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The Mineral Rights Podcast: Mineral Rights | Royalties | Oil and Gas | Matt Sands
MRP 160: Strategies for Investing in Mineral Rights

The Mineral Rights Podcast: Mineral Rights | Royalties | Oil and Gas | Matt Sands

Play Episode Listen Later Jun 30, 2022 34:54


In this episode, we talk about the different strategies to consider when investing in mineral rights and royalty interests.  Ultimately, the strategy that you employ will determine the types of properties that meet your investment criteria.  From the type of interest, the geographic location, whether it already has producing wells or is undeveloped, to the product mix, all of these factors can contribute to the potential for generating near-term yield or whether it is a longer-term capital appreciation play. In case you missed it, we provide an overview of the different ways to invest and the specific step-by-step process for directly purchasing minerals and royalties in previous episodes so be sure to listen to these as well: MRP 26: Investing in Mineral Rights and Royalties MRP 126: Deep Dive on Investing in Mineral Rights, Royalties, and Working Interests MRP 128: Managing and Investing in Minerals and Royalties with Jarrett Kitch MRP 159: Guide to Buying Mineral Rights Links to the resources mentioned in this episode can be found in the show notes at mineralrightspodcast.com.

Un-Common
Off The Cuff

Un-Common

Play Episode Listen Later Jun 24, 2022 50:01


Email: Uncommonpodcast@outlook.comFacebook: @UncommonPODTwitter: @UncommonPC Instagram:  @dustin.duff     @Bpop80    Gettr: @DuffdbGab: @Duffdb   Clips:Joy behar clip on gunshttps://rumble.com/v17s7z5-june-8-2022.htmlBill Mahr on Wokesters - no one wants to hire you - Noodle Boyhttps://noagendaassets.com/enc/1655675754.167_billmahronwokesters-noonewantstohireyou-noodleboy.mp3  Rand Paul - Fauci - Royalties from Big Pharma https://noagendaassets.com/enc/1655675813.122_randpaul-fauci-royaltiesfrombigpharma.mp3 COVID vaccination for kids MPRhttps://noagendaassets.com/enc/1655675794.955_covidvaccinationforkidsmpr.mp3Inflation supercuthttps://noagendaassets.com/enc/1655070297.062_oneyearofinflationmessagingsupercut.mp3

