on a comprehensive restructuring initiative aimed at achieving $2.5 billion in annual cost savings by 2029. This ambitious initiative underscores the company's commitment to strengthening its late-stage research and development capabilities. The strategy involves optimizing mature product lines, procurement processes, and supply chain efficiencies, reflecting broader industry trends where financial prudence is balanced with innovation. As part of this transformation, GSK plans to relocate its research headquarters near AstraZeneca's facilities, though specifics on employment impacts remain under wraps. This restructuring highlights the competitive nature of the pharmaceutical landscape and GSK's intent to maintain its edge through enhanced R&D initiatives. Meanwhile, Johnson & Johnson is nearing a resolution in its extensive talc litigation by proposing a $5.5 billion settlement to resolve approximately 76,000 lawsuits. These lawsuits allege that J&J's talc-based baby powder caused ovarian cancer. This potential settlement represents a significant step toward closing a protracted chapter of legal scrutiny for J&J, offering the company a chance to mitigate ongoing legal risks and refocus on core business operations. On the regulatory front, MannKind has secured FDA approval for its fast-acting edema autoinjector, reflecting an ongoing emphasis on addressing unmet medical needs with innovative delivery mechanisms. Conversely, Baxter has issued a recall for one lot of cefazolin in dextrose injection due to contamination concerns, underscoring the continuous challenges of ensuring product safety within complex manufacturing and supply chain environments. In terms of public health initiatives, Gilead Sciences is employing a novel approach to HIV prevention through its "Up to Date" campaign featuring comedians Nicole Byer and Devon Walker. This effort aims to destigmatize HIV discussions within the Black community by leveraging humor and relatability—a testament to evolving strategies in patient engagement and education. In drug development news, Atea Pharmaceuticals is making strides with its hepatitis C treatment candidate following positive Phase 3 trial results showing equivalence with Gilead's Epclusa. This positions Atea for further clinical evaluations and potential market entry with a simplified treatment regimen. Similarly, Hansoh Pharmaceutical's collaboration with GSK has yielded another Phase 3 success for their B7-H3-directed antibody-drug conjugate in China, highlighting the growing importance of targeted therapies in oncology. Emerging biotech hubs are reshaping the industry's landscape as cities beyond traditional centers like Boston and San Francisco gain prominence. This geographical diversification reflects global trends in biotech innovation and investment. In clinical advancements, Altimmune's GLP-1/glucagon receptor-targeting drug shows promise in reducing heavy drinking among individuals with alcohol use disorder (AUD). This finding opens new therapeutic avenues for AUD by leveraging mechanisms traditionally associated with weight loss medications. Concurrently, regulatory scrutiny remains high as Replimune faces setbacks with its melanoma data package deemed "not interpretable" by the FDA—an indication of the rigorous standards required for gaining regulatory approval. The geopolitical landscape also influences industry dynamics, particularly in China where intellectual property risks are heightened under new legislative acts. Companies must navigate these complexities strategically to protect innovations while capitalizing on market opportunities. Financially, Novo Holdings-backed Claris has secured $118 million in Series B funding to advance its corneal disease drug candidate—a substantial investment underscoring growing interest in ophthalmology therapeutics. Additionally, RA Capital has launched Oak Hill Bio onto Nasdaq via a special purpose acquisition company (SPAC), focusing on rare genetic diseases—a strategy showcasing continued momentum within biotech to leverage financial tools for niche therapeutic advancements. Overall, these developments reflect an industry characterized by rapid scientific progress and evolving regulatory landscapes. Companies are under pressure to optimize operations while ensuring robust clinical data to meet regulatory standards. As these sectors strive for innovation and patient care advancements amidst competitive global markets, balancing innovation with safety and efficacy remains paramount. As always, we'll continue to track these stories closely and bring you the latest insights right here on Pharma Daily.Support the show

In today's episode, you'll discover: 1.     Why authenticity is an important part of leadership? 2.     What kind of masks do you, the leaders, wear, and what is it costing you? 3.     What Emotional Contagion is and how to Use the Emotional Contagion Effect in Positive Ways? To support these three takeaways, I chose a quote from Theodore Roosevelt: "The best executive is the one who has sense enough to pick good men to do what he wants done, and self-restraint to keep from meddling with them while they do it."  About Frans Campher: Today, my guest is Frans Campher, an executive coach, leadership strategist, and facilitator with over two decades of experience guiding high-performing leaders through the challenges of growth, authenticity, and meaningful impact. As CEO and US President of a global leadership development firm, he has worked with senior executives and teams at companies like BP, Ford Europe, GlaxoSmithKline, Deloitte, Citibank, and Johnson & Johnson. How to Get in Touch with Frans Campher: Email: frans@ildynamics.com Website: https://www.ildynamics.com/ Free Gift: https://teamtrust.ildynamics.com/ Stalk me online! Linktr.ee: https://linktr.ee/conniewhitman Communication Style Assessment (CSA)™:  https://changingthesalesgame.com/communication-style-assessment/

Send us Fan MailFor decades, the war on cancer has focused on destroying cancer cells directly - with chemotherapy, radiation, and targeted drugs. But what if the future of cancer treatment is not about attacking cancer ourselves...but teaching our own immune system to do it for us?Today we're exploring a new generation of immunotherapies designed to turn the body's own defenses into a precision weapon against cancer.Over the past decade, immunotherapies such as checkpoint inhibitors and CAR-T cell therapies have transformed the treatment landscape for many cancers. But major challenges remain - including limited response rates, treatment resistance, toxicity, and the enormous complexity and cost of manufacturing many next-generation therapies.Our guest today believes the next breakthrough may come from a new generation of personalized immunotherapies designed to activate a patient's own immune system against their cancer - while also being manufactured as an accessible, off-the-shelf treatment.Joining us is Dr. William Williams, MD - President and CEO of BriaCell Therapeutics ( https://briacell.com/ ).Dr. Williams brings more than 35 years of experience spanning academia and the biopharmaceutical industry. He has helped advance numerous medicines from discovery through clinical development, including work contributing to therapies such as Jakafi and Olumiant during his time at Incyte, and multiple oncology programs during his career at GlaxoSmithKline.Before entering industry leadership, Dr. Williams was a researcher at the University of Pennsylvania focused on molecular immunology, receptor biology, and early DNA vaccine approaches.Today we'll discuss the evolution of cancer immunotherapy, BriaCell's Bria-IMT platform, the challenges of treating advanced breast cancer, and whether the future of oncology lies in creating therapies that can truly mobilize each patient's own immune system.#CancerResearch #CancerImmunotherapy #Immunotherapy #CancerTreatment #Oncology #PrecisionMedicine #PersonalizedMedicine #Biotechnology #Biotech #LifeSciences #DrugDiscovery #ClinicalTrials #BreastCancer #MetastaticBreastCancer #CancerVaccine #CellTherapy #TumorImmunology #TCells #ImmuneSystem #MedicalInnovation #FutureOfMedicine #HealthcareInnovation #BiomedicalResearch #Pharma #PharmaceuticalInnovation #SciencePodcast #ProgressPotentialAndPossibilities #PPPShowSupport the show

Unlocking Leadership in a Disruptive World with Frans Campher -Executive Coach and Program Director at Imperial College Business School London.Book on Amazon: Dynamic Leadership in a Disruptive WorldWeb: https://www.ildynamics.com/ In this episode, Frans Campher, an executive coach and leadership strategist, shares his insights on how leaders can navigate the complexities of today's disruptive environment. From shifting identities to cultivating authenticity and strategic agility, Frans offers practical frameworks for leaders at every level.Key topics:The evolving definition of leadership and the shift from expert to catalytic rolesThe importance of identity and ego in leadership developmentHow to foster authenticity and trust within leadership teamsThe orchestra analogy for understanding leadership transitionsThe significance of voice, listening, and shared thinking in decision-makingPractical approaches for coaching senior leaders and facilitating growthLeveraging AI while maintaining human connection and empathyDesigning impactful leadership programs rooted in relevance and personalizationThe role of inside-out development—who I am—and its impact on organizational cultureDynamic Leadership in a Disruptive World by Frans CampherImperial College Business SchoolRichard Pascal on Behavior and ThinkingLinkedInTimestamps:00:00 - Why leadership development matters in a disruptive world01:17 - Leaders must be present and curious for effective leadership01:47 - Lightning round: common misconceptions about leadership02:02 - Leaders often try to have all the answers, limiting growth02:20 - Authenticity hinges on trusting oneself02:32 - The biggest surprise: leaders don't need to have all the answers02:54 - The orchestra analogy: transitioning from expert to conductor03:46 - Identity shifts required to grow from managing to leading04:43 - Creating shiny eyes: impact as leadership metaphor05:12 - The amnesia of new leaders and rediscovering genuine leadership05:46 - The importance of letting go of controlling behaviors06:11 - Scaling leadership from small teams to enterprise-wide impact07:52 - The three leadership buckets: Expert, Achiever, Catalytic08:45 - Impact of the catalytic leader: orchestrating system-wide impact10:00 - The danger of micromanagement and the importance of trust10:51 - Hiring smart people and setting them free11:42 - The inside-out personal development for authentic leadership12:10 - The importance of human presence over superficial skills13:15 - Practical coaching with senior leaders: feedback, awareness, growth pathways14:23 - How leaders influence culture through vulnerability and openness15:15 - The process of gathering stakeholder feedback for leadership growth16:55 - Leaders operating below their potential and AI's role in organizational squeeze18:17 - Ownership of outcomes and empowering teams19:03 - Using narrative 360 for leadership self-awareness20:12 - The essence of purpose: understanding the “why” in leadership and organizations21:56 - Fundamental human needs: being seen, ideas matter, growth22:43 - Supporting development through personalized conversations and recognition23:58 - Leaders owning their own development, beyond HR and L&D25:36 - The importance of sharing thinking in decision-making processes26:23 - The metaphor of baking a cake: timing and readiness in decision-making30:12 - Leading academic programs: designing relevant, practical leadership education31:48 - Grounding oneself and holding steady against expert ego32:11 - The evolving role of AI and the irreplaceable value of human connection34:03 - Behaving your way into new thinking, not just thinking into new behaviourFrans Campher is an executive coach and has worked with senior executives and teams at companies like BP, Ford Europe, GlaxoSmithKline, Deloitte, Citibank, and Johnson & Johnson.

The central divide in psychiatry, the split between mind and brain, has been holding the field back and preventing people from getting the help they truly since its inception. Dr. Edward Bullmore, psychiatrist and author of The Inflamed Mind and The Divided Mind, has spent 35 years witnessing psychiatry struggle with this false dichotomy. In this conversation, we trace how the trauma of WWII rewrote the diagnostic manual, how antidepressants were discovered by accident and the science was reverse-engineered to justify them, and why the biggest genetic hits in schizophrenia research point not to neurons but to the immune system. If you've ever felt that the current system offers too little too late or that the answers must lie somewhere between biology and biography, this episode is for you.In this episode we discuss:The false brain/mind split that has defined and distorted psychiatry for over a centuryWhy the DSM is rooted in false science and has not held up to recent findingsWhy treatment for schizophrenia hasn't fundamentally changed since the 1980sGenome-wide association studies: what they reveal about schizophrenia, immunity, and shared genetic risk across diagnosesEarly life stressors and epigenetic riskThe case for integrating psychiatry with the rest of medicinePublic health interventions as mental health interventions; why maternal and child health may be the highest-leverage pointHow psychiatry might fundamentally change and what Dr. Bullmore hopes to leave for the next generationBioEd Bullmore studied medicine at the University of Oxford and St Bartholomew's Hospital in London, before training as a psychiatrist at the Maudsley Hospital, and completing a PhD in brain MRI analysis at the Institute of Psychiatry, King's College London. He moved to Cambridge as Professor of Psychiatry in 1999 and his research on brain networks and development of severe mental health disorders has since been highly cited. He was Head of the Department of Psychiatry, then Deputy Head of the School of Clinical Medicine in the University of Cambridge from 2014 to 2024.From 2005 to 2019, he also worked half-time for GlaxoSmithKline, focusing on the links between inflammation and depression, as described in his first book, The Inflamed Mind. He has recently published another book, The Divided Mind, about the past, present and future of schizophrenia. His scientific work has been recognised by election to the Royal Society and the Academy of Medical Sciences. In 2025, he returned to King's College London as the Regius Professor of Psychiatry and Head of the School of Academic Psychiatry.Links:The Guardian: Review of The Divided Mind https://www.theguardian.com/books/2025/dec/17/the-divided-mind-by-edward-bullmore-review-do-we-now-know-what-causes-schizophreniaThe Times Interview: https://www.thetimes.com/life-style/health-fitness/article/psychiatrist-edward-bullmore-divided-mind-schizophrenia-cause-childhood-infection-gm99jzjhm?gaa_at=eafs&gaa_n=AWEtsqfDuktSniOg_lxW5VLwPpLbpeIXNW3mCiER6PIWqRn99oF0SO8llQH-&gaa_ts=69c1a808&gaa_sig=l3rw9dUnzBnRd5S1Q7xd7qTqOE8Kpu63ROoP6N2ANWLN9bJw0cf4d24hJd3JqEhDoXiGaotrTHKgjV0ZMafQKw%3D%3DTelegraph Interview: https://www.telegraph.co.uk/health-fitness/conditions/dementia/prevent-schizophrenia-alzheimers/Resources:Find videos and bonus episodes: ⁠⁠⁠DEPTHWORK.SUBSTACK.COM⁠⁠⁠Get the book: ⁠⁠⁠⁠Mad Studies Reader: Interdisciplinary Innovations in Mental Health⁠⁠⁠Become a member: ⁠⁠⁠The Institute for the Development of Human Arts⁠⁠⁠Train with us: ⁠⁠⁠Transformative Mental Health Core Curriculum⁠⁠Sessions & Information about the host: ⁠⁠⁠⁠JazmineRussell.com⁠⁠⁠⁠Disclaimer: The DEPTH Work Podcast is for educational and entertainment purposes only. Any information on this podcast in no way to be construed or substituted as psychological counseling, psychotherapy, mental health counseling, or any other type of therapy or medical advice.

"Until immunomodulators, patients [with myeloma] did not have a great overall survival rate. But when we introduced lenalidomide, we started seeing our patients have life expectancies between five and seven years—which was unheard of prior to these immunomodulators going forward. I think it's promising and allows patients to have quality of life versus therapy of life," ONS member Daniel Verina, DNP, RN, ACNP-BC, nurse practitioner for the multiple myeloma program at Mount Sinai Medical Center in New York, NY, told Lenise Taylor, MN, RN, AOCNS®, BMTCN®, oncology clinical specialist at ONS, during a conversation about immunomodulators. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 0.75 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by June 12, 2027. Daniel Verina is on the speakers' bureau for Johnson & Johnson, GlaxoSmithKline, and Pfizer. This financial relationship has been mitigated. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome:  Learners will report an increase in knowledge about the use of immunomodulators to treat cancer. Episode Notes  Complete this evaluation for free NCPD.  ONS Podcast™ episodes: Pharmacology 101 series Episode 401: Multiple Myeloma Treatment Considerations for Oncology Nurses Episode 386: Interprofessional Navigation and the Oral Anticancer Medication Care Compass Episode 290: Cancer Symptom Management Basics: Peripheral Neuropathy ONS Voice articles: Maintain Oral Adherence With ONS Guidelines™ Multiple Myeloma Prevention, Screening, Treatment, and Survivorship Recommendations Sexual Considerations for Patients With Cancer Clinical Journal of Oncology Nursing article: Optimizing Transitions of Care in Multiple Myeloma Immunotherapy: Nurse Roles Oncology Nursing Forum articles: Changes in Health-Related Quality of Life During Multiple Myeloma Treatment: A Qualitative Interview Study Facilitators of Multiple Myeloma Treatment: A Qualitative Study ONS book: Multiple Myeloma: A Textbook for Nurses (third edition) ONS Symptom Intervention resource: Peripheral Neuropathy Risk Evaluation and Mitigation Strategies (REMS) Lenalidomide Pomalidomide Thalidomide International Myeloma Foundation: Using Immune Therapy to Fight Multiple Myeloma International Myeloma Society Multiple Myeloma Research Foundation: Treatments for Multiple Myeloma To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode "We definitely want the diagnosis of multiple myeloma before initiating these drugs. We're going to look at serum protein electrophoresis. We want to make sure that we know the patient has serum free light chains and myeloma proteins to really confirm their disease. Plus, a bone marrow biopsy." TS 7:21 "Each immunomodulator has slightly different side effects. Thalidomide's biggest side effects are constipation, weakness, fatigue, somnolence, peripheral neuropathy, mood swings, hand tremors, and depression. With each generation, less of the side effects actually occurred. Most of lenalidomide's side effects, not discounting the deep vein thrombosis, are pancytopenia—the neutropenia, the anemia, and the thrombocytopenia. [The side effects] are very similar in pomalidomide." TS 15:40 "The REMS program is critical for oral immunomodulator therapies—thalidomide, pomalidomide, and lenalidomide. It was developed due to the risk of developing embryofetal toxicities. ... It is mandatory testing and counseling, so all females of reproductive potential must have two negative pregnancy tests prior to starting the therapy and then monthly pregnancy tests while on the therapy alone. Again, they must use two forms of effective contraceptives or abstain from heterosexual sex four weeks prior, during, and after. And the same thing for men. I focus on that because males may say, 'I have a vasectomy.' These therapies tend to bind to the semen. So, males must still use a latex or synthetic condom during any sexual contact with a female of reproductive potential, even if they did have a vasectomy." TS 18:31 "The capsule itself cannot be chewed, crushed, or opened. I bring that up because as healthcare professionals, we have educated our patients. If it's difficult to swallow capsules or tablets, we've always said to them, 'Oh, don't worry, just crush it into applesauce or open it up and sprinkle it on your mashed potatoes.' But because of this embryofetal toxicity, I advise my patients not to open the capsule. If they can't swallow it for any reason, they have a sore throat or they're just unable to, then [we tell them] to hold the therapy and then call us." TS 22:49 "We spoke about three generations already, but there's actually a fourth generation [of immunomodulators]. They're called cereblon E3 ligase modulators(CELMoDs). They're still in clinical trials but really showing promise in the therapy of myeloma. They're showing very good affinity to cereblons, just like the immunomodulators do. I think, in all cancer therapies, as newer generations come out or newer therapies move forward, some of the older generations might move aside, but they get integrated later on. So I don't think [immunomodulators] will disappear totally, but they will probably be modified." TS 36:39

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. The industry is buzzing with significant shifts driven by scientific advancements, strategic acquisitions, and regulatory changes. A noteworthy transaction is Bayer's $2.4 billion acquisition of Perfuse, aimed at gaining control over an eye disease implant that has shown promising results in phase 2 trials. This acquisition speaks to Bayer's commitment to expanding its ophthalmology portfolio, a field with substantial unmet medical needs due to aging populations. The move highlights how companies are investing heavily in areas expected to see growing patient demand. In the realm of artificial intelligence, Recursion Pharmaceuticals is undergoing a strategic transformation under new leadership. After a decade of AI-driven research without yielding tangible products, the focus is shifting towards translating AI's potential into viable therapeutic solutions. This reflects a broader industry trend where the promise of AI must be balanced with pragmatic strategies to ensure commercial success. Novo Nordisk is making strides with its GLP-1/amylin combo treatment Cagrisema, maintaining its launch plans despite technical setbacks with a single-chamber device design. This demonstrates the company's adaptability in overcoming hurdles to bring innovative diabetes treatments to market, crucial in the competitive landscape of diabetes care. Additionally, Novo Nordisk's obesity treatment Wegovy has posted impressive quarterly revenues of $355 million thanks to strategic pricing and timely market entry ahead of competitors like Eli Lilly in the emerging oral obesity therapy segment. Such success suggests potential redefinition of market dynamics in obesity treatments. GlaxoSmithKline has entered into a $1 billion agreement with China's Siranbio for an oligonucleotide therapy targeting abdominal fat reduction. This partnership highlights GSK's strategic focus on cardiometabolic diseases through nucleic acid-based therapies, which offer high specificity and efficacy. Such therapeutics are becoming increasingly attractive for investment due to their potential impact on diverse health conditions. CellCentric's successful Series D funding round, raising $220 million for its myeloma drug, positions it well for pursuing clinical milestones independently. This signifies a shift towards self-reliant biotech models, illustrating how smaller companies are increasingly able to navigate the drug development landscape without traditional pharma partnerships. Gilead's acquisition of Arcellx for $7.8 billion and its subsequent workforce consolidation reflect ongoing realignments within the CAR-T therapy space. These consolidations indicate strategic prioritization within large biopharmaceutical companies to streamline operations while focusing on promising therapeutic areas like CAR-T cells. In corporate restructuring news, Gilead Sciences announced workforce reductions following its acquisition of Arcellx. While aimed at optimizing operations post-acquisition, it raises concerns about job security amid increasing merger activities within the biotech sector. Avalo's promising phase 2 results in skin disease treatment have renewed interest despite challenges from placebo comparisons. This emphasizes the competitive dynamics and high stakes in dermatological drug development, where even modest efficacy signals can significantly drive market activity. BioCryst's decision to halt its diabetic macular edema program to concentrate on rare diseases exemplifies a strategic pivot towards niche markets with potentially higher returns and less competition. This aligns with broader industry trends emphasizing precision medicine and targeted therapies. Eli Lilly's substantial $4.5 billion investment into its Indiana manufacturing complex underscores a commiSupport the show

Christopher A. Wilson (Chris Wilson) is a seasoned tax practitioner, entrepreneur, and author dedicated to making personal finance simple, accessible, and actionable. As CEO of Wilson Enterprise, Inc., he oversees 14 H&R Block offices across North Carolina and Virginia, serving thousands of clients each year. With more than 20 years focused on financial education and empowerment — plus prior corporate experience at GlaxoSmithKline, Bristol-Myers Squibb, and Ashland Oil — Chris holds a Business & Accounting degree from Winston-Salem State University and currently serves on its Foundation Board.He is the visionary behind upcoming book concepts including Investment Clubs, S&P 500, and Mortgage Magic, all designed to help everyday people understand investing, smart tax strategies, and building a nest egg that lasts a lifetime. His core mission: “to make financial understanding accessible and empower people to take control of their financial future.”https://www.christopherawilson.com/

