Michael Yee

Michael Yee followed up on BIIB080, asking about the importance of subgroup analyses (e.g., high vs. low tau) and the tau sub-study using PET tau imaging, beyond the primary endpoint of CDR sum of boxes, for the upcoming readout.

Answer

Priya Singhal, Head of Development at Biogen, affirmed the critical importance of evaluating tau PET, fluid biomarkers, and clinical data trends, along with triangulating all available information. She noted that the study's design, which includes a tau sub-study and tests three doses across two dosing regimens in a randomized controlled trial, is well-suited to provide comprehensive insights and assess the scientific hypotheses.

Michael Yee of Jefferies Financial Group asked about the SMA market dynamics, specifically how emerging myostatin inhibitors might impact the market and whether they would be additive or competitive to therapies like Spinraza.

Answer

Alisha Alaimo, President & Head of North America, responded that Biogen views myostatin inhibitors as providing an additive benefit for SMA patients. She clarified that the company does not see them as a direct competitor to Spinraza or other existing SMN-modifying therapies and does not anticipate a significant issue for their franchise.

Michael Yee of Jefferies Financial Group asked about the SMA market dynamics, focusing on how upcoming myostatin inhibitors might impact the competitive landscape and if they would be additive to SMN correctors like Spinraza.

Answer

Alisha Alaimo, President & Head of North America, responded that Biogen views myostatin inhibitors as a potential additive benefit for SMA patients. She clarified that the company does not see them as a direct competitor to Spinraza or other existing SMA therapies and does not anticipate them being a significant issue for the franchise.

Michael Yee asked for details on the AHEAD 3-45 study, its positioning against competitors, and the basis for confidence in a successful readout.

Answer

Head of Development Dr. Priya Singhal explained that the AHEAD 3-45 study is uniquely designed to assess LEQEMBI across the full spectrum of presymptomatic Alzheimer's, unlike competitor studies with mixed populations. CEO Christopher Viehbacher added that this design will provide crucial data on the risk-benefit of treating patients at different amyloid levels, which he believes will make it a landmark study for physicians.

Michael Yee asked about the importance of blood-based diagnostics for LEQEMBI's launch, their potential to replace PET scans, and the timeline for availability.

Answer

Dr. Priya Singhal, Head of Development, explained that an FDA-approved, widely reimbursed in-vitro diagnostic is a critical near-term catalyst to build physician confidence and streamline the care pathway. She noted that while triage tests exist, full approval and data demonstrating concordance with PET scans will be key for broad adoption.

Michael Yee asked about the AHEAD 3-45 study, specifically regarding the timeline for a potential readout and the possibility of an interim analysis.

Answer

Dr. Priya Singhal, Head of Development, confirmed that enrollment for the study was completed in October. While the trial has a 216-week primary endpoint, she mentioned that Biogen is actively engaging with regulators to explore all options for when the study might read out and will provide future updates.

Michael Yee asked about the Milvexian AFib study, specifically regarding previously suggested lower blinded safety event rates (bleeding) and the frequency of Data Monitoring Committee (DMC) reviews. He also questioned if metabolic obesity is a fair area for investors to consider for Bristol Myers Squibb's business development.

Answer

Chris Boerner (Board Chair and CEO, Bristol Myers Squibb) stated that while metabolics is an exciting area, Bristol Myers Squibb's primary business development focus remains on building breadth and depth in existing therapeutic areas. Cristian Massacesi (Executive Vice President, Chief Medical Officer, and Head of Global Drug Development, Bristol Myers Squibb) confirmed that Milvexian AFib enrollment is complete with over 20,000 patients, and the DMC regularly endorses trial progression, checking both efficacy and safety. He expressed confidence in achieving the benefit of reduced bleeding risks while maintaining similar efficacy to Eliquis.

Michael Yee asked for an update on Milvexian's AFib study, specifically regarding lower blinded safety event rates (bleeding) and the frequency of DSMB safety looks. He also questioned if metabolic obesity is a fair area for investors to consider for Bristol Myers Squibb's business development.