ASCO Daily News
Spotlight on Immunotherapy at ASCO22

ASCO Daily News

Play Episode Listen Later Jun 23, 2022 27:22


Dr. Diwakar Davar and Dr. Jason Luke, both of the University of Pittsburgh's Hillman Cancer Center, highlight key advances in early phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting and also address toxicities, including immune checkpoint inhibitor-associated myocarditis. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. My name is Dr. Diwakar Davar, and I'm an assistant professor of Medical Oncology, specializing in melanoma and phase 1 therapeutics at the University of Pittsburgh's Hillman Cancer Center. I am the guest host of today's podcast. My guest today is Dr. Jason Luke, a colleague and the director of the Cancer Immunotherapeutics Center at the UPMC Hillman Cancer Center here.  Today, we'll be discussing advances in early-phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting.   You'll find our full disclosures in the show notes, and the disclosures of all guests on the podcast are available on our transcripts at asco.org/podcasts.  Jason, thank you for coming on the podcast today.  Dr. Jason Luke: Thanks so much for the invitation. It was a great ASCO, and I hope everyone had a good time.  Dr. Diwakar Davar: So, onto our abstracts. So, the first one that we'll be discussing, and Jason as you know we've done this before. We'll be rapidly transitioning between phase 1 therapeutics, melanoma, and advanced phase 2 and 3 trials, but you know this is something you do very well. So Abstract 2504, it's a phase 1 trial of TIM-3 inhibitor cobomilab immunotherapy and in combination with PD-1 inhibitors nivolumab and dostarlimab. The AMBER Trial that was presented recently, and in full disclosure, both you and I actually are on this abstract. So, what do you think of this abstract? What do you think of the data that is discussed, and how do we contextualize this in relation to what needs to be done in this space?  Dr. Jason Luke: So, I think this is an exciting abstract because it brings forward what may be the next high-priority immune checkpoint to try to target in clinical oncology. To level-set, I think everybody listening will know about PD-1 and CTLA-4 as immune checkpoints. In the last year, we've had LAG-3 come forward as now a standard of care element of armamentarium in melanoma, and we look forward to further studies of LAG-3 and other tumor types as we think it should be a good partner where PD-1 is otherwise approved.  So here now, we hear about TIM-3, which is another negative regulatory checkpoint on a number of different immune subsets. And in this abstract, the antibody targeting TIM-3 was cobolimab. So, TIM-3 is a very interesting molecule. It has, what you might call, pleiotropic effects in the immune system. So, while in the context of this abstract, it was being targeted as another immune checkpoint on T cells, it's important to point out that TIM-3 has other regulatory roles in other immune subsets such as myeloid cells and very particularly dendritic cells, and that's important because it might bring in another element of the innate immune system to try to drive anti-tumor responses. So, it's an exciting target because it might be able to expand the groups of patients who could benefit from immune checkpoint blockade.  So, in this abstract, we see initially the phase 1 data of combining cobolimab, anti-TIM-3 with anti-PD-1 of a couple of different flavors. And what you could take from this abstract is that in the phase 1 setting, the drug was well-tolerated and combined well, and had pharmacokinetic properties that would be consistent with what we'd expect for this kind of a monoclonal antibody. I think we have to marry this abstract, which is really the phase 1 data about safety in pharmacokinetic (PK) to another abstract presented in the melanoma session, which showed an expansion cohort of patients who got cobolimab plus nivolumab or dostarlimab.  And there we did see a 50% response rate, albeit that there was heterogeneity of patients being treatment naïve versus treatment-experienced. So, what I would say to this on a high level is that I think these data are preliminarily exciting, suggesting that further investigation into TIM-3 may be valuable in terms of expanding the population of patients initially in melanoma, but there will data coming soon in lung cancer and in other tumor types with another novel checkpoint. And I think if we think ahead into the future, the question is probably going to end up being, which combinations of checkpoints for which patients. That's pretty exciting to think about. We've seen a lot of data of PD-1 plus other molecules, and I think some future biomarker stratification really will be necessary to know which patient would benefit the most from which of these combos, but for the time being, this is exciting data to see where the field is going to go over the next couple of years.  Dr. Diwakar Davar: Great. And I guess, to your point, one important thing to highlight from the abstract is your point about the role of the different compartments. There was actually a very interesting dose-response relationship with the highest dose of the drug not necessarily being the most effective dose, suggesting that yes, as you escalate, you may have different effects in different compartments, and maybe therefore a broad selection of doses might be required to ensure that you have optimal engagement of the optimal target.  So, the next abstract is Abstract 3007. This is the tumor-agnostic efficacy and safety of erdafitinib. So, we now know that FGFR pathway aberrations are found from 77% of all malignancies, FGFR targets are now U.S. Food and Drug Administration (FDA) approved in cholangiocarcinoma with pemigatinib, infigratinib, and as well with erdafitinib metastatic urothelial cancer. We know that these agents are not necessarily effective tests in 1 tumor type because these alterations have risen in multiple tumor types. So, the RAGNAR trial, looking at this across multiple tumor types, what do you make of the interim analysis result presented by Dr. Loriot?  Dr. Jason Luke: So, I'd say that this is probably the future of targeted therapy. And so, I think that where we have activity in 1 disease, it's very likely we would have activity in others. So, the author has described this as the largest basket trial of a molecularly defined subset that's been pursued to date. There are upwards of more than 200 patients in the study. I think it's really important, as we think about the data, to realize, though, that all FGFR alterations are not exactly the same thing. And so, in this study, they gave erdafitinib to patients with solid tumors of any FGFR altered status. And so that's FGFR1, 2, 3, 4 mutations or gene fusions. And that's a lot of heterogeneity in there actually.  And in this study, there were two-thirds fusions and one-third mutations, mostly in FGFR2 and 3. That will become relevant as we start to think about the results. On a high level, I have to say that it is impressive in pan-cancer fashion, just selecting by FGFR alteration, there's about a 30% response rate observed. I think that no matter what, that's going to be valuable considering these were patients with refractory tumors with 3 lines of prior therapy on median. I think what we need to know more is the breakdown of which specific molecular alteration and FGFR in which tumor types drove most of the benefit.  So, for example, in bladder cancer where erdafitinib is already approved, that's almost entirely an FGFR3 fusion setting. So we know the drug is effective there. And so I think there will be a further breakdown of the data. As it matures more, you really start to tease out, is it really the case that any FGFR alteration can be treated or there are some that really ought to be the high priorities that we really ought to be going after. I think it would be remiss not to also note, however, that while there's excitement about this sort of pan-cancer approach, the current generation of FGFR inhibitors are not exactly the easiest drugs to take.  And so, the in-class, hypophosphatemia and stomatitis really does lead to dose reductions in a lot of the patients. And I think that that's probably really important to emphasize is that despite the pan-tumor activity, there's still a lot of potential in this field to refine further because it's almost certainly the case that if we had less off-target toxicity, so to say, we could improve the efficacy beyond that 30% that we saw here.  All the same, I think this is exciting for the concept of a pan-cancer tumor agnostic sort of approach, and we'll really look forward to more data to come from this study over the next, hopefully, few months.  Dr. Diwakar Davar: And I guess 1 corollary to that is that we now need to start looking for FGFR alterations in multiple tumor types. So, tests, tests, tests. All right, Abstract 3004, phase 1a/1b dose escalation and expansion study of the MDM2-p53 antagonist BI 907828 in patients with multiple solid tumors including advanced, metastatic, liposarcoma. So, we've recently had data of the previously undruggable KRAS, and now we've got previously undruggable p53, for which we now have targets. So, Jason, what do you make of the p53 targeting approach, in this case, using MDM2 and this particular drug from Boehringer Ingelheim?  Dr. Jason Luke: So, I think that this is an exciting abstract exactly for the reason that you mentioned, which is that p53 has been, and unfortunately, to some degree, still remains, one of those holy grails but undruggable targets in oncology. So MDM2, for those who are listening but might not be aware, is a negative regulator of p53. So, the concept here then is if you drug it, you might release p53 to reactivate activity in that pathway, and then p53 being the guardian of the genome, so to say, potentially leading to apoptosis of cancer cells.  And so, this drug binds MDM2 and MDM2 can be amplified as a resistance mechanism in p53 and several tumor types. And so here, they showed data for the early part of a clinical trial investigating the small molecule, BI 907828, but then they focus specifically in liposarcoma, which is a disease known to be an MDM2 amplified. And so, the results were pretty interesting. The toxicity of this kind of an approach, just to note, is really in class. It leads to some gastrointestinal (GI) toxicities as well as hematologic problems, and this goes again for most regulators of the cell cycle will have these effects, whether they're CDK inhibitors or MDM2 or p53 modulators.  But I think what was very interesting, this is a disease liposarcoma where chemotherapy, functionally speaking, has no role. We, unfortunately, give it to some patients sometimes, but it has almost no activity, and they observe that in poorly differentiated liposarcomas, the response rate was about 12%, but the stable disease was quite durable. And so, I think that really is potentially a big deal because this is an orphan disease. It really lacks any other treatment. But as you zoom out from that, if you start to think about targeting amplified MDM2 in other settings, I think the activity that we see here is intriguing, and potentially suggests that we may be coming to a future where we'll have multiple, sort of, orthogonal approaches after reactivating p53. There were actually other abstracts at ASCO Annual Meeting of other molecules that were less mature also along this line.  So, I think, very exciting to take away from this, one, a potential treatment for liposarcoma for all of those patients that anybody listening actually sees, but secondarily this concept of targeting p53, which I think we'll see a lot more of over the next couple of years.  Dr. Diwakar Davar: Excellent. Moving on to the Abstract 3002, this is a phase 1, two-part multicenter, first-in-human study of DS-6000a of an antibody-drug conjugate comprising the anti-CDH6 IgG1 monoclonal antibody that is attached to a topoisomerase I inhibitor payload via a cleavable linker. And so basically, a way in which you can give topoisomerase: (1) TOP1 inhibitor, (2) CDH6-expressing cells. This was studied in advanced renal cell carcinoma (RCC) and advanced ovarian cancer in this abstract presented by Dr. Hamilton. Jason, what do you think of the results and what do you think of this approach in general, this antibody-drug conjugate (ADC) approach using novel targets as well as novel payloads?  Dr. Jason Luke: I think this is one of those that you can't help but be pretty excited about, and I think in the context of the data shown at the plenary session in breast cancer for antibody-drug conjugates (LBA3), I think this is really where the field is going to start to go. So, you mentioned that this is an antibody-drug conjugate that targets cadherin 6 or CDH6, which people will remember from biochemistry class and medical school, or something is a cell-cell adhesion molecule, really a basement membrane protein. So, the concept of targeting it really is just to go after a latch mechanism to get the molecule into the tumor where you want. And CDH expression is very high in renal cell carcinoma, upwards of 80% of samples, also high in ovarian cancer, which is why they chose those 2 tumors to go after.  So, the ADCC, and you described its structure just a little bit, but it's essentially the same backbone as trastuzumab deruxtecan, which we saw this outstanding activity for HER2 and breast cancer on the plenary, with these 8 chemotherapies moieties attached to it, but here now, targeting it instead to HER2, with this molecule now to CDH6. And I think, again, you can't help but be impressed. There were treatment responses on almost every dose level of the dose escalation in this study. There's in fact only 1 patient whose tumor was not, at least, stable disease or a PR, and I think that that just goes to show the power of truly bringing the chemotherapy in a targeted manner into the tumor microenvironment. Responses were heterogeneous. They were not super deep responses per se, but the stable disease was quite durable in the study, and the patients were going out more than 7 months. And again, realizing this is at the lower dose levels as we're increasing the dose and move this in their earlier lives of therapy is likely to be even more effective.  They did show a waterfall plot of the reduction in CA 125 for the patients with ovarian cancer that really looked quite impressive. And given that that's our clinical biomarker that we commonly follow, it may actually even more indicative of the benefit we would see as opposed to resist.  Now, again, there is some toxicity. It is a chemotherapy moiety that's conjugated to the ADCs. So, the most common toxicities were nausea, vomiting, and low platelet counts, but these are kind of toxicities that we're quite accustomed to with chemotherapy. Just to summarize, I think there's a lot of promise for this kind of antibody-drug conjugate targeting, and I think it can only be impressive that they had this amount of activity in the dose escalation of the study. [I] very much look forward to the expansion cohorts in renal and ovarian, which we'll presumably expect to see later this year, early in the next year.  Dr. Diwakar Davar: And as you alluded to, this really was parallel that ASCO, by the standing ovation given to Dr. Modi when she presented the DESTINY04 data of trastuzumab deruxtecan in HER2-low breast cancer, basically now redefining breast cancer from 4 camps, now we have to think of not just HER2 amplified or HER2-high, but also HER2-low. So yes, really have to now rethink how we classify these diseases (LBA3).  So Abstract 2509, the efficacy of anti-PD-1/PD-L1 immunotherapy in non–small cell lung cancer dependent based on CD8 and PD-L1 status. So really Dr. Galon taking us into what he has now described as the immunoscore—really a way of characterizing tumors. A way of thinking about tumors that you've also championed, Jason, in terms of this T cell-inflamed and uninflamed hypothesis. So, tell us a little bit about how these jives with your work and how you would think about lung cancer patients responding and not responding to immune checkpoint inhibitors (ICI) therapy in this context?  Dr. Jason Luke: Yeah. I think the focus quickly here on the immunoscore, so the people are aware of that, I think is really important for diving into these specific results. You have to realize our fundamental underlying predicate for immune checkpoint blockade inhibitor response is that patients have mounted an adaptive immune response. So, CD8 T-cells have gone into the tumor where they elaborate chemokines and cytokines like interferon gamma, which upregulates the expression of PD-L1 in the tumor but also in the surrounding immune cells.  So, you realize that even though antibodies are targeting PD-1, it's really that we're targeting that tumor microenvironment. So, the more robustly we can measure that, and we understand it, the more likely we are to know whether or not the patient is going to benefit. So, this is where the immunoscore comes in. The immunoscore is actually a fairly simple test. It's one slide, immunohistochemistry slide where they can stain jointly for CD8 and PD-L1 on the same slide. And that allows them to do a number of different things beyond just testing the total level of PD-L1. They can test the CD8 density, the PD-L1 expression, but then also the interaction between CD8 T-cells, their distance from each other, from PD-L1 expressing cells, and so on and so forth.  And so really [this] can give us a much more robust analysis of what all is going on in the tumor microenvironment again, off of a single slide. So here then, in this abstract, for patients with non–small cell lung cancer receiving anti-PD-1, they then compared the utility of only PD-L1 testing versus doing the immunoscore. And so, it was actually quite a large set. They had about 250 patients in their analytical set and then split about 150 or 180 or something into the training and validation sets, and they compared the immunoscore against 2 different standard PD-L1 antibodies, the 22C3 as well as the SP263. And what they saw was a high concordance for expression between PD-L1 and the immunoscore.  That's good, because, again, they're measuring PD-L1 in both of those. And so that was a good, sort of, level set. The immunoscore, however, allows them to look to 7 different parameters, again, beyond just PD-L1, as I mentioned. So, CD8 density, interaction, distance, and this kind of thing. Then in these test and training cohorts, they were able to actually split out patients who are PD-L1 positive into further groups, those that were immunoscore low and that were high. And in so doing, they were actually able to sort of dramatically predict the likely progression-free survival on PD-1 checkpoint blockade in those different non–small cell lung cancer groups.  So why is this important? Selection of patients by PD-1 has been very useful in the field of non–small cell lung cancer, but it's hardly a panacea. You're not at all assured your patient is going to do well just because they're PD-L1. And here comes a second assay that can be done in a standard of care setting. So, the immunoscore is a test. You could just order it, and that really does give you much more predictive power about who's likely to do well and who isn't. And I think this test and more broadly multi-spectral imaging is really going to become a core component to how we risk stratify and predict outcomes to checkpoint blockade and lung cancer, but broadly in other tumor types over the next couple of years.  Dr. Diwakar Davar: Okay. Now, moving on from a biomarker for PD-L1 and PD-1 to a setting in which PD-1 was just recently U.S. Food and Drug Administration (FDA)-approved, so I'll give a brief background to the trial that you've actually developed and led. And so, this is KEYNOTE-716, the abstract in question is LBA9500 (late-breaking abstract) 9500, but this is the distant metastasis-free survival (DMFS) data readout. The DMFS, distant metastasis-free survival with pembrolizumab versus placebo in the adjuvant setting for patients with stage IIB or IIC, that is high-risk node-negative melanoma and the data from the phase 3 KEYNOTE-716 study.  So, this data, at least the recurrence-free survival (RFS) data was actually earlier published, you had presented it earlier last year and also more recently this year, but it was published recently in Lancet. And we know that 716 is a study in which, for the first time ever, we have an immune checkpoint inhibitor PD-1 that was studied against placebo with the high-risk node-negative setting in stage IIB and C melanoma, demonstrated a significant RFS benefit in the setting against placebo. And now we have the DMFS readout.  Maybe you could tell us a little bit about both the RFS and the DMFS data, and why this is such an important advance for these patients.  Dr. Jason Luke: Thanks. And I agree this really is a sea change in how we thought about stratification of patients with melanoma, but I think this broadly has implications for other tumor types as well. So, in melanoma, we've historically thought of its involvement of the lymph nodes—stage III as being the high-risk disease, but we also, if you look at the outcomes from the AJCC, we see the patients with stage IIB and IIC, so deep primary lesions, actually have similar bad outcomes as those patients with stage IIIA and IIIB. And so anti-PD1 and adjuvant therapy and melanoma were originally proved for stage III, but having understood that about 5 years ago actually, started to think, well, why not also treat the patients with stage II if they're at similar risk.  And we pursued KEYNOTE-716 as you mentioned, and it read out last year as a positive trial for recurrence-free survival. And the abstract here then was to look at the impact on distant metastasis-free survival. So, while the regulatory consideration for approval, and it is approved and it's available for patients now, was based on relapse, what we really want to be preventing is the development of metastatic disease because presumably that would correlate with the eventual death of the patient from cancer.  So, in the abstract here, we see the first update for DMFS, which also was positive on its first analysis, the hazard ratio at 0.64. And so, again, very similar to the RFS benefit, showing about a 35-36% reduction in distant metastasis-free survival. And this is a theme that we've seen across adjuvant studies in melanoma, all the adjuvant studies in fact, is that the RFS improvement, the relapse-free survival hazard ratio mirrors very closely the distant metastasis-free survival ratio. We saw that again here. I think it just emphasizes that anti-PD-1 immunotherapy is highly effective in melanoma no matter what stage it's in, but rather related to the risk of death for melanoma.  And so this really has a practice changing in the field of melanoma oncology. Patients need to be referred to medical oncology early for discussion around risk stratification and consideration of adjuvant therapy—I think even at the same time that they're having resection of their primary lesion, and it even calls into  question of whether or not we should even fully be doing procedures like sentinel lymph node biopsies any longer, considering we can make the decision to give adjuvant therapy now based on the primary—albeit that's a controversial area of discussion.  And I would just love for this to start to penetrate into other disease settings. We've seen more recently, approval for neoadjuvant therapy in lung cancer and we see in kidney cancer, bladder cancer. We see adjuvant therapy in—I think we're going to see immunotherapy starting to become an important part of the armamentarium in these hard-to-treat cancers, even at the time that perioperatively before or after surgery.  So definitely a major change in the way we're thinking about stratifying patients and emphasizes that you need to get those patients with melanoma in to have that discussion around adjuvant therapy probably at the time of the primary lesion resection.  Dr. Diwakar Davar: And finally, Abstract 2507, single-cell profiling of human heart and blood in patients with checkpoint inhibitor-associated myocarditis. So, this is data from the NGH Group, Dr. Villani and colleagues are presented by Dr. Blum. We know that myocarditis is an uncommon but very serious immune related adverse event (irAE), and here in this particular dataset, this group which has done a lot of underlying work to really uncover the role of certain key phenotypes, cellular phenotypes, in the development of myocarditis it's presenting the data in the context of ICI-related myocarditis. So, what do you think of this data, what do you think of the use of checkpoint inhibitors are now, as you've said, migrated linear in the lifecycle of the patient, what do we need to be thinking about and how does this improve our understanding of both the use of the drug and what we need to be worried about?  Dr. Jason Luke: I think the toxicities of immunotherapy, while, less frequent than, say, chemotherapy, can actually be more disastrous. In the rare patients, we have extreme immune-related adverse events, there is an incidence of actually life-threatening and fatal events. And so, myocarditis, associated with checkpoint blockade, is one of those things that could be seen, and here at ASCO Annual Meeting, we saw a couple of abstracts summarizing the experience from the National Cancer Institute following myocarditis events, and then this abstract in a translational level trying to better understand what is actually going on in terms of the immune response in those myocarditis cases.  And so, I thought this was actually a very interesting abstract. There was only a small number of patients. They had 13 samples from patients who had had endomyocardial biopsies in the context of immune-related myocarditis, and you might say, well, only 13 samples, but fortunately, this is quite a rare event, less than 1% of patients who get immune checkpoint inhibitors. And what they saw was relatively unsurprising, which is that in patients who were having myocarditis, they saw an increase in T cells and in K-cells, as well as activated CD8 and CD4 T-cells.  I think what was very interesting was when they started to dig into what were the phenotypes of the cells and what were the pathways that were turned on. Again, it was not especially surprising to see that they saw increased levels of interferon signaling and immune-receptor signaling as well as motility and adhesion, but this really, I think emphasizes that there are potentially interventions beyond just the general immune-suppression approaches that we give. They could be more nuanced but perhaps more efficacious because sadly, patients do pass away when they develop this. And in their cohort of 13 patients, 3 of those patients died. And specifically, in looking in those 3 patients, they actually saw that all 3 patients had a shared T cell cluster. And they can't exactly say what it is exactly yet, but I think it's very interesting to see that because it suggests that there's probably something about the T cell response in those patients that disproportionately triggered a fatal event.  And if we can understand that better, we then may be able to really tailor our interventions in a way that is more useful. Because, frankly, the way these patients usually present is they show up in the emergency room (ER), and they're seen by an ER doctor who thinks they're having acute coronary. They ship them off to the catheterization (cath) lab. They open him up, and then they get in there, and there's nothing going on. There's no plaque. And so now, all of a sudden, everyone is quite confused. And so, if we had better ways to search for that ahead of time to be aware of it, we might have better interventions because usually what happens right at that moment is everybody gets very confused and starts calling the oncologist, and we start slapping on steroids and other immunomodulatory agents, but sometimes it's late.  So, I think this is a great abstract. It's really starting to preliminary give us an idea of what is the actual biology that underpins these terrible events, and we can hope that we can build off that over time hopefully to eventually come up with better predictors and then obviously better interventions to try to avoid these outcomes in a small but real number of patients.  Dr. Diwakar Davar: Excellent. One other point is you and I are both involved in drug development, and as we start thinking of side effects. Side effects are really on the flip side of responses in drug development. So really 1 point to make of this is that when people start developing side effects rather than, as you say, putting your hands up in the air and waving them around, 1 of the things that we should be doing in drug development is possibly biopsying these patients because we could get new PD insights into how these drugs work, why they work, and particularly which sub-populations themselves they work on, particularly in the early-drug development setting when you oftentimes don't have that many responses.  With that, thank you, Jason, for sharing your insights with us today.  Dr. Jason Luke: Thank you.  Dr. Diwakar Davar: And thank you to our listeners for your time today. 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. So, thank you for your attention, and we will sign out.      Disclosures:  Dr. Diwakar Davar:   Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences  Consulting or Advisory Role: Instil Bio, Vedanta Biosciences  Consulting or Advisory Role (Immediate family member): Shionogi  Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences  Research Funding (Inst.): Zucero Therapeutics  Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy  Dr. Jason Luke:   Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical , Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine  Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure  Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)  Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio  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.     

