Biren Amin

Biren Amin questioned what Sarepta believes the FDA requires from Cohort 8 data to demonstrate safety, specifically regarding acute liver injury and ALT/AST elevations, and the current status of restarting the ENVISION trial.

Answer

Executive VP, Chief Scientific Officer, and Head of Research and Development Louise Rodino-Klapac confirmed that all liver parameters, including AST and ALT, are being collected for ALI calculation. She stated that the Cohort 8 data will help inform restarting the ENVISION trial in the U.S., with findings expected by year-end.

Biren Amin asked about the requirements for FDA to demonstrate safety with Cohort 8 data, specifically regarding acute liver injury (ALI) and acceptable thresholds for ALT/AST elevations. He also inquired about the status of the ENVISION trial and when Sarepta anticipates restarting it.

Answer

Louise Rodino-Klapac, Executive VP, Chief Scientific Officer, and Head of Research and Development, confirmed that all liver parameters, including AST and ALT, are being collected for ALI calculation, which will be a key focus for the FDA. Regarding ENVISION, she stated that Sarepta expects to first review the Cohort 8 data to inform the decision on restarting that trial.

Biren Amin asked how site capacity changed in the last two months, contrasting with previous comments about ample capacity, and what risk mitigation strategies the company can provide to physicians.

Answer

President and CEO Douglas Ingram clarified that aggregate capacity is good, but there's an imbalance, with top sites being fully booked for a year or more. The issue is making all sites more productive, which is a focus for the company. For risk mitigation, he highlighted the extensive monitoring in the label and the Sarepta Exchange program for real-time expert access, emphasizing that the greatest confidence will come from understanding the therapy's strong overall safety and efficacy data.

Biren Amin of Piper Sandler asked if protein expression in non-ambulatory patients in the EMERGENE trial for LGMD is expected to be similar to that seen in ambulatory patients from the Phase I study, and if the data will be compared to a natural history cohort.

Answer

Chief Scientific Officer Dr. Louise Rodino-Klapac confirmed they have seen similar expression levels in both ambulatory and non-ambulatory patients. She clarified that while the EMERGENE trial's primary endpoint is expression, the follow-on confirmatory study will analyze functional outcomes for the two populations separately and will use Sarepta's own JOURNEY natural history study as the comparator.

Biren Amin of Piper Sandler requested a breakdown of commercial ELEVIDYS patients in Q3 between ambulatory and non-ambulatory populations and asked about the market access trends for each group.

Answer

President and CEO Doug Ingram explained that while they do not provide a granular breakdown, there is an expected bias towards ambulatory patients early in the launch. However, he stressed that a 'very significant percentage' of start forms are for late and non-ambulatory patients, and he is confident this segment will grow. Chief Customer Officer Dallan Murray added that this mix is not expected to fluctuate significantly quarter-to-quarter in the near term.

Biren Amin noted an increase in infusing sites and asked for commentary on the number of patients treated per site and the consistency of patient volume across centers.

Answer

CCO Dallan Murray corrected the premise, stating the number of sites has been very consistent at around 75. CEO Douglas Ingram added that this number already exceeds their original goals. Murray emphasized that the model is flexible, allowing them to rapidly bring on new sites, including adult neuromuscular centers, as needed to support patient demand, ensuring more than enough capacity.

Biren Amin asked about the key drivers of momentum for BridgeBio beyond 2025, given its impressive productivity and sustainable development model, and when investors should expect new assets from the pipeline.

Answer

CEO Neil Kumar stated that the near-term focus is on approval and successful launch of the recently successful Phase 3 drugs, followed by additional indications for existing medicines (e.g., chronic hypoparathyroidism for encaleret, hypochondroplasia for infigratinib). He emphasized leveraging the growing scientific substrate from GondolaBio for organic growth, bringing in new assets if the cost of capital is corrected and current launches are successful. Kumar reiterated that the company prefers organic growth over expensive M&A.

Biren Amin inquired about the key drivers of momentum for BridgeBio beyond 2025 and when investors should anticipate new assets emerging from the pipeline, considering the company's sustainable development model.

