Leonid Timashev

Leonid Timashev inquired about the BTK degrader's development pathway, specifically the incremental value of its three Phase III studies given a potential accelerated approval, and whether all three are necessary to fully realize its opportunity.

Answer

Amit Aggarwal, Chief Medical Officer of Hematology, emphasized the BTK degrader's potential as a foundational BTK asset. He explained the incremental value of the Phase III studies, including a head-to-head trial against bortezomib, which is crucial for establishing its role as monotherapy, alongside plans for a combination with sonrotoclax.

Leonid Timashev asked about the BTK degrader's development pathway, particularly the incremental value of its three ongoing Phase 3 studies given a potential accelerated approval.

Answer

Amit Aggarwal, Chief Medical Officer of Hematology, highlighted the BTK degrader's potential as a foundational treatment. He explained the incremental value of the Phase 3 studies, including one in a later line setting and a head-to-head trial against bortezomib, and mentioned future combination plans with sonrotoclax.

Leonid Timashev asked about RMC-055 and its new class of molecules, specifically whether it addresses secondary mutations or only direct RAS mutations, if patient selection will be needed, and its potential positioning as a next-line option or a replacement for daraxonrasib.

Answer

Chairman and CEO Mark A. Goldsmith indicated that more details would be presented at an upcoming scientific meeting. He clarified that point mutations have not emerged as the major form of resistance for daraxonrasib; instead, resistance typically involves reactivation of the RAS pathway through other means, such as amplification or increased signaling. The RMC-055 class is designed to address this pathway reactivation, not primarily new oncogenic mutations.

Leonid Timashev asked about RMC-055 and the new class of molecules, specifically if they address secondary mutations or only RAS mutations, the need for patient selection, and whether they are positioned as a next-line option or a superior alternative to daraxonrasib.

Answer

Mark Goldsmith, Chairman and CEO, indicated that more clarity would be provided at an upcoming scientific meeting. He noted that point mutations are not the major form of resistance for daraxonrasib; rather, reactivation of the RAS pathway through other means, like amplification or increased signaling, is the primary problem this new class aims to address.

Leonid Timashev asked about the commercial opportunity in the European Union, including the landscape, patient concentration, awareness, and diagnostic opportunities, given the recent hire of a President of EU Strategy.

Answer

Anthony Mancini, Chief Global Commercialization Officer, stated that second-line pancreatic cancer represents a meaningful opportunity with many patients in key European markets. He believes the company will bring a compelling value proposition, and Europe is a priority market alongside the U.S. and Japan.

Leonid Timashev asked about Revolution Medicines' commercial strategy and landscape assessment in the European Union for Diraxonrasib, considering patient concentration, awareness, and diagnostic opportunities.

Answer

Anthony Mancini, Chief Global Commercialization Officer, stated that significant thought has gone into bringing Diraxonrasib to patients, viewing the second-line pancreatic cancer indication as meaningful. He noted a substantial patient population in key European markets, including Germany and the EU4, and expressed confidence in a compelling value proposition for these priority markets.

Leonid Timashev inquired about potential sales force synergies between Alkermes' psychiatry team and the newly integrated Avadel sleep sales force, and the onboarding progress of the LUMRYZ team.

Answer

Todd Nichols, Chief Commercial Officer of Alkermes, expressed excitement about the Avadel commercial team integration. He stated there is currently little overlap between the psychiatry and sleep medicine sales forces, allowing the psychiatry team to focus on LYBALVI and ARISTADA. Synergies are expected when preparing for the alixorexton launch, at which point the sales force will be expanded for both LUMRYZ and alixorexton.

Leonid Timashev inquired about potential sales force synergies between Alkermes' psychiatry team and the newly integrated sleep sales force from Avadel, and the progress of the LUMRYZ team's onboarding.

Answer

Todd Nichols, Chief Commercial Officer, expressed excitement about the Avadel commercial team's integration. He clarified that there is currently minimal overlap between the psychiatry and sleep medicine sales forces, allowing each to remain focused. Synergies are anticipated later, particularly with the potential launch of alixorexton, when the sales force will be built out to maximize opportunities for both LUMRYZ and alixorexton.

Leonid Timoshev asked about the differences between NT2 and IH populations, the ability to accurately capture them in separate trials, physician diagnostic practices, and the impact on their relative market opportunities.

