Jay Olson

Jay Olson asked a financial question regarding Leqembi's product margin, current investment levels, long-term targets, and the expected steady-state product margin.

Answer

Robin C. Kramer, EVP and CFO of Biogen, stated that specific product margins for Leqembi are not disclosed but expects improved margins over the near to mid-term as the launch progresses and manufacturing processes are enhanced. Christopher A. Viehbacher, President and CEO, added that margin expansion will primarily be driven by revenue growth, as significant R&D investments (e.g., AHEAD 3-45 study, subcutaneous formulations) and commercial investments (for market creation and education) are ongoing. He anticipates increasing margins over time as revenue grows to absorb the OpEx level.

Jay Olson inquired about the product margin for Leqembi, the current level of expenses invested, the desired longer-term state, and the steady-state target for its product margin.

Answer

Robin C. Kramer, EVP and CFO, Biogen, stated that specific product margins for Leqembi are not disclosed but expects improved margins over the near to mid-term as the launch progresses and manufacturing processes are enhanced. Christopher A. Viehbacher, President and CEO, Biogen, added that margin expansion will be driven by revenue growth catching up to the significant R&D and commercial investments, including the AHEAD 3-45 study and subcutaneous formulations.

Jay Olson from Oppenheimer & Co. Inc. asked about the subcutaneous formulation of Leqembi, including physician feedback from AAIC, the potential incremental patient population, and opportunities for direct-to-consumer education.

Answer

Priya Singhal, EVP & Head of Development, highlighted the upcoming PDUFA date and noted subcu offers convenience and a safety advantage with fewer infusion reactions. Alisha Alaimo, President & Head of North America, added that physicians and patients value the flexibility. She expects the choice will be patient-driven, particularly benefiting those in rural areas, with physicians offering all available options.

Jay Olson from Oppenheimer & Co. Inc. asked about the subcutaneous formulation of Leqembi, seeking physician feedback from AAIC, the potential incremental patient population, and opportunities for direct-to-consumer education.

Answer

Priya Singhal, EVP & Head of Development, highlighted the upcoming PDUFA date and noted subcu Leqembi offers convenience, optionality, and a safety advantage. Alisha Alaimo, President & Head of North America, added that physicians will offer patients the choice between IV and subcu formulations, with the latter being particularly beneficial for patients in rural areas. She confirmed that even the IV maintenance option is being well-received.

Jay Olson asked for details on the $14 billion peak revenue potential cited for four key pipeline programs, specifically their relative contribution and timing.

Answer

CEO Christopher Viehbacher declined to provide individual product forecasts but framed the figure as a measure of the pipeline's potential magnitude. He highlighted BIIB080 in Alzheimer's and the lupus franchise as significant opportunities, clarifying that the $14 billion is a cumulative peak sales estimate at the high end of a $9 billion to $14 billion range, contingent on clinical success.

Jay Olson from Oppenheimer asked about the expected impact of the Repatha Vesalius CV results on its overall market opportunity and what specific details to look for at the American Heart Association presentation. He also inquired about lessons learned from Vesalius CV that could be applied to Olpasiran.

Answer

James Bradner, EVP of Research and Development, highlighted Vesalius CV as the first PCSK9 to prevent first cardiovascular events, a major advance for primary prevention, and noted the study's global conduct learnings. Murdo Gordon, EVP of Global Commercial Operations, emphasized the data as a "call to action" for primary care physicians, reinforcing Repatha's affordable, incremental risk reduction. Robert Bradway, CEO, added that Amgen Now enhances access.

Jay Olson asked about the expected impact of the VESALIUS-CV results on Repatha's overall market opportunity, key details to anticipate from the American Heart Association presentation, and any lessons learned applicable to the Olpasiran program.

Answer

James Bradner, EVP of Research and Development, emphasized VESALIUS-CV as a landmark study, being the first and only PCSK9 to demonstrate prevention of first cardiovascular events, a significant advance for primary prevention patients on optimized lipid management. Murdo Gordon, EVP of Global Commercial Operations, reinforced the study's importance as a 'call to action' for primary care physicians and highlighted AmgenNow's role in improving access and affordability. Lessons learned included effective global study conduct and the potential of targeting inflammatory lipoproteins.

Jay Olson inquired about the filing timeline for bemarituzumab (BEMA) following positive FORTITUDE-101 results, asking if data from the FORTITUDE-102 trial is required for submission and when detailed 101 results will be presented.

Answer

James Bradner, EVP of R&D, stated that the regulatory strategy has not yet been disclosed. He noted that the strategy will integrate data from both the positive FORTITUDE-101 study and the FORTITUDE-102 study, which is expected to read out in H2 2025 or H1 2026.

Jay Olson from Oppenheimer asked for expectations regarding the upcoming Phase III bemarituzumab study readout in Q2 and for an overview of its potential market opportunity in gastric cancer.

Answer

James Bradner, EVP of R&D, stated they are hopeful the FORTITUDE-101 study will demonstrate a meaningful improvement in overall survival. Murdo Gordon, EVP of Global Commercial Operations, outlined the market as the fifth most common cancer globally, with an initial addressable U.S. population of about 7,000 patients and a significant opportunity in Asia, highlighting the drug's combinability with standard chemotherapy.

Jay Olson asked about the key learnings expected from the Repatha VESALIUS cardiovascular outcomes study and how those insights could create synergies for olpasiran and MariTide.