Mornings with John Mackenzie
John MacKenzie chats with Ian Macfarlane, CEO of Queensland Resources Council, about the Palaszczuk government's post-budget decision to increase mining royalties which will negatively affect the coal industry in Australia.

Mornings with John Mackenzie

Play Episode Listen Later Jun 23, 2022 6:55


John MacKenzie chats with Ian Macfarlane, CEO of Queensland Resources Council, about the Palaszczuk government's post-budget decision to increase mining royalties which will negatively affect the coal industry in Australia. Treasurer Cameron Dick has defended the announcement which is anticipated to inject $1.2 billion into the Queensland treasury over the next four years. This legislation would mean that Queensland would pay the highest mining taxes in the world.

Courier Mail - News Feed
Qld's New Coal Royalties Regime Threatens Damage To Sector 23/06/2022

Courier Mail - News Feed

Play Episode Listen Later Jun 22, 2022 3:30


QUEENSLAND'S new coal royalties regime threatens to damage the sector, according to global investment banks, as industry figures claim future projects have been thrown into “jeopardy”.  Union boss Michael Ravbar has taken aim at Annastacia Palaszczuk, urging the Premier to take swift action against lobbying if she is serious about restoring public trust.  QUEENSLAND children are failing to meet basic literacy and numeracy targets, with new data showing the alarming levels state school students are falling behind.  Queensland researchers have developed a world-first vaccine against a common virus that can cause severe disabilities in unborn babies.  For updates and breaking news throughout the day take out a subscription at couriermail.com.au. See omnystudio.com/listener for privacy information.

Who's The Worst?
I'm The Worst #5 - Kristen Lundberg Fails At Public Relations

Who's The Worst?

Play Episode Listen Later Jun 22, 2022 31:53


My guest this week is comedian Kristen Lundberg. Kristen Lundberg is a mixed bag of talent, a comedian, actress, violinist, ice sculptor, and the self-proclaimed commercial queen! The one thing she's the worst at though is public relations. She shares a WILD story about how she turned her commercial into an NFT and tried to sell it to Jeff Bezos himself.SUBSCRIBE TO MY YOUTUBE and watch full episodes of the podcast every week: https://www.youtube.com/channel/UCsSeaqP56zWVTzZ2_U76wcA

4BC Breakfast with Neil Breen Podcast
'Short-term sugar hit': Increase to coal royalties slammed

4BC Breakfast with Neil Breen Podcast

Play Episode Listen Later Jun 21, 2022 5:54


The Queensland Resources Council has slammed the Queensland government's decision to hike coal royalty rates in the state budget as a "cash grab". See omnystudio.com/listener for privacy information.

