Akash Tewari

Akash Tewari (represented by Amy) asked about an accelerated path to registrational studies for the two next-generation FcRns, ARGX-124 and ARGX-213, and insights into their potential indications and trial sizes.

Answer

Karen Massey, Chief Operating Officer, explained that the strategy for next-generation FcRns is to expand argenx's FcRn leadership, offering improved patient experiences in existing indications and pushing the biology further to address new indications. She emphasized that these molecules will broaden the impact of FcRn therapies for patients.

Akash Tewari asked about an accelerated path to registrational studies for ARGX-124 and ARGX-213, including thoughts on indication strategy and trial size.

Answer

Karen Massey, COO, explained that the next-generation FcRn molecules (ARGX-124 and ARGX-213) aim to enhance patient experience in existing indications and expand into new ones, pushing the biology further. She emphasized the strategy to establish FcRn leadership for decades.

Akash Tewari from Jefferies questioned the drivers behind the significant growth in gMG patient additions, the role of the prefilled syringe (PFS) in this trend, and the company's confidence in the upcoming seronegative MG trial, given the change in its primary endpoint.

Answer

COO Karen Massey confirmed the strong quarter in MG was fueled by the PFS expanding the prescriber base, with 150 of 1,000 PFS prescribers being new to Vyvgart. She also noted parallel growth in the IV business. CMO Luc Truyen expressed high confidence in the seronegative trial, explaining the primary endpoint was changed to 'change from baseline in MG-ADL' to increase statistical power, a move negotiated with regulators.

Akash Tewari noted a potential sequential flattening in U.S. VYVGART patient additions and asked if gMG will remain a growth market and whether there are signs of uptake in the larger, earlier-line patient population.

Answer

COO Karen Massey asserted that Argenx is just at the beginning of the gMG growth curve, citing consistent new patient starts with over 50% coming from orals. She emphasized Hytrulo's role in expanding into earlier lines. CEO Tim Van Hauwermeiren added that the ongoing trial in seronegative gMG could expand the label by another 15%.

Akash Tewari inquired about the impact of the infigratinib data on BioMarin's 2027 revenue outlook scenario analysis for Voxzogo, and the importance of full approval for Voxzogo with final adult height data on patient preference.

Answer

Brian Mueller, Chief Financial Officer, stated there are no new updates on the 2027 outlook, but the infigratinib data aligns with previous assumptions for 'more competition impacted scenarios' (assuming two competitors with comparable data). Greg Friberg, Chief R&D Officer, explained that full approval is an opportunity to present the totality of 7-10 years of safety/efficacy data, including health and wellness measures (Foramen Magnum, physical function, tibial bowing) for potential label inclusion, which builds confidence and offers tactical benefits.

Akash Tewari from Jefferies asked for details on the BMN 333 superiority trial design, including the statistical power and expected efficacy difference versus VOXZOGO, and also inquired about the potential for less frequent dosing.

Answer

Gregory Friberg, EVP and Chief R&D Officer, stated that while specific powering details would not be shared, the company is confident in the hypothesis based on preclinical data. The goal is to show a meaningfully differentiated improvement in growth and health markers. He added that while less frequent dosing could be considered, the current priority is maximizing efficacy to improve patient health and wellness.

Akash Tewari of Jefferies asked for details on the BMN-333 superiority trial design, the level of growth improvement needed to demonstrate superiority over VOXZOGO, and the potential for less frequent dosing.

Answer

Gregory Friberg, EVP and Chief R&D Officer, explained that while specific powering details are not being shared, the hypothesis is supported by preclinical data showing doubled skeletal growth and human genetic data. He noted that with BMN-333, they have the right molecule to test for greater growth and that while less frequent dosing is possible, the company is prioritizing maximizing efficacy and health benefits for patients.

An analyst on behalf of Akash Tewari from Jefferies raised questions about BMN 351, citing potential safety signals in preclinical mouse data and asking about the implications for chronic dosing and what safety data will be included in the upcoming clinical update.

Answer

Greg Friberg, Executive Vice President and Chief R&D Officer, stated that the observed signals are known class effects for ASOs at high doses. He explained that BioMarin's choice of chemistry was intended to widen the therapeutic window by enhancing potency. He assured that patients are being monitored closely and that the upcoming data presentation will include the totality of available safety data from the cohort.

Akash Tewari asked about BioMarin's appetite to in-license an oral FGFR inhibitor for achondroplasia, similar to infigratinib, to address investor concerns about the long-term terminal value of VOXZOGO.

Answer

CEO Alexander Hardy responded that while their BD focus is on genetically defined conditions, they are confident in their current CNP-based leadership strategy. He highlighted CNP's ability to treat other skeletal conditions and its critical safety profile for treating infants, which he described as a very high hurdle for any competing FGFR inhibitor to overcome.

Akash Tewari asked about the relationship between Voxzogo's quarterly patient additions and its incremental revenue, questioning the forward-looking growth assumptions. He also pressed for details on BioMarin's IP strategy against Ascendis, asking if the goal is a royalty payment or a preliminary injunction.

