Salveen Richter

Salveen Richter questioned the high conviction in litifilimab's Phase III outcomes for Systemic Lupus Erythematosus (SLE), given the mixed Phase II datasets and the inherent risks associated with lupus drug development.

Answer

Priya Singhal, Head of Development, Biogen, expressed strong scientific conviction, citing litifilimab's target of the BDCA2 pathway, which is exclusive to pDC cells and regulates the type 1 interferon signature. She referenced published LILAC study data in the New England Journal of Medicine, which showed proof of concept in both systemic and cutaneous lupus. She also highlighted the primary endpoint, SRI-4, as robust for capturing disease activity and the trial design's focus on appropriate patient inclusion for the mechanism of action.

Salveen Richter questioned the basis for Biogen's high conviction in Litifilimab's Phase 3 outcomes for lupus, given the mixed Phase 2 datasets and the inherent risks associated with lupus development.

Answer

Priya Singhal, Head of Development at Biogen, explained that the high scientific conviction for Litifilimab stems from its targeted mechanism, the BDCA2 pathway, which is exclusively expressed on pDC cells and regulates the type 1 interferon signature. She referenced published LILAC study data in the New England Journal of Medicine, which demonstrated proof of concept in both systemic and cutaneous lupus. She added that the Phase 3 trials (TOPAZ-1 and TOPAZ-2) are designed with the SRI-4 primary endpoint, effectively capturing disease activity, and the inclusion criteria are specifically tailored to the mechanism of action, particularly for skin and joint manifestations.

Salveen Richter of Goldman Sachs inquired about the importance of business development for Biogen's growth, asking if the focus is on earlier-stage assets and if immunology is a primary area of interest.

Answer

CEO Christopher Viehbacher confirmed a strong focus on early-stage business development as a cost-effective way to build the future pipeline, citing the recent Citi Therapeutics deal. While still open to later-stage M&A, he stressed that high confidence in the internal pipeline means any deal must be strategically fitting and financially disciplined. The goal is to add value across the entire development spectrum.

Salveen Richter of Goldman Sachs inquired about Biogen's business development strategy, its current importance, the focus on early-stage assets, and whether immunology is a primary area of interest.

Answer

CEO Christopher Viehbacher confirmed that early-stage BD is a key focus to prevent future pipeline gaps, citing the Citi Therapeutics deal as a model. He stated that while the company remains open to later-stage M&A, its interest is inversely proportional to its growing confidence in the internal pipeline. Any deal must be strategic and financially sound, with the main focus on executing across the entire development spectrum.

Salveen Richter questioned the potential for LEQEMBI's growth uptick, considering the upcoming subcutaneous maintenance dosing and Fujirebio's in-vitro diagnostic.

Answer

CEO Christopher Viehbacher stated that while the company has limited information on the diagnostic's approval, he believes blood-based diagnostics will be extremely important. He referenced an Alzheimer's Association report on the need for early diagnosis, noting that getting patients on treatment earlier leads to better outcomes, as shown in their CTAD 2023 data. He sees this as a critical future driver for the therapy.

Salveen Richter inquired about Biogen's capacity and timelines for external business development, and the strategic balance between its existing pipeline and potential acquisitions.

Answer

President and CEO Christopher Viehbacher stated that Biogen is prioritizing internal research and preclinical collaborations while seeking financially sound acquisitions in immunology and rare diseases. CFO Michael McDonnell affirmed the company has significant capacity for deals, citing a strong balance sheet, an EBITDA run rate over $3 billion, and growing free cash flow.

Salveen Richter asked for updated thoughts on Biogen's business development strategy to bridge the revenue gap before the late-stage pipeline matures.

Answer

CEO Christopher Viehbacher affirmed they are actively seeking assets for near-term growth but will remain disciplined on valuation. CFO Michael McDonnell quantified the company's capacity, stating that strong free cash flow and a modest debt profile provide '$8 billion to $10 billion of capacity' for transactions over the next one to two years.

Salveen Richter from Goldman Sachs followed up on Uplizna, asking about the confidence in advancing to a Phase III study for CIDP and the market opportunity, and separately, how Amgen plans to adapt its commercial strategy for Repatha given the potential launch of Merck's oral PCSK9 inhibitor.

Answer

James Bradner, EVP of Research and Development, expressed bullishness for Uplizna's unique CD19 pathologic B-cell depletion mechanism, which targets both mature and pre-B cells, making it suitable for autoantibody-mediated conditions like CIDP, where 5-10% of patients have autoantibodies. Murdo Gordon, EVP of Global Commercial Operations, outlined Repatha's strategy, focusing on promoting the landmark VESALIUS data for primary and secondary prevention of cardiovascular events. He emphasized Repatha's unique data package, broad access, and strong prescriber trust, asserting that while the market has room for other therapies, they will not match Repatha's established profile.

Salveen Richter inquired about Amgen's confidence in advancing Uplizna to a Phase 3 study in CIDP and the market opportunity, as well as the potential impact of Merck's oral PCSK9 on Repatha and Amgen's commercial strategy.

Answer

James Bradner, EVP of Research and Development, explained the biological rationale for Uplizna in CIDP, emphasizing its CD19 B-cell depletion mechanism for autoantibody-mediated conditions. Murdo Gordon, EVP of Global Commercial Operations, detailed Repatha's commercial strategy, focusing on the landmark VASALIA-CV data for primary and secondary prevention and its established market leadership.