Answer

Richard Pops, CEO, stated that the full answer will be known after completing both studies, acknowledging potential regional differences in diagnosis. He highlighted the de novo nature of the clinical research for orexin-2 receptor agonists in these populations and the value of phase two data for informing phase three design, noting that patients are currently enrolled without discrimination.

Leonid Timashev of RBC Capital Markets asked if MWT is still considered the best primary endpoint over ESS and whether exploratory endpoints like cognition and fatigue could be elevated to key secondaries in Phase 3 to support label claims.

Answer

Craig Hopkinson, EVP and Chief Medical Officer, affirmed that both MWT and ESS are important, noting the strategic decision to use a dual primary in the NT2 study. Richard Pops, Chairman & CEO, highlighted the clear and robust signals on cognition and fatigue. Marcus Yountz, VP of Clinical Development, confirmed the team is actively working to elevate these endpoints for the Phase 3 program.

Leonid Timashev asked if the ongoing Phase II orexin studies are gathering data on cognition and attention, and whether the company is testing for abuse potential or 'likability' as part of the program.

Answer

COO Blair Jackson and CEO Richard Pops explained that while patient-reported outcomes in the Phase II studies touch on these domains, the primary readouts are focused on core sleep endpoints. CEO Pops confirmed that standard human abuse potential studies are being conducted as a routine part of the neuroscience program's development.

Leonid Timashev asked about Epidiolex, specifically how Jazz plans to continue growing the adult segment given the extended patent runway into the late 2030s, current adult uptake trends, educational needs, and the adult opportunity size relative to the pediatric segment.

Answer

Sam Pearce, Chief Commercial Officer, highlighted Epidiolex's blockbuster status ($1.1 billion in 2025) and identified the adult segment as a key growth source. She detailed investments in long-term care teams using the REST-LGS tool for diagnosis, efforts to increase JazzCares program utilization for patient persistency, and generation of data reinforcing seizure and non-seizure benefits. She also mentioned future investments in new adult-beneficial formulations and a Phase Ib trial in focal onset seizures.

Leonid Timashev asked about Jazz Pharmaceuticals' strategy for Epidiolex, specifically how the company plans to continue growing the adult patient segment, current adult uptake trends, areas requiring additional education, and the adult opportunity's size relative to the pediatric market.

Answer

Sam Pearce, Chief Commercial Officer, highlighted Epidiolex's blockbuster status and 9% growth, identifying the adult segment as a key future growth source. She detailed investments in long-term care teams using the REST-LGS tool for diagnosis, and the JazzCares Nurse Navigator program to improve patient persistency. She also mentioned investments in new formulations and a Phase 1b trial in focal onset seizures, leveraging the brand's durability into the late 2030s.

Leonid Timashev asked for color on the types of patients being started on MYQORZO during its launch, including whether they are new patients, switches, or patients needing higher efficacy or with lower baseline ejection fraction, and how physicians are approaching initial use compared to the initial mavacamten launch.

Answer

Robert Blum, President and CEO, and Andrew Callos, EVP and CCO, stated that they do not have patient-level data but anecdotally, it appears to be 'all of the above' (new patients, switches, etc.). They noted it is too early to observe specific trends like switching.

Leonid Timashev of RBC Capital Markets asked what primary message Cytokinetics will use to drive physician and patient enthusiasm for aficamtan, focusing on either gradient, symptoms, or cardiac function.

Answer

President and CEO Robert Blum stated that specific messaging would not be revealed pre-approval. Andrew Callos, EVP & Chief Commercial Officer, added that physicians focus on efficacy balanced with safety and the REMS. He expressed confidence in aficamtan's differentiation across these areas, with details to be unveiled at launch.

Leonid Timashev of RBC asked about the potential uptake of aficamten in nHCM as a first-in-class therapy and whether the projected 50% market share for nHCM is a global or U.S. dynamic.

Answer

Andrew Callos, EVP and CCO, projected that aficamten's uptake in nHCM would be faster than in oHCM. This is due to ongoing market development, growing physician familiarity with cardiac myosin inhibitors, and the potential for positive MAPLE and ACACIA data to expand use beyond centers of excellence.

Leonid Timashev of RBC Capital Markets asked about the endpoints for the ACACIA-HCM trial, questioning the choice of KCCQ as a single primary endpoint versus a dual primary including peak VO2, and whether this was based on internal data or FDA consultation.

