Larimar Therapeutics (LRMR) Status Update summary

Regulatory and Clinical Development Updates

• FDA provided written recommendations for BLA submission, requiring safety data from at least 30 participants with six months' exposure and 10 with one year, mainly at the 50 mg dose.

• FDA is open to using skin frataxin (FXN) concentrations as a surrogate endpoint for accelerated approval, with final acceptability to be determined during BLA review.

• BLA submission for accelerated approval is targeted for Q2 2026, with a planned U.S. launch in early 2027.

• Participation in the FDA's START pilot program has clarified regulatory expectations and expedited development.

• The global phase III study will serve as the confirmatory trial, enrolling 100-150 ambulatory patients aged 2-40, focusing on upright stability and mFARS as primary endpoints.

Clinical Data and Safety Profile

• Nomlabofusp has shown dose-dependent increases in tissue frataxin, with 25 mg daily dosing raising skin FXN to 72% of healthy volunteers at Day 90.

• The drug is generally well tolerated; most adverse events are mild injection site reactions, though anaphylaxis has occurred in some with prior exposure, leading to antihistamine premedication protocols.

• Early trends suggest potential clinical benefit, including improvements in MFARS, fatigue, and other functional measures.

• The lyophilized formulation, stable at room temperature, is being introduced to improve patient convenience and commercialization.

• The OLE study evaluates safety, PK, FXN levels, pharmacodynamic markers, and clinical outcomes with daily subcutaneous dosing.

Study Design and Enrollment

• The open-label extension (OLE) study is ongoing, now including adolescents, children, and patients new to Nomlabofusp trials, with data from 30-40 participants expected in September 2025.

• Adolescents from the PK run-in study are transitioning into the OLE study; PK run-in data from 14 participants expected September 2025.

• Considering direct enrollment of children aged 2-11 years into the OLE study, pending FDA and DMC discussions.

• Global Phase 3 study site identification and qualification are ongoing in the US, Europe, UK, Canada, and Australia.

• The phase III study is double-blind, placebo-controlled, and will serve as the confirmatory trial for clinical benefit.