Huidong Wang

Gena Wang asked for the latest thinking on FDA submission requirements for the flu-COVID combo vaccine and for details on the statistical hierarchy for the CMV trial's new secondary endpoints.

Answer

President Stephen Hoge responded that consultations with the FDA on the flu-COVID combo are just beginning, so requirements are not yet finalized, but flu efficacy data is key. For CMV, he confirmed a hierarchical testing approach for the secondary endpoints but did not disclose specifics. He reiterated a 'fall' timeline for the data readout but declined to commit to a more precise two-month window.

Huidong Wang questioned if the low Q1 U.S. COVID revenue signaled a future market share loss and asked for the number of events planned for the flu vaccine's interim analysis.

Answer

CFO Jamey Mock attributed the low Q1 revenue to customer inventory management rather than market share loss, pointing to script data showing a stable 38% share. President Stephen Hoge declined to provide a specific number of events for the flu analysis but confirmed it was a large number due to an intense flu season.

Huidong 'Gena' Wang followed up on the Norovirus program, asking what the FDA would need to see to lift the clinical hold, and questioned if the final data readout for the CMV vaccine would still occur in the first half of 2025.

Answer

President Stephen Hoge stated that for the Norovirus hold, the FDA needs time to review the submitted materials and that the outcome is up to the agency. For the CMV vaccine, he confirmed cases continue to accrue and results are still expected in 2025, but did not commit to a specific half of the year.

Huidong Wang asked about the implied net price per dose in the U.S., the final sales return reserve from the last season, the reserve assumption for the current season, and the rationale for not using a priority review voucher for the flu/COVID combo.

Answer

CFO Jamey Mock confirmed the analyst's pricing calculation was not far off and stated that a $140 million provision was released from the prior season's return reserve. President Stephen Hoge explained that a priority review voucher for the combo vaccine was not used because it would not accelerate approval in time for the 2025 contracting season.

Gena Huidong Wang asked about the financial impact of the community expansion effort, including its contribution to Q2 revenue, the percentage of treatment centers with outpatient capabilities, and the portion of Q2 revenue from outpatient settings.

Answer

Alan Bash, President of CARVYKTI, stated that while it is too early to quantify the revenue contribution from specific community expansion efforts, 70% of patients originate from the community setting. He also confirmed that over half of patients are administered CARVYKTI in an outpatient setting, which helps free up inpatient capacity and improve the experience for treatment centers.

Huidong Wang inquired about the key efficacy and safety data points to watch in the upcoming ASH update comparing CARVYKTI's CARTITUDE-1 trial to a competitor's. She also asked about the timeline for incorporating the overall survival (OS) benefit into NCCN guidelines and the product label.

Answer

CEO Ying Huang emphasized that the competitor's patient population appears less sick and that CARVYKTI's durability and progression-free survival (PFS) are the key differentiators. For safety, he noted proactive management is effective. SVP of Commercial Development, Steven Gavel, anticipated an NCCN guideline update by the end of Q4. Ying Huang added that submissions to the FDA and EMA are planned, with label updates expected by the end of the following year.

Gena Huidong Wang asked for clarification on the Suravec pivotal study, including the rationale for adding a fourth dose level, the primary endpoint timing, the reason for the amended AbbVie agreement, and the cost of the new Phase 2b study. She also inquired about recent FDA interactions for the DMD program.

Answer

President & CEO Curran Simpson noted consistent FDA interactions and no shifts in clinical trial design expectations for DMD. He and CFO Mitch Chan explained the AbbVie agreement was amended to accommodate the new Phase 2b trial, accelerating a $100 million milestone payment which will more than cover the study's cost. CMO Dr. Steve Pakola confirmed the primary endpoint is at one year and the fourth dose level was added to explore higher efficacy given the strong safety profile.

Huidong 'Gena' Wang of Barclays asked about the upcoming MDA data update for RGX-202, specifically the number of patients from the 1-to-3-year-old cohort and whether higher protein expression is expected. She also inquired about the timing and nature of the data update for the ALTITUDE trial's DME cohort.