Answer

EVP of R&D Fady Malik explained that while KCCQ is the primary endpoint, regulators want to see consistency across both symptomatic (KCCQ) and functional (exercise) endpoints. He noted that ACACIA includes an exercise endpoint as a secondary measure and that, practically, there isn't a significant difference between their approach and a dual primary endpoint design, as both aim to show strength of evidence across domains.

Leonid Timashev inquired about the implications of the new FDA one-trial policy for Axsome's ongoing studies, specifically asking if single Phase 3 trials could suffice for binge eating and shift work disorder, and why two separate studies are planned for pediatric and adolescent ADHD patients.

Answer

Mark Jacobson, Chief Operating Officer, stated that the team is assessing the new FDA guidance and always vets clinical plans with the FDA, noting existing alignment for shift work disorder. Herriot Tabuteau, CEO, added that ADHD affects different patient populations, requiring data from both children and adolescents, which is why two concurrent studies are planned, without impacting filing timelines.

Leonid Timashev inquired about the implications of the new FDA one-trial policy for Axsome's ongoing studies, specifically asking if single Phase III trials for binge eating and shift work disorder could be approvable, and why two studies are being run for ADHD in pediatric and adolescent patients despite the policy.

Answer

Mark Jacobson (COO, Axsome Therapeutics) stated that the team is assessing the new FDA guidance and always vets clinical plans with the FDA, noting that existing clinical packages for shift work disorder could serve as supportive evidence. Herriot Tabuteau (CEO, Axsome Therapeutics) added that each indication is specific, and for ADHD, two studies are required due to the sub-segmentation of pediatric patients (children vs. adolescents), which will not impact filing timelines.

Leonid Timashev inquired about the recent expansion in payer coverage for Auvelity, asking if it stemmed from a new contracting organization and why the gross-to-net (GTN) guidance remains unchanged despite the added lives.

Answer

Chief Commercial Officer Ari Maizel clarified that the coverage expansion was the result of pull-through from previously announced GPO contracts. Chief Financial Officer Nick Pizzie added that despite the improved access for 28 million new lives, the company is able to maintain the mid-50s gross-to-net percentage range for Auvelity.

Leonid Timashev inquired about Axsome's recent interactions with the FDA, specifically asking about any changes in review teams, agency responsiveness, or messaging regarding the approval requirements for AXS-05 in Alzheimer's disease agitation, and questioned the company's confidence in receiving a priority review.

Answer

Mark Jacobson, Chief Operating Officer, stated that engagement with the FDA remains "status quo" with no changes to the feedback received for the planned sNDA submission for AXS-05 in AD agitation. He confirmed that the drug has Breakthrough Therapy designation, making it eligible for priority review, a determination the agency makes at the time of filing.

Leonid Timashev requested additional details on the patent settlement for Auvelity with Teva, including how the 2038-2039 dates were determined, and how this resolution affects the company's peak sales assumptions.

Answer

General Counsel Hunter Murdock explained the settlement dates were a negotiated resolution and not tied to a specific event. Chief Financial Officer Nick Pizzie added that with the loss of exclusivity (LOE) date now clearer, the company plans to update and refine its guidance as the launch progresses.

Leonid Timashev of RBC Capital Markets asked for a comparison of the enrolled patient populations in the ADVANCE-2 vs. ADVANCE-1 trials for AXS-05 in ADA, and how the event rate in the ACCORD-2 trial compared to the company's expectations.

Answer

CEO Herriot Tabuteau explained that the patient populations in ADVANCE-2 and ACCORD-2 are very similar to their respective predecessor trials, as they are designed to be replicative studies. He confirmed that event rates in ACCORD-2 are in line with expectations, reinforcing confidence in the Q4 data readout timeline.

Leonid Timashev inquired about the expected growth from RCC in 2026, whether it would come from new patient starts or maintaining share, given better-than-expected gross-to-net and strong NET launch.

Answer

P.J. Haley (EVP of Commercial) stated that the company expects significant growth in 2026, driven by both neuroendocrine tumors and RCC. He emphasized that the first-line RCC market remains a focus, and they believe they can continue to achieve growth from new patients in that setting.

Leonid Timashev asked about the expected growth for cabozantinib in RCC for 2026, whether it would be driven by new patient starts or increased utilization in underutilized segments, and the strategy for maintaining market share.

Answer

P.J. Haley (EVP of Commercial, Exelixis) stated that significant growth is expected in 2026 from both neuroendocrine tumors and RCC. He indicated that the first-line market remains a key focus for driving continued growth in RCC.

