Gil Blum

Gil Blum requested clarification regarding the LGMD program, specifically whether Sarepta would need to dose any patients with sirolimus prophylaxis before submitting a BLA, or if data from the DMD study would be sufficient.

Answer

Doug Ingram, President and Chief Executive Officer, stated that more conversations with the agency are needed. He acknowledged suggestions from the agency about potentially dosing an LGMD patient prophylactically with sirolimus, but also highlighted the relevance of the significant prophylactic dosing data from the DMD therapy, which uses the exact same construct. Louise Rodino-Klapac, Executive VP, Chief Scientific Officer, and Head of Research and Development, added that the FDA specifically requested to see Cohort 8 data first before further discussions.

Gil Blum sought clarification on the LGMD program, specifically whether Sarepta would need to dose patients with sirolimus prophylaxis before a BLA submission, or if data from the DMD study would suffice.

Answer

President and Chief Executive Officer Doug Ingram and Executive VP, Chief Scientific Officer, and Head of Research and Development Louise Rodino-Klapac stated that more conversations with the agency are needed. They noted suggestions from the FDA to see a patient dosed prophylactically with sirolimus, but also that significant prophylactic dosing data from the DMD therapy (same construct) should be relevant. They will discuss after Cohort 8 data is in hand.

Gil Blum asked if there was any commonality (e.g., ambulatory status) among the patients who paused treatment after the recent safety event.

Answer

President and CEO Douglas Ingram clarified that there was no commonality other than timing. He explained that the patients who paused were scheduled for infusion in March, immediately following the late February announcement of the safety event, and simply needed more time and information before proceeding.

Gil Blum from Needham & Company inquired about the planned move to suspension manufacturing, asking about potential cost savings and the broad applicability of this process to other gene therapy programs beyond DMD.

Answer

CEO Douglas Ingram stated the goal is to transition almost all gene therapy programs to suspension, with SRP-9003 being a likely exception due to timing. He noted the move could yield significant efficiencies, potentially 5x or more, which could drive margins well over 90%. The plan is to complete GMP runs and begin the bridging study in 2025, targeting a full transition to suspension in 2027, aligning with global expansion plans.

Gil Blum of Needham & Company asked about the future of the PMO franchise, including life cycle management plans, and questioned if the discontinuation of SRP-5051 signaled a strategic shift away from exon-skipping therapies.

Answer

President and CEO Doug Ingram firmly stated that Sarepta is not moving away from exon skippers and is exploring other modalities. He emphasized the significant and proven benefit of the current PMOs, supported by strong real-world evidence and a laudable safety profile, which sets a very high bar for any potential alternatives.

Gil Blum asked if the perceived launch bottleneck ultimately boils down to the number of treating physicians available at each infusion center.

Answer

CEO Douglas Ingram reiterated his consistent message that there are no bottlenecks to solve. He stated the company has a successful launch curve with a significant number of sites and treating physicians, extraordinary demand, strong payer interactions, and ample manufacturing capacity. He concluded that the company is in great shape to execute a successful launch and achieve its financial targets.

Gil Blum inquired about the current number of second-line patients on RYTELO and their proportion relative to third-line patients, and the expected cadence for Q4's 9% demand growth and 15% increase in prescribing accounts to translate into revenue.

Answer

Harout Semerjian, President and CEO, stated that Geron is targeting approximately 8,000 second-line lower-risk MDS patients in the US, with about one-third of current patients coming from first or second-line settings. He explained that demand growth and increased prescribing accounts (150 new in Q4) are crucial, with revenue translation involving different timings due to gross-to-net adjustments, emphasizing consistent quarter-over-quarter growth from high-volume community accounts.

Gil Blum asked for anecdotal details on the types of physicians prescribing Rytello in earlier lines and inquired about the reasons for patient discontinuation or lack of retention at certain centers.

Answer

Jim Ziegler, EVP & CCO, and Dr. Joseph Eid, EVP of R&D, noted that both community and academic physicians are prescribing in earlier lines, often for ESA-ineligible patients. Ziegler acknowledged that some discontinuations are due to cytopenias, which Geron views as an opportunity for further physician education, supported by ongoing data generation efforts.

Gil Blum of Needham & Company questioned if there was specific pushback from physicians hesitant to use RYTELO and whether the main adoption barrier is simply initiating treatment. He also asked why OpEx guidance was unchanged despite higher commercial spending.

