Sean McCutcheon

Sean McCutcheon asked about the trend of improving CARVYKTI out-of-spec rates, particularly with more real-world patients in earlier lines, ongoing efforts to lower this rate, and a feasible minimum steady state. He also asked about the early impact of loosening REMS requirements for auto CAR-T and any uptake in referrals for earlier line patients.

Answer

Alan Bash, President of CARVYKTI, cited an ASH abstract showing out-of-spec rates of 6-9%, lower in earlier lines due to stronger T-cell fitness, and expects continued reduction to be competitive. Regarding REMS, he noted mixed reactions from sites but overall it's a burden lifted, enabling more robust conversations about expanding CARVYKTI's benefits.

Sean McCutcheon asked about the trend in improving out-of-spec rates for CARVYKTI, particularly with more real-world earlier-line patients, ongoing efforts to lower these rates, and a feasible minimum steady state. He also inquired about the early impact of loosening REMS requirements for auto CAR-T on referrals for earlier-line patients.

Answer

Alan Bash, President of CARVYKTI, reported out-of-spec rates between 6%-9% (per an ASH abstract), noting they are lower in earlier lines due to better T-cell fitness, with continued efforts to drive them down. Regarding REMS, he described early, mixed reactions from sites, but emphasized it's a burden lifted, enabling more robust conversations about extending CARVYKTI's benefits to more patients.

Sean McCutcheon from Raymond James asked about the clinical bar for advancing the Claudin 18.2 program, given competitor data, and whether the development strategy would be similar to the DLL-3 program, potentially involving a partner.

Answer

Chief Medical Officer Mythili Koneru stated that dose escalation for the Claudin 18.2 study should complete by late summer, with expansion cohorts to follow. She highlighted the opportunity for CAR-T in this space due to its sensitivity in lower-expressing cells, which could be an advantage over approved antibodies. The company did not comment on the partnership strategy for the program.

Sean McCutcheon inquired about the breadth of implementation for the ALC monitoring protocols and whether clinical data is a gating factor for adoption. He also asked if the 2028 Tech Lane expansion is part of the current CapEx initiative.

Answer

Executive Jessie Yeung explained that while the Tandem data was from single centers, it opened a conversation, and many centers are interested. The company is actively investigating the strategy in internal and external studies to provide more data. An Unknown Executive clarified the Tech Lane expansion plan: Phase 1 will be completed this year, and Phase 2 is an incremental $150 million investment starting in the second half of 2025 and completing in 2028.

Sean McCutcheon asked for more specific reasons why additional follow-up is needed for the CARTITUDE-2 frontline cohorts and requested an update on the manufacturing out-of-spec rate.

Answer

CEO Ying Huang and CMO Mythili Koneru explained that with very high long-term PFS rates in frontline myeloma, short-term follow-up is not meaningful. Regarding manufacturing, Ying Huang stated the out-of-spec rate is improving quarterly, is in the low teens, and that preliminary data suggests a lower rate for the earlier-line patient population.

Sean McCutchen inquired about the progress of initiating the NPDR studies (Helios program), specifically how leveraging a similar site footprint to the Wet AMD program is expected to accelerate these studies.

Answer

Pravin U. Dugel, Executive Chairman, President and CEO, confirmed that the NPDR study process commenced immediately after the recent financing, utilizing many existing high-performing sites from SOL1 and SOLar, along with additional sites. He expressed confidence in efficient enrollment due to the significant unmet need for advanced severe NPDR patients and strong enthusiasm from investigators and patients for a sustainable, single-injection treatment.

Sean McCutcheon inquired about the progress of getting the NPDR (Helios) studies up and running, the use of a similar site footprint to the Wet AMD program, and how this might accelerate the studies.

Answer

Dr. Pravin Dugel (Executive Chairman, President and CEO) confirmed that the NPDR (Helios) studies began immediately after the recent financing, leveraging many of the same high-performing sites as the Wet AMD program. He highlighted the company's strong execution in previous trials with over 95% on-protocol and retention rates, expressing confidence this would accelerate Helios progression.

Sean McCutcheon of Raymond James Financial inquired about the read-through from the 12-month SOUL-one data to the SOLAR trial and whether there would be visibility into the impact of redosing at later time points like 15 or 18 months.