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into a series of pivotal advancements and strategic moves that are reshaping the landscape of drug development and patient care. In vaccine development, Sanofi has recently reported promising results from a comparative trial of its protein-based COVID-19 vaccine, Nuvaxovid, against Moderna's latest mRNA vaccine, MNEXspike. The focus here was primarily on tolerability, and Sanofi's candidate demonstrated a superior safety profile. This marks a significant moment in the ongoing evolution of vaccine technology, underscoring the importance of diversifying vaccine platforms to effectively address global public health challenges. Shifting to regulatory landscapes, the U.S. Food and Drug Administration has been tasked with expediting the review process for psychedelic drugs under a directive from former President Donald Trump. This move aims to enhance access to novel treatments for serious mental health conditions, reflecting a broader trend in medicine towards exploring therapeutic avenues beyond traditional pharmaceuticals. It highlights an increasing openness to alternative therapies that could potentially transform mental health care. Strategic acquisitions continue to fuel innovation within the sector. Eli Lilly's acquisition of Kelonia Therapeutics for up to $7 billion is particularly noteworthy. This investment marks Lilly's second venture into in vivo CAR-T technology this year, emphasizing its commitment to advancing cell-based therapies. Kelonia's work on phase 1-stage myeloma therapy showcases the potential of CAR-T modalities in treating complex diseases, promising expanded treatment options for patients. Globally, infrastructure development is gaining momentum with Biovac securing a $108 million finance package to establish Africa's first fully integrated vaccine production facility. This initiative is crucial for enhancing regional healthcare autonomy by addressing local health needs and reducing reliance on external supply chains—a step forward in building resilient healthcare systems. In oncology, Merck & Co. has unveiled clinical data for its PD-1xVEGF bispecific antibody in non-small cell lung cancer (NSCLC). The results reveal similar efficacy and safety profiles compared to existing treatments, suggesting promising prospects for this bispecific approach in oncology therapeutics. Bispecific antibodies are engineered to engage two different targets simultaneously, potentially enhancing anti-tumor efficacy by not only stimulating immune responses but also disrupting angiogenesis. This innovation represents a continued focus on targeted cancer therapies that enhance treatment precision. Similarly, AstraZeneca's IL-33 inhibitor has achieved another phase 3 success in treating chronic obstructive pulmonary disease (COPD). This reinforces the therapeutic potential of targeting interleukin pathways in inflammatory diseases and reflects AstraZeneca's strategic focus on respiratory conditions. Such successes highlight the promise of precision medicine in improving patient outcomes. On the topic of market expansion, GlaxoSmithKline's multiple myeloma treatment Blenrep has entered the Chinese market. This move exemplifies the growing importance of global market access strategies, ensuring that patients worldwide can benefit from cutting-edge therapies. Now let's turn our attention to some intriguing scientific developments. A former Genentech leader has launched a synthetic design lab focused on adaptive "smart" antibody-drug conjugates (ADCs) for cancer therapy. ADCs represent a significant leap forward in precision medicine by offering targeted cancer treatments that minimize damage to healthy cells. These "smart" ADCs could provide more effective and less toxic options for cancer patients. Support the show

Dr. Monty Pal speaks with internationally acclaimed hematologists Dr. Vincent Rajkumar and Dr. Saad Usmani about the AQUILA trial in high-risk smoldering multiple myeloma, as well as advances in CAR-T and other evolving treatment strategies in the myeloma space. TRANSCRIPT Dr. Monty Pal: Hello everyone and welcome to the ASCO Daily News Podcast. I'm your host, Monty Pal. I'm a medical oncologist, underline medical oncologist, a professor, and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. You're going to understand why I underlined "medical oncologist" there. I'm actually on the line today with two amazing hematologists. Today, we're going to actually explore treatments for high-risk smoldering multiple myeloma following the FDA's approval last year of daratumumab for the first-ever treatment of this indication. Now, this is based on the AQUILA trial, and this represents a huge shift in our traditional watch-and-wait approach to active disease interception. We're going to consider whether this landmark trial published in The New England Journal translates to day-to-day practice. I think it does, and we'll certainly make an argument for that. And I'm so fortunate today to have two internationally acclaimed experts here in the conversation: Dr. Vincent Rajkumar, senior author on the manuscript, and Dr. Saad Usmani, also an expert in his own right in myeloma. Dr. Rajkumar is the lead investigator of the AQUILA study. He's a professor of medicine and consultant in the divisions of hematology and hematopathology at the Mayo Clinic in Rochester, Minnesota. He actually chairs the Myeloma, Amyloidosis, Dysproteinemia Program. He is also editor-in-chief of the Blood Cancer Journal. Dr. Usmani, he and I actually go way, way back. We actually did the AACR Molecular Biology in Clinical Oncology course, I want to say in 2006, so this is our 20-year anniversary, Saad. He's the chief of the myeloma service at the MSK Cancer Center and a professor of medicine at the Weill Cornell Medical College in New York.  Saad, Vincent, welcome. Dr. Saad Usmani: Thank you so much for having me, Monty. Dr. Vincent Rajkumar: Yeah, thanks, Monty. A pleasure to be here. Dr. Monty Pal: Thanks. And just a quick note for our listeners, all of our disclosures are available in the transcript of this episode. First off, Saad, did I get that right? Was it 2006 when we did that course together? Dr. Saad Usmani: Yeah, 20 years. We are coming up to our 20-year anniversary. It's remarkable to have seen our careers move the way they have, Monty. Dr. Monty Pal: Oh my gosh. And for all the fellows who are on the line, that AACR Molecular Biology and Clinical Oncology course, it's sometimes overlooked. Wonderful primer on translational science. Okay, now we're going to get to the heart of the matter here, the AQUILA trial. So this was a study, Vincent, that you led. I wonder if you'd walk us through the primary endpoints in the study. What are we looking at in the AQUILA trial specifically? Dr. Vincent Rajkumar: Thanks so much. Again, as you mentioned, smoldering multiple myeloma has just been a condition that we watch and wait. And the first thing that I want to clarify here is that the AQUILA trial is looking at only a subset of smoldering multiple myeloma. That is the high-risk smoldering multiple myeloma. It was defined the way high-risk smoldering myeloma was defined at the time the trial was designed. It randomized 390 patients. One arm got daratumumab single agent in an attempt to delay progression to active myeloma and possibly prolong survival. And the other arm was the traditional observation. The primary endpoint, therefore, was time to active multiple myeloma. Other endpoints included time to when patients needed to start therapy for active multiple myeloma, which can vary based on physician judgment, and overall survival. Of course, response rate, complete response rate, and others were also endpoints. Dr. Monty Pal: That's interesting. And you know, I wanted you to riff a little bit on this definition of high-risk smoldering myeloma. Can you tell our audience how that's sort of evolved over the years? Dr. Vincent Rajkumar: Yes. I mean, if you step back, monoclonal gammopathy of undetermined significance has only a 1% per year risk of progression. Smoldering multiple myeloma, all comers have a 10% per year risk of progression. And over the years, trials have been done in the whole population, and then more recently, we felt we should really focus on the people with high-risk smoldering, defined as a 50-50 risk of progression in 2 years. That's like a 25% per year risk of progression in the first 2 years, which is a very high risk for the patient and something that would justify prophylactic intervention. And that definition initially was based on just high levels of monoclonal protein like more than 3 grams, the IgA subtype of myeloma, the suppression of uninvolved immunoglobulins. Others have used bone marrow flow cytometry markers, cytogenetics. Those combinations of factors were available at the time the AQUILA trial was designed, and a select combination was used. Later on, we found that we could match almost all of that in a very simple risk stratification using just the percentage of bone marrow plasma cells, the level of the M-spike, and the free light chain ratio, all three of which are available to all patients with smoldering at the time of diagnosis. So you don't need any special testing. So more than 20% plasma cells, more than 20 for the light chain ratio, and more than 2 grams for the M-spike. If someone has any two of the three, that is high-risk smoldering multiple myeloma according to the IMWG, but that definition, of course, came in 2020 after the AQUILA trial completed accrual. Dr. Monty Pal: That's interesting because this sort of flips the traditional paradigm where biomarkers get more and more complex as time goes on. Am I right in saying this sort of simplifies things a little bit? It uses standard laboratory or clinical parameters to gauge this category? Dr. Vincent Rajkumar: Absolutely. People were using suppression of uninvolved immunoglobulins, and those levels are not standardized, often vary by race. Also, the other aspect was the abnormal plasma cells on flow cytometry. Again, labs define it differently. So this makes it much more simple. But the IMWG also did a separate exploratory cohort within that paper where we added cytogenetics and we added scoring systems to improve on this further. So it simplified it for regular clinical practice and for like trials. But if you have a patient in front of you, the IMWG paper also has more complex scoring systems where you can take more than 20; 21 is more than 20, so is 51. And so, you can use the actual numbers that a patient has, additional variables like cytogenetics, and get a more refined estimate of what is the true risk of progression. Dr. Monty Pal: That's really helpful. Now, you told us about the primary endpoints, you've helped us define high-risk smoldering myeloma. Can you give us a sense of the top-line results from AQUILA? Dr. Vincent Rajkumar: Yes, I think the most important one was the primary endpoint, time to multiple myeloma, was at 5 years, the progression-free survival was 63% in the daratumumab arm compared to 41% in the observation arm. So, you know, approximately 60% of patients in the observation arm had already progressed by 5 years. And that number was about 40% for the daratumumab arm. We also looked at time to starting myeloma therapy, which is clinically actually quite meaningful because, you know, myeloma therapy means patients get a quadruplet for induction, they get stem cell transplant, they get endless maintenance, they get ongoing therapy virtually for the entire duration. So, preventing the need for myeloma therapy is in and of itself, I think, a major endpoint. And that at 3 years, 40% of people in the observation arm required full myeloma therapy compared to only 20% in the daratumumab arm. So there's a significant reduction in the risk of developing active myeloma as well as the need for myeloma therapy by using a time-limited 3 years of daratumumab single agent. Dr. Monty Pal: Perfect summary of the results. And maybe, Saad, I'm going to bring you into the conversation now. How does this sort of influence your day-to-day practice for smoldering myeloma? Is this something that you've incorporated for that high-risk subset? Dr. Saad Usmani: Thank you, Monty, and I agree. I think that's a really nice summary from Vincent. This study is very important for several reasons. It's actually the third clinical trial that has demonstrated that patients who are in the high-risk smoldering myeloma category benefit from an early intervention that delays the progression to active myeloma or to end-organ damage. And so having a nuanced discussion with our patients in the clinic becomes very important. Having this discussion around as an option becomes very important. And like Vincent said, when we look at that high-risk smoldering myeloma patient population, someone who has 22, 23% plasma cells versus, you know, 45, 50, you know, it's going to be a different discussion each time. But I think it's a very important first step. And I think this sets up the stage for us to design clinical trials where we can ask other questions on what would be better than daratumumab alone in terms of delaying progression in these patients. The other thing that I do want to highlight, and Vincent touched upon this a little bit, that the treatment in this clinical trial was for a fixed duration of treatment. So it was not forever treatment. This is maybe something that Vincent, you can even comment on a little bit more because the question we get after having this discussion is, "Okay, what do we do with patients who are going to be progressing to active myeloma?" Whether we can utilize anti-CD38 therapies for those. So Vincent, I would love your take on this too. Dr. Vincent Rajkumar: Yeah, I think, you know, the main philosophical change for me was previously, the thing was 'don't treat', and now for high-risk smoldering multiple myeloma, the question is, is daratumumab the best treatment or can we do something better? And those trials are thankfully ongoing. One of them has already completed accrual, isatuximab-len-dex versus len-dex. And another one is ongoing in ECOG, almost close to finishing accrual. And in the future, we'll be trying to see if we can use early intervention to even cure and prevent progression altogether.  So we are in this phase where we have one approved regimen, one approved drug, and we are not sure whether we can improve on that. The question is, "is a myeloma-like therapy better than monotherapy" would be the next question, and then what would we do further beyond that? In this context, whenever we have patients like this, one of the questions that comes up, as Saad mentioned, is how does this affect newly diagnosed myeloma therapy if somebody has been treated for smoldering and things like that? How will they be considered for clinical trials? Would they be considered as relapse myeloma or still newly diagnosed myeloma? And those are important discussions for clinical trialists to keep in mind, but I think for clinical practice, your duty is to the patient in front of you. If they have high-risk smoldering myeloma and there's data that there's treatments that can delay progression significantly, delay the need for myeloma therapy significantly, that's the highest priority. We'll cross that bridge.   There are so few patients going on clinical trials right now that if such a patient were to later on progress and wants to enter in a newly diagnosed myeloma trial later, years later, we can figure that out later. I feel like the most important discussion is what to do for that patient today. I still prefer a clinical trial if one was available. If one was not available, I'd prefer early intervention, but have an informed discussion with the patient because some of them may wish to delay therapy still. Some of them may have very borderline numbers that you want to watch them closely. Some of them may be having other comorbidities that prevent need for therapy. Some of them maybe have had the smoldering for a long time and you already know it's stable. So a lot of factors go in, and I think it's not a one-size-fits-all. Dr. Monty Pal: This is a terrific discussion, and you know, it sort of segues into maybe a question around biology. And this is something I was going to get to a little bit later, but Saad, I'm glad you brought it up. I'll liken it to the only thing I know, which is kidney cancer. So, you know, in kidney cancer, we use checkpoint inhibitors as adjuvant therapy. And there's this question of whether or not it breeds some resistance in the localized setting to ultimately what the patient might potentially be exposed to in the metastatic setting. Tell me your thoughts on this, Vincent, then maybe Saad separately. If you treat a patient with daratumumab in this high-risk smoldering setting, could it theoretically sort of limit options in the refractory setting now that we have regimens like DRBD that are kind of being utilized, or daratumumab with teclistamab? Vincent, I'll throw that to you first. Dr. Vincent Rajkumar: This is a great question, and it's usually asked when we've done the lenalidomide trials actually. We try to put the question back. If that was your concern, how would you actually solve it? Is it really biology that's going to answer that? Or is it a randomized trial? So the experiment has been done three times now where early intervention has been given. And if there was some detriment because of that, that would be reflected in the overall survival. In all three trials, there's no such detriment seen. In the first lenalidomide-dex trial, there was an improvement in overall survival. In the AQUILA trial again, the confidence interval doesn't cross one, and patients had better long-term survival on AQUILA, but certainly not less. We've also examined PFS2 data, and that doesn't seem to be affected. So yes, there is a theoretical concern, and that concern cannot be allayed for new treatments which we have not even tried, like tec-dara, and whether that effect would be there or not. But so far, I don't see it. And I think the onus is on proof of that in order to prevent people from getting early therapy. Dr. Monty Pal: Yeah. Saad, your thoughts on that? And before you jump in, I'll mention, we're kind of taking the same approach in kidney cancer, we're trying to really do studies to see whether or not, you know, immunotherapy rechallenge in these contexts, you know, really lends any substantial benefit. So far, the results have been interesting. I don't think we have enough numbers as yet to capture the impact of adjuvant therapy as it translates to metastatic, but I see so many similarities between the scenarios that you're facing in myeloma and what we're facing in RCC. Saad, your thoughts? Dr. Saad Usmani: Thanks, Monty. I'll go back to something that Vincent alluded to a few minutes ago about the way that we risk-stratify patients within smoldering myeloma. Right now, we are relying more on a disease burden-based stratification looking at the percentage of plasma cells in the bone marrow, the monoclonal protein, as well as the involved light chain versus the uninvolved light chain ratio. However, there are efforts underway to actually incorporate genomics into that schema and try to refine that definition of high-risk smoldering. And there have been two papers that came out in the latter half of last year. In fact. Dr. Rajkumar and I are co-senior authors on one effort where we can identify genomic myeloma in patients in precursor conditions. One of the key things that came out of that effort was that within the high-risk smoldering myeloma category, about 90% of the patients are genomically myeloma. So this whole debate of whether we need to intervene for those patients, I think, you know, we have sufficient biologic evidence that yes, we need to intervene for those patients.  I think that the next real step, like Vincent stated, is how do we intervene in those patients? And those clinical trials kind of are ongoing. We will probably need to have more validation of those genomic models being incorporated, but that's what I see in the future. I wouldn't be concerned for the patients being seen today with that query about the disease biology evolving because if I'm seeing a patient today in March of the first quarter of 2026 and offering them monotherapy daratumumab in their high-risk smoldering situation for the next 3 years and then they progress to myeloma after another couple of years, we are talking about what would be the treatment options for them in 2031, 2032. So I think the field is moving so fast, we have a lot of novel therapies coming into that frontline setting rapidly, so our options at that time would be very different. So, you know, I just wanted to kind of set up the stage for saying, you know, our tools are getting better in delineating which patients will need that intervention. And then eventually, I think, you know, we'll have much better options for newly diagnosed myeloma patients at the time when they need it in the future. Dr. Monty Pal: Just absolutely brilliant, absolutely brilliant. I love that summary. I think that you're absolutely right in saying that, you know, you've got to think about what you're going to do for that patient sort of in the moment, what's going to optimize their outcome and agree that the landscape is evolving very rapidly.  I'd be remiss, Saad, if I didn't ask you about something that I've been following in terms of your career trajectory. You've developed quite a reputation for your leadership in trials looking at CAR T-cell therapies for myeloma. Can you give us a sense of where that stands in broad terms? Dr. Saad Usmani: Certainly, Monty. I think the CAR Ts have slowly made their way from late relapse to early relapse. And now we have clinical trials that have completed accrual in the frontline setting comparing them to standard-of-care treatment for both older myeloma patients or transplant-ineligible patients, as well as younger transplant-eligible patients where we're actually trying to replace transplants with BCMA-directed CAR T-cell therapies. The nuance there would be we want to equal or better the survival outcomes that we've accomplished without compromising on the safety side of things for patients. Those therapies are moving into earlier lines. And more excitingly, you know, that's just the first wave of CARs. The next wave of CAR technology is coming, and it's going to be in vivo CARs where we may not need lymphodepleting chemotherapy, we may not even need as stringent regulatory nuances that we do for cellular therapies today. So, you know, I think the field is moving rapidly, and it's going to be a very interesting landscape to see over the next 5 to 6 years. Dr. Monty Pal: Yeah, you know, it's so interesting. I know in the solid tumor space, we're trying to replicate the success that you've had with CAR T and bispecifics, and I do see some light at the end of the tunnel. I'm seeing some really promising agents being developed, but clearly, we have so much to learn from our colleagues in hematology. Well, I have to tell you, this has just been a phenomenal conversation. Vincent, congratulations on your leadership of the AQUILA trial. Clearly, a big paradigm shift in the field. Saad, thank you for offering your expert insights and really giving us also a glimpse at the future of myeloma. Really appreciate having you both on the podcast today. Dr. Vincent Rajkumar: Thank you, Monty. Dr. Saad Usmani: Thank you so much. Dr. Monty Pal: And thank you so much to our listeners for your time today. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:      Dr. Monty Pal    @montypal   Dr. Vincent Rajkumar @VincentRK Dr. Saad Z. Usmani @szusmani   Follow ASCO on social media:           ASCO on X     ASCO on Bluesky          ASCO on Facebook           ASCO on LinkedIn           Disclosures:        Dr. Monty Pal:      Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview      Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical    Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis    Dr. Vincent Rajkumar: Honoraria: Research to Practice, Medscape Patents, Royalties, Other Intellectual Property: Authorship Royalties from Up To Date Dr. Saad Usmani: Consulting or Advisory Role: Janssen Oncology, GlaxoSmithKline, Abbvie, Bristol-Myers Squibb/Celgene, Regeneron, AstraZeneca, Sanofi Research Funding: Janssen Oncology, Bristol-Myers Squibb, K36 Therapeutics, Abbvie, Regeneron  

In this episode of The Business of Coaching, we sit down with Beverley (Bea) McCloskey, a former corporate pharmaceutical professional turned successful coach. Bea shares her powerful journey from the high-stakes world of big pharma to a catastrophic burnout that eventually became the "gift" that launched her business.If you've ever felt like you're spinning 25 plates at once—or keeping 25 browser tabs open in your brain—this conversation is for you.About the Guest:Beverley (Bea) McCloskey is a specialist coach and mentor with a deep-rooted background in the corporate pharmaceutical industry. Having spent much of her career in field-based roles for global giants like AstraZeneca, GlaxoSmithKline, and Novo Nordisk, she experienced firsthand the transition from high-performance sales to leadership and dedicated coaching roles.Bea's professional journey took a pivotal turn following a catastrophic burnout and a diagnosis of chronic fatigue syndrome, triggered by a combination of high-pressure work and challenging personal circumstances. After a two-year recovery period, she transformed this lived experience into a successful business.Today, Bea focuses her expertise on helping women in the pharma sector—her "ideal client" who mirrors her own experiences from 15 years ago. She works with high-achievers to help them navigate the pressures of corporate life, avoid burnout, and rediscover joy in their careers by balancing soft and hard power.Key Takeaways:The "Tell-as-Coach" Trap: In many corporate environments, coaching is often mistakenly used interchangeably with "training" or simply telling people how to do their jobs.The Cost of Perfectionism: Bea reflects on how her perfectionism wasn't about excellence, but rather an "away motivation" fueled by a terror of making mistakes.The Reality of Burnout: Burnout isn't just about working too hard; it's a multifactorial collapse of resilience often triggered by a combination of personal and professional challenges.The "Niche" vs. The "Chasm": Having a broad niche like "women in danger of burning out" can feel like a chasm where no one can hear you. Success comes from a "tight focus" on people who share your specific lived experience.Employee vs. Business Owner: Transitioning from an employee mindset to a business owner mindset requires a "different manual". Simply replicating corporate structures (like expensive websites and VAT registration) doesn't equate to having a business if you don't have clients."I thought I had a niche, but it was a chasm and no wonder no one could hear me... My words were just words. They were not targeted." — Beverley McCloskeyHave you enjoyed this episode? Find out more and take the FREE quiz at: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://thecoachingrevolution.com/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Join the FREE Facebook group at: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.facebook.com/groups/buildacoachingbusiness⁠