Answer

James Bradner, EVP of R&D, described the VESALIUS study as a large and valuable dataset that will yield significant insights. Murdo Gordon, EVP of Global Commercial Operations, added that there are substantial commercial synergies in applying their LDL-lowering leadership to Lp(a) with olpasiran, while acknowledging the unique market dynamics for an Lp(a)-targeting therapy.

Jay Olson asked about the development of subcutaneous BLINCYTO, noting the registrational study is planned for the second half of next year, and inquired about what might have changed regarding its timeline.

Answer

EVP of R&D James Bradner emphasized that subcutaneous BLINCYTO is a 'major priority,' citing impressive efficacy data from earlier studies. He stated that the program is progressing and that there is 'nothing to read into the timing' of the study initiation.

Jay Olson asked about the advantages and disadvantages of combining Rezdiffra with MGL-2086 versus other oral GLP-1s like orforglipron, and explored other potential mechanisms that could be synergistic with Rezdiffra.

Answer

Bill Sibold, Chief Executive Officer, clarified that MGL-2086 is an orforglipron derivative. David Soergel, Chief Medical Officer, detailed the rationale for GLP-1 combination, noting that even modest weight loss enhances Rezdiffra's efficacy. He added that Madrigal is broadly evaluating other mechanisms with strong scientific rationale for combination, aiming for combined efficacy benefits. Bill Sibold emphasized that Rezdiffra's IP extending to 2045 allows for a thoughtful and disciplined pipeline build.

Jay Olson asked about the pros and cons of combining Rezdiffra with MGL-2086 versus other oral GLP-1s like orforglipron, and inquired about other potential mechanisms that might be synergistic with Rezdiffra.

Answer

CEO Bill Sibold clarified that MGL-2086 is an orforglipron derivative. CMO David Soergel explained that even modest weight loss (as little as 5%) enhances Rezdiffra's anti-fibrotic efficacy, providing the rationale for GLP-1 combination. He added that Madrigal is evaluating 'pretty much every mechanism of action' for scientific rationale and combined efficacy. Bill Sibold noted Rezdiffra's IP until 2045 allows for thoughtful pipeline development.

Jay Olson of Oppenheimer & Co. Inc. asked about the due diligence supporting a fixed-dose combination of the new oral GLP-1 with ResDiffera and inquired about other mechanisms being considered for future business development.

Answer

CEO Bill Sibold stated that business development remains a key strategy and that the market will move toward combinations with ResDiffera as the foundational therapy. CMO David Soergel added that the scientific rationale is strong, as 5% weight loss enhances ResDiffera's efficacy. He confirmed the chosen molecule has a de-risked structure and favorable properties. Sibold noted a fixed-dose combo is ideal but not essential.

Jay Olson asked for feedback on the direct-to-consumer (DTC) marketing campaign and inquired about the types of complementary assets Madrigal is seeking through business development.

Answer

CEO William Sibold reported positive feedback on the DTC campaign, which aims to educate patients and spur action. On business development, he stated the focus is on extending MASH leadership by acquiring assets with compelling new mechanisms or those that could be combined with Rezdiffra, emphasizing a financially disciplined approach across all stages of development.

Jay Olson asked about the event rate in the MAESTRO-NASH trial, the importance of fibrosis improvement for clinical outcomes, and expectations for the fibrosis endpoint in the competing ESSENCE trial.

Answer

CEO William Sibold declined to comment on event rates in the ongoing trial. Regarding the ESSENCE trial, he stated they will wait for the full data, as top-line results can be misleading without details on dosing and discontinuation handling. He reiterated confidence in Rezdiffra's strong market position and product profile regardless of competitive data readouts.

Jay Olson inquired about the governance structure of the collaboration with Bristol Myers Squibb, asking which party makes decisions for new trials and who leads the initiation of these clinical trials.

Answer

Uğur Şahin, Chief Executive Officer and Co-founder, explained that it's a classical collaborative approach with multiple arms, including a Joint Steering Committee (JSC) for discussions. He noted that all decisions made so far are based on interoperable partners, and both partners have the flexibility to conduct combination trials with their products, regardless of direct interest from the other, aiming to exhaustively exploit each other's pipelines.

Jay Olson inquired about the governance structure of the collaboration with Bristol-Myers Squibb, asking which party makes decisions for new trials and who leads their initiation.

Answer

Uğur Şahin, Chief Executive Officer and Co-founder, described the collaboration as a classical approach with multiple collaborative arms and a Joint Steering Committee (JSC) for discussions. He stated that decisions are based on interoperable partners, and both parties have the flexibility to conduct combination trials with their respective products, aiming to comprehensively exploit the pipelines.

Jay Olson inquired about the expected increase in R&D spending over the next few years given the expansion of Phase III programs and asked if there is an ideal number of late-stage trials the company aims to manage.

Answer

CFO Jens Holstein stated it was too early for future guidance but noted the company is comfortable with its current R&D spending levels and will invest wisely in high-potential assets like BNT327 while controlling costs. Chief Strategy Officer Ryan Richardson added that the current R&D level already supports 10 ongoing Phase II or III trials, demonstrating significant scale in the mid- and late-stage pipeline.

Jay Olson asked Beth Hougen about Ionis's capital allocation priorities, specifically regarding external versus internal investments, given the company's strong balance sheet.

Answer

Beth Hougen, CFO, Ionis, stated that the top priority for capital allocation is internal growth, emphasizing the tremendous opportunity within the company's pipeline and existing/upcoming marketed products. She affirmed a commitment to disciplined investment to support future growth.

Jay Olson asked Beth Hougen about Ionis's priorities for capital allocation, specifically regarding internal versus external investments, given the company's strong balance sheet.