Answer

Pravin Dugel, Executive Chairman, President & CEO, acknowledged the importance of demonstrating a clear link between the SOUL-one results and the SOLAR trial. He assured that the company intends to provide data cuts that will directly address this translation, although he did not specify the exact nature of the data to be released.

Sean McCutcheon asked for details on the expectations for an acceptable number and timing of rescue treatments in the SOL-R trial, especially in relation to achieving the non-inferiority margin.

Answer

President and CEO Dr. Pravin Dugel stated that while specific rescue criteria are not yet public for competitive reasons, they will align with traditional standards and FDA guidance. He highlighted a key strategic advantage: regulatory agencies will review SOL-R's rescue data in the context of a positive SOL-1 study, which will have already established AXPAXLI's 9-to-12-month durability. This, he believes, will provide a favorable context for the evaluation of the SOL-R rescue data.

Sean McCutcheon requested more details on Ocular's commercial efforts and asked for high-level thoughts on the pricing model for a long-duration product like AXPAXLI, particularly concerning the buy-and-bill model.

Answer

President and CEO Dr. Pravin Dugel highlighted the advantage of leveraging the successful commercial team from DEXTENZA. While stating it is too early to discuss specific pricing strategies, he affirmed that the company firmly believes it will be able to obtain premium pricing for AXPAXLI.

Sean McCutcheon asked about the strategic significance of including the 8mg aflibercept (high-dose Eylea) comparator arm in the SOL-R trial, even if it's only for masking. He questioned if having these data could provide a commercial or marketing advantage and asked about the decision process behind this study design.

Answer

Dr. Pravin Dugel, President and CEO, responded that while the primary goal was regulatory alignment, the data will have significant commercial value. It will allow for a comparison against what may be considered the 'next generation' of Eylea. He emphasized that the totality of data from SOL-1 (a superiority study showing durability) and SOL-R (a non-inferiority study showing dosing flexibility) will collectively answer nearly all physician questions about AXPAXLI's performance.

Sean McCutcheon from Raymond James Financial asked about the necessary magnitude of PFS benefit for Tivesimig to be clinically meaningful over paclitaxel. He also inquired about the FDA's potential view on the intent-to-treat (ITT) versus the crossover-adjusted OS analysis.

Answer

CEO Thomas Schuetz stated the PFS analysis is powered for a hazard ratio of approximately 0.6, which recent market research suggests would be highly meaningful. He noted the high progression rate in the paclitaxel arm suggests its efficacy is low. Regarding the OS analysis methods, he said the company has not received specific feedback from the FDA on the difference between the ITT and the crossover-adjusted (RPSFT) analyses.

Sean McCutcheon from Raymond James Financial questioned the necessary magnitude of PFS benefit for Tivesimig to ensure clinical adoption over FOLFOX and asked about the FDA's likely view on ITT versus crossover-adjusted OS data.

Answer

CEO Thomas Schuetz responded that the PFS analysis is powered for a hazard ratio of approximately 0.6, which recent market research suggests would be highly compelling to KOLs. He noted the high progression rate in the paclitaxel arm suggests its efficacy is low. Regarding the OS analysis, he stated the company has not received specific FDA feedback on the difference between ITT and the rank-preserving structural failure time (RPSFT) method.

Asked about the required magnitude of PFS benefit for tivesimig to ensure clinical adoption over standard treatments like FOLFOX, and how the FDA might view the overall survival data given the patient crossover.

Answer

The study is powered for a hazard ratio of approximately 0.6 on PFS, which market research suggests would be very well-received by KOLs. The company expects the paclitaxel arm's PFS to be low, similar to what's seen with FOLFOX. The company has not received specific feedback from the FDA regarding how it will weigh the intent-to-treat analysis versus the crossover-adjusted analysis for OS.

Sean McCutcheon asked if the accelerated enrollment timeline for the RGX-202 pivotal cohort provides flexibility to over-enroll or start the confirmatory study early to mitigate potential FDA uncertainty.

Answer

President & CEO Curran Simpson confirmed this is the strategy. He stated that once the pivotal cohort is enrolled by October, the company will continue enrolling patients directly into the confirmatory study cohort. This approach aims to expand the safety database, which will be important for regulatory discussions and addresses potential risk around sample size requirements.