Dr. Monty Pal and Dr. Vamsi Velcheti discuss the evolving treatment landscape in EGFR-mutated non-small cell lung cancer, including landmark trials like FLAURA2, novel drug therapies, and the growing importance of ctDNA and MRD testing. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, I'm truly delighted to introduce Dr. Vamsi Velcheti, who's a professor of medicine and the chief of hematology-oncology at the Mayo Clinic in Jacksonville, Florida. We'll be discussing the expanding treatment landscape in EGFR-positive lung cancer and how to navigate the challenges of balancing treatment efficacy, toxicity, and patient quality of life in the EGFR-positive space.  Just FYI, our full disclosures are available in the transcript of this episode.  Vamsi, it's so great to have you on the podcast. Thank you so much for being here. Dr. Vamsi Velcheti: Thank you, Monty. It's a pleasure to be here with you. It's a really exciting topic and there are a lot of updates in the EGFR space. Dr. Monty Pal: So, I'm going to need your help with this because I'll be honest with you, I see very little lung cancer, if any, in my practice. I'm pretty much exclusively kidney cancer these days. I'm coming on 20 years at City of Hope now, and I still remember when trials like ECOG 1599 were presented with, you know, platinum doublets. And, of course, the field has changed a lot since then. But tell us a little bit about the first-line landscape, and I think just for the sake of time, we're going to stick with EGFR-positive disease here. What does it look like these days? Dr. Vamsi Velcheti: Monty, the foundation of care remains the third-generation EGFR inhibitors. These are selective EGFR inhibitors, like osimertinib. We've had an evolution of the development of these TKIs. Like, you know, we had the first-generation, second-generation, not-so-selective EGFR inhibitors. Now we have mutant-selective EGFR inhibitors in the clinic, and they're doing a really good job. And these are quite effective in patients who have classical activating mutations. But the reality is that these have not been transformative. These agents have fundamentally changed the response patterns, excellent CNS penetration, and very good tolerability profile. However, we don't see a lot of durability in terms of the response. So, what's different today is now there have been several trials in combination with these third-generation EGFR inhibitors that have really laid the foundation of how we kind of think about EGFR-positive disease. At the high level, there are a lot of challenges to selecting the patients for these combination-based modalities. I'm assuming we'll be talking more about these different trials and different approaches. Some of these combination-based strategies have really moved the needle in terms of improving overall survival and really improving long-term outcomes and durability in our patients. Dr. Monty Pal: And we are going to get into the weeds on this in just a moment. But I did kick off this podcast talking about chemotherapy, ECOG 1599. It does seem as though chemotherapy is still a component of management in advanced non-small cell lung cancer. So, can you tell us about, perhaps first, you mentioned osimertinib, you know, some of these next-generation EGFR inhibitors. Tell us about the role of chemo plus osimertinib. Dr. Vamsi Velcheti: That's exactly where I was going with the combination-based strategies. You know, we first started off with our earlier trials in the EGFR space evaluating the question of, are targeted therapies, are these highly effective, third-generation, EGFR-selective inhibitors, superior to platinum-doublet chemotherapy? And we've had multiple trials demonstrating that, like the FLAURA trial and in the past with second-generation EGFR inhibitors like erlotinib and gefitinib and afatinib. So, we know that these TKIs actually perform better than platinum-doublet chemotherapy. Now, we have a large, global, phase 3 trial data from the FLAURA2 trial, which looks at the question, "Hey, you know, osimertinib is better than chemotherapy, platinum-doublet chemotherapy. Can we do even better by combining osimertinib with platinum-doublet chemotherapy?" So, FLAURA2 answered that question. This is a large, phase 3 trial, and it's a positive trial with improved durability of disease control and improving overall survival with combination with chemotherapy. So, it's a very important and landmark trial, and essentially combining osimertinib with a platinum-based chemotherapy improved responses, deepened responses, and improved overall survival and really changing the disease trajectory. And this strategy is definitely compelling, especially in patients who have certain clinical high-risk features like, you know, patients who have high disease burden or patients who are sometimes having rapid disease progression early on osimertinib, especially with patients who have a lot of visceral disease burden. So, intensifying treatments up front could alter the natural trajectory of the disease. Dr. Monty Pal: So, you sort of alluded to this in that last part there, but is that kind of how you in clinical practice select? Is it based on, you know, visceral involvement? Is it based on rapidity of disease where you think about adding chemotherapy to osimertinib? Maybe you can give us the corollary. Which patients do you just use osimertinib alone in, for instance? Dr. Vamsi Velcheti: Definitely, there are some patients who have low disease burden and they have the classical mutations, like an exon 19 deletion. And these patients, especially if they don't have a lot of disease burden, they don't have CNS involvement, there may be a subset of patients who could just do fine on osimertinib of course, with close monitoring of the disease. I guess we'll get into that later, how do we do that with either ctDNA or like closer imaging or both. So, there may be some opportunity to kind of escalate patients' treatments based on certain clinical characteristics or radiographic characteristics or certain biological characteristics informed by ctDNA or other approaches. Dr. Monty Pal: No, that's interesting. And you're right, we will chat about ctDNA in just a bit. But before we get there, I think one of the big agents that has really sort of come to the fore in advanced non-small cell lung cancer is amivantamab. I've heard a lot about this in the context of even kidney cancer because in certain subsets, I'm interested in MET-directed therapies and so forth, right? So maybe tell us a little bit about the mechanism of amivantamab first, and then maybe tell us about this pivotal MARIPOSA trial where it's combined with lazertinib. Dr. Vamsi Velcheti: So, the MARIPOSA trial compared lazertinib alone with amivantamab plus lazertinib. And this trial demonstrated overall survival advantage, and there were key differences in terms of tolerability and the safety of amivantamab, which is an EGFR and MET bispecific, and there were certain kind of unique toxicity profiles that make it a little different than the intensification approach with chemotherapy through the FLAURA2 trial. So, there's a trade-off in terms of the toxicity profile. It's a different agent and a different management protocol in terms of dermatological toxicity management that clinicians need to be comfortable with. And also, there are certain unique issues in terms of amivantamab; there's a higher rate of infusion-related reactions, there's an increased risk for edema and VTEs because of amivantamab. Certainly a different toxicity profile, different management paradigm there in terms of longitudinal care of these patients requiring dermatological care and like, you know, close monitoring and prophylaxis VTEs. But having said that, definitely it's a different strategy, and it kind of changes the biology and the natural history of the cancers, and we do see some durability of responses that we see with the MARIPOSA. So, it's certainly a great alternative, at least for some patients. Dr. Monty Pal: That was a great overview of MARIPOSA. Now comes the really difficult question, which is, how do you choose between the two? You have these two great options, right, for EGFR-positive patients. You've already highlighted some of the distinctions in terms of toxicity. I think the audience is well aware of the side effects of chemo-doublet, perhaps even the EGFR-based therapies. Amivantamab is quite new. Give us a sense of how you in clinical practice decide between the two potential options here. Dr. Vamsi Velcheti: Yeah, I think that's the big challenge. I think these are two independent strategies that have evolved through the phase 3, and both of them have demonstrated overall survival benefit. So, the way I think about this is in three dimensions, right? Like, the disease biology, the patient priorities, and feasibility of care delivery. So, when I talk about the disease biology, you know, the mechanism is very different, and MET is a very dominant driver of disease in EGFR-altered patients and it's a significant mechanism of resistance, acquired resistance to TKIs. So, certainly I think there's a patient population that could benefit from a MET-directed therapy up front. However, we don't have great data to kind of really demonstrate how using amivantamab in the front line is going to change that. And are there like perhaps like some patients who we could identify who would benefit from such a strategy? Very recently, there have been some approvals in the second-line setting in lung cancer, not in the EGFR space, but like in generally in lung cancer, with the MET ADCs, and those drugs are approved with a companion diagnostic, which requires MET IHC testing. So, what has happened, at least in large academic practices and also I think in the community now, they have been checking for MET IHC expression more routinely in lung cancer. What we have been doing in our institution is we have been doing MET IHC as a reflex for all patients with EGFR, not just EGFR, but all non-small cell lung cancer patients. What that has done is now, like, we have been increasingly testing patients with EGFR for MET. And there's clearly a subset of patients who have de novo MET expression and a high MET expression. And those patients, I've been kind of like preferentially treating them with the MARIPOSA regimen. But again, I have to caution the audience that we still don't have data that MET IHC is going to help us make those decisions, whether it's better than like a FLAURA2 regimen. But however, in the second-line setting in the CHRYSALIS trial, we know that MET is a very powerful predictor of response to amivantamab. We really need more data there, but that's what I have been doing in my practice. But also, there's a lot of patient preference here. Like, there are some patients who don't want chemotherapy, and they want a non-chemotherapy approach. So, certainly there are some patients who prefer to have amivantamab. And now with the amivantamab, the subcutaneous version, the infusion reactions and the logistics of actual administration of amivantamab are more favorable with the subcutaneous approval. So, those are some of the elements that we need to take into account. Dr. Monty Pal: Well, I want to hone in on that because this subcutaneous administration route has been a big debate that I've seen on social media. Tell us, how much easier does it actually make the amivantamab experience? Does it cut down on the rash? Is it just infusion reactions? What's been your clinical experience? Vamsi Velcheti, MD: So, the subcutaneous administration of amivantamab has definitely improved the infusion reaction issue. Very rarely patients have infusion reaction now with the subcutaneous injections. And also, the infusion time is much, much shorter. Like we don't need a lot of infusion time, which is sometimes a challenge in busy infusion clinics. We need to take that into account. As far as the impact of the subcutaneous formulation on dermatological toxicity, we haven't really seen significant difference in terms of the intensity or rates of dermatological toxicity with subcutaneous. The benefits are really with the infusion reaction, the ease of administration. And interestingly, in the PALOMA trial, it also seems to be, even though this was not the primary endpoint of the study, there seems to be some suggestion that the subcutaneous amivantamab seems to have improved OS compared to the IV amivantamab. We don't really understand why, but that's a finding from the trial that's very intriguing. Dr. Monty Pal: That is really fascinating. I'm kind of curious to see how that's going to pan out. I'm going to shift gears a little bit here. And, you know, as we sort of close, I wanted to talk a little bit about biomarkers. I mean, this is obviously not a lung cancer-specific issue. It's something we think about across the board. But what I will say is that there are certain commonalities, and in bladder cancer, we think a lot now about ctDNA. But you've been way ahead of the game in lung cancer. Tell us how you guys use ctDNA, maybe both from the standpoint of monitoring for mutational status, but if you can, maybe offer some insights into some of these new MRD tests that are available too. Dr. Vamsi Velcheti: Yeah, it's rapidly evolving. Certainly, I think in the lung cancer space, you know, this has really kicked off in the lung cancer space with incorporating ctDNA into the workflow. Of course, you know, like baseline evaluation, we still kind of heavily rely on tissue genomic sequencing. But as you know, with targeted therapy, a lot of these patients have disease that evolves over time, and changes in terms of mutational pattern driving acquired resistance is a major issue across different molecular subtypes. And especially so in EGFR, when there are certain actionable opportunities associated with that transformation. So, we need to kind of have like a longitudinal snapshot of how we monitor these patients. So, the ctDNA has come to be like a tool that has now come to the forefront of clinical workflow, and almost all my patients who are having disease progression have ctDNA for kind of evaluating for resistance and informing treatment decisions, especially in EGFR. But having said that, there are a lot of challenges in terms of using ctDNA as a tool for monitoring. There are a lot of different types of assays and different platforms, and being able to use this as a quantitative tool that would be used along with the CT scans that we routinely use in clinical practice has been a challenge. And I think I would love to hear your perspectives as well, Monty, about how you're thinking about that in bladder and other disease contexts. But having said that, I think there's a lot of opportunity to incorporate ctDNA and MRD assays into clinical decision-making. Right now, in terms of clinical trials and clinical development, there have been some very interesting trials that are currently ongoing, especially in the EGFR space. We know that patients who clear ctDNA, based on some retrospective data and also like some retrospective-prospective data from trials that have already read out, that patients who clear ctDNA early with target therapy tend to do much better. They have a longer durability of response. There may be a subset of patients who have, even though they're having radiographic response, they have persistent ctDNA after a certain time point of initiation of targeted therapy. Those patients may require escalation of therapy. We don't yet know. I can't recommend that as a standard right now because we don't have clinical evidence to support that. But however, some of the clinical trials, like the ELIOS trial that's being done right now, that's actually completed enrollment, we'll hopefully see the results very soon. So, there is an emerging thought that instead of intensifying treatment for all patients with EGFR, there may be a population that may be just fine with frontline osimertinib monotherapy and introducing the intensification strategy at the time of emergence of MRD or progression on ctDNA before radiographic progression. So, there are a lot of adaptive molecular response criteria that we are kind of exploring in clinical trials that could inform how the future is going to look like for EGFR and other perhaps targeted therapies as well. So, it's fascinating, and I think there's a lot of opportunity there. Dr. Monty Pal: You know, you asked for my perspective. I actually think that what you highlighted there is the most interesting opportunity for ctDNA: the ability to de-escalate therapy. In terms of drug development, we've done so much to bring new therapies to patients, and now it's a bit of an embarrassment of riches, but the downside is that I feel like we tend to overtreat a lot of patients in the clinic. So, I definitely view MRD, you know, some of these other ctDNA techniques with methylation and so forth that may not be sort of tumor-dependent or bespoke could be incredibly, incredibly helpful. You touched on sort of the future, right, in this last section here with biomarkers. But give us a sense now in terms of novel drug therapies in the EGFR space. What are you most excited about moving forward in 2026 and beyond? Dr. Vamsi Velcheti: Yeah, I think there's a lot going on in this space, and not just this space, but across lung cancer and others as well. Like looking at the next generation of targets for ADCs. And I think a lot of these have to do with…so far in the drug development space, as you know, the improvements in clinical outcomes has been very incremental. So, we really need to make that big leap. And I think the big leap is not going to come from, in my opinion, from the next ADC, but it's going to come from how we tailor treatments and how we monitor disease better and how do we kind of incorporate the next treatment earlier and not wait for the radiographic progression. So, there's a lot of opportunity there to integrate biomarkers and dynamic biomarkers into clinical trial design and incorporating the recent advances in terms of drug design. You know, we have a lot of assets in the EGFR space, the next-generation EGFR inhibitors that are kind of designed with resistance in mind and rational combination, knowing when to introduce those combinations is also equally important. So, there's a lot going on, really exciting times to be in drug development. The one thing that I really hope will come to the forefront in drug development, not just for lung cancer, but all disease groups, is to kind of really be thoughtful about how we incorporate these really cool molecular monitoring tools and creating a composite score with imaging to be able to like really design the next generation of clinical trials. Dr. Monty Pal: You're so spot-on with that. I definitely think that we're getting to this point where, you know, we could think about the next BiTE, the next CAR-T, the next ADC. But, you know, maybe it's time for us to start really honing in on appropriate applications of these drugs, honing in on the right dose and what have you, because I definitely see some issues there.  Vamsi, this has just been terrific. I really want to thank you so much for sharing your fantastic insights with us today on the ASCO Daily News Podcast, and I really appreciate all your efforts to move the field of lung cancer forward. Dr. Vamsi Velcheti: Thanks, Monty. I really enjoyed the conversation. Dr. Monty Pal: Yeah, this was terrific.  And thanks to our listeners as well. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:     Dr. Monty Pal   @montypal  Dr. Vamsi Velcheti @VamsiVelcheti Follow ASCO on social media:          ASCO on X    ASCO on Bluesky         ASCO on Facebook          ASCO on LinkedIn          Disclosures:       Dr. Monty Pal:      Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview     Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical     Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Vamsi Velcheti:   Honoraria: Galvanize Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, AstraZeneca/MedImmune, GSK, Amgen, Taiho Oncology, Novocure, Regeneron, Takeda, Janssen Oncology, Picture Health Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline

Meet the Fantastic—and Controversial—Dr. David Healy Psychiatric Drug Companies-- What Are They NOT Telling Us? Today, we are thrilled to interview the famed and courageous Dr. David Healy. I have admired his work for many years, but never imagined I'd have the chance to meet him and chat with him. First things first. You may know Dr. David Healy for some of his highly controversial books, like "The Antidepressant Era," "Let Them Eat Prozac," and "Pharmageddon." But who is he, really? According to AI, Dr. David Healy is a prominent Welsh psychiatrist, psychopharmacologist, and critic of the pharmaceutical industry known for his research on antidepressants, their links to suicide, and exposing industry practices like ghostwriting and disease-mongering, operating through initiatives like RxISK.org to promote drug safety. He has a long history of challenging Big Pharma, facing academic backlash (like losing a University of Toronto post) for his views, and serving as an expert witness in legal cases involving psychotropic drugs, advocating for greater transparency and patient safety.  Healy initially worked with pharmaceutical companies, gaining firsthand knowledge of how SSRIs were marketed despite their trial weaknesses, focusing on the oversimplified serotonin hypothesis. He then became a vocal critic, highlighting issues like ghostwriting articles and manipulating academic opinion to sell drugs, leading to conflicts with industry-funded institutions. He founded RxISK.org, a platform for patients to report adverse drug reactions, aiming to make medicines safer. His strong stance (on research linking SSRI antidepressants to increased suicidal thoughts and urges) led to intense and corrosive controversy, including losing a professorship at the University of Toronto (though later settled as a visiting role) and harassment, noted here and here. In recent years, he has acted as an expert witness in cases involving drug-related suicides and homicides, bringing issues to regulators.  In essence, Dr. David Healy is a significant, often controversial, figure dedicated to drug safety, academic integrity, and patient awareness in psychiatry, challenging established narratives and industry power.  Taking a deeper dive, AI has added this critically important information: David Healy has discussed numerous examples of conflicts of interest that mainly involve the influence of the pharmaceutical industry on medical research, publication, and practice.  Key examples he has highlighted include: Ghostwriting of Articles: Pharmaceutical companies hire medical communication firms to draft research articles or reviews, and then get prominent academics or clinicians to put their names on the papers as the sole or primary authors, a practice known as ghostwriting. The named authors often have little to no involvement in the actual research or writing. Hiding or Misrepresenting Data: Drug companies have concealed unfavorable data or miscoded raw data on drug risks, such as the link between antidepressants and suicidal acts. This manipulation can make a drug appear safer or more effective than it actually is. Biased Clinical Trial Design: Healy notes instances where clinical trials are designed with "tricks," such as using inadequate or excessive doses of comparison medications to make the company's own drug look superior. Marketing-Driven Education: A large portion of continuing medical education (CME) classes for doctors are sponsored by industry. Healy argues this leads to a bias in the information presented to doctors, with an emphasis on the benefits of brand-name drugs rather than an objective assessment of all treatment options. Gifts and Payments to Physicians: Drug companies spend billions annually on marketing directed at doctors, including free samples, sales visits, and small non-educational gifts or lunches. Healy points out that while many doctors believe these gifts don't affect their own prescribing, studies show they influence prescribing patterns and create subtle biases. Industry Influence on Academia: Healy's own experience with a job offer being rescinded at the University of Toronto, which had received a large donation from a drug company (Eli Lilly), is a prominent case he uses to illustrate how industry funding can infringe upon academic freedom and stifle critical research. "Disease Mongering": Healy argues that the pharmaceutical industry often engages in "disease mongering," marketing conditions to the public and physicians to create a market for their products rather than simply addressing genuine medical needs.  So that hopefully gives you some idea of the scope of his work, and his vision of transparency and integrity in the reporting one the effectiveness and risks of psychotropic medications. In our conversation today, he emphasized the importance of listening to patients who describe side effects of medications, such as SSRIs, in described the efforts of Big Pharma to suppress such complaints, giving psychiatrists "talking points" to reassure and quiet concerned patients. In general, a main focus of his career has been to challenge and confront the efforts of drug companies to suppress negative information about their products and troublesome and dangerous side effects. He said that one of the rationales the drug companies use is to say that disseminating that type of information will discourage many potential patients from using their products, and therefore miss out on the potential benefits of the medications. In fact, they have a name for this, "treatment hesitancy," and discourage open discussion of negative effects for this reason. I asked Dr. Healy if he's experienced direct negative pushback from drug companies, and he gave a surprising answer—he said no, that the major pushback he's gotten has actually been from colleagues—psychiatrists who have bought the party line disseminated by the drug manufactures. For example, when he gave his famous talk at the University of Toronto on the increase in suicidal urges associated with SSRI antidepressants, a famous psychopharmacologist, Dr. Charlie Nemeroff, got him fired. Here's the story on Dr. Nemeroff, According to AI: In the late 2000s, Nemeroff faced investigations and sanctions from Emory University for failing to disclose significant speaking and consulting fees from pharmaceutical companies like GlaxoSmithKline, raising questions about research integrity and conflicts of interest, notes The BMJ and The New York Times.  Although the antidepressant effects of SSRIs are controversial and hotly debated, their effects on the nervous system are not. Dr. Healy's research indicates that they have a suppression effect on the nervous system, which dulls the senses, and this can happen within 1 to 2 days. One of the more troublesome of these effects is called "genital numbing," which affects 9 out of 10  people talking SSRIs. This can result in difficulties with sexual arousal and greatly delayed orgasm, and apparently these effects can persist long after drug discontinuation. He said that these sensory effects can develop quickly, within a day or two of starting the medications. Even more chilling, he said that the problem can actually get worse when you discontinue the medication, and can sometimes persist for life. In addition, quite a few individuals have "bad trips" on SSRIs, although a minority clearly have "good trips." He said the best thing to do for a bad trip is to take the patient off of the medication immediately—and NOT increase the dose. He confirmed my impression that a common error with all antidepressants is to increase the dose—which simply increases the side effects. In addition to the genital numbing described above, he said the SSRIs cause "emotional numbing," which means a decreased capacity for joy as well as sorrow. One of the main activities in David Healy's life has been listening to patients, rather than discounting their complaints when they describe negative effects of medications. When asked about what alternatives to drugs he might recommend to someone struggling with depression, he said that sometimes, just doing nothing will be helpful, since most mood problems clear up spontaneously in 12 to 14 weeks. He said that most are simply human problems, not "mental disorders," but real-life problems, like relationship conflicts or social issues. Although we did not discuss it extensively on the show, I would point out that skillful, drug-free therapy with TEAM CBT can sometimes help as well, and that recent research has confirmed rapid often dramatic mood improvements with individuals using the Feeling Great app, which has been entirely free to anyone since the summer of 2025.  Finally, we do not advise anyone to discontinue or modify the dosages of any medications you have been prescribed without consultation with your doctor. The information in the Feeling Good podcast is of a strictly educational nature, and is not intended as treatment or medical advice. We thank you for listening to today's shocking but incredibly important dialogue with one of the pioneers and champions of greater ethical integrity and transparency in the psychiatric profession. It is sad, indeed, that we don't have more visionary critical thinkers like Dr. David Healy! David (H), Rhonda, and David (B)

Over 1.5million adults in the UK tried weight loss drugs in 2024-25. Many swear by them, but they have been associated with side effects including nausea and, in some cases, extremely painful gallstones. But what does the evidence actually tell us, and what is the wider impact on the way we view our bodies in society?James Gallagher is joined by Professor of Cardiometabolic Medicine at the University of Glasgow Naveed Sattar, Dr Beverley O'Hara, Lecturer in Public Health Nutrition at Leeds Beckett University, and Dr Margaret McCartney, resident Inside Health GP. They discuss what the evidence tells us about the potential known side effects of these weight loss drugs, and the potential impact their use has on our view of obesity as a society. We also hear from Sarah Le Brocq, who has struggled with obesity all her adult life and has been on these drugs for the past 2-3 years about her experiences. Margaret McCartney has no conflicts of interest to declare.Beverley O'Hara has no conflicts of interest to declare. She has 2 roles with the Association for the Study of Obesity (voluntary academic positions).Naveed Sattar has consulted for and/or received speaker honoraria from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GlaxoSmithKline, Hanmi Pharmaceuticals, Kailera, Mass Medicines, Menarini-Ricerche, Metsera, Novo Nordisk, Pfizer, Regeneron, Roche, UCB Pharma, and Verdiva Bio; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche.Presenter: James Gallagher Producer: Hannah Fisher Researcher: Tom Hunt Production coordinator: Stuart Laws Content Editor: Ilan Goodman

Brett and Joel sincerely apologise (no we don't) for the dB-meter-breaking laughs that are audible throughout this episode (recorded earlier today). They're obviously very excited to be back in the studio after a 12 month hiatus. TRAINING WEEK Brett takes the listeners through his training week while shedding light on a recent glute-scare (previously only known to "FTK Friends of the Show) that (thankfully) is all but fully healed. Joel asks him why he chose not to head up the mountain to Falls Creek to join his training partners which leads to a long conversation on training smart and peaking at the right time of the year. To contradict training smart - Joel updates the listeners on where he's at and announces a high-pressure pacing gig for the end of Feb. BIG Q With the Pulse 5000m next month Brett & Joel answer a question that was asked at Tuesday evening's PTC workout regarding goal-time-strategy for the 12.5 laps of the track. GIVE SOME KUDOS Trying out a new personality in 2026, Joel decides to take the piss for the first GSK (don't sue us GlaxoSmithKline) of the year. Brett holds up the integrity of the segment by highlighting the upcoming Pulse 5000m. TWHSOITWTWATSA Joel kicks off the segment with a reel from a bloke completing a 5000m Strava run on the top of his fridge while Brett gets absolutely punk'd by his co-host in repeating a submission from last week. PULSE 5000M: ENTER HERE It's fantastic to be back on the airwaves - see you all next week :) SIGN UP TO OUR PATREON TODAY: www.patreon.com/forthekudos Instagram: https://www.instagram.com/forthekudos Facebook: https://www.facebook.com/forthekudos TikTok: https://www.tiktok.com/@forthekudos Brett: https://www.instagram.com/brett_robinson23 Joel: https://www.instagram.com/joeltobinblack

In this episode of the Vital Health Podcast, host Duane Schulthess speaks with two experts on evidence standards for early oncology access at ISPOR Europe 2025 in Glasgow, Scotland: Oriana Ciani: Associate Professor of Practice at SDA Bocconi School of Management Denis Lacombe: Director General at EORTC They discuss why accelerated pathways are used in oncology, what becomes feasible and risky when patient populations are small, how surrogate endpoints such as progression-free survival can differ from overall survival and quality of life, and why post-authorization evidence generation and treatment optimization shape whether early access translates into sustained patient benefit. Key Topics: Accelerated Approvals: Unmet need concepts, regulatory pathways, and access pressure in oncology. Rare Trial Design: Small populations, randomization feasibility, comparator constraints. Surrogate Endpoints: Progression-free survival, early-stage endpoints, evidence needed to validate surrogates. HTA Variation: Differing national standards, uncertainty handling, reimbursement timing effects. Treatment Optimization: Post-authorization evidence gaps, dose and duration questions, aligning evidence needs earlier. Opinions expressed are those of the speakers. This podcast was supported by Merck Sharp & Dohme as part of the APACE project, in collaboration with GlaxoSmithKline and AstraZeneca.See omnystudio.com/listener for privacy information.