Answer

CEO Curran Simpson responded that they expect to present microdystrophin data for one patient from the 1-to-4-year-old cohort at the MDA conference, noting a general trend of higher expression in younger patients. Chief Medical Officer Dr. Steve Pakola addressed the second question, stating that while no specific timing has been guided for the ALTITUDE DME cohort data, any update would include standard endpoints like visual acuity, retinal thickness, treatment burden reduction, and safety.

Gena Huidong Wang from Barclays asked if the December 2026 primary completion date for the 48-week ECLIPSE-1 study implies that most patients are already enrolled. She also questioned the low starting dose for VIR-5525 and plans for testing different dosing frequencies.

Answer

EVP & Chief Medical Officer Dr. Mark Eisner clarified that trial enrollment typically ramps up over time and declined to give specific numbers but expressed satisfaction with the progress. EVP of Oncology Dr. Mika Derynck explained the VIR-5525 starting dose is standard per regulatory guidance (MABEL dose) but anticipates rapid dose escalation due to learnings from other programs. She confirmed that while weekly dosing is required initially, less frequent dosing schedules are planned.

Huidong (Gena) Wang asked about the rationale for Alnylam's decision not to opt into the profit-sharing arrangement for elebsiran and inquired about the expected timing for the next data update from VIR's oncology programs.

Answer

Marianne De Backer (Executive) explained that Alnylam's decision was based on its own strategic portfolio prioritization and was made before VIR's latest HBV functional cure data was available. Regarding the oncology update, she stated that new data would be shared once more mature results from higher dose levels are available, likely at a future medical congress or a focused investor event.

Huidong Wang asked two questions: first, whether the 'target not detectable' rate and ALT normalization should be considered the key benchmarks for the upcoming HDV data readout. Second, she inquired if the monotherapy activity for the new T-cell engagers has held up with more patient data since the Sanofi deal.

Answer

Dr. Mark Eisner, Chief Medical Officer, confirmed that 'target not detectable' (TND) is a critical measure and that the FDA guidance includes a composite endpoint of TND plus ALT normalization, which will be presented. CEO Dr. Marianne De Backer added that since the Sanofi deal closed recently, they are still in a transition phase but will share initial monotherapy data for two T-cell engagers in Q1 2025.

Gena Wang from Barclays questioned the TRINGOZA full-year guidance of $75-80 million, noting it implies a slowdown in quarterly growth for the second half of the year. She also sought more specific numbers on the anticipated acute pancreatitis (AP) events in the CORE studies.

Answer

CGO Kyle Jenne explained the launch's initial bolus included converting clinical trial participants and previously identified patients. He stated that future growth relies on identifying new patients, which takes more time and educational effort, justifying the guidance. CEO Brett Monia reiterated that while total AP events will exceed the FCS study, he would not provide a more specific number ahead of the September data release.

Huidong Wang inquired about the MAGNITUDE Phase III trial's enrollment progress and the baseline characteristics of patients, specifically the percentage on baseline stabilizers and the rate of patients dropping off to use silencers.

Answer

Chief Medical Officer David Lebwohl confirmed that enrollment is progressing well and that the company expects over 50% of patients to be on baseline tafamidis, which is valuable for demonstrating added benefit. He noted that while no patients have crossed over to a silencer therapy yet, the trial's statistical plan accounts for this possibility.

Huidong 'Gena' Wang questioned the confidence behind the projection of enrolling 550 patients in the ATTR cardiomyopathy trial by year-end and whether that implies full enrollment in the first half of 2026.

Answer

CEO John Leonard expressed high confidence, citing the company's track record of under-promising and over-delivering. He stated that enrolling 550 patients by year-end is a 'very highly likely outcome' based on robust current enrollment rates and that the study is expected to complete enrollment well within the 2027 timeframe.

Gena Wang of Barclays asked if the submitted REMS was consistent with prior investor communications and if the MAPLE-HCM trial data could be submitted during the PDUFA extension.

Answer

Robert I. Blum, President and CEO, stated that the MAPLE data will not be submitted during the current review cycle to avoid disruption but will be part of a subsequent submission post-approval. Fady Malik, EVP of R&D, confirmed the submitted REMS aligns with aficamten's previously discussed differentiated properties, such as less frequent monitoring and minimal drug-drug interactions.