Sean McCutcheon from Raymond James asked for details on the suprachoroidal opportunity in wet AMD, including the dose needed to move forward and its value proposition compared to the subretinal approach.

Answer

Chief Medical Officer Dr. Steve Pakola highlighted the large market opportunity and the increased optionality provided by the in-office suprachoroidal delivery. He emphasized that for diabetic retinopathy (DR) in particular, a one-time in-office treatment is highly compelling for patients to avoid indefinite injections, addressing a significant unmet need.

Sean McCutcheon of Raymond James asked about the non-proliferative diabetic retinopathy (NPDR) market, questioning what level of treatment durability would be required to drive significant utilization and how a gene therapy would compete against sustained-release TKIs.

Answer

Chief Medical Officer Dr. Steve Pakola argued that the primary barrier to current NPDR treatments is the burden of repeated injections, a problem that even long-acting TKIs do not fully solve. He positioned REGENXBIO's ABBV-RGX-314 as a 'paradigm shift,' where a onetime, in-office injection could address this massive unmet need. He cited the program's 89% reduction in vision-threatening complications at one year as the key data point driving the program into pivotal studies.

Sean McCutcheon from Raymond James asked about the patient population being enrolled in the VIR-5500 study, specifically if post-PSMA radioligand therapy patients are being prioritized. He also inquired about the biological rationale and importance of less frequent dosing for T-cell engagers.

Answer

EVP of Oncology Dr. Mika Derynck explained that the current Phase 1 study enrolls patients who have exhausted standard of care, and since it's open in Australia and Europe, there are fewer patients with prior radioligand therapy. However, they plan to open U.S. sites to generate this data. She highlighted the importance of less frequent (Q3 week) dosing for convenience in earlier lines of therapy, noting that data from the HER2 program showed no resensitization or loss of efficacy with a less frequent schedule, which bodes well for VIR-5500.

Sean McCutcheon asked about the design of the ACACIA-HCM trial for aficamten, its probability of success, and the importance of dose escalation in non-obstructive hypertrophic cardiomyopathy (nHCM).

Answer

Robert I. Blum, President and CEO, expressed strong optimism for ACACIA-HCM, highlighting its design based on encouraging Phase II results and enthusiastic global enrollment. Fady Malik, EVP of R&D, added that confidence is high due to using the same successful dosing regimen from the REDWOOD-HCM Phase II study, the availability of a higher dose proven effective in the FOREST study, and a rigorous patient screening process by experienced investigators.

Sean McCutcheon of Raymond James asked about the MAPLE-HCM patient population, specifically the enrollment criteria of less than 100% predicted peak VO2, and how this contrasts with the more impaired population in SEQUOIA-HCM.

Answer

SVP & CMO Stuart Kupfer explained that observations from SEQUOIA-HCM showed that the specific threshold for exercise incapacity (e.g., <90% or <80%) did not make a significant difference, as patients were already significantly symptomatic with exercise deficits due to their obstruction. Therefore, the company felt comfortable relaxing the criteria for MAPLE-HCM while still enrolling patients who could benefit from treatment.

Sean McCutcheon from Raymond James asked about the development of CK-586 for HFpEF, focusing on lessons from competitor data, the target patient profile in the AMBER trial, and key pharmacologic properties.

Answer

Stuart Kupfer, SVP and CMO, explained that data from nHCM patients and competitor trials are encouraging. The AMBER trial will enrich for patients with EF of at least 60% and is a rigorous, placebo-controlled study. He highlighted CK-586's favorable Phase I data, which showed a shallow and predictable PK/PD relationship for LVEF, as a key valuable property.

Sean McCutcheon asked if an approval for mezigdomide could be obtained based on MRD negativity as an intermediate endpoint from the EXCALIBER study, and how the increasing use of CAR-T in earlier lines of therapy shapes the drug's opportunity.

Answer

CMO Samit Hirawat explained that an MRD-based approval would require supportive evidence from other endpoints. Both Hirawat and CCO Adam Lenkowsky noted that the opportunity for oral CELMoDs remains large, as CAR-T therapy is concentrated in academic centers while the majority of myeloma patients are treated in the community setting, where oral options are needed.