Answer

Chris Boerner, Board Chair and CEO, reiterated that Bristol Myers Squibb's primary BD focus is on building breadth and depth in existing therapeutic areas, not metabolic obesity, despite its excitement. Cristian Massacesi, Executive Vice President, Chief Medical Officer, and Head of Development, confirmed Milvexian's AFib study completed enrollment with over 20,000 patients, and the DSMB regularly endorses trial progression, checking efficacy and safety. He expressed confidence in achieving benefit by reducing bleeding risks, based on blinded data and comparison to Eliquis.

Michael Yee asked about Lilly's expectations for the Orforglipron launch, specifically regarding unit volume scripts compared to the Tirzepatide launch, and how access or other channels might differ for Orforglipron.

Answer

Ilya Yuffa, President of Lilly USA and Global Customer Capabilities, expressed high expectations for Orforglipron's Q2 launch, noting that it enters a larger market with greater consumer and provider awareness. He highlighted the difference in launch dynamics, with a significant self-pay and consumer awareness component, supported by Lilly's scaled direct-to-consumer platform, expecting it to be market expansive and bring new patients to obesity therapy.

Michael Yee from UBS asked about Eli Lilly's expectations for the Orforglipron launch, specifically regarding unit volume scripts compared to Tirzepatide's launch, and how access or other channels might differ.

Answer

Ilya Yuffa, President of Lilly USA and Global Customer Capabilities, expressed excitement for Orforglipron's Q2 launch, noting it enters a larger market with greater consumer and provider awareness. He highlighted that unlike typical launches, this space has significant self-pay and consumer awareness, supported by LillyDirect. He stated high expectations for Orforglipron's launch, anticipating it will expand the market and bring new people to obesity therapy. Mike Czapar, SVP of Investor Relations, directed the question.

Michael Yee asked about expectations for AbbVie's Crohn's disease immunology platform program, specifically the goal of raising efficacy and extending leadership with Skyrizi in combination with ABBV-382 and lutikizumab.

Answer

Roopal Thakkar, EVP, R&D, and Chief Scientific Officer, explained the goal is to increase efficacy, particularly in second and third-line patients who have received Skyrizi or cycled off anti-TNFs. He emphasized the importance of tolerability (avoiding boxed warnings), exploring other combinations like TL1A, and developing co-formulation and patient-friendly delivery methods, with data expected this year.

Michael Yee asked for details on AbbVie's ongoing Crohn's disease immunology platform program, specifically what is expected from the study and if the goal is to raise the bar in efficacy to extend leadership.

Answer

Roopal Thakkar, Executive Vice President, Research and Development, and Chief Scientific Officer, confirmed that increasing efficacy is a key goal, with the degree depending on patient types (naive vs. Skyrizi-experienced). He emphasized the importance of studying patients who have already received Skyrizi, as second and third lines in IBD are expanding. The strategy also focuses on tolerability, avoiding boxed warnings, and exploring combinations with alpha-4 beta-7, LUDI, and TL1A, with data expected this year. Parallel efforts are underway for co-formulation and patient-friendly delivery.

Michael Yee from UBS Financial asked about Amgen's overall obesity portfolio, specifically MariTide's positioning given competitors' combination therapies, and the company's strategy for other assets in the pipeline.

Answer

Robert Bradway, CEO of Amgen, and James Bradner, EVP of Research and Development, explained that Amgen is well-positioned for MariTide across various indications. They noted the presence of another clinical-stage asset, AMG 513, in Phase I, and a pipeline of preclinical programs including both incretin-based and non-incretin-based, injectable, and oral medicines, indicating a broad competitive strategy in the obesity field.

Michael Yee of Jefferies questioned two aspects of the MariTide obesity program: management's confidence in achieving competitive tolerability with a new titration schedule, and how the injectable drug will compete against emerging oral therapies.

