Gena Wang

Gena Wang of Barclays PLC inquired about the CARVYKTI price difference between the U.S. and ex-U.S. markets, the FDA approval process for the new Raritan facility expansion, and the expected timeline for data from pipeline assets.

Answer

Alan Bash, President of CARVYKTI, stated the U.S. vs. ex-U.S. price differential is approximately 30%. Guowei Fang, President of R&D, and Mythili Koneru, Chief Medical Officer, detailed upcoming clinical readouts for the in vivo CAR-T and allogeneic platforms, as well as for Claudin 18.2 and DLL-3 programs later in the year. CEO Ying Huang added that the Raritan expansion will use the CB30 pathway, expecting on-time approval without delays.

On behalf of Gena Wang, an analyst asked for a breakdown of CARVYKTI revenue between second/third-line patients versus later-line patients and for more color on market demand, including physician capacity.

Answer

Executive Alan Bash stated that the company has seen strong uptake for the second- to fourth-line indication, with nearly 60% of usage already converted to this earlier-line population. He highlighted positive receptivity to the clinical profile. Executive Ying Huang added that the combined field forces are targeting 8,000 hematologists in 3,000 clinics to drive deeper penetration into the community setting.

Gena Wang asked about the expected timing for the Orbit and Cosmic study data readout for osteogenesis imperfecta, inquiring if it would be presented at JP Morgan, whether both studies' data would be shared simultaneously, and the company's strategy for advancing the program based on different data scenarios.

Answer

Erik Harris, Chief Commercial Officer, confirmed that data from both the Cosmic and Orbit studies would be released together in December or January, citing the ongoing data cleaning and analysis process. Emil Kakkis, CEO and President, elaborated on the expected fracture reduction range of 40% to 70% and emphasized the importance of functional improvements for patients, drawing parallels to the adoption drivers for Crysvita in XLH.

Gena Wang asked about the expected timing for the Orbit and Cosmic data readout for osteogenesis imperfecta, whether both study results would be shared simultaneously, and potential scenarios for advancing the program.

Answer

Erik Harris, Chief Commercial Officer, confirmed that both Cosmic and Orbit data would be released together, with the readout expected in December or January, allowing for database cleaning and analysis.

Gena Wang of Barclays posed two statistical questions: one on the rationale for the COSMIC trial in osteogenesis imperfecta and the potential impact of its failure if the ORBIT trial succeeds, and another on the alpha split for the Phase III ASPIRE trial's primary endpoints.

Answer

Emil Kakkis, Founder, President & CEO, addressed both points. He explained that COSMIC evaluates severely affected young patients on bisphosphonates who couldn't enter a placebo trial. For ASPIRE, he clarified that splitting the primary alpha (90% for Bayley, 10% for MDRI) provides a more secure statistical design, ensuring the trial can succeed even if the Bayley endpoint alone does not hit, as it is not dependent on a sequential hierarchy.

Gena Wang posed two questions: first, about the potential impact of a recent CBER nomination on the rare disease space, and second, whether skipping the bisphosphonate washout period for late-enrolling OI patients could negatively affect the placebo arm's fracture rate.

Answer

CEO Emil Kakkis addressed the CBER nomination by acknowledging industry concerns but expressed confidence in UX111's strong clinical data. Regarding the OI trial, both Kakkis and CMO Eric Crombez explained that the bisphosphonate washout effect would be present in both arms, but the transformative effect of setrusumab would far outweigh it. An executive added this factor was not included in the original power calculations and could represent a potential upside for the study's success.

Huidong Wang, on behalf of Gena Wang, asked about the specific timing of the second interim OI update, the communication plan if it fails, and how quickly data would be shared if it succeeds.

Answer

CEO Emil Kakkis confirmed a mid-year timeframe for the interim analysis but did not commit to a specific month. He explained that if the analysis is successful, the company would be unblinded and could release top-line results relatively quickly, faster than after the first interim analysis.

Gena Wang sought confirmation on the mid-single-digit year-over-year price decline for AMVUTTRA® in the U.S., expectations for price changes in Europe, and color on the first-line versus second-line ratio of AMVUTTRA® use in U.S. ATTR cardiomyopathy.