Salveen Richter from Goldman Sachs asked about Amgen's confidence in Olpasiran, given the lower-than-expected event rate in the Ocean A study, and how this might impact the readout timeline. She also inquired about the implications of returning to pre-Horizon debt levels on Amgen's business development strategy for 2026.

Answer

Peter Griffith, CFO, reiterated strong conviction in Olpasiran due to clear genetic associations and best-in-class properties, but did not provide an updated readout date. Robert Bradway, CEO, stated that returning to pre-Horizon debt levels does not significantly alter their active pursuit of earlier-stage business development opportunities in their therapeutic areas of interest.

Salveen Richter asked about Amgen's confidence in Olpasiran, the event rate for the Ocean A outcome study and its implications for the readout timeline, and the impact of returning to pre-Horizon debt levels on Amgen's business development strategy heading into 2026.

Answer

Peter Griffith, CFO, reiterated strong conviction in Olpasiran, citing its best-in-class properties and clear genetic association with cardiovascular disease, but declined to provide a specific readout date for the event-driven Ocean A study. Robert Bradway, CEO, stated that the return to pre-Horizon leverage does not significantly alter Amgen's business development approach, which remains active and focused on earlier-stage opportunities within their established therapeutic areas.

Salveen Richter inquired about Amgen's perspective on the shifting landscape of drug pricing reform, including the Medicaid MSN clause, and the company's strategy regarding direct-to-consumer (DTC) advertising.

Answer

Robert Bradway, Chairman & CEO, stated that while it's premature to comment on specific proposals, Amgen supports reforms for affordability and access while preserving innovation, and noted a constructive relationship with the administration.

Salveen Richter from Goldman Sachs asked for details on the commercial strategy for UPLIZNA, covering both the recent approval in IgG4-related disease and the potential future indication in myasthenia gravis, with a focus on prescriber targeting and patient identification.

Answer

Murdo Gordon, EVP of Global Commercial Operations, explained the IgG4 launch targets rheumatologists, leveraging Amgen's existing presence, and noted a new diagnostic code aids patient identification. For myasthenia gravis (GMG), he highlighted its differentiated mechanism. James Bradner, EVP of R&D, added that UPLIZNA's strong efficacy and convenient dosing could establish it as a new standard of care in both diseases.

Salveen Richter asked where Amgen's 2025 sales guidance might be underappreciated by the market and how the Medicare Part D redesign has been factored into projections.

Answer

Murdo Gordon, EVP of Global Commercial Operations, described the Part D redesign impact as 'relatively neutral' for the portfolio. Peter Griffith, EVP and CFO, highlighted several areas of potential underappreciation, including the growth trajectories of Repatha, EVENITY, TEZSPIRE, the rare disease portfolio, innovative oncology, and biosimilars, all of which have strong momentum.

Salveen Richter inquired about the specifics of the upcoming MariTide Phase II data release, including the level of detail to be shared, and the expected timeline and scope of the Phase III development plan.

Answer

CEO Robert Bradway confirmed that the Phase II study in type 2 diabetes has been initiated and the main obesity trial is progressing well, with data expected by year-end. He stated that Amgen looks forward to sharing the data with investors once it is available, but did not provide specifics on the format or venue of the release.

Salveen Richter asked about the frontline metastatic melanoma data, specifically regarding the expected hazard ratio bar and the PD-L1 expression levels of enrolled patients for the first interim read.

Answer

Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President, and Chief Scientific Officer, Regeneron Pharmaceuticals, explained that the study is powered for PFS analogous to the current standard of care, with hopes for better, and is appropriately powered to pick up an overall survival benefit. Ryan Crowe, Senior Vice President of Investor Relations, Regeneron Pharmaceuticals, clarified that PD-L1 status is screened but not used as an inclusion/exclusion criterion, expecting the population to represent a true first-line advanced melanoma cohort.

Salveen Richter asked for clarification on the expected hazard ratio bar for the frontline metastatic melanoma data, anticipated in the first half, and sought commentary on the PD-L1 expression levels of patients in the study.

Answer

Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President, and Chief Scientific Officer, Regeneron Pharmaceuticals, explained the study is powered for PFS analogous to the current standard of care, with hopes for better outcomes and appropriate powering for an overall survival benefit. Ryan Crowe, Senior Vice President of Investor Relations, Regeneron Pharmaceuticals, clarified that PD-L1 status is screened but not an inclusion/exclusion criterion, ensuring the population represents true first-line advanced melanoma.

Salveen Richter asked about novel targets in I&I and ophthalmology, specifically for the Geographic Atrophy (GA) program, including FDA expectations for study designs (slowing growth vs. vision, evaluation against current agents), and the timeline for hearing about novel I&I targets.

Answer

President and CSO George Yancopoulos stated that their pivotal GA study is designed against placebo, primarily looking at slowing growth and vision control. He expects data from cohort A of their Phase III trial in H2 2026 to inform the opportunity for their novel systemic approach. For novel I&I programs, he indicated that one of the first additional ones (beyond the CD3 mAb) would be rolled out over the next couple of months, with a new clinical program initiating next year.

Salveen Richter from Goldman Sachs inquired about the FDA's expectations for study designs in the geographic atrophy (GA) program, specifically regarding endpoints like slowing lesion growth versus vision improvements, and whether evaluation against current agents is required. She also asked about timelines for novel INI targets.