Answer

Neil Kumar, CEO, outlined the near-term focus on the approval and successful launch of current Phase III drugs, followed by pursuing additional indications for existing medicines like encaleret and infigratinib. He emphasized long-term organic growth from the BridgeBio ecosystem, particularly the Gondola pipeline, and reiterated a preference for internal development over M&A for growth.

Biren Amin asked about market access as a top priority for BridgeBio and the anticipated impact of Pfizer matching the 28-day free trial for Vindamax.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, and Matt Outten, Chief Commercial Officer, BridgeBio Pharma, viewed Pfizer's matching program as a positive, welcoming competition and noting that BridgeBio's programs remain the most generous. They stated no impact has been observed from Pfizer's matching program. Neil emphasized Atrobi's differentiated LDN design and high-touch, white-glove rare disease approach, which provides meaningful advantages in patient and physician experience.

Biren Amin asked about Pfizer matching BridgeBio's 28-day free trial for Vindamax and any foreseen impact from this program on Attruby.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, viewed Pfizer's matching program as a positive, encouraging further innovation in patient support. He asserted that BridgeBio's programs remain the most generous. Matt Outten, COO, BridgeBio Pharma, added that they have not observed any negative impact, noting that being the first to offer such a program creates a lasting impression. Kumar highlighted the differentiated design of Attruby's patient access programs, emphasizing a superior patient and physician experience.

Biren Amin of Piper Sandler Companies questioned the market share dynamics for Atruvi between community and academic centers, and also asked about the potential market share for infigratinib in achondroplasia and its positioning in hypochondroplasia.

Answer

CEO Neil Kumar stated that while the majority of Atruvi prescribing remains in Centers of Excellence (COEs) and affiliated practices, uptake in the community setting is growing. Justin To, CEO of QED Therapeutics, added that market research suggests an oral therapy like infigratinib could capture 60% of the achondroplasia market and expressed confidence in its potential for hypochondroplasia based on recent preclinical data.

Biren Amin from Jefferies inquired about what clinical data is resonating most with physicians for Attruby, the biggest hurdles to adoption, the gross-to-net percentage for the quarter, and any observed impact from the Medicare Part D redesign.

Answer

CCO Matt Outten stated that the messaging around a 3-month onset of effect and a 50% reduction in cardiovascular hospitalizations is resonating strongly. CEO Neil Kumar added that emerging data on TTR stabilization is also compelling. CFO Tom Trimarchi explained that gross-to-net trended favorably this quarter due to lower-than-expected use of patient assistance programs, but he expects this to normalize over the year. The floor for gross-to-net is the 20% IRA rebate.

Biren Amin asked if Viking has reached an agreement with the FDA on patient numbers and duration for the oral Phase III program, about the supply status of oral VK2735 for Phase III, and if it's a gating item for the Q3 start. He also inquired about the autoinjector status for VANQUISH and the amylin program's Phase I start, data timing, and expectations.

Answer

Viking Therapeutics' President and CEO, Brian Lian, stated that Viking outlined its clinical development plan to the FDA and is comfortable proceeding with the presented design. He doesn't anticipate supply challenges for oral VK2735 for Phase III. The autoinjector bioequivalence study was successfully completed, and its introduction into the VANQUISH program is expected this quarter. For the amylin agonist, the IND will be filed later this quarter, with first dosing likely in Q2, and SAD data potentially available later in 2026.

Biren Amin of Piper Sandler Companies sought to confirm if the 78-week duration of the Phase III trials implies a 26-week titration period and asked when the trials would be posted on clinicaltrials.gov. He also questioned how long it would take to manufacture clinical supply for a potential Phase III oral study.

Answer

President & CEO Brian Lian confirmed the trial duration includes a titration window plus 52 weeks at the final dose, and that the trial listings would be posted 'very soon'. He also stated that manufacturing supply for a potential Phase III oral study would not be a gating factor for its initiation, as multiple batches are already in progress.