In this episode of the Vital Health Podcast, host Duane Schulthess speaks with two experts on reimbursement-facing evidence questions for accelerated oncology approvals at ISPOR Europe 2025 in Glasgow, Scotland: Anja Schiel: Senior Advisor, Norwegian Medical Products Agency Niklas Hedberg: Chief Pharmacist at The Dental and Pharmaceutical Benefits Agency (TLV) They unpack why results that are strong inside a clinical trial can be harder to apply to real-world national populations, how decision-makers weigh patient-relevant outcomes and uncertainty at the time of access decisions, and what risk management can look like when early approvals require follow-up evidence and potential reassessment. Key Topics: Trial Generalizability: Selection in trials, real-world populations, and health system variation. Reimbursement Evidence: Patient-relevant outcomes, absolute versus comparative benefit, small-sample challenges. Conditional Approval: Evidence at authorization, reassessment expectations, withdrawal, and restriction risk. Risk Tradeoffs: Approving too early versus delaying access, urgency in progressive disease, and equity constraints. Adaptive Follow-up: Real-world evidence plans, managed entry approaches, learning while treating. Opinions expressed are those of the speakers. This podcast was supported by Merck Sharp & Dohme as part of the APACE project, in collaboration with GlaxoSmithKline and AstraZeneca.See omnystudio.com/listener for privacy information.

Dr. Hope Rugo and Dr. Vivek Subbiah discuss innovative trial designs to enable robust studies for smaller patient populations, as well as the promise of precision medicine, novel therapeutic approaches, and global partnerships to advance rare cancer research and improve patient outcomes. TRANSCRIPT  Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center [in Los Angeles]. The field of rare cancer research is rapidly transforming thanks to progress in clinical trials and treatment strategies, as well as improvements in precision medicine and next-generation sequencing that enable biomarker identification. According to the National Cancer Institute, rare cancers occur in fewer than 150 cases per million each year, but collectively, they represent a significant portion of all cancer diagnoses. And we struggle with the appropriate treatment for these rare cancers in clinical practice. Today, I am delighted to be joined by Dr. Vivek Subbiah, a medical oncologist and the chief of early-phase drug development at the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Subbiah is the lead author of a paper in the ASCO Educational Book titled "Designing Clinical Trials for Patients with Rare Cancers: Connecting the Zebras," a great title for this topic. He will be telling us about innovative trial designs to enable robust studies for small patient populations, the promise of precision medicine, and novel therapeutic approaches to improve outcomes, and how we can leverage AI now to enroll more patients with rare cancers in clinical trials. Our full disclosures are available in the transcript of this episode.  Dr. Subbiah, it is great to have you on the podcast today. Thanks so much for being here. Dr. Vivek Subbiah: Thank you so much, Dr. Rugo, and it is an honor and pleasure being here. And thank you for doing this podcast for rare cancers. Dr. Hope Rugo: Absolutely. We are excited to talk to you. And congratulations on this fantastic paper. It is such a great resource for our community to better understand what is new in the field of rare cancer research. Of course, rare cancers are complex and multifaceted diseases. And this is a huge challenge for clinical oncologists. You know, our clinics, of course, cannot be designed as we are being very uni-cancer focused to just be for one cancer that is very rare. So, oncologists have to be a jack of all trades in this area. Your paper notes that there are approximately 200 distinct types of rare and ultra-rare cancers. And, by definition, all pediatric cancers are rare cancers. Of course, clinical trials are essential for developing new treatment strategies and improving patient outcomes, and in your paper, you highlight some unique challenges in conducting trials in this rare cancer space. Can you tell us about the challenges and how really innovative trial designs, I think a key issue, are being tailored to the specific needs of patients with rare cancer and, importantly, for these trials? Dr. Vivek Subbiah: Rare cancers present a perfect storm of challenges. First, the patient populations are very small, which makes it really hard to recruit enough participants for traditional type trials. Second, these patients are often geographically dispersed across multiple cities, across multiple states, across multiple countries, across multiple zip codes. So, logistics become complicated. Third, there is often limited awareness among clinicians, which delays referrals and diagnosis. Add to that regulatory hurdles, funding constraints, and you can see why rare cancer trials are so tough to execute. To overcome these barriers, we are seeing some really creative novel trial designs. And there are four different types of trial designs that are helping with enrolling patients with rare cancers. The first one is the basket trial. So let us talk about what basket studies are. Basket studies group patients based on shared genetic biomarkers or shared genetic mutations rather than tumor type. So instead of running separate 20 to 30 to 40 trials, you can study one therapy across multiple cancers. The second type of trial is the umbrella trial. The umbrella trials flip that concept of basket studies. They focus on one cancer type but test multiple targeted therapies within it. The third category of innovative trials are the platform studies. Platform trials are another exciting innovation. They allow new treatment arms to be added or removed as the data matures and as the data evolves, making trials more adaptive and efficient. The final category are decentralized tools in traditional trials, which are helping patients participate closer to where they are so that they can sleep in their own bed, which is, I think, a game changer for accessibility.  These designs maximize efficiency and feasibility for rare cancer research and rare cancer clinical trials. Dr. Hope Rugo: I love the idea of the platform trials that are decentralized. And I know that there is a trial being worked on with ARPA-H (Advanced Research Projects Agency for Health) funding in triple-negative breast cancer as well as in lung cancer, I think, and others with this idea of a platform trial. But it is challenged, I think, by precision medicine and next-generation sequencing where some patients do not have targetable markers, or there isn't a drug to target the marker. I think those are almost the same thing. We have really seen that these precision medicine ideas and NGS have moved the needle in helping to identify genetic alterations. This helps us to be more personalized. It actually helps with platform studies to customize trial enrollment. And we hope that this will result in better outcomes. It also allows us, I think, to study drugs even in the early stage setting more effectively. How can these advances be best applied to the future of rare cancers, as well as the challenges of not finding a marker or not having a drug? Dr. Vivek Subbiah: Thank you so much for that question. I think precision medicine and next-gen sequencing, or NGS, are truly the backbone of modern precision oncology. They have transformed how we think about cancer treatment. Instead of treating based on where the tumor originated or where the tumor started, we now look at the genetic blueprint of cancer. The NGS or next-gen sequencing allows us to sequence millions of DNA fragments quickly. Twenty, 30 years ago, they said we cannot sequence a human genome. Then it took almost a decade to sequence the first human genome. Right now, we have academic centers and commercial sequencing companies that are really democratizing NGS across all sites, not just in academic centers, across all the community sites, so that NGS is now accessible. This means that we can identify these actionable alterations like picking needles in haystacks, like NTRK fusions, RET fusions, or BRAF V600E alterations, high tumor mutational burden. This might occur across not one tumor type, across several different tumor types. So for rare cancers, this is critical because some of these mutations often define the best treatment option. Here is why this matters. Personalized therapy, right? Instead of a one-size-fits-all approach, we can tailor treatment to the patient's unique molecular profile. For trial enrollment, this can definitely help because patients can join biomarker-driven trials even if their cancer type is rare or ultra-rare. NGS technology has also helped us in designing rational studies. Many times monotherapy does not work in these cancers. So we are thinking about rational combination strategies. So NGS technology is helping us. Looking ahead, I see NGS becoming routine in clinical practice, not just at major niche academic centers, but everywhere. We will see more tumor-agnostic approvals, more molecular tumor boards guiding treatment decisions in real time. And I think we are seeing an expanded biomarker setup. Previously, we used to have only a few drugs and a handful of mutations. Now with homologous recombination defects, BRCA1/2 mutation, and expanding the HRD and also immunohistochemistry, we are expanding the biomarker portfolio. So again, I personally believe that the future is precision. What I mean by precision is delivering the right drug to the right patient at the right time. And for rare cancers, this isn't just progress. It is survival. And it is maybe the only way that they can have access to these cutting-edge precision medicines. Dr. Hope Rugo: That is so important. You mentioned an important area we will get to in a moment, the tumor-agnostic therapies. But as part of talking about that, do you think that the trials should also include just standard therapies? You know, who do you give an ADC to and when with these rare cancers? Because some of them do not have biomarkers to target and it is so disappointing for patients and providers where you are trying to screen a patient for a trial or a platform trial where you have one arm with this mutation, one arm with that, and they do not qualify because they only have a p53 loss, you know? They just do not have the marker that helps them. But we see this in breast cancer all the time. And it is tough because we don't have good information on the sequencing. So I wonder, you know, just because for some of these rare cancers it is not even clear what to use when with standard treatments. And then that kind of gets into this idea of the tumor-agnostic therapies that you mentioned. There are a lot of new treatments that are being evaluated. We have seen approval of some treatments in the last few years that are tumor-agnostic and based on a biomarker. Is that the best approach as we go forward for rare cancers? And what new treatment options are most exciting to you right now? Dr. Vivek Subbiah: Tumor-agnostic therapies, really close to my heart, are real breakthrough therapies and represent a major paradigm shift in oncology. Traditionally, for the broad listeners here, we are used to thinking about designing clinical trials and therapy like where the cancer originated, breast cancer, kidney cancer, prostate cancer, lung cancer. A tumor-agnostic therapy flips that model. Instead of focusing on the organ, they target the specific genetic alteration or biomarker that drives cancer growth regardless of where the tumor started, regardless of the location of the tumor, regardless of the zip code of the tumor. So why is this so important for rare cancers? Because many rare cancers share molecular features with more common cancers. For instance, NTRK fusion might occur in pediatric sarcoma, a salivary gland tumor, or a thyroid cancer. Historically, each of these would require separate trials, which is nearly impossible, unfeasible to conduct in these ultra-rare cancers like salivary gland cancer or pediatric sarcomas. Tumor-agnostic therapies allow us to treat all those cancers with the same targeted drug if they share that biomarker. Again, we are in 2025. The first tissue-agnostic approval, the historic precedent, was in fact an immunotherapy. Pembrolizumab was approved in 2017, May 2017, as the first immunotherapy to be approved in a tumor-agnostic way for a genomic biomarker, for MSI-High and dMMR cancers. Then came the NTRK inhibitors. So today we have not one, not two, but three different NTRK inhibitors: larotrectinib, entrectinib, and repotrectinib, which show response rates of nearly more than 60 to 75% across a handful of dozens and dozens of cancer types. Then, of course, we have RET inhibitors like selpercatinib, which is approved tissue-agnostic, and pralsetinib, which also shows tissue-agnostic activity across multiple cancers. And more recently, combination therapy with a BRAF and MEK combination, dabrafenib and trametinib, received tumor-agnostic approval for all BRAF V600E tumors with the exception of colorectal cancer. And even recently, you mentioned about antibody drug conjugates. Again, I think we live in an era of antibody drug conjugates. And Enhertu, trastuzumab deruxtecan, which was used first in breast cancer, now it is approved in a histology-agnostic manner for all HER2-positive tumors defined by immunohistochemistry 3+. So again, beyond NGS, now immunohistochemistry for HER2 is also becoming a biomarker. So again, for the broad listeners here, in addition to comprehensive NGS that may allow patients to find treatment options for these rare cancers for NTRK, RET, and BRAF, immunohistochemistry for HER2 positivity is also emerging as a biomarker given that we have a new FDA approval for this. So I would say personally that these therapies are game changers because they open doors for patients who previously had no options. Instead of waiting for years for a trial in their specific cancer type, they can access a treatment based on their molecular profile. I think it is precision medicine at its finest and best. Looking ahead, the third question you asked me is what is exciting going on? I think we will see more of these approvals. My hope is that today, I think we have nine to ten approvals. My hope is that within the next 25 to 50 years, we will have at least 50 to 100 drugs approved in this space based on a biomarker, not based on a location of the tumor type. Drug targeting rare alterations like FGFR2 fusions, FGFR amplifications, ALK fusions, and even complex signatures like high tumor mutational burden. I think we will be seeing hopefully more and more drugs approved. And as sequencing becomes routine, we will identify more patients for these therapies. I think for rare cancers, this is not just innovative approach. This is essential for them to access these novel precision medicines. Dr. Hope Rugo: Yeah, that is such a good point. I do think it is critical. Interestingly in breast cancer, it hasn't been, you know, there is always like two patients in these tumor-agnostic trials, or if that. You know, I think I have seen one NTRK fusion ever. I think that highlights the importance for rare cancers. And you know, I am hoping that that will translate into some new directions for some of our rarer and impossible-to-treat subtypes of breast cancer. It is this kind of research that is really going to make a difference. But what about those people who do not have biomarkers? What if you do not fit into that? Do you think there is a possibility of trying to do treatments for rare cancers in some prospective way that would help with that? You know, it is really a huge challenge. Dr. Vivek Subbiah: Absolutely. I think, you know, you're right, usually many of these rare cancers are driven by specific biomarkers. And again, some of the pediatric salivary gland tumors or pediatric sarcomas like fibrosarcomas, they are pathognomonic with NTRK fusions. And again, given that we have a tumor-agnostic approval, now these patients have access to these therapies. And I do not think that we would have had a trial just for pediatric fibrosarcomas with NTRK fusions. So that is one way. Another way is SWOG, right? The SWOG DART [1609] had this combination dual checkpoint, it was called the DART study dual combination chemotherapy with ipi/nivo. Now here the rare cancer subtype itself becomes a biomarker and they showed activity across multiple rare cancer subtypes. They didn't require a biomarker. As long as it was a rare or ultra-rare cancer, these patients were enrolled into the SWOG DART trial and multiple arms have read out. Angiosarcoma, Kaposi sarcoma, even gestational trophoblastic disease. Again, they have shown responses in these ultra-rare, rare cancers. Sometimes they might be seeing one or two cases a whole year. And I think this SWOG effort, this cooperative group effort, really highlighted the need for such studies without biomarkers as well. Dr. Hope Rugo: That is such a fantastic example of how to try and treat patients in a collaborative way. And in the paper, you also emphasize the need for collaborative research efforts, you know, uniting resource expertise across different ways of doing research. So cooperative groups, advocacy organizations that can really help advance rare cancer research, improve access to new therapies, and I think importantly influence policy changes. I think this already happened with the agnostic approvals. Could you tell us more about that? How can we move forward with this most effectively? Dr. Vivek Subbiah: Personally, I believe that collaboration is absolutely critical and essential for rare cancer research. No single institution, no single individual, or no single state or entity can tackle these challenges alone. The patient populations are small and dispersed. So pooling resources is the only way to run these meaningful trials. Again, it is not like singing, it is like putting a huge, huge, I would say, an opera piece together. It is not a solo, vocal therapy, but rather putting a huge opera piece like Turandot. You know, you mentioned cooperative groups. Cooperative groups, as I mentioned earlier, the SWOG DART program, the ASCO [TAPUR study]. ASCO is doing a phenomenal work of the TAPUR study. Again, this ASCO TAPUR program has enrolled so many patients with rare cancers who otherwise would not have treatment options. NCI-MATCH, the global effort, right? NCI-MATCH and the ComboMATCH are great examples. They bring together hundreds of sites, thousands of clinicians to run large-scale trials that would be impossible for any individual center or institution. These trials have already changed practice. For instance, the DART demonstrated the power of immunotherapy in rare cancers and influenced NCCN guidelines. One of the arms of the NCI-MATCH study from the BRAF V600E arm contributed towards the BRAF V600E tissue-agnostic approval. So, the BRAF V600E tissue-agnostic approval was by a pooled analysis of several studies. The ROAR study, the Rare Oncology Agnostic Research study, the NCI-MATCH dataset of tumor-agnostic cohort, and another pediatric trial, and also evidence from literature and evidence of case reports. And all this pooled analysis contributed to the tissue-agnostic approval of BRAF V600E across multiple rare cancers. There are several patient advocacy organizations which are the real unsung heroes here. Groups like, for instance, we mentioned in the paper, Target Cancer Foundation, don't just raise awareness for rare cancer research, they actively connect patients to trials providing financial, emotional support, and even run their own studies like the TRACK trial. They also influence policy to make access easier. On a global scale, initiatives like DRUP in the Netherlands, the ROME study in Italy, the PCM4EU in Europe are expanding precision medicine across these borders. These collaborations accelerate research, improve trial enrollment, and ensure patients everywhere can have access to these cutting-edge therapies. Again, it is truly a team effort, right? It is a multi-stakeholder approach. Researchers, clinicians, investigators, industry, regulators, academia, patients, patient advocates, and their caregivers all working together. And it takes a village. Dr. Hope Rugo: Absolutely. I mean, what a nice response to that. And I think really exciting and it is great to see your passion about this as well. But it helps all of us, I think, getting discouraged in treating these cancers to understand what is happening moving forward. And I think it is also a fabulous opportunity for our junior colleagues as they rise up in academics to be involved in these international collaborative efforts which are further expanding. One of the things that comes up for clinical trials for patients, and I think it is highlighted with rare cancers because, as you mentioned, people are all over the place, you know, they are so rare. They are all far away. Our patients are always saying to us, "Should I go here for a phase 1 trial?" Can you talk a little bit about how we can overcome these financial and geographic burdens for the patients? You talked about having trials locally, but it is a big financial and just social burden for patients. Dr. Vivek Subbiah: Great point. Financial cost is a major barrier in rare cancer clinical trials. It is a major barrier not just in rare cancer clinical trials, but in clinical trials in general. The economics of rare cancer research are one of the toughest challenges we face. Developing a new drug is already expensive, often billions of dollars. On an average, it takes 2 billion dollars or 2.8 billion dollars according to some data from drug discovery to approval. For rare cancers, the market is tiny, which means the pharmaceutical companies have really little financial incentive to invest. That is why initiatives like the Orphan Drug Act were created to provide tax credits, grants, and market exclusivity to encourage development for rare diseases. Clinical trials themselves are expensive because the small patient populations mean longer recruitment times and higher per-patient costs. Geographic dispersion, as you mentioned, for the patients adds travel, coordination. That is why we need to think out of the box about decentralized trial infrastructure so that we can mitigate some of these expenses. Complex trial designs like basket or platform trials sometimes require sophisticated data systems and regulatory oversight. That is a challenge. And I think some of the pragmatic studies like ASCO TAPUR have overcome those challenges. Advanced technologies like next-gen sequencing and molecular profiling also add significant upfront cost to this. Funding is also limited because rare cancers receive less attention compared to common cancers. Public funding and cooperative group trials help a lot, but I think they cannot cover everything. Patient advocacy organizations sometimes step in to bridge these gaps, but sustainable financing remains a huge challenge. So, the bottom line is without financial incentives and collaborating funding models, many promising therapies for rare cancers would never make it to patients. That is why we need system-wide policy changes, global partnerships, and innovative, effective, seamless trial designs which are so critical so that they can help reduce the cost and make research feasible so that we can deliver the right drug to the right patient at the right time. Dr. Hope Rugo: There is a lot of excitement about the future integration of AI in screening. Just at the San Antonio Breast Cancer meetings, we have a number of different presentations about AI to find markers, even like HER2, and using AI where you would screen and then match patients to clinical trials. Do you have any guidance for the rare cancer community on how to leverage this technology in order to optimize patient enrollment and, I think, identification of the best treatment matches? Dr. Vivek Subbiah: I think artificial intelligence, AI, is a game-changer in the making. Right now, clinical trial is clunky. Matching patients to trial is often manual, time consuming, laborious. You need a lot of personnel to do that. AI can automate this process by analyzing genomic data, medical records, and trial eligibility criteria to find the best matches quickly, accurately, and effectively. For the community, the key is to invest in data standardization and interoperability because AI needs clean, structured data to work effectively. Dr. Hope Rugo: Thank you so much, Dr. Subbiah, for sharing these fantastic insights with us on the podcast today and for your excellent article. Dr. Vivek Subbiah: Thank you so much. Dr. Hope Rugo: We thank you, our listeners, for joining us today. You will find a link to Dr. Subbiah's Educational Book article in the transcript of this episode. And please join us again next month on By the Book for more insightful views on key issues and innovations that are shaping modern oncology.  Thank you. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:        Dr. Hope Rugo   @hoperugo   Dr. Vivek Subbiah @VivekSubbiah Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:       Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx   Dr. Vivek Subbiah: Consulting/Advisory Role: Loxo/Lilly, Illumina, AADI, Foundation Medicine, Relay Therapeutics, Pfizer, Roche, Bayer, Incyte, Novartis, Pheon Therapeutics, Abbvie Research Funding (Inst.): Novartis, GlaxoSmithKline, NanoCarrier, Northwest Biotherapeutics, Genentech/Roche, Berg Pharma, Bayer, Incyte, Fujifilm, PharmaMar, D3 Oncology Solutions, Pfizer, Amgen, Abbvie, Mutlivir, Blueprint Medicines, Loxo, Vegenics, Takeda, Alfasigma, Agensys, Idera, Boston Biomedical, Inhibrx, Exelixis, Amgen, Turningpoint Therapeutics, Relay Therapeutics Other Relationship: Medscape, Clinical Care Options