Answer

Regeneron President and CEO, Leonard Schleifer, explained that their pivotal GA study is designed against placebo, primarily focusing on slowing lesion growth and vision control. He noted that data from cohort A of their Phase III trial, expected in the second half of 2026, will inform the opportunity for their novel systemic approach. He also mentioned that additional novel INI programs, beyond the CD3 monoclonal antibody, will be rolled out over the next couple of months, with a new clinical program initiating next year.

Salveen Richter of Goldman Sachs asked for more detail on Regeneron's consideration of differentiated, later-stage business development opportunities and how that fits into the company's overall strategy.

Answer

President & CEO Dr. Leonard Schleifer reiterated that while their internal R&D is highly productive, they are always looking for external opportunities and have the flexibility to act. He emphasized that business development is not a 'lifeline' for Regeneron as it may be for others, but they approach it with an open mind to find the best science for patients.

Salveen Richter of Goldman Sachs asked for more detail on the company's business development strategy, specifically regarding its consideration of differentiated, later-stage opportunities.

Answer

President & CEO Dr. Leonard Schleifer reiterated that while they evaluate many external opportunities, the company believes its internal R&D is more productive and less risky. He stressed that business development is not a 'lifeline' for Regeneron as it may be for others, but they maintain flexibility and an open mind to external assets.

Salveen Richter of Goldman Sachs asked for clarification on the tightened capital expenditure guidance, seeking context given recent manufacturing expansion announcements and the expected cadence of future spending.

Answer

EVP and CFO Chris Fenimore clarified that the modest reduction in the top end of the guidance range was purely a matter of expenditure timing. He reaffirmed that the company remains fully committed to its long-term capital investment plans and that nothing has fundamentally changed.

Salveen Richter from Goldman Sachs asked for details on the magnitude of the EYLEA HD inventory impact in Q4 and the current market dynamics with the aflibercept biosimilar.

Answer

EVP of Commercial, Marion McCourt, noted a net favorable inventory impact of about $85 million to the combined EYLEA franchise, mainly benefiting standard EYLEA. CEO Dr. Leonard Schleifer added that recent legal victories could limit biosimilar competition to a single player, significantly altering market dynamics.

Salveen Richter of Goldman Sachs inquired about the drivers of pricing pressure on EYLEA HD, its potential persistence, and the growth outlook for the overall branded anti-VEGF market amidst biosimilar entry.

Answer

EVP of Commercial Marion McCourt explained that pricing pressure impacts all products in the competitive anti-VEGF category, including branded and biosimilar drugs. She stated that product profile, including efficacy, safety, and durability, often prevails. She noted the overall category is growing in the mid-single-digit range and that EYLEA HD's differentiation allows it to compete successfully despite these pressures.

Salveen Richter asked about Moderna's forward-looking expense management strategy, specifically what is being deprioritized or changed to achieve cost reductions, and the company's strategy regarding IP dynamics, particularly concerning the Roy, Vent, and other IP disputes.

Answer

Jamey Mock, Chief Financial Officer, explained that recent cost reductions are split evenly across R&D and cost of sales, driven by accelerating efficiencies in manufacturing and more efficient execution of clinical trials, with some prioritization decisions. Stéphane Bancel, Chief Executive Officer, stated confidence in Moderna's pioneering technology, including its lipid nanoparticle delivery system, and affirmed the company is vigorously defending its IP in the U.S. trial scheduled for March 9, 2026, and responding to new international filings.

Salveen Richter (Goldman Sachs) inquired about the specific changes and deprioritizations driving Moderna's forward expense management, particularly in the context of the 2026 outlook. She also asked for an update on Moderna's strategy regarding the ongoing IP dynamics and legal challenges.

Answer

CFO Jamey Mock explained that recent cost reductions were split evenly across R&D and cost of sales, with cost of sales driven by efficiency gains and R&D by more efficient clinical trial execution and some prioritization. CEO Stéphane Bancel stated confidence in Moderna's technology and its vigorous defense against patent infringement claims, noting the U.S. trial is scheduled for March 9, 2026.

Salveen Richter inquired about the rationale for adding new secondary endpoints to the CMV trial and the expected cadence of data readouts for the intismarin cancer therapy over the next year.

Answer

President Stephen Hoge explained that the CMV trial's secondary endpoints were added while the company remains blinded to enhance the scientific value of the final analysis, particularly concerning congenital CMV. Regarding intismarin, he noted the Phase 3 melanoma trial is accruing events and expects a consistent cadence of results from various randomized studies over the next one to two years.

Salveen Richter asked for more detail on the FDA's feedback requiring flu efficacy data for the flu/COVID combo vaccine and questioned the broader risk to the vaccine business under the new administration.

Answer

President Stephen Hoge explained that including the imminent and robust standalone flu efficacy data in the combination vaccine's review is scientifically sound, though it will extend the approval timeline into 2026. He affirmed that interactions with the FDA across all programs remain "business as usual" and emphasized the ongoing public health need for COVID vaccines, citing high effectiveness in preventing severe outcomes.

Salveen Richter asked about the clinical bar for success in the Norovirus program and whether any data or enrollment updates would be provided for the INT oncology programs beyond the adjuvant melanoma indication.

Answer

President Stephen Hoge explained the Norovirus trial aims for a meaningful decrease in moderate-to-severe gastrointestinal symptoms but did not disclose specific powering assumptions. He also confirmed that additional INT trials in bladder and renal cell carcinoma are ongoing and could have readouts in the coming years, depending on event accrual.

Salveen Richter inquired about the specific countries contributing to Rest of World revenue in Q3 and Q4 2024, whether these contracts would recur in 2025, and the process for releasing CMV trial data upon DSMB review.