Biren Amin questioned whether the formulation for oral VK2735 is finalized and asked for details on the planned trial for the monthly subcutaneous regimen, including patient numbers and duration.

Answer

Brian Lian, President and CEO, responded that the current oral formulation is 'pretty set,' though minor optimizations are always being explored. For the monthly regimen trial, he described it as a smaller, PK-focused study to evaluate exposures during the transition from weekly dosing. He estimated it would last slightly longer than three months to accommodate the necessary dose titration.

Biren Amin asked about the planned doses for the monthly subcutaneous study and its start time relative to the weekly Phase III trial. He also inquired about the remaining requirements for the amylin program's IND submission.

Answer

CEO Brian Lian declined to disclose specific doses for the monthly study until initiation but mentioned a plan to use a weekly regimen for about four weeks before transitioning. For the amylin program, he confirmed that all IND-enabling work, particularly toxicology studies, must be completed to enable a filing later in the year.

Biren Amin of Piper Sandler Companies inquired if a 30% delta in MRD conversion could translate to a similar Event-Free Survival (EFS) benefit as seen in other CAR T trials, and if the cash runway into 2027 would cover the EFS data readout.

Answer

President and CEO Dr. David Chang affirmed that assuming MRD conversion equates to complete remission, a similar EFS benefit could be expected. CFO Geoffrey Parker added that the cash runway extends into 2027, and its sufficiency for the EFS readout depends on trial enrollment pace, noting that 2027 is 'in the ballpark' for when those events could occur.

Biren Amin questioned if ALPHA3 clinical sites are now adequately staffed and asked for specifics on the conversion rate and average time from patient consent to randomization.

Answer

EVP of R&D and CMO Dr. Zachary Roberts stated that sites are now generally staffed and operational workflows are established, but deferred providing granular metrics on conversion rates and timing. CEO David Chang added that the time to randomization varies, as patients can consent anytime during their 12-18 week treatment, followed by logistics post-MRD testing, which contributed to the revised timeline.

Biren Amin from Piper Sandler asked for confirmation that ALPHA3 enrollment is on track for completion by H1 2026 and inquired about the patient enrollment split between community and academic trial sites.

Answer

Dr. David Chang, President and CEO, indicated that enrollment is 'more or less tracking' with prior guidance, with the focus remaining on the unchanged data readout timelines. Dr. Zachary Roberts, EVP of R&D and CMO, added that despite a 50/50 site split, patient enrollment shows robust activity from both community and academic centers without a heavy skew.

Biren Amin asked what level of durability data for ALLO-316 would be needed to justify a meeting with the FDA about a pivotal trial design. He also inquired about the specific indications Allogene plans to pursue in the Phase I trial for ALLO-329.

Answer

Dr. Zachary Roberts, EVP of R&D and CMO, responded that for ALLO-316, the bar is low, noting two patients have ongoing deep partial remissions at 4 and 6 months. He said the RMAT designation facilitates FDA discussions, and they will engage the agency once more durability data is available. For ALLO-329, he stated the initial focus will be on rheumatologic conditions like lupus, following the proof-of-concept data emerging in the field.

Biren Amin of Piper Sandler inquired about any CMC changes between the Part A and Part B material batches, particularly the full-to-empty capsid ratio, and asked about the commercial supply capacity upon potential approval.

Answer

CEO Sean Nolan confirmed that the FDA has agreed the Part A and pivotal materials are analytically comparable. The pivotal trial product, manufactured using the planned commercial process at scale, has been cleared for clinical use. He also noted that the recent financing provides the flexibility to begin building commercial inventory to meet the large unmet need, should the program advance quickly.

Biren Amin from Piper Sandler inquired about the logistical process of transitioning from Part A to the pivotal Part B trial with existing sites and asked about plans for engaging with the European Medicines Agency (EMA).

Answer

CEO Sean Nolan stated the transition will be seamless by leveraging existing, contracted sites, with the potential to add new ones to expedite enrollment. Regarding Europe, he noted it's a significant opportunity and that the regulatory team has been working in the background to enable the EMA pathway, which could be pursued more actively with additional capital.