Sean McCutcheon of Raymond James asked about the expected data cadence for the targeted radiotherapeutics portfolio and the company's prioritization of further investment in that area.

Answer

CMO Samit Hirawat detailed the radiotherapeutics pipeline, highlighting a Phase III readout in 2026 for the lead asset and several earlier-stage programs. CEO Christopher Boerner added that the company believes in the platform and would consider further business development to enhance the RayzeBio acquisition if the science and financials are compelling.

Sean McCutchen asked about Cobenfi's M1 component in relation to cognitive benefits and whether the twice-daily regimen and GI side effects could be barriers to compliance.

Answer

Head of Global Drug Development Samit Hirawat highlighted the M1 direct agonism as key for potential cognitive benefits. Chief Commercialization Officer Adam Lenkowsky argued that the drug's unprecedented efficacy and avoidance of major side effects like weight gain would outweigh compliance concerns, noting that patients are already on complex medication schedules.

Sean McCutcheon from Raymond James asked for the number of PCNSL patients treated with the 100mg BID dose of emavusertib and inquired about the steps needed to satisfy the FDA's requirement on individual component contributions.

Answer

Chief Development Officer Jonathan Zung stated that 13 patients have been dosed at the 100mg level in Part B of the study. He also noted that the U.S. and Europe would likely use similar data, and dose selection could be determined after approximately nine patients have been dosed at both the 100mg and 200mg levels.

Sean McCutcheon of Raymond James asked for details on the required data package for PCNSL approval, specifically the number of patients needed for the safety database. He also inquired about enrollment challenges for the triplet study in MRD-positive CR AML patients.

Answer

President and CEO James Dentzer stated that the required data package for PCNSL is the subject of current FDA discussions, but pointed to Ono Pharmaceuticals' studies (n=45-75) as a potential precedent for a smaller trial size. Regarding the triplet study, he confirmed the challenge is finding stable MRD-positive patients on aza-ven, explaining the current focus is on establishing safety and tolerability with a small group before expanding the trial.

Sean McCutcheon of Raymond James asked about the strategy for using the DOSED study as a regulatory bridge to a new formulation of OPC1. He inquired about the status of comparability studies and management's confidence in being able to amend the current IND to include the new formulation.

Answer

CEO Brian Culley confirmed that substantial comparability testing, including in vivo efficacy studies, is complete for the new OPC1 manufacturing process. He explained that Lineage strategically separated the IND submissions for the new delivery device and the new cell formulation to streamline FDA review. The company plans to introduce the new formulation into the DOSED study and is confident the FDA will find the new process comparable to the old one.

Sean McCutcheon from Raymond James questioned the source of management's confidence in the new OPC1 timeline given past delays and asked about plans for the comparability study for the newly manufactured OPC1 product.

Answer

CEO Brian Culley attributed his confidence to his personal attendance at the recent FDA meeting and the significant involvement of the device division (CDRH), which had not been as engaged previously, resolving a key bottleneck. He explained that a compelling comparability package for the new OPC1 manufacturing process is substantially complete but has been intentionally held back to allow the FDA to focus solely on clearing the delivery device for the DOSED study first.

Asked about the broader development strategy for building the portfolio, particularly in targeted oncology, and inquired about the company's view on the potential of degraders as a therapeutic modality.

Answer

The strategy is to focus on precision medicine for validated targets where they can create differentiated, next-generation therapies for high unmet needs, aiming for breakthrough designation. They are accessing external platforms (e.g., BridGene, Frontier) to do this. They plan to provide a more detailed update on the early-stage portfolio in a future quarter.

Sean McCutcheon from Raymond James asked about the company's development strategy in targeted oncology, using the BridGene collaboration as an example, and inquired about their view on degraders as a potential therapeutic modality.

Answer

CEO Paul Stoffels outlined a strategy focused on precision medicine against validated targets where Galapagos can create differentiated, next-generation therapies to address high unmet needs, aiming for breakthrough designation. He cited the BridGene and Frontier collaborations as examples and indicated a more detailed review of the early-stage portfolio would be provided in a future quarter.