Answer

EVP, Chief Commercial Officer Cristin Hubbard highlighted the 65% year-over-year growth in patients and reiterated the company's confidence in its projected 25% CAGR for Voxzogo through 2027, driven by its broad label and global reach. President and CEO Alexander Hardy declined to elaborate on the specific legal strategy regarding IP, stating the company will provide updates when action is taken.

Aakash Tewari asked about the rationale behind the LITESPARK-033 trial design in post-adjuvant first-line RCC compared to CheckMate-9ER, the current and projected percentage of first-line RCC patients receiving adjuvant PD-1, and the required profile for zanzalintinib plus belzutifan in second-line plus to support a LITESPARK-001-like trial.

Answer

Mike Morrissey (President and CEO, Exelixis) emphasized a forward-looking strategy for zanzalintinib to become a standard of care for RCC in the 2030s, considering the evolving standard of care. He noted that the non-clear cell trial and the two Merck trials are just the beginning of building a franchise for RCC.

Aakash Tewari asked about the rationale behind running LITESPARK-033 in the post-adjuvant first-line RCC setting versus CheckMate-9ER's PD-1 naive approach, the evolving percentage of first-line RCC patients receiving adjuvant PD-1, and the required profile for ZANZA plus belzutifan in second-line plus to support a LITESPARK-001-like trial.

Answer

Mike Morrissey (President and CEO) explained that the strategy for Zanza in RCC is forward-looking, targeting the early to mid-2030s to establish Zanza as a standard of care. He emphasized that the ongoing trials (non-clear cell, two Merck trials) are just the beginning of building a franchise for RCC, with discussions for other orthogonal MOA combination partners underway.

Akash Tewari of Jefferies questioned the decision to halt the STELLAR-305 head and neck trial, referencing prior management commentary suggesting a low bar to proceed, and asked if the zanzalutinib data was unfavorable compared to historical cabozantinib data.

Answer

EVP & CMO Amy Peterson responded that the decision was based on a continuous assessment of a dynamic competitive and regulatory landscape. She emphasized the company is reallocating resources to other high-priority development opportunities for zanzalutinib as part of its 'Wave two' franchise strategy.

Akash Tewari asked about the event rate hurdles for advancing the STELLAR-305 head and neck study and whether Exelixis has considered acquiring a PD-1/VEGF bispecific asset.

Answer

Chief Medical Officer Amy Peterson declined to specify event rate targets for STELLAR-305, stating they await data maturation for the IDMC review. President and CEO Michael Morrissey addressed the BD question, indicating that while they evaluate all opportunities, they do not currently see clear differentiation in the crowded PD-1/VEGF bispecific space and are awaiting key clinical data from the class.

Anna Stan, on behalf of Akash Tewari, asked about the potential to expand the Merck partnership beyond RCC and head and neck, and how zanzalintinib's head and neck data might compare to competitors in the PD-L1 refractory setting.

Answer

Chief Medical Officer Amy Peterson stated that Exelixis is always looking to expand zanzalintinib into new indications. She clarified that in head and neck cancer, their trial is focused on the frontline setting, where they have a lead, rather than competing directly with bispecifics in the refractory space.

Akash Tewari from Jefferies asked Dave Ricks about consumer analogs for long-term penetration of Eli Lilly's weight loss products in the U.S. and ex-U.S., and whether the company's guidance anticipates meaningful cannibalization between oral and injectable obesity products.

Answer

Dave Ricks, Chair and CEO, reiterated that cannibalization is not expected and strategically less concerning as Lilly aims for patients to use the best Lilly medicine. He found consumer analogs difficult to pinpoint, noting differences from ED drugs or cosmetics due to profound health benefits. He emphasized learning from other industries to reduce consumer friction, leverage first-party data, and explore platforms, pricing, and subscription models, enabled by LillyDirect and the out-of-pocket business, citing 1 million U.S. and hundreds of thousands international users. Mike Czapar, SVP of Investor Relations, directed the question.

Akash Tewari asked Dave Ricks to discuss consumer analogs for long-term penetration of Lilly's weight loss products in both US and ex-US markets, given Lilly's view as a consumer stock, and whether the guidance expects meaningful cannibalization between oral and injectable obesity products.

Answer

Dave Ricks, Chair and CEO, stated that cannibalization is not currently observed or expected, and strategically, Lilly aims for patients to use the best medicine from its portfolio. He found consumer analogs difficult to identify due to the unique nature of high out-of-pocket prescription medication with profound health benefits. He highlighted learnings from other industries to reduce consumer friction, leverage first-party data, and explore platform interfaces, pricing opportunities, and subscription models through LillyDirect.

Akash Tewari referenced Dave Ricks' previous comments on orforglipron pricing ($100/month) and its potential for global impact, asking if Eli Lilly can achieve both continuous innovation and broad patient access with a parity pricing model.

Answer

Dave Ricks, Chair and CEO, confirmed Eli Lilly's strategy to bridge both goals. He highlighted the unique consumer self-pay channel and price elasticity in the GLP-1 category, committing to both strong consumer offerings and proving health benefits for chronic diseases to compete for healthcare dollars.

