Larimar Therapeutics, Inc. announced positive top-line data and successful completion of its four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp (CTI-1601) in participants with Friedreich?s ataxia (FA). Nomlabofusp was generally well tolerated and demonstrated dose dependent increases in frataxin (FXN) levels in all evaluated tissues (skin and buccal cells) after daily dosing of 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts. Participants in the 25 mg (n=13) and 50 mg (n=15) cohorts were randomized 2:1 to receive subcutaneous injections of nomlabofusp or placebo.

Key Phase 2 Results · Median changes in FXN levels from baseline for the 25 mg and 50 mg cohorts of nomlabofusp · Skin cells: 2.81 pg/µg for the 25 mg cohort and 5.57 pg/µg for the 50 mg cohort · Buccal cells: 0.56 pg/µg for the 25 mg cohort and 0.72 pg/µg for the 50 mg cohort · As seen in multiple ascending dose (MAD) study, when dosing is switched to every other day, FXN levels decline from the levels achieved with daily dosing but remain above baseline. All treated patients demonstrated increases in FXN levels in skin cells and the majority of patients also demonstrated increases in FXN levels in buccal cells. At Day 14, all patients with quantifiable levels at baseline and Day 14 treated with 50 mg of nomlabofusp achieved FXN levels in skin cells greater than 33% of the average level found in healthy volunteers, and 3 of the patients achieved levels greater than 50% of the average healthy volunteer level.

While FXN levels measured in buccal cells show a high degree of correlation with FXN levels measured in skin cells, higher variability in FXN levels was seen in buccal cells compared to skin cells in both the multiple ascending dose study and the Phase 2 dose exploration study. Skin cells have a lower turnover rate and skin is a more stable tissue. The collection method for skin cells is also well-established and standardized, which provides a more reliable and reproducible measure of changes in FXN levels with treatment compared to buccal cells.

Median baseline tissue FXN levels in skin cells were 3.70 pg/µg and 2.12 pg/µg for the 25 mg and 50 mg cohorts, respectively, and in buccal cells were 1.78 pg/µg and 1.61 pg/µg for the 25 mg and 50 mg cohorts, respectively. Changes in FXN levels after nomlabofusp administration in the Phase 2 trial at day 14 (QD: once daily for 14 days) and day 28 (QOD: every other day after day 14 Key Phase 2 Pharmacokinetic and Safety Data for 25 mg and 50 mg Cohorts of Nomlabofusp. Quick absorption after subcutaneous administration of nomlabofusp with dose proportional increases in exposure were observed with increasing doses · Generally well tolerated with no serious adverse events reported · No severe adverse events in the 50 mg cohort.

One severe adverse event for an allergic reaction to the study drug was reported in the 25 mg cohort and was resolved with standard treatment · 18 of the 19 participants dosed with nomlabofusp completed the trial, with one participant in the 25 mg cohort withdrawing due to the aforementioned allergic reaction that resolved with standard treatment. Most common adverse events were mild and moderate injection site reactions. Updates on the Nomlabofusp Regulatory Pathway in FA · FDA acknowledgment that frataxin deficiency appears to be critical to the pathogenic mechanism of FA, and that there continues to be an unmet need for treatments for FA patients that address the underlying disease pathophysiology.

Ongoing discussions with the FDA on evidence needed to support an accelerated approval application, including supplementary nonclinical pharmacology investigations, FXN, supportive PD and clinical outcomes information from the OLE study, and additional clinical safety data. Initiation of a confirmatory study planned prior to BLA submission. Potential BLA submission targeted for 2H 2025.