Rafael (RFL) 3rd Annual Guggenheim Healthcare Innovation Conference summary

Program and pivotal study

• The two businesses combined in March 2025; Trappsol Cyclo has been in development since the 1990s, with Phase I, Phase I/II and pivotal Phase III studies for NPC neurovisceral manifestations.

• The Phase III trial began in 2021, enrolled 94 patients and ran for 2 years, with a 48-week interim look; the design was developed collaboratively with the FDA.

• The primary composite 4D endpoint covered swallowing, ambulation, fine motor skills and speech; patients entered after 3 months on background miglustat, used in both active and placebo groups.

• The study completed in June; topline data were reported in September, and the NDA for remibetadex was submitted in October.

Efficacy and filing rationale

• The primary endpoint was missed; the pre-specified covariate analysis covered 78 patients, and the treatment arm showed 0.46 over 2 years in both the 94-patient cohort and the 78-patient subgroup.

• In the 0–3-year-old sub-study, 8 of 10 patients stabilized or improved at 48 weeks; at 96 weeks, 6 of 7 patients who completed remained stable or improved.

• Responder analyses, the infant sub-study and overall survival analysis contributed to the rationale for filing based on the totality of data.

• The study covered ages 7 months to 68 years; the requested indication is monotherapy for NPC neurovisceral manifestations from birth onward.

Regulatory and commercialization outlook

• FDA pre-NDA discussions took place in February; the infantile sub-study was included in the submission, and the team expects no AdCom while preparing for all outcomes.

• Remibetadex may be used alongside existing therapies at physician and caregiver discretion; no drug-drug interaction issues with other treatments have been observed to date.

• Commercial priorities include working with patient groups on newborn screening; the treatment targets neurovisceral symptoms, while other therapies were described as focused on neurological symptoms.

• EMA discussions are ongoing; its primary endpoint is 5D versus 4D in the U.S. Regulatory work is planned for early H1 next year, with a likely commercial partner outside the U.S.