Answer

Jim Ziegler (CCO) and Dr. Joseph Eid (EVP, R&D) explained that barriers for non-users, like cytopenia concerns, diminish significantly with education and experience. Dr. Eid noted that explaining the drug's on-target mechanism shifts physician attitudes. CFO Michelle Robertson clarified that the company can absorb the increased commercial investment by adjusting other planned spending, such as on manufacturing redundancy, thus maintaining the full-year OpEx guidance.

Gil Blum of Needham & Company questioned how operating expense guidance could remain unchanged despite plans for increased commercial outreach. He also sought to confirm if the core launch challenge is simply convincing physicians to try Rytelo for the first time, given that patient retention appears strong.

Answer

CFO Michelle Robertson and CCO Jim Ziegler explained that increased spending on outreach is being funded by reallocating funds within the existing budget, which had already accounted for additional 2025 investments. CEO John Scarlett confirmed that the central challenge is driving initial clinical experience among the large group of physicians who have not yet prescribed Rytelo, thereby expanding beyond the early adopter base.

Gil Blum from Needham & Company asked if the newly raised capital is earmarked for expanding U.S. sales efforts and whether the company's profitability assumptions include potential revenue from the myelofibrosis indication.

Answer

EVP & CFO Michelle Robertson clarified the capital provides flexibility to invest in a second drug substance supplier, support the ongoing U.S. launch, and prepare for a potential EU launch. She confirmed that internal scenarios for reaching breakeven include projected revenues from both lower-risk MDS and a potential future approval in myelofibrosis.

Gi Blum asked about the competitive positioning of Obe-cel in pediatric patients, specifically whether it differentiates on safety similar to the adult relapsed refractory patient setting.

Answer

Dr. Christian Itin, CEO of Autolus Therapeutics, explained that the focus includes high-risk pediatric patients currently ineligible for CAR-T therapy. He highlighted Obe-cel's good safety and efficacy profile in children, consistent, reliable product access, and the significant unmet need in high-risk pediatric patients.

Gil Blum inquired about the competitive positioning of obe-cel in pediatric patients, asking if the differentiation strategy, particularly regarding safety, mirrors that in adult relapsed refractory patients.

Answer

CEO Dr. Christian Itin stated that the focus includes high-risk pediatric patients currently ineligible for CAR-T therapy. He highlighted obe-cel's good safety and efficacy profile in children, consistent with prior CARPALL study publications, and emphasized the critical need for consistent, reliable product access for this population.

Gil Blum from Needham & Company asked for anecdotal feedback on Ocatsol's reception in the U.S. medical community, including reorder rates. He also requested additional details on the ongoing market access negotiations with NICE in the UK.

Answer

CEO Christian Itin reported a very positive reception in the U.S., highlighting the product's manageable safety profile as a key driver for early and consistent reorders across centers. Regarding NICE, he described it as a regulated process involving data submission and input from physicians and patients, noting that Autolus is currently in the midst of the process and cannot yet predict the outcome.

Gil Blum from Needham & Company asked if Autolus is already expanding the CAR-T patient pool beyond those who would have received a competitor's product and requested details on the upcoming data update for the autoimmune disease program.

Answer

CEO Christian Itin suggested that Autolus is likely treating some sicker patients who might not have been candidates for other CAR-T therapies, thereby expanding the market, though it's too early to tell if they are capturing patients earlier in relapse. For the autoimmune update, he expects to present longer-term follow-up on the first six patients, plus initial data from three patients at a higher dose and three adolescent patients.

Gil Blum of Needham & Company asked for context on the upcoming SLE data for the first six patients, specifically what metrics will be presented. He also questioned where the majority of resources for the commercial launch are being invested.

Answer

Executive Christian Itin detailed that the SLE data will cover product properties (expansion, persistence), safety (CRS, neurotoxicity), and efficacy (B-cell depletion, autoantibodies, disease scores). He emphasized it's a 'more real-world population.' For launch resources, Itin explained the model is focused on delivering services and support to centers through a single point of access, rather than a traditional sales and marketing function.

Gil Blum asked for a summary of the company's strategy for the commercial rollout of its product in Europe.

Answer

CEO Christian Itin described a two-stage process for Europe. First, the company must obtain centralized regulatory approval from the European Medicines Agency (EMA). Following approval, it will pursue reimbursement and access on a country-by-country basis, noting that Germany is typically one of the first markets to target for launch.