Answer

Beth Hougen, CFO, stated that the top priority for capital allocation is internal growth, emphasizing the tremendous opportunities within Ionis's pipeline and existing/upcoming marketed products. She affirmed a commitment to disciplined investment to drive future growth.

Jay Olson of Oppenheimer & Co. Inc. asked how the successful TRINGOZA launch impacts the company's strategy for its early-stage pipeline, specifically the decision to partner versus retain assets. He also inquired about long-term plans for building an ex-U.S. commercial infrastructure.

Answer

CEO Brett Monia stated that the company's priority remains its wholly-owned pipeline, focusing on cardiology and neurology, but they will continue to partner assets outside these core areas, as exemplified by the recent sapaglutizine deal. Regarding ex-U.S. expansion, he said the immediate focus is on executing U.S. launches successfully, and while internal discussions are happening, it is not yet time to build out an international commercial presence.

Jay Olson inquired about the prescriber overlap between FCS and sHTG for olezarsen and how Ionis plans to leverage it. He also asked if the sHTG pivotal studies were sufficiently powered to demonstrate a reduction in acute pancreatitis (AP) events.

Answer

Chief Global Product Strategy Officer Kyle Jenne confirmed a significant prescriber overlap (cardiologists, endocrinologists) and noted the TRYNGOLZA launch is building the foundation for sHTG. CEO Brett Monia explained that while the sHTG studies are not formally powered for the secondary AP endpoint, they are combining data from the CORE and CORE2 studies and extending the observation period to maximize the potential to see a signal. He stressed the primary endpoint is triglyceride reduction, a key driver for physician adoption.

Jay Olson of Oppenheimer & Co. Inc. asked for details on the TRYNGOLZA launch, including how many of the estimated 3,000 U.S. FCS patients are currently diagnosed and what early launch metrics could be shared.

Answer

Chief Global Product Strategy Officer Kyle Jenne reported a very successful early launch, noting that "several hundred" of the addressable patients are currently identified. While declining to provide specific metrics, he highlighted encouraging trends, including a broad prescriber base of endocrinologists and cardiologists, rapid prescription fulfillment times, and positive feedback on the Ionis Every Step patient support program.

Jay Olson asked if the Phase III design for ION582 in Angelman syndrome would support ex-U.S. regulatory filings and about partnering plans. He also inquired about the rationale for starting the APP ASO program in Down syndrome and its development strategy.

Answer

CEO Brett Monia stated they are nearing alignment with EU regulators for the Angelman trial and that it's too early to comment on ex-U.S. commercial plans. EVP of Research Eric Swayze explained that Down syndrome was a logical starting point for the APP ASO because patients have an extra APP gene, causing amyloid accumulation. Chief Clinical Development Officer Eugene Schneider added that sporadic Alzheimer's is a potential future indication.

Jay Olson asked about Directlidine's pipeline, specifically if Neurocrine Biosciences is considering Alzheimer's psychosis beyond schizophrenia and bipolar, and what lessons might be learned from the upcoming Cobenfe Phase III study in Alzheimer's.

Answer

Sanjay Keswani, Chief Medical Officer, confirmed that while Directlidine's Phase III is for schizophrenia and Phase II for bipolar mania, the company is interested in Alzheimer's psychosis for one of its follow-on muscarinic molecules, which has safety advantages for the elderly. He stated they will closely watch BMS's Cobenfe data for lessons for the field.

Jay Olson asked about potential indications for Directlidine beyond schizophrenia and bipolar, specifically if Alzheimer's psychosis is being considered, and what lessons might be learned from the upcoming Cobenfe Phase III study readout.

Answer

Sanjay Keswani, Chief Medical Officer, confirmed Directlidine's Phase III program targets schizophrenia and a Phase II bipolar mania study was initiated. He expressed interest in Alzheimer's psychosis for follow-on molecules within their robust muscarinic portfolio, which will be unveiled at R&D Day. Keswani noted they would closely watch BMS's Cobenfe ADEPT Phase III study readout for lessons for the field.

Jay Olson from Oppenheimer & Co. Inc. welcomed new CMO Sanjay Keswani and asked what key findings from his due diligence attracted him to join Neurocrine.

Answer

CMO Sanjay Keswani stated he was drawn to Neurocrine's transformational stage, evolving into a multi-modality company. He highlighted the high quality of the late-phase psychiatry portfolio with its validated targets and expressed excitement for the early-phase pipeline, which includes large molecules like bispecifics, ADCs, and peptides with transformational potential.

Jay Olson asked about the timing for the valbenazine JOURNEY study results in schizophrenia and what learnings could be applied to next-generation VMAT2 inhibitors, particularly in light of a recent competitor failure.

Answer

Chief Medical Officer Dr. Eiry Roberts confirmed the JOURNEY study data is expected around mid-2025 and will provide key learnings on efficacy and patient subgroups to guide future development. She noted that a competitor's recent trial failure highlights the difficulty of research in this area but does not diminish their confidence in their own NBI-'568 muscarinic program for acute psychosis.

Jay Olson from Oppenheimer inquired about Neurocrine's level of commitment to the epilepsy therapeutic area and whether it plans to replace its recently discontinued asset with another.

Answer

CEO Kyle Gano affirmed a strong commitment to epilepsy, highlighting a number of preclinical programs. He stated that while the company will not pursue another T-type calcium channel blocker, it is looking forward to bringing a mixed NAV1.2/1.6 inhibitor into the clinic next year, pending completion of preclinical studies.