Crossroads of Rockland History
Prof. David Bisaha on Millia Davenport - Crossroads of Rockland History

Crossroads of Rockland History

Play Episode Listen Later Jun 20, 2022 30:18


Episode originally aired on Monday, June 20, 2022, at 9:30am, on WRCR 1700AMWe turned our attention to the life and legacy of Millia Davenport. David Bisaha, Assistant Professor of Theater at SUNY Binghamton joined host Clare Sheridan to discuss this remarkable and trailblazing woman who lived most of her life in Rockland County. Among her many contributions include writing the definitive book of theatrical costume history, The Book of Costume. Published in 1948, it remains the gold standard. (Royalties from the book were donated to the New City Library.)Born in Cambridge, Massachusetts, on March 31, 1895, to Charles B. and Gertrude Crotty Davenport, Millia Davenport lived in New City for more than 70 years. Her father and mother were biology teachers at Harvard and Radcliffe, respectively. They were genetic researchers and helped establish the Station for Experimental Evolution of the Carnegie Institute of Washington in Cold Spring Harbor, NY.After attending Barnard and Parsons, Millia Davenport created artwork for and edited The Quill, a literary magazine. Later, she became one of the first female scenic design painters in America. She worked as a costume designer for a number of Broadway theater companies, including Maxwell Anderson's Playwrights Company and Orson Welles's Mercury Theater.In 1981, she received an honorary doctorate in fine arts from the Parsons School of Design in Manhattan the same year that she received the highest honor given by the United States Institute for Theatre Technology for a lifetime of distinguished contribution to the performing arts. In 1991 the Costume Society of America established the Millia Davenport Publication Award recognizing excellence in costume scholarship.Davenport died in 1992.David Bisaha is a scholar and practitioner who studies performance design, theatrical space and architecture, and the history of theatrical creativity. He is an Assistant Professor in the Department of Theater at SUNY Binghamton. He specializes in the history of scenic design in the United States, mostly in the first half of the twentieth century, and in the more recent history of immersive and participatory performance. His other research interests include theatre historiography, cognitive sciences and performance, directing theory, and memory studies.Bisaha's current book project, American Scenic Design and Freelance Professionalism, is a cultural labor history of scenic designers and designing in the United States. At Binghamton, Bisaha teaches theater and performance history, dramaturgy, and theater theory in the MA and BA programs. He is the Curator of the Theatre Collection of the Department of Theatre, and is affiliate faculty and a steering committee member of the Material and Visual Worlds Transdisciplinary Area of Excellence (TAE).  The Millia Davenport papers are housed there.***Crossroads of Rockland History, a program of the Historical Society of Rockland County, airs on the third Monday of each month at 9:30 am, right after the morning show, on WRCR Radio 1700 AM and www.WRCR.com. Join host Clare Sheridan as we explore, celebrate, and learn about our local history, with different topics and guest speakers every month. We are pleased to announce that we have begun loading our archived podcasts to all major Podcast platforms.The Historical Society of Rockland County is a nonprofit educational institution and principal repository for original documents and artifacts relating to Rockland County. Its headquarters are a four-acre site featuring a history museum and the 1832 Jacob Blauvelt House in New City, New York.www.RocklandHistory.org

Scott Adams Show on Red State Talk Radio
061722 Podcast, Fauci Kickbacks (Royalties), J6 Charade, Biden Inflation, Watergate Revisited

Scott Adams Show on Red State Talk Radio

Play Episode Listen Later Jun 17, 2022 55:05


061722 Podcast, Fauci Kickbacks (Royalties), J6 Charade, Biden Inflation, Watergate Revisited

Proactive - Interviews for investors
Electric Royalties announces company has acquired royalty on Zonia Copper Project in Arizona

Proactive - Interviews for investors

Play Episode Listen Later Jun 14, 2022 2:55


Electric Royalties CEO Brendan Yurik joined Steve Darling from Proactive to share news the company has announced an agreement with World Copper to acquire a 0.5% gross revenue royalty on the Zonia Copper Project in Arizona. Yurik telling Proactive the deal will include cash and stock and the Company will also have the right, for a period of 15 months, to acquire a further 0.5% royalty.

Mining Stock Daily
Elemental Royalties Merges with Altus Strategies

Mining Stock Daily

Play Episode Listen Later Jun 14, 2022 9:18


This morning, Elemental Royaltiesand Altus Strategies announced an All-Share Merger of Equals of the two companies. Fred Bell, CEO of Elemental connected with Paul Harris for his corporate commentary on the deal and why this merger made the most sense for the company.

Invention Licensing with David Fedewa
Why Improvement Clause is Important to a Potential Licensee

Invention Licensing with David Fedewa

Play Episode Listen Later Jun 14, 2022 5:29


The improvements clause is very important to me or a potential licensee. This is because product improvements and design changes all come about, and they usually happen throughout the process. A company, if they make improvements, they want rights to it. Or if an inventor, makes an improvement on the product, the inventor doesn't want to get improvement out of the deal. So, what are the ways to handle this? In today's episode, I'll share ways in finding the middle ground that works for both parties on the improvements clauses, how they work, and how to get them into contracts. P.S. Getting to the point of making money off your invention is hard. That's why I'm hosting a very special webinar for you on how to get through all of this. At the end of just 1 hour, you'll know the techniques to get your invention licensed easily and make a monthly passive income. Sign up for the webinar here: https://bit.ly/3cZZQ7v

The Art of Automation
Conversational AI with Andrew Freed

The Art of Automation

Play Episode Listen Later Jun 13, 2022 12:18


Conversational AI is the topic of this episode where Jerry is joined by Andrew Freed, author of Conversational AI –Chatbots that work.Today's chatbots have come a long way. They can handle complex requirements of larger organizations like banks, insurance companies and telcos… Specifically today's chatbots are now AI-powered. This enhances their ability to understand human language and perform more complex tasks and transactions. In relation to chatbots, this branch of artificial intelligence is called conversational AI.During the episode you will hear Andrew and Jerry discuss the art of designing, developing, and deploying human-like AI solutions that chat with your customers, solve their problems, and streamline your support services. Connect with Jerry on LinkedIn here. And Jerry's Digital Twin (DJ) here. Here is a link to Andrew's book – Conversational AI: Chatbots that work. With Discount code: FREEDPCAlso buy the Paperback of Art of Automation here.Buy a signed copy of Paperback Book here.Royalties from Art of Automation book are donated to the American Cancer Society.

Culture Factor 2.0
Ridhima Ahuja Kahn: Dapper Labs make the Top Shots using Flow Blockchain and serve up Brand Partnerships like Cryptokitties

Culture Factor 2.0

Play Episode Listen Later Jun 9, 2022 29:43


Ridhima Ahuja Kahn is the VP of Business Development at Dapper Labs. Her focus is helping build meaningful partnerships with the world's top IPs, creators, and social media platforms as they look to build blockchain-based experiences.Prior to Dapper Labs, she was a Partner at Andreessen Horowitz (a16z) where she focused on sports, social, media & entertainment, collectibles (both in digital & physical), hospitality/travel and food.She has also spent time on the investment teams at the Hewlett Foundation & Grovenor Capital Management.- Tell me about how you shifted into this role at Dapper Labs and was the inspiration behind TopShot birthed at Dapper or was your sports background the impetus to this idea?- What does fandom look like in metaverse ? What does TopShot and Cryptokitties experiences look like there? And do you think experiences are the magic of an NFT and your utility? What do experiences look like in the Metaverse?- Flow blockchain technology is unique to Dapper, reducing the friction of Web 2 native users and Web 3 adventurers, do you think this shift in creating your own blockchain has been part of the the secret sauce for Dapper Labs?- Digital Fashion will likely see a ton of growth due to the concept of wearables and shopping in the Metaverse: Luxury brands will soar to the top fast bc of virtue signaling and the marketing machine they are built on. Can Dapper help creators or smaller brands with NFTs for this use case?- Because we are also an education platform on Culture Factor, can you define DAO  and is Dapper getting involved in the DAO space?- And what would a brainstorming session at Dapper look like in terms of iterating on best use cases, verticals or simply coming up with experiences?Ridhima Ahuja Kahn of Dapper LabsHolly Shannon's WebsiteZero To Podcast on AmazonHolly Shannon, LinkedinHolly Shannon, InstagramHolly Shannon, Clubhousehttps://youtu.be/PKCND4FqGLc#dapper, #metaverse, #blockchain, #creators, #digital, #flow, #create, #labs, #web3, #community, #physical, fashion, #technology, #experience, #nft, #brands 

The Steve Gruber Show
Phil Kerpen, New Commitment to Seniors campaign “Celebrating” AARP's $1 Billion Milestone in Corporate Royalties.

The Steve Gruber Show

Play Episode Listen Later Jun 3, 2022 11:00


Phil Kerpen is the president of American Commitment (www.AmericanCommitment.org). New Commitment to Seniors campaign “Celebrating” AARP's $1 Billion Milestone in Corporate Royalties.

The POZCAST: Career & Life Journeys with Adam Posner
Todd Kaplan: CMO @ Pepsi: Culture Bending Creative & Entrepreneurial Leader

The POZCAST: Career & Life Journeys with Adam Posner

Play Episode Listen Later Jun 3, 2022 49:03


1:30 -  2022 Show2:44 - Things that could go wrong4:57 - Eminem's viral video5:54 - Todd's Career Journey7:04 - Todd's establishment9:19 - Consumer Psychology / The Aha Moment10:20 - In-house role11:31 - Power of Internships14:10 - Flexibility and non-working environment15:09 - Meeting with Indra16:30 - Credit to confidence18:54 - Trajectory at Pepsi21:12 - Mistakes along the way / Key Learnings22:52 - Thought of Leaving24:35 - Bubbly - Ups and Downs28:59 - Kendall Jenner Episode31:01 - Side Hustles / Hobbies32:30 - VeeFriends32:52 - Current Projects34:22 - Royalties and NFTs37:08 - Go-to interview Questions39:01 - Red Flags40:55 - The word 'Authentic'41:55 - Single Greatest Piece of Advice44:20 - Todd's North Star

Chuck Shute Podcast
Jim McCarty (The Yardbirds)

Chuck Shute Podcast

Play Episode Listen Later Jun 2, 2022 45:55


Jim McCarty is the drummer and founding member of the Yardbirds. The Yardbirds featured three legendary guitarists: Eric Clapton, Jeff Beck and Jimmy Page. The band was inducted into the Rock & Roll Hall of Fame in 1992 and rank #89 on Rolling Stone's list of “100 Greatest Artists of All Time.”  Jim has a new book out titled “She Walks in Beauty: My Quest for the Bigger Picture.” In this interview we discuss the best Yardbirds guitarist, playing Ouija boards with Jimmy Page, Jim's bad experience with LSD, hearing Paul McCartney play him an early version of “Yesterday” and more! 00:00 - Intro00:38 - Quitting the Day Job 03:05 - Putting Out Albums Vs. Singles 05:05 - Pussycat Dolls Song & Royalties 08:30 - Recording New Music 09:20 - Best Guitarist? 11:30 - Jimmy Page & Ouija Boards 14:30 - Linked Together & Global Consciousness 18:15 - Visions Before Death & Charlie Watts 19:40 - Birds & Butterflies 21:30 - Signs, Synchronicity  & Salvador Dali 24:42 - Drugs & LSD 30:20 - Religion, Morality & Philosophy 36:30 - Success, Fame & Gratitude 37:48 - Interactions with The Beatles 40:18 - Other Memories & Touring w/ The Yardbirds 42:35 - Sarcoma Foundation 44:40 - Outro Jim McCarty website:http://www.jamesmccarty.comSarcoma Foundation of America website:https://www.curesarcoma.orgChuck Shute website:http://chuckshute.comSupport the show