Answer

Robert Bradway, CEO, expressed high confidence in MariTide's Phase III design, stating it was informed by Phase I and II data showing dose escalation improves tolerability without sacrificing efficacy. Murdo Gordon, EVP of Global Commercial Operations, added that while an oral market is expected, MariTide's monthly or less frequent dosing makes it less vulnerable to competition than weekly injectables.

Michael Yee asked about Amgen's broader strategic view on obesity beyond MariTide, questioning the depth of the portfolio and the company's appetite to add assets.

Answer

CEO Robert Bradway and EVP of R&D James Bradner refuted the idea of 'slip-ups,' clarifying that early-stage programs are held to a high bar. Dr. Bradner affirmed confidence in a deep pipeline behind MariTide, including oral and subcutaneous candidates with diverse mechanisms, and noted an openness to external partnerships.

Michael Yee questioned the overall competitiveness of Amgen's obesity portfolio, noting that while MariTide is in late-stage development, other assets like AMG-513 are early and there is no disclosed oral candidate.

Answer

EVP of R&D James Bradner responded that while MariTide is the primary focus, Amgen is actively developing a broader portfolio. He confirmed the company is pursuing both injectable and oral medicines, as well as incretin and non-incretin mechanisms, to address the diverse needs of the obesity market.

Michael Yee from UBS Group AG asked for more information on the recently in-licensed oral GLP-1, specifically what data Pfizer had prior to the deal and the status of its Phase 1 study. He also questioned Dave Denton about the ability to pursue more business development given the reiterated $7 billion capacity, in the context of the recent dividend growth pause.

Answer

Dave Denton, CFO, Pfizer, reiterated the focus on maintaining and growing the dividend over time, confirming $7 billion in BD capacity, which increased with the pending liquidation of the ViiV asset. Dr. Chris Boshoff, Chief Scientific Officer, Pfizer, explained that the Yao Pharma oral small molecule (5002), which is not on a donepezil scaffold, is currently in Phase 1, and Pfizer plans to conduct Phase 1 and combination studies with its GIP antagonist, transitioning work to the U.S. for manufacturing and studies.

Michael Yee asked for more information on the recently in-licensed oral GLP-1 from Yao Pharma, specifically what data Pfizer knew at the time of licensing, and inquired about Pfizer's ability to pursue further M&A given the recent dividend growth pause and the company's overall dividend strategy.

Answer

CFO Dave Denton reiterated Pfizer's focus on maintaining and growing its dividend over time, calling it a critical component of capital allocation. He noted that BD capacity increased to approximately $7 billion with the pending liquidation of the ViiV asset. Chief Scientific Officer Chris Boshoff stated that the Yao Pharma oral small molecule (5002), which is not on a danuglipron scaffold, is currently in phase I, and Pfizer plans to conduct phase I and combination studies with its GIP antagonist, transitioning work to the U.S.

Michael Yee asked about the upcoming obesity data from the EMBRAZE study, questioning if the June readout will be a complete data package and what magnitude of muscle loss reduction would be considered a successful outcome.

Answer

CEO David Hallal positioned the study as an initial exploration of Scholar Rock's potential role in obesity. President of R&D Akshay Vaishnaw clarified that the readout's primary focus will be the 24-week data on lean mass changes and safety. He emphasized the importance of addressing muscle loss but did not commit to a specific quantitative benchmark for success.

Michael Yee asked about the expected biological effect of apitegromab on total weight loss in the EMBRAZE study, questioning whether preserving muscle might lead to more, less, or a comparable amount of total weight loss compared to tirzepatide alone at the 24-week mark.

Answer

Executive Jay Backstrom clarified that at the 24-week timepoint, they expect total weight loss to be comparable between the combination arm and the placebo arm. He explained that the magnitude of weight loss from tirzepatide is so significant that any effect from muscle preservation on total weight would likely be a 'wash' at this early stage. However, he acknowledged the potential for incremental weight loss over a longer treatment period.