Answer

Tolga Tanguler, Chief Commercial Officer, confirmed an anticipated gradual net price decline over time and noted ongoing EU negotiations for 2026, with a broader outlook to be provided later. He described increasing competitiveness in first-line use and a balanced uptake between first and second-line after the initial launch phase. Yvonne Greenstreet, Chief Executive Officer, added that HELIOS-B data and quarterly subcutaneous administration are resonating well with physicians.

Gena Wang at Barclays inquired about confirming a mid-single-digit year-over-year price decline for AMVUTTRA in the U.S., expectations for price changes in Europe upon ATTR cardiomyopathy launch, and specific color on the ratio between first-line and second-line AMVUTTRA use in U.S. ATTR cardiomyopathy.

Answer

Tolga Tanguler, Chief Commercial Officer, confirmed an anticipated gradual net price decline over time, consistent with prior expectations, and stated that European pricing negotiations are ongoing, with a broader outlook for volume and price expected in mid-to-late 2026. Regarding U.S. ATTR CM, he noted increasing competitiveness in first-line use and a balanced uptake between first and second-line patients after the initial launch month, expecting continued growth in first-line presence. Yvonne Greenstreet, CEO, added that HELIOS-B data, including rapid TTR knockdown, 37% relative risk reduction in mortality/CV events, and reduction in GI events, strongly resonates with physicians, positioning AMVUTTRA well in both first-line and for patients progressing on stabilizers.

Gena Wang from Barclays sought to clarify if over half of the 1,400 patients treated so far were first-line and asked how many of these patients received free drugs through assistance programs.

Answer

CCO Tolga Tanguler described the patient mix as 'broad and balanced' but did not provide a specific percentage split, reiterating the goal is to establish Amvuttra as the first-line choice. CFO Jeff Poulton confirmed that the use of the Quick Start (free drug) program was 'de minimis' and very low.

Gena Wang asked about the ALN-HTT02 program for Huntington's disease, questioning if a 50% knockdown is the benchmark and what other endpoints will be assessed in the Phase I study.

Answer

Chief Medical Officer Pushkal Garg detailed that the Phase I study for ALN-HTT02 will assess safety, tolerability, PK/PD, and changes in mutant Huntington levels, along with biomarkers like neurofilament light chain (NFL). He highlighted the program's unique targeting of the exon 1 fragment, which could offer distinct efficacy, and noted they are proceeding with the study despite a dose cap in the U.S.

Gena Wang inquired about potential concerns regarding acute pancreatitis (AP) events in the olzarsen CORE and CORE2 data to be presented at AHA, asking if the events were balanced between the two studies. She also asked for peak revenue potential views for DAWNZERA, olzarsen, and Alexander disease.

Answer

Brett Monia, CEO, Ionis, stated there was nothing concerning about the AP data, describing it as groundbreaking and noting that higher triglycerides correlated with more AP events, consistent with expectations. Kyle Jenne, Chief Global Product Strategy Officer, Ionis, provided peak sales expectations: greater than $500 million for DAWNZERA, greater than $1 billion for olzarsen, and greater than $100 million for Alexander disease.

Gena Wang from Barclays asked for confirmation on Sefiance's IP status, questioning if it relies solely on orphan designation. She also asked if revenue contribution would begin in Q3 2025 and requested more detail on the discussions during the vutiquinone late-cycle review.

Answer

CEO Dr. Matthew Klein corrected that Sefiance is protected by a composition of matter polymorph patent extending to 2038, with an expected extension to 2039, not just orphan exclusivity. He confirmed Q3 revenue is expected. Regarding vutiquinone, he said the late-cycle meeting focused on the evidence, with a key question being whether the data for upright stability, though not a pre-specified primary endpoint, is persuasive enough to support approval, especially given the FDA's evolving view on this endpoint.

An analyst on behalf of Gena Wang asked about the revenue sustainability for Translarna in ex-EU countries and the rationale for using different natural history controls for the 24-month Huntington's disease data.

Answer

CBO Eric Pauwels confirmed no revenue disruption for Translarna in ex-EU markets like Latin America. CEO Dr. Matthew Klein clarified for the Huntington's data that a direct comparison was only made for functional measures against the ENROLL-HD registry; the NFL data was contextualized with a reference publication, not a direct comparison.