Gil Blum of Needham & Company asked about the practical implications for physicians of having both a doublet and a triplet therapy option, and also inquired about the company's commercial partnering strategy for the launch.

Answer

CEO Brian Sullivan explained that offering both a triplet and a doublet provides physicians with flexibility. The triplet offers maximum efficacy, while the doublet is a highly effective option for patients who may be less suited for the triplet's side effect profile, thereby broadening the addressable market. Regarding partnering, Sullivan stated that Celcuity intends to launch Gadafelicitinib independently, as the company is well-capitalized and believes a solo launch offers the best financial return for shareholders.

Gil Blum from Needham & Company asked for clarification on the reason for the slight timing change for the VIKTORIA-1 wild-type readout, confirmation of the PIK3CA mutant cohort timeline, and the financial investment required for the new endometrial cancer collaboration.

Answer

CEO Brian Sullivan explained the wild-type timeline adjustment was due to the inherent imprecision of forecasting event thresholds in a three-arm trial, but noted that variability is now minimal, solidifying the June data cutoff. He confirmed confidence in the Q4 2025 timeline for the mutant cohort. Regarding the endometrial study, Sullivan stated Celcuity will supply the drug and clinical support, anticipating no incremental financial impact on the company.

Gil Blum from Needham & Company asked if the VIKTORIA-1 study is sufficiently powered to show an effect in the ESR1 mutant population and if data would be broken out by patient response to prior CDK4/6 therapy.

Answer

CEO Brian Sullivan responded that preliminary Phase Ib data did not show activity differences based on ESR1 status, though the sample size was small. He reiterated that PIK3CA status is the most important mutation for gedatolisib. Regarding prior therapy response, he indicated that such detailed data would likely be rolled out over time at subsequent medical meetings.

Gil Blum of Needham & Company inquired about the timing of revenue recognition from partnerships and whether ongoing discussions with large pharma are contingent on specific upcoming data readouts.

Answer

CFO Zach Jonasson clarified that revenue from platform partnerships is milestone-based and will therefore be 'lumpy' rather than continuous. He also stated that current partnership discussions are not predicated on a specific data release but are driven by the platform's proven capabilities, such as its success with difficult targets like the ion channel in the Almirall collaboration. He reiterated guidance of signing at least one large pharma deal this year.

Gil Blum of Needham & Company inquired about the timing and nature of revenue recognition from partnerships and whether new pharma discussions are dependent on upcoming data.

Answer

CFO & CBO Zach Jonasson confirmed that revenue recognition from partners is expected but will be 'relatively lumpy' due to its milestone-based nature. He clarified that ongoing pharma discussions are catalyzed by the platform's proven ability to address difficult targets, not a specific data release, and reiterated guidance of signing at least one large pharma deal this year.

Gil Blum of Needham & Company inquired about the anticipated human dosing regimen for ABS-201 based on recent non-human primate (NHP) pharmacokinetic data and asked about the level of systemic exposure observed in the NHP model.

Answer

SVP of Drug Creation Christian Stegmann stated that while the full PK data set will be disclosed later, the NHP data supports a potential dosing interval of every 8 to 12 weeks in humans. He noted a 6-month treatment period could be achieved in just 2 or 3 doses. He deferred answering the specific question on total systemic exposure until the full data disclosure.

Gil Blum from Needham & Company asked if the achievement of binding to the HIV 'Caldera' region was influencing pharma discussions and requested more detail on the strategy for the TL1A bispecific program.

Answer

CEO Sean McClain confirmed the HIV case study is a 'big driver' in large pharma discussions, with CFO Zachariah Jonasson adding that the platform's rapid model improvement resonates with partners. Regarding the bispecific, McClain and SVP Christian Stegmann clarified it targets a novel mechanism, not IL-23 or alpha 4 beta 7, creating a potential first-in-class asset both as a monotherapy and a bispecific.

Gil Blum from Needham & Company inquired about the clinical trial design for PRISMEL, specifically how patients on the discontinued dose will be handled, and asked about the company's timeline to reach profitability.

Answer

David Berman, EVP of R&D, clarified that patients on the dropped dose will continue on it, though the IDMC may recommend a switch, and they will not be included in the final ITT analysis. Travis Coy, CFO, stated it is too early to discuss profitability due to ongoing investments in three Phase III trials and an expected increase in R&D expenses, despite strong ChemTrak growth.