Huidong (Gena) Wang asked for more color on the tolerability issue that led to the temporary pause of the VX-522 study. She also inquired how the ALYFTREK launch trajectory compares to previous CFTR modulator launches and if the trend is expected to pick up.

Answer

CEO Reshma Kewalramani declined to provide more detail on the VX-522 pause to maintain study integrity, reiterating that the team is assessing a tolerability issue. COO Stuart Arbuckle explained that comparing ALYFTREK's launch to ORKAMBI or TRIKAFTA is difficult because those drugs opened up treatment to tens of thousands of new patients, whereas ALYFTREK's new patient population is smaller. He affirmed the company is pleased with the launch to date.

Huidong Wang asked for a detailed walkthrough of the process that enabled the significant and rapid improvement in the ORLADEYO paid rate. She also inquired about the specific benchmark for retinal edema reduction in the DME trial that would be considered encouraging enough to advance the program.

Answer

CEO Jon Stonehouse described the paid rate improvement as a 'snapback.' Chief Commercial Officer Charlie Gayer elaborated that it was driven by the IRA resolving Medicare affordability issues and the team's use of long-term real-world data to convince commercial payers. For the DME program, Chief R&D Officer Dr. Helen Thackray stated they are looking for a 'clear and uncontroversial reduction in edema' rather than a specific micron number, which would signal that the dose is effective. If not, the dose will be increased.

Huidong Wang, on behalf of Gena Wang, asked for the percentage of ORLADEYO patients covered by Medicare and the expected trend in their paid status. She also requested details on the Netherton syndrome trial design, including dose escalation and the KLK5 activity benchmark for advancing to patients.

Answer

Chief Commercial Officer Charlie Gayer stated that Medicare patients constitute about 20% of the total patient base and their paid rate was around 55-56% at year-end, a figure that is now improving. Chief R&D Officer Dr. Helen Thackray explained the Phase 1 trial design involves dose escalation in healthy volunteers to establish safety before moving to patients to assess KLK5 activity, with the goal of achieving nearly complete suppression of the target.

Huidong Wang asked what actions BioCryst could take if the Medicare paid rate situation becomes unfavorable and requested details on the upcoming Phase 1 data for BCX-17725, including the use of biopsies and specific biomarkers.

Answer

CEO Jon Stonehouse stated the Medicare trend is positive, with the paid rate already improving to 55%, and the only uncertainty is the speed of further improvement. Chief R&D Officer Dr. Helen Thackray confirmed that skin biopsies are a critical first step for BCX-17725 to demonstrate drug penetration and target binding. Key biomarkers will assess KLK5 inhibition and potentially downstream cytokines, with the drug's potency possibly allowing for extended dosing intervals.

Huidong (Gena) Wang from Barclays asked a multi-part question regarding the VOXZOGO franchise: how BMN 333 PK data will be defined as supportive for registration, the company's view on competitor CNP plus growth hormone studies, and the manufacturing location for VOXZOGO.

Answer

Greg Friberg (Chief R&D Officer) said the BMN 333 PK goal is to show multifold increases in sustained free CNP exposure. He dismissed competitor growth hormone combos, citing historical data showing transient benefits and added risks. Brian Mueller (CFO) confirmed that VOXZOGO drug substance is sourced from the United States.

Huidong Wang, on behalf of Gena Wang, requested an update on the intellectual property strategy for the CNP franchise in Europe and the U.S. She also asked what to expect from the upcoming data update for BMN 349 in AATD.

Answer

CEO Alexander Hardy confirmed that IP action was initiated in Munich against a competitor with a decision expected in 12-15 months, and that the company will defend its IP in the U.S. as needed. Chief R&D Officer Gregory Friberg explained that for BMN 349, the healthy volunteer study may provide early pharmacodynamic insights into circulating Z protein levels from a small number of AATD patients enrolled.

Huidong (Gena) Wang asked for guidance on a comparable benchmark for AMVUTTRA's first full quarter revenue in cardiomyopathy, referencing competitor launches. She also sought to confirm if any of the Q1 TTR franchise revenue growth was attributable to the new indication.