Answer

CEO Stéphane Bancel identified the UK, Canada, and Australia as key contributors to Rest of World revenue, noting that Q4 is largely contracted but expecting a decline in 2025 before an uptick in 2026. President Stephen Hoge clarified that if the CMV trial's Data Safety and Monitoring Board (DSMB) recommends unblinding at the interim analysis, the company will share those results.

Salveen Richter asked if any statistical work or study design changes were made for the osteogenesis imperfecta program following the second interim analysis.

Answer

Howard Horn, Chief Financial Officer, and Eric Crombez, Chief Medical Officer, confirmed that no changes were made to the statistical plan. They stated that the opportunity was used to verify assumptions and the existing plan, which provided confidence for the final data readout.

An analyst on behalf of Salveen Richter asked how Ultragenyx plans to communicate the outcome of the setrusumab interim analysis and whether specific data would be shared at the time of the announcement.

Answer

CEO Emil Kakkis stated that the company will promptly announce whether the trial has met its endpoint or if it will continue to the final analysis. He noted that because the database is being fully cleaned for a potential regulatory filing, the time from the top-line announcement to the release of detailed data would be shorter than it would have been for the first interim analysis. He did not commit to whether the result and data would be in the same press release.

Salveen Richter asked for the potential reasons why the OI study's second interim analysis might not be successful and the timeline for the final analysis in that scenario.

Answer

CEO Emil Kakkis explained that the primary risk would be high variation in baseline fracture rates among the diverse patient population (Type I, III, and IV OI). If the study does not hit the interim mark mid-year, he expects the final data analysis to be released by the end of the year.

Salveen Richter at Goldman Sachs inquired about AMVUTTRA's U.S. launch momentum, specifically the balance between first-line and switch populations, any observed combination therapy use, and sought clarity on ex-U.S. pricing strategies.

Answer

Yvonne Greenstreet, CEO, expressed satisfaction with AMVUTTRA's continued growth. Tolga Tanguler, Chief Commercial Officer, detailed broad and balanced adoption across academic and community settings, with increasing first-line share and maintained leadership in second-line patients. He noted compelling early pricing in Japan and ongoing negotiations in Germany and other European markets for 2026 launches, emphasizing the goal of securing appropriate value. Greenstreet added that while some combination use exists, monotherapy remains dominant, with anticipation of increased combination use as generics become available.

Salveen Richter asked about AMVUTTRA®'s momentum in first-line versus switch populations, any observed combination use, and clarity on ex-U.S. pricing strategies.

Answer

Yvonne Greenstreet, Chief Executive Officer, and Tolga Tanguler, Chief Commercial Officer, highlighted strong, balanced adoption across academic and community settings, with growing first-line share and leadership in second-line patients. They noted compelling pricing in Japan, early negotiation stages in Germany, and that the majority of use remains monotherapy, with increasing combination use anticipated as generics emerge.

Salveen Richter from Goldman Sachs asked for details on the patient profiles for Amvuttra's cardiomyopathy launch, specifically regarding the mix of frontline versus stabilizer-progressing patients and the current focus of the sales force.

Answer

CEO Yvonne Greenstreet stated that while initial uptake was faster among patients progressing on stabilizers, the mix has now become broad and balanced with a healthy share of first-line patients. She noted the strong resonance of the HELIOS-B data. CCO Tolga Tanguler added that these early trends validate the company's clinical thesis and commercial strategy.

Salveen Richter inquired about the planned Phase III study for Nucresiran in ATTR-CM, specifically regarding enrollment timing and interim analysis strategy given the availability of new treatment options.

Answer

Chief Medical Officer Pushkal Garg stated that Nucresiran's profile suggests it could be a best-in-class therapy. He explained the development plan aims to bring it to market quickly while building a clinical profile for broad, durable uptake. He deferred further details on the study design to the upcoming R&D Day.

Salveen Richter asked about the expected VAF reduction for mCALR (989) and the correlation between VAF and clinical outcomes. She also inquired about the evolution of the company's target margin profile over the next few years and through the Jakafi LOE, given Bill Meury's focus on managing operating expenses.

Answer

President Pablo Cagnoni explained that three molecular endpoints (VAF in whole blood, CD34+ mutant CALR cells in peripheral blood, mutant CALR megakaryocytes in bone marrow) will be reported, emphasizing bone marrow effects as critical disease-modifying effects, with VAF being a lagging indicator. He noted that while VAF reduction correlates with better hematologic responses in ET, initial approvals for 989 will likely be based on traditional clinical endpoints. CEO Bill Meury stated a multi-year view for OpEx, expecting spending growth percentage to decrease due to increased sales and leverage. He emphasized creating the steepest growth curve post-2029 and a long-duration revenue stream, streamlining costs without compromising growth, and expecting margins to improve over time.

Salveen Richter of Goldman Sachs asked about the reason for the delay in initial data for the V617F program to 2026 and sought more detail on povorcitinib's competitive differentiation in hidradenitis suppurativa (HS).

Answer

President and Head of R&D Pablo Cagnoni clarified the V617F delay was due to the need for higher doses and longer follow-up in the Phase 1 study. CEO Bill Meury addressed HS, describing it as a complex disease where povorcitinib's strong data on pain and flare control, along with its potential as a first oral option, provides a competitive profile.

Salveen Richter of Goldman Sachs asked about the povorcitinib Phase II data, specifically the drop in efficacy from week 12 to week 16 and the potential read-through risk for the Phase III trial. She also inquired about how the Medicare Part D redesign was modeled into the 2025 guidance for Jakafi.

