Larimar Therapeutics Shares New Phase 1 and Phase 2 Data on Nomlabofusp at ICAR 2024

Larimar Therapeutics, a clinical-stage biotechnology company, recently showcased data from their Phase 1 and Phase 2 studies of nomlabofusp at the International Congress for Ataxia Research (ICAR) in London. The studies involved 61 adults with Friedreich’s ataxia (FA) and examined the effects of subcutaneous administration of nomlabofusp in doses ranging from 25 to 100 mg over a short-term period of up to 28 days. The data was presented in three separate posters during the conference.

Dr. Carole Ben-Maimon, President and CEO of Larimar, highlighted the potential of nomlabofusp in reaching tissue FXN levels in patients comparable to those in asymptomatic heterozygous carriers. She pointed out that gene expression and lipid profiles in study participants showed improvements that aligned more closely with those seen in healthy individuals. This indicates that nomlabofusp can positively impact disrupted metabolic pathways in FA patients.

Dr. Ben-Maimon also emphasized the importance of considering comprehensive data as the nomlabofusp program progresses. The studies have shown dose-dependent increases in tissue FXN levels, gene expression, and lipid profiles. Larimar plans to expand their studies to include children and adolescents, starting with a pediatric pharmacokinetic (PK) trial. They are also conducting an open-label extension study to gather long-term safety, PK, and FXN data, which could support an accelerated approval using FXN levels as a novel surrogate endpoint. The company aims to submit a Biologics License Application (BLA) by the second half of 2025, with a program update anticipated in mid-December 2024.

Dr. Rusty Clayton, Larimar's Chief Medical Officer, expressed satisfaction with the consistency of the relationships between tissue FXN levels and disease characteristics in FA patients across their studies. The data supports the dose prediction modeling used to select appropriate nomlabofusp doses for patients of various ages and baseline characteristics. Larimar plans to refine this model with upcoming pediatric PK study data and long-term data from the ongoing open-label study. The initial results from the Phase 2 study showed encouraging trends towards normalizing gene expression and lipid profiles in FA patients, compared to healthy volunteers.

Friedreich’s ataxia is a neurodegenerative disorder caused by GAA repeats in the FXN gene, leading to FXN deficiency. The number of GAA repeats correlates with disease characteristics, such as age of onset and rate of progression. The data presented at ICAR detailed the FXN levels and disease characteristics of adult participants in the nomlabofusp studies, which were reflective of the broader FA population.

Research showed that lower tissue FXN levels were associated with younger onset and more severe disease progression. Baseline buccal cell FXN levels correlated with baseline skin cell FXN levels in study participants, consistent with previous studies. Larimar used these baseline levels to predict potential skin FXN level increases following nomlabofusp administration.

Short-term administration of nomlabofusp resulted in dose-dependent increases in skin FXN levels among adults with FA. Long-term daily administration of 50 mg is predicted to raise FXN levels to over 50% of those in healthy controls, a level similar to that in asymptomatic carriers. Larimar plans to optimize this prediction model with data from ongoing studies and upcoming pediatric trials.

The studies also explored the effects of nomlabofusp on plasma lipid profiles and tissue gene expression in FA patients. FA patients typically show metabolic dysfunction and abnormal gene and lipid profiles due to FXN deficiency. Preliminary analysis indicated improvements in gene expression and lipid profiles post-treatment, trending towards values seen in healthy individuals. Further evaluation is ongoing, including assessments following long-term administration in the open-label extension study.

Larimar Therapeutics is dedicated to developing treatments for rare diseases, with nomlabofusp being their lead compound for Friedreich’s ataxia. The company is also leveraging its platform to create fusion proteins targeting other rare diseases characterized by deficiencies in intracellular bioactive compounds.