BALA CYNWYD, Pa. — Larimar Therapeutics, Inc. (“Larimar”) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, 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.
“Our preliminary Phase 2 data provide the first clinical indication that a 25 mg dose of CTI-1601 can increase frataxin levels in peripheral tissues, building upon our proof-of-concept Phase 1 results,” said Carole Ben-Maimon, MD, President and Chief Executive Officer of Larimar. “Importantly, the frataxin increases achieved with a relatively low 25 mg dose in our Phase 2 trial suggest a continuous daily dosing regimen is preferred for maintaining increases achieved with 25 mg CTI-1601. I would like to thank all those who participated in our trials and look forward to our upcoming meeting with the FDA later this quarter.”
The median change from baseline in FXN levels at day 14 (last day of daily dosing) and day 28 (end of treatment and after switching to every other day dosing) in the Phase 2 trial are shown in the table below.
| TABLE 1: FXN Change from Baseline in Skin Biopsies# Units: pg FXN / μg total protein Data presented as: median (25th percentile, 75th percentile) (n) |
|||||||
| Dose Group | Day 14 | Day 28 | |||||
| Placebo | -0.66 | (-1.08, -0.37) | (n=4) | -0.30 | (-0.90, 0.77) | (n=4) | |
| 25 mg CTI-1601 | 2.81 | (2.16, 3.32) | (n=7) | 2.28 | (-0.03, 2.71) | (n=7) | |
#Day 14 and 28 skin biopsies were not collected from one CTI-1601 treated participant who discontinued treatment and one CTI-1601 treated participant had FXN levels below quantifiable levels at day 14 and day 28
| TABLE 2: FXN Change from Baseline in Buccal Cells# Units: pg FXN / μg total protein Data presented as: median (25th percentile, 75th percentile) (n) |
||||||
| Dose Group | Day 14 | Day 28 | ||||
| Placebo | -0.35 | (-0.58, -0.13) | (n=2) | 0.01 | (-0.52, 0.53) | (n=2) |
| 25 mg CTI-1601 | 0.56 | (-0.28, 0.64) | (n=7) | 0.03 | (-0.66, 0.86) | (n=6) |
# For the placebo group, one participant had buccal cell FXN levels below quantifiable levels at baseline and one participant had buccal cell FXN levels below quantifiable levels at day 14 and day 28
#For 25 mg group, day 28 buccal FXN were not collected from one participant who discontinued treatment and two participants had buccal FXN levels below quantifiable levels at baseline
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.
Dr. Ben-Maimon added, “Our Phase 2 results add to our safety database indicating that CTI-1601 is generally well tolerated. Thirty-seven adults with FA have been dosed with CTI-1601 across our Phase 1 and 2 trials, with 35 completing treatment, one withdrawing due to an allergic reaction, and another withdrawing after a single 50 mg dose in the multiple ascending dose trial due to mild to moderate nausea and vomiting. We believe the safety, pharmacokinetic, and pharmacodynamic data generated to date support evaluation of a 50 mg dose of CTI-1601 in our Phase 2 trial and look forward to discussing our findings with the U.S. Food and Drug Administration (FDA) at our meeting later this quarter.”
The initiation of additional cohorts in the Phase 2 trial and/or the initiation of other clinical trials of CTI-1601 are contingent on a review of data and analyses from the Phase 2 trial’s 25 mg cohort by the FDA, in accordance with a partial clinical hold on the CTI-1601 program first put into place after a full clinical hold was lifted in September 2022. 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. Larimar expects to provide an update on the next steps for the CTI-1601 program in the third quarter of 2023, after it has received feedback from the upcoming FDA meeting.
First Quarter 2023 Financial Results
In addition to preliminary top-line data from its Phase 2 trial’s 25 mg cohort, Larimar today announced financial results for the first quarter of 2023.
As of March 31, 2023, the Company had cash and cash equivalents totaling $111.5 million.
The Company reported a net loss for the first quarter of 2023 of $6.5 million, or $0.15 per share, compared to a net loss of $8.9 million, or $0.49 per share, for the first quarter of 2022.
Research and development expenses for the first quarter of 2023 were $4.6 million compared to $5.8 million for the first quarter of 2022. The decrease in research and development expenses compared to the prior year period was primarily driven by a decrease of $0.7 million in nonclinical development costs a decrease of $0.4 million in drug manufacturing costs, and a decrease of $0.1 million in clinical trial expense.
General and administrative expenses were $3.1 million in both the first quarter of 2023 and the first quarter of 2022. Decreases in recruiting and professional service fees were offset by increases in stock-based compensation expense and other personnel-related expenses.
Conference Call and Webcast
Larimar will host a conference call and webcast today, May 15, 2023 at 8:00 a.m. ET. To access the webcast, please visit this link to the event. To participate by phone, please dial 1-877-407-9716 (domestic) or 1-201-493-6779 (international) and refer to conference ID 13738708, or click on this link and request a return call. Following the live event, an archived webcast will be available on the “Events & Presentations” page of the Larimar website.
About CTI-1601
CTI-1601 is a recombinant fusion protein intended to deliver human frataxin to the mitochondria of patients with Friedreich’s ataxia who are unable to produce enough of this essential protein. CTI-1601 has been granted Rare Pediatric Disease designation, Fast Track designation and Orphan Drug designation by the U.S. Food and Drug Administration (FDA), Orphan Drug Designation by the European Commission, and a PRIME designation by the European Medicines Agency.
About Larimar Therapeutics
Larimar Therapeutics, Inc. (Nasdaq: LRMR), is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases. Larimar’s lead compound, CTI-1601, is being developed as a potential treatment for Friedreich’s ataxia. Larimar also plans to use its intracellular delivery platform to design other fusion proteins to target additional rare diseases characterized by deficiencies in intracellular bioactive compounds. For more information, please visit: https://larimartx.com.