Akash Tewari referenced Dave Ricks' previous comments on orforglipron pricing ($100/month impacting innovation) and its potential for global human health impact (billions of doses), asking if Lilly can achieve both goals of preserving innovation and ensuring global access with a parity pricing model.

Answer

Dave Ricks, Chair and CEO, confirmed Lilly's strategy to bridge both goals. He highlighted the unique consumer self-pay channel in GLP-1s due to consistent benefits and price elasticity, incentivizing compelling self-pay prices. He also emphasized building indications for chronic diseases to compete for healthcare dollars, believing it's possible to do both as the market is only scratching the surface of global treatment.

Akash Tewari of Jefferies LLC asked about Lilly's willingness to launch new drugs at net price parity between the U.S. and Europe, and his confidence in reaching a pricing solution with the administration without new legislation.

Answer

David Ricks, Chair and CEO, affirmed that rebalancing pricing between the U.S. and Europe is a rational long-term goal. He suggested that using new products as an 'on-ramp' is a reasonable approach, provided structural changes occur in both markets, such as higher reimbursement in Europe and a deflation of the U.S. gross-to-net bubble. He stated Lilly is engaging constructively with the administration.

Akash Tewari asked if long-term net pricing for GLP-1s would need to approach insulin levels to reach the entire overweight and obese population. He also questioned the gap between Street margin estimates of over 50% and Lilly's insistence on a sustainable 40-45% range.

Answer

Patrik Jonsson, President of Cardiometabolic Health, noted a disciplined approach to pricing and an evolution toward a smaller delta between list and net prices. CFO Lucas Montarce added that current pricing trends are consistent with forecasts and that the company remains disciplined in its approach to provide optionality and open access for patients, implicitly addressing the volume-over-price dynamic.

Akash Tewari of Jefferies sought clarification on the comment that GLP-1 pricing would be 'relatively stable' in 2025, asking if it implied offsets to new discounts or a steady state.

Answer

An executive clarified that 'stable' refers to a continuation of the recent single-digit price erosion trend. Executive Patrik Jonsson added that Mounjaro adherence is already strong and access is high, suggesting a mature dynamic.

Akash Tewari questioned Pfizer's confidence in SV (sigvotatug vedotin) delivering a superior profile against docetaxel in second-line plus metastatic non-small cell lung cancer (mCLCs), asking if enrichment in B6A high-expressing patients would be necessary and for expectations regarding the upcoming readout.

Answer

Chief Scientific Officer Chris Boshoff clarified that SV is being tested in a second-line study against docetaxel and a first-line study with pembrolizumab. He expressed confidence in the trials, citing single-agent activity with over 30% response rate and 16.3 months median overall survival in phase II, and a 57% overall response rate with pembrolizumab combination. He acknowledged that other ADCs haven't shown benefit over docetaxel but stated Pfizer is encouraged by its data.

Akash Tewari inquired about Pfizer's upcoming phase III EZH2 readout in CRPC, asking about confidence in adequate target exposure after food effect studies and expectations for overall survival benefit, specifically a 20-30% improvement.

Answer

Chris Boshoff, Chief Scientific Officer and President of Research and Development, Pfizer, confirmed that the EZH2 program is a first-in-class, internally discovered asset. He highlighted previously shared randomized data showing significant PFS benefit and expressed confidence in the selected dose based on ASCO data, which demonstrated compatibility with reduced GI adverse events. Albert Bourla, Chairman and CEO, Pfizer, also contributed.

Akash Tewari inquired about the upcoming phase three EVH2 readout in CRPC, expressing surprise it wasn't more prominently flagged. He asked about Pfizer's confidence in achieving adequate target exposure after food effect studies and expectations for overall survival benefit.

Answer

Chris Boshoff, Chief Scientific Officer and President of Research and Development, described EVH2 as a first-in-class, internally discovered program with previously shared randomized data showing significant PFS benefit. He confirmed three phase three studies are ongoing, with the first readout expected in coming months. He also noted recent ASCO data on the food effect supported the selected phase three dose, which showed reduced gastrointestinal adverse events, affirming confidence in the dose.

Akash Tewari asked if it would be fair to assume that the bottom-line impact of a hypothetical 25% tariff on transfer prices would be a single-digit percentage after mitigation.

Answer

CEO Albert Bourla explicitly declined to confirm any specific financial impact from a hypothetical tariff scenario, stating he was cautious about making such statements. He emphasized that the company's primary focus is on preventing tariffs, while having detailed contingency plans in place if they are enacted.

Akash Tewari asked a technical question about the development of once-daily danuglipron, questioning if a formal update is pending data from a specific formulation being tested later in its trial.

Answer

CEO Albert Bourla and Executive Chris Boshoff declined to comment on the specifics of the formulation technology or the trial design, stating they had nothing to add at this time.

Akash Tewari questioned Pfizer's confidence in its 25-valent pneumococcal vaccine against competitors with potentially broader coverage and asked for clarification on the 'special properties' of the modified-release oral GLP-1, danuglipron.