CruxCasts
Deterra Royalties (DRR) - $62M Dividend to Shareholders 1H/22

CruxCasts

Play Episode Listen Later Jun 2, 2022 32:06


Deterra Royalties Limited is an Australia-based company, which is engaged in the management and growth of a portfolio of royalty assets across a range of commodities, primarily focused on bulks, base and battery metals. The Company's portfolio includes royalties held over Mining Area C, its cornerstone asset, in the Pilbara region of Western Australia, as well as five smaller royalties, including Yoongarillup/Yalyalup, Wonnerup, Eneabba and St Ives. Its key royalty investment activities involve acquisition of royalties from third parties and providing finance to resource companies in return for royalties. The Company's projects include Mining Area C (MAC), Yoongarillup / Yalyalup Mineral Sands Mines, Wonnerup Mineral Sands, St Ives Gold Project and Eneabba Project. MAC is located approximately 90 kilometers (km) north west of Newman Township in the Pilbara region of Western Australia, which is an iron ore province. MAC produces approximately 145 million tons of iron ore per annum.

Klopotek Publishing Radio
Episode 19. For Books “Too Loud to Ignore”: Voice from an Independent Publisher-Bookstore – With Eric Obenauf and His Two Dollar Radio

Klopotek Publishing Radio

Play Episode Listen Later Jun 1, 2022 35:48


**Who You will Hear**Guest: Eric Obenauf (Co-founder and Editorial Director of Two Dollar Radio)Co-host: Luna Tang (Cloud Service Delivery Manager at Klopotek)Co-host: Dwayne Parris (Senior Consultant at Klopotek)Klopotek Publishing Radio is proud to dedicate this episode to the millions of independent publishers, independent bookstores, and the people who are wholeheartedly dedicated to running their own small publishing business.Our guest Eric Obenauf is Co-founder and Editorial Director of Two Dollar Radio, a publisher who refuses to crimp any of their books to convention but only produces the ones that are “too loud to ignore." The conversation begins with Eric sharing his entrepreneurial experience - how Two Dollar Radio launched, evolved, and how it has grown into a multi-award-winning publishing house with both local and national acclaim. Eric then comments on the increased corporate consolidation in the industry and the impact of the global pandemic on small publishers. He also talks about how his family-run brick-and-mortar, as well as his multi-functional bookstore Two Dollar Radio Headquarters, took root and made their names in the local community through books, publishing, events, mentorship programs, and catering services.Hopefully, after listening to this episode, you'll be more aware of where to get your next favorite read and pay more attention to those equivalently great books that are away from the spotlight of mainstream media.For more bold works of literary merit and more adventurous, original, and highly creative reads, please visit Two Dollar Radio and Two Dollar Radio Headquarters.Tell us what is going on with your publishing projects or business on Twitter (@Klopotek_AG), LinkedIn, or email us at podcast@klopotek.com.  For more information about the Klopotek software solution, please write to info@klopotek.com, or register to receive emails from us on technology innovations & events from Klopotek.* The views, information, or opinions expressed in the program are solely those of the individuals involved and do not necessarily represent those of Klopotek and its employees. It is the goal of Klopotek Publishing Radio to support cultural diversity, the exchange of opinions, and to create an environment where the conversation of a global publishing industry can thrive.

The Korelin Economics Report
Sailfish Royalty – Q1 Financials, Update On Key Royalties, And Lead Order Commitment Received on Previously Announced Swordfish Silver Spinout Transaction

The Korelin Economics Report

Play Episode Listen Later May 27, 2022


Paolo Lostritto reviews the Q1 financials, key royalty assets, and ongoing progress with the Swordfish Silver spinout transaction.

