8-K: Larimar Therapeutics Announces Positive Phase 2 Results for Nomlabofusp in Friedreich's Ataxia

Larimar Therapeutics reported positive top-line data from its Phase 2 dose exploration study of nomlabofusp, showing dose-dependent increases in frataxin levels in patients with Friedreich's ataxia.

Summary

• Larimar Therapeutics announced positive results from a Phase 2 study of nomlabofusp in patients with Friedreich's ataxia.
• The study showed that nomlabofusp increased frataxin (FXN) levels in skin and buccal cells in a dose-dependent manner.
• Patients in the 50 mg cohort, who had baseline FXN levels less than 17% of healthy volunteers, achieved levels greater than 33% after 14 days of daily treatment, with some reaching over 50%.
• The company has initiated an open-label extension (OLE) study with a 25 mg daily dose, with initial data expected in Q4 2024.
• Larimar is in discussions with the FDA regarding the use of tissue FXN levels as a surrogate endpoint for accelerated approval, targeting a Biologics License Application (BLA) submission in the second half of 2025.
• As of December 31, 2023, the company had approximately $86.8 million in cash, cash equivalents, and marketable securities, expected to provide runway into the first quarter of 2025.

Sentiment

Score: 8

Explanation: The document presents positive clinical trial results, a clear regulatory pathway, and a strong financial position, indicating a favorable outlook for the company and its lead drug candidate.

Positives

• The Phase 2 study showed significant dose-dependent increases in frataxin levels in both skin and buccal cells.
• Nomlabofusp was generally well-tolerated with no serious adverse events reported in the 50 mg cohort.
• The initiation of the open-label extension study provides an opportunity to gather long-term safety and efficacy data.
• Discussions with the FDA regarding the use of tissue FXN levels as a surrogate endpoint could lead to accelerated approval.
• The company has a strong cash position of $86.8 million, providing financial stability for ongoing development.

Negatives

• One severe adverse event, an allergic reaction, was reported in the 25 mg cohort, though it resolved with standard treatment.
• There was higher variability in FXN levels measured in buccal cells compared to skin cells.
• The reported cash balance is an unaudited, preliminary amount and may change after the completion of financial closing procedures.
• The company is still under a partial clinical hold which requires FDA review of clinical data before initiating additional US clinical trials.

Risks

• The actual financial results for the year ended December 31, 2023, may differ materially from the preliminary estimate.
• The FDA may not ultimately agree with Larimar's nomlabofusp development strategy or the use of tissue FXN levels as a surrogate endpoint.
• The company's ability to obtain regulatory approvals for nomlabofusp and future product candidates is not guaranteed.
• There is a risk that the company may not be able to raise the necessary capital to conduct its product development activities.
• The company is still under a partial clinical hold which requires FDA review of clinical data before initiating additional US clinical trials.

Future Outlook

The company expects the current cash balance to provide runway into the first quarter of 2025. They are planning a confirmatory study and targeting a BLA submission in the second half of 2025. The company also plans to expand the clinical program to ex-US geographies.

Management Comments

• We believe the dose-response and increases in FXN levels seen in peripheral tissues further reinforce the therapeutic potential of nomlabofusp to address FXN deficiency, the known root cause of disease in patients with FA, said Carole Ben-Maimon, MD, President, and Chief Executive Officer of Larimar.
• We intend to pursue an accelerated approval using FXN levels, supportive pharmacodynamics and clinical information, and safety data from the OLE study, along with additional nonclinical pharmacology information needed to support the novel surrogate endpoint approach.
• These promising Phase 2 dose exploration data further expand our nomlabofusp safety database and strengthen clinical support for the generally well tolerated profile and low discontinuation rates seen across studies, said Dr. Russell Clayton, Chief Medical Officer of Larimar.

Industry Context

This announcement is significant in the context of Friedreich's ataxia, a rare disease with limited treatment options. The positive Phase 2 results for nomlabofusp, a potential protein replacement therapy, could represent a major advancement in addressing the underlying cause of the disease. The company is also pursuing an accelerated approval pathway which could bring the treatment to market faster.

Comparison to Industry Standards

• The current standard of care for Friedreich's ataxia does not address the underlying frataxin deficiency, making nomlabofusp a potentially groundbreaking therapy.
• Omaveloxolone (SKYCLARYS) by Reata Pharma/Biogen is an approved treatment for FA, but it works by modifying mitochondrial oxidative stress, not by directly increasing frataxin levels like nomlabofusp.
• Other companies like PTC Therapeutics and Design Therapeutics are exploring different approaches, such as 15-Lipoxygenase inhibitors and gene expression regulators, respectively, but these are still in earlier stages of development.
• Lexeo Therapeutics is developing a gene therapy for FA, which is a different approach than protein replacement therapy.
• The results from the Phase 2 study of nomlabofusp show a clear dose-response relationship and significant increases in frataxin levels, which is a key differentiator compared to other treatments in development.

Stakeholder Impact

• Shareholders: The positive clinical trial results and regulatory progress are likely to be viewed favorably by investors.
• Patients: The potential for a new treatment that addresses the underlying cause of Friedreich's ataxia is a significant positive development.
• Employees: The progress of the clinical program and the company's financial stability are positive for employee morale and job security.
• Suppliers: The company's ongoing clinical trials and development plans may lead to increased demand for their services.

Next Steps

• Continue the open-label extension (OLE) study with a 25 mg daily dose.
• Submit 25 mg treatment data for FDA review to potentially escalate the dose in the OLE study.
• Plan for a confirmatory study.
• Prepare for a Biologics License Application (BLA) submission targeted for 2H 2025.
• Expand the nomlabofusp clinical program to ex-U.S. geographies.

Key Dates

Keywords

nomlabofusp, Friedreichs ataxia, frataxin, FXN, clinical trial, Phase 2, open-label extension, FDA, accelerated approval, Biologics License Application, rare disease, protein replacement therapy