Biotech Matters

Bluestar is once again heading to ASN Kidney Week, this time in Houston, TX. Since our last episode, Otsuka, the manufacturer of sibeprenlimab, announced that the FDA has granted Priority Review of their BLA application; its PDUFA date is November 28th of this year. Additionally, Vera Therapeutics, the manufacturer of atacicept put out a press release this past summer that the ORIGIN Phase 3 trial met its primary endpoint of reduction in proteinuria (UPCR); participants receiving atacicept achieved a 46% reduction from baseline, and 42% reduction compared to placebo at week 36 (p<0.0001). Vera plans to submit the BLA for atacicept in 2025, which may allow for a commercial launch in 2026. And these are just the recent developments in IgAN. Travere Therapeutics, manufacturer of FILSPARI (sparsentan) presented data from their FSGS trial – DUPLEX – at Kidney Week 2023 in Philadelphia. In contrast to the contemporaneous PROTECT study in IgAN, DUPLEX did not meet the primary endpoint. Subsequently, Travere has worked with an FDA advisory committee, reanalyzed the trial data, and announced last month that it has filed a sNDA for approval in FSGS; the PDUFA date is January 13th, 2026. After the 2023 conference, Dr. Pietro Canetta joined Bluestar Principal Jeff Fineberg on the Biotech Matters podcast to talk about all things IgAN, as well as the two FILSPARI trials and the data presented at the conference. So, it's only fitting that Dr. Canetta is back on the podcast to revisit that conversation, discuss what has happened in the two years since, and tell us what he's most looking forward to at this year's conference. Where to find Dr. Canetta: Columbia University Glomerular Center Where to learn more: Columbia CME Courses Glomerular Disease-Focused CME Course Topics and Timestamps 00:00 - Intro + recap 04:00 - Reflection on Filspari in FSGS; implications for UPCR in FSGS and other diseases going forward 12:40 - DKD: better/newer surrogate endpoints; matching patients to the right Tx 19:30 - IgAN: the 4-hit model of disease and the role of B cells 22:45 - Where do B cell-targeting therapies fit in the evolving IgAN Tx Paradigm? 26:45 - The counter argument to using Bcells early in IgAN treatment 30:10 - Bcells beyond IgAN: Lupus Nephritis and other glomerular diseases 33:00 - Different B cell-targeting mechanisms for different glomerular diseases and/or heterogeneous patient populations 36:45 - A homecoming for complement inhibitor therapies 42:00 - Other recommended sessions at Kidney Week 2025 45:00 - Where to learn more from Dr. Canetta

Principal Jeff Fineberg, PhD sits down with Vlado Perkovic, MBBS, PhD, to discuss the IgA nephropathy trial data presented at Kidney Week 2024 in San Diego. Jeff begins by asking Dr. Perkovic to talk about why targeting B-cells is an attractive target, and why BAFF/APRIL might prove more promising than CD20. The two then discuss the data with two agents in development for the treatment of IgAN, atacicept (targeting BAFF/APRIL) and sibeprenlimab (targeting APRIL only). The conversation then pivots to the prospect of complement inhibition with FABHALTA® (iptacopan) in IgA nephropathy, including a comparison of the strategy to target certain complement factors/pathways over others in IgAN. Finally, the discussion takes a broader lens to the evolving IgAN treatment landscape, that may include both of these novel therapeutic mechanisms, in addition to recently approved drugs FILSPARI® (sparsentan) and TARPEYO® (budesonide), as well as other CKD therapeutic classes, such as SGLT2 inhibitors and GLP-1 receptor agonists. Vlado Perkovic Bio Vlado Perkovic is the Provost at UNSW Sydney and Scientia Professor at UNSW, and was previously the Dean of the Faculty of Medicine and Health as well as Professorial Fellow at The George Institute, Australia, and a Staff Specialist in Nephrology at the Royal North Shore Hospital. His research focus is clinical trials and epidemiology, in particular, in preventing the progression of kidney disease and its complications. He leads several major international clinical trials with a focus on diabetic kidney disease, IgA nephropathy and CKD more broadly, and has Chaired the Steering Committees of many trials including CREDENCE, FLOW, TESTING, PROTECT, and APPLAUSE, along with several ongoing trials. Dr. Perkovic holds a Doctor of Philosophy from the University of Melbourne and is a Fellow of the Royal Australasian College of Physicians, of the Australian Academy of Health and Medical Sciences, and of the American Society of Nephrology.