ASCO Daily News
ASCO22: Key Posters on Advances in Immunotherapy

ASCO Daily News

Play Episode Listen Later May 27, 2022 21:37


Dr. Diwakar Davar and Dr. Jason Luke, both of the University of Pittsburgh's Hillman Cancer Center, share the latest news on immunotherapy trials KEYNOTE-A10, LIBRETTO-001, and other key IO studies across tumor types featured at the 2022 ASCO Annual Meeting.  Transcript Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Diwakar Davar, and I'm an assistant professor of Medical Oncology in phase 1 therapeutics, at the University of Pittsburgh's Hillman Cancer Center, and the guest host of today's podcast. I'm delighted to welcome Dr. Jason Luke to this podcast. He's the director of the Cancer Immunotherapeutic Center at the Hillman Cancer Center, University of Pittsburgh, and a great colleague and friend.  Today we'll be discussing some key posters that highlight some advances in immunotherapy that will be featured and the 2022 ASCO Annual Meeting. You will find our collective disclosures in the show notes and the disclosures of all guests on the podcast are available on our transcripts at asco.org/podcasts.  So, Jason, thank you for coming on the podcast today.  Dr. Jason Luke: Well, thanks very much for the invitation. I always love doing these podcasts for ASCO, and never love anything more than hanging out with my friend Diwakar Davar.  Dr. Diwakar Davar: Well, thank you! Below are the abstracts we've selected. We will start with Abstract 2504. This is a phase 1 trial of the TIM-3 inhibitor cobolimab monotherapy, singly and in combination with the PD-1 inhibitors nivolumab or dostarlimab. Phase 1 data from the AMBER trial with the presenting author being Dr. Gerald Falchook. And this is a trial that initially started several years ago. And I know Jason, that you were involved with the inception of this agent, that TIM-3 inhibitor. So, walk us through, TIM-3. It's a third-generation checkpoint, we now have TIGIT LAG coming into the landscape. Definitely a first indication for LAG-3 melanoma with a positive trial, RELATIVITY 047. So, where are we with TIM-3? Why should we be excited about TIM in general, and this data in particular?  Dr. Jason Luke: It is quite exciting, especially building off the recent data that we saw for relatlimab or LAG-3 because it's becoming clearer that a number of these other immune checkpoints that we have been talking about for many years, actually really can be effective when used in the right setting.  So, this drug, this anti-TIM-3 antibody cobolimab monotherapy, as you mentioned, started out in a phase 1 clinical trial dating all the way back to I think about 2015. And that was at the time in immuno-oncology when everybody was so excited, [and] they thought everything was going to work immediately.  Subsequent to that, obviously, we've had some hurdles that we've had to come over. But we're coming back to some of these agents now, which are looking very exciting. So, just in the same way we think about blocking PD-1 or now blocking LAG-3 to reinvigorate T cells in the tumor microenvironment, there's a good chance and a high probability based on preclinical data that blocking TIM-3 could be just as effective as blocking LAG-3, so to say.  Now, one thing that I note in this abstract is really the safety finding and early PK analysis. And so, this is the important work we do early on to understand the drug. It's important to be aware that in a study like this, it's very hard to seek efficacy signals.  So, when you see this poster, really, you probably shouldn't be thinking, ‘Oh, this is a frontline phase 3 trial,' but rather that the efficacy is going to be a secondary consideration. Rather, what's quite important is looking at the properties of the drug and looking at the safety signals around that. And what we can see here is that TIM-3 appears to be quite safe when blocking it in conjunction with anti-PD-1 across several different tumor types. And that really sets the stage then to think about moving this into earlier lines of therapy across many different cancers.  And so, here we see advanced solid tumors but focused on lung cancer and melanoma and kind of the usual tumors we think about, and people can keep their eyes open because there are other posters of this molecule with PD-1 in some of the other sections outside of developmental therapeutics.  Now, one thing I would like to get your opinion on because your group has focused a lot on TIM-3, as I described it as this T cell centric mechanism to reinvigorate exhausted T cells. But it's possible that TIM-3 does other things as well. And I don't know if you want to comment on that or give any other feedback that you've had when thinking about this AMBER Trial.  Dr. Diwakar Davar: That was an excellent summary, Jason, of really what is a truncated 8-year track record of developing this agent all the way from 2015. But you bring up a very interesting point, which is: exactly what does this drug does in the non-T-cell compartment?  Some very interesting data from Brian Ruffell in a paper that was published about 3 years ago now suggested that TIM-3 was actually potentially a myeloid checkpoint, meaning that, in a tumor model in which Dr. Ruffell was studying this in the context of breast cancer, the drug primarily appeared to work on the effect of antigen-presenting cells and augment the presentation of antigen to T cells suggesting that it may be, in addition to being a chronicle T cell exhaustion marker, it may also be reinvigorating antigen-presenting cells. And the question of whether or not the role of TIM-3 on APCs as well as the role of TIM-3 on T cells, and which of these compartments are more important, and how these compartments segregate in any given cancer across many different lines of therapy will hopefully be something that we disengage, and understand a little bit better as we look at biomarkers of this drug across different settings.  And especially to that point, Jason, the biomarker question, you'll notice that very interestingly, that was a signal in which that drug had a certain response rate. Again, as you correctly point out, we cannot read too much into response rates in very small patient numbers. But very interestingly, there was a slightly higher response rate at the 300 milligrams, which is not the top dose level of the drug, and a slightly lower response rate at the ceiling dose of the drug that was tested, 900 milligrams, leading the investigators to conclude that the RP2D, was actually 300 milligrams every 3 weeks and not 900 milligrams.  What are your thoughts on dose in the context of immunotherapy (IO) drug development? And why might it be that 300 is the optimal dose as opposed to 900?  Dr. Jason Luke: That's a complicated question. I mean, when we think about checkpoint blockade, we classically think about it as only blocking on T cells. But to your point, if there are multiple mechanisms in play, sort of modulating other cell compartments actually may start to do different things at different doses that maybe weren't our primary intent as we went into the trial.  That's a little bit of hand waving, immunologic hand waving, but I think the data are the data and once we hit an effective dose level, there's really no need to really push the dose that much further. But that really emphasizes the importance of these kinds of early phase clinical trials.  So, I'm really looking forward to seeing this data. For disclosure, obviously, we have both been investigators on this trial. But we're very excited about the idea that there may be hope for a fourth checkpoint to come forward in the field beyond just PD-1 CTLA-4, and LAG-3, maybe now here with TIM-3.  Dr. Diwakar Davar: So, with that we'll go to the next abstract and that is Abstract 2516, “Phase I trial of adjuvant autogene cevumeran, an individualized mRNA neoantigen vaccine, for pancreatic ductal adenocarcinoma.”  So, this is an mRNA vaccine from our good friend, BioNTech. And that's been essentially evaluated in the context of highly lethal cancer, pancreatic ductal cancer, and specifically in the context of adjuvant vaccines, specifically in the setting of patients who had followed definitive pancreatic cancer surgery.  So, Jason, you know a lot of neoantigen vaccines, you've led some of these trials, really, the neoantigen vaccine is really the primary reason we are actually having an in-person meeting this year, because if not for this company and others like this, really this pandemic would not be behind us.  What are your thoughts on the role of neoantigen vaccines in cancer therapeutics, and also, particularly this particular trial in the data, the immunological data, and the clinical data regarding the development of neoantigen-specific T cells in this setting, and what this means for you?  Dr. Jason Luke: Right. So, the idea of targeting neoantigens as cancer immunotherapy was really all the rage a few years back, and it was thought based on preclinical animal models that this was just going to be the secret sauce, and this would be the new targeted therapy for immunotherapy. And it isn't to say that that's not true, but the first generation of neoantigen, peptide-based vaccines for the most part, unfortunately, just kind of didn't end up moving the needle the way we had hoped.  The question then was raised: is that because targeting neoantigens isn't reasonable, or is that because the setting where we were trying to do it in the refractory disease area was not the optimal way to leverage this?  And so, a couple of different companies and trials now are coming forward looking at targeting neoantigen in a minimal residual disease setting where the idea could be that immunologic responses that you could generate wouldn't be hampered by all the immunosuppression associated with the tumor microenvironment.  And so, here we have this molecule, which you eloquently pronounced, ‘autogene cevumeran.' It's an RNA-lipoplex neoantigen vaccine. So, it's not a peptide. It's more like the COVID-19 vaccines actually. And it's being given after surgery, followed by anti-PD-L1 followed by chemotherapy.  So, it's a complicated regimen, but it's very intriguing these early data, which do show that the patients who got the vaccine seemed to have better and longer-term outcomes. But then as you emphasize, really, I think probably what's at the heart of this that really makes it exciting is their ability to immune monitor the patients, meaning to look for antigen-specific immune cells from the peripheral blood in these patients to be able to identify those immune responses as being specific to cancer. Because this kind of a clinical trial, it's still signal seeking and proof of concept kind of trial.  In order to actually establish that a vaccine approach in a post-surgical setting would have efficacy, we need to do a large randomized trial. And so, this is not that yet. But I think these data really point in the direction that that could be a reasonable thing to try. And when you think about pancreatic cancer, where we've made no success with immunotherapy, really in a meaningful way in terms of checkpoint blockade, at least, that's pretty exciting actually to think about.  I would actually marry this dataset with another that we actually saw at the American Association for Cancer Research (AACR) meeting that also looked at neoantigen targeting and antigen-specific responses in colorectal cancer, again, and in a similar setting with the minimal residual disease setting.  And so, I think this highlights that we may need to start thinking about using immunotherapy in different ways than we had before. Obviously, everybody knows about using PD-1 blockade in lots of different cancer types that are really for metastatic disease, or maybe even for adjuvant now in melanoma a little bit. But maybe there's this space, which is the minimal residual disease setting where you might be able to detect by ctDNA after surgery, the patients are still positive. And maybe you could treat that before there's visible cancer, and maybe certain immunotherapies could be more valuable in that setting than others. And that's where I think maybe some of these mRNA technologies really might find their sweet spot.  So, coming back to this abstract, I think really, the emphasis point here is the novelty of generating patient-specific neoantigen vaccines, and then being able to track linearly over time the immune response against those vaccines.  I think with that kind of technology and being able to leverage that, I think we're really headed towards a real shift in the way we think about managing cancer in a post-surgical setting, again, thinking about MRD, or minimal residual disease, maybe in a way that our leukemia colleagues have been thinking it about for a long time.  Dr. Diwakar Davar: That's an excellent summary of a very, very complicated, both setting, and in this case, a therapeutic landscape. So, well said, well summarized, and we'll now pivot to Abstract 2514. So, this is ‘Efficacy and safety of NT-I7, long-acting interleukin-7, plus pembrolizumab in patients with advanced solid tumors: Results from the phase 2a study' [and] the presenting author is Dr. Aung Naing from [The University of Texas] MD Anderson [Cancer Center].  So, Jason, you know, with checkpoints, we've got so many thoughts about checkpoints, particularly given the rather unfortunate failure of BEMPEG in the context of melanoma.  So, we've got lots of interesting cytokines that we think of as important in the context of immuno-oncology 2, certainly 12, 15. You've been very involved with IO-15. We've got a lot of clinical trials studying IL-12. And now we've got one studying IL-7. So, tell us what do you think of this IL-7 targeting approach in the context of cytokine-based therapeutics?  Dr. Jason Luke: I think it's really important to emphasize on first principles, for those that are listening, who don't think about immunology all the time that not all cytokines are the same thing.  So, interleukin 2 that many people have heard of is very different actually than interferon. And that's very different from many of the other cytokines, the ILs, and everything, right?  So, IL-7 is a very potent cytokine that's associated with the expansion of immune responses, and that can drive interferon gamma-dependent effects. And you should hear whenever I say interferon-gamma is sort of a link through to PD-1 responsiveness. Because we think the mechanism that underpins anti-PD-1 effectiveness in patients really is interferon gamma biology.  So, IL-7 has been a molecule, it's been of a lot of interest but really was too toxic to try to deliver. But now we have novel drug delivery sorts of approaches that are being developed to try to bring the drug in, in a way that doesn't cause such systemic toxicity.  So, in this clinical trial, this NT-I7 molecule is given intramuscularly, every 6 weeks in conjunction with pembrolizumab, and very interestingly, in a small number of patients, but there were resist responses observed across a series of tumors that you really wouldn't expect should be responsive in any way to pembrolizumab alone. And so, we're talking about microsatellite stable colorectal cancer, pancreatic cancer, and some others as well.  And in conjunction with that, they were able to identify some of the biomarker effects we would think we would see with IL-7, such as expansion of peripheral immune compartments. And the toxicity profile was really consistent with what we've seen with fevers and chills, but manageable in a way that previous approaches really weren't.  So, I think this is really exciting because I think the idea here then is with this IL-7 approach, we might expand the kinds of cancers that we could go after, in conjunction with anti-PD-1 again, pancreas, colorectal cancer. I think that's really where the unmet need lies in oncology.  So, I really applaud these kinds of approaches and several of these cytokine approaches, and what we're going to talk about them, I think, have the potential to do that over the next couple of years.  Dr. Diwakar Davar: Excellent! Pivoting now to a different cytokine, but one that was alluded to before IL-12. So, Abstract 2518 is ‘Phase II evaluation of the combination of PDS0101, M9241, and bintrafusp alfa in patients with HPV 16+ malignancies,' and the presenting author here is Dr. Julius Strauss of the NCI Cancer Center and the Clinical Center of the National Cancer Institute at the National Institutes of Health.  So, what do you think, Jason, about the role of the HPV targeting vaccine, in this case, that was added to IL-12 immune-cytokine and bintrafusp alpha contextualizing the recent data that we have of bintra along with what is a very interesting result here?  Dr. Jason Luke: Yes, I think building on the last abstract where we talked about IL-7 as some novel biology now we move to IL-12, which again introduces other biology. So, interleukin-12 is a complicated cytokine, but one that's strongly associated with initial immune responses or immune priming, as well as enhancement of anti-tumor effects in the tumor microenvironment.  So, here we have sort of a 3-legged approach. So, the vaccination approach against HPV really can generate a strong immune response initially, and that can be supported with the IL-12. And then you come in with anti-PD-L1 and to whatever extent the TGF data is relevant here. And so, you have this cocktail where you're generating tumor-specific responses with a vaccine, you're supporting them with IL-12, and then blocking PD-L1.  And as we go back even a couple of abstracts we talked about, now we sort of have a cocktail right of approaches. And so, I think this is very exciting. It's unique in that, in these tumors, obviously, HPV is the driving force of cancer. So, developing a vaccine against that is fairly straightforward. But I really like this concept of bringing forward sort of a multi-dimensional immunotherapy approach. And we'll note they have previously presented data on this trial, I think last year at ASCO, actually. But what they see are pretty strong response rates, almost 30% range in PD-1 refractory tumors.  Again, that's our area of really high unmet need. It's hard to read through how useful a PD-1 naive treated patient here, although the response rates were high. But to me, it's really those patients who had progressed on PD-1 where they're getting these responses that tells me that this really could be something that's useful and potentially could be expanded beyond just say head neck cancer to any HPV relevant malignancy.  Dr. Diwakar Davar: Excellent! Now on to our last abstract. Abstract 2520, ‘Effect of intratumoral INT230-6 on tumor necrosis and promotion of a systemic immune response: Results from a multicenter phase 1/2 study of solid tumors with and without pembrolizumab (PEM) [Intensity IT-01; Merck KEYNOTE-A10].' The first author is Dr. Jacob Thomas.  Jason, we've seen a lot of interesting intratumoral therapies. You and I have both done a lot of studies in looking at intratumoral agents from toll-like receptor agonists, TLR-9, TLR 7-8, and more recently, oncolytic viruses.  So, contextualizing IT230-6 in the spectrum of intratumoral therapies, how do you feel about this drug, which is actually a very interesting novel drug. It's not just a TLR agonist, or for that matter, an OV, very interestingly, it's an intratumoral therapy that has actually got chemotherapy in it. So, how do you feel about this drug? How do you feel about the responses that we've seen? And particularly how do you feel about the setting in neoadjuvant breast cancer?  Dr. Jason Luke: Yeah. I would pick up where you said that this drug INT230-6 is just a really interesting concoction. So, it's cisplatin mixed with vinblastine, in a specific amphiphilic molecule that allows it to diffuse in through the cancer.  And so, if you had said that to me a few years ago, I would have looked at you and been like, ‘What are you talking about?' But I think the data that's been emerging for this is just really interesting because something about this chemotherapy cocktail actually drives immune responses. And really what the focus of this abstract is on is showing that you get an influx of CD foreign CDTa cells into the tumor microenvironment that's associated with a therapeutic benefit.  I think that's just really, really interesting to think about. It sort of makes one wonder when we're doing these intratumoral injections, how much of it is just the injection, and how much of it is the therapeutic agent, but I think it's a really novel therapy, and one that appears to be very well tolerated as well. And that's also the exciting part. When you hear cisplatin and vinblastine, you think, ‘Oh, well, that's not going to work.'  But apparently, it stays right in the tumor and generates these immune effects. I think it's very exciting. I think their approach here—going after what we usually call cold tumors, ones that don't respond to immunotherapy, you mentioned breast cancer—I think it's really interesting. I'm really looking forward to seeing the actual data from this abstract because, on first pass, it wouldn't have been what I thought about in terms of driving immune responses, but maybe it just goes to show that there's a lot more to understand there about immunogenic cell death and some of these other concepts that we bandy about. But I think this will be one of the most interesting abstracts actually to see the data for once it's available.  Dr. Diwakar Davar: Great! Taking a slight pivot from that. You've been involved in the development of novel response endpoints. One of the issues that we have with intratumoral therapies is that you're measuring a lesion that you inject, so now you inject something and it gets a little bigger. Is it getting bigger because it's growing? Is it getting bigger because the drug is working? We don't know. We have now itRECIST, which you have been working on.  What's very interesting is that whether you look at itRECIST, or RECIST, irRECIST, or imRECIST, when you have the monopoly of different response endpoints we have to deal with these days, these patients have monotherapy responses in non-injected tumors. How do you feel about that as a drug developer and somebody who's giving patients drugs like that? What is your impression of having shrinkage in the non-injected tumor?  Dr. Jason Luke: I think it's really exciting about this concept of the abscopal effect that we've bandied about for years. Despite being an investigator in this space, I'm really excited to actually see the data and to understand what these out of field responses are. If it's really true that this is robust, I mean, it could potentially be like a game-changer kind of thing. But I'll reserve judgment until I see the actual scans of the tumors that actually shrank that weren't injected.  Dr. Diwakar Davar: Fantastic insights, Jason. So, thank you for taking the time to join us on this podcast and to highlight these extraordinarily important advances in immunotherapy.  Dr. Jason Luke: I appreciate the opportunity to participate today.  Dr. Diwakar Davar: So, thank you, and thank you to our listeners for your time today, you will find the links to the abstracts that we discussed today in the transcript of the episode.  Finally, if you're enjoying the content on the ASCO Daily News podcast, please take a moment to rate review and subscribe wherever you get your podcasts.  So, thank you, Jason. And thank you to the team for putting this together.      Disclosures:   Dr. Diwakar Davar:   Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences  Consulting or Advisory Role: Instil Bio, Shionogi (Immediate Family Member), Vedanta Biosciences  Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, Zucero Therapeutics (Inst), GSK, Merck, Arcus Biosciences  Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231, and Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy  Dr. Jason Luke:  Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, Stipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences , Hotspot Therapeutics, SERVIER , STINGthera, Synthekine  Research Funding (Inst): Merck, Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma, EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure  Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)  Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio  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. 