Answer

Chief Scientific Officer Mikael Dolsten expressed confidence in the 25-valent vaccine, highlighting its superior immunogenicity for serotype 3, a key driver of disease. For danuglipron, he hypothesized that the modified-release formulation could offer a smoother pharmacokinetic profile with fewer peaks, potentially improving the patient experience and tolerability.

Akash Tewari asked about Merck's development strategy for sac-TMT, questioning if there were plans to explore it in first-line and cLTS settings or head-to-head against the KEYNOTE-189 regimen, and why Merck's Trop-2 development seemed conservative compared to competitors.

Answer

Dean Li, President of Research Labs, stated that sac-TMT is considered a "workhorse ADC" with best-in-class potential, emphasizing the impact of linker and payload changes. He highlighted Merck's ambitious program with 16 Phase 3 studies for sac-TMT, including differentiated approaches in non-small cell lung cancer and breast cancer, and aiming to be first in other tumor types.

Akash Tewari inquired about Merck's development strategy for sac-TMT, asking if there are plans to explore it in first-line and CLT settings for PD-1 low expressing patients or head-to-head against KEYNOTE-189, and questioned if the Trop-2 development strategy is conservative compared to competitors.

Answer

Dean Li, President of Research Laboratories, Merck & Co. Inc, characterized sac-TMT as a 'workhorse ADC' with best-in-class potential, highlighting that Merck has 16 Phase III studies underway, including differentiated approaches in non-small cell lung cancer and breast cancer, and aims to be first in other tumor types, challenging the notion of a conservative strategy.

Akash Tewari of Jefferies asked about the future cadence of patient additions for Winrevir, its adoption in earlier lines of therapy, and for confirmation that the Hanzo GLP-1 asset has entered the clinic.

Answer

Chairman & CEO Robert Davis noted consistent patient adds of 400-500 per month. EVP & CFO Caroline Litchfield added that while 75% of use is in sicker patients, over half of prescribers have used it in less severe cases. Dr. Dean Li, President of Merck Research Labs, confirmed the Hanzo GLP-1 is on schedule to enter the clinic this year.

Akash Tewari of Jefferies asked about the future cadence of new patient additions for Winrevir, its adoption in earlier lines of therapy, and sought confirmation on whether the Hanzo-partnered GLP-1 asset has entered clinical trials.

Answer

Chairman & CEO Robert Davis noted Winrevir has been consistently adding 400-500 patients per month. EVP & CFO Caroline Litchfield added that use in less severe patients is increasing. Dr. Dean Li, President of Merck Research Laboratories, confirmed that the Hanzo GLP-1 asset is on schedule to move into the clinic this year.

Akash Tewari of Jefferies posed several questions about potential tariffs, including the expected rate, implementation process, and the potential earnings impact after mitigation efforts.

Answer

CEO Robert Davis stated he would not speculate on the specifics of potential tariffs. He reiterated that Merck is well-positioned to manage impacts through short-term inventory and long-term manufacturing repositioning, but could not provide a specific financial impact without knowing the final tariff language.

Akash Tewari asked for the key components of the upgraded $25 billion oncology new product guidance and how Merck's TROP2 ADC strategy differs from competitors like AstraZeneca.

Answer

CEO Robert Davis explained the $25B+ figure is comprised of ADCs, small molecules, and the individualized neoantigen therapy, with the recent increase driven by the Harpoon acquisition and greater confidence in their TROP2 program. Dr. Dean Li, President of Merck Research Labs, added that their TROP2 ADC (SAC-TMT) is a differentiated molecule and emphasized the strategy of matching the right ADC to the right patient population.

Akash Tewari inquired about the co-formulation of Regeneron's PCSK9 GIP/GLP combo, specifically how both drugs can be delivered in a single auto-injector, and asked about any potential partnering discussions to share development costs.

Answer

Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President, and Chief Scientific Officer, Regeneron Pharmaceuticals, highlighted the company's best-in-class formulations group for enabling the delivery of both an antibody and a peptide in a small auto-injector. He emphasized the differentiated benefit of combining profound weight loss with 50%-60% LDL lowering, addressing cardiovascular risk in obese patients. He did not comment on partnering discussions but stated the company is always open to deals that enhance shareholder value.

Akash Tewari inquired about the co-formulation of Regeneron's PCSK9 GIP/GLP combo, specifically how both drugs are delivered in a single auto-injector, and asked about the potential for partnering this asset to share development costs, including any ongoing discussions.

Answer

Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President, and Chief Scientific Officer, Regeneron Pharmaceuticals, highlighted the advanced formulation capabilities enabling the delivery of both an antibody and a peptide in a small auto-injector. Dr. Leonard Schleifer, Board Co-Chair, Co-Founder, President, and Chief Executive Officer, Regeneron Pharmaceuticals, emphasized the differentiation for obese patients with high cholesterol, noting the existing co-use of GLP and PCSK9 inhibitors. Dr. Yancopoulos added that the strategy is to provide a new benefit (LDL lowering) beyond just weight loss.