In this episode of the Vital Health Podcast, host Duane Schulthess speaks with three experts on accelerated patient access to cancer medicines at ISPOR Europe 2025 in Glasgow, Scotland: Martina Garau: Director at Office of Health Economics Bettina Ryll: Founder at MPNEurope Kathleen Grieve: Director - European Public Policy, Access, Pricing and Affordability Lead at MSD Europe They explore why accelerated access matters when evidence is still emerging, how the APACE framework proposes a structured path from eligibility through reassessment, what it could take to reduce fragmentation across national HTA and reimbursement processes, and why pragmatic pilots and agreed data expectations are central to learning while treating. Key Topics: Accelerated Access: Urgency in life-threatening cancer, uneven uptake across countries, and patient time sensitivity. APACE Framework: Eligibility screening, initial assessment, temporary reimbursement, reassessment, and exit decisions. National Alignment: EU-level assessment versus country decisions, shared principles, local implementation limits. Evidence Uncertainty: Early evidence tradeoffs, real-world data needs, and affordability pressure under uncertainty. Getting Started: Pilot use cases, coalition of the willing, dynamic evidence expectations over time. Opinions expressed are those of the speakers. This podcast was supported by Merck Sharp & Dohme as part of the APACE project, in collaboration with GlaxoSmithKline and AstraZeneca.See omnystudio.com/listener for privacy information.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today we're diving into a landscape rich with scientific advancements, strategic industry shifts, and regulatory developments that are shaping the future of healthcare.Let's start with AstraZeneca's recent success in the lupus treatment field. Their Phase 3 clinical trial for a self-administered subcutaneous form of Saphnelo marks a significant milestone. This new administration route could enhance patient convenience and accessibility, positioning AstraZeneca favorably against competitors like GlaxoSmithKline's Benlysta. The move underscores a growing trend in the industry towards more patient-friendly drug delivery systems, which could revolutionize treatment adherence and outcomes for autoimmune diseases.Turning our attention to Argenx, the company is navigating a pivotal leadership transition following the launch of Vyvgart, their autoimmune drug. This shift highlights the company's strong footing in the market after successfully obtaining regulatory approval and introducing Vyvgart. The potential expansion of its reach could further solidify Argenx's standing in the competitive autoimmune sector.Alumis is also making waves with its TYK2 inhibitor for psoriasis treatment, having reported promising Phase 3 data. This development places it as a formidable contender to Bristol Myers Squibb's Sotyktu. The positive trial results have not only boosted Alumis' stock value but also reflect a broader interest in immunomodulatory treatments which offer patients alternative therapeutic options with potentially fewer side effects.In an innovative leap within obesity management, Arrowhead Pharmaceuticals is advancing its dual gene-silencing assets aimed at reducing fat. Early-phase data indicates promising results, highlighting gene therapy's potential as a viable strategy for tackling complex conditions like obesity. This approach could pave the way for more personalized and effective treatments, aligning with the industry's gradual shift towards precision medicine.On the regulatory front, there's been notable movement with significant updates affecting drug approvals and recommendations. The Centers for Disease Control and Prevention's decision to remove six vaccines from the recommended childhood immunization schedule has stirred controversy due to its opaque review process. Such decisions carry profound implications for public health policies and vaccine uptake, sparking debates about safety and transparency.Meanwhile, GlaxoSmithKline's Exdensur has gained approval in Japan for two new indications, showcasing efforts to expand existing drugs' therapeutic applications across different markets. However, Sanofi has faced hurdles with the FDA rejecting its multiple sclerosis drug due to serious safety concerns, including liver injury risks. This rejection underscores the delicate balance regulatory bodies must maintain between efficacy and safety when evaluating new therapeutics.Amgen's strategic acquisition of a UK biotech firm for up to $840 million exemplifies ongoing industry consolidation trends. By integrating preclinical blood cancer programs into its portfolio, Amgen aims to strengthen its oncology pipeline—a critical area in today's competitive cancer treatment landscape. Similarly, Roche has strategically invested $100 million in a licensing deal with Structure Therapeutics to secure its position within the GLP-1 therapeutics sphere for metabolic disorders.These strategic acquisitions and partnerships highlight an industry focused on bolstering pipelines through external collaborations—essential for maintaining competitive edges in high-stakes therapeutic areas like oncology and metabolic disorders. As companies endeavor to innovate while ensuring safety, their efforts promise to enhance patient care by addressing unmet mSupport the show

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. As we close out the year 2025, it's clear that the pharmaceutical and biotech industries have experienced a period of significant transformation. This year has been marked by groundbreaking drug approvals, strategic partnerships, and a focus on innovative therapies that promise to redefine patient care.One of the standout achievements this year comes from GlaxoSmithKline, which received approval from the U.S. FDA for its ultra-long-acting biologic, Exdensur, aimed at treating severe asthma with an eosinophilic phenotype in adolescents and adults. This approval underscores the growing trend toward personalized medicine and biologics, offering new hope for patients with chronic respiratory conditions by providing more sustainable and personalized treatment options.In the oncology sector, Merck's Keytruda and Astellas Pharma's Padcev have demonstrated significant overall survival benefits when used as perioperative treatments for cisplatin-eligible muscle-invasive bladder cancer. This combination therapy of a PD-1 checkpoint inhibitor and an antibody-drug conjugate highlights the evolving landscape of cancer treatment, emphasizing the role of immunotherapy and targeted therapies in improving patient outcomes in challenging cancer subtypes.However, not all developments have been positive. Hansa Biopharma faced challenges with its kidney transplant drug, imlifidase. Despite success in kidney transplant trials, it failed to achieve desired results in treating anti-glomerular basement membrane disease. This serves as a reminder of the complexities involved in drug repurposing efforts within autoimmune diseases.Alnylam Pharmaceuticals announced a significant investment to enhance its Norton, Massachusetts facility into a dedicated site for small interfering RNA (siRNA) production. This move reflects the industry's shift towards RNA-based therapies that offer targeted gene-silencing capabilities and positions Alnylam at the forefront of RNAi therapeutics production.In another promising development, ImmunityBio reported positive data from its QUILT-3.032 study on Anktiva for BCG-unresponsive non-muscle-invasive bladder cancer with high-grade papillary disease. The potential expansion of Anktiva's use reinforces the importance of personalized immunotherapies in oncology.The launch of Ambros Therapeutics with $125 million in Series A funding highlights efforts to develop non-opioid pain medications already approved abroad. This initiative addresses chronic pain management without relying on opioids, potentially advancing analgesic therapies amidst the ongoing opioid crisis.In China, Fosun Pharma's acquisition of a majority stake in Green Valley Pharmaceuticals aims to revive a controversial seaweed-derived Alzheimer's medication. Despite skepticism over its efficacy, this investment signals continued innovation efforts amid growing demand for effective Alzheimer's treatments.Siemens Healthineers' partnership with Alzpath to incorporate pTau-217 antibodies into its Atellica immunoassay platforms marks a significant step forward in Alzheimer's diagnostics. This collaboration aims to enhance biomarker detection capabilities crucial for early diagnosis and intervention strategies in neurodegenerative diseases.On the strategic front, Bristol Myers Squibb entered into a substantial research agreement with Harbour BioMed valued at up to $1.1 billion. This deal underscores Big Pharma's ongoing pursuit of alliances to advance therapeutic pipelines and antibody technologies.Finally, Cencora's acquisition of OneOncology for $5 billion underscores consolidation trends within specialty practice networks. By valuing OneOncology at $7.4 billion, this acquisition reflects the growing importance of integrated oncology care models and collaborative netSupport the show

For our last episode of the year, we're pleased to welcome back to the podcast Justin Ergler. Justin is a consultant focused on legal operations, outside counsel management, and client value strategy. Listeners may know Justin from his work at GlaxoSmithKline, where he pioneered the award-winning Outside Counsel Selection Initiative and led the company's global transition away from the billable hour to non-hourly, value-based fee arrangements. Justin also co-founded the Legal Value Network and continues to serve as a board member. Additionally, Justin is co-host of the podcast Off the Clock with Keith Maziarek. Justin and Keith had previously joined us for a two-part discussion in May. Today, Justin returns for a one-on-one conversation about finding the procurement path, why he values being part of a team, helping law firms tackle the challenges of data, and his thoughts on generative AI's impact on legal services pricing. We will be off the next two weeks. Happy holidays to all our listeners and thank you for another great year! We will return January 7 with a new episode. Read the full transcript of today's episode here: https://www.seyfarth.com/dir_docs/podcast_transcripts/Pioneers_JustinErgler.pdf

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into the exciting, yet challenging, landscape of gene therapies and their potential to revolutionize healthcare. Recent scientific advancements have pushed the boundaries of what's possible, offering potential lifetime cures for diseases once considered incurable. However, this breakthrough comes with a significant economic caveat: the staggering cost of these therapies, often ranging between $3 to $4 million per patient. This price tag presents a formidable challenge to current healthcare infrastructures.The disconnect between these innovative treatments and existing payment systems is evident in what industry experts term the "$4 million payment problem." Therapies like Lenmeldy and Hemgenix highlight this issue. Lenmeldy, for instance, can prevent metachromatic leukodystrophy with a single infusion priced at $4.25 million, while Hemgenix offers a cure for hemophilia B at $3.5 million. These therapies effectively convert lifelong treatment costs into a singular, substantial payment, challenging traditional insurance models that are built to spread costs over time.The primary obstacle is not the efficacy of these treatments but rather the financial and logistical infrastructures needed to support them. The current insurance model is ill-equipped to handle such large, one-time payments. Employers who often provide health insurance face a dilemma: investing millions in curing an employee who might leave the company shortly after receiving treatment could result in significant financial risk and disincentivizes employers from covering such therapies.Enter Aradigm Health, which has emerged as a potential solution to this conundrum. Aradigm aims to create an "infrastructure layer" specifically for these high-cost cures. With $20 million in funding backing their initiative, Aradigm seeks to pool financial risk across multiple employers, thus mitigating the impact of substantial individual claims. Their model involves employers contributing a fixed monthly fee into a shared fund that covers these expensive treatments when needed. This approach distributes financial volatility across a broader base rather than placing it on individual employers.Aradigm's strategy is not only about financial solutions but also about streamlining logistical complexities associated with delivering gene therapies. Their patient journey management includes coordinating with biotech companies for manufacturing schedules, arranging travel and accommodation for patients and families, and ensuring seamless insurance paperwork handling. This comprehensive support system reduces barriers that often delay or disrupt treatment delivery.Operating as a public benefit corporation with a "cost-plus" model, Aradigm ensures that any surplus from lower-than-expected claims is returned to employers rather than kept as profit. This aligns incentives towards patient care rather than profit maximization. Their approach highlights a critical need within the biotech and pharmaceutical industries: developing adaptable infrastructures that align with rapid scientific advancements.Meanwhile, Amgen has secured significant ground in 2023 with its second FDA approval for Uplizna in treating generalized myasthenia gravis—a chronic autoimmune neuromuscular disorder characterized by varying degrees of skeletal muscle weakness. Uplizna's mechanism involves targeting CD19 on B cells implicated in autoimmune diseases' pathogenesis. This expansion marks an advancement in therapeutic options for patients and underscores Amgen's growing footprint in treating complex autoimmune conditions.GlaxoSmithKline has also made headlines with Blujepa, marking it as the first new class of antibiotics for gonorrhea in over three decades while receiving approval for treating uncomplicSupport the show

Ever wondered what happens when you take the leadership lessons from flying military helicopters and apply them to corporate America? In this conversation with Carl Sharperson Jr., author of "Sharp Leadership" and former Marine Corps pilot, Cam and Otis explore the fascinating transition from military service to business leadership."The plant ran better with us not being there than it did when we were there," Carl reveals, sharing a powerful story about what happened when all the managers went on a two-day retreat. This counterintuitive insight highlights one of Carl's core leadership principles: when you truly empower your people with the right tools and resources, they'll often exceed your expectations.What makes this episode particularly valuable is Carl's candid reflection on his own leadership journey. "My team leader pulled me aside one day and said, 'Carl, you're micromanaging, you don't need to do that,'" he shares, explaining how this direct feedback helped him "flip the script" and transform his approach. From discussing the delicate balance of allowing people to fail without catastrophic consequences to exploring how he applied leadership principles as an entrepreneur, Carl offers practical wisdom drawn from his unique experience across military, corporate, and entrepreneurial settings.Whether you're transitioning from one leadership context to another or simply looking to elevate your team from mediocrity to excellence, Carl's insights on building relationships and taking care of your people provide a roadmap for authentic, effective leadership.More About Carl:Carl Sharperson Jr. is a renowned Leadership Innovation Strategist, speaker, and coach, celebrated for his ability to elevate leaders from mediocrity to their fullest potential in both professional and personal realms. He is the acclaimed author of Sharp Leadership: Overcome Adversity to Lead with Authenticity and Sharp Leadership: Parenting Principles for Rearing Young People. Carl's expertise lies in recognizing that many individuals operate at only 50% capacity due to inadequate leadership, development, or job fit. Through his proprietary Sharp Leadership coaching process, combined with his rich experiences in the military, corporate America, and entrepreneurship, Carl delivers transformative results for his audiences and corporate clients. A proud graduate of the United States Naval Academy and a former United States Marine Corps pilot with a BS in Engineering, Carl has also documented his military experiences in Short Rations for Marines and For My Sons and Brothers. Following his distinguished military service, Carl held senior sales and operational positions at prestigious companies such as Procter & Gamble, Frito-Lay, and Colgate-Palmolive. He was Vice President of Manufacturing for an international sports company before answering the call to entrepreneurship in 2000, launching Sharperson's Executive Leadership. Carl has since worked with executives at major organizations, including Purdue Farms, Harley-Davidson, GlaxoSmithKline, Sara Lee, BMW, Edward Jones, Houston Independent School District, Lockheed Martin, Honeywell, the University of North Carolina, and Chick-fil-A, among others. As a dynamic speaker, Carl travels nationwide, inspiring students to explore military training, sharing his triumphant journey of surviving Stage 4 Non-Hodgkin's Lymphoma and Stage 1 Colon cancer, and empowering leaders with the principles of servant leadership. Dedicated to giving back, Carl actively participates in several community and faith-based initiatives, mentoring youth and helping them reach their maximum potential. He resides in the Upstate of South Carolina with his wife, and they are proud parents of a son and a daughter. If you are ready to elevate your team from mediocrity to excellence, book Carl Sharperson Jr. today.Chapter Times and Titles:From CH-46 to Corporate America [00:00 - 05:00