She Turned Entrepreneur
What's Recession-Proof, Recurring and Cuddly? A Woofies Pet Service Franchise!

She Turned Entrepreneur

Play Episode Listen Later May 27, 2022 20:30


More than 70% of households have a pet, which explains why there is a $100 billion – with a “b” – industry offering related services. What the co-founder of the franchise featured on this episode of She Turned Entrepreneur saw 18 years ago was simple: “We knew the business could be so much more than what it was,” says Amy Reed, whose vision for a multi-service, mobile pet service option is today a thriving franchise opportunity. Pet sitters, walkers and groomers all in one, Woofies offer a 360-degree answer to pet care needs – many of which represent recurring business. Along with her co-founder Leslie Barron, Amy recognized early on the level of intimacy and trust involved. Pet owners are handing over security codes, keys and access to their homes, not to mention their beloved pets. That's why Woofies franchises maintain a gold standard of customer service and reliability. Another reason to become the owner of a Woofies franchise? All the furry friends! The model is adaptable, allowing owners to match their pet sitters with compatible pets and create ongoing relationships with the dogs that they groom. Franchise owners also receive a clear road map that speeds the process and prevents costly startup mistakes. Their intensive two-week training at headquarters in Ashburn, VA, covers every aspect of the business, from customer relations management and other tech systems to scheduling, hiring and marketing. It's pandemic-resistant. Recession-resistant. A member of the venerable Authority Brands family. The mobile nature of the business limits overhead and your van itself acts as a rolling billboard. Franchisees also have the fun of joining a community of pet-lovers, sponsoring popular “Yappy Hours” and other fun events. Establishing the Woofies model took time and a lot of trial and error. If you want to combine a love of animals and entrepreneurialism, you might be the perfect franchisee. Amy and Leslie learned the hard way – so that you don't have to! Click here to listen to, rate and review this or previous She Turned Entrepreneur episodes. Here are key takeaways from the conversation:· Shoot for the stars! If you see a niche that could be so much more, think big about how you might grow and expand a business sector with new services or a twist.· People say you're crazy to quit your corporate job? Could mean you're exactly on track!· Authority Brands is a powerful parent company for home-related franchise services.· The franchise model affords a nice balance between entrepreneurial independence and guardrails to build in success.· Want a marketing twofer? Mobile services out of vans double as rolling advertisements. Here's a quick look into the episode:· Woofies came to be in 2004 – the brainchild of two neighbors looking for pet care in an industry that was sparse. · Seeing a need and having a passion, Amy and her co-founder Leslie Barron quit their corporate jobs and dove into reinventing pet care.· They started walking dogs seven days a week and building a reputation, family by family, for being trustworthy and reliable. Customers who were relocating wanted to know how to find a similar service in their new zip codes.· A Decision Point: How to grow the business – with more corporate locations or a franchise model?· In 2018, Woofies launched its first franchise and in 2022 became part of the Authority Brands family, which is taking Woofies from a local to national profile.· What Woofies provides: o Dog walking (a great recurring revenue stream)o Pet sitting (in-house or overnight at a sitter's house)o Grooming (another great recurring revenue stream)· Woofies Differentiator: Pet sitting is not usually offered by services providing grooming or dog walking. But Amy has found that the three elements are all mutually reinforcing and synergistic. The more involvement, the deeper the bond with pet owners.· Ideal Franchisees: o #1: Understand and share a passion for pets.o #2: Have some amount of business acumen and the operational ability to coordinate and maximize various Woofies services. o #3: Know customer service and how to manage human resources.o #4: Value community, service, charity events and marketing through good will!· What it looks like to join the Woofies family:o A two-week training at headquarters in Ashburn, VA.o Hands-on help learning customer relations management systems, scheduling and live practice with new client consults. o “We try to make it as comprehensive and hands-on as possible!”o Subsequent to training, there are weekly and monthly follow-up calls and supplemental field support.o Franchise owners are the ultimate customer, so the Woofies ethic is all about tending to their success and satisfaction first.· Why being part of the Authority Brands family was pivotal: Amy and her partner wanted access to the most sophisticated resources possible to support franchisees.· The franchise model offers a balance between entrepreneurial independence and the know-how and experience acquired over time in developing the brand.· Initial Investment: The one-time franchise fee is $48,500, which is included in overall startup costs that run between $115,000-$200,000 (somewhat dependent on whether the franchisee works from home the first year). The mobile nature of the business reduces overhead while the van itself acts as a marketing tool. Royalties are 6.5% with a 1% brand marketing fee. · Interested in owning a Woofies franchise? Here's the baseline:o A net worth of at least $350,000-$400,000.o Liquid capital of $70,000-$80,000.· About the vans: Most people don't buy them outright. There is a lease option through Authority Brands. · The best part of being a Woofies franchisee? Hands down the interaction with pets. Being able to create your own independent business is icing on the cake!· It's an incredible time to be part of the $100 billion pet industry!To learn more about Woofies or other franchise opportunities, click here to set up a call.

Ryan's Method: Passive Income Podcast
Scaling an Amazon Merch Account to $128,737 Royalties (w/ Geno)

Ryan's Method: Passive Income Podcast

Play Episode Listen Later May 26, 2022 34:15


In this episode I'm joined by Geno who's sharing the story of his Amazon journey, which is strikingly similar to my own One of the coolest things Geno has accomplished includes making over $128,000 in Amazon Merch royalties!

The Mineral Rights Podcast: Mineral Rights | Royalties | Oil and Gas | Matt Sands

The current helium supply crunch is likely to get worse before it gets better but in the meantime we talk about how royalty owners can profit from Helium production and prices upwards of $600/mcf for this rare gas. Resources mentioned in this episode can be found in the show notes at mineralrightspodcast.com.

The Korelin Economics Report
Elemental Royalties – Significant Gold Equivalent Ounce Production And Revenue Growth On Tap For 2022

The Korelin Economics Report

Play Episode Listen Later May 25, 2022


Fred Bell, President and CEO of Elemental Royalties (TSX.V:ELE – OTCQX:ELEMF), discussed the significant growth in production and revenues for 2022.

