Larimar Therapeutics (LRMR) Study Update summary

Study Design and Objectives

• Ongoing open-label extension (OLE) study evaluates daily subcutaneous nomlabofusp (25mg and 50mg) in adults with Friedreich’s Ataxia (FA), focusing on long-term safety, pharmacokinetics, frataxin (FXN) levels, and clinical outcomes compared to natural history data.

• OLE study initially used 25mg daily dosing, now escalating to 50mg, with all current and new participants transitioning to this dose; long-term 50mg data expected mid-2025.

• Pediatric PK run-in study is enrolling adolescents and will expand to children, using weight-based dosing equivalent to adult 50mg; adolescent dosing expected early 2025, children in 1H 2025.

• Confirmatory global, double-blind, placebo-controlled study is planned for mid-2025, with BLA submission targeted for the second half of 2025, aiming for accelerated approval using FXN as a surrogate endpoint.

• Participants from prior Phase 1 and 2 studies are eligible for the OLE study, with over half non-ambulatory at baseline.

Efficacy and Biomarker Results

• Daily 25mg nomlabofusp increased tissue FXN levels: buccal cells rose from 15% to 30% and skin cells from 16% to 72% of healthy volunteer levels at Day 90; mean change at Day 90 was 1.32 pg/μg in buccal and 9.28 pg/μg in skin cells.

• Dose-dependent increases in FXN were observed, with 50mg predicted to achieve ≥50% of healthy control FXN levels in most patients.

• FXN levels reached steady state by Day 30 and were maintained over time, with pharmacokinetics consistent across studies.

• Increases in FXN correlated with improved gene expression and lipid profiles toward healthy control values.

• Early trends of improvement were observed in clinical outcomes (MFARS, FARS-ADL, fatigue, Nine-Hole Peg Test), especially upper limb function, at Day 90.

Safety and Tolerability

• Nomlabofusp was generally well tolerated for up to 260 days; most adverse events were mild, brief injection site reactions.

• Two serious adverse events (allergic reaction, seizure) resolved within 24 hours and led to withdrawal; no discontinuations due to injection site reactions.

• Safety profile supports dose escalation to 50mg in the OLE study.