Akash Tewari with Jefferies inquired about Regeneron's re-tooled commercial strategy for EYLEA, specifically regarding volume-based discounts, price erosion on EYLEA and EYLEA HD, and the outlook for volume and revenue gains ahead of potential label enhancements.

Answer

Regeneron President and CEO, Leonard Schleifer, noted that competitive issues prevent detailed disclosure of ground-level strategy and rebates. Executive Vice President of Commercial, Marion McCourt, emphasized EYLEA HD's strong performance is driven by its clinical efficacy, safety, and durability, leading to robust physician demand. She anticipates sequential demand growth for EYLEA HD to moderate to high single digits awaiting label enhancements and a 10% demand reduction for EYLEA 2mg in the coming quarter.

Akash Tewari asked about Regeneron's retooled commercial strategy for EYLEA, specifically regarding volume-based discounts, price erosion on EYLEA and EYLEA HD, and anticipated volume and revenue gains ahead of potential label enhancements.

Answer

President and CEO Leonard Schleifer indicated that competitive issues prevent detailed discussion of ground-level strategy and rebates. EVP of Commercial Marion McCourt highlighted EYLEA HD's strong performance driven by its clinical efficacy, safety, and durability. She noted anticipated sequential demand growth for EYLEA HD to moderate to high single digits awaiting label enhancements and a similar 10% demand reduction for EYLEA 2 mg in the coming quarter.

Akash Tewari from Jefferies asked about the Eylea biosimilar 'Pavlo,' noting its ASP hasn't declined as expected, and questioned its impact on Eylea's outlook and how Regeneron might combat the strategy.

Answer

President & CEO Dr. Leonard Schleifer questioned whether deferred rebates could be a factor in the competitor's strategy and stated they are looking into it. He emphasized that EYLEA HD is the ultimate answer to competition, given its superior profile and the trust physicians have in the Regeneron brand.

Akash Tewari from Jefferies asked about the impact of the EYLEA biosimilar PAVLOU, noting its stable ASP might suggest deferred discounts, and questioned Regeneron's strategy to combat this.

Answer

President & CEO Dr. Leonard Schleifer stated they are looking into competitor rebate practices but emphasized that EYLEA HD is the company's 'real answer' to competition. He believes physicians will prefer EYLEA HD over both original EYLEA and its biosimilars as they gain more experience with its profile.

Akash Tewari of Jefferies asked for specifics on the patient assistance funding, including the percentage of the U.S. patient base that received aid in 2024 and Regeneron's contingency plan if other manufacturers do not join the proposed matching program.

Answer

President and CEO Dr. Leonard Schleifer stated that the company cannot correlate its foundation contributions to EYLEA usage, as it is not permissible. Regarding the contingency plan, he reiterated the strategy is to 'stimulate a community of givers' and did not outline an alternative if the matching program fails to attract other donors.

Akash Tewari from Jefferies asked for perspective on the Factor XI program and confidence in REGN-7508, given issues with other drugs in the class and Regeneron's positive proof-of-concept data.

Answer

President and CSO, Dr. George Yancopoulos, detailed the two-antibody strategy. REGN-7508 is designed for maximum anticoagulant activity, while REGN-9933 is a gentler option with a potentially lower bleeding risk. He explained this dual approach provides physicians and patients with flexibility to balance efficacy and safety, addressing a significant unmet need.

Akash Tewari asked for confirmation on Rezdiffra's adherence rate, noting feedback of 80%+ compared to the 40-60% range cited for similar drugs. He also questioned expectations for Rezdiffra's net pricing stability after reaching the high 30s gross-to-net range in 2026, specifically if it would see annual declines similar to GLP-1s.

Answer

Bill Sibold, Chief Executive Officer, confirmed that current adherence data aligns with well-tolerated orals (60-70% at one year), with strong positive anecdotal feedback from clinicians. Regarding net pricing, he stated that gross-to-net typically declines over time due to future bidding (e.g., Medicare 2027), but emphasized Madrigal's strong position for 2026 with broad first-line access and improved utilization management criteria.

Akash Tewari asked for confirmation on Rezdiffra's adherence rates (specifically if they are 80%+ versus the cited 40-60%) and about expectations for Rezdiffra's net pricing, particularly if it will be stable after reaching the high 30s gross-to-net, unlike GLP-1s' mid-single-digit annual declines.

Answer

CEO Bill Sibold confirmed adherence rates are similar to well-tolerated orals (60-70% at one year), with anecdotal feedback suggesting strong adherence. Regarding net pricing, he stated gross-to-net will generally decline after 2026 due to factors like Medicare bidding, but emphasized the strong position for 2026 with broad first-line access and improved utilization management criteria. He believes Rezdiffra's cost-effectiveness, as highlighted by ICER, supports its value despite GLP-1 price erosion.

An analyst on behalf of Akash Tewari of Jefferies followed up on gross-to-net, asking for the drivers behind the price improvement in Q2, the impact from the Part D redesign, and details on any inventory stocking contribution.

