Samantha Corwin

Samantha Corwin asked about the long-term strategy for evaluating AMT-130 in earlier or later-stage Huntington's disease and inquired about the number of U.S. physicians capable of performing the administration procedure.

Answer

CMO Dr. Walid Abi-Saab explained that while there is great interest in exploring earlier or later-stage intervention, it's early days and requires discussion with regulators. For administration, he stated that upwards of 50 U.S. sites are capable of performing the MRI-guided intraparenchymal infusion, describing it as a relatively common procedure for neurosurgeons.

Samantha Corwin inquired about the expected cadence of patient starts in the EU, given the in-office first-dose requirement, and asked for any statistics on patients who have discontinued therapy permanently.

Answer

Krish Krishnan, Chairman and CEO, explained that while the first EU dose is in-office, the company is working to streamline this potential gating factor, noting patients can quickly transition to home administration. He stated that a very small percentage of patients stop therapy permanently, typically due to severe disease complications like squamous cell carcinoma, not due to issues with the drug itself. He emphasized that other patients who pause do come back on treatment.

Samantha Corwin asked for insight into the delayed European regulatory decision, which was previously expected in late 2024. She also inquired about the company's strategy to maintain and expand market share in the face of potential competition in the DEB space.

Answer

Suma Krishnan, President of R&D, explained the regulatory delay was strategic to secure a more favorable label, including home dosing and caregiver administration. Krish Krishnan, Chairman and CEO, addressed competition by highlighting VYJUVEK's strong value proposition and high rate of home administration, expressing confidence in hitting sales targets despite a potentially more competitive market.

Samantha Corwin from William Blair & Company asked about the event-free survival difference the ALPHA3 trial is powered to show and sought clarification on a 10-K disclosure regarding the futility analysis if both treatment arms outperform control but are similar to each other.

Answer

Dr. David Chang, President and CEO, stated the trial is 'very well powered' but did not specify the exact EFS difference. Regarding the futility scenario, he explained that if the arms show similar efficacy, the company might enroll more patients to better assess a difference, but the decision will be data-driven based on the initial patient cohort.

Samantha Corwin asked about the average time from a MIPLYFFA enrollment form submission to reimbursement approval, the potential to expand the treated NPC population beyond the currently diagnosed patients, and if any patients have faced ultimate reimbursement denials.

Answer

CEO Neil McFarlane expressed confidence in expanding the market toward the 900 prevalent patient estimate, citing early success with media campaigns. CMO Adrian Quartel stated it was too early for an average time-to-reimbursement metric but noted some patients received refills within the first five weeks. He confirmed that while initial denials occur, very few have been ultimate denials, and a robust patient assistance plan is in place to ensure access.

Samantha Corwin requested more details on the status of the remaining 60 MIPLYFFA enrollment forms, whether any had been denied, and what proportion of the 90 total enrollments were for patients already taking miglustat.

Answer

President and CEO Neil McFarlane clarified that the 90 enrollments were as of October 31 and that denials are a normal part of the benefits investigation process, some of which have already been successfully appealed to reach the 30% approval figure. Chief Commercial Officer Joshua Schafer added that the patient services team is diligently working through the remaining forms and estimated that, similar to the EAP population, about 80-85% of the enrolled patients are on miglustat.

Samantha Corwin asked if new patient starts for Translarna in Europe would continue, inquired about the timing of future FDA meetings for the Huntington's program, and asked if Novartis would now lead regulatory interactions.

Answer

CEO Dr. Matthew Klein expects new Translarna starts in Europe to continue while the drug remains authorized, due to strong physician and patient conviction. For the Huntington's program, he stated that after the next data readout, PTC and Novartis will engage the FDA, but planning for the pivotal trial is already at full speed. He confirmed regulatory interactions will be a joint effort.

Samantha Corwin of William Blair asked about the expected early adopters for sepiapterin, the mix of classical PKU patients, potential payer step-edits, and the penetration assumptions behind the $1 billion U.S. revenue opportunity.

Answer

CEO Matthew Klein identified Kuvan non-responders as likely early adopters. CBO Eric Pauwels added that with 90% of PKU patients untreated, payers recognize the high unmet need, supporting premium pricing with minimal step-edit hurdles due to rapid efficacy measurement. He noted that a modest penetration of 20-30% could achieve the $1 billion-plus U.S. revenue target.

Samantha Corwin of William Blair inquired about the expected evolution of gross margins in 2025 and 2026 as ELEVIDYS becomes a larger part of revenue, and asked for more detail on the DUX4 assay for the FSHD program.

Answer

CFO Ian Estepan projected gross margins to trend into the high 70s as more non-ambulatory (heavier) patients are treated, but expects margins to improve significantly, trending towards 90%, upon the successful implementation of suspension manufacturing around 2027. Dr. Louise Rodino-Klapac described the DUX4 assay as a quantitative tool developed by Arrowhead that can successfully measure the very low levels of the protein, a key technical achievement.

Samantha Corwin of William Blair asked about potential synergies between the upcoming limb-girdle (LGMD) launch and the existing ELEVIDYS commercial infrastructure, and if cost savings from the discontinued SRP-5051 program could accelerate LGMD development.

Answer

President and CEO Doug Ingram confirmed there would be '100% absolute' synergy, leveraging Sarepta's seasoned commercial team and the shared gene therapy platform components like the AAVrh74 capsid. He noted that while they are already moving as fast as possible on LGMD, the cost savings will be reinvested into R&D to advance the entire pipeline.

Samantha Corwin of William Blair & Company asked about the rationale for expanding the ESCAPE technology into beta thalassemia and whether the associated clinical trials would be conducted in the U.S. or ex-U.S.

Answer

President Dr. Giuseppe Ciaramella explained that ESCAPE's improved risk-benefit profile could justify transplant for a broader population of beta thalassemia patients, beyond just the most severe transfusion-dependent cases. He noted that the location for the initial healthy volunteer study will be determined by efficiency and speed.

Samantha Corwin of William Blair asked about the rationale for expanding the ESCAPE technology into beta-thalassemia and whether the associated clinical trials would be conducted in the U.S. or ex-U.S.

Answer

President Dr. Giuseppe Ciaramella explained that ESCAPE's improved risk-benefit profile could justify transplant for a broader population of beta-thalassemia patients, beyond the most severe cases. He stated that the location for the initial healthy volunteer study has not been decided and will be chosen based on what is most efficient and rapid.