Larimar Therapeutics, Inc. announced preliminary top-line data from the 25 mg cohort of its Phase 2, four-week, placebo-controlled, dose exploration trial of CTI-1601 in participants with Friedreich's ataxia (FA). Participants in the trial's 25 mg cohort (n=13) were randomized to receive subcutaneous injections of 25 mg CTI-1601 (n=9) or placebo (n=4) daily for 14 days and then every-other-day thereafter until day 28. Data from the cohort indicate CTI-1601 was generally well tolerated and showed increases in frataxin (FXN) levels from baseline compared to placebo in all evaluated tissues (skin and buccal cells) at day 14.

In skin, a median placebo-adjusted increase from baseline of 3.5 pg/µg in frataxin levels was observed on day 14 (frataxin concentration normalized to total protein). Of the seven CTI-1601-treated participants with quantifiable levels of frataxin in skin at both baseline and day 14, all seven had increases in skin frataxin concentrations, compared to none of the four placebo participants with quantifiable levels of frataxin in skin at both baseline and day 14. In buccal cells, a median placebo-adjusted increase from baseline of 0.9 pg/µg in frataxin levels was observed on day 14 (frataxin concentration normalized to total protein).

Of the seven CTI-1601-treated participants with quantifiable levels of frataxin in buccal cells at both baseline and day 14, five had increases in buccal cell frataxin concentrations, compared to neither of the two placebo participants with quantifiable levels of frataxin in buccal cells at both baseline and day 14. In a non-interventional study that used the same sampling technique and assay as Larimar's Phase 2 trial to measure frataxin levels in 60 homozygous healthy volunteers, median frataxin concentrations observed in skin and buccal cells were 16 pg/µg and 8 pg/µg, respectively (frataxin concentration normalized to total protein). Larimar therefore estimates phenotypically healthy heterozygous carriers of the FA-causing gene to have median frataxin concentrations of approximately 8 pg/µg and 4 pg/µg in skin and buccal cells, respectively, based on published literature indicating heterozygous carriers have frataxin levels that are approximately 50% of those of homozygous healthy people.

Larimar's Phase 2 data and non-interventional study results follow Phase 1 data that showed dose-dependent increases in frataxin levels in peripheral tissue with daily dosing of 50 and 100 mg of CTI-1601 for at least 7 days, and no detectable increase in FXN levels with daily dosing of 25 mg of CTI-1601 for only 4 days. Larimar has submitted the data from the trial's 25 mg cohort to FDA and has a meeting scheduled with the Agency for later this quarter to discuss the information needed to gain clearance to initiate a 50 mg cohort in the Phase 2 trial. Pharmacokinetic data suggest that steady state was achieved by day 14 in the Phase 2 trial's 25 mg cohort, which was the last day of daily dosing.

Safety data indicate that CTI-1601 was generally well tolerated in the Phase 2 trial's 25 mg cohort. A summary of safety data from the cohort is shown below: No serious adverse events were reported, No important medical events were reported, One severe adverse event was reported, which was an allergic reaction to study drug that resolved with standard treatment, Of the nine participants dosed with CTI-1601, eight completed the trial, with one participant withdrawing due to the aforementioned allergic reaction that resolved with standard treatment, The most common adverse events were mild and moderate injection site reactions. At least one injection site reaction was seen in two of four placebo treated participants and in all CTI-1601 treated participants.