Answer

CEO Yvonne Greenstreet and CCO Tolga Tanguler clarified that none of the Q1 revenue was from the ATTR-CM indication, as approval occurred in the final days of the quarter. Tolga Tanguler avoided direct competitor comparisons, instead pointing to Alnylam's full-year guidance of approximately 36% TTR franchise growth and emphasizing that the overall treatment category is expanding.

Huidong Wang asked about the key factors influencing the pricing decision for AMVUTTRA and what percentage of current sites have the necessary J-code for billing.

Answer

CEO Yvonne Greenstreet reiterated that pricing considers the product's value and ensuring optimal access. Chief Commercial Officer Tolga Tanguler confirmed that a J-code for AMVUTTRA is already in place, so no disruption is expected. He also highlighted patient affordability, noting that 70% of current patients have a $0 co-pay, a dynamic he expects to continue.

Huidong Wang inquired about the upcoming Q3 data release for UCART22, asking for specifics on the amount of data, patient numbers, key data points, and the venue for the announcement.

Answer

Chief Medical Officer Dr. Adrian Kilcoyne confirmed that the full Phase I dose escalation data set for UCART22 will be released in Q3, with additional data to be shared at the ASH conference. Chief Business Officer Arthur Stril added that the primary data release is planned for a company-hosted ad hoc event, with more details to be provided soon.

Huidong Wang asked if the FDA had confirmed no AdCom for vatiquinone and how the correlation between huntingtin lowering and clinical benefit would be defined for the PIVOT-HD trial, including the relative importance of CSF versus blood biomarkers.

Answer

CEO Dr. Matthew Klein stated the FDA has not yet decided on an AdCom for vatiquinone. For PIVOT-HD, he explained the FDA was not prescriptive on a specific correlation metric but wants to see associations between HTT lowering and clinical measures. He added that the entire biomarker package, including both blood and CSF, is important for the assessment.

Huidong Wang of Barclays requested specifics on the upcoming data for the FSHD and DM1 programs, asking if they would be from single ascending dose (SAD) studies and what metrics would be shared.

Answer

Chief Scientific Officer Dr. Louise Rodino-Klapac confirmed that the data readouts for both FSHD1 and DM1 in the second half of the year will be from the SAD studies. The data will focus on safety, muscle concentration, and early biomarker signals like knockdown and splicing restoration. CEO Douglas Ingram added they are particularly excited about the potential to directly measure DUX4 protein knockdown in FSHD, a significant proof-of-biology milestone.

Huidong 'Gena' Wang from Barclays asked for more details on the discontinuation of the PPMO program SRP-5051, questioning if hypomagnesemia was the primary FDA concern and whether the entire PPMO franchise would be discontinued.

Answer

Dr. Louise Rodino-Klapac, Head of R&D and Chief Scientific Officer, confirmed the entire PPMO franchise is being discontinued. She explained the decision was multifactorial, based on FDA feedback that the accelerated approval pathway was not open, an internal benefit-risk assessment citing prolonged hypomagnesemia, and the evolving Duchenne treatment landscape with ELEVIDYS. CEO Doug Ingram added that the high safety bar for PMOs was a key consideration.

Huidong Wang sought confirmation on the 'modest' Q3 growth expectation and asked if the 2025 revenue guidance of $2.9B-$3.1B aligns with the consensus estimate of $2B for ELEVIDYS alone.

Answer

CEO Douglas Ingram clarified that 'modest' Q3 growth for ELEVIDYS translates to a robust 30% increase over Q2, followed by a doubling of revenue in Q4. He confirmed the 2025 guidance is largely in line with external consensus, attributing the company's confidence to deep experience with Duchenne launches, granular data on patient start forms, and strong knowledge of the epidemiology.

Inquired about the timing of the 30 patient starts scheduled for 2025, the average cell collection cycle for LYFGENIA patients, and the strategy to cover the upcoming cash gap.

Answer

The company confirmed the vast majority of the 30 scheduled 2025 starts are for Q1. They expect commercial LYFGENIA cell collection cycles to be similar to clinical trials (1-2 cycles for 85% of patients). To manage the cash gap, they are renegotiating key contracts and working closely with their partner, Hercules.

