Dina Ramadane

Dina Ramadane, on for Jason Gerberry, asked where seizure freedom fits within the statistical hierarchy for X-TOLE2 and about assumptions for this endpoint. She also inquired about the lead indication selection for XEN1120 and the desired pharmacology profile from its Phase I trial.

Answer

President and CEO Ian Mortimer stated that for XEN1120, the Phase I trial will assess PK and safety, with the goal of advancing into a proof-of-concept study in pain. Chief Medical Officer Dr. Chris Kenney clarified that seizure freedom is not in the statistical hierarchy for the double-blind portion of the study, as it's an endpoint best measured over a longer term, making the open-label extension data the primary focus for that outcome.

Dina Ramadan from Bank of America asked about the broader market opportunity for FILSPARI in FSGS, including whether it requires market building and the potential challenges for a new therapy in a space with no approved treatments.

Answer

Chief Commercial Officer Peter Heerma estimated the addressable U.S. market at 15,000 to 30,000 patients, noting it's the same prescriber base as IgAN, which should lead to rapid uptake. Chief Medical Officer Dr. Jula Inrig added that there is a high unmet need for effective, non-immunosuppressive therapies. President and CEO Dr. Eric Dube concluded that they expect to become the leader and new standard of care.

Asked about the drivers for the expected acceleration in LYFGENIA patient starts in the second half of the year and the competitive dynamics influencing prescriber choice between sickle cell gene therapies.

Answer

The LYFGENIA acceleration was always anticipated for the second half of the year due to the longer patient journey involving payer approvals and clinical readiness; it is a timing issue, not a demand issue. The company believes it holds a competitive lead due to its larger QTC network, higher U.S. patient start numbers, and favorable market research showing physician preference for LYFGENIA.