Stephen Willey

Stephen Willey asked if the single Phase III PAH trial for TPIP would target a patient population similar to Phase II, and about feedback on potential label claims and additional studies for broader functional class patients.

Answer

Will Lewis, Chairman and CEO of Insmed, highlighted TPIP's 35.5% PVR reduction as potentially best-in-class. Martina Flammer, Chief Medical Officer, confirmed that the Phase III study design would be consistent with Phase II, but would allow for titration up to 1280 micrograms (maximum tolerated dose) based on open-label extension experience.

Stephen Willey asked if the single Phase 3 PAH trial for TPIP, aligned with the FDA, would target a patient population similar to Phase 2, and inquired about potential label claims and additional studies for broader functional class patients.

Answer

Will Lewis, Chairman and CEO, highlighted TPIP's potential for patient impact and convenience due to its titratability and once-daily dry powder formulation, noting its 35.5% PVR reduction in Phase 2. Martina Flammer, Chief Medical Officer, confirmed that Phase 3 will aim for consistency with Phase 2, but will allow titration up to 1280 micrograms, the maximum tolerated dose, based on OLE safety experience.

Stephen Willey asked what to expect from the 989 abstract publication relative to the full presentation, and about the read-through of Sanofi's failed frontline trial with Resurrect steroids to Naktinvo's ongoing Phase 3 trial, including potential biological differences in newly diagnosed patients.

Answer

President Pablo Cagnoni advised focusing on the later 989 presentation before year-end, as it will include a later data cut, more patients, and longer follow-up than the abstract. Chief Medical Officer Steven Stein explained that the controversy around primary endpoint measurement (event-free survival) and event definitions is key in first-line GVHD trials, expressing confidence in Naktinvo's robust endpoint definition and its potential for steroid withdrawal. CEO Bill Meury highlighted Naktinvo's two combination studies (with steroids and Jakafi) as significant opportunities to expand its addressable population and potentially offer a non-steroid regimen.

Stephen Willey from Stifel questioned the expected patient throughput at qualified treatment centers (QTCs), both at launch and at steady-state, and asked how the PRV sale impacts the prioritization of the company's early-stage pipeline.

Answer

Chief Commercial Officer Dr. Madhav Vasanthavada stated that physicians at potential QTCs are comfortable with a throughput of two patients per month per site, with some institutions indicating capacity for up to four. CEO Dr. Vish Seshadri addressed the pipeline, confirming that the RS1 ophthalmology program remains on track for in-human studies in the second half of 2026, a cadence that fits well with the ZEVASKYN commercial ramp. He noted the PRV proceeds support this without accelerating timelines that are dictated by scientific processes.

Asked about screening protocols for pneumonitis and whether dyspnea could be miscategorized. Also requested the median duration of follow-up for the study arms and the distribution of patients based on prior ARPI stability.

Answer

The executive confirmed there is no routine pneumonitis screening protocol as it wasn't a prior signal, and the recent cases are under investigation. He did not provide the median follow-up but noted the mean number of doses is now five. The split of patients by prior ARAT exposure duration was approximately 40% to 60%.

Asked about the enrollment kinetics (new vs. experienced sites), whether a go-forward dose has been selected between the 2.7 and 2.0 mg regimens, and if rPFS data maturity would delay the initiation of new expansion cohorts.

Answer

Scott Koenig clarified that the rapid enrollment surge in late 2023 was primarily from newly opened sites in Europe. He stated it's too early to decide on a final go-forward dose, as they are waiting for more complete data, and the data safety monitoring committee recommended continuing both doses. The rPFS data maturity will not slow down the initiation of the new expansion cohorts.

Inquired about the specifics of the planned CUE-101 Phase II trial, including the second dose being considered, the trigger for the interim analysis, the rationale for a standalone Phase II versus a seamless Phase II/III design, and how recent competitor data influences expectations.

Answer

The company is considering 4 mg/kg and likely 2 mg/kg as the two doses for the Phase II trial. The interim analysis will be triggered when 70-80% of patients have completed their cycle 5 scan. A standalone Phase II was chosen as a more cost-effective and confidence-building step before a larger Phase III investment, a decision reinforced by unexpected results in other recent trials. The final analysis of the Phase II, not the interim, would support moving to Phase III.

Stephen Willey of Stifel inquired about the expected response rates for venetoclax retreatment in the voruciclib AML trial and whether patients in the ME-344 study would be naive to salvage therapies like LONSURF. He also asked for context on the 20% 4-month PFS threshold for ME-344 and questioned the significant sequential drop in Q4 R&D spending.

Answer

President and CEO David Urso indicated that a 20-30% response rate for the voruciclib combination in relapsed/refractory AML would be considered exciting. Chief Medical Officer Dr. Richard Ghalie clarified that ME-344 patients are not required to be naive to LONSURF or regorafenib and that the 20% PFS is a 'floor,' with the data's significance depending on the enrolled patients' prior treatments. CFO Jay File explained the R&D decline was due to the wind-down of the zandelisib trials, which accounted for approximately $26 million of the annual R&D spend.

Stephen Willey from Stifel asked for guidance on the continued paydown of the 9% notes, commentary on a citizen petition regarding the closed triple, insights into BREO scripts written with LAMA, and the reason for the timing of the new ANORO DTC campaign.

Answer

CFO Eric d'Esparbes confirmed the plan to continue paying down the 2029 notes remains active. CEO Michael Aguiar addressed the closed triple, acknowledging the logic of a competitor's petition but expressing confidence in their filing with the FDA. He estimated that about 40% of the COPD LABA/ICS market involves an 'open triple' combination. Regarding the ANORO DTC campaign, he declined to comment on specific timing decisions but noted its positive launch and expected contribution to growth.