Jay Olson asked for the rationale behind terminating the BET inhibitor program, questioning if it was related to a strategic focus on targeted therapies like mCALR. He also inquired how soon mCALR could move into registrational studies, given the BET inhibitor was on track for such studies.

Answer

CEO Bill Meury stated the BET inhibitor termination was due to the complex risk-benefit calculus for BET inhibitors, prioritizing programs with a higher probability of technical and regulatory success (PTRS) and a clearer path to market. President Pablo Cagnoni added that the goal is to start one or more pivotal trials for 989 in 2026, with ET likely first in H1 2026 and MF in H2 2026, emphasizing that the BET program termination does not reduce ambition in MPNs.

Jay Olson of Oppenheimer & Co. Inc. asked new CEO Bill Meury about the strategic prioritization of Incyte's three core therapeutic areas: oncology, hematology, and immunology.

Answer

CEO Bill Meury stated that myeloproliferative neoplasms (MPNs) in hematology are the company's number one priority, citing an "asymmetrical advantage" and the transformative potential of assets like the mutant CalR antibody, 989. He described immunology as having a credible path to building a large product with povorcitinib in specific skin conditions. For broader oncology, he emphasized a disciplined approach to finding the right products in defensible markets.

Jay Olson asked about the key data points to expect from the CDK2 inhibitor update at ASCO and the gating factors for initiating the Phase III trial in ovarian cancer, including the companion diagnostic's progress.

Answer

Executive Pablo Cagnoni described the upcoming ASCO data as an incremental update to the comprehensive ESMO presentation. He confirmed that the pivotal trial in platinum-resistant ovarian cancer is being implemented, the companion diagnostic is advancing well, and a required combination study with bevacizumab is underway.

Jay Olson from Oppenheimer & Co. Inc. asked about the commercialization plans for the once-daily ruxolitinib XR formulation following its successful bioequivalence study. He also inquired about the timeline for developing a fixed-dose combination of ruxolitinib XR with the company's BET inhibitor.

Answer

Herve Hoppenot, CEO, outlined that ruxolitinib XR is expected to be submitted to the FDA by year-end 2025, with a commercial launch anticipated in 2026. The goal is to switch as many patients as possible before the 2029 generic entry. He added that a decision on a fixed-dose combination with the BET inhibitor is pending further data on the frontline combination's profile and the evolution of the broader MPN portfolio.

Jay Olson from Oppenheimer & Co. Inc. asked which one or two near-term catalysts are most important for reshaping top-line growth and inquired about any portfolio gaps and the company's business development strategy.

Answer

Herve Hoppenot, CEO, highlighted the near-term launches of Niktimvo, tafasitamab, and retifanlimab, which could collectively add around $800 million in revenue by 2029. He pointed to povorcitinib and the CDK2 inhibitor as the next wave of larger opportunities. He stated that the current pipeline is strong, so the BD focus is on early-stage technology or potentially late-stage commercial products, rather than assets that would require significant near-term R&D spending.

Jay Olson asked about lessons learned from recent dynamics in the oral GLP-1 space, particularly regarding attrition and safety/tolerability concerns with small molecule oral GLP-1s. He also inquired about rate-limiting steps and ongoing work for the DACRA IND filing.

Answer

Brian Lian (President and CEO, Viking Therapeutics) highlighted VK2735's strong safety and tolerability profile, noting that the Venture Oral Dosing Study provided insights into optimal starting doses and titration windows. He acknowledged the difficulty in developing oral therapeutics, leading to high attrition. For the DACRA IND, he mentioned exploring its potential as an oral therapy due to better potency, which could lead to a differentiated compound.

Jay Olson asked about lessons learned or read-across from recent dynamics in the oral GLP-1 space, specifically regarding attrition and safety/tolerability concerns with small molecule oral GLP-1s. He also asked about rate-limiting steps and ongoing work for the DACRA IND filing.

Answer

Brian Lian (President and CEO, Viking Therapeutics) highlighted VK2735's strong safety and tolerability profile, noting that the VENTURE-Oral Dosing Study provided insights into optimal starting doses and titration windows. He acknowledged the general difficulty and high attrition in developing oral therapeutics. For the DACRA IND, he mentioned exploring its potential as an oral therapy due to better potency, which could allow for reasonably low dosing, making it a potentially differentiated compound.

Jay Olson from Oppenheimer & Co. Inc. asked if patient dosing had commenced in the Phase III VANQUISH program and for any projections on enrollment completion timelines. He also inquired if the planned subcutaneous monthly maintenance study would utilize a randomized withdrawal design.

Answer

President & CEO Brian Lian confirmed that patient dosing is underway in the VANQUISH studies and that enthusiasm is high, but it is too early to project enrollment timelines. He clarified that the maintenance study will not be a randomized withdrawal design; instead, patients will be titrated to a high dose and then transitioned to various monthly or daily oral maintenance doses.

Jay Olson asked if Viking plans to test oral VK2735 in indications beyond obesity, such as type 2 diabetes. He also requested commentary on recent M&A activity in the obesity space and the overall level of strategic interest.

Answer

Brian Lian, President and CEO, confirmed that the Phase III program for VK2735 will include a study in obese patients with type 2 diabetes, which will assess both weight change and glycemic control. Regarding M&A, he acknowledged the high level of interest in the obesity space and Viking's attractive portfolio but declined to comment on specific business development discussions.

Jay Olson inquired about the study design for a potential monthly subcutaneous formulation of VK2735 and its path to label inclusion. He also asked about plans to study a transition from the subcutaneous to the oral formulation for maintenance.

