Larimar Therapeutics (LRMR) Study Update summary

Study Design and Objectives

• Ongoing open-label extension (OLE) study evaluates daily subcutaneous nomlabofusp (initially 25mg, escalating to 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.

• Initial cohort received 25mg; positive data led to dose escalation to 50mg for all participants and new enrollees, with long-term 50mg data expected mid-2025.

• Pediatric PK run-in study initiated, starting with adolescents and expanding to children, using weight-based dosing equivalent to adult 50mg.

• Confirmatory global, double-blind, placebo-controlled study planned for mid-2025, with protocol finalized based on regulatory feedback.

• BLA submission for accelerated approval targeted for 2H 2025, aiming to use FXN as a surrogate endpoint.

Efficacy and Biomarker Results

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

• Dose-dependent, sustained increases in tissue FXN observed, with modeling suggesting ≥50% of patients on 50mg may exceed 50% of healthy volunteer levels.

• FXN levels reached steady state by Day 30 and were maintained over time, with consistent pharmacokinetics and no accumulation.

• Early trends toward improvement seen in clinical outcomes (MFARS, FARS-ADL, fatigue, 9-Hole Peg Test), especially upper limb function, in both ambulatory and non-ambulatory patients.

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

Safety and Tolerability

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

• Two serious adverse events (one severe allergic reaction, one seizure) resolved within 24 hours and led to withdrawal; both cases reported to the FDA.

• No study discontinuations due to injection site reactions; ongoing monitoring for anti-drug antibodies, with no neutralizing effect observed.

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

• Two additional discontinuations due to protocol compliance challenges, not related to treatment.