Gena Wang of Barclays asked for confirmation of no AdCom for sepiapterin, the procedural steps following a potential negative EU decision on Translarna, an update on the renewal process in Brazil, and manufacturing readiness for AADC gene therapy.

Answer

CEO Matthew Klein confirmed no AdCom is expected for sepiapterin. For Translarna, he reiterated the EU timeline is approximate and next steps remain uncertain. He viewed continued bulk orders in Brazil as a positive sign for its independent renewal process. For AADC, he affirmed the company is fully prepared with more than adequate supply for a U.S. launch.

Gena Wang of Barclays asked for more detail on why the MAPLE HCM trial data for aficamtan could be guideline-changing and what magnitude of benefit would be needed to drive first-line use over beta-blockers.

Answer

Fady Malik, EVP of R&D, explained that as a rare comparative efficacy trial, MAPLE HCM will illustrate the absolute benefit of aficamtan versus metoprolol, which could lead to a re-evaluation of its place in treatment algorithms beyond a last-line therapy. President and CEO Robert Blum noted full details would be presented at the upcoming ESC congress.

Gena Wang from Barclays inquired about the potential outcomes of the Servier arbitration decision expected by December 15 and asked for high-level details on the pivotal Phase II trial design for lasmacell following discussions with the FDA and EMA.

Answer

CEO André Choulika stated that while Cellectis hopes to regain its CD19 products and receive compensation from the Servier arbitration, he could not detail potential scenarios due to the ongoing legal process. Chief Medical Officer Dr. Adrian Kilcoyne added that interactions with the FDA and EMA were productive, resulting in a clear path for the Phase II trial with agreement on endpoints and no concerns raised about the statistical plan or database size. More details will be shared at the October 16 R&D Day.

Inquired about the clinical programs, asking for an updated timeline for UCART123 data, the next steps for UCART22 regarding a potential pivotal study, and details on the AstraZeneca deal concerning the timeline for target selection.

Answer

For UCART123, data is now expected sometime in 2024 as dose escalation continues. For UCART22, the study has already dose-escalated to 2.5 million cells/kg with the P2 product. Regarding the AstraZeneca deal, AstraZeneca will select up to 10 candidates from a pool of 25, and any unselected targets will revert to Cellectis.

Gena Wang from Barclays inquired about the BMN 333 program, asking about the target Area Under the Curve (AUC) in patients, any safety limits, and the AUC comparison between VOXZOGO's low and high doses.

Answer

Gregory Friberg, EVP and Chief R&D Officer, explained that several doses in the upcoming patient study are expected to achieve an AUC of 3x or greater than the competitor. He noted that comparing AUCs for VOXZOGO is not very meaningful due to its very short half-life (minutes vs. days for BMN 333), but confirmed the levels were much lower than those seen with the long-acting agent.

Gena Wang of Barclays asked about the BMN-333 program, specifically the target Area Under Curve (AUC) in patients, any upper safety limits, and the historical AUC comparison between VOXZOGO's low and high doses.

Answer

Gregory Friberg, EVP and Chief R&D Officer, explained that they anticipate selecting doses for the patient study that are at or above the 3x AUC level. He noted that calculating a precise AUC for the original VOXZOGO studies is difficult due to its very short half-life (minutes vs. days for BMN-333), making a direct, meaningful comparison challenging. The final dose selection for BMN-333 will occur after the current study is complete.

Gena Wang from Barclays requested an update on Q2 launch metrics like reimbursement and retention rates, the timing for data from two key pipeline assets, and the reasoning behind CEO Jon Stonehouse's planned transition.

Answer

President & CCO Charlie Gayer confirmed the one-year patient retention rate is stable at 60%. Chief R&D Officer Dr. Helen Thackray stated that data for both the Netherton syndrome and DME programs remain on track for year-end. CEO Jon Stonehouse explained his retirement timing is personal, as he is turning 65 after nearly 19 years with BioCryst, and that the board's multi-year succession plan led to the unanimous selection of Charlie Gayer as the next CEO.

Asked about the alisertib lung cancer trial timeline after a dose increase, response data at the current dose, tumor selection strategy for the NERLYNX combination trial, and the impact of the Medicare Part D redesign.

