Nomlabofusp (nomla) is a protein replacement therapy designed to address the deficiency of frataxin in FA. Nomlabofusp is manufactured as a cell penetrating peptide (CPP) bound to frataxin, which allows it to cross cell membranes. With the addition of a Mitochondrial Targeting Sequence, the frataxin protein enters the mitochondria, restoring the functions of frataxin in electron transport chain and energy production. It is delivered by a subcutaneous (under the skin) injection.
Larimar Therapeutics is developing nomlabofusp for FA; clinical trials of nomlabofusp are in progress. Nomlabofusp has been selected for the FDA’s START pilot program, and it has been granted Rare Pediatric Disease, Fast Track, Orphan Drug, and Breakthrough Therapy designations by the U.S. Food and Drug Administration (FDA), Orphan Drug designation by the European Commission, PRIME designation by the European Medicines Agency, and Innovative Licensing and Access Pathway designation from the UK’s Medicines and Healthcare Products Regulatory Agency.
On March 20, 2026, Russell Clayton, DO, Chief Medical Officer at Larimar Therapeutics, shared updates about the nomlabofusp clinical program including information about opportunities for children, adolescents, and adults to enroll in the open label study as well as the upcoming phase 3 study.
The drug development process can be thought of as a series of stages, and successful drugs must pass through each stage to become available to patients.
Dr. Mark Payne, a physician and researcher at Indiana University, first described the potential for a frataxin replacement therapy using TAT-Frataxin and led its early development as a treatment for FA. This approach combines a recombinant fusion frataxin protein with a Mitochondrial Targeting Sequence (MTS) and is partnered with a cell-penetrating delivery system (a protein fragment called a Trans-Activator of Transcription or TAT), which helps get the frataxin protein into the cell and ultimately to the mitochondria.
Dr. Payne has tested TAT-frataxin in FA mice and demonstrated proof of principle and compelling results. (See publication below).
Dr. Payne demonstrated that TAT-frataxin increases the life span and weight of FA mice and improves their cardiac function. Dr. Payne formed a company, Chondrial Therapeutics, to further develop this approach and generate preclinical data. Chondrial is now Larimar Therapeutics.
In 2016, Chondrial Therapeutics announced that its lead drug candidate, TAT-Frataxin (TAT-FXN; then called CTI-1601; now called nomlabofusp), was accepted into the National Center for Advancing Translational Sciences’ (NCATS) Therapeutics for Rare and Neglected Diseases (TRND) program. Support from the program provided additional expertise and resources to complete IND-enabling studies and advance nomlabofusp into Phase I clinical testing.
In 2025, Larimar Therapeutics published data demonstrating that frataxin delivered by nomlabofusp is detected in the mitochondria in cells in culture. Mature frataxin, which is thought to be an active form of the protein, was found in the cells. In addition, buccal swap samples from people in the Phase I clinical trial who received nomlabofusp, showed increases in mature frataxin levels along with changes in gene expression post-administration suggesting the drug was active in cells following dosing. Together, these results demonstrate that nomlabofusp enters the cell and localizes to the mitochondria.
In a second publication, Larimar Therapeutics reported data on mouse studies aimed at understanding where the drug distributes in the body. The data suggest that following subcutaneous administration in mice, nomlabofusp distributes in a dose-dependent way to several organs including the dorsal root ganglion, heart, and skeletal muscle. Plasma nomlabofusp concentrations correlated with levels of human frataxin delivered by nomlabofusp into mouse tissues, and the increases in frataxin were correlated amongst tissues, especially with skin. Data from rats and monkeys were also included in the paper. These data are important because they support the use of skin frataxin levels following dosing with nomlabofusp as a way to understand the distribution of the drug in other parts of the body.
In February 2017, Chondrial Therapeutics announced that it secured up to $22.6 million in Series A financing with plans to file an IND application for CTI-1601 (TAT-FXN, now known as nomlabofusp) with FDA in order to initiate Phase 1 clinical trials of the compound.
Chondrial Therapeutics also received Orphan Drug Designation for CTI-1601.
The Phase I clinical program for nomlabofusp (formerly CTI-1601) included single and multiple ascending dose studies in people with Friedreich’s ataxia.
In 2021, Larimar reported that nomlabofusp was generally well tolerated at doses up to 100 mg daily for 13 days and produced more than a two-fold increase in frataxin levels in blood, buccal cells, and skin at the 50 mg and 100 mg dose levels. The results supported continued clinical development and represented the first clinical evaluation of a frataxin replacement therapy in FA.
In 2025, Larimar completed a pharmacokinetic study in adolescents with FA to support pediatric development.
Prior to dosing any patients in the Phase II trial, the FDA placed a clinical hold on the program due to non-human primate deaths at the highest dose levels. After data analysis and continued dialogue with FDA, the hold was partially lifted in September 2022, allowing the company to begin the placebo-controlled Phase II dose exploration study of nomlabofusp in people with FA. By May 2024, the FDA removed the partial hold entirely. The study evaluated safety, tolerability, pharmacokinetics, and changes in frataxin levels at 25 mg and 50 mg dose levels.
In February 2024, Larimar Therapeutics reported dose-dependent increases in skin frataxin, including a 33% increase at 25 mg and a 59% increase at 50 mg after 14 days of dosing. Buccal cell frataxin also increased, though results were more variable. These data supported continued development and selection of 50 mg daily, or the weight-based equivalent, for ongoing studies.
Participants continue to be followed in an open-label study evaluating longer-term safety and frataxin changes. Larimar Therapeutics has reported sustained increases in skin frataxin, along with positive directional trends on clinical measures compared with outcomes observed in a FA-COMS natural history reference population. The program has also identified anaphylaxis as a potential risk, and Larimar has amended the study protocol to include measures intended to reduce allergic reactions. It has also been amended to include eligible adolescent and adult patients who have not participated in a prior nomlabofusp study.
In June 2026, Larimar Therapeutics announced that the first module of a rolling Biologics License Application (BLA) has been submitted to the FDA.
Larimar Therapeutics has announced plans for a global confirmatory Phase III study. Dosing of the first patient in this study is expected Q3 2026. Dr. Rusty Clayton shared additional information about this planned study in a March 2026 webinar, which can be viewed here.
