Podcasts about receptos

Synopsis: In this episode of the Biotech 2050 podcast, host Rahul Chaturvedi engages in a thought-provoking conversation with Ray Stevens, a prominent figure in the biotech industry who co-founded Structure Therapeutics. Ray's extensive experience and pivotal role in advancing structure-based drug discovery make him a compelling guest for biotech entrepreneurs seeking to navigate the challenges of entrepreneurship and funding strategies. The episode delves into Ray's journey as a serial entrepreneur, the evolution of structure-based drug discovery, and the strategies employed by Structure Therapeutics to drive innovation and create impactful treatments for global health challenges. Ray's insights into the changing funding environment, the impact of distributed teams on value creation, and the significance of shared passion and mission in a company's success offer valuable knowledge for industry professionals and entrepreneurs. His reflections on the industry's future trends and the personal growth aspect add a relatable and human element to the discussion, making it a valuable resource for individuals at all career stages. Biography: Dr. Stevens helped pioneer the field of structure-based drug discovery. He has been involved in the discovery and development of several therapeutic molecules that have become breakthrough drugs including Palnziq™, which was developed at BioMarin Pharmaceutical and approved in 2018 to treat phenylketonuria. Dr. Stevens also founded Receptos which developed Zeposia™—a GPCR agonist targeting the S1PR1 receptor approved in 2020 for multiple sclerosis and 2021 for ulcerative colitis. Prior to Structure, Dr. Stevens founded the Bridge Institute at the University of Southern California (USC), and the iHuman Institute at ShanghaiTech University. He was previously a tenured chaired chemistry professor at Scripps Research and before that, an assistant professor of chemistry at the University of California, Berkeley. Dr. Stevens' laboratory and students have launched several successful biotech startups including Syrrx (acquired by Takeda), MemRx (acquired by Chiron/Novartis), Receptos (acquired by Celgene/BMS), and RuiYi (now Bird Rock Bio). A prolific scholar, Dr. Stevens has authored more than 400 peer-reviewed publications and received several academic and industry awards. Dr. Stevens conducted postdoctoral research in structural biology at Harvard University with William Lipscomb, who was awarded the Nobel Prize for Chemistry in 1976. Dr. Stevens earned his Ph.D. in chemistry from USC with Robert Bau and George Olah, the latter of whom received the Nobel Prize for Chemistry in 1994. He completed his undergraduate degree in chemistry from the University of Southern Maine.

In this episode of Meeting Mic, we bring you Healio's top headlines from ACG 2023. Paul Feuerstadt, MD, FACG, AGAF, discusses data that link health-related quality of life and microbiome composition among patients with recurrent Clostridioides difficile infection. :38 Edward V. Loftus Jr., MD, FACG, discusses results from the INSPIRE trial for ulcerative colitis. 7:52 Jan Wehkamp, MD, PhD, discusses results from the QUASAR study, in which Tremfya outperformed placebo in clinical response patients with ulcerative colitis. 12:08 Paul Feuerstadt also discusses the evolution of treatment for Clostridioides difficile infection, from antimicrobials to recently FDA-approved live biotherapeutics. 15:32 Thomas F. Imperiale, MD, discusses the results of the BLUE-C study, which evaluated the clinical performance of Cologuard, a next-generation, multitarget stool DNA test. 21:08 Read the full coverage here: https://www.healio.com/news/gastroenterology/20231023/video-rebyota-not-only-shuts-down-recurrence-also-affects-quality-of-life-in-c-diff https://www.healio.com/news/gastroenterology/20231025/video-risankizumab-a-great-option-for-patients-induces-clinical-remission-in-uc https://www.healio.com/news/gastroenterology/20231024/video-more-than-75-of-uc-patients-achieve-clinical-response-at-24-weeks-with-tremfya https://www.healio.com/news/gastroenterology/20231025/video-future-is-now-here-for-recurrent-c-difficile-thanks-to-live-biotherapeutics https://www.healio.com/news/gastroenterology/20231025/sensitivity-of-nextgeneration-cologuard-in-precancer-detection-numerically-exceeded-fit Disclosures: Feuerstadt reports financial relationships with Ferring Pharmaceuticals, Regeneron Pharmaceuticals, Seres Therapeutics and Takeda Pharmaceuticals. Imperiale reports grant and research support from Exact Sciences. Loftus reports financial relationships with AbbVie, Alvotech, Amgen, Arena, Avalo Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Exact Sciences, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iota Biosciences, Iterative Scopes, Janssen, KSL Diagnostics, Lilly, Morphic, Ono Pharma, Pfizer, Protagonist, Receptos, Robarts Clinical Trials, Scipher Medicine, Sun Pharma, Surrozen, Takeda, Theravance and UCB. Wehkamp reports no relevant financial disclosures.