Answer

Pablo Cagnoni, President, Head of R&D, attributed the Phase II efficacy drop to typical clinical trial variability and noise, stating the Phase III studies are well-powered for the week 12 endpoint. Christiana Stamoulis, CFO, explained that for Jakafi, expected savings from the Part D redesign are anticipated to be offset by the continued growth in 340B volumes.

Salveen Richter of The Goldman Sachs Group, Inc. asked for an overview of the development strategy for the acquired SGM portfolio, including how Incyte sees the different mechanisms playing out and their differentiation.

Answer

An unnamed executive detailed the strategy for the MRGPRX2 and MRGPRX4 programs. MRGPRX2 is being developed for chronic spontaneous urticaria, chronic inducible urticaria, and atopic dermatitis, with its high selectivity for mast cells in the skin expected to yield an excellent safety profile. MRGPRX4 is being developed for cholestatic pruritus, targeting the bile acid receptor. Data for both programs are expected in Q1 2025, after which next steps will be clarified.

Salveen Richter inquired about the quarter-over-quarter decline in VOXZOGO sales and sought an update on BioMarin's business development strategy, particularly how it aligns with the focus on VOXZOGO amidst competitive dynamics and when new growth levers might emerge.

Answer

Brian Mueller (CFO, BioMarin Pharmaceutical) attributed the Q3 VOXZOGO sales dip to timing shifts of larger contracted orders, reaffirming full-year guidance and emphasizing steady patient additions. Alexander Hardy (President and CEO, BioMarin Pharmaceutical) highlighted strong underlying business performance and significant cash flow, stating that business development is a high priority, pursuing early-stage collaborations and looking at phase III, pre-commercial, and commercial assets.

Salveen Richter asked for insights into the quarter-over-quarter decline in Voxzogo sales and sought an update on BioMarin's business development strategy, particularly how new levers might emerge to strengthen the portfolio amidst competitive dynamics.

Answer

Brian Mueller, Chief Financial Officer, attributed the Q3 Voxzogo sales dip to timing shifts in contracted orders, reiterating the full-year guidance and emphasizing steady patient additions as a key long-term demand indicator. Alexander Hardy, President and CEO, highlighted strong underlying business performance and cash flow, affirming business development as a high priority. He noted an evolution in strategy to include phase three, pre-commercial, and commercial assets, aiming to leverage BioMarin's rare disease capabilities for incremental growth.

Tommie Reerink, on behalf of Salveen Richter from Goldman Sachs, asked for an update on the timing and focus of business development activities and requested clarity on the level of detail to expect from the BMN 333 data update later this year.

Answer

Alexander Hardy, President and CEO, reiterated that BioMarin is methodically pursuing business development opportunities aligned with its strategy, with a goal of completing at least one deal this year. Greg Friberg, Executive Vice President and Chief R&D Officer, explained the upcoming BMN 333 update will be a top-line summary of Phase 1 data to confirm if it supports moving forward, with more detailed pharmacokinetic data to be presented in the first half of 2026.

An analyst on behalf of Salveen Richter asked for BioMarin's perspective on a potential growth hormone and CNP combination therapy, and whether the company would pursue it with BMN 333. They also asked what to look for in the upcoming BMN 333 data.

Answer

Chief R&D Officer Gregory Friberg clarified that BioMarin's goal is to develop BMN 333 as a best-in-class single agent, not a combination therapy. For the upcoming healthy volunteer study data, he said the key metric will be pharmacokinetic (PK) data, specifically looking for several-fold increases in sustained free CNP levels, which would support the potential for superior efficacy seen in animal models.

Salveen Richter asked for details on the development strategy for BMN 333, including its potential expansion into other indications, and sought clarity on BioMarin's intellectual property strategy for its CNP franchise in light of competition from Ascendis.

Answer

EVP, Worldwide R&D Greg Freiberg stated that BMN 333 aims to elongate its half-life to potentially increase pharmacodynamic effect, with healthy volunteer PK data expected next year. He noted the potential to accelerate development into other skeletal disorders. President and CEO Alexander Hardy reiterated the company's confidence in its IP and its intent to vigorously defend it, declining to elaborate further.

Salveen Richter asked for clarification on the HARMONi-6 data, specifically why PD-L1 negative patients appeared to outperform PD-L1 positive patients, and what translational work Summit Therapeutics plans to help oncologists understand this.

Answer

Jack West, VP of Clinical Development, explained that the differential effect was greater in PD-L1 negative patients, suggesting the VEGF component might be particularly relevant in this setting. He cautioned against over-interpreting subset analyses and emphasized the need for education to overcome historical perceptions of anti-angiogenic therapies' safety profiles.

Salveen Richter inquired about the Phase 3 trial for ACP101 in Prader-Willi syndrome (PWS), asking if functional endpoints like hyperglycemia control and weight loss are being evaluated and what would constitute a clinically meaningful bar for success.

Answer

EVP, Head of R&D, Elizabeth Thompson, stated that a clinically meaningful result would be a magnitude of effect similar to that seen with the 3.2mg dose in the prior study, a level deemed meaningful by physicians and patient advocates. She clarified that the study is not specifically focused on endpoints like weight circumference due to the complex interplay of the disease and family-managed food access.

Mark, on behalf of Salveen Richter from Goldman Sachs, asked for the company's perspective on recent data from autologous dual-targeting CAR-Ts and how Eticell (UCART20x22) is differentiated beyond its allogeneic nature.

