Sami Corwin

Sami Corwin asked for a detailed explanation of the rescue arm in the Orbit study for osteogenesis imperfecta and how it is factored into the statistical analysis plan. She also inquired about neurologists' views on the utility of Bayley 4 cognition versus Bayley 4 communication endpoints for Angelman syndrome.

Answer

Howard Horn, Chief Financial Officer, explained that patients in the Orbit study could enter the rescue arm after one year if they experienced a high number of fractures, allowing them to remain in the trial. All time on drug, including rescue, is included in the analysis to estimate the annualized fracture rate (AFR). Regarding Angelman, he stated that parents focus on the overall well-being of their children, not specific primary or secondary endpoints. Ultragenyx will provide comprehensive data across multiple domains, including receptive and expressive communication, cognition, sleep, behaviors, and fine motor skills.

Sami Corwin asked for details on the rescue arm in the Orbit study and how it's factored into the statistical analysis plan. She also inquired about neurologists' views on the utility of Bayley-4 cognition versus Bayley-4 communication endpoints.

Answer

Howard Horn, Chief Financial Officer, explained that the rescue arm allows patients with a high number of fractures to cross over after one year, with their annualized fracture rate (AFR) still included in the analysis. He stated that for Angelman syndrome, parents prioritize the 'whole story' of their child's progress over specific primary or secondary endpoints. He confirmed that the program covers all domains, including receptive and expressive communication, with a focus on Bayley-4 cognition due to observed effects.

Sami Corwin of William Blair asked if the leadership changes at CBER would impact the UX-111 CRL resolution and whether Ultragenyx is considering modifying its AAV immunosuppression regimens in light of recent industry safety events.

Answer

Emil Kakkis, Founder, President & CEO, stated he does not expect the CBER leadership change to affect the CRL resolution, as it's a practical process handled by the existing team. Regarding AAV safety, he noted their programs use lower doses and have not seen major issues. While they are exploring enhanced immunomodulation to optimize efficacy, it is not a response to major safety concerns.

Sami Corwin of William Blair questioned the change in stance on sharing MRD conversion rates, given prior concerns about influencing physician behavior, and asked if the ALLO-329 data would include both lymphodepletion cohorts.

Answer

CEO Dr. David Chang explained that since MRD conversion is a secondary biomarker endpoint in a novel setting, sharing the data on a limited number of patients at the futility analysis is not expected to compromise the trial's integrity. He also confirmed the ALLO-329 study is testing both cyclophosphamide-only and no-lymphodepletion cohorts, with updates on the data disclosure to come as the study progresses.

Representing Sami Corwin of William Blair, an analyst asked if site-related challenges from ALPHA3 are expected at ex-U.S. sites and if the ALLO-329 autoimmune study will also expand internationally.

Answer

Dr. Zachary Roberts, EVP of R&D and CMO, stated they expect a smoother rollout for ALPHA3 ex-U.S. due to lessons learned and less fragmented lymphoma care abroad. For ALLO-329, he said the near-term focus is on U.S. sites, but the company is open to ex-U.S. expansion in the future given the competitive landscape.

Sami Corwin of William Blair inquired about the number of unique Myclifa prescribers, how that figure has trended, and the potential for further expanding the percentage of covered lives.

Answer

Chief Commercial Officer Joshua Schafer explained that the number of unique prescribers has grown significantly as the launch moves beyond EAP investigators to community clinicians treating fewer patients, a trend he expects to continue. He noted that covered lives stand at 52%, which is typical for this stage of a launch, and anticipates this will increase as more health plans complete their reviews, using Olpruva's 79% coverage as a potential long-term analog.

Sami Corwin from William Blair requested an update on the FDA's review of Translarna in the U.S., including any recent interactions. She also asked about the company's perspective on additional business development opportunities given its strong balance sheet.

Answer

CEO Dr. Matthew Klein reported that the Translarna NDA remains under active review, with clinical site inspections completed in the spring and easily addressed information requests received in the early summer. Regarding business development, CFO Pierre Gravier and Dr. Klein stated that with a strong financial position, PTC is actively looking for disciplined, value-creating opportunities. They are seeking assets that could fit into their existing global commercial infrastructure or complement their R&D portfolio, focusing on their sweet spot of rare diseases.

Sami Corwin from William Blair inquired about the European launch, specifically if patients require an initial physician office visit and if there is a patient onboarding goal similar to the U.S. target.

Answer

SVP & GM for Europe Laurent Goux confirmed that an initial appointment at a specialty center is customary in Europe. He stated there is no specific patient ramp number communicated, but the strategic goal is to reach 60% of the eligible patient pool within two to three years.

Sami Corwin of William Blair asked if the FDA has provided specific guidance on what it wants to see from the NfL biomarker data and whether hospital capacity could be a limiting factor for the commercial launch of AMT-130.

Answer

CMO Walid Abi-Saab stated there have been no specific FDA discussions on NfL targets, though the agency agreed it could be supportive. He cautioned that interpreting 3-year NfL data will be difficult without a comparator. CEO Matt Kapusta asserted that hospital bed capacity is not expected to be a significant factor for the launch, citing the short hospital stay required for the procedure.

An analyst on behalf of Sami Corwin asked what specific data sets families want to see to gain confidence in ELEVIDYS after the safety event, particularly regarding older, non-ambulatory patients.

Answer

President and CEO Douglas Ingram speculated that families need context: understanding the event was one in over 800 patients dosed and that safety signals do not differ by ambulatory status. He stressed the importance of communicating the full efficacy picture, especially the muscle MRI data, which shows the urgency of treatment to prevent irreversible muscle damage. Chief Customer Officer Dallan Murray pointed to new educational tools available on elevidys.com.

Sami Corwin of William Blair & Company asked what prompted the decision to explore the ESCAPE technology in 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 transfusion-dependent cases. Regarding trial location, he stated that the decision for the healthy volunteer study has not yet been made and will be guided by the goal of rapid and efficient data generation.

Asked about the control arm for the adult GVHD trial, sought confirmation on the saline control for the back pain trial, and questioned the difference in outcomes between the old Study 280 and new data, seeking reasons for confidence in the upcoming adult study.

Answer

The GVHD trial may use contemporaneous controls via the CTN network or a randomization strategy. The FDA accepts a saline control for the back pain trial. Confidence in the new adult study stems from using a more potent product (RYONCIL) with improved manufacturing, which has shown superior survival rates (63%) in expanded access compared to the older product (Prochymal) used in Study 280.

Asked about the potential control arm for the new adult GVHD trial, sought confirmation on the FDA's acceptance of a saline control for the back pain trial, and questioned the basis for confidence in the new adult study given the results of the older Study 280.

Answer

For the GVHD trial, using contemporaneous control data from the CTN network is an option being discussed with the FDA. The FDA is fine with a saline control for the back pain trial. Confidence in the new adult GVHD study stems from using the improved Ryoncil product, which has shown superior efficacy (63% survival) compared to the older PROCHYMAL product used in Study 280, attributed to its greater potency.