Larimar Therapeutics (LRMR) Study Update summary

Study background and disease overview

• Friedreich's Ataxia (FA) is a rare, progressive disease caused by genetic defects lowering frataxin (FXN) levels, affecting about 20,000 patients globally, with significant unmet medical need.

• Lower FXN levels are linked to earlier onset, faster progression, and shorter time to loss of ambulation in FA.

• Nomlabofusp is designed to deliver additional frataxin to mitochondria, aiming to address the underlying FXN deficiency.

Study design and objectives

• Ongoing long-term open-label study evaluates daily subcutaneous nomlabofusp in FA patients, with both 25 mg and 50 mg doses assessed over up to one year.

• Study includes adults, adolescents, and plans to enroll children aged 2–11, with about 50% non-ambulatory at baseline.

• Protocol amended to include new titration regimen and pre-treatment with antihistamines to mitigate hypersensitivity.

• Study aims to assess safety, tolerability, pharmacokinetics, frataxin level increases, and clinical outcomes compared to a reference population from the FACOMS Natural History Study.

• Global Phase III double-blind, placebo-controlled study is planned, enrolling 100-150 ambulatory patients aged 2-40 years.

Efficacy and biomarker results

• 100% of participants with 6 months of treatment achieved skin FXN levels over 50% of healthy volunteer median, similar to asymptomatic carriers.

• Median skin FXN levels increased from 2.70 pg/μg at baseline to 13.44 pg/μg at 6 months, approaching healthy volunteer levels (16.34 pg/μg).

• Median mFARS score improved by 2.25 points at one year, while the FACOMS reference population worsened by one point.

• Consistent improvements observed in FARS-ADL, Nine-Hole Peg Test, and MFIS, all outperforming the FACOMS reference group.

• Clinical benefit observed even in advanced-stage, wheelchair-bound patients, suggesting potential for disease modification.