Biren Amin of Piper Sandler Companies sought to understand the basis for the Q1 2026 OS analysis timeline for Tivesimig, asked for an update on the quadruplet combination IST, and posed detailed questions about the CTX-8371 responses, including why they weren't considered complete responses and the patients' prior treatment and PD-L1 status.

Answer

CEO Thomas Schuetz confirmed the Q1 projection is based on the current, slower mortality rate. He had no update on the IST. Regarding CTX-8371, he explained the responses were classified as partial (PR) instead of complete (CR) due to non-target lesions that did not disappear. He noted the TNBC patient had prior pembrolizumab and the NSCLC patient had low PD-L1 expression at original diagnosis, but patients were not re-biopsied for the study.

Biren Amin of Piper Sandler Companies asked if the Tivesimig OS timeline projection is based on the current, slower event rate. He also inquired about the CTX-8371 responses, questioning why they were not considered complete responses (CR) and asking about prior therapies and PD-L1 status.

Answer

CEO Thomas Schuetz confirmed the Q1 2026 projection for Tivesimig's OS analysis is based on the current, decreased mortality rate. For CTX-8371, he explained the responses were partial (PR) due to non-target lesions that did not disappear, despite target lesions showing a CR. He stated all patients had prior checkpoint inhibitors but did not have PD-L1 status upon entry into the Phase 1 study.

Questioned the basis for the Q1 2026 OS analysis timeline for tivesimig and asked for an update on the Phase 1 IST. For CTX-8371, he asked why a patient with zero tumor was not a complete response and inquired about the prior treatment and PD-L1 status of the responding patients.

Answer

The Q1 projection for the tivesimig OS analysis is based on the current, slower mortality rate. There is no update on the IST study. The responding patients were classified as partial responses (PR) due to non-target lesions that did not disappear, per RECIST criteria. The company did not re-biopsy patients for PD-L1 status in the Phase 1 study, but noted the NSCLC patient had low PD-L1 expression at initial diagnosis.

Biren Amin of Piper Sandler Companies asked for an update on the SOLAR trial, including the timeline for completing randomization, the rationale for changing the rescue criteria, and whether masked data from SOLAR prompted the change.

Answer

Pravin Dugel, Executive Chairman, President & CEO, stated that enrollment for SOLAR is complete and the trial is proceeding well. He clarified the change in rescue criteria was a strategic decision made from a position of confidence based on masked data from the SOUL-one trial, not an FDA requirement. The goal is to enhance the trial's clinical relevance for physicians to support immediate adoption upon approval.

Biren Amin asked for the rationale behind the week 76 redosing in SOL-1 and whether all patients, including those in the control arm or with prior rescues, would be redosed. He also inquired if the SOL-R size reduction was primarily due to the new safety data from SOL-1 and if these trial changes were contemplated when the Board set executive performance targets.

Answer

President and CEO Dr. Pravin Dugel clarified that the week 76 redosing is to maximize drug exposure to satisfy FDA safety requirements. He confirmed all patients in SOL-1 will be redosed at weeks 52 and 76 with their originally randomized drug, regardless of prior rescue status. He affirmed the SOL-R size reduction was a direct result of fulfilling safety requirements across both studies. Regarding performance targets, Dr. Dugel stated that while FDA discussions are confidential, the company's confidence in the trials' success is 'higher than ever.'

Biren Amin asked for clarification on what constitutes a 'differentiated product label' for AXPAXLI, questioning if it would be based on treatment frequency or other specific metrics.

Answer

President and CEO Dr. Pravin Dugel explained that a differentiated label would address key clinical questions on durability, repeatability, and flexibility (6-to-9-month dosing). He added that if successful, the label could also include a unique superiority claim, providing both regulatory and commercial advantages.

Biren Amin asked for an update on the SOL-1 trial's enrollment completion timeline, which was previously guided for the first half of 2025. He also inquired about any feedback from the European Medicines Agency (EMA) on the SOL-1 and SOL-R study designs and asked for details on the retreatment criteria for the SOL-R trial.

