Luke Herrmann

Luke Herrmann asked for clarification on whether the phase III endpoints for the ADCS study might change based on phase II data, if this is pre-agreed with the FDA, and what would trigger such a change.

Answer

Dr. Scott Struthers, Founder and CEO, clarified that the primary endpoint for phase III, normalization of urine-free cortisol, is set by the FDA and is highly unlikely to change. He explained that the phase II part primarily aims to identify the optimal dose for phase III and emphasized that a prospective parallel group, placebo-controlled trial is considered the most definitive design, avoiding methodological problems associated with randomized withdrawal studies.

Luke Herrmann, on behalf of Brian Skorney, asked about the ADCS study, specifically if Phase 3 endpoints might change based on Phase 2 data, whether this is agreed upon with the FDA, and what would trigger such a change.

Answer

CEO Scott Struthers clarified that the primary purpose of the Phase 2 part is to determine the optimal dose for Phase 3. He stated that the primary endpoint for Phase 3, normalization of 24-hour urine free cortisol, is largely set by the FDA and is very unlikely to change.

Luke Herrmann from Baird asked for clarification on whether Firdapse's 2026 growth would be backloaded or smoothed out by strong idiopathic LEMS traction in the first half, and followed up on the impact of the XBI trajectory on business development activities and inbound quality.

Answer

Jeff Del Carmen, EVP and Chief Commercial Officer, indicated that strong enrollments from idiopathic LEMS are expected to provide traction in the first half of 2026, with incremental cancer-associated LEMS patients contributing more in the second half. Rich Daly, President and CEO, added that while efforts accelerate diagnosis, the patient journey has a typical cadence. Regarding business development, Mr. Daly stated that the company has observed no change in the quality of inbound opportunities despite the XBI trajectory, maintaining focus on alignment, differentiated care, and quick returns.

Luke Herrmann asked for clarification on the expected growth trajectory for Firdapse in 2026, specifically whether it would be backloaded or smoothed by strong idiopathic LEMS traction in the first half. He also followed up on how the recent favorable trajectory of the XBI biotech index might affect Catalyst Pharmaceuticals' business development activities, particularly the breadth and quality of inbound opportunities.

Answer

Jeff Del Carmen, EVP and Chief Commercial Officer, and Rich Daly, President and CEO, indicated that strong enrollments from idiopathic LEMS are expected to provide a smoother growth profile in the first half of 2026, with incremental patients from cancer-associated LEMS anticipated in the second half. Rich Daly stated that the company has observed no change in the quality of inbound business development opportunities despite the XBI's trajectory, maintaining focus on differentiated care, strategic alignment, and accretive returns.

Luke Herrmann asked about Alkermes' internal bar for ESS in the LUMRYZ phase III IH study and the importance of key secondary endpoints for prescribers.

Answer

Richard Pops, CEO, and Todd Nichols, Chief Commercial Officer of Alkermes, stated that the LUMRYZ IH study design mirrors previous FDA-approved oxybate programs like XYWAV's randomized withdrawal study, expecting a similar profile. The primary endpoint is ESS, with key secondaries PGIC and IHSS. The IH eligible population is estimated at 40,000 in the US with low penetration.

Luke Herrmann asked about Alkermes' internal bar for the Epworth Sleepiness Scale (ESS) in the LUMRYZ Phase 3 idiopathic hypersomnia (IH) study and the importance of key secondary endpoints to prescribers.

Answer

Richard Pops, CEO, stated that the IH study design for LUMRYZ mirrors previous FDA-approved oxybate programs, expecting a similar profile for the once-nightly medicine. Todd Nichols, Chief Commercial Officer, added that the primary endpoint is ESS, with key secondaries being PGIC and IHSS, anticipating results similar to the current market product. He highlighted the significant opportunity in the IH market due to low penetration.

Luke Herrmann asked for additional color on the base case for Vatiquinone's external control matching strategy to maximize the likelihood of a statistical hit, and the key features that need to be aligned with the FDA at this point.

Answer

Matthew Klein, CEO, explained that PTC has experience with natural history matching from the MOVE-FA study and regulatory precedence with the FA-COMS registry. Key matching factors include age, age of onset, and baseline mFARS scores. Alignment with the FDA is needed on the matching approach, details of the statistical model, analysis methodology, study duration, and subject numbers to ensure a robust and aligned path forward for this open-label natural history comparison study.

Luke Herrmann asked for additional color on PTC Therapeutics' base case for the external control matching strategy for vatiquinone, aiming to maximize the likelihood of a statistical hit. He also inquired about the key features that need to be aligned with the FDA at this point for the new study.

Answer

CEO Dr. Matthew Klein explained that PTC has prior experience with natural history matching from the MOVE-FA study and regulatory precedent with the FA natural history registry. Key matching factors would include age, age of onset, and baseline mFARS scores. Alignment with the FDA will focus on the matching approach, statistical model details, analysis plan, study duration, and subject numbers to ensure a robust and agreed-upon path forward.