Representing Gil Blum of Needham & Company, an analyst asked if the reimbursement challenges seen with KIMMTRAK in Europe are expected to be similar for brenetafusp, or if they are specific to KIMMTRAK's indication.

Answer

CEO Bahija Jallal highlighted the company's successes, including 14 country approvals and overturning the NICE decision in the U.K., while acknowledging the generally challenging European environment. Ralph Torbay, Head of Commercial, added that this is an industry-wide issue. Bahija Jallal concluded that securing an overall survival (OS) endpoint for brenetafusp, similar to KIMMTRAK, would likely facilitate the reimbursement process.

Gil Blum of Needham & Co. questioned if the FDA might still provide significant feedback on the study protocol and statistical analysis plan (SAP) after the 30-day review period, despite the positive alignment.

Answer

CEO Sean Nolan stated that a 'showstopper' is highly unlikely, as the purpose of an end-of-phase meeting is to resolve misalignments, which they don't have. President and Head of R&D Sukumar Nagendran added that the FDA would have requested further review before this stage if they were uncomfortable, making significant new comments improbable, though minor correspondence is possible.

Gil Blum asked if prior experience with Zolgensma influenced the successful CMC comparability demonstration and questioned the feasibility of a randomized trial in adults versus using a natural history control.

Answer

CEO Sean Nolan confirmed that learnings from Zolgensma, particularly around maximizing product purity via downstream process improvements, were key to the successful comparability. He stated that CMC is now off the critical path. Regarding trial design, he explained that due to disease heterogeneity, using the patient as their own control is the optimal approach being discussed with the FDA.

Gil Blum questioned whether a potential clinical endpoint could be dependent on a patient's baseline condition, such as their seizure burden.

Answer

CEO Sean Nolan described it as an "evolving situation." He suggested that while a primary or co-primary endpoint might be standardized (e.g., motor function), the restoration of a lost function, like seizure reduction, would be highly impactful supportive data for regulators and payers. President and Head of R&D, Sukumar Nagendran, added that ongoing analysis of natural history data will help inform the Part B trial design to best assess these varied clinical impacts.

Gil Blum of Needham & Company asked about future investments needed to manage tariff impacts beyond 2025 and the financial effect of a weakening U.S. dollar.

Answer

President and CEO Bradley Campbell stated that he does not foresee significant new investments to manage tariffs, citing the company's proactive supply chain diversification, including moving manufacturing to Ireland and onshoring some drug product to the U.S. He also noted that with a majority of revenue coming from ex-U.S. markets, a weakening dollar generally provides a top-line benefit from favorable foreign exchange rates.

Gil Blum asked for Amicus's perspective on recent FDA feedback about potential accelerated approval pathways for genetic medicines in Fabry disease and whether this could accelerate their own internal program.

Answer

President and CEO Bradley Campbell responded that he views other gene therapies in development as primarily targeting patients with non-amenable mutations, which does not compete with Galafold. While he finds the FDA's regulatory flexibility exciting, he reiterated that Amicus's own program is still in early stages, a lower priority, and is also focused on the non-amenable population for the future.

On behalf of Gil Blum of Needham & Company, an analyst noted that FT819's B-cell depletion appeared less durable than FT522's in ASGCT charts and asked about its clinical relevance. He also inquired if discontinuing certain oncology programs would positively impact near-term R&D spending.

Answer

CEO Scott Wolchko clarified the FT819 data set was much larger and included patients with higher baseline disease burden. Dr. Bob Valamehr added that B-cell recovery is expected and the FT522 data is from only two patients. CFO Edward Dulac addressed spending, stating that while the R&D mix will shift, overall cash burn is expected to remain consistent as investments are redirected to advancing the autoimmune and solid tumor programs.

Asked about the go/no-go criteria for the PLD combo in ovarian cancer, the current relevance of PLD, and the clinical behavior of non-responding patients, particularly those with stable disease.

Answer

A go decision would be supported by a response rate over 25% and a duration of response exceeding 5 months, which would lead to an expansion cohort. While PLD has low efficacy alone, the emerging data for the combo is changing investigator perceptions and accelerating enrollment. It is too early to comment on the duration or characteristics of stable disease in non-responders until the full cohort data is available.

Gil Blum asked about the potential pricing strategy for eftansomatropin alfa in China and posed a technical question about whether givastomig's 4-1BB signaling is subject to a hook effect.