Principal Jeff Fineberg, PhD welcomes back returning guest nephrologist Beatrice Goilav, MD, to discuss the program featured at Kidney Week 2024 in San Diego. Dr. Goilav reflects on what has happened in the field since last year's Kidney Week conference, as well as her hopes for what will be presented at a variety of sessions, including more data in IgA nephropathy, lupus nephritis, and FSGS. She also offers her perspective on the newest advancements with complement inhibitors in glomerular diseases – including approval of FABHALTA® (iptacopan) in IgA nephropathy – as well as recommendations for educational symposia and scientific sessions on the topic. Finally, she and Jeff discuss GLP-1 receptor agonists, and what this class of drug may mean for the management of CKD. Dr. Goilav hangs out on the social network X. Her handle is @BGoilav, and her DM is open to listeners with follow-on questions. For more information about Bluestar BioAdvisors, please visit our website.

Bluestar Managing Director Erin Olsen is back from the ASCO conference in Chicago and joins Principal Jeff Fineberg on the podcast again, this time to talk about all things antibody drug conjugates (ADCs) in oncology.  Given the number and value of deals in this space over the past couple of years, as well as the 170+ ADCs now in clinical development, Jeff asks Erin to take stock of what we've learned about the potential of these molecules, with all their moving parts, and opine on what lies ahead. Over the course of this brief conversation, Erin and Jeff touch on some key questions about ADCs, including: •    Are ADCs living up to their promise? (1:48) •    What are some lessons learned from Enhertu? (3:20) •    What have we learned about TOP1 payloads and TROP2 targeting? (6:10) •    Have ADCs delivered on better safety than chemo? (8:40) •    What's next for ADCs? (10:50) Bluestar BioAdvisors LLC is a boutique consulting firm comprised of strategic experts in the business of life sciences. We help clients answer key strategic questions about asset value, positioning, and future market potential, serving as an independent, objective advisor through the critical decision-making points of portfolio planning and business development. For more information about us, please visit Bluestar BioAdvisors' website, Erin's bio, and Jeff's bio.  

As the Bluestar team prepares to head to ASCO 2024 this upcoming weekend, Bluestar Principal Jeff Fineberg sits down with Bluestar Managing Director Erin Olsen to talk about interesting abstracts related to two topics: What are the unmet needs in 1L therapy? The KRAS G12C mutation landscape

After attending ASN Kidney Week, Bluestar Principal Jeff Fineberg sits down with Dr. Pietro Canetta to talk all things IgA nephropathy (IgAN). After Dr. Canetta provides a brief summary of his IgAN lecture at Kidney Week, Emerging Therapeutic Options in IgA Nephropathy, the two discuss the Filspari (sparsentan) data presented from both the PROTECT study, in IgAN, the DUPLEX study, in FSGS. From there, Dr. Canetta opines on the value of surrogate endpoints in predicting the three D's of CKD: death, dialysis, and doubling of serum creatinine (SCr). Dr. Canetta briefly discusses Novartis' press release announcing the positive Phase II data with atrasentan, another ETA RA, before the conversation shifts to other drug classes and therapeutic targets, including SGLT2 inhibitors, and B-cell activation (i.e., APRIL/BAFF). Finally, Jeff asks Dr. Canetta about whether the recent advancements in IgAN are generalizable to other glomerular diseases, and what might be the determinants of this. Jump to specific topics in the conversation: 00:00 Recap + guest intro/bio + Kidney Week lecture summary 05:05 Filspari (sparsentan) trial results from PROTECT (IgAN) and DUPLEX (FSGS) 12:25 Value of surrogate endpoints in predicting three D's - death, dialysis, and doubling of SCr - in glomerular disease 19:55 Atrasentan press release 23:05 The "four-hit" hypothesis of IgAN pathogenesis and SGLT2i 26:10 B-cell activation (APRIL/BAFF) as a therapeutic approach in IgAN 31:55 Generalizability (and lack thereof) of therapeutic approaches to other glomerular diseases 37:25 Where to learn more Helpful links: PROTECT Study (Filspari/sparsentan in IgAN) DUPLEX Study (Filspari/sparsentan in FSGS) Novartis press release (atrasentan in IgAN) ENVISION Study (sibeprenlimab in IgAN) Columbia Glomerular Center For more information about Bluestar BioAdvisors, please visit our website.

In the first ever Biotech Matters podcast episode, Principal Jeff Fineberg, PhD, sits down with nephrologist Beatrice Goilav, MD, to talk all things Kidney Week. Dr. Goilav offers her thoughts on an ideal day-by-day itinerary, as well as her hopes for what will be presented at a variety of sessions, including drug trials in IgAN, and new studies of SGLT2 inhibitors. She also offers her perspective on the potential for complement inhibitors in glomerular diseases, and which of these drugs in development she is most interested in. Finally, she makes some recommendations on poster abstracts to visit in the exhibit hall. For more information about Bluestar BioAdvisors, please visit our website. Dr. Goilav hangs out on X (formerly known as Twitter) @BGoilav. Her DM is open to episode listeners with follow-on questions.