Answer

Dr. Pravin Dugel, President and CEO, stated that while the pace of SOL-1 enrollment is ahead of expectations, the official guidance for completion by the end of Q1 2025 has not been changed yet. He mentioned that conversations with the EMA are progressing well and updates will be provided when appropriate. Regarding SOL-R's retreatment criteria, Dr. Dugel explained they are still under discussion with the FDA but are expected to align with other non-inferiority studies.

Biren Amin of Piper Sandler Companies questioned why Q2 commercial doses for Cyfovri were lower than in Q4 2024 and asked if the lower Q2 R&D expense represents a new run rate.

Answer

CFO Tim Sullivan explained that Q4 2024 is not a good comparable due to significant inventory stocking at the physician office level, and that injection growth is the best demand metric. He also advised using an average of recent quarters for R&D expense, as pivotal studies for DGF and FSGS are expected to ramp up.

Biren Amin of Piper Sandler Companies asked about the decline in Cyfovri commercial doses from a high in Q4 2024 to Q2 2025, and whether the lighter Q2 R&D expense is the new run rate.

Answer

CFO Tim Sullivan explained that Q4 2024 was not a good barometer due to significant inventory stocking at the physician office level, and reiterated that injection growth is the best demand metric. Regarding R&D, he advised using the average of recent quarters rather than the Q2 figure, as pivotal studies for DGF and FSGS have not yet fully ramped up.

Biren Amin of Piper Sandler Companies asked for an explanation for the decline in Cyfovri commercial doses from 89,000 in Q4 2024 to 82,000 in Q2 2025. He also questioned if the Q2 R&D expense is the new run rate or if an average of recent quarters is more appropriate.

Answer

CFO Timothy Sullivan explained that Q4 2024 was not a good barometer due to significant inventory stocking at the physician office level and advised focusing on injection growth as the true demand metric. Regarding R&D, he suggested using an average of recent quarters is safer than the Q2 run rate, as pivotal studies for DGF and FSGS have not yet fully ramped up.

Biren Amin of Piper Sandler questioned the decline in Cyfovri commercial doses from Q4 2024 to Q2 2025 and asked if the lower Q2 R&D expense represents a new run rate.

Answer

CFO Tim Sullivan explained that Q4 2024 is not a good comparable due to significant inventory stocking at physician offices, reiterating that injection growth is the key demand metric. For R&D, he advised that using the recent average is safer than the Q2 figure, as pivotal studies for DGF and FSGS have not yet fully ramped up.

Biren Amin sought confirmation that the quarterly increase in SYFOVRE samples was primarily due to the co-pay foundation funding issue and asked if sample volume is expected to continue growing along with new patient starts.

Answer

Executive Cedric Francois noted that physicians are using samples to ensure patient care continues despite co-pay challenges, indicating strong underlying demand. Executive David Acheson confirmed that samples are true demand and that Apellis is actively working to educate practices on benefit designs to help transition these patients to commercial doses. This effort has been underway since mid-Q1.

Biren Amin of Piper Sandler inquired about the number of patient switches from the competitor, IZERVAY, contributing to new patient share growth, and asked about the expected SG&A increase for the upcoming C3G/IC-MPGN launch.

Answer

COO Adam Townsend stated that while switching occurs, it is not frequent, and the company's focus is on bringing new prescribers into the market. For the nephrology launch, he noted they will leverage the existing PNH infrastructure and are currently determining the appropriate field force size. CEO Dr. Cedric Francois added that switches happen in both directions and the market is still settling.

Biren Amin from Jefferies LLC asked about the expected data from the XOMA 358 trial in congenital hyperinsulinism and the company's plans for the drug's formulation, specifically regarding intravenous infusion.

Answer

SVP of R&D Paul Rubin explained that the study is designed for each patient to serve as their own control to demonstrate XOMA 358's ability to prevent hypoglycemia and determine optimal dose and duration. He noted that while a subcutaneous or intramuscular injection is preferred, a less frequent intravenous dose would still be a significant improvement over current treatments.