Dr. Linda Duska and Dr. Kathleen Moore discuss key studies in the evolving controversy over radical upfront surgery versus neoadjuvant chemotherapy in advanced ovarian cancer. TRANSCRIPT Dr. Linda Duska: Hello, and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Linda Duska. I am a professor of obstetrics and gynecology at the University of Virginia School of Medicine.  On today's episode, we will explore the management of advanced ovarian cancer, specifically with respect to a question that has really stirred some controversy over time, going all the way back more than 20 years: Should we be doing radical upfront surgery in advanced ovarian cancer, or should we be doing neoadjuvant chemotherapy? So, there was a lot of hype about the TRUST study, also called ENGOT ov33/AGO-OVAR OP7, a Phase 3 randomized study that compares upfront surgery with neoadjuvant chemotherapy followed by interval surgery. So, I want to talk about that study today. And joining me for the discussion is Dr. Kathleen Moore, a professor also of obstetrics and gynecology at the University of Oklahoma and the deputy director of the Stephenson Cancer Center, also at the University of Oklahoma Health Sciences.  Dr. Moore, it is so great to be speaking with you today. Thanks for doing this. Dr. Kathleen Moore: Yeah, it's fun to be here. This is going to be fun. Dr. Linda Duska: FYI for our listeners, both of our full disclosures are available in the transcript of this episode.  So let's just jump right in. We already alluded to the fact that the TRUST study addresses a question we have been grappling with in our field. Here's the thing, we have four prior randomized trials on this exact same topic. So, share with me why we needed another one and what maybe was different about this one? Dr. Kathleen Moore: That is, I think, the key question. So we have to level-set kind of our history. Let's start with, why is this even a question? Like, why are we even talking about this today? When we are taking care of a patient with newly diagnosed ovarian cancer, the aim of surgery in advanced ovarian cancer ideally is to prolong a patient's likelihood of disease-free survival, or if you want to use the term "remission," you can use the term "remission." And I think we can all agree that our objective is to improve overall survival in a way that also does not compromise her quality of life through surgical complications, which can have a big effect. The standard for many decades, certainly my entire career, which is now over 20 years, has been to pursue what we call primary cytoreductive surgery, meaning you get a diagnosis and we go right to the operating room with a goal of achieving what we call "no gross residual." That is very different – in the olden days, you would say "optimal" and get down to some predefined small amount of tumor. Now, the goal is you remove everything you can see.  The alternative strategy to that is neoadjuvant chemotherapy followed by interval cytoreductive surgery, and that has been the, quote-unquote, "safer" route because you chemically cytoreduce the cancer, and so, the resulting surgery, I will tell you, is not necessarily easy at all. It can still be very radical surgeries, but they tend to be less radical, less need for bowel resections, splenectomy, radical procedures, and in a short-term look, would be considered safer from a postoperative consideration. Dr. Linda Duska: Well, and also maybe more likely to be successful, right? Because there's less disease, maybe, theoretically. Dr. Kathleen Moore: More likely to be successful in getting to no gross residual. Dr. Linda Duska: Right. Yeah, exactly. Dr. Kathleen Moore: I agree with that. And so, so if the end game, regardless of timing, is you get to no gross residual and you help a patient and there's no difference in overall survival, then it's a no-brainer. We would not be having this conversation. But there remains a question around, while it may be more likely to get to no gross residual, it may be, and I think we can all agree, a less radical, safer surgery, do you lose survival in the long term by this approach? This has become an increasing concern because of the increase in rates of use of neoadjuvant, not only in this country, but abroad. And so, you mentioned the four prior studies. We will not be able to go through them completely. Dr. Linda Duska: Let's talk about the two modern ones, the two from 2020 because neither one of them showed a difference in overall survival, which I think we can agree is, at the end of the day, yes, PFS would be great, but OS is what we're looking for. Dr. Kathleen Moore: OS is definitely what we're looking for. I do think a marked improvement in PFS, like a real prolongation in disease-free survival, for me would be also enough. A modest improvement does not really cut it, but if you are really, really prolonging PFS, you should see that-  Dr. Linda Duska: -manifest in OS. Dr. Kathleen Moore: Yeah, yeah. Okay. So let's talk about the two modern ones. The older ones are EORTC and CHORUS, which I think we've talked about. The two more modern ones are SCORPION and JCOG0602. So, SCORPION was interesting. SCORPION was a very small study, though. So one could say it's underpowered. 170 patients. And they looked at only patients that were incredibly high risk. So, they had to have a Fagotti score, I believe, of over 9, but they were not looking at just low volume disease. Like, those patients were not enrolled in SCORPION. It was patients where you really were questioning, "Should I go to the OR or should I do neoadjuvant? Like, what's the better thing?" It is easy when it's low volume. You're like, "We're going." These were the patients who were like, "Hm, you know, what should I do?" High volume. Patients were young, about 55. The criticism of the older studies, there are many criticisms, but one of them is that, the criticism that is lobbied is that they did not really try. Whatever surgery you got, they did not really try with median operative times of 180 minutes for primary cytoreduction, 120 for neoadjuvant. Like, you and I both know, if you're in a big primary debulking, you're there all day. It's 6 hours. Dr. Linda Duska: Right, and there was no quality control for those studies, either. Dr. Kathleen Moore: No quality control. So, SCORPION, they went 451-minute median for surgery. Like, they really went for it versus four hours and then 253 for the interval, 4 hours. They really went for it on both arms. Complete gross resection was achieved in 50% of the primary cytoreduced. So even though they went for it with these very long surgeries, they only got to the goal half the time. It was almost 80% in the interval group. So they were more successful there. And there was absolutely no difference in PFS or OS. They were right about 15 months PFS, right about 40 months OS.  JCOG0602, of course, done in Japan, a big study, 300 patients, a little bit older population. Surprisingly more stage IV disease in this study than were in SCORPION. SCORPION did not have a lot of stage IV, despite being very bulky tumors. So a third of patients were stage IV. They also had relatively shorter operative times, I would say, 240 minutes for primary, 302 for interval. So still kind of short. Complete gross resection was not achieved very often. 30% of primary cytoreduction. That is not acceptable. Dr. Linda Duska: Well, so let's talk about TRUST. What was different about TRUST? Why was this an important study for us to see? Dr. Kathleen Moore: So the criticism of all of these, and I am not trying to throw shade at anyone, but the criticism of all of these is if you are putting surgery to the test, you are putting the surgeon to the test. And you are assuming that all surgeons are trained equally and are willing to do what it takes to get someone to no gross residual. Dr. Linda Duska: And are in a center that can support the post-op care for those patients. Dr. Kathleen Moore: Which can be ICU care, prolonged time. Absolutely. So when you just open these broadly, you're assuming everyone has the surgical skills and is comfortable doing that and has backup. Everybody has an ICU. Everyone has a blood bank, and you are willing to do that. And that assumption could be wrong. And so what TRUST said is, "Okay, we are only going to open this at centers that have shown they can achieve a certain level of primary cytoreduction to no gross residual disease." And so there was quality criteria. It was based on – it was mostly a European study – so ESGO criteria were used to only allow certified centers to participate. They had to have a surgical volume of over 36 cytoreductive surgeries per year. So you could not be a low volume surgeon. Your complete resection rates that were reported had to be greater than 50% in the upfront setting. I told you on the JCOG, it was 30%. Dr. Linda Duska: Right. So these were the best of the best. This was the best possible surgical situation you could put these patients in, right? Dr. Kathleen Moore: Absolutely. And you support all the things so you could mitigate postoperative complications as well. Dr. Linda Duska: So we are asking the question now again in the ideal situation, right? Dr. Kathleen Moore: Right. Dr. Linda Duska: Which, we can talk about, may or may not be generalizable to real life, but that's a separate issue because we certainly don't have those conditions everywhere where people get cared for with ovarian cancer. But how would you interpret the results of this study? Did it show us anything different? Dr. Kathleen Moore: I am going to say how we should interpret it and then what I am thinking about. It is a negative study. It was designed to show improvement in overall survival in these ideal settings in patients with FIGO stage IIIB and C, they excluded A, these low volume tumors that should absolutely be getting surgery. So FIGO stage IIIB and C and IVA and B that were fit enough to undergo radical surgery randomized to primary cytoreduction or neoadjuvant with interval, and were all given the correct chemo. Dr. Linda Duska: And they were allowed bevacizumab and PARP, also. They could have bevacizumab and PARP. Dr. Kathleen Moore: They were allowed bevacizumab and PARP. Not many of them got PARP, but it was distributed equally, so that would not be a confounder. And so that was important. Overall survival is the endpoint. It was a big study. You know, it was almost 600 patients. So appropriately powered. So let's look at what they reported. When they looked at the patients who were enrolled, this is a large study, almost 600 patients, 345 in the primary cytoreductive arm and 343 in the neoadjuvant arm. Complete resection in these patients was 70% in the primary cytoreductive arm and 85% in the neoadjuvant arm. So in both arms, it was very high. So your selection of site and surgeon worked. You got people to their optimal outcome. So that is very different than any other study that has been reported to date. But what we saw when we looked at overall survival was no statistical difference. The median was, and I know we do not like to talk about medians, but the median in the primary cytoreductive arm was 54 months versus 48 months in the neoadjuvant arm with a hazard ratio of 0.89 and, of course, the confidence interval crossed one. So this is not statistically significant. And that was the primary endpoint. Dr. Linda Duska: I know you are getting to this. They did look at PFS, and that was statistically significant, but to your point about what are we looking for for a reasonable PFS difference? It was about two months difference. When I think about this study, and I know you are coming to this, what I thought was most interesting about this trial, besides the fact that the OS, the primary endpoint was negative, was the subgroup analyses that they did. And, of course, these are hypothesis-generating only. But if you look at, for example, specifically only the stage III group, that group did seem to potentially, again, hypothesis generating, but they did seem to benefit from upfront surgery.  And then one other thing that I want to touch on before we run out of time is, do we think it matters if the patient is BRCA germline positive? Do we think it matters if there is something in particular about that patient from a biomarker standpoint that is different? I am hopeful that more data will be coming out of this study that will help inform this. Of course, unpowered, hypothesis-generating only, but it's just really interesting. What do you think of their subset analysis? Dr. Kathleen Moore: Yeah, I think the subsets are what we are going to be talking about, but we have to emphasize that this was a negative trial as designed. Dr. Linda Duska: Absolutely. Yes. Dr. Kathleen Moore: So we cannot be apologists and be like, "But this or that." It was a negative trial as designed. Now, I am a human and a clinician, and I want what is best for my patients. So I am going to, like, go down the path of subset analyses. So if you look at the stage III tumors that got complete cytoreduction, which was 70% of the cases, your PFS was almost 28 months versus 21.8 months. Dr. Linda Duska: Yes, it becomes more significant. Dr. Kathleen Moore: Yeah, that hazard ratio is 0.69. Again, it is a subset. So even though the P value here is statistically significant, it actually should not have a P value because it is an exploratory analysis. So we have to be very careful. But the hazard ratio is 0.69. So the hypothesis is in this setting, if you're stage III and you go for it and you get someone to no gross residual versus an interval cytoreduction, you could potentially have a 31% reduction in the rate of progression for that patient who got primary cytoreduction. And you see a similar trend in the stage III patients, if you look at overall survival, although the post-progression survival is so long, it's a little bit narrow of a margin.  But I do think there are some nuggets here that, one of our colleagues who is really one of the experts in surgical studies, Dr. Mario Leitao, posted this on X, and I think it really resonated after this because we were all saying, "But what about the subsets?" He is like, "It's a negative study." But at the end of the day, you are going to sit with your patient. The patient should be seen by a GYN oncologist or surgical oncologist with specialty in cytoreduction and a medical oncologist, you know, if that person does not give chemo, and the decision should be made about what to do for that individual patient in that setting. Dr. Linda Duska: Agreed. And along those lines, if you look carefully at their data, the patients who had an upfront cytoreduction had almost twice the risk of having a stoma than the patients who had an interval cytoreduction. And they also had a higher risk of needing to have a bowel resection. The numbers were small, but still, when you look at the surgical complications, as you've already said, they're higher in the upfront group than they are in the interval group. That needs to be taken into account as well when counseling a patient, right? When you have a patient in front of you who says to you, "Dr. Moore, you can take out whatever you want, but whatever you do, don't make me a bag." As long as the patient understands what that means and what they're asking us to do, I think that we need to think about that. Dr. Kathleen Moore: I think that is a great point. And I have definitely seen in our practice, patients who say, "I absolutely would not want an ostomy. It's a nonstarter for me." And we do make different decisions. And you have to just say, "That's the decision we've made," and you kind of move on, and you can't look back and say, "Well, I wish I would have, could have, should have done something else." That is what the patient wants. Ultimately, that patient, her family, autonomous beings, they need to be fully counseled, and you need to counsel that patient as to the site that you are in, her volume of disease, and what you think you can achieve. In my opinion, a patient with stage III cancer who you have the site and the capabilities to get to no gross residual should go to the OR first. That is what I believe. I do not anymore think that for stage IV. I think that this is pretty convincing to me that that is probably a harmful thing. However, I want you to react to this. I think I am going to be a little unpopular in saying this, but for me, one of the biggest take-homes from TRUST was that whether or not, and we can talk about the subsets and the stage III looked better, and I think it did, but both groups did really well. Like, really well. And these were patients with large volume disease. This was not cherry-picked small volume stage IIIs that you could have done an optimal just by doing a hysterectomy. You know, these were patients that needed radical surgery. And both did well. And so what it speaks to me is that anytime you are going to operate on someone with ovary, whether it be frontline, whether it be a primary or interval, you need a high-volume surgeon. That is what I think this means to me. Like, I would want high volume surgeon at a center that could do these surgeries, getting that patient, my family member, me, to no gross residual. That is important. And you and I are both in training centers. I think we ought to take a really strong look at, are we preparing people to do the surgeries that are necessary to get someone to no gross residual 70% and 85% of the time? Dr. Linda Duska: We are going to run out of time, but I want to address that and ask you a provocative question. So, I completely agree with what you said, that surgery is important. But I also think one of the reasons these patients in this study did so well is because all of the incredible new therapies that we have for patients. Because OS is not just about surgery. It is about surgery, but it is also about all of the amazing new therapies we have that you and others have helped us to get through clinical research. And so, how much of that do you think, like, for example, if you look at the PFS and OS rates from CHORUS and EORTC, I get it that they're, that they're not the same. It's different patients, different populations, can't do cross-trial comparisons. But the OS, as you said, in this study was 54 months and 48 months, which is, compared to 2010, we're doing much, much better. It is not just the surgery, it is also all the amazing treatment options we have for these patients, including PARP, including MIRV, including lots of other new therapies. How do you fit that into thinking about all of this? Dr. Kathleen Moore: I do think we are seeing, and we know this just from epidemiologic data that the prevalence of ovarian cancer in many of the countries where the study was done is increasing, despite a decrease in incidence. And why is that? Because people are living longer. Dr. Linda Duska: People are living longer, yeah. Dr. Kathleen Moore: Which is phenomenal. That is what we want. And we do have, I think, better supportive care now. PARP inhibitors in the frontline, which not many of these patients had. Now some of them, this is mainly in Europe, will have gotten them in the first maintenance setting, and I do think that impacts outcome. We do not have that data yet, you know, to kind of see what, I would be really interested to see. We do not do this well because in ovarian cancer, post-progression survival can be so long, we do not do well of tracking what people get when they come off a clinical trial to see how that could impact – you know, how many of them got another surgery? How many of them got a PARP? I think this group probably missed the ADC wave for the most part, because this, mirvetuximab is just very recently available in Europe. Dr. Linda Duska: Unless they were on trial. Dr. Kathleen Moore: Unless they were on trial. But I mean, I think we will have to see. 600 patients, I would bet a lot of them missed the ADC wave. So, I do not know that we can say we know what drove these phenomenal – these are some of the best curves we've seen outside of BRCA. And then coming back to your point about the BRCA population here, that is a really critical question that I do not know that we're ever going to answer. There have been hypotheses around a tumor that is driven by BRCA, if you surgically cytoreduced it, and then chemically cytoreduced it with chemo, and so you're starting PARP with nothing visible and likely still homogeneous clones. Is that the group we cured? And then if you give chemo first before surgery, it allows more rapid development of heterogeneity and more clonal evolution that those are patients who are less likely to be cured, even if they do get cytoreduced to nothing at interval with use of PARP inhibitor in the front line. That is a question that many have brought up as something we would like to understand better. Like, if you are BRCA, should you always just go for it or not? I do not know that we're ever going to really get to that. We are trying to look at some of the other studies and just see if you got neoadjuvant and you had BRCA, was anyone cured? I think that is a question on SOLO1 I would like to know the answer to, and I don't yet, that may help us get to that. But that's sort of something we do think about. You should have a fair number of them in TRUST. It wasn't a stratification factor, as I remember. Dr. Linda Duska: No, it wasn't. They stratified by center, age, and ECOG status Dr. Kathleen Moore: So you would hope with randomization that you would have an equal number in each arm. And they may be able to pull that out and do a very exploratory look. But I would be interested to see just completely hypothesis-generating what this looks like for the patients with BRCA, and I hope that they will present that. I know they're busy at work. They have translational work. They have a lot pending with TRUST. It's an incredibly rich resource that I think is going to teach us a lot, and I am excited to see what they do next. Dr. Linda Duska: So, outside of TRUST, we are out of time. I just want to give you a moment if there were any other messages that you want to share with our listeners before we wrap up. Dr. Kathleen Moore: It's an exciting time to be in GYN oncology. For so long, it was just chemo, and then the PARP inhibitors nudged us along quite a bit. We did move more patients, I believe, to the cure fraction. When we ultimately see OS, I think we'll be able to say that definitively, and that is exciting. But, you know, that is the minority of our patients. And while HRD positive benefits tremendously from PARP, I am not as sure we've moved as many to the cure fraction. Time will tell. But 50% of our patients have these tumors that are less HRD. They have a worse prognosis. I think we can say that and recur more quickly. And so the advent of these antibody-drug conjugates, and we could name 20 of them in development in GYN right now, targeting tumor-associated antigens because we're not really driven by mutations other than BRCA. We do not have a lot of things to come after. We're not lung cancer. We are not breast cancer. But we do have a lot of proteins on the surface of our cancers, and we are finally able to leverage that with some very active regimens. And we're in the early phases, I would say, of really understanding how best to use those, how best to position them, and which one to select for whom in a setting where there is going to be obvious overlap of the targets. So we're going to be really working this problem. It is a good problem. A lot of drugs that work pretty well. How do you individualize for a patient, the patient in front of you with three different markers? How do you optimize it? Where do you put them to really prolong survival? And then we finally have cell surface. We saw at ASCO, CDK2 come into play here for the first time, we've got a cell cycle inhibitor. We've been working on WEE1 and ATR for a long time. CDK2s may hit. Response rates were respectable in a resistant population that was cyclin E overexpressing. We've been working on that biomarker for a long time with a toxicity profile that was surprisingly clean, which I like to see for our patients. So that is a different platform. I think we have got bispecifics on the rise. So there is a pipeline of things behind the ADCs, which is important because we need more than one thing, that makes me feel like in the future, I am probably not going to be using doxil ever for platinum-resistant disease. So, I am going to be excited to retire some of those things. We will say, "Remember when we used to use doxil for platinum-resistant disease?" Dr. Linda Duska: I will be retired by then, but thanks for that thought. Dr. Kathleen Moore: I will remind you. Dr. Linda Duska: You are right. It is such an incredibly exciting time to be taking care of ovarian cancer patients with all the opportunities.  And I want to thank you for sharing your valuable insights with us on this podcast today and for your great work to advance care for patients with GYN cancers. Dr. Kathleen Moore: Likewise. Thanks for having me. Dr. Linda Duska: And thank you to our listeners for your time today. You will find links to the TRUST study and other studies discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:   Dr. Linda Duska  @Lduska Dr. Kathleen Moore Follow ASCO on social media:     @ASCO on X (formerly Twitter) ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures of Potential Conflicts of Interest:    Dr. Linda Duska:   Consulting or Advisory Role: Regeneron, Inovio Pharmaceuticals, Merck, Ellipses Pharma  Research Funding (Inst.): GlaxoSmithKline, Millenium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, Tesaro, Cerulean Pharma, Aduro Biotech, Advaxis, Ludwig Institute for Cancer Research, Leap Therapeutics  Patents, Royalties, Other Intellectual Property: UptToDate, Editor, British Journal of Ob/Gyn  Dr. Kathleen Moore: Leadership: GOG Partners, NRG Ovarian Committee Chair Honoraria: Astellas Medivation, Clearity Foundation, IDEOlogy Health, Medscape, Great Debates and Updates, OncLive/MJH Life Sciences, MD Outlook, Curio Science, Plexus, University of Florida, University of Arkansas for Medical Sciences, Congress Chanel, BIOPHARM, CEA/CCO, Physician Education Resource (PER), Research to Practice, Med Learning Group, Peerview, Peerview, PeerVoice, CME Outfitters, Virtual Incision Consulting/Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, Merck, Eisai, Verastem/Pharmacyclics, AADi, Caris Life Sciences, Iovance Biotherapeutics, Janssen Oncology, Regeneron, zentalis, Daiichi Sankyo Europe GmbH, BioNTech SE, Immunocore, Seagen, Takeda Science Foundation, Zymeworks, Profound Bio, ADC Therapeutics, Third Arc, Loxo/Lilly, Bristol Myers Squibb Foundation, Tango Therapeutics, Abbvie, T Knife, F Hoffman La Roche, Tubulis GmbH, Clovis Oncology, Kivu, Genmab/Seagen, Kivu, Genmab/Seagen, Whitehawk, OnCusp Therapeutics, Natera, BeiGene, Karyopharm Therapeutics, Day One Biopharmaceuticals, Debiopharm Group, Foundation Medicine, Novocure Research Funding (Inst.): Mersana, GSK/Tesaro, Duality Biologics, Mersana, GSK/Tesaro, Duality Biologics, Merck, Regeneron, Verasatem, AstraZeneca, Immunogen, Daiichi Sankyo/Lilly, Immunocore, Torl Biotherapeutics, Allarity Therapeutics, IDEAYA Biosciences, Zymeworks, Schrodinger Other Relationship (Inst.): GOG Partners

The best biotech and pharmaceutical innovations mean nothing if they can't be protected—and protected fast. Our next guest, Josh Goldberg, is solving this challenge as co-managing partner at Nath, Goldberg & Meyer, the #1 ranked patent law firm for biotech and pharmaceutical technologies. With nearly three decades of IP law experience and a unique background as a lab researcher, Josh brings an insider's understanding of how innovation actually happens. He's helped industry leaders like Amgen, Takeda, and GlaxoSmithKline turn breakthrough treatments into patent-protected portfolios—often in under a year instead of the typical four-year timeline. Driven by a passion for focus and strategic IP timing, Josh shares his pioneering approach to biotech and pharmaceutical patent prosecution. Join us to discover how smart IP strategy drives licensing power, regulatory success, and company valuation. Let's go!Episode Highlights:Focus drives success – Companies fail by trying to do everything at once; staying deliberate and focused is key to making real impactOne-year patent timelines vs. four years – Josh uses USPTO's Track 1 program to secure patents in record time, improving fundraising and M&A positioningClient-centered approach wins – Listening to unique client needs instead of one-size-fits-all strategies earned the firm its #1 rankingDiagnostic patents are back – New USPTO Director signals the patent office is "open for business" again after a decade of restrictionsScientist turned patent attorney – Josh's lab background gives him insider understanding of how innovation actually happensAbout our Guest: Joshua is the patent attorney innovation-driven pharmaceutical companies call when they need to turn complicated technologies into protected assets in record time.As co-managing partner at Nath, Goldberg & Meyer—the #1 ranked patent law firm for biotech and pharmaceutical technologies in both 2024 and 2025—Joshua leads IP efforts across industries like biotech, pharma, agriculture, renewable energy, and advanced materials. Whether it's a blockbuster acne treatment like DUAC, a vitamin D analog lotion like Sorilux, OTC solutions like Salonpas and Germagic, or a leading drug used to reduce stomach acid and treat conditions like GERD, ulcers, and heartburn—like Protonix—Joshua helps turn high-stakes R&D into patent-protected portfolios, often in under a year instead of the typical four-year timeline.Though his climate and agricultre IP expertise has made him famous as the “green patent guy,” Joshua moves between disciplines skillfully and has helped industry leaders like Amgen, Takeda, Guilford Pharmaceuticals, Mayne, and Stiefel Laboratories (which was acquired by GlaxoSmithKline) build pharma portfolios that hold up under investor, acquirer, and FDA scrutiny.His journey didn't begin in IP law, but in the lab, researching experimental pharmaceutical delivery systems. It gave him an edge most attorneys don't have: understanding how innovation actually happens, and how to protect it without slowing a business down. Links Supporting This Episode: Nath, Goldberg & Meyer Website: CLICK HEREJoshua Goldberg LinkedIn page: CLICK HERENath, Goldberg & Meyer LinkedIn: CLICK HEREMike Biselli LinkedIn page: CLICK HEREMike Biselli Twitter page:...

Vidcast:  https://www.instagram.com/p/DQdlztLFFi-/The hot flashes and night sweats of menopause create a miserable midlife for so many women.  Hormones do offer relief, but many women cannot take them.  Enter a new non-hormonal drug just approved by the FDA.This medication, elinzanetant to be marketed as Lynkuet by Bayer, GlaxoSmithKline, and Nerre Therapeutics, is an oral neurokinin/tachykinin antagonist that normalizes thermal and sleep regulation.  A phase 3 multi-national study headed by researchers at the University of Virginia School of Medicine shows that 120 mg elinzanetant taken daily relieves both the frequency and intensity of hot flashes, improves sleep quality, and elevates moods. Improvement occurred for some study participants within the first week of therapy.Last year, the FDA approved another Bayer oral menopause drug fezolinetant, branded as Veozah. With one neurokinin receptor blocker, it reduces hot flashes only. This year's new entry is more powerful as it blocks two neurokinin receptors and affects not only thermoregulation, the hot flashes, but also sleep and mood.Since these drugs contain no estrogen, they lack the risks of blood clots, possible strokes, or exacerbation of certain hormone-dependent cancers including breast, uterine, and ovarian. Once readily available at your pharmacy, they provide safe, effective, and non-hormonal options for controlling bothersome menopausal symptoms.  Currently not approved for women with pre- or peri-menopausal symptoms, that approval should come soon,https://medicalxpress.com/news/2025-10-fda-nonhormonal-drug-ease-menopause.htmlhttps://newsroom.uvahealth.com/2025/09/16/drug-reduces-hot-flashes-by-73-trial-finds/#women #elinzanetant #Lynkuet #menopaue #hotflashes #nightsweats

In this episode, we dive into how advisory boards can be a game-changer for small businesses with Barbara Taylor and Ed Henkler . Unlike corporate boards, these groups are built on relationships and connections—bringing together people who share their expertise, networks, and insights to help a business grow. We'll discuss how to form an advisory board, the role connections play in bringing the right people to the table, and the impact these relationships can have on guiding strategy, opening doors, and creating new opportunities. If you're a small business owner looking for guidance, or a professional considering how your network could make a difference, this episode shows how advisory boards turn connections into lasting business growth.Barbara Taylor, CPCU, offers 20+ years of expertise in business coaching, talent management leadership development and performance management. Barbara has built a reputation for designing creative leadership development programs.She has designed and implemented effective talent management strategies for numerous Fortune 500 clients including L'Oreal, Comcast, GlaxoSmithKline, AstraZeneca, L3, Goodwill and The Kellogg Company.Currently, Barbara is a business partner of JanBara & Associates, a coaching and executive development firm specializing in accelerating the performance of people and organizations. The JanBara partners believe that purposeful human performance is the greatest contributing factor to a company's success. Barbara has co-created two leading-edge leadership programs: Silo-Busting Networking and Strategic Thinking for Middle Managers.Ed Henkler is a social entrepreneur who is passionate about improving the quality of life and employability of people who are blind or visually-impaired. He believes there is a business ROI to hire people with disabilities. He is working with several veteran-owned businesses which focus on increasing the meaningful employment of veterans, military spouses, and people with disabilities.Music by: ⁠⁠⁠⁠jorikbasov⁠⁠⁠⁠ from ⁠⁠⁠⁠Pixabay⁠⁠⁠⁠Contact InformationBarbara Taylor- btaylor@janbara.comEd Henkler- edhenkler@theblindguide.com or theblindguide.comBenny Carreon- Velocity Technology Group- benny@velocitytechnology.groupDennis Jackson-WorX Solution- dennisj@worxsolution.com

Zoe Harcombe didn't set out to become a controversial figure in nutrition science. With a background working inside both Mars candy company and pharmaceutical giant GlaxoSmithKline, she witnessed firsthand how corporate interests shape public health messages. But when she decided to pursue her PhD, what she discovered about the origins of our dietary guidelines shocked even her.In this revealing conversation with Dr. Philip Ovadia, Harcombe breaks down her groundbreaking research showing that America's low-fat dietary guidelines - the foundation for nutritional advice affecting hundreds of millions of people - were based on just six randomized controlled trials involving fewer than 2,500 exclusively sick men. No women. No healthy people. Yet these became the blueprint for what we're told to eat.Harcombe traces how Senator George McGovern's 1977 committee, influenced by his recent experience at a Pritikin bootcamp, essentially ignored the available scientific evidence and pushed through recommendations that had no solid research foundation. The ripple effects created our modern processed food epidemic and contributed to skyrocketing rates of obesity, diabetes, and metabolic dysfunction.But this isn't just about diet. Harcombe also shares her five-year legal battle against a major UK newspaper that attempted to silence her criticisms of statin research through personal attacks rather than scientific debate. Her victory in court has implications for free speech in scientific discourse and establishes important precedents for researchers challenging medical orthodoxy.From her unique insider perspective having worked at the highest levels of both big food and big pharma, Harcombe offers an unflinching look at how corporate interests have hijacked public health policy. She explains why the Mediterranean diet isn't what Harvard researchers claim it is, why an apple affects your body similarly to a candy bar, and why real change has to come from individuals taking control of their own health rather than waiting for institutions to reform themselves.This conversation cuts through decades of nutritional mythology to reveal the uncomfortable trSend Dr. Ovadia a Text Message. (If you want a response, you must include your contact information.) Dr. Ovadia cannot respond here. To contact his team, please send an email to team@ifixhearts.com Like what you hear? Head over to IFixHearts.com/book to grab a copy of my book, Stay Off My Operating Table. Ready to go deeper? Talk to someone from my team at IFixHearts.com/talk.Stay Off My Operating Table on X: Dr. Ovadia: @iFixHearts Jack Heald: @JackHeald5 Learn more: Stay Off My Operating Table on Amazon Take Dr. Ovadia's metabolic health quiz: iFixHearts Dr. Ovadia's website: Ovadia Heart Health Jack Heald's website: CultYourBrand.com Theme Song : Rage AgainstWritten & Performed by Logan Gritton & Colin Gailey(c) 2016 Mercury Retro RecordingsAny use of this intellectual property for text and data mining or computational analysis including as training material for artificial intelligence systems is strictly prohibited without express written consent from Dr. Philip Ovadia.

