Larimar Therapeutics (LRMR) investor relations material

Program overview and disease background

• Developing a protein replacement therapy targeting Friedreich's ataxia, a rare autosomal recessive disease caused by frataxin deficiency, leading to severe disability and early mortality.

• Therapy aims to deliver frataxin via subcutaneous injection, enabling cellular and mitochondrial uptake to address the root cause.

• Approximately 5,000 patients in the US and 20,000 globally, with higher prevalence in Europe and underdiagnosis in regions like India.

• Existing approved therapy (SKYCLARYS) addresses oxidative stress but not frataxin deficiency, leaving unmet needs, especially for patients under 16.

• The approach is differentiated by directly replacing the missing protein rather than modulating downstream effects.

Clinical development and data highlights

• Four clinical trials completed since 2019, including SAD, MAD, dose exploration, and pediatric PK studies, with ongoing open-label extension.

• Demonstrated increased frataxin levels in patients, with 100% of patients at six months exceeding 50% of normal levels, a threshold associated with asymptomatic carriers.

• Clinical outcomes showed a 2.25-point improvement in mFARS, surpassing the 1.5-point improvement seen with the approved comparator.

• Additional functional measures (activities of daily living, nine-hole peg test, fatigue scale) also improved compared to reference populations.

• Breakthrough Therapy designation granted based on these data.

Biomarker strategy and mechanistic validation

• Frataxin measured in skin and buccal cells due to strong correlation with disease burden and feasibility of frequent sampling.

• Animal studies confirmed proportional increases in frataxin across key tissues (heart, skeletal muscle, dorsal root ganglion) and correlation with skin/buccal levels.

• Lipid biomarker analysis showed dose-dependent normalization of triglyceride profiles, correlating with frataxin increases.

• Dose-response observed across multiple efficacy and biomarker metrics, supporting 50 mg as the target dose.