Answer

The executive confirmed that interim data for the alisertib lung cancer trial is still expected later in the year despite the dose increase. For the NERLYNX combination, the enhanced activity in certain tumors is mechanistically based, and more data is needed to define future strategy, with a public presentation likely in early 2026. The Medicare Part D redesign has been beneficial, lowering patient co-pays and increasing the percentage of business through Medicare.

Tony, on behalf of Gena Wang, asked for color on payer coverage amid suggestions some are not covering ELEVIDYS, and requested an update on the clinical hold in the EU.

Answer

President and CEO Douglas Ingram stated that while some payers always require more work, ELEVIDYS policies are generally very good, and their ultimate success rate in gaining access is currently 100%. Head of R&D Dr. Louise Rodino-Klapac said the EU restart requires a substantial amendment with a typical 95-day review, so approval to restart is expected around the end of summer, noting the trial continues to enroll outside the EU.

Gena Wang inquired about the reasons for the Fabry deal's revised Q2 timeline and its expected financial scope. She also asked about the goals for the ST-503 trial, including dose selection and targeted pain score reduction by the Q4 2026 data update.

Answer

CEO Sandy Macrae affirmed the goal of the Fabry deal is to secure funding through key 2026 neurology readouts but did not detail the reasons for the Q2 timeline. For ST-503, Chief Development Officer Nathalie Dubois-Stringfellow explained the trial aims to show efficacy within 12 weeks. Macrae added that the company has not set a specific target for pain score reduction in this initial study.

A representative for Gena Wang asked about Intellia's assumptions for the TTR silencer drop-in rate in its ATTR study and the strategies to manage this if the rate is higher than anticipated.

Answer

CMO David Lebwohl stated that this possibility has been factored into the trial design. He believes a high drop-in rate is unlikely based on recent competitor data, which suggests payers would not cover both a silencer and gene editing therapy. He does not expect potential switches to affect the primary endpoint.

Asked for specifics on QTC activation for LYFGENIA, details about the first patient's cell collection process, and an update on the number of QTCs that have received patient referrals.

Answer

The company could not comment on the number of cell collection cycles for the first patient. They stated that about 50 of the 64 QTCs have received referrals for LYFGENIA and they expect all 64 centers to eventually evaluate patients.

Asked for clarification on the FDA agreement for the RUBY trial, specifically regarding patient numbers and study duration, and inquired about the number of active clinical trial sites and future goals for commercial readiness.

Answer

The company confirmed the FDA agreement on a single Phase I/II/III study design, with the Vertex trial serving as a good benchmark for patient numbers. The current RUBY study will be used for the BLA. They have over 20 active sites, which they believe provides a strong foundation for a future commercial launch, and are activating a few more for pediatric patients.

Gena Wang inquired about Solid Biosciences' SGT-003 program, specifically asking if the microdystrophin transgene was tested in the new capsid and what the potential Phase I dose range might be. She also asked if additional CMC or comparability studies would be required for SGT-001's new transient transfection-based manufacturing process before advancing to a pivotal study.

Answer

Chief Scientific Officer Dr. Carl Morris explained that for SGT-003, nonhuman primates were dosed with a luciferase reporter, not microdystrophin, but mouse data showed a strong correlation, with a goal of at least a twofold dose reduction versus AAV9. Chief Operating Officer Dr. Joel Schneider confirmed that for SGT-001, comparability for the new manufacturing process will need to be demonstrated through analytical methods and potentially some in vivo studies, expressing confidence in a seamless transition. CEO Ilan Ganot added that internal analysis shows the new material is of high quality.

Gena Wang of Barclays asked for more details on the inflammatory response in Patient 8, including any relation to complement activation and the patient's baseline characteristics. She also inquired about the preclinical data for the novel capsid SLB101 and how the company prioritizes its internal SGT-003 program against its collaboration with Ultragenyx.

Answer

Acting CMO Dr. Cathryn Clary confirmed Patient 8's event had similarities to previous cases and that complement activation has been seen in all patients, though specifics are still under review. CSO Dr. Carl Morris added that this is a known AAV class effect. Regarding the pipeline, Dr. Morris noted the SGT-003 program is in lead optimization, while CEO Ilan Ganot described the Ultragenyx partnership as complementary and stressed the large unmet need in Duchenne, negating concerns of internal competition.