Dr. Sheila Gujrathi is a physician-executive with a deep track record in translational science and drug development. She currently sits on the board for Ventyx Biosciences, IMMPACT Bio, ADARx Pharmaceuticals, and Janux Therapeutics and is prior Venture Advisor at OrbiMed and prior chair of Turning Point Therapeutics. She is co-founder and former CEO of Gossamer Bio, a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology. Prior to Gossamer Bio, Dr. Gujrathi served as Chief Medical Officer of Receptos, which was acquired by Celgene in 2015. Prior to Receptos, Dr. Gujrathi was Vice President of the Global Clinical Development Group in Immunology at Bristol-Myers Squibb, where she led clinical development and supported numerous global regulatory filings and approvals for Orencia® and Nulojix®. Prior to Bristol-Myers Squibb, Dr. Gujrathi held roles in the immunology, tissue growth and repair clinical development groups at Genentech. --- Support this podcast: https://podcasters.spotify.com/pod/show/theia-hc/support

Dr. Sheila Gujrathi, a biotech industry veteran with a strong track record as an entrepreneur, physician executive, translational scientist, board member, and drug developer, speaks with Venrock's Nimish Shah about the lessons learned in her career at biotech companies both big (Genentech) and small (Gossamer Bio, Receptos, Inc.). Dr. Gujrathi also discusses the importance of building a team of people with shared values, the most challenging parts of being a CEO, and how she's helping to push diversity in biotech forward.    

Today in FirstWord:

[intro music]   Host – Dan Keller Hello, and welcome to Episode Forty-nine of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features Dr. Hugh Rosen of the Scripps Research Institute. But first here are some new items in the MS Discovery Forum.   If you’re an MS researcher, you may want to keep an eye on our Bulletin Board section, where we post a variety of news items that may be of interest. One of the items we posted this week is directly related to Dr. Rosen’s work. It’s a notice that a phase 3 trial of a sphingosine 1-phosphate receptor modulator called RPC1063 has started recruiting twelve hundred patients with relapsing remitting MS in the US. RPC1063 had its origins in Dr. Rosen’s lab.   We also recently added a notice of another clinical trial to the Bulletin Board. That one’s a phase 2 trial of oral laquinimod in primary progressive MS. And a third new Bulletin Board announcement is a request for information from the Patient Centered Outcomes Research Institute to identify patient registries and research groups with established cohorts of patients for potential collaborative research opportunities on comparative effectiveness research in MS treatment.   To read any of these announcements, go to msdiscovery.org and click first on Professional Resources and then on Bulletin Board. And if you have an announcement you think may be of interest to MS researchers, please send it to editor@msdiscovery.org. We won’t post purely promotional press releases, but if we judge the notice to be of general interest, we’ll be happy to post it at no charge.   In other news, it was a relatively slow week in published MS research. According to our curated list of the latest scientific articles related to MS, only 22 such articles were published last week. Typically at least 40 MS-related peer-reviewed articles are published weekly, and we’ve seen some weeks with more than a hundred. To see the weekly lists going back to March 2012, go to msdiscovery.org and click on Papers.   Our Drug-Development Pipeline includes continually updated information on 44 investigational agents for MS. This past week we added 2 new trials and 7 other pieces of information. The drugs with important additions are dalfampridine, fingolimod, masitinib, and natalizumab. To find information on all 44 compounds, visit msdiscovery.org and click first on Research Resources and then on Drug-Development Pipeline   [transition music]   Now to the interview. Dr. Hugh Rosen studies chemical and biological approaches to the molecular mechanisms regulating lymphocyte trafficking. I met with him in his office at the Scripps Research Institute in La Jolla, California.   Interviewer – Dan Keller We're talking about mostly new compounds, S1P1 receptor compounds; the prototype now I suppose is fingolimod. What's in development and do they appear to offer advantages?   Interviewee – Hugh Rosen So, firstly, let me disclose that I am a cofounder of a biotechnology company called Receptos that has licensed an S1PR1 agonist from the Scripps Research Institute, so I have and my institution have a significant interest in this particular field.   Sphingosine 1-phosphate receptors act in a number of ways to modulate immune tissue damages in both autoimmune diseases and in viral infections. They've proven to be particularly efficacious in multiple sclerosis. Gilenya, of course discovered by Yoshitomi in Japan and developed by Novartis, has proven to be a clinically useful compound in the treatment of relapsing-remitting multiple sclerosis. And it appears to do so, at least in part, by altering the ability of lymphocytes to recirculate, and thus lymphocytes to reach the target tissues where they, in fact, produce demyelinating damage to the white matter of the central nervous system, and then the signs and symptoms of multiple sclerosis. So clearly these are useful compounds.   Gilenya, of course, is not a selective small molecule, it is an agonist of four of the five high affinity receptors for sphingosine 1-phosphate – S1P1, 3, 4, and 5 – and some of the associated side effects may be attributable in part to activity of Gilenya on other receptors like the S1P3 receptor that are not required for modulation in the treatment of multiple sclerosis.   MSDF I see that it's referred to as an immunomodulator, not necessarily referred to as a receptor agonist. Does it not have pure agonist effect? Does it have any effects either because of the other receptors or at that same S1P1 receptor?   Dr. Rosen No. In fact, Gilenya when phosphorylated is a full agonist of the sphingosine 1-phosphate receptors, and the newer compounds that are much more selective are also agonists of the sphingosine 1-phosphate 1 receptor. And some of the effects on them for cyto-mediated by downmodulation of the receptor, but I don't use the term modulators or immunomodulators because of the activity on the sphingolipid receptors per se, I use the term immunomodulator because of some of the unique advantages that we've demonstrated in model systems and in man about altering the activity of the sphingosine 1 receptor, because one of the beauties of immunomodulation is to blunt the immune response that causes collateral damage to the tissues whilst leaving sufficient of the immune response intact to allow protection from opportunistic pathogens – bacteria, viruses, and yeasts.   So one of the most striking features that we found – and these have been in some experiments done as a collaboration between my laboratory and the laboratory of Professor Michael Oldstone here at Scripps – has been in the area of influenza; pandemic influenza causes significant collateral tissue damage by having an overactive immune response. What we show is that the sphingosine 1-phosphate 1 receptor blunts that immune response and blunts the amplification of cytokines and chemokines so that you protect from the collateral tissue damage, but you leave intact the ability to mount protective, sterilizing T cell and B cell immunity to the virus. So you can eradicate the virus, sterilize it, you can provide a long-term memory both on the T-lymphocyte side as well as on the antibody side; there's class switching, there's affinity maturation, there are good protective immunity that is produced, and all this while blunting the immune response.   This is the Holy Grail as we think about treating patients, because the window for patients with autoimmune diseases like multiple sclerosis is that window between effective blunting of the immune response and the prevention of deleterious opportunistic infections that can have life-threatening consequences. So one of the advantages that I suspect we will see over time is that the sphingosine 1-phosphate agonists will prove to be particularly well-tolerated and have a wide window between the ability to limit tissue damage and progression of RRMS, and the need to protect patients from intercurrent infections or subclinical infections that become expressed later.   MSDF Do the other sphingosine 1-phosphate receptors interfere with lymphocyte trafficking also, or do they have other effects which nonselective ligands would then induce these adverse effects through them, or do they also have some effect in terms of trafficking?   Dr. Rosen They don't have significant effects on lymphocyte trafficking the way that S1PR1 does, both from the chemical approaches and the genetic evidence. S1P1 is clearly a toggle switch for lymphocyte trafficking. S1P2 is involved in the maintenance of hearing and in the function of vascular smooth muscle, so it regulates blood pressure. S1P3 is involved in cardiac contractility and also in the control of coronary artery caliber and the control of the airways, so S1P3 agonism is not a useful thing, it's actually quite deleterious. S1P4 and 5 have really no rate-limiting functions, at least of which I am aware, so there may be some redundancy and may not play a critical role in the modulation of health and disease.   MSDF Do you see compounds coming along which will be more selective and therefore not lead to the adverse effects so much? And if so, are these compounds chemically similar or do they have different structures to attach to the receptor, the S1P1?   Dr. Rosen These are clearly different structures, they're structurally very distinct from Gilenya and from each other. Novartis have a backup called siponimod. Actelion had a compound but it's only being used in psoriasis called ponesimod. Receptos has a compound now known as ozanimod – formerly known as RPC1063 – that is in two phase 3 studies for relapsing-remitting multiple sclerosis, a two-year study called RADIANCE and a one-year study called SUNBEAM, both of which are enrolling twelve hundred patients each.   MSDF And the RADIANCE trial results looked pretty good; I mean, you had 85, 90% effects at 12 to 24 weeks or even at a year in terms of relapse rate. Does this look like the next compound to emerge?   Dr. Rosen I think it's likely that ozanimod will be the next compound to be submitted for the regulatory process here in the United States and probably in Europe as well. The pleasing thing about the phase 2 data for ozanimod was, in fact, both the strong efficacy signal and a very well-tolerated safety profile; in fact the adverse effect profile of ozanimod and placebo were, in fact, indistinguishable and overlapping in the phase 2 studies. In addition, this very well-tolerated, favorable safety profile has been replicated in a highly successful phase 2 study in ulcerative colitis called TOUCHSTONE that was released recently. So clearly this is a mechanism of immunomodulation that could well prove to be useful for relapsing-remitting multiple sclerosis, but also in a range of other autoimmune diseases where treatments are hard to come by.   MSDF Even with Gilenya, I think there have been reports of a couple of cases of progressive multifocal leukoencephalopathy, so it gives a nice balance between immune surveillance and inhibiting T cell trafficking, but it seems like not a perfect balance. Does it look like that margin will be narrowed in the future with other compounds?   Dr. Rosen It's possible that it will be. I think the critical point to bear in mind is that real-world experience in tens of thousands of patients with hundreds of thousands of patient-years is really ultimately what is required to define these very rare events that on occasions do occur, and preexisting treatments with other immune-modifying agents such as Tysabri, for instance, may predispose to issues being seen later with PML. And I think that we always have to say that long-term patient experience and physician comfort are ultimately the best guides to the risk-benefit ratio.   MSDF I think you've identified something like four compounds in development, those are some that I had seen. Are there others, or these are really the ones to focus on at this point for people to keep an eye on?   Dr. Rosen There may well be others that are further behind. There have been a number of others that have had safety signals, particularly liver enzyme elevations, and significant first-dose cardiac effects. Arena have a compound that has recently completed a phase 1 multiple-dosing study and will go on to phase 2. So, you know, there are additional compounds and there will be additional compounds. Ultimately, patients do best when the best compounds appear, and the only way one knows that is to test them in man over the long-haul and define that risk-benefits for patients. And, you know, these multiple efforts really reflect the fact that a field has advanced, and that advancing field really does improve through intelligent intervention our ability to offer patients a better set of choices and a better set of long-term outcomes, which is what we're all about.   MSDF We're still focusing here on RRMS, none of this applies to the progressive phase. Is there anything coming along there?   Dr. Rosen You know, there's been one trial in primary-progressive; this was the Gilenya trial which didn't meet its endpoints. It may be that the mechanisms in rapidly progressive MS are a little different and that we don't yet, I think, understand the pathogenesis of that rather different presentation. So I'm not aware of a good alternate approaches to that, but that doesn't mean that the understanding isn't there for that to happen over time, it simply means that I'm not yet aware of it.   MSDF Finally, in secondary-progressive MS, we can understand what's going on, what led to it; if you limit relapses, that's good. But does it look like primary and secondary really may be overlapping but not the same disease?   Dr. Rosen I think there may be balances of pathogenesis where you can intervene more easily in some than in others. Clearly the sphingosine 1-phosphate agonists work particularly well by inhibiting the movement of lymphocytes into the brain. The movement of lymphocytes from the perivascular cuff into the parenchyma, into the white matter, where the demyelination proceeds. However, in parallel in multiple sclerosis, there are also events where there is collateral damage to neurons; we see axonal severing, we see elements of neuronal loss. Certainly with the sphingosine 1-phosphate agonists, there is some evidence that there is a diminution of cortical thinning over time with treatment, and that may be a really good thing.   I think that the neurodegenerative components is one that is hard to get a handle on right now, and that I think that these differences will become more obvious with early treatments of the immunopathology of multiple sclerosis. And that may well separate the autoimmune inflammatory damage and its sequelae from neurodegenerative mechanisms that may be entrained, and I think we will learn a lot from looking at those subsets of patients over time, particularly as more, better, and earlier treatment modalities allow the avoidance of significant damage in most patients.   MSDF Is there anything important we've missed or you'd like to add?   Dr. Rosen You know, I think for all of us who try to work at this interface of therapeutics, we do so because disease is, in fact, personal. We all know patients, we've all seen the multigenerational impact and depredations of multiple sclerosis on friends and family. And I think this is the very strong underlying motivator that drives us as scientists and as physician scientists to really try and bear in mind that the basic mechanisms and the basic therapeutic approaches that we pursue ultimately need a safe and effective human face to change the lives of patients in a positive way.   MSDF Very good. Thank you.   [transition music]   Thank you for listening to Episode Forty-nine of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]