Answer

Chief Medical Officer Dr. Adrian Kilcoyne described Eticell as a well-differentiated product for later-line lymphoma, with a clearer strategy to be presented at ASH. CFO & Chief Business Officer Arthur Stril added a key differentiator is that Eticell targets CD20 and CD22, not CD19. This provides a unique, off-the-shelf alternative for physicians after a patient has already received a CD19-targeted therapy, a growing need as CD19 therapies move to earlier lines of treatment.

An analyst on behalf of Salveen Richter asked about the potential late-stage development strategies for UCART22 and how the upcoming data might influence the final decision.

Answer

CEO Dr. André Choulika explained that while Cellectis believes there is a clear registration path for UCART22, the specific strategy is contingent on upcoming discussions with the FDA and EMA. He stated that more granularity will be available to share after the Q3 data release.

Salveen Richter from Goldman Sachs asked about the revised strategy to achieve a broad peripheral neuropathic pain (PNP) label for suzetrigene and sought clarity on the expected gross-to-net trajectory for Gernavix for the remainder of the year.

Answer

President and CEO Dr. Reshma Kewalramani stated the immediate plan is to secure the DPN indication first, then broaden the label over time, with a broad PNP label remaining the ultimate goal. EVP, COO & CFO Charles Wagner explained that Gernavix's gross-to-net was initially high due to patient support programs but will normalize as payer coverage expands.

Salveen Richter asked for details on the early adopters of ALYFTREK and which patient pools were driving uptake. She also questioned the nuances of JOURNAVX's commercial payer coverage, specifically regarding tiered and preferred versus non-preferred status.

Answer

COO Stuart Arbuckle explained that ALYFTREK uptake is seen across all patient groups, with the fastest adoption among those newly eligible or with rare mutations. CCO Duncan McKechnie addressed the JOURNAVX question by stating the goal is to secure broad coverage with minimal restrictions and patient affordability. He highlighted a recent agreement with a large PBM covering 22 million commercial lives as progress toward this goal.

Salveen Richter inquired about Vertex's pre-launch strategies to accelerate retail pharmacy stocking and P&T committee reviews for JOURNAVX, and also asked for the definition of success for the cystic fibrosis mRNA program.

Answer

COO Stuart Arbuckle explained that Vertex has been working with national and regional retail chains to ensure broad availability and providing clinical data to payers to expedite access. CEO Reshma Kewalramani stated that for the VX-522 mRNA program, a ppFEV1 improvement between 3% and 14% would be considered a clinical success, referencing the range established by prior CFTR modulators.

Salveen Richter from Goldman Sachs inquired about the upcoming Phase II suzetrigine data in lumbosacral radiculopathy (LSR), asking what NPRS score delta Vertex needs to see to advance to Phase III and about the company's confidence in defining this patient population.

Answer

CEO Dr. Reshma Kewalramani explained the study is designed to assess the magnitude of treatment effect in both the drug and placebo arms to properly size a Phase III trial, not for a direct statistical comparison. She expressed high confidence based on the drug's mechanism, existing clinical evidence, and careful patient selection.

Salveen Richter of Goldman Sachs requested clarification on the initial target patient population for the upcoming thalassemia launch.

Answer

Chief Commercial Officer Tsveta Milanova explained the initial focus is on 4,000 of the 6,000 diagnosed adult patients in the U.S. who are symptomatic and actively managed, including both transfusion-dependent and non-transfusion-dependent individuals. CFO Cecilia Jones added that thalassemia revenues are not expected to be material in 2025 due to the timing of the launch.

On behalf of Salveen Richter of Goldman Sachs, an analyst asked about the expected pricing strategy for PYRUKYND in thalassemia, considering payer feedback, the drug's existing price in PK deficiency, and the different patient population.

Answer

CCO Tsveta Milanova stated that specific pricing will be determined closer to the September PDUFA date and will be based on the product's value and final label. She shared that payer research has been positive, with payers recognizing the high unmet need in thalassemia, a rare disease not expected to be heavily managed. She expressed confidence in the market access team's ability to secure favorable pricing and access based on the drug's strong profile.

Lydia Erdman, on behalf of Salveen Richter at Goldman Sachs, asked about the consistency of the AMT-130 data at the 2.5-year mark compared to the 2-year data presented previously.

Answer

Chief Medical Officer Walid Abi-Saab clarified that the company has not conducted any formal interim analysis since the June 2024 data cut. The next formal analysis will be of the three-year data from the June 2025 cutoff, which is scheduled to be presented in September.

Lydia Erdman, on for Salveen Richter, asked if data from Cohort 3 of the AMT-130 trial will be included in the potential BLA filing.

Answer

CMO Dr. Walid Abi-Saab confirmed that all available data as of the cutoff date, which includes the 12 patients from Cohort 3, will be part of the BLA submission to provide the FDA with the totality of the data for its review.

Lydia, on behalf of Salveen Richter from Goldman Sachs, asked management to frame the 'bar for success' for the upcoming TSHA-102 data update in light of the recent positive FDA feedback.

Answer

CEO Sean Nolan outlined a three-part framework for the upcoming update: 1) presenting a natural history analysis to establish a baseline, 2) detailing the FDA-aligned pivotal trial design and primary endpoint, and 3) sharing long-term low-dose and initial high-dose clinical data through the lens of that endpoint. He noted this alignment obviates an end-of-phase meeting, potentially accelerating the timeline to a BLA submission.