Jenna Lee, on behalf of Michael Yee, asked for a comparison between Scholar Rock's EMBRAZE trial and a new Phase II study by Lilly in obesity, focusing on trial design, dosing, and patient populations. She also inquired about potential data scenarios for the EMBRAZE readout and the key parameters that would define a successful outcome.

Answer

Executive Jay Backstrom explained that the EMBRAZE trial is a proof-of-concept study using apitegromab to validate their selective anti-myostatin approach, with the primary endpoint being lean muscle mass at 24 weeks. This is intended to guide the development of SRK-439, which will be a subcutaneous formulation. He noted that for the EMBRAZE data, success would be defined by the preservation of lean muscle mass, which is considered clinically meaningful for improving the durability of weight loss, reducing fat mass, and enhancing glucose metabolism.

Michael Yee inquired about the specific logistical issues causing enrollment delays in the ALPHA3 first-line study and sought clarity on the conversion of the 250 consented patients into the trial.

Answer

CEO David Chang explained that a 3-to-4-month lag between site activation and patient screening was due to site-level staffing shortages, an issue now understood and improving. EVP of R&D and CMO Dr. Zachary Roberts clarified that the 250 consented patients represent the 'top of the funnel' for MRD screening, not final enrollment, but noted the strong consenting trend is a positive leading indicator for future enrollment.

Michael Yee from Jefferies sought confirmation that ALLO-647 is unlikely to be needed in the ALPHA3 trial and asked for details on the criteria for the H1 2026 interim DSMB efficacy analysis, including the statistical bar.

Answer

Dr. Zachary Roberts, EVP of R&D and CMO, stated the company is agnostic about needing ALLO-647, as both outcomes have benefits. He confirmed the H1 2026 interim analysis is a formal efficacy test on event-free survival with a minimal ALPHA spend, making a statistically significant finding possible, which could accelerate regulatory conversations.

Michael Yee asked about the early screening rates for MRD positivity and the enrollment pace for the first-line lymphoma ALPHA3 study. He also inquired about how Allogene views the positioning of its allogeneic CAR-T therapy against T-cell engagers in the competitive autoimmune disease landscape.

Answer

Dr. David Chang, President and CEO, addressed the autoimmune question, stating that while multiple modalities can coexist, allogeneic CAR-T offers the unique advantages of being an off-the-shelf, 'once-and-done' therapy, with ALLO-329 specifically designed to overcome the lymphodepletion hurdle. Dr. Zachary Roberts, EVP of R&D and CMO, commented on ALPHA3, noting 'through the roof' enthusiasm from clinical sites and that the trial is progressing as expected, with strong engagement from community centers.

Michael Yee asked for more color on VYVGART's sequential sales decline, questioning if it was due to inventory changes or seasonality, and inquired about the company's strategy for acquiring more wholly-owned global assets from China.

Answer

Joshua Smiley, President and COO, attributed the VYVGART sales dip to Chinese New Year seasonality affecting IV infusions and a Q4 inventory build for Hytrulo, but noted a strong rebound in April. Dr. Samantha Du, Founder and CEO, affirmed that Zai Lab maintains a high bar for business development but will actively pursue differentiated, high-potential assets for both regional and global rights.

Michael Yee asked for more detail on VYVGART's 2025 growth trajectory between the first and second half of the year, and questioned the competitive dynamics and speed-to-market strategy for the DLL3 ADC, ZL-1310.

Answer

Joshua Smiley, President and COO, explained that VYVGART's growth will accelerate in the second half of 2025 due to the compounding effect of returning patients and an expected update to treatment guidelines. Dr. Rafael Amado, President and Head of Global R&D, added that for ZL-1310, they are in discussions with regulators for an accelerated approval pathway, plan to start a pivotal study in 2025, and are confident they are about 1.5 years ahead of competitors.