1) Switching from natalizumab to fingolimod in patients with remitting-relapsing multiple sclerosis and 2) Topic of the month: Plenary sessions AAN Meeting April 2015. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Mark Keegan interviews Dr. Ludwig Kappos about his paper on switching from natalizumab to fingolimod in patients with remitting-relapsing multiple sclerosis. Dr. Sarah Wesley is reading our e-Pearl of the week about dopamine-responsive dystonia. In the next part of the podcast Dr. Alberto Espay interviews Dr. Timothy Pedley about his Presidential Lecture at the AAN Meeting about the topics of neurologists' burnout, cost and quality of healthcare, value of neurology to congress and payers along with maintenance of certification. The participants had nothing to disclose except Drs. Keegan, Kappos, Wesley, Espay and Pedley.Dr. Keegan serves as Chief Editor of eMedicine; serves as an editorial board member of Multiple Sclerosis and Related Disorders; is a consultant for Novartis, Bristol-Meyers Squibb, Bionest Partners and receives research support from Terumo BCT and Caridian BCT.Dr. Kappos serves as an editorial board member of Multiple Sclerosis Journal, Multiple Sclerosis and Related Disorders and Journal of Neurology; receives research support from Actelion Pharmaceuticals Ltd, Addex, Bayer Schering Pharma, Biogen Idec, Biotica, CSL Behring, Genzyme Corporation, Eli Lilly and Company, Merck Serono, Mitsubishi, Novartis, Ono Pharma, Pfizer Inc, Receptos, Roche, Sanofi-aventis, Santhera, Siemens, Teva Pharmaceutical Industries Ltd., UCB, Xenoport, Swiss National Research Foundation and the European Union and The Swiss MS Society; honoraria and other payments for all these activities have been exclusively used for funding of research of his department.Dr. Wesley serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Espay serves as an Associate Editor of Movement Disorders, Frontiers in Movement Disorders and Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; receives royalties for publications of books from Lippincott, Williams & Wilkins and from Cambridge University Press; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics, Teva Pharmaceutical Industries Ltd., Impax Pharmaceuticals, Merz, Pfizer Inc, Solstice Neurosciences, LLC, Eli Lilly and Company, US WorldMeds; is a consultant for Chelsea Therapeutics, Solvay Pharmaceuticals, Inc. (now Abbvie); serves on the speakers' bureaus of UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology, Movement Disorders Society; receives research support from CleveMed/Great Lakes Neurotechnologies, Michael J. Fox Foundation and the NIH.Dr. Pedley serves as an editorial board member of Journal of Clinical Neurophysiology and Nature Reviews Neurology and as Editor-in-Chief (Neurology) for UpToDate; serves as President for the American Academy of Neurology; receives royalties form the publication of the books Current Practice of Clinical Electroencephalography, Epilepsy: A comprehensive Textbook and Merritt's Neurology.