ARC ENERGY IDEAS
Alberta Headline Replay: Politics, Court Decision on Bill C-69, Royalties and CCS Incentives

ARC ENERGY IDEAS

Play Episode Listen Later May 24, 2022 31:41


While the Battle of Alberta is front page news, this week Jackie and Peter take a break from hockey and talk about some other game-changing local headlines.  First, they talk about the political change with Premier Jason Kenney announcing that he is stepping down as leader of the United Conservative Party (UCP).  Next, an Alberta court found the Impact Assessment Act (formerly Bill C-69) to be unconstitutional.  The Act defines the review process for large energy infrastructure projects in Canada.After that, an update on the Canadian oil and gas industry's fiscal pulse.  With higher oil and gas prices, the outlook for revenue and cashflow for 2022 has increased and can be viewed on the last page of our weekly ARC Energy Charts publication.  Today's higher prices have significant implications for royalties, specifically, speeding up the timeline for oil sand projects to achieve the higher post-payout royalty rates.  Finally, Peter and Jackie weigh in on the debate about who should pay for Carbon Capture and Storage (CCS) – federal and provincial governments, or industry. Here's the Calgary Herald article Jackie mentions re carbon capture Please review the ARC Energy Institute disclaimer.

DAOn the Rabbit Hole
S2 E1: NFTs and the Future of Music (Cherie Hu)

DAOn the Rabbit Hole

Play Episode Listen Later May 23, 2022 49:29


On this episode of DAOn the Rabbit Hole, we're talking to Cherie Hu, Co-Founder of Water and Music, a research publication focused on the intersection of music and tech which has recently undergone the process of becoming a DAO. We kicked off the conversation discussing the state of the web2 music industry today and how blockchain technology and NFTs offer an alternative business model for musical artists and their fans.We discuss how digital scarcity is possible in the music industry, which is typically thought of as not scarce at all, with unlimited music streaming virtually for free. Cherie says that what is scarce however, is the relationship between artists and their fans, and it is this scarcity that NFTs can monetize. Cherie also lays out for us her definition of a music NFT and shares how these NFTs can be used to enhance the relationship between artists and their fans.Next, we break down some big topics into simpler terms. We go over the ways in which fans can acquire NFTs from their favorite web3 music artists and ways that artists can start onboarding themselves into web3. We dive into the complicated topic of DAOs and break down some possible definitions of a DAO. We discuss the creator economy and how NFTs can benefit not only artists, but their fans as well. Finally we wrap up our conversation by leaving you with some advice on how to onboard into web3 and get started with music NFTs. We hope you enjoy this episode of DAOn the Rabbit Hole!To continue this conversation and stay up to date on all things DAOn the Rabbit Hole, you can follow Anay on Twitter @anaysim and RabbitHole @rabbithole_gg. You can also follow Cherie on Twitter @cheriehu42. ⌛ TIMESTAMPS:0:00 Intro1:07 State of the music industry today4:09 How blockchain technology can affect the music industry11:35 What defines a music NFT?14:56 How does digital scarcity work in the music space? 18:03 How to acquire a token from a musical artist21:31 Web3 maximalist ideals in the NFT music space27:02 Defining a DAO32:31 Co-ownership and the creator economy37:44 Onboarding web2 audiences into web343:11 Getting started in music NFTs47:21 Follow Cherie! 

CruxCasts
Sandstorm Gold Royalties (SSL) - $1.1B Acquisitions & Dividends

CruxCasts

Play Episode Listen Later May 20, 2022 15:53


Sandstorm Gold Ltd. is a Canada-based gold-focused streaming and royalty company. The Company offers financing solutions to the gold mining companies. The Company has acquired a portfolio of over 229 royalties, of which approximately 28 of the underlying mines are producing. It is focused on investments towards production profile through the acquisition of additional gold royalties. The Company's projects include Altintepe, Aurizona, Black Fox, Bracemac-McLeod, Cerro Moro, Chapada, Agi Dagi, Hugo North Extension, Kirazli, Prairie Creek, Altan Nar, Goldwedge, Ruddock Creek, Emigrant, Forrestania, Fruta del Norte, Gualcamayo, HM Claim, Hounde, Karma, Triangle Zone, Ajax, Bayan Khundii, Buffelsfontein, Coringa and Hackett River.

The Darren Smith Show
Hour 1- Records are back, Marty wants Reach Around Show royalties, Damon Bruce joins the show

The Darren Smith Show

Play Episode Listen Later May 19, 2022 43:37


Hour 1- Darren says records are back, Marty wants Reach Around Show royalties, Damon Bruce discusses imperfect Warriors improbable run, same ol' Blake Snell.

Franchise Findings | Buying a Franchise Made Simple
Fat Brands Portfolio Continues to Grow But FAT Stock Performance Is Volatile

Franchise Findings | Buying a Franchise Made Simple

Play Episode Listen Later May 19, 2022 5:41


FAT Brands is a multi-brand restaurant operator headquartered in Beverly Hills, California. The name represents the value the company embraces and the food that they expect to provide to customers – Fresh, Authentic, and Tasty. FAT Brands strategically acquires, markets, and develops fast-casual and quick dining franchises around the world. The company currently owns 17 restaurant brands: Round Table Pizza, Fatburger, Marble Slab Creamery, Johnny Rockets, Fazoli's, Twin Peaks, Great American Cookies, Hot Dog on a Stick, Buffalo's Cafe & Express, Hurricane Grill & Wings, Pretzelmaker, Elevation Burger, Native Grill & Wings, Yalla Mediterranean and Ponderosa and Bonanza Steakhouses. This podcast was based on an exclusive Vetted Biz analysis, click here for the full report: https://www.vettedbiz.com/fat-brands-franchise/ Link to Franchise Times Article: https://www.franchisetimes.com/franchise_insights/business-as-usual-for-fat-brands-amid-sec-inquiry-shareholder-suit/article_14bc5e34-c01b-11ec-80d3-7fb17642cce3.html Want to have a franchise specialist support you day-to-day in your franchise search/ analysis? Click here for more information: https://www.vettedbiz.com/franchise-search/ 00:00 Introduction 00:24 About FAT Brands 00:56 Their 17 Restaurant Concepts 01:40 FAT Brands Franchise Opportunities 01:52 FAT Brands IPO and Market Capitalization 02:16 Global Franchise Group Purchase 02:39 FAT Brands CEO Faced Multiple Allegations 03:03 FAT Brands Franchisees 03:27 Royalties & Revenues 04:13 Conclusion #FatBrandsPortfolioContinuesToGrow #FranchiseFindings If you are looking for more information, you can connect with us through our networks: https://www.vettedbiz.com/ https://www.linkedin.com/company/vettedbiz/ https://www.facebook.com/vettedbiz

Culture Factor 2.0
Vladislav Ginzburg: P2: Alpha on Creator to Fan to Creator, what Utility do you Want?

Culture Factor 2.0

Play Episode Listen Later May 19, 2022 39:23


Vladislav Ginzburg is the Chief Executive Officer at Blockparty.Ginzburg leads Blockparty and the mission to build a blockchain-agnostic platform for collectible NFTs at the intersection of art, music and culture. Blockparty launched their MVP In August 2020 with a number of mainstream oriented drops, including first digital artworks by 3lau Slime Sunday, Adventure Club, Dave Krugman and others.Earlier, Ginzburg was Chief Business Development officer at Blockparty Tickets where he introduced blockchain as an NFT powered ticketing system to music festivals and professional sports teams, including a partnership with the Sacramento Kings of the NBA.Before entering the Blockchain and entertainment spaces, Ginzburg managed a fine art fund where he transacted more than $150 million in blue chip artworks. Ginzburg studied at Miami University in Oxford, Ohio as well as The New School in New York.Let's dig into your art background first, I believe it lays the groundwork for your interest in NFT related art and event?In the art world,  Vladislav Ginzburg has managed several high-value growth funds in the fine art industry where he has executed transactions for iconic canvas works by Pablo Picasso, Andy Warhol, Jean-Michele Basquiat, Salvador Dali, Pierre Auguste Renoir, and hundreds of others for clients., including placing works into museum exhibitions globallyWhat is your relationship with Warner Music and how will it compliment Blockparty goals for the artist?Opensea is the amazon for NFTs; it's the most common and most costly to mint because there's so many people on it. Rarible and a few others are less expensive. By having their own storefront on Blockparty (part Website, Etsy and Shopify?, Is this a solution to the two ends of the spectrum of Opensea and Rarible?Wants to dive into the live event aspect because of Lively partnership. Does Blockparty expect to be more of an event platform in the end? Or are they primarily a storefront/tools provider? What's the endgame?Ginzburg is the co-founder for Moonwalk. No code: there is code that sits behind the NFT. Moonwalk, being a no code platform, allows people who don't have developers in their back pocket to mint NFTs and play in the same arena as people who do have their own developers. Is Moonwalk going to eventually live on Blockparty?Are Ginzburg's platforms working toward democratizing crypto/NFTs for any and all?We are speaking on NFT.NYC in June!!Data to market yourself, your wallet, online habits, or curated social media look?Creators pushing for Blockparty to push further with them, innovating togetherEasy vs. creating smart contracts that work for the artists on the platformDali and Warhol experimented with digital art, NFT artists that were painters, sculptors and photographers using AR and image recognitionToken, receive it into your wallet, send it out of your wallet or stake it.look forward alpha: music NFTs will thrive with UGC (user generated content) selling viral content from fans taking and creating NFTs and sending to the viral TikTok artist.Vladislav Ginsburg on Twitter Holly Shannon's WebsiteZero To Podcast on AmazonHolly Shannon, LinkedinHolly Shannon, InstagramHolly Shannon, Clubhousehttps://youtu.be/PKCND4FqGLc#utility #creator #warner #brands #art #creativetechnologist #music #musician #spinnin'records #integrity #intention #purpose #impact #lockeddiscord #accesskeys #rightsownership #Fortnight #wearables #legacy #warnermusic #indieartist #fans #nfts #nft #nftart #cryptocurrency #blockchain #metaverse #culturefactor #web3 #smartcontracts #bitcoin #nftartist #nftcollectors #eth #ethereum #youtubers #tiktok #instagram #reels #branding #bitcoin #web3 #smartcontracts #bitcoin #nftartist #nftcollectors #community #decentralizedeconomy