Michael Yee from Jefferies sought clarification on VYVGART's sales potential, noting that the 2,700 new patients in Q1 could imply a run rate at or above the $70 million guidance. He also asked about the company's top priorities for business development.

Answer

President and COO Josh Smiley confirmed the company is on a trend to meet or exceed the $70 million VYVGART guidance but noted it's early to precisely model patient cycles. Executive Officer Jonathan Wang addressed business development, stating priorities are late-stage, de-risked regional deals and earlier-stage assets with global potential.

Michael Yee asked for expectations on the upcoming SGR-1505 MALT1 inhibitor data, questioning the balance between single-agent activity and safety. He also inquired about the future cash burn trajectory in light of R&D plans and the optimal timing for partnerships.

Answer

Karen Akinsanya, President of R&D and Therapeutics, stated that the initial SGR-1505 data update will cover safety, pharmacokinetics (PK), and pharmacodynamics (PD), along with preliminary efficacy. Geoffrey Porges, CFO, addressed cash burn, noting he does not anticipate a substantial increase next year as the company maintains optionality with its lead programs.

Michael Yee noted a perceived deceleration in third-party weekly script data for JOURNAVX and asked for Vertex's perspective. He also inquired about the upcoming VX-993 acute pain data and how its potential for better exposure might compare to JOURNAVX.

Answer

CEO Reshma Kewalramani explained that the VX-993 study will explore its full dose range to assess if it can improve upon JOURNAVX's efficacy and serve as an option for future combinations. CCO Duncan McKechnie clarified that third-party retail data doesn't capture hospital usage, and the total prescription number was 25,000. He noted that week-to-week variability is common early in a launch and that growth will increase with payer coverage.

Michael Yee asked about Vertex's confidence in achieving broad public and commercial payer coverage for JOURNAVX without significant hurdles, considering the political and social environment surrounding the opioid crisis.

Answer

COO Stuart Arbuckle expressed high confidence in securing broad coverage over time across all payer segments. He cited the significant unmet need for effective non-opioids and supportive federal and state policy initiatives as key factors that should facilitate smooth market access for JOURNAVX.

Michael Yee of Jefferies posed two pipeline questions: one on the strategic benefit of the follow-on NaV1.8 inhibitor VX-993 beyond potency, and another on the possibility of filing for inaxaplin (APOL1) based on proteinuria data, given the evolving regulatory landscape.

Answer

CEO Dr. Reshma Kewalramani explained that VX-993 supports serial innovation, enables an IV formulation, and provides optionality for a future NaV1.7 combination. On inaxaplin, she noted the current regulatory agreement is for an accelerated approval based on GFR slope, but acknowledged the positive evolution of regulatory discussions around proteinuria.

Requested more detail on the expected shape of revenue growth for the remainder of the year, specifically for Q2, Q3, and Q4.

Answer

The company expects consistent underlying patient growth throughout the year, pointing to the updated annual guidance. They noted a specific calendar dynamic where an ordering day missed in Q1 is made up in Q3, which could shift some growth into that quarter.

Michael Yee asked about Gilead's expectations for the lenacapavir for PrEP launch, focusing on the timeline for commercial and Medicaid reimbursement and the role of guideline changes.

Answer

Chief Commercial Officer Johanna Mercier stated the team is ready for the launch following the anticipated June 19 PDUFA date. She projected that access would ramp to 75% of covered lives within six months and peak at 90% within a year, with initial access facilitated through medical exceptions. This gradual build-out is expected to support a strong launch trajectory through 2025 and into 2026.

Michael Yee asked about the lenacapavir PrEP approval process, seeking updates on FDA interactions for a timely approval, and questioned the commercial opportunity in Europe, where PrEP revenue has historically been limited.

Answer

CEO Daniel O'Day stated that interactions with the FDA are on track for a summer approval, supported by its Breakthrough Therapy designation. CCO Johanna Mercier added that the European strategy involves a tiered, country-specific approach and highlighted the EU filing's importance for the EU-M4all initiative, which facilitates access in over 130 low- and middle-income countries.