Answer

CFO Mardi Dier attributed the quarter's strength to high demand, not inventory stocking. She reiterated that gross-to-net will fall within the 20-30% range for the year and that the Part D impact was minimal due to the 2024 baseline. CEO Bill Sibold added that gross-to-net is inherently choppy and includes factors like their widely used $0 co-pay assistance program, which is crucial for patient adherence.

Akash Tewari asked about the company's confidence in demonstrating a clinical outcomes benefit in F4 compensated cirrhosis patients, questioning the correlation between liver fat reduction and hepatic events.

Answer

CEO William Sibold expressed high confidence, citing Rezdiffra's liver-directed mechanism of action and the meaningful 6.7 kPa reduction in liver stiffness observed at two years. He stated this data gives the team confidence in the ongoing MAESTRO-NASH OUTCOMES trial's ability to show a benefit in preventing adverse liver events.

An analyst on behalf of Akash Tewari asked which outcomes trial Madrigal is more confident in hitting—the MAESTRO-NASH expansion or the F4 cirrhosis trial—and the rationale for this confidence.

Answer

CEO William Sibold expressed confidence in both trials. He highlighted that positive results from a cirrhosis patient subset in a prior open-label study support the potential for Rezdiffra to work in this advanced population. He also noted that the significant interest and enrollment in the cirrhosis trial underscore the community's desire for a treatment and will generate important learnings.

Akash Tewari asked about the ADEPT program two, specifically why the data has not been locked despite indications of no site irregularities and similar dropouts to schizophrenia studies, and why more ex-U.S. sites were opened. He also requested insights from the open-label period in Cabenfi's relapse prevention studies for Alzheimer's psychosis.

Answer

Chris Boerner, Board Chair and CEO, reiterated that ADEPT 2 results are expected by year-end and declined to provide additional specifics, emphasizing confidence in the overall Cabenfi program based on external data, positive feedback in schizophrenia, and internal data. Cristian Massacesi, Chief Medical Officer and Head of Global Drug Development, clarified that ADEPT 1:1 is a relapse prevention design, an ongoing study, and data from the open-label leading phase will not be shared until the full study data is released, noting patient randomization is based on response.

Akash Tewari asked about the ADEPT 2 program, specifically if there were any site irregularities or if dropouts were similar to schizophrenia studies, why the data hasn't been locked, and why more ex-U.S. sites were opened. He also asked about learnings from the open-label period in Cabenfi's relapse prevention studies for Alzheimer's psychosis.

Answer

CEO Chris Boerner reiterated that the ADEPT 2 study will read out in the next couple of months and declined to provide additional specifics, but reaffirmed confidence in the overall COBENFY program, citing compelling external data, positive feedback on psychosis symptoms in schizophrenia, and internal data. CMO Christian Massacesi explained that ADEPT 1 is a relapse prevention design with a different primary endpoint, and the study is ongoing, with patients needing a certain degree of response to be randomized after a 20-week open-label phase.

Akash Tewari from Jefferies asked for specifics on the upcoming COBENFI AD psychosis trial, including expected dosing levels and dropout rates, and questioned if the company's bullishness has changed.

Answer

EVP & Chief Medical Officer Samit Hirawat stated that he could not comment on trial specifics like dropout rates as the study remains blinded, but noted the current formulation has better tolerability than earlier versions of the drug. CEO Chris Boerner closed by reiterating that the company remains very excited about COBENFI's potential in Alzheimer's disease psychosis.

Akash Tewari of Jefferies questioned the perceived risk of the adjunctive schizophrenia trial for Cobenfy, given historical failures in the setting, and asked if the company is aiming for a 6-month echo monitoring update for Camzyos.

Answer

CMO Samit Hirawat expressed confidence in the adjunctive schizophrenia trial, citing maintained efficacy in long-term data from other studies. For Camzyos, CCO Adam Lenkowsky confirmed the European label was updated to once every 6 months for echo monitoring in the maintenance phase, a change intended to increase capacity at Centers of Excellence.

Akash Tewari asked if there was potential to renegotiate the milvexian partnership with J&J and questioned why BMS seems more conservative than Merck on the patent life of its subcutaneous IO therapy.

Answer

CEO Christopher Boerner stated there is no change to the J&J partnership and that they remain fully supportive of the milvexian program. Chief Commercialization Officer Adam Lenkowsky addressed the subcu Opdivo question by confirming the goal is to convert 30-40% of the U.S. business before the 2028 LOE, which, based on its broad patent estate, will extend the franchise into the next decade.

Akash Tewari from Jefferies inquired about what to look for in the competitor's ODYSSEY data that would support the hypothesis that Cytokinetics' ACACIA trial will succeed and demonstrate a clear exposure-response relationship.

Answer

President and CEO Robert Blum distinguished between trial conduct and mechanism, highlighting ACACIA's optimized dosing. Fady Malik, EVP of R&D, added that the key question is whether the competitor's trial failure was due to drug-specific issues or the mechanism itself, which will inform confidence in ACACIA's potential success.