Leonid Timashev asked about the relevance of emerging investigator-sponsored data for Cabozantinib in meningioma to Zanzalintinib's potential, the company's confidence in this opportunity, and the estimated market size.

Answer

Dana Aftab, Executive Vice President of Research and Development, explained that prior investigator-sponsored trials with Cabozantinib showed significant response rates (25%-75%) in meningioma, which is uncommon for targeted therapies. Given Zanza's 'Cabo-like' target profile, it was a natural progression to explore this 'white space' opportunity, with a trial expected to start in 2026.

Leonid Timashev asked about Exelixis' confidence in Zanzalintinib for meningioma, based on emerging investigator-sponsored data with Cabozantinib, and the potential size of that opportunity.

Answer

Dana Aftab, EVP of Research and Development, explained that Cabozantinib showed substantial tumor reduction in meningioma in an investigator-sponsored trial, with response rates of 25-75%. Given Zanzalintinib's 'best-in-class' Cabozantinib-like target profile, Exelixis is excited about a white-space targeting trial for Zanzalintinib in meningioma, expected to start in 2026.

Leonid Timashev inquired about the specific CRS subgroups the company might consider for deeper analysis beyond eosinophil counts, and whether this is driven by commercial opportunity or maximizing clinical benefit.

Answer

Will Lewis, Chairman and CEO, stated that the company doesn't yet know which subgroups might benefit, as there's limited background in chronic rhinosinusitis without nasal polyps. He clarified that the study is designed to find signals, and while eosinophil count was theorized to be relevant, it wasn't controlling in the ASPEN data. He emphasized following the science to concentrate efforts where the medicine shows the greatest benefit.

Leonid Timashev asked about specific subgroups being considered for deeper analysis in CRS beyond eosinophil counts, and whether this is driven by commercial opportunity or maximizing clinical benefit.

Answer

Will Lewis, Chairman and CEO of Insmed, stated that they don't yet know which subgroups might respond, as there's limited background in CRS without nasal polyps sub-segmentation. He clarified that while they aren't suggesting only subpopulations will respond, even a subset represents a substantial commercial opportunity, and they will follow the science.

Leonid Timashev inquired about the expected shape of the brensocatib launch in Europe and other ex-U.S. geographies, considering physician excitement and potential pricing dynamics.

Answer

CEO William Lewis described physician enthusiasm as 'universal or uniform' across geographies, citing strong relationships built through international congresses and the ARIKAYCE launch. He noted positive regulatory interactions in Europe and the UK. He also reminded analysts that Insmed's strategy for ARIKAYCE was to set the same list price across the US, Europe, and Japan, suggesting a consistent global approach.

Leonid Timashev from RBC Capital Markets asked about ZYNLONTA's potential in indolent lymphomas, specifically marginal zone lymphoma (MZL). He questioned its fit given the different risk-benefit profile, the clinical bar for NCCN inclusion, and whether the company would consider bispecific combinations in these indications.

Answer

CEO Ameet Mallik expressed strong encouragement from the MZL data, noting the ongoing trial's 50-patient target is sufficient for NCCN consideration, citing precedents. He stated that ZYNLONTA's current CR rates are 'well above' the ~29% benchmark for existing therapies. Due to the high single-agent efficacy and favorable safety profile, which is critical in indolent settings, Mallik confirmed the company sees no current need to explore bispecific combinations for MZL.

Leonid Timashev asked about the outlook for the supply and demand curves in 2026, specifically comparing the U.S. and European markets and whether European growth could eventually approach parity with the U.S.

Answer

Alan Bash, President of CARVYKTI, stated that the company will drive both supply and demand simultaneously and expects the ex-U.S. contribution to become increasingly meaningful as more markets launch in 2026. He detailed U.S. demand drivers including growing awareness from ASCO data, the positive impact of REMS removal, and new direct-to-patient marketing efforts.

Leonid Timashev from RBC Capital Markets inquired about the community referral process, asking if it builds brand stickiness for CARVYKTI specifically or for all CAR-Ts, and questioned the commercial messaging given that partner J&J also offers bispecifics.

Answer

Alan Bash, President of CARVYKTI, stated that while general CAR-T awareness is growing, their efforts are focused on driving action specifically for CARVYKTI based on its earlier-line approval. He affirmed that both Legend and J&J are committed to positioning CAR-T as the best option for eligible patients, citing IMWG recommendations, and noted that dedicated sales teams from both companies are delivering this message.