Huidong Wang inquired about the specifics of the FDA's guidance for the Fabry disease program, asking for clarification on the statistical requirements for the 52-week and 104-week eGFR slope data. She also asked for an update on the company's partnership strategy for the program and the valuation expectations.

Answer

CEO Sandy Macrae and Chief Development Officer Nathalie Dubois-Stringfellow responded. Dubois-Stringfellow confirmed the 52-week eGFR slope data from all patients in the STAR study will serve as the primary basis for accelerated approval, with 104-week data used to verify clinical benefit for full approval. Macrae stressed that no additional confirmatory study is required, which pulls the BLA timeline forward by three years. Regarding partnerships, Macrae stated that the positive regulatory update has generated significant interest and refreshed ongoing discussions, with the goal of securing a partner to support a BLA filing in H2 2025.

Huidong Wang (Gena Wang) asked if the Angelman data at the FAST and CNS meetings would be the same, questioned the increased clarity on the setrusumab Phase 3 interim timelines, and requested details on the trial's baseline patient characteristics.

Answer

CEO Emil Kakkis confirmed the Angelman data would be the same at both conferences. He clarified that the setrusumab interim timing updates were for specificity, not due to incoming fracture data. He declined to share baseline characteristics until the Phase 3 data release but noted the study has a higher proportion of more severe Type III and IV patients compared to Phase 2, and is primarily a pediatric study.

Huidong Wang of Barclays asked for more details regarding the patient death in the BEACON trial, specifically questioning the four-month timeframe and the attribution to busulfan conditioning.

Answer

CEO John Evans acknowledged the sad outcome as a reflection of the known risks of chemotherapy and transplant, which underscores the severity of the underlying disease. Chief Medical Officer Dr. Amy Simon elaborated that the event was consistent with busulfan's known pulmonary toxicity, which can manifest up to 100 days post-transplant and can be fatal. She confirmed the event was deemed unrelated to BEAM-101 by the investigator and that the patient's blood profile was correcting as expected.

Huidong Wang inquired about the safety of BEAM-101, specifically questioning the cause and timing of a patient death four months post-infusion and its attribution to busulfan conditioning.

Answer

CEO John Evans stated the event highlights the known risks of chemotherapy and transplant, which are weighed against the severity of sickle cell disease. Chief Medical Officer Dr. Amy Simon added that busulfan has known dose-dependent pulmonary toxicity that can manifest months post-transplant, and the event was consistent with this known risk profile, leading to no changes in the trial protocol.

Huidong Wang of Guggenheim Securities inquired about the patient death in the BEACON trial, asking for more detail on why the event, occurring four months post-infusion, was attributed to busulfan conditioning.

Answer

CEO John Evans acknowledged the known risks of chemotherapy and transplant, emphasizing the severity of the underlying sickle cell disease. Chief Medical Officer Dr. Amy Simon elaborated that busulfan has known dose-dependent pulmonary toxicity which can manifest up to 100 days post-transplant, and an extensive workup ruled out other causes, making the event consistent with known complications of the conditioning regimen.

Asked about the average processing time from enrollment to dosing for reni-cel, and for clarification on whether the indel upregulation technology works by knocking down repressors.

Answer

The time from enrollment to dosing varies significantly (3 to 10+ months) and appears to be faster for adolescent patients. The indel upregulation strategy is differentiated from a knockdown strategy; it works by creating an indel to disrupt a repressor's binding site, thereby upregulating gene expression, rather than knocking down the repressor itself.

Huidong (Gena) Wang asked about the average time from patient enrollment to dosing for reni-cel, any differences between adults and adolescents, and for clarification on whether the 'indel' upregulation technology works by knocking down a repressor.

Answer

Chief Medical Officer Baisong Mei noted that vein-to-vein time varies from 3 to 10+ months and that the process has been faster for adolescents. Chief Scientific Officer Linda Burkly clarified that the indel strategy is differentiated and is *not* a knockdown approach; instead, it disrupts a repressor's binding site to upregulate gene expression.