Answer

CEO Raj Kannan responded that it was too early to discuss specific pricing for eftansomatropin alfa but assured it would be competitive. CMO John Hayslip addressed the technical question, stating that a hook effect has not been an issue for givastomig in preclinical studies and that they observe a predictable pharmacodynamic effect.

Gil Blum of Needham & Company asked how the strategic refocus would enhance the SEL-212 program, affect the Sobi partnership, and what the next key milestone for investors should be.

Answer

Executive Blaine Davis clarified that the relationship with Sobi remains unchanged, with Selecta continuing its responsibility for ImmTOR manufacturing, for which it is fully reimbursed. He identified the BLA filing for SEL-212 in the first half of 2024 and potential pipeline partnerships as the next major catalysts for investors to watch.

Gil Blum asked when the financial impact of the recent headcount reduction would become visible in the company's operating expenses and sought clarification on the status of the IgA nephropathy program.

Answer

CFO Blaine Davis explained that a decrease in operating expenses, particularly in R&D, should be seen in subsequent quarters, contributing to the extended cash runway into H2 2025. CEO Carsten Brunn added that for IgA nephropathy, the company is currently evaluating the best path forward for the asset, which they still believe has significant potential.

Gil Blum asked when the financial impact of the recent headcount reduction would be reflected in operating expenses and sought an update on the IgA nephropathy program, which was not mentioned in the prepared remarks.

Answer

CFO Blaine Davis indicated that a decrease in OpEx, mainly in R&D, would become apparent in subsequent quarters, contributing to a cash runway into H2 2025. CEO Carsten Brunn explained that the company is currently evaluating the best path forward for the IgA nephropathy asset, noting its potential is similar to SEL-212 but that it is under strategic review.

Gil Blum asked when the financial impact of the recent headcount reduction would become visible in the company's operating expenses. He also requested clarification on the status and future plans for the IgA nephropathy program.

Answer

CFO Blaine Davis explained that a decrease in operating expenses, particularly in R&D, should be expected in subsequent quarters as a result of the strategic prioritization. CEO Carsten Brunn clarified that for the IgA nephropathy (IgAN) program, the company is currently evaluating the best path forward. He noted they remain excited about the asset's potential, drawing parallels to the now-validated approach used in the SEL-212 program.

Gil Blum of Needham & Company asked when the impact of the recent headcount reduction would be reflected in operating expenses and requested clarification on the status of the IgA nephropathy program.

Answer

CFO Blaine Davis projected a decrease in operating expenses, particularly in R&D, in subsequent quarters, which supports the cash runway guidance into H2 2025. CEO Carsten Brunn explained that the IgA nephropathy program is currently being evaluated for the best path forward, as resources have been prioritized for the ImmTOR IL platform due to its broader potential.

Gil Blum of Needham & Company asked about the role of partnerships in advancing programs for large autoimmune indications in the liver and inquired about the potential milestones expected from a positive readout of the pivotal studies for SEL-212 with Sobi.

Answer

President and CEO Carsten Brunn explained that while Selecta could potentially commercialize treatments for smaller, orphan-type liver indications, larger indications would likely require partnerships after initial proof-of-concept. Regarding the Sobi deal, he noted that of the $630 million in total milestones, $65 million in development and regulatory milestones are still receivable, in addition to double-digit royalties.

Gil Blum of Needham & Company inquired about the extent to which the strategy for large autoimmune indications relies on partnerships and asked about the potential milestones associated with a positive readout from the Sobi pivotal studies.

Answer

President and CEO Carsten Brunn explained that while Selecta could commercialize some orphan-type indications independently, the strategy for larger indications would involve an initial proof-of-concept study followed by a partnership. Regarding milestones, he reiterated that of the $630 million total, $65 million in development and regulatory milestones remain, in addition to double-digit royalties, though specific triggers were not detailed.

Gil Blum asked about any significant differences between the conditioning regimen used in the infantile malignant osteopetrosis (IMO) gene therapy trial and the regimen for a standard hematopoietic stem cell transplant.

Answer

Chief Medical Officer & SVP of Clinical Development, Jonathan Schwartz, clarified that the gene therapy conditioning regimen is a less extensive and less immunomodulatory regimen compared to what is typically utilized in an allogeneic transplant for IMO, which often involves more intensive chemotherapy combinations.