In today's episode, we're unpacking an important yet often misunderstood component of effective publication planning: the Publication Steering Committee (PSC).We're joined by industry leaders Cindy Toste, Senior Director of Publications at GlaxoSmithKline, and Paul Ricigliano, Senior Director and Head of Oncology Global Publications at Daiichi Sankyo, Inc.Together, we explore what makes a PSC truly successful, from establishing clear governance and managing cross-functional dynamics to defining roles across medical affairs and clinical teams. Cindy and Paul also share real-world lessons on how to navigate disagreement, maintain momentum, and ensure decisions don't stall progress.Whether you're forming your first PSC or optimizing an existing one, this episode offers practical guidance on turning conflict into collaboration, and collaboration into meaningful publication outcomes.To join ISMPP, visit our website at https://www.ismpp.org/This episode is generously sponsored by Avalere Health.

Pablo García, director general de Divacons-Alphavalue, repasa con lupa las cotizaciones de Astrazeneca, GlaxoSmithKline, TotalEnergies, Stellantis y Antofagasta.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world. The FDA has revived a long-dormant drug from GlaxoSmithKline as a potential treatment for autism. The agency also mentioned the potential link between the use of Tylenol and other acetaminophen products during pregnancy and neurological and developmental defects in children. In other news, Scholar Rock's spinal muscular atrophy drug faced manufacturing site issues, while Lexicon's type 1 diabetes drug experienced regulatory delays. Merck's ProQuad vaccine history was examined amid changing vaccine guidelines. Kennedy's criticism of childhood vaccines was also discussed. Biotility offers industry-recognized credentials for bioscience professionals, while a variety of biopharma news and upcoming events were highlighted.

In this episode of Molecule to Market, you'll go inside the outsourcing space of the global drug development sector with Stephen Dilly, Chairman, President and Chief Executive Officer at Codexis. Your host, Raman Sehgal, discusses the pharmaceutical and biotechnology supply chain with Stephen, covering: His journey of almost 40 years in the industry, including 20 years as a CEO. Leading two therapeutic companies to two, successful, $billion+ exits... Not making snap judgements and instant opinions early on in your role as a senior leader. Why he took on the challenge of leading Codexis at this phase of his career. The importance of values as guiding principles, and spending in-person time with your team. As President & CEO of Codexis since August 2022, Stephen brings more than three decades of executive management experience in the biopharmaceutical industry. Most recently, he served as President and CEO of Sierra Oncology (NASDAQ: SRRA) through its recent sale to GlaxoSmithKline for $1.9 billion.  Previously, Dr. Dilly served as CEO of Aimmune Therapeutics, acquired by Nestle Health Science for $2.6 billion. Dr. Dilly has served in executive roles at Genentech, Chiron and SmithKline Beecham and has been associated with the development, approval and launch of more than twenty marketed drugs across multiple therapeutic areas. He holds both an MBBS and a PhD in Cardiac Physiology from the University of London.   Molecule to Market is also sponsored by Bora Pharma (boracdmo.com) and Charles River (www.criver.com), and supported by ramarketing.    Please subscribe, tell your industry colleagues and join us in celebrating and promoting the value and importance of the global life science outsourcing space. We'd also appreciate a positive rating!

In a world where marketing agencies are racing to keep up with rapid change, how do you grow faster without losing your people, your culture, or your edge? In this episode of Leader Generation, Mod Op's new COO, Stuart Goldstein, joins Tessa Burg to share his playbook for scaling agencies. With years of experience leading firms through mergers, digital transformations, and process overhauls, Stuart reveals why the real challenge isn't the technology or the tools—it's bringing people along for the ride. Listeners will get an inside look at why Mod Op is uniting specialized agencies under one platform to offer clients deep expertise without the coordination headaches of managing multiple vendors. Listeners will get an inside look at why Mod Op is uniting specialized agencies under one platform, how to turn skeptics into champions, and the leadership moves that make change stick. From integrating AI across disciplines to avoiding the “shiny object” trap, he offers candid advice and relatable stories that apply to any leader facing transformation. This conversation delivers practical ways to align people, processes, and platforms—to keep your team motivated and your clients happy. Leader Generation is hosted by Tessa Burg and brought to you by Mod Op.  About Stuart Goldstein: As an experienced operations leader with over 20 years of success, Stuart can captain any ship. From start-up to heavyweight, Stuart has helped agencies and organizations pave their path to greatness. His expertise has been instrumental in driving growth and fame for renowned clients such as Johnson & Johnson, Oreo, Coca-Cola, American Express, Novartis, Diageo, eBay, GlaxoSmithKline, Time Warner, and Marvel, among others. And somehow, he still finds a way to drop a joke and take life one day at a time as long as it fits the brief. About Tessa Burg: Tessa is the Chief Technology Officer at Mod Op and Host of the Leader Generation podcast. She has led both technology and marketing teams for 15+ years. Tessa initiated and now leads Mod Op's AI/ML Pilot Team, AI Council and Innovation Pipeline. She started her career in IT and development before following her love for data and strategy into digital marketing. Tessa has held roles on both the consulting and client sides of the business for domestic and international brands, including American Greetings, Amazon, Nestlé, Anlene, Moen and many more. Tessa can be reached on LinkedIn or at Tessa.Burg@ModOp.com.  

On this episode, Jason and Matt are joined by their close friend Luis Fernando Mises, along with Jennifer Gillis and Misty Brown, two tireless advocates with the American Kratom Association. Together, we dive deep into the criminalization of kratom — from Louisiana's looming ban to the federal government's quiet war on natural medicine. Luis Fernando Mises is a consultant who teaches leadership across the U.S., a yoga and meditation teacher, a student of Austrian economics, a statesman with the Libertarian Party, a curandero, an entrepreneur, and a family man. He also runs a successful kratom business and brings rare clarity on both the plant and the marketplace. Misty Brown is a fierce kratom advocate and consumer who uses her voice to protect whole-leaf kratom and keep it legal and safe. Her work is personal — helping others fight addiction, chronic pain, anxiety, and depression. Jennifer Gillis has lived with chronic pain for 19 years. After finding real relief through kratom six years ago, she became a dedicated advocate, educator, and truth-teller who supports efforts to keep kratom accessible for all. We begin with the Louisiana ban, where Misty reveals troubling claims of bribery between a sheriff and a rehab clinic pushing the ban behind closed doors. From there, we move to the federal level — breaking down the media's obsession with 7-OH (a lab-concentrated alkaloid being falsely labeled as “kratom”) and how it's fueling disinformation, addiction, and panic. Luis gives clear and grounded advice on avoiding dangerous gas station extracts and choosing safe, whole-leaf kratom instead. We then explore the FDA's alliance with Big Pharma, RFK Jr.'s recent crackdown on 7-OH, and how this could pave the way for a nationwide ban. We dive into Scott Gottlieb's ties to GlaxoSmithKline, the push for synthetic patents, and the blatant monopolization of nature. Then we bring it home with a hard look at the horrors of prohibition through the heartbreaking stories of Shaina Brown and Marshall Price, two innocent people whose lives were upended — and in one case, ended — over this plant. We close with each guest offering real solutions and a final word of encouragement to the millions of Americans who use kratom safely, responsibly, and with purpose. This is a must-listen for anyone who cares about bodily autonomy, plant medicine, and the rising tide of pharmaceutical control. (Length: 1:08:44) Donate/Subscribe to TFTP: https://tftpsubdomain.wpengine.com/tftp-membership/  Jason's 'Know Your Right's 1-Hour Online Seminar: https://www.jasonbassler.com/book-online Sign the petition: https://www.protectkratom.org/  American Kratom Association: https://www.americankratom.org/  Facebook: https://www.facebook.com/emancipatedhumanWebsite: https://emancipatedhuman.com/Kratom: https://bestdamnkratom.com/Contact Luis at his Website Here: https://luisfernandomises.com/

Stocks hovering around record highs ahead of a Fed decision and key report cards out of Big Tech: Sara Eisen and David Faber broke down the latest on the data front (Q2 GDP, new payrolls data, and pending home sales at the top of the hour) along with some new commentary around prices and tariffs from consumer-facing earnings. RBC Tech analyst Brad Erickson broke down his bull case for Meta ahead of results tonight, while former Fed President Esther George discussed her predictions when it comes to Fed Chair Powell and rates.  Plus: the view from the C-Suite… This hour: the CEO of pharmaceutical giant GlaxoSmithKline talked her expectations for tariffs on the industry; hear the CEO of Starbucks' take on competition, as same-store sales there disappoint; the CEO of Hershey joined the team for her last broadcast interview in the role with the her latest on the consumer, M&A expectations, and legacy; and more from the CEO of Palo Alto as the company announces plans to acquire CyberArk for ~$25B. Squawk on the Street Disclaimer

In this episode of the Epigenetics Podcast, we talked with Sarah Teichmann from the University of Cambridge about the Human Cell Atlas. In the Interview we explore Sarah Teichmann's impressive career trajectory, covering her current role as Chair of Stem Cell Medicine at the Cambridge Stem Cell Institute and Vice President of Translational Research at GlaxoSmithKline. Professor Teichmann explains her unique dual appointments, a rare arrangement that allows her to bridge academia and industry effectively. As the conversation shifts focus to computational biology, she takes us on a historical journey from her PhD work at the MRC Laboratory of Molecular Biology to the present advancements driven by next-generation sequencing and artificial intelligence methods. Professor Teichmann emphasizes that the landscape of biological research has evolved significantly, particularly in the realm of data-driven methodologies. The conversation then transitions seamlessly into her pivotal role in advancing single-cell genomics, where she discusses the motivation behind using single-cell RNA sequencing methods in her research on T cells. This technique offered unmatched insights compared to bulk sequencing techniques, allowing for a more detailed understanding of cell states and their complex interactions within tissues. A highlight of the episode is Professor Teichmann's insights on the Human Cell Atlas project, which she co-founded in 2017. She elaborates on the ambitious vision to map all human cells, likening the endeavor to the Human Genome Project. Through the atlas, researchers aim to create a detailed reference map that facilitates a deeper understanding of human health and disease. Professor Teichmann shares the collaborative efforts that led to its inception and the importance of international cooperation in scientific research. The discussion culminates with an exploration of the biggest scientific findings thus far from the Human Cell Atlas. Among the revelations, she notes the astounding complexity and diversity of cell types identified, particularly within the immune system, and the unexpected locations of certain cell types during human development. She also highlights significant discoveries related to COVID-19, demonstrating the immediate real-world impact of their work.   References https://www.humancellatlas.org The Human Cell Atlas: towards a first draft atlas Kock, K. H., Tan, L. M., Han, K. Y., Ando, Y., Jevapatarakul, D., Chatterjee, A., Lin, Q. X. X., Buyamin, E. V., Sonthalia, R., Rajagopalan, D., Tomofuji, Y., Sankaran, S., Park, M. S., Abe, M., Chantaraamporn, J., Furukawa, S., Ghosh, S., Inoue, G., Kojima, M., Kouno, T., … Prabhakar, S. (2025). Asian diversity in human immune cells. Cell, 188(8), 2288–2306.e24. https://doi.org/10.1016/j.cell.2025.02.017   Related Episodes The Discovery of Genomic Imprinting (Azim Surani)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

Dr. John Sweetenham and Dr. Marc Braunstein highlight top research on hematologic malignancies from the 2025 ASCO Annual Meeting, including abstracts on newly diagnosed chronic phase CML, relapsed B-cell lymphoma, and multiple myeloma. Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. On today's episode, we'll be discussing promising advances in newly diagnosed chronic phase CML, relapsed B-cell lymphoma, multiple myeloma, and other hematologic malignancies that were presented at the 2025 ASCO Annual Meeting. Joining me for this discussion is Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center. Our full disclosures are available in the transcript of this episode.  Marc, there were some great studies in the heme space at this year's Annual Meeting, and it's great to have you back on the podcast to highlight some of these advances. Dr. Marc Braunstein: Yes, I agree, John, and thank you so much for inviting me again. It's great to be here.  Dr. John Sweetenham: Let's start out with Abstract 6501. This was a study that reported on the primary endpoint results of the phase 3B ASC4START trial, which assessed asciminib versus nilotinib in newly diagnosed chronic phase CML. And the primary endpoint of this, as you know, was time to treatment discontinuation because of adverse events. Can you give us your insights into this study? Dr. Marc Braunstein: Absolutely. So, like you mentioned, you know, asciminib is an allosteric inhibitor of the BCR-ABL kinase that has activity in CML, and that includes patients with the T315I mutation that confers resistance to first- and second-generation TKIs. So, the ASC4FIRST study, which was published last year in the New England Journal of Medicine, showed superior efficacy of asciminib compared to investigator-selected first- or second-generation TKIs, actually leading to the FDA approval of asciminib in first-line CML. So, the authors of that study presented data at this year's ASCO meeting from the phase 3 ASC4START comparing safety and time to discontinuation due to adverse events of asciminib versus nilotinib, a second-generation TKI. So, 568 patients with newly diagnosed CML were randomized one-to-one to once-daily asciminib or twice-daily nilotinib. So, at a median follow-up of 9.7 months, about 11% in the asciminib group and 17% in the nilotinib group discontinued treatment, with significantly fewer discontinuations with asciminib due to adverse events. There was also a secondary endpoint of major molecular response, which was also better with asciminib. For example, the MR 4.5, which is a deep response, was 2.5% versus 0.4% favoring asciminib by week 12. So, I think in conclusion, these results build on the ASC4FIRST study, making the case for the superior safety and efficacy of asciminib versus other first- or second-generation TKIs in newly diagnosed CML. Dr. John Sweetenham: Thanks, Marc. Do you think this is going to change practice? Dr. Marc Braunstein: I think so. I think there are still some questions to be answered, such as what resistance mutations occur after first-line treatment with asciminib. But I think the sum of these studies really make the case for using asciminib upfront in CML. Dr. John Sweetenham: Okay, great. Thank you. And let's move on to our second abstract. This was Abstract 7015 and was reported from Mass General Hospital. And this was a study in patients with relapsed and refractory diffuse large B-cell lymphoma and reported the 2-year results of the so-called STARGLO study. This is a comparison of glofitamab, a T-cell engaging bispecific antibody, with gemcitabine and oxaliplatin in this group of patients. Can you tell us a little bit about your impressions of this study? Dr. Marc Braunstein: Absolutely. So just for background, the treatment landscape for relapsed/refractory large B-cell lymphoma is expanding, now with two bispecific antibodies targeting CD20 that are approved after two or more lines of therapy. Among these, glofitamab was approved in 2023 based on phase 2 data showing an objective response rate of 52%, with 39% complete responses in relapsed/refractory large B-cell lymphoma patients after a median of three prior lines of therapy. Distinguishing glofitamab from epcoritamab, the other approved bispecific, glofitamab was given for 12 cycles and then stopped. Additionally, when combined with gemcitabine and oxaliplatin in the phase 3 STARGLO study, there was significantly improved overall survival compared to rituximab plus gemcitabine and oxaliplatin in transplant-ineligible relapsed/refractory large B-cell lymphoma patients at a median follow-up of 11 months.  The authors of that study published last year in Lancet now present at ASCO this year the 2-year follow-up of the STARGLO study. Two hundred and seventy-four patients with a median of one prior line of therapy were randomized two-to-one to glofitamab plus GemOx versus rituximab plus GemOx, with the primary endpoint of overall survival. Here, the median overall survival was not reached versus 13.5 months, with a median PFS also significantly improved at about 14 months versus 4 months in the control. CRS of note in the glofitamab arm was mostly grade 1 or 2, with only about 2.3% grade 3 events. And three of the four patients had grade 1 or 2 neurotoxicity. So, John, putting this into context, I think it's encouraging that we now have randomized data showing the superiority of a bispecific plus chemotherapy over rituximab plus chemotherapy in transplant-ineligible patients. And while only 8% of the patients in the STARGLO study had prior anti-CD19 CAR T-cell therapy, I think this regimen could be considered in those patients who are ineligible for transplant or CAR T-cell therapy. Dr. John Sweetenham: Yeah, I agree. I think a couple of other compelling numbers to me were the fact that around 55% of these patients were alive at 2 years in the group who'd received glofitamab, and that almost 90% of those having that arm of the study who had a CR at the end of treatment were alive at 12 months. So, clearly, it's an active agent and also a kind of great off-the-shelf fixed-duration alternative in these relapsed and refractory patients. Dr. Marc Braunstein: I agree, and I would also note that the phase 3 SKYGLO study is looking at glofitamab plus Pola-R-CHP versus Pola-R-CHP alone. So, we may even be using these eventually in the first-line setting. Dr. John Sweetenham: Absolutely. Let's stay on the theme of diffuse large B-cell lymphoma and look at one other abstract in that space, which was Abstract 7000. This was a study from the HOVON group in the Netherlands, which looked at the prospective validation of end-of-treatment circulating tumor DNA in the context of a national randomized trial. What are your thoughts on this? Dr. Marc Braunstein: So, non-invasive liquid biopsies to detect and monitor cancers via circulating tumor-derived DNA or ctDNA, you know, is really emerging as a valuable tool in both solid and liquid tumors to understand disease biology, and also for drug development. So, to date, the most established application of ctDNA in lymphoma, I would say, is really for monitoring of minimal residual disease. So, in this correlative study by Steven Wang and colleagues in the HOVON group, they evaluated the prognostic significance of MRD status as assessed by ctDNA following first-line treatment with curative intent with either R-CHOP or dose-adjusted R-EPOCH. At the end of treatment, encouragingly, 76% of patients were MRD-negative, and 24% were MRD-positive. Now, of note, MRD-positive status at the end of treatment predicted inferior progression-free survival at 2 years, with only 28% of patients who are MRD-positive being progression-free versus 88% who are MRD-negative. And in fact, all the patients who failed to achieve a complete response after first-line treatment and were MRD-positive ultimately relapsed. So, circulating tumor cells are rarely found in large B-cell lymphomas, and so this study really builds on accumulating data that ctDNA has clinical value to detect residual disease with a non-invasive approach. So, there are many implications of how we could potentially use this to detect early signs of relapse, to potentially escalate treatment for consolidation if patients remain MRD-positive. So, I think this will eventually become utilized in clinical practice. Dr. John Sweetenham: Yeah, I agree. I think it's interesting that it provided an independent assessment of response, which was independent, in fact, of the results of PET-CT scanning and so on, which I think was very interesting to me. And the authors of the abstract actually commented in their presentation that they think this should be integrated as part of the standard response assessment now for patients with large B-cell lymphoma. Would you agree with that? Dr. Marc Braunstein: I would. For one thing, it allows repeated sampling. It's a non-invasive approach; it doesn't necessarily require a bone marrow biopsy, and it may have more sensitivity than conventional response measures. So, I think having a standardized system to assess ctDNA will be helpful, and definitely, I think this will be a valuable biomarker of disease response. Dr. John Sweetenham: Okay, great. Thanks. We're going to change gear again now, and we're going to highlight two abstracts in the multiple myeloma space. The first one of these is Abstract 7507. And this abstract reported on the long-term results of the CARTITUDE study for patients with relapsed and refractory multiple myeloma. What are your comments on this presentation? Dr. Marc Braunstein: So, this study actually got a lot of press, and I've already had multiple patients asking me about CAR T-cells as a result. Just as some background, CAR T-cells targeting BCMA, which is pretty much universally expressed on malignant plasma cells in myeloma, have really shown remarkable responses, especially in heavily pretreated patients, showing superior progression-free survival in both later and earlier phases of the disease, including in randomized studies in patients with second-line or beyond. So, the CARTITUDE-1 was really the original Phase 1/2 study of ciltacabtagene autoleucel, one of the two approved anti-BCMA CAR T-cell products, which was investigated in patients with a median of six to seven prior lines of therapy. So, these were patients who were pretty heavily pretreated. So, in the study presented by Voorhees at this year's ASCO meeting, this was the long-term follow-up at a median of 5 years from the one-time CAR infusion in these patients with a median of five prior lines of therapy. And remarkably, of the 97 patients, 33% remained progression-free at 5 years plus, without needing any further myeloma treatment during that time. And among those 33% of patients, 23% had high-risk cytogenetics, which we know are notoriously difficult to achieve responses in. What was interesting that they presented as correlative studies was there were some biomarkers that were distinguishing the patients who had the long PFS, including enrichment of more naive T-cells in the product, lower neutrophil-to-T-cell ratio, higher hemoglobin and platelets at baseline, and higher CAR T-cell levels relative to soluble BCMA levels. And the fact that they reported a median overall survival of 61 months in these really heavily pretreated patients, I think these data are impressive. I think we're going to continue to be using CAR T even earlier in the disease status than fifth or sixth line, as it was studied in CARTITUDE-1. There are even ongoing studies looking at first-line treatment with CAR T-cells. Dr. John Sweetenham: So, do you think that those 33% of patients who are disease-free at 5 years, do you think any of those are cured?  Dr. Marc Braunstein: That was one of the headlines in the press. I think if we're going to discuss things like "operational cures," where we're transforming myeloma into really a chronic disease, where patients can live practically a normal life expectancy, I think the measure of 5 years, especially in this population that was explored in CARTITUDE-1, I think we can call that close to a cure. Dr. John Sweetenham: Okay. Well, thank you. Exciting data, for sure. We're going to conclude today with another abstract in the multiple myeloma space. And this was Abstract 7500, which looked at an MRD, minimal residual disease-driven strategy following induction and transplant-eligible newly diagnosed multiple myeloma patients and reported on the primary endpoints of the phase 3 MIDAS trial. Can you walk us through this one, Marc? Dr. Marc Braunstein: Absolutely. It is a bit more complicated than the prior one we discussed because this is a randomized study with four arms. So, I'll start by saying that anti-CD38-based quadruplet regimens continue to show superior outcomes in both transplant-eligible and -ineligible newly diagnosed multiple myeloma patients. The MIDAS study mentioned is an open-label phase 3 trial with four arms in transplant-eligible newly diagnosed myeloma patients.  And initially, these patients were all treated with quadruplet therapy with the anti-CD38 antibody isatuximab combined with carfilzomib, lenalidomide, and dexamethasone in 718 newly diagnosed myeloma patients. So, they received the quadruplet regimen for six cycles and then were randomized based on their MRD status at 10 to the negative fifth following six cycles of induction. And that first randomization, if they were MRD-negative, was to either consolidation with six more cycles of the quadruplet regimen or transplant, autologous transplant, plus two cycles additionally of the quadruplet regimen. And both arms were followed by lenalidomide maintenance. The primary endpoint was MRD negativity at 10 to the negative sixth prior to entering the lenalidomide maintenance component. And in addition, the patients who were MRD-positive after induction were randomized to transplant plus two cycles of consolidation or a tandem autologous transplant. So, the median follow-up of the study was about 16 months, and the pre-maintenance rate of MRD negativity was high, between 84 to 86% between the two arms who were MRD-negative, which was not significantly different. And as far as the 233 patients who were MRD-positive, the pre-maintenance MRD negativity was also not significantly different at 40% for those who received autologous transplant, and 32% who received a tandem transplant. So, there's a lot of debate in the myeloma field about the evolving role of autologous transplant and whether transplant still plays a significant role in patients who are either MRD-negative after induction or who have deep remissions and are of standard risk. So, I think these data suggest that patients who are MRD-negative after induction with a quadruplet regimen studied here, which was Isa-KRd, plus consolidation, may possibly be able to forego consolidation with autologous transplant. And likewise, for those patients who are MRD-positive after induction, tandem transplant didn't seem to provide much of a benefit compared to single transplant, which is consistent with prior studies such as the StaMINA study. Dr. John Sweetenham: So, where do you think this leaves us, Marc? Are we going to need more studies before we have any definitive guidance on whether an autologous transplant is still appropriate for those patients who are MRD-negative? Dr. Marc Braunstein: Well, as clinicians, we want to do what's best for our patient. And in myeloma, the best we can do is to get as deep remissions as possible, meaning MRD negativity. And so, I think it's clear from the MIDAS study and others that quadruplet regimens provide the deepest remissions when given upfront. We can debate the role of autologous transplant. I think certainly the role of tandem autologous transplant is fading. But as far as a single autologous transplant as consolidation, I think it's reasonable as a goal to try to achieve MRD negativity after the transplant, especially for patients who remain MRD-positive after induction. Dr. John Sweetenham: Okay, great. Marc, thanks as always for sharing your insights on the heme malignancies studies from the ASCO meeting this year and for joining us on the ASCO Daily News Podcast. Always appreciate hearing your thoughtful and balanced input on these. Dr. Marc Braunstein: My pleasure. Thank you, John. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's guest:  Dr. John Sweetenham Dr. Marc Braunstein   @docbraunstein     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:  Dr. John Sweetenham:  Consulting or Advisory Role: EMA Wellness  Dr. Marc Braunstein:  Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp  Speakers' Bureau: Janssen Oncology  Research Funding (Institution): Janssen, Celgene/BMS