Leonid Timashev asked about the long-term outlook beyond 2025, questioning why 2026 consensus estimates seem low given the target of a 10,000-dose annualized run rate and whether the company will no longer be supply-capped in 2026.

Answer

Executive Alan Bash clarified that the 10,000-dose target is an annualized run rate exiting 2025, positioning the company to supply the market in 2026. He highlighted significant upside from expanding treatment sites and community penetration. Executive Ying Huang added that Legend and J&J have jointly decided to invest in further expanding the Tech Lane facility in Belgium, with additional capacity expected online in 2028, signaling confidence in long-term demand.

Speaking for Leonid Timashev, Joe asked about expectations for CARVYKTI in Europe with new commercial capacity online and the key differences in how European versus U.S. physicians select CAR-T therapies.

Answer

SVP Steven Gavel noted that European adoption is slower due to pricing negotiations and a different care model, with Germany being the key market. CEO Ying Huang stressed that overall survival data is paramount for Europe's single-payer systems, making CARVYKTI's OS benefit a powerful tool in reimbursement discussions. CMO Mythili Koneru added that strong trial enrollment in Europe shows high physician interest.

Anish Nikhanj, on behalf of Leonid Timmasheev, asked how the launch curve for AvmapKefaxin Jakobak might evolve with the switch from specialty pharmacies to broader specialty distributors, and requested early details on the patient mix based on prior lines of therapy.

Answer

President and CEO Dan Paterson suggested that with the full distribution network and publications now in place, they should see an acceleration, though it will be a steady uptick rather than a large bolus. COO Matthew Ros added that the patient mix includes those with multiple prior therapies as well as patients at their first recurrence, which is consistent with both pre-launch market research and the RAMP-201 trial population.

Leonid Timashev from RBC Capital Markets asked about the safety profile of COMP360, specifically regarding the risk of suicidality with redosing, and requested more detail on safety signals from the anorexia study.

Answer

CMO Dr. Guy Goodwin explained that while detailed time-course data is not yet available, there is no imbalance in suicidality between the drug and placebo arms in the TRD trials, suggesting it's illness-related. In the anorexia study, he noted higher overall rates of suicidality, reflecting the high-risk population, but again saw no imbalance between arms, which he described as reassuring for the overall program.

Leonid Timashev asked how Compass measures treatment durability, especially if patients begin other medications like SSRIs after their dose, and how the FDA might view this scenario.

Answer

Chief Medical Officer Dr. Guy Goodwin outlined two ways durability is measured: the maintenance of the change in MADRS score from baseline and the time until a new treatment intervention is required. He noted that from a clinical perspective, it would be unsurprising for patients who respond well to start maintenance antidepressants, and this could be a valid form of achieving durability.

Leonid Timashev of RBC asked for clarification on whether the complexities in clinical trial recruitment could signal similar logistical challenges for the commercial rollout of COMP360, or if these issues are specific to the trial setting.

Answer

Kabir Nath (Executive) and Lori Englebert (Executive) distinguished between the trial and commercial settings. Lori Englebert explained that trial protocols are inherently more rigid. For commercialization, she outlined a strategy focused on physician education for referrals and optimizing patient flow at treatment centers, drawing parallels to the successful adaptation of centers for Spravato. She expressed confidence that learnings from collaborations will help streamline the process for COMP360.

Leonid Timashev asked about the stability of INGREZZA's market share, what could change competitive dynamics in the coming year, and whether the complex payer environment is expected to persist.

Answer

Chief Commercial Officer Eric Benevich acknowledged that their competitor gained some share in 2024 with its XR launch but affirmed INGREZZA remains the leader in a growing class with significant headroom. He confirmed the complex payer environment will persist. CEO Kyle Gano added that Neurocrine's 'small biotech exemption' delays its IRA price negotiation event to 2029, providing time to learn and prepare.

Leonid Timashev from RBC Capital Markets inquired about the potential activity of the initial IGM-7354 (IL-15) dose and the competitive positioning of IGM-2644 in the crowded multiple myeloma market.

Answer

Chief Medical Officer Dr. Chris Takimoto suggested that for IGM-7354, they could see pharmacodynamic effects even at low doses, with efficacious exposures expected around Cohort 3 or 4. CEO Fred Schwarzer and Dr. Takimoto positioned IGM-2644 as a next-generation CD38 therapy, aiming to differentiate from the many BCMA-targeted bispecifics by potentially showing superiority to daratumumab, even in refractory patients.