Answer

CEO Brian Lian confirmed the long-term goal is label inclusion for a monthly dose. The initial study will assess weight maintenance by titrating patients to a high dose and then switching to a monthly cadence. Regarding the transition to an oral formulation, he indicated this would ideally be studied by first conducting a PK exploratory study, followed by a longer-term maintenance trial.

Jay Olson asked about the safety and tolerability profile needed at the 100mg oral dose to consider testing higher doses, the status of securing a synthetic manufacturing route, and how the company views the value split between the subcutaneous and oral forms of VK2735.

Answer

Executive Brian Lian indicated a comfortable tolerability profile, as the review committee never recommended halting dose escalation. He stated that discussions on synthetic manufacturing routes are in progress. He estimated the value of the VK2735 franchise is split approximately 80% for the subcutaneous formulation and 20% for the oral version, viewing the injectable as the anchor product.

Jay Olson of Oppenheimer & Co. Inc. inquired about the specific timing for the Q3 top-line data from the RECONNECT study for ZYN-two in Fragile X syndrome, the definition of a clinically meaningful outcome, and the evidence supporting Harmony's confidence in a successful result.

Answer

Chief Medical & Scientific Officer Dr. Kumar Budur, introduced by President & CEO Dr. Jeffrey Dayno, confirmed the Q3 data readout is on track. Dr. Budur stated that success is defined by achieving a statistically significant outcome on the primary endpoint of social avoidance in patients with complete methylation. He expressed high confidence, noting the study is designed to replicate the strong, statistically significant findings from the prior Phase II/III CONNECT study.

Jay Olson of Oppenheimer & Co. Inc. inquired whether vormatrogene could demonstrate a disease-modifying benefit and if the RADIANT results suggest potential utility in Developmental and Epileptic Encephalopathies (DEE).

Answer

President & CEO Marcio Souza and Chief Scientific Officer Steven Petrou both suggested the data points towards disease modification. Petrou explained that the sustained reduction in seizures indicates a reversal of the "seizures beget seizures" process by resetting the brain's excitability level. Regarding DEE, Souza stated that while theoretically possible, the company's strategy is to focus vormatrogene on adult epilepsy and advance raletirgene, which is better suited, for DEE conditions like SCN2A and SCN8A.

Jay Olson from Oppenheimer & Co. Inc. asked about the expected durability of MM120's efficacy beyond twelve weeks and the anticipated real-world dosing frequency following potential approval.

Answer

CEO Robert Barrow noted that Phase 2 data showed no loss of separation at twelve weeks, suggesting durability could extend further. Chief Medical Officer Dr. Daniel Karlin explained that real-world dosing would likely be variable based on individual patient response patterns rather than a prespecified interval, with some patients potentially achieving long-term remission from a single dose.

Jay Olson from Oppenheimer & Co. Inc. asked about expectations for the durability of MM120's efficacy beyond twelve weeks and what the anticipated dosing interval might be in a real-world setting.

Answer

CEO Robert Barrow noted that Phase 2 data suggested durability could last beyond 12 weeks. CMO Dr. Daniel Karlin added that they don't anticipate a pre-specified dosing interval. Instead, treatment patterns will be variable, ranging from a single dose providing long-term remission to potential redosing every few months or annually, depending on individual patient response.

Jay Olson from Oppenheimer inquired if INO-3107's label would include a 'surgery-sparing' claim, asked about the ex-U.S. registration strategy, and questioned the initial target indication for the dMAb platform.

Answer

CCO Michael Sumner explained that while the FDA recognizes surgery reduction as the key benefit, it is too early to predict the exact label terminology. CEO Jacqueline Shea stated that the placebo-controlled confirmatory trial is designed to meet European and U.K. regulatory requirements for future submissions. Regarding the dMAb platform, Shea noted that specific target indications are not yet disclosed but highlighted the technology's broad potential for antibodies and protein replacement therapies.

Jay Olson asked for clarification on the timeline for testing and validating the new CELLECTRA device manufacturing process and questioned whether the confirmatory study must be initiated prior to the BLA submission.

Answer

CEO Dr. Jacqueline Shea confirmed the device issue is resolved and outlined a timeline to complete validation testing in the first half of 2025, begin a rolling BLA submission mid-year, and complete it within 3-4 months. Dr. Shea and Chief Medical Officer Dr. Michael Sumner affirmed that the confirmatory trial must be initiated before the BLA submission, noting significant progress has already been made on site activation to demonstrate commitment to the FDA.

Jay Olson inquired about the regulatory strategy and timelines for INO-3107 outside the U.S., specifically in the EU, UK, Japan, and China. He also asked for physician feedback on the recently presented immunology data.

Answer

Chief Medical Officer Dr. Mike Sumner stated that compelling, placebo-controlled data would be required for approval in the EU and UK, and the current trial is designed to provide this data. He noted that outreach to Japan and China has not yet occurred. Both Dr. Sumner and CEO Dr. Jacqueline Shea confirmed that feedback from clinicians and Key Opinion Leaders (KOLs) on the new immunology data has been very positive, as it clearly illustrates the mechanism of action and builds confidence in the clinical results.

Jay Olson of Oppenheimer inquired about the scope of the upcoming REZOLVE Phase IIb data release, asking which secondary endpoints are most critical. He also followed up to clarify if the planned Phase III study would use weight-based or fixed dosing.