Akash Tewari of Jefferies asked what real-world data would be needed to achieve a yearly echo monitoring requirement and if the company is confident in securing an educational REMS versus an ETASU.

Answer

Robert I. Blum, President and CEO, declined to specify details about echo monitoring frequency to protect competitive advantage but stated that it is reasonable for investors to assume an ETASU (Elements To Assure Safe Use) REMS is the approach being taken.

On behalf of Akash Tewari from Jefferies, an analyst asked for Zymeworks' perspective on the updated Q4 2025 timing for the HORIZON-GEA-01 readout, questioning if it was a delay and what reasons might be behind the new guidance.

Answer

CEO Kenneth Galbraith corrected the premise, stating it was not a delay as the prior guidance was for the second half of 2025, which includes Q4. He emphasized that the trial is event-driven, and the timing is dictated by reaching the prespecified number of progression-free survival events, which is monitored blindly to maintain data integrity.

On behalf of Akash Tewari, an analyst asked how a competitor's DESTINY-Gastric03 study in HER2-positive gastric cancer might impact the market potential for zanidatamab (Zani).

Answer

CEO Kenneth Galbraith expressed strong confidence in zanidatamab's clinical data, highlighting its ability to generate high, durable responses with a favorable tolerability profile. He stated that while they follow competitors, they feel very comfortable with Zani's position and look forward to their own upcoming data readouts to confirm its potential.

Akash Tewari inquired about any shifts in the FDA's willingness to accept Chinese clinical data for BioNTech's assets and asked when the company expects to satisfy Project Optimus requirements for the Phase 3 dose of BNT327.

Answer

Chief Medical Officer Özlem Türeci reported that discussions with the FDA are positive and being finalized. She highlighted that the company is supplementing Chinese data with dose optimization data from Western populations in its global Phase 3 trials and expects to finalize the go-forward dose for all three indications shortly.

Akash Tewari asked about the long-term outlook for the non-small cell lung cancer (NSCLC) standard of care, questioning if a bispecific with chemotherapy would suffice or if an ADC combination would be necessary, and about the comparative safety profile.

Answer

Chief Medical Officer Özlem Türeci explained that both approaches will be relevant. She stated that BNT327 with chemotherapy aims to replace current CPIs, but as the treatment bar rises, ADC combinations with their bispecific will also become important. CEO Ugur Sahin added that several of BioNTech's proprietary ADCs are candidates for such combinations in NSCLC.

Akash Tewari from Jefferies asked about BioNTech's current position on partnering for the BNT327 program and the desired capabilities in a potential collaborator.

Answer

CSO Ryan Richardson stated that while BioNTech is currently developing BNT327 independently for its initial trials, the company recognizes the program's broad potential. He confirmed they have been approached by other firms and are evaluating collaborations, suggesting a partnership is likely within the next 12-18 months to accelerate and expand development, particularly for combination therapies.

An analyst on for Akash Tewari asked about expectations for the control arm performance in the HERIZON-GEA trial and the company's confidence that it would not outperform historical benchmarks.

Answer

Head of R&D Rob Iannone explained that data from three prior Phase III trials show consistent control arm performance with a median PFS between 6.9 and 8.1 months, which was factored into their trial design. He expressed confidence in zanidatamab, citing promising Phase II data and an upcoming overall survival data update at ASCO.

An analyst on behalf of Akash Tewari requested details on the Phase III trial of zanidatamab in HER2+ breast cancer post-T-DXd, including study design, timing, patient opportunity, and confidence in overcoming HER2 resistance.

Answer

EVP, Global Head of R&D Robert Iannone highlighted zanidatamab's differentiated mechanism. He explained the ongoing Phase III trial is designed to address the data gap for patients who have progressed on T-DXd. The study randomizes patients to a physician's choice of chemotherapy backbone plus either zanidatamab or trastuzumab, aiming to be the first to show efficacy in this setting.

An analyst on behalf of Akash Tewari at Jefferies requested more details on the Phase III trial of zanidatamab in HER2+ breast cancer post-T-DXd, including study design and confidence in overcoming resistance.

Answer

EVP, Global Head of R&D, Rob Iannone, highlighted zanidatamab's differentiated mechanism as key to its potential. The ongoing Phase III trial targets the significant unmet need of patients who have progressed on T-DXd. The study randomizes patients to receive a physician's choice of chemotherapy plus either zanidatamab or trastuzumab, with the goal of being the first therapy to demonstrate efficacy in this setting.

A representative for Akash Tewari asked for more details on CRENESSITY's payer dynamics, noting the 70% reimbursement rate was higher than anticipated, and questioned how this might evolve.

Answer

Chief Commercial Officer Eric Benevich acknowledged the 70% reimbursement rate exceeded expectations but cautioned that this was achieved primarily through medical exceptions, as most health plans have not yet conducted formal formulary reviews. Chief Financial Officer Matthew Abernethy credited the market access team for effectively educating payers on the drug's value.

Akash Tewari asked if the 60-40 market share split for INGREZZA is expected to hold given payer dynamics, and also inquired about the use of telehealth for new CRENESSITY patient starts.