Salveen Richter requested specific details on the objective measures, milestones, and functional gains that Taysha is considering for Part B of the REVEAL study following its recent FDA feedback.

Answer

CEO Sean Nolan stated that while he could not share specific details pending final alignment with the FDA, the focus is on validated, pre-existing metrics for milestones, gross motor function, and hand function. He indicated that the company expects to finalize these plans with the FDA in the first half of 2025.

Representing Salveen Richter, Mark asked for details on the upcoming ALLO-329 autoimmune data, including the length of follow-up, the type of clinical data to be presented, and the company's view on the bar for success.

Answer

CEO David Chang stated that the revised timeline to H1 2026 will naturally provide longer follow-up for the initial 'handful of patients' in the dose-escalation study. He deferred providing specific details on the data presentation or the bar for success, emphasizing that the immediate focus is on patient enrollment.

Mark on for Salveen Richter asked what data for ALLO-329 in autoimmune disease would constitute proof-of-concept by year-end and how the approach is differentiated from the many other CD19-targeting therapies.

Answer

President and CEO Dr. David Chang explained that year-end proof-of-concept will be biomarker-based from a handful of patients, focusing on CAR T expansion, B-cell depletion, and autoantibody levels. He highlighted differentiation through its allogeneic nature and dual targeting of B-cells (CD19) and activated T-cells (CD70), which could enable longer remissions and broader applicability.

Mark on for Salveen Richter questioned why the ALLO-316 cohort with FC lymphodepletion performed better than the FCA cohort that included a CD52 antibody, given the small patient numbers. He also asked what data threshold from the Phase Ib expansion would provide confidence for a clear regulatory path.

Answer

Dr. David Chang, President and CEO, cautioned against over-interpreting the difference due to small numbers, highlighting the most important finding is that responses were seen with a standard FC regimen, thanks to the intrinsic Dagger biology. Dr. Zachary Roberts, EVP of R&D and CMO, added that the current response rate is already numerically superior to approved third-line options, and the key determinant for the path forward will be durability, with an update expected next year.

An analyst on behalf of Salveen Richter asked about the magnitude of expected benefit from the Phase II combination study of SYFOVRE with an siRNA product versus SYFOVRE monotherapy.

Answer

Executive Cedric Francois described the program as the next big innovation in geographic atrophy. He explained that while SYFOVRE's protection of photoreceptor cells is strong, the combination aims to improve the effect on retinal pigmented epithelial cells beyond the current 30-40% slowdown, potentially pushing efficacy north of 50%. He also noted the trial will better assess functional impact on vision.

Salveen Richter of Goldman Sachs asked for more color on the expected cadence of the SYFOVRE launch in 2025, given the Q1 dynamics and competitive landscape.

Answer

CEO Dr. Cedric Francois emphasized that underlying demand, measured by injections, continues to grow, reflecting the large unmet need with fewer than 10% of GA patients being treated. He stated that Apellis is in an 'enviable position' competitively, as the competitor's data shortcomings are now clearer to physicians, creating a more level playing field.

Salveen Richter from Goldman Sachs requested more detail on the 'next group of retina specialists' driving market growth and asked for clarification on the gross-to-net assumptions underlying the Q4 guidance of flat to modest revenue growth.

Answer

CEO Dr. Cedric Francois described this group as the 'next wave' of physicians who adopt a new therapy after the initial launch phase. CMO Dr. Caroline Baumal added this includes younger, recently trained specialists. CFO Timothy Sullivan clarified that the Q4 guidance incorporates the expectation for gross-to-net to be in the low to mid-20% range through 2025, noting the Q3 increase was an anomaly due to specific launch-related factors.

Salveen Richter inquired if Arcus would consider a commercialization partnership for casdatifan after the PEAK 1 trial readout and asked for commentary on the newly announced FDA director.

Answer

CEO Terry Rosen stated that Arcus's intent is to commercialize casdatifan themselves, particularly in the U.S., viewing it as a manageable and significant opportunity, though a partner for Europe might be considered. He declined to comment on the FDA news but affirmed that from a practical standpoint, interactions with the agency have been 'business as usual'.

An analyst from Goldman Sachs, on behalf of Salveen Richter, asked about the potential registrational pathway for etrumadenant in colorectal cancer and the timeline for announcing the next steps for the program.

Answer

CEO Terry Rosen stated that Arcus and its partner Gilead are actively planning the next steps for etrumadenant. He noted that clinical advisors have suggested exploring an earlier-line setting, potentially frontline colorectal cancer, but a final decision is still under discussion.

Salveen Richter asked for a reminder of the timelines for seeing data from the confirmatory studies for both the exon-skipping (PMO) franchise and ELEVIDYS (the ENVISION trial).

Answer

Head of R&D Dr. Louise Rodino-Klapac clarified that for the ELEVIDYS confirmatory trial, ENVISION, the last patient's last visit is expected in 2027. The company did not provide a specific update on the PMO confirmatory trial data timeline in this response, but noted in prepared remarks that the studies are fully enrolled and on track.

Salveen Richter pressed further on the gating factor for the 2025 guidance, asking if it is patient capacity at infusion centers or manufacturing supply, and also requested details on the PMO cannibalization assumption.

Answer

CEO Douglas Ingram reiterated that there is no significant bottleneck and the launch curve is defined by the entire process, including infusions and payer interactions. Regarding cannibalization of the PMO franchise, he stated that it is expected to be quite modest in the current year and into 2025, allowing for strong performance from all therapies.