Michael Yee of Jefferies inquired about the launch strategy for lenacapavir for PrEP, asking about the potential for rapid adoption, dynamics of switching from Descovy, and the role of the buy-and-bill model.

Answer

Johanna Mercier, Chief Commercial Officer, expressed high excitement for the launch, outlining clear growth opportunities in expanding the market size to new consumers (Black, Latino, women) and prescribers. She anticipates lenacapavir will impact both Descovy and the generic oral market. Mercier confirmed that commercialization plans are well underway to ensure a seamless experience for providers and consumers, with more details to be shared at the December HIV analyst event.

Michael Yee inquired about the timing for the INT cancer vaccine data, asking if a readout by late 2025 or H1 2026 is plausible, and asked if the Norovirus trial requires data from both hemispheres to reach its primary endpoint.

Answer

President Stephen Hoge described a 2026 readout for the INT vaccine as 'possible, plausible' but emphasized it is event-driven and timing remains uncertain. For Norovirus, he explained that since the Northern Hemisphere cohort is fully enrolled and constitutes the majority of the study, it's possible that participants from the Southern Hemisphere may not be needed to hit the efficacy endpoint.

Michael Yee questioned the factors contributing to the uncertainty around filing the flu/COVID combo vaccine and asked for commentary on the RSV market dynamics and Moderna's confidence in becoming a significant competitor.

Answer

President Stephen Hoge stated that discussions with the FDA are ongoing for the combo vaccine's BLA submission. CEO Stéphane Bancel addressed the RSV market, noting that lower-than-expected demand, new CDC guidelines, and significant channel inventory from competitors have impacted sales, but expressed confidence for 2025 with a full contracting season and ex-U.S. approvals.

Michael Yee of Jefferies inquired about the upcoming HIV trial results, specifically asking if all 16 patients would have sufficient off-therapy time to assess viral rebound and what the company considers a good non-rebound rate. He also asked about the sequential decline in European sales.

Answer

David Berman, Head of R&D, clarified that for the HIV trial, the focus of the Phase 1 dose escalation is not on a specific rate but on observing activity, noting a commercially successful target product profile (TPP) would involve suppressing viral copies to less than 200 copies/ml for two years in 20-30% of patients. Ralph Torbay, Head of Commercial, addressed European sales, attributing the performance to a challenging reimbursement environment and ongoing price negotiations in key markets like Germany and France.

Michael Yee of Jefferies asked for clarification on the Q2 European reimbursement reserve for KIMMTRAK, questioning if it was a one-time event, and sought more detail on the 'biologically active' comment regarding the HIV program.

Answer

Ralph Torbay, Head of Commercial, explained the $6.7 million reserve was a 'onetime thing' based on negotiations with France and Germany but cautioned against simply adding it back in future quarters. David Berman, Head of R&D, stated that for the HIV program, seeing any biological activity is significant for a first-in-class therapy in a low-target-density setting. He confirmed they are enrolling more patients and exploring higher doses, with a full data release planned for Q1 2025.

Michael Yee of Jefferies asked for clarification on the Q2 European reimbursement reserve for KIMMTRAK and for more details on the 'biologically active' status of the HIV program.

Answer

Ralph Torbay, Head of Commercial, explained the $6.7 million reserve was a one-time adjustment based on negotiations in France and Germany, cautioning it affects future periods as well. David Berman, Head of R&D, stated the HIV program shows biological activity at low target densities, and they are enrolling more patients and exploring higher doses before the Q1 2025 data release.

Asked for clarification on the expected performance of the AFFIRM-AL control arm in the context of daratumumab use and the ANDROMEDA trial data. Also asked about the definition of success for the upcoming PRX012 data readout.