Answer

CEO Kyle Gano addressed the market share question, stating that Neurocrine expects to remain the market leader due to INGREZZA's differentiated profile. On the second question, Chief Commercial Officer Eric Benevich noted that while some endocrinologists may use telehealth, their research indicates the majority will prefer an in-person visit to initiate treatment with a novel medication like CRENESSITY.

An analyst on behalf of Akash Tewari from Jefferies asked why Neurocrine is confident its M1/M4 asset does not require co-dosing like KarXT and what to expect from its initial Phase I data.

Answer

CEO Kyle Gano explained that the molecule, NBI-570, has high selectivity for M1 and M4 receptors and is designed to be more CNS-penetrant, which avoids the need for a peripheral blocker. He noted that data from the Phase I muscarinic programs in 2025 will inform next steps and potential patient populations.

Amy Li, on behalf of Akash Tewari, asked about Alkermes's safety bar for ALKS 2680 and the company's confidence in demonstrating a better safety profile than competitor TAK-861 in the NT1 population.

Answer

CEO Richard Pops noted the programs are at different development stages and highlighted that ALKS 2680's true once-daily profile, which promotes daytime wakefulness while allowing for normal nighttime sleep, is a key differentiator. He deferred further comparison until Phase II data is available.

Amy Li, on behalf of Akash Tiwari, asked about Alkermes's confidence in ALKS 2680's ability to differentiate on safety from competitors in NT1 and what the FDA requires for Phase II dose exploration before moving to Phase III.

Answer

CEO Richard Pops declined to comment on competitor programs but highlighted the rigorous design of Alkermes's Phase II studies (80 patients, multi-week, parallel design) to fully characterize the drug's profile. He stated the program is already differentiated by its dosing flexibility and that the orexin class has generally shown profound efficacy with mild, transient side effects.

On behalf of Akash Tewari, an analyst asked if overall survival data would be required for the vepdegestrant regulatory submission, the expected market entry timeline, and if Arvinas is considering partnerships for its neuro programs.

Answer

CMO Noah Berkowitz explained that while regulators review overall survival (OS) for adverse trends, trials are typically submitted based on progression-free survival (PFS) and are not powered for OS. CEO John Houston added that while Arvinas can advance its neuro pipeline, it remains open to a strategic partner for later-stage development and will review options as data matures.

Akash Tewari asked for help framing expectations for the upcoming vepdegestrant-CDK4 combination data, including potential response rates. He also raised a question about the VERITAC-2 trial design, specifically whether the 6-month prior endocrine therapy requirement was sufficient to exclude fast progressors.

Answer

Chief Medical Officer Noah Berkowitz clarified that the decision to advance the first-line combination is primarily driven by safety, with efficacy already established in later-line settings. CEO John Houston declined to comment on any questions related to the VERITAC-2 trial, citing the proximity of the data readout.

Kathy Wang, on for Akash Tewari of Jefferies, asked about competitor claims of 'warehousing' patients, the competitive dynamics post-IZERVAY label update, and SYFOVRE inventory levels in Q4.

Answer

CEO Dr. Cedric Francois and CMO Dr. Caroline Baumal refuted the 'warehousing' idea, emphasizing SYFOVRE's market leadership, growing injections, and differentiated long-term data. EVP of Commercial David Acheson added that Q4 channel inventory was within the typical 2-3 week range and not a cause for concern.

Akash Tewari of Jefferies questioned the Phase III trial design for olezarsen in sHTG, focusing on how it was powered for endpoints like acute pancreatitis and abdominal pain, and what KOLs consider a clinically meaningful reduction.

Answer

CEO Brett Monia and Chief Clinical Development Officer Eugene Schneider responded. Monia clarified the study is well-powered for its primary endpoint of triglyceride reduction. While not explicitly powered for acute pancreatitis (AP) reduction due to a lack of precedent, the large trial size and positive AP data from the FCS study provide confidence in seeing a meaningful signal. Schneider added that there is no established threshold for a clinically meaningful AP reduction, so any significant decrease would be viewed positively.

Speaking for Akash Tewari, Phoebe asked about the Angelman syndrome program, inquiring if EEG benefits are persisting in the long-term extension study, whether EEG is considered a clinical endpoint or a biomarker, and if there are signal variations between children and adults.

Answer

CEO Brett Monia clarified that EEG is being measured as an exploratory biomarker in the Phase III and long-term extension studies to better understand the disease's biology, not as a clinical endpoint. He acknowledged that EEG patterns differ by age, with adults having a more muted signal, and stated that the long-term extension EEG data has not yet been formally assessed.

Questioned the confidence in uveitis efficacy being Cmax driven and whether izokibep's exposure would be sufficient for significant clinical benefit compared to secukinumab.

Answer

The company's modeling equates 160mg subcu izokibep to 10mg/kg IV secukinumab in terms of exposure. Due to its smaller size, izokibep penetrates the blood-retinal barrier, allowing for both systemic and local action in the eye, which they hope will lead to an improved outcome compared to secukinumab.