Julian Pino

Julian Pino asked about the relative contributions of potential commercial competition versus litigation risk to BioMarin's revised market views for 2027 guidance. He also inquired about the 10% dystrophin bar for the DMD program (BMN-351), questioning its rationale given lower regulatory approval bars for existing Exon skippers.

Answer

Brian Mueller (CFO, BioMarin Pharmaceutical) reiterated that the lower end of 2027 estimates assumes two successful competitors, while the higher end includes less competition or intellectual property defense success. Cristin Hubbard (Chief Commercial Officer, BioMarin Pharmaceutical) noted continued patient additions for VOXZOGO, with strong adherence rates. Greg Friberg (Chief R&D Officer, BioMarin Pharmaceutical) explained the 10% dystrophin bar for BMN-351 is ambitious, chosen due to human genetic data suggesting dramatically improved functional outcomes at such levels, similar to Becker's muscular dystrophy.

Julian Pino asked about the relative contributions of potential commercial competition versus litigation risk to BioMarin's revised market views and the likelihood of a positive outcome in intellectual property litigation. He also inquired about the 10% dystrophin bar set for the BMN-351 DMD program, questioning what informs this ambitious target given lower regulatory approval bars for existing Exon skippers.

Answer

Brian Mueller, Chief Financial Officer, explained that the lower-end 2027 revenue estimates assume two competitors launch successfully and gain significant share, while higher-end scenarios include less competition or successful intellectual property defense. Cristin Hubbard, Chief Commercial Officer, noted that Voxzogo continues to add patients globally, with strong adherence rates, suggesting patients satisfied with treatment are likely to remain on therapy. Greg Friberg, Chief R&D Officer, stated the 10% dystrophin bar for BMN-351 is ambitious, chosen due to human genetic data suggesting dramatically improved functional outcomes at such levels, aiming for an undeniable advance in the field compared to other Exon 51 skippers.

Julian Pino, on for Paul Mattias, asked what was learned from the two early 12-week biopsies in the DMD study and what provided confidence in the 10% dystrophin goal.

Answer

Chief R&D Officer Gregory Friberg stated that the two early biopsies were directionally positive. They confirmed that the drug reached the muscle, the novel splice variant was being produced, and near full-length dystrophin was measurable, consistent with their models. He said this removed key 'pertinent negatives' and provides confidence for the more informative 25-week data readout.

Julian Pino of Stifel Financial Corp. inquired about the timeline for the PALISADE III study, specifically asking if Vistagen still plans to announce the completion of enrollment and when that might occur. He also asked for commentary on patient dropout rates, retention, and the conversion rate to the open-label extension study.

Answer

President and CEO Shawn Singh confirmed that Vistagen will announce the last patient out (LPO) and reiterated the guidance for top-line results in Q4 of the current year. Chief Operating Officer Joshua Prince added that the conversion rate from the main study to the open-label extension is strong at over 80%, which is higher than in previous PALISADE trials, and that retention has been good, helping to meet ICH requirements for drug exposure.

Julian Pino of Jefferies inquired about the enrollment pace for Vistagen's PALISADE-3 and PALISADE-4 trials, investigator feedback, whether the parallel studies share trial sites, and for confirmation on the data readout timelines.

Answer

CEO Shawn Singh confirmed the previously guided timelines of mid-2025 for PALISADE-3 and late 2025 for PALISADE-4. He noted significant excitement from investigators and site staff, with 16 activated sites for PALISADE-3 and 12 for PALISADE-4, with no overlap between the studies. COO Joshua Prince added that in-person investigator meetings have highlighted the enthusiasm from PIs to participate in these unique trials.

Julian Pino, on for Paul Matteis, sought clarification on the ability to modify the statistical analysis plan (SAP) for ACP101 while blinded. He also asked why Daybue guidance was not narrowed given the strong performance and expectation for accelerating growth.

Answer

EVP, Head of R&D, Elizabeth Thompson, clarified that while an SAP can technically be changed before unblinding, there are no planned modifications for ACP101. CFO Mark Schneyer explained that the NUPLAZID guidance was narrowed because its initial range was unusually wide, whereas the company will revisit other guidance ranges, including Daybue's, in the third quarter as is typical.

Julian Pino of Stifel inquired about the final sample size for the KOASTAL-1 study and whether there was any potential upside to the original powering assumptions.

Answer

Robert Lenz, Head of Research and Development, explained that all three replicate Phase III studies are powered at approximately 90% and target around 332 patients each. He highlighted that the study design includes the flexibility to increase enrollment by up to 25% without a protocol amendment, with final numbers to be shared at the top-line data readout.

Julian Pino of Stifel inquired about the upcoming AL002 (TREM2) data readout, specifically the proportion of patient data at 48 and 96 weeks. He also asked about the potential rollover of APOE4 homozygotes into the long-term extension study and sought clarification on the FDA's view of progranulin (PGRN) biomarkers as 'confirmatory evidence' for latozinemab.

Answer

Dr. Gary Romano, Chief Medical Officer, explained that all completers (~250) will have 48 weeks of data, with half having 72 weeks and a third having 96 weeks. He confirmed that APOE4 homozygotes are not rolling over into the long-term extension. Regarding latozinemab, he clarified that 'confirmatory' means positive biomarker data would supplement a positive primary clinical outcome, noting it could also serve as a backup for an accelerated approval strategy if the clinical outcome is only directionally positive.