This Oncology PER®Spectives™ podcast explores the role of EZH2 in metastatic castration-resistant prostate cancer (mCRPC) progression and its synergy with androgen receptor inhibitors. In this podcast, experts Neeraj Agarwal, MD, FASCO; Himisha Beltran, MD; and Maha Hussain, MD, FACP, FASCO, discuss the management of mCRPC. Acknowledgment of Educational Grant Support This activity is supported by an educational grant from Pfizer Inc. Accreditation/Credit Designation Physicians' Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians' Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians' Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669, for 1.5 Contact Hours. Instructions on How to Receive Credit Listen to this podcast in its entirety. Go to gotoper.com/credit and enter code: 6947 Answer the evaluation questions. Request credit using the drop-down menu. You may immediately download your certificate. Today's faculty are: Neeraj Agarwal, MD, FASCO Professor of Medicine Senior Director for Clinical Research HCI Presidential Endowed Chair of Cancer Research Director, Center of Investigational Therapeutics Director, Genitourinary Oncology Program Huntsman Cancer Institute, University of Utah (NCI-CCC) Salt Lake City, UT Disclosures: Grant/Research Support (paid to institution): Arvinas, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GlaxoSmithKline, Immunomedics, Janssen, Lava, Merck, Nektar, Neoleukin, Novartis, Oric, Pfizer, Roche, Sanofi, Seagen, Takeda, Tra-con Himisha Beltran, MD Associate Professor of Medicine Director of Translational Research Within Medical Oncology Harvard Medical School Lank Center for Genitourinary Oncology and the Division of Molecular and Cellular Oncology Dana Farber Cancer Institute Boston, MA Disclosures: Grant/Research Support: Circle Pharma, Daiichi Sankyo, Novartis; Adviser: Amgen, AstraZeneca, Daiichi Sankyo, Novartis Maha Hussain, MD, FACP, FASCO Genevieve E. Teuton Professor of Medicine Professor, Medicine (Hematology/Oncology) Deputy Director Robert H. Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine Chicago, IL Disclosures: Advisory Board: AstraZeneca, Bayer, Convergent Therapeutics, Honoraria: AstraZeneca, Bayer The staff of Physicians' Education Resource®, LLC, have no relevant financial relationships with ineligible companies. PER® mitigated all COI for faculty, staff, and planners prior to the start of this activity by using a multistep process. Off-Label Disclosure and Disclaimer This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this accredited activity is for continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient's medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any company that provided commercial support for this activity. Release Date May 14, 2025 Expiration Date May 14, 2026

This week, on Pioneers and Pathfinders, we're doing something a little different, with a special two-part conversation featuring Justin Ergler and Keith Maziarek, co-hosts of the Off the Clock podcast and board members of the Legal Value Network. Now, you may remember Keith from a previous episode. He's the Director of Pricing and Legal Project Management at Katten Muchin Rosenman. Justin, a veteran of GlaxoSmithKline, now leads his own consulting practice focused on alternative fee arrangements and innovative legal service delivery. In part one of our wide-ranging discussion, we talked about why this is a great time to enter the legal profession, the ongoing frustrations with the pace of change, and how law firms and legal departments are rethinking billing structures.  Read the full transcript of this episode here: https://www.seyfarth.com/dir_docs/podcast_transcripts/Pioneers_KeithMaziarek_JustinErlger_Pt.1.pdf

     Trump's war on free speech escalates with the "Take It Down Act," a satire-slaying Trojan horse, as he targets the Constitution and Thomas Massie as well     Meanwhile, the CIA's satanic puppet masters arm jihadists to butcher Christians in Syria they supported with A-10 Warthogs inter alia     Enter Unreal Milk, a lab-grown climate con blessed by Trump's USDA cronies and Bill Gates' millions—no cows, all control!     The elder-killing scandal: midazolam and morphine as chemical executioners, courtesy of Hancock's stockpiles.     Peter McCullough's bird flu grift collapses under scrutiny, but real heroes—like a West Texas doc defying BigPharma & MMR's—shine through NBC's smear campaign.2:30 Trump Wants Massey Gone, Constitution Next, and Satire Outlawed“Continuing Resolution” is an oxymoron.  They CONTINUE to kick the can down the road expecting something different because they have no RESOLUTION, simply feckless cowards.  But the manufactured outrage is NOT about the CR or budget — just like the Canadian tariffs are NOT about fentanyl.  Meanwhile, Trump pushes the “Take It Down Act”, a trojan horse anti-speech bill to outlaw satire.  Heres how it could be fixed — but won't be fixed. 15:45 The Importance of Constitutional Government VS Trump Ego-nomicsA much needed lesson for our time. 25:59 The Who & Why  Behind Trump's Attack on Massie Promises Bought, Promises Paid — BOUGHT & PAID It's easy to see…follow the money.  42:07 Trump Violates Due Process & Law to Follow His Masters: ADL & GreenblattIsrael's shadowy influence looms large. Is this anti-Semitism or anti-Netanyahu-ism? 57:10 CIA's Satanic Shadow Government Unleashes Jihadist Hell: Christians ButcheredFrom Afghanistan to Syria, they've armed bloodthirsty jihadists—like the Al-Qaeda poster child now slaughtering thousands in Latakia—with A-10 Warthogs and heavy weapons, all to topple Assad and install a terrorist worse than ever. Door-to-door executions, women paraded naked and shot, kids forced to kill their families—these U.S.-backed monsters proudly post their atrocities online, screaming "Allah Akbar" over bleeding corpses. Meanwhile, geospatial intel tracks your every move, building AI lifelogs to hunt you by faith and politics 1:19:54 MegaChurch Sued Over “Money-Back Guarantee” on Tithing Are you suing for more when you're already rich in wonders? 1:22:27 Miracles or “Intentional Blindness”? Wake Up to the Divine Spectacle You're Ignoring Every Day!Life wouldn't be a bore, or a chore, if we lived with childlike curiosity to see the miracles permeating in our lives.  Be aware of “intentional blindness”.1:35:57 Trump's Censorship Bombshell: Take It Down Act Unleashes a Speech-Stealing Tyranny!Billed as a shield against nonconsensual deep fakes it will let the powerful zap satire, memes, and criticism with zero proof—just accusations!  With vague terms, no recourse, and tech giants caving to avoid feds, it's civil asset forfeiture for your words!1:50:15 Trump Lists 60 More Elite Universities to Have Grants Removed$400 MILLION from Columbia to start — except for the wrong reasons.  Why was the anti-Americanism of these Marxist universities ignored for decades and funding ONLY CUT for anti-semitism?  It shows what we can expect from a rebranding Dept of Education2:06:51 Will the New CDC Head Look at Vaccine-Autism Connection?Dave Weldon, a vaccine-autism crusader from Vaxxed fame, steps into the ring today for a confirmation showdown—will he strike a Faustian bargain with Senator Cassidy like RFK Jr. did?2:12:02 “UnReal Milk”: Lab-Grown Dairy for the Climate Con GameHailed by Forbes as a climate-saving marvel, this Boston-born Franken-dairy is a “solution” for a non-problem. But wait—who's in charge? The USDA, meant for farm-fresh fare, bizarrely claims jurisdiction over this petri-dish potion, while the FDA sits on the sidelines. Critics cry foul: no cows, no agriculture—yet Trump's crew, including Brooke Rollins, rubber-stamps it alongside mRNA jabs for livestock! Bill Gates and Israel fuel the frenzy, pumping millions into this “no-milk milk” to dodge methane-farting cows. It's an unreal saga that reeks of the climate MacGuffin BS2:30:41 Chemical Restraints Exposed: Midazolam & Morphine Used to Kill the Elderly During “Covid”A shocking revelation that'll turn your stomach!  Matt Hancock's UK midazolam stockpile and GlaxoSmithKline's Irish vaccine agenda hint at a sinister elder-cleansing scheme—pension relief by lethal injection 2:41:39 Peter McCullough's Bird Flu Grift Unravels He can't even make a coherent argument for his “lab leak” nonsense.  And other people are starting to point out his grift.  It's Alex Jones 2.0, spinning half-truths into a fear-fest to sell product.    But there are REAL wins with REAL doctors who have REAL character—like the West Texas family physician who's ditching vaccines.  NBC attacks him for their BigPharma masters but in doing so, they prove his point 2;57:37 What Happens to Gold When the Stock Market Drops by 10% or More?Historical data looks good for gold bugsIf you would like to support the show and our family please consider subscribing monthly here: SubscribeStar https://www.subscribestar.com/the-david-knight-show Or you can send a donation throughMail: David Knight POB 994 Kodak, TN 37764Zelle: @DavidKnightShow@protonmail.comCash App at: $davidknightshowBTC to: bc1qkuec29hkuye4xse9unh7nptvu3y9qmv24vanh7Money should have intrinsic value AND transactional privacy: Go to DavidKnight.gold for great deals on physical gold/silverFor 10% off Gerald Celente's prescient Trends Journal, go to TrendsJournal.com and enter the code KNIGHTFor 10% off supplements and books, go to RNCstore.com and enter the code KNIGHTBecome a supporter of this podcast: https://www.spreaker.com/podcast/the-david-knight-show--2653468/support.

     Trump's war on free speech escalates with the "Take It Down Act," a satire-slaying Trojan horse, as he targets the Constitution and Thomas Massie as well     Meanwhile, the CIA's satanic puppet masters arm jihadists to butcher Christians in Syria they supported with A-10 Warthogs inter alia     Enter Unreal Milk, a lab-grown climate con blessed by Trump's USDA cronies and Bill Gates' millions—no cows, all control!     The elder-killing scandal: midazolam and morphine as chemical executioners, courtesy of Hancock's stockpiles.     Peter McCullough's bird flu grift collapses under scrutiny, but real heroes—like a West Texas doc defying BigPharma & MMR's—shine through NBC's smear campaign.2:30 Trump Wants Massey Gone, Constitution Next, and Satire Outlawed“Continuing Resolution” is an oxymoron.  They CONTINUE to kick the can down the road expecting something different because they have no RESOLUTION, simply feckless cowards.  But the manufactured outrage is NOT about the CR or budget — just like the Canadian tariffs are NOT about fentanyl.  Meanwhile, Trump pushes the “Take It Down Act”, a trojan horse anti-speech bill to outlaw satire.  Heres how it could be fixed — but won't be fixed. 15:45 The Importance of Constitutional Government VS Trump Ego-nomicsA much needed lesson for our time. 25:59 The Who & Why  Behind Trump's Attack on Massie Promises Bought, Promises Paid — BOUGHT & PAID It's easy to see…follow the money.  42:07 Trump Violates Due Process & Law to Follow His Masters: ADL & GreenblattIsrael's shadowy influence looms large. Is this anti-Semitism or anti-Netanyahu-ism? 57:10 CIA's Satanic Shadow Government Unleashes Jihadist Hell: Christians ButcheredFrom Afghanistan to Syria, they've armed bloodthirsty jihadists—like the Al-Qaeda poster child now slaughtering thousands in Latakia—with A-10 Warthogs and heavy weapons, all to topple Assad and install a terrorist worse than ever. Door-to-door executions, women paraded naked and shot, kids forced to kill their families—these U.S.-backed monsters proudly post their atrocities online, screaming "Allah Akbar" over bleeding corpses. Meanwhile, geospatial intel tracks your every move, building AI lifelogs to hunt you by faith and politics 1:19:54 MegaChurch Sued Over “Money-Back Guarantee” on Tithing Are you suing for more when you're already rich in wonders? 1:22:27 Miracles or “Intentional Blindness”? Wake Up to the Divine Spectacle You're Ignoring Every Day!Life wouldn't be a bore, or a chore, if we lived with childlike curiosity to see the miracles permeating in our lives.  Be aware of “intentional blindness”. 1:35:57 Trump's Censorship Bombshell: Take It Down Act Unleashes a Speech-Stealing Tyranny!Billed as a shield against nonconsensual deep fakes it will let the powerful zap satire, memes, and criticism with zero proof—just accusations!  With vague terms, no recourse, and tech giants caving to avoid feds, it's civil asset forfeiture for your words! 1:50:15 Trump Lists 60 More Elite Universities to Have Grants Removed$400 MILLION from Columbia to start — except for the wrong reasons.  Why was the anti-Americanism of these Marxist universities ignored for decades and funding ONLY CUT for anti-semitism?  It shows what we can expect from a rebranding Dept of Education 2:06:51 Will the New CDC Head Look at Vaccine-Autism Connection?Dave Weldon, a vaccine-autism crusader from Vaxxed fame, steps into the ring today for a confirmation showdown—will he strike a Faustian bargain with Senator Cassidy like RFK Jr. did?2:12:02 “UnReal Milk”: Lab-Grown Dairy for the Climate Con GameHailed by Forbes as a climate-saving marvel, this Boston-born Franken-dairy is a “solution” for a non-problem. But wait—who's in charge? The USDA, meant for farm-fresh fare, bizarrely claims jurisdiction over this petri-dish potion, while the FDA sits on the sidelines. Critics cry foul: no cows, no agriculture—yet Trump's crew, including Brooke Rollins, rubber-stamps it alongside mRNA jabs for livestock! Bill Gates and Israel fuel the frenzy, pumping millions into this “no-milk milk” to dodge methane-farting cows. It's an unreal saga that reeks of the climate MacGuffin BS2:30:41 Chemical Restraints Exposed: Midazolam & Morphine Used to Kill the Elderly During “Covid”A shocking revelation that'll turn your stomach!  Matt Hancock's UK midazolam stockpile and GlaxoSmithKline's Irish vaccine agenda hint at a sinister elder-cleansing scheme—pension relief by lethal injection 2:41:39 Peter McCullough's Bird Flu Grift Unravels He can't even make a coherent argument for his “lab leak” nonsense.  And other people are starting to point out his grift.  It's Alex Jones 2.0, spinning half-truths into a fear-fest to sell product.    But there are REAL wins with REAL doctors who have REAL character—like the West Texas family physician who's ditching vaccines.  NBC attacks him for their BigPharma masters but in doing so, they prove his point 2;57:37 What Happens to Gold When the Stock Market Drops by 10% or More?Historical data looks good for gold bugsIf you would like to support the show and our family please consider subscribing monthly here: SubscribeStar https://www.subscribestar.com/the-david-knight-show Or you can send a donation throughMail: David Knight POB 994 Kodak, TN 37764Zelle: @DavidKnightShow@protonmail.comCash App at: $davidknightshowBTC to: bc1qkuec29hkuye4xse9unh7nptvu3y9qmv24vanh7Money should have intrinsic value AND transactional privacy: Go to DavidKnight.gold for great deals on physical gold/silverFor 10% off Gerald Celente's prescient Trends Journal, go to TrendsJournal.com and enter the code KNIGHTFor 10% off supplements and books, go to RNCstore.com and enter the code KNIGHTBecome a supporter of this podcast: https://www.spreaker.com/podcast/the-real-david-knight-show--5282736/support.

American culture is everywhere, shaping everything from entertainment to fast food—but could its most profound influence be something far more unsettling? Across the globe, from Hong Kong to Japan, Western mental health concepts are spreading, often replacing traditional ways of understanding distress. Depression, PTSD, and eating disorders are appearing in regions where they were once rare, raising the question: is this organic, or is something more deliberate at play? In this episode, we dive into the unsettling case from Japan, where pharmaceutical giant GlaxoSmithKline saw an untapped market for antidepressants and set out to change the nation's perception of sadness itself. Through marketing, media manipulation, and cultural rebranding, they turned “feeling down” into a medical condition overnight—selling billions in pills along the way. Could this be an example of a memetic virus, an idea so powerful that it rewires an entire society's approach to mental illness? Then, for our Plus+ members, we uncover reports of bizarre shape-shifting UFOs, eerie green mist that seems to transport people between dimensions, and chilling encounters with dark entities that should have never been summoned. Links Crazy Like Us: The Globalization of the American Psyche Mental illnesses can be acquired via memetic viruses Chris Lakin Blog Anorexia In Hong Kong Dentsu chief to resign over employee's suicide from overwork Plus+ Extension The extension of the show is EXCLUSIVE to Plus+ Members. To join, click HERE. The Case of the Morphing Flying Saucer David Grusch seen at Esalen at Skywatcher UFO summoning event When UFOs Attack - Documented Cases of Hostile Alien Encounters I Experienced Terrifying Visits From A Succubus Yale News Mabel White Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr. Dan Cohen is the former Chairman of CNS, Incorporated. Dr. Cohen was the driving force behind the meteoric rise of Breathe Right nasal strips, acquiring the rights to manufacture and sell the product for the medical equipment company he founded in 1982. In 2006, GlaxoSmithKline acquired CNS, including its Breathe Right nasal strips and FiberChoice chewable fiber supplement products, for $566 million. Dr. Cohen's training is in neurology at the University of Minnesota and he is a Diplomat of the American Board of Psychiatry and Neurology.  Doctor Cohen also authored the books, Addicted To My Ego and Co-Authored Claim Your Basic Rights.   This Episode is Sponsored By: Jon Ostenson, Founder of FranBridge Consulting and Top 1% US Franchise Consultant is here to help you explore the world of non-food franchising opportunities today. Jon and his team are part of the largest brokerage in the US and have vetted the market thoroughly. Sign up for a free consultation call with Jon today at millionaire-interviews.com/franbridgeconsulting and receive a FREE copy of his new book Non-Food Franchising. Franbridge Consulting offers five more non-food franchise opportunities in 2024 that you can explore. FranBridge is hands down the premier source of the best opportunities in the non-food franchising world. You can hear more of Jon's story and how he started FranBridge Consulting on Episode 250 of our podcast. Sign up for a free consultation call with Jon today at millionaire-interviews.com/franbridgeconsulting and receive a FREE copy of his new book Non-Food Franchising.   Want to Support the Show? Well we'd love for you to join our Patreon Group!  What's in it for you?  Well you'll instantly get a scheduled call from Austin, where he'll help you with your current or future business... Sign-Up Now at millionaire-interviews.com/patreon.

Dr. Daniel Cohen is a Neurologist and serial entrepreneur. He co-founded SOLTEC Health to study the healing effect of magnetic waveforms on sleep and neurodegenerative conditions.SOLTEC Health (https://soltechealth.com/) has developed a safe, non-invasive, drug-free platform technology that can greatly expand the already growing field of neuromodulation. With this new disruptive technology, it is now possible to influence a region of the central nervous system, the brainstem, which includes the autonomic nervous system. The technology addresses the #1 health complaint in the U.S. – POOR SLEEP!Previously, Dr. Cohen co-founded and managed CNS, Inc. until it was acquired by GlaxoSmithKline in 2006 for $566M. CNS, a developer and marketer of hi-tech medical products (brainwave monitors and sleep disorders diagnostic equipment) was best known for its consumer products, the Breathe Right® nasal strip and the FiberChoice™ chewable fiber supplement.Dr. Cohen holds numerous patents related to EEG and sleep analysis algorithms and devices and additional utility patents related to synchronized sound, vibration and electromagnetic fields. Dr. Cohen received his MD from Temple Medical School with high distinction. His training is in Neurology at the University of Minnesota and is a Diplomat of the American Board of Psychiatry and Neurology. SHOWNOTES:

On this episode, hear the 2024 updates on COVID-19, long COVID and the latest developments in research in rheumatology. Hosted by Dr. Leonard Calabrese. Intro 0:12 In this episode 0:21 Coming up on Healio Rheuminations 0:56 COVID-19, long COVID and the rheumatologist with Leonard Calabrese, DO 2:19 Questions 3:12 Long COVID 4:46 Calabrese's bias 10:15 The evidence 13:08 Auto antibodies 14:54 Why does the body develop auto antibodies? 17:47 COVID-19 and epidemiologic association 22:25 New clinical entity 26:40 Therapeutic implications 31:00 In conclusion 32:00 Thanks for listening 33:18 Leonard H. Calabrese, DO, is the chief medical editor, Healio Rheumatology, and professor of medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic. Disclosures: Calabrese reports professional relationships with AbbVie, AstraZeneca, Bristol Myers Squibb, Galvani, Genentech, GlaxoSmithKline, Janssen, Novartis, Regeneron, Sanofi and UCB. We'd love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum.

Is quantum computing the next big thing? This week, Autonomous Technology and Robotics Director of Research Sam Korus and Associate Portfolio Manager Nick Grous are joined by ARK Chief Futurist Brett Winton to discuss the latest advancements in quantum computing and AI drug discovery. They discuss Google's recent quantum chip announcement, the challenges of scaling quantum technology, and the potential applications in drug discovery. The conversation shifts to the partnership between GlaxoSmithKline and Relation Therapeutics, highlighting the promise of AI in revolutionizing drug development processes, reducing costs, and improving efficiency. The episode concludes with insights on the future of drug development and the potential for significant market changes in the pharmaceutical industry.If you know ARK, then you probably know about our long-term research projections, like estimating where we will be 5-10 years from now! But just because we are long-term investors, doesn't mean we don't have strong views and opinions on breaking news. In fact, we discuss and debate this every day. So now we're sharing some of these internal discussions with you in our new video series, “The Brainstorm”, a co-production from ARK and Public.com. Tune in every week as we react to the latest in innovation. Here and there we'll be joined by special guests, but ultimately this is our chance to join the conversation and share ARK's quick takes on what's going on in tech today.Key Points From This Episode:Quantum computing is still 15 years away from commercial viability.AI is transforming drug discovery, making it faster and cheaper.AI drug discovery could reduce development costs to $600 million.The future of healthcare may focus on curing diseases rather than just treating them.For more updates on Public.com:Website: https://public.com/YouTube: @publicinvestTwitter: https://twitter.com/public