Salveen Richter of Goldman Sachs asked for more color on the competitive dynamics for Pombiliti/Opfolda in the U.S. and how physicians are deciding between it and Nexviazyme as more patients become eligible to switch.

Answer

President and CEO Bradley Campbell highlighted that Sanofi's Pompe franchise declined 5% globally in Q1, suggesting Amicus is taking market share. He explained that physicians typically wait two years before considering a switch from Nexviazyme, and the decision is driven by declines in clinical measures and patient-reported outcomes. He stressed that a growing body of real-world evidence and case studies supporting the switch is key to driving adoption.

Salveen Richter requested further commentary on the competitive dynamics between Pombiliti and Nexviazyme in both U.S. and ex-U.S. markets, particularly in light of recent growth reported by Sanofi for their asset.

Answer

Chief Business Officer Sebastien Martel detailed that the switch dynamics reflect the respective market shares of competing products. In the U.S., where Nexviazyme has a larger share, about two-thirds of Amicus's switches come from that therapy. Conversely, ex-U.S., where Myozyme is more dominant, a greater proportion of switches are from Myozyme, supplemented by new, treatment-naive patients.

An analyst on behalf of Salveen Richter asked if physicians are switching patients to Nexviazyme before considering Pombiliti and Opfolda, and when the prescription-to-infusion lag time might reach the 30-45 day target.

Answer

President and CEO Bradley Campbell stated they are not seeing a trend of physicians switching to Nexviazyme first. He clarified that they are taking switch patients proportionally from all segments, and the market dynamics simply reflect that Nexviazyme was available earlier. He projected that the prescription-to-infusion time should reach the 30-45 day target by the end of 2024, mirroring the timeline seen with the Galafold launch.

Salveen Richter asked for details on Gilead's exposure to potential U.S. tariffs, its manufacturing footprint, and for clarification on the impact of the Medicare Part D redesign relative to guidance.

Answer

CEO Daniel O'Day explained that Gilead has lower exposure to pharmaceutical-specific tariffs because the vast majority of its intellectual property is already registered in the U.S. CFO Andrew Dickinson added that current guidance absorbs the impact of known indirect tariffs. Regarding Part D, CCO Johanna Mercier reiterated that assumptions are unchanged, with an expected $1.1 billion total impact ($900 million for HIV), and noted that underlying HIV business grew 9% excluding this headwind.

Salveen Richter of Goldman Sachs questioned if the forecast for the HIV PrEP market to grow to 600,000 people by 2030 is still a fair assumption, where the growth will originate, and what portion of users might prefer an oral option.

Answer

Johanna Mercier, Chief Commercial Officer, affirmed the company's belief that the market will reach at least 600,000 by 2030. She stated that growth will primarily come from new consumer segments, including Latino and Black individuals, cisgender women, and young adults, driven by the broad data from the PURPOSE trials. She expects most of this growth will be driven by the new, differentiated twice-yearly lenacapavir option.

An analyst on behalf of Salveen Richter asked about the discontinuation of NTLA-3001, whether there were unfavorable signals, and for details on the second-generation approach.

Answer

CEO John Leonard confirmed there were no unfavorable clinical signals with NTLA-3001. The decision to discontinue was part of the broader pipeline prioritization announced in January. He mentioned that a 'Gene Writer' approach has significant utility for the target disease and that more details would be shared at an appropriate time.

A representative for Salveen Richter requested a discussion on the read-through from the Phase II data of NTLA-2002 in HAE to the recently initiated Phase III HAELO study.

Answer

CEO John Leonard highlighted that 12 of 15 patients treated with the 50mg dose across Phase I and II achieved a 'functional cure,' meaning no attacks after a single dose. He described this as a new category of response and expects similar outstanding results from the Phase III trial, which has a longer observation period.

An analyst on behalf of Salveen Richter asked for clarification on the inventory dynamics that led to a disconnect between prescription growth and revenue growth in Q4, and also inquired about the proportion of free drug provided during the quarter.

Answer

CEO Barry Greene emphasized that patient demand, measured by shipments to patients, grew over 20% quarter-over-quarter and is the best leading indicator. COO Chris Benecchi explained that reported revenue is based on shipments to wholesalers and can fluctuate due to inventory management in the channel. He also noted that the percentage of free drug provided to uninsured or underinsured patients decreased in Q4 compared to Q3 and is expected to decline further as coverage expands.

Salveen Richter inquired about the discrepancy between ZURZUVAE's reported sales versus shipment demand and the impact of the free drug program on these figures.

Answer

CEO Barry Greene highlighted strong launch dynamics and a paradigm shift in treatment by OB/GYNs. CBO Chris Benecchi explained that while patient shipments nearly doubled, reported revenue was affected by wholesalers reducing inventory from 8 weeks in Q1 to 5.5 weeks in Q2. He added that the free goods program is a strategic tool to ensure rapid patient access while payer coverage and specialty pharmacy processes are optimized.

Matthew Dellatorre, on behalf of Salveen Richter, asked about the drivers for improved ABECMA margins, whether the breakeven sales target has changed, and how the company is positioned for 2025 given the Q4 guidance.

Answer

Vicki Eatwell explained that improved margins were driven by strong sales demand and manufacturing efficiencies, with success rates over 95%. She also updated the breakeven sales estimate from $400 million to closer to $300 million. William Baird added that they are encouraged by market growth heading into 2025 but are not providing specific guidance yet.