Answer

The company expects the AFFIRM-AL control arm to behave similarly to the VITAL control arm (median survival ~8.3 months), as the ANDROMEDA data shows daratumumab does not impact early mortality in the first 15 months. The timing and nature of blinded events in AFFIRM-AL appear similar to VITAL. The question about PRX012 success criteria was not answered.

Michael Yee from Jefferies asked for clarification on the AFFIRM-AL control arm's expected performance given the use of daratumumab, and how that impacts study power. He also asked about the success criteria for the upcoming PRX012 data in terms of ARIA and amyloid reduction.

Answer

President and CEO Gene G. Kinney clarified that they expect the control arm to perform similarly to the VITAL trial's control arm (approx. 8.3 months median survival), as data from the ANDROMEDA study suggests daratumumab does not impact early mortality. Chief Development Officer Chad Swanson added that blinded event data in AFFIRM-AL appears consistent with VITAL, supporting their powering assumptions. The question on PRX012 was not addressed in the response.

Michael Yee from Jefferies sought clarification on whether the AFFIRM-AL control arm is expected to perform like the control arm or the daratumumab arm from the ANDROMEDA study. He also asked if expectations for a successful PRX012 outcome, in terms of ARIA and amyloid reduction, have evolved.

Answer

President and CEO Gene G. Kinney clarified that the control arm is expected to behave similarly to the VITAL trial's control arm (median survival ~8.3 months), as daratumumab has not shown an impact on early mortality. Chief Development Officer Chad Swanson added that blinded event timing in AFFIRM-AL appears consistent with VITAL, reinforcing this expectation.

Michael Yee asked for clarification on expectations for the AFFIRM-AL control arm, given the use of daratumumab, and whether expectations for PRX012's success metrics, like ARIA and amyloid reduction, have changed over time.

Answer

CEO Gene G. Kinney stated they expect the control arm to behave similarly to the VITAL trial, where median survival was ~8.3 months, noting that daratumumab has not impacted early mortality in the ANDROMEDA study. Chief Development Officer Chad Swanson added that blinded event timing and nature in AFFIRM-AL appear similar to VITAL, reinforcing their assumptions.

Asked for specifics on the 'consistent with placebo' ARIA rate, whether there were any cases in the placebo group, and what gives the company confidence they can safely increase the dose significantly.

Answer

The study is double-blind, and the ARIA rates at 70mg were consistent with placebo. This favorable therapeutic index gives them the ability to move up in dose. All dose cohorts, including 200mg, are active, and they are exploring the full exposure-response relationship from 45mg to 400mg, indicating their belief in the potential for a best-in-class molecule.

Inquired about the expected pace of revenue growth (modest vs. significant), the impact of seasonality on revenue in Q1 and Q2, and the expected changes in operating expenses, particularly R&D, to achieve profitability.

Answer

The company expects revenue growth to be driven by increased penetration in the immunocompromised population, which is not considered seasonal. They are early in their growth, so seasonality is not a major factor yet. Profitability will be driven by significant reductions in OpEx, primarily from the R&D line, as major manufacturing campaigns for PEMGARDA and VYD2311 are largely complete and were previously expensed.

Michael Yee from Jefferies asked for clarification on the expected trajectory of revenue growth for PEMGARDA, questioning whether it would be modest or a significant step-up, and the potential impact of seasonality. He also inquired about the planned changes in operating expenses, particularly in R&D, to achieve profitability.

Answer

Chairman Marc Elia and CFO William Duke explained that a significant reduction in operating expenses is expected, driven primarily by lower R&D spend as major manufacturing campaigns for PEMGARDA and VYD2311, which were expensed through R&D, are now substantially complete. Chief Commercial Officer Timothy Lee addressed revenue, stating that seasonality is not a major factor for the core immunocompromised patient population and that the company is focused on driving deeper penetration, with Marc Elia adding that the launch is too early to see seasonal effects.

Michael Yee of Jefferies asked about the evolution of reimbursement from single-case agreements to broader contracts and for an update on the timeline for the pivotal study in second-line lung cancer.