Answer

Executive Jonathan Zalevsky explained the top-line data will feature the primary endpoint (EASI score change) and key secondary endpoints like EASI-75, EASI-90, vIGA, and itch scores. He confirmed that Nektar plans to continue with precise, weight-based dosing in Phase III, likely administered via an auto-injector with weight bands.

Jay Olson of Oppenheimer asked about the scope of the upcoming atopic dermatitis data release, the profile needed to capture first-line market share, and the expected timing for the NKTR-255 JAVELIN Bladder Medley study results.

Answer

CEO Howard Robin and CRDO Dr. Jonathan Zalevsky responded. Dr. Zalevsky indicated the top-line release will cover the 16-week induction data, with full results reserved for a medical meeting. He stated that replicating Phase Ib efficacy is the primary way to impact the first-line setting, but REZPEG's novel, durable mechanism offers another path. For NKTR-255, they reiterated Merck's guidance for a potential PFS readout in mid-2025, as the analysis is event-driven.

Jay Olson of Oppenheimer & Co. Inc. requested details on body composition findings from the DIO model, particularly regarding lean muscle mass preservation. He also asked about the relative commercial opportunity for Nimacimab as a monotherapy versus a combination therapy, and the feasibility of a fixed-dose combination.

Answer

CSO Chris Twitty confirmed that in the DIO model, Nimacimab showed significant fat mass reduction with lean mass preservation, an effect that was even greater in combination with tirzepatide. Tu Diep, a commercial executive, stated that both monotherapy and combination therapy represent large, multi-billion dollar opportunities of relatively equal size. CEO Punit Dhillon noted that while a fixed-dose combination is a future possibility, the immediate priority is demonstrating monotherapy efficacy.

Jay Olson inquired about what to expect from the upcoming preclinical data for nimacimab and asked for insights on the read-through from recent M&A deals in the non-GLP-1 obesity space.

Answer

CSO Christopher Twitty stated the upcoming preclinical data will be more robust, including biomarker work on key mechanisms and differentiation, and will begin to explore combination approaches. President and CEO Punit Dhillon and COO Tu Diep commented that recent industry deals validate the market's interest in alternative mechanisms beyond GLP-1s. They noted that KOLs are increasingly seeking tolerable and convenient options, positioning nimacimab favorably.

Jay Olson asked for feedback from Key Opinion Leaders (KOLs) on the preclinical data presented at ObesityWeek, especially regarding body composition and lean muscle mass preservation. He also inquired about the commercial strategy for nimacimab as a combination therapy versus a monotherapy.

Answer

Punit Dhillon, President and CEO, stated that KOLs appreciated the new data distinguishing peripheral from central CB1 inhibition, especially following recent data from monlunabant. He noted the preclinical results showed significant dose-dependent weight loss, improved glucose metabolism, and lean mass preservation. Regarding commercial strategy, Dhillon positioned nimacimab as a complementary alternative to GLP-1s, targeting metabolism rather than just appetite. He sees a significant opportunity for a monotherapy in the overweight and Class 1 obesity populations where extreme weight loss isn't always necessary.

Jay Olson followed up on the MAGNITUDE trial, asking how the baseline characteristics of enrolled patients might impact the estimated time to reach the required number of events for the primary endpoint.

Answer

Chief Medical Officer David Lebwohl stated that the baseline characteristics, including the proportion of patients with variant disease (10-15%) and Class III patients (10-15%), are similar to other recent Phase III studies in the field. This suggests that the event rate should evolve similarly, though he noted more patients are on baseline tafamidis.

Jay Olson inquired about Intellia's strategy for commercializing NTLA-2002 outside the United States and whether this could involve a partnership.

Answer

CEO John Leonard stated that the company's primary focus is on a successful U.S. launch. He confirmed they are evaluating various options for ex-U.S. commercialization, and a partnership is one of the possibilities being considered, though no decision has been made yet.

Jay Olson inquired about Intellia's strategy for the ex-U.S. commercial opportunity for NTLA-2002 and whether the company is considering partnerships for the program outside the U.S.

Answer

CEO John Leonard confirmed a substantial ex-U.S. commercial opportunity exists. He stated that Intellia's current plan is to be positioned to launch the drug themselves but that they continuously evaluate potential partnerships that could extend their reach. Any such plans would be shared as the strategy evolves.

Asked for details on the luvelta wind-down process, spending, and the ideal partnership structure, and also inquired about the differentiation of STRO-006 compared to Pfizer's competing program.

Answer

The company is winding down its own spending on luvelta and seeks a partner to assume full development responsibility and expenses. For STRO-006, differentiation comes from a proprietary antibody targeting a specific integrin beta-6 confirmation and the use of a unique DAR8 exatecan payload, which they believe is competitive and potentially superior to competitor approaches.

Jay Olson from Oppenheimer sought clarity on the operational and financial mechanics of deprioritizing luvelta, including study enrollment and partnership structure, and inquired about the key differentiators for the STRO-006 program compared to Pfizer's competing asset.

Answer

Executive Jane Chung confirmed Sutro is winding down luvelta-related expenses and is seeking a partner to take over and lead future development. CSO Dr. Hans-Peter Gerber detailed that STRO-006 is differentiated by its selective antibody that binds to a specific tumor confirmation of integrin beta-6 without interfering with target biology, and by its use of an exatecan payload, a combination he believes is unique for this target.

Jay Olson asked about the target level of tau mRNA knockdown, the most important brain regions for this effect, and the company's indication strategy for the tau silencing program, particularly whether they would start with Alzheimer's or other tauopathies.