Today in FirstWord:

1) Migraine and structural changes in the brain and 2) Topic of the month: Multiple sclerosis therapy and treatment. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Jennifer Bickel interviews Dr. Messoud Ashina about his paper on migraine and structural changes in the brain. Dr. Adam Numis is reading our e-Pearl of the week about manganese neurotoxicity. In the next part of the podcast Dr. Mark Keegan interviews Dr. Paul O' Connor about teriflunomide for the treatment of multiple sclerosis. The participants had nothing to disclose except Drs. Ashima, Numis, Keegan, and O'Connor.Dr. Ashina serves as an Associate Editor of Cephalalgia; serves on the scientific advisory board for The Journal of Headache and Pain; is a consultant for ATI, Allergan, Inc., Amgen and Alder Biopharmaceuticals, Inc.; received honoraria for lecturing from Allergan Inc.Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Keegan serves as Chief Editor of eMedicine and receives research support from Terumo BCT.Dr. O'Connor serves on the scientific advisory boards of Novartis Fingolimod Steering Committee, Sanofi-aventis Teriflunomide Steering Committee, BRAVO (laquinimod) study DMC-chairman, Genetech, Inc. Roche, Acetelion Pharmaceuticals Ltd, Receptos, Inc; received honoraria for attending two Advisory board meetings; served on the editorial advisory board for the MS Journal; serves as a consultant for Biogen Idec, Merck Serono, is currently a consultant for Teva Pharmaceutical Industries Ltd., Sanofi-aventis, Novartis; receives research support from Novartis, Sanofi-aventis, Roche, Biogen Idec, and from the MS Society of Canada as National Scientific and Clinical Advisor.