Answer

Interim CEO Frederick Vogt responded that reimbursement time has been reduced to an average of 3 weeks, which aligns well with ATC scheduling needs and is not seen as a bottleneck. For the lung cancer trial (IOV-LUN-202), he reiterated that data is expected in 2025, with a potential U.S. approval in 2027.

Michael Yee of Jefferies asked about the BEAM-302 program for AATD, noting the first cohort dosing was complete, and inquired about the timing for a data disclosure, given that proof-of-concept could emerge quickly.

Answer

CEO John Evans confirmed the progress and reiterated guidance for a data release in 2025. He explained that the company is dose-escalating from a low but biologically active dose. He stated that data would be shared once a 'clear profile of the drug' emerges, which he indicated would mean results from at least multiple patient cohorts, and that the company would narrow the timing guidance when possible.

Michael Yee of Jefferies asked about the BEAM-302 program for AATD, inquiring when there might be sufficient data for a public disclosure, given that the first cohort has now been fully dosed.

Answer

CEO John Evans confirmed the first cohort is dosed and the trial is progressing, with initial data expected in 2025. He reiterated that the company plans to release data when a clear profile of the drug emerges, which would likely mean after results from multiple dose cohorts are available. He expressed confidence in the 2025 guidance for this data release.

Michael Yee of Jefferies asked about the BEAM-302 program in AATD, inquiring at what point there would be sufficient proof-of-concept data to disclose, given the first cohort is now dosed.

Answer

CEO John Evans confirmed the 2025 guidance for an initial data release. He stated the company would share data once a 'clear profile of the drug' emerges, which he suggested would mean results from at least multiple dose cohorts. Key data points will include levels of normal M alpha-1 protein, reduction of toxic Z protein, and safety.

Michael Yee of Jefferies inquired about the plan to use single-agent Cytoxan in the FT819 autoimmune study and its potential impact, and also asked about the expected results from the FT522 cohort without lymphodepletion and its read-through for autoimmune applications.

Answer

CEO Scott Wolchko explained that positive data from the FT819 oncology study using a non-fludarabine regimen provides confidence to amend the IND and add a Cytoxan-only option, enhancing physician choice. For FT522, he highlighted the extensive preclinical work supporting the no-conditioning arm. Dr. Bob Valamehr, Chief Research and Development Officer, added that preclinical data shows FT522 with ADR technology maintains persistence and targets B-cells effectively in an allogeneic system, and the trial will assess key biomarkers to inform the autoimmune strategy.

Michael Yee from Jefferies asked how the THRIVE study controls for pre-existing hearing issues in patients and requested details on the recent Type C meeting with the FDA regarding the subcutaneous VRDN-003 program, including the company's confidence in moving directly to Phase III trials.

Answer

President and CEO Stephen Mahoney described the FDA meeting for VRDN-003 as positive and reiterated guidance for a pivotal program start in mid-2024, pending receipt of official minutes. Chief Medical Officer Thomas Ciulla explained that for hearing, the study uses an exclusion criterion for baseline hearing loss, which is detailed on clinicaltrials.gov, in addition to standard monitoring via MedDRA terms and audiometry.

An analyst on behalf of Michael Yee from Jefferies asked about the dose escalation strategy for IMM-1-104, the potential for observing efficacy at initial doses, the specifics of the pharmacodynamics (PD) modeling, and the anticipated safety profile based on the deep cyclic inhibition hypothesis.

Answer

President and CEO Benjamin Zeskind did not specify dose levels but pointed to the company's detailed data release schedule. Chief Scientific Officer Brett Hall described the PD modeling, which uses two orthogonal assays to measure MAP kinase pathway attenuation. Zeskind addressed safety, noting excellent preclinical tolerability and emphasizing that the drug's short half-life and high CMAX are designed to improve the therapeutic index compared to traditional MEK inhibitors.