Answer

CSO Dr. Todd Carter confirmed the target knockdown is in the 50-73% range. CEO Dr. Al Sandrock identified the cerebral cortex as the key target region. He stated that while the program is intended for partnership, Voyager would prioritize Alzheimer's disease first due to the well-established natural history and validated biomarkers like tau PET, a point echoed by CMO Dr. Toby Ferguson.

Jay Olson asked for the latest thinking on the read-across from UCB's bepranemab data to VY7523, what additional data from UCB would be of interest, how Voyager is prioritizing its antibody versus its gene therapy for tau, and the potential for combination therapies.

Answer

CEO Dr. Alfred Sandrock viewed the bepranemab data as a positive sign that an antibody can affect tau biology in the human brain, reinforcing potential read-through given VY7523's comparable performance in preclinical models. Chief Scientific Officer Dr. Todd Carter added that detailed PK/PD data from UCB would be important to see. Dr. Sandrock stated that both the antibody and gene therapy are high priorities. He sees a potential role for combination with anti-amyloid therapies for patients who show a partial response, but noted monotherapy data is needed first.

An analyst on behalf of Jay Olson at Oppenheimer asked about the mechanism for liver detargeting with TRACER capsids and which modalities are being prioritized for the ALPL receptor binding platform.

Answer

CSO Dr. Todd Carter explained that liver detargeting is an empirical observation, possibly related to capsid charge modifications, and is a key selection criterion. CEO Dr. Al Sandrock stated that for the ALPL platform, Voyager is currently experimenting with its ability to transport various macromolecules, including therapeutic antibodies, enzymes, and oligonucleotides like ASOs and siRNAs, across the blood-brain barrier.

An analyst on for Jay Olson of ACO asked about the expression variability of the ALPL receptor in humans due to aging or disease, and whether Voyager plans to develop other therapeutic modalities using ALPL internally or via collaborations.

Answer

Executive Todd Carter explained that ALPL is expressed robustly from birth and its expression may even increase slightly with age, suggesting consistent or better delivery in older populations. Executive Alfred Sandrock added that while much of the follow-on development work will be done internally, Voyager is always open to collaborations that can enhance its discovery and development efforts.

Jay Olson inquired about the key steps required for the ZW1528 (autoimmune) IND filing, whether it could be accelerated, and the company's interest in developing multi-payload ADCs.

Answer

CSO Dr. Paul Moore outlined the necessary IND-enabling activities, including tox studies and materials manufacturing, maintaining a guidance of H2 2026. Chair and CEO Kenneth Galbraith added they always look to accelerate high-impact programs. Regarding multi-payload ADCs, Dr. Moore confirmed it's an area of investigation, but development would depend on a strong therapeutic rationale for a specific target.

Jay Olson of Oppenheimer & Co. Inc. asked about the adjuvant PDAC trial design, specifically regarding dosing duration and the potential use of ctDNA. He also inquired about the company's strategic interest in earlier lines of therapy for non-small cell lung cancer (NSCLC).

Answer

CEO Dr. Mark Goldsmith stated it was too early to comment on specific adjuvant trial design details like dosing duration. Regarding NSCLC, he confirmed strong interest in moving into earlier lines of therapy, such as adjuvant settings, but noted the strategy is less developed than for PDAC. He highlighted the recent initiation of the second/third-line NSCLC trial as a key first step.

Jay Olson asked for details on the clinical development strategy and target indications for the collaboration with Tango Therapeutics, which evaluates combinations of Revolution's RAS(ON) inhibitors with Tango's PRMT5 inhibitor.

Answer

Dr. Mark Goldsmith, Chairman and CEO, explained that since Tango Therapeutics is sponsoring the studies, Revolution Medicines could not provide additional details beyond what Tango has disclosed. He noted the scientific rationale is strong, as preclinical results were encouraging for suppressing two distinct oncogenic signaling pathways in patients with both a RAS mutation and MTAP deletion.

Jay Olson from Oppenheimer asked about the baseline characteristics of patients in the AFFIRM-AL trial, particularly the utilization of daratumumab, and what would constitute a clinically meaningful overall survival benefit.

Answer

President and CEO Gene G. Kinney noted the trial's focus on Mayo Stage IV patients, where daratumumab has not shown an early survival benefit. Chief Development Officer Chad Swanson confirmed that baseline characteristics are similar to the VITAL trial's Stage IV population, approximately 80% of subjects are on daratumumab, and success is defined by achieving a p-value of 0.1 or less per the FDA SPA agreement.

Jay Olson from Oppenheimer asked about the baseline characteristics of patients enrolled in the AFFIRM-AL trial, particularly regarding daratumumab use, and what would constitute a clinically meaningful overall survival benefit.

Answer

President and CEO Gene G. Kinney noted the trial's focus on Mayo Stage IV patients, where daratumumab has not shown an early survival benefit. Chief Development Officer Chad Swanson confirmed that baseline characteristics are similar to the VITAL trial's Stage IV cohort, approximately 80% of patients are on daratumumab, and success is defined by the FDA SPA agreement's p-value of ≤ 0.10.

Jay Olson asked about the baseline characteristics of patients in the AFFIRM-AL trial, particularly regarding daratumumab utilization, and what would be considered a clinically meaningful overall survival benefit.

Answer

CEO Gene G. Kinney noted the focus on Mayo Stage IV patients and reiterated that daratumumab has not shown an impact on early mortality. Chief Development Officer Chad Swanson confirmed that baseline characteristics are similar to the VITAL trial's Stage IV cohort, with about 80% of AFFIRM-AL participants on daratumumab, and that success is defined by a p-value of 0.1 or less per the FDA agreement.

Asked about the 6-month open-label extension of the PRX012 MAD study, what the company hopes to learn from it, how patients will be dosed, and its impact on future plans.

Answer

The study is a double-blind, placebo-controlled trial for 6 months, after which patients can enter an open-label extension where enrollment has been strong. Placebo patients will receive the drug for the first time, and others will continue for up to 12 months of treatment. The company will capture safety, tolerability, PK, and pharmacodynamic data during this period.

Jay Olson of Oppenheimer & Co. Inc. asked new CEO Catherine Owen Adams about the due diligence process and key considerations that led her to join Acadia, as well as her long-term vision for the company.

Answer

CEO Catherine Owen Adams shared that she was attracted to Acadia by the combination of three factors: a strong commercial base with NUPLAZID and Daybue where she could add value, an exciting pipeline with two late-stage assets, and a strong financial position with a solid board and investors. She stated that six weeks into the role, she is even more motivated and believes the company will go from 'strength to strength.'

Jay Olson asked what gives Exelixis the conviction to share a $5 billion peak U.S. sales potential for zanzalintinib at this time and why the outlook was focused specifically on U.S. revenues.

Answer

President and CEO Michael Morrissey explained that with the ANDA litigation overhang removed, it is the right time to focus stakeholders on the company's future. The goal is to highlight the forward momentum with CABOMETYX, the high-potential zanzalintinib program, and the pipeline as Exelixis builds a multi-franchise business.

Jay Olson inquired about the collaboration with Talkiatry and its potential to drive Zurzuvae uptake in postpartum depression through telehealth services.

Answer

CEO Barry Greene explained that while OB/GYNs are the primary point of care, telehealth is crucial for women who are diagnosed later or need immediate psychiatric access. Chief Business Officer Chris Benecchi added that telehealth platforms like Talkiatry are a much-needed resource that expands the opportunity for women to engage with healthcare professionals.

Jay Olson inquired about Sage's plans to increase the PPD diagnosis rate and expand ZURZUVAE uptake among psychiatrists and PCPs, including any planned investment in sales resources.

Answer

CEO Barry Greene reiterated that the primary focus and the upcoming sales force expansion are aimed at OB/GYNs, who are the key point of interception for PPD. CBO Chris Benecchi added that ACOG guidelines provide a significant tailwind for screening and diagnosis. He also noted that personal and non-personal promotion efforts are in place to reach psychiatrists and PCPs for patients on different care journeys.

Jay Olson of Oppenheimer & Co. Inc. asked about the key differentiators for Enanta's oral KIT inhibitor compared to competitors and its positioning against other oral CSU therapies like BTK inhibitors. He also inquired about plans for additional indications beyond CSU.

Answer

Dr. Tara Kieffer, Chief Product Strategy Officer, explained that the primary goal is to achieve best-in-disease efficacy, similar to what has been seen with KIT-targeting monoclonal antibodies, but with the convenience and safety of a potent, selective, once-daily oral drug. She noted that beyond CSU, the company is interested in other mast cell-driven diseases such as chronic inducible urticaria, eosinophilic esophagitis (EOE), and prurigo nodularis (PN).

The analyst asked about the desired differentiation for Enanta's oral KIT inhibitor compared to competitors, its positioning against other oral therapies like BTK inhibitors, and potential future indications beyond CSU.

Answer

The company aims for their oral KIT inhibitor to match or exceed the best-in-disease efficacy seen with anti-KIT monoclonal antibodies, but with the convenience of an oral, once-daily dose and a good safety profile. Key differentiators will be potency, selectivity, and a tunable dosing regimen. For additional indications, they are interested in other mast cell-driven diseases such as chronic inducible urticaria, eosinophilic esophagitis (EOE), prurigo nodularis (PN), and potentially asthma.

Asked about the impact of RSV vaccines on pivotal trial design for zelicapavir, the positioning of their oral KIT inhibitor for CSU against other treatments like BTK inhibitors, and potential safety advantages over antibody approaches. The questions were asked by Cheng Li on behalf of Jay.

Answer

The company plans to include vaccinated patients in future RSV trials as breakthrough infections will occur. For CSU, they are targeting best-in-class efficacy similar to what's been seen with antibody KIT inhibitors, potentially exceeding BTK inhibitors. They believe the known side effects of KIT inhibitors are manageable and not a limitation.

Asked about the expectations for the EDP-323 challenge study, what would be a meaningful viral load reduction, how it will be differentiated from EDP-938, and which disease areas the new nonvirology programs will target.

Answer

The company hopes to see strong viral load and symptom reduction in the EDP-323 study, comparable to the high bar set by EDP-938. Differentiation will come later, but having two mechanisms offers flexibility. They declined to comment on specific nonvirology areas until early 2024.

Inquired about the SHINE study's baseline patient characteristics and the plan for disclosing top-line results, as well as investigator interest and site activation progress for the START study.

Answer

The company stated that SHINE baseline characteristics are not yet available. Top-line results will be shared via press release, with a full data set at the AAIC meeting. They reported positive investigator enthusiasm and progress in site activation for the START study.

Asked about the timing and format for sharing preclinical proof of concept for the in vivo program, whether it would cover both undisclosed targets, and the choice of editing and delivery tools.

Answer

The company is on track to establish in vivo preclinical proof of concept for one undisclosed indication this year, with more details on the timing and forum to be shared later. The chosen editing tool is their proprietary AsCas12a enzyme, and the delivery method is focused on non-viral nanoparticles.