8-K: Larimar Therapeutics Doses First Patient in Nomlabofusp Long-Term Extension Study, Targets Accelerated Approval

Larimar Therapeutics has dosed the first patient in its open-label extension study of nomlabofusp for Friedreich's ataxia, aiming for accelerated approval based on frataxin levels.

Summary

• Larimar Therapeutics has initiated an open-label extension (OLE) study for nomlabofusp (CTI-1601), a protein replacement therapy for Friedreich's ataxia (FA).
• The first patient has been dosed with 25 mg daily subcutaneous injections of nomlabofusp.
• The OLE study will assess long-term safety, tissue frataxin levels, and real-life self-administration of the drug.
• Participants from previous Phase 1 and Phase 2 trials are eligible for the OLE study.
• The company intends to use frataxin levels as a surrogate endpoint to support accelerated approval.
• Initial data from the OLE study is expected in the fourth quarter of 2024.
• A Biologics License Application (BLA) submission for accelerated approval is targeted for the second half of 2025.
• The company has completed a Phase 2 dose exploration study showing dose-dependent increases in frataxin levels.
• Larimar has a strong IP portfolio with a composition of matter patent extending to 2040.
• The company estimates a cash runway into 2026, supported by $86.8 million at the end of 2023 and $161 million from a February 2024 public offering.

Sentiment

Score: 8

Explanation: The document is generally positive, highlighting the initiation of the OLE study, promising Phase 2 data, and a clear path towards accelerated approval. The company also has a strong cash position. However, the partial clinical hold and some adverse events temper the overall sentiment slightly.

Positives

• The initiation of the OLE study is a significant step in the development of nomlabofusp.
• The company is targeting accelerated approval based on frataxin levels, which could expedite the drug's availability.
• Phase 2 data demonstrated dose-dependent increases in frataxin levels, a key indicator of the drug's effectiveness.
• Nomlabofusp has been generally well-tolerated in clinical trials.
• The company has a strong cash position, providing financial stability for ongoing development.
• The company has a strong IP portfolio with a composition of matter patent extending to 2040.

Negatives

• The company is still under a partial clinical hold, requiring FDA review of data to escalate the dose in the OLE study.
• There was one severe adverse event in the Phase 1 and Phase 2 studies, an allergic reaction that resolved with standard treatment.
• There was one Phase 2 participant in the 25 mg cohort who withdrew due to an allergic reaction.
• There was one Phase 1 participant in the 50 mg cohort who withdrew due to mild-to-moderate nausea and vomiting.

Risks

• The FDA may not agree with Larimar's development strategy for nomlabofusp.
• Clinical trial results may differ from preliminary data.
• The company's ability to obtain regulatory approvals 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, requiring FDA review of data to escalate the dose in the OLE study.

Future Outlook

The company plans to pursue accelerated approval for nomlabofusp, with a BLA submission targeted for the second half of 2025. They also plan to expand the clinical program to ex-US geographies and include pediatric patients in future studies.

Management Comments

• We are pleased to dose the first patient in our OLE study, further advancing the nomlabofusp clinical program and building on the successful completion of our Phase 2 dose escalation study, said Carole Ben-Maimon, MD, President, and Chief Executive Officer of Larimar.
• Based on our Phase 1 and Phase 2 findings, we expect to continue daily dosing throughout the study, said Carole Ben-Maimon, MD, President, and Chief Executive Officer of Larimar.

Industry Context

The announcement is significant in the context of Friedreich's ataxia, a rare disease with limited treatment options. Larimar's approach of directly addressing frataxin deficiency is a novel strategy compared to other treatments that focus on symptom management or other pathways. The company is positioning itself as a potential leader in this space.

Comparison to Industry Standards

• Larimar's nomlabofusp is a protein replacement therapy, which is a different approach than Reata Pharma/Biogen's Omaveloxolone (SKYCLARYS), an Nrf2 activator, which is already approved for FA.
• PTC Therapeutics' Vatiquinone is a 15-Lipoxygenase Inhibitor in Phase III trials, while Design Therapeutics' DT-216 is a GeneTAC in Phase I, and Lexeo Therapeutics' LX2006 and Voyager/Neurocrine's gene therapies are also in early stages of development.
• Nomlabofusp aims to directly increase frataxin levels, which is a key differentiator from other therapies that do not address the underlying cause of FA.
• The company's Phase 2 results showing dose-dependent increases in frataxin levels are promising compared to the lack of such data from other companies.

Stakeholder Impact

• Shareholders: The positive clinical trial progress and financial stability are likely to be viewed favorably.
• Patients: The initiation of the OLE study and the potential for accelerated approval offer hope for a new treatment option.
• Employees: The company's progress and financial health provide job security and opportunities for growth.
• Investors: The company's progress and financial health provide a positive outlook for investment.

Next Steps

• Continue the open-label extension study with 25 mg daily dosing.
• Submit data from the 50 mg cohort of the Phase 2 study and available data from the OLE study for FDA review to potentially escalate the dose.
• Report initial data from the OLE study in Q4 2024.
• Present final Phase 2 data at a conference in the second half of 2024.
• Submit a Biologics License Application (BLA) for accelerated approval in the second half of 2025.
• Expand the clinical program to ex-US geographies.
• Include pediatric patients in future clinical trials.

Key Dates

Keywords

nomlabofusp, Friedreich's ataxia, frataxin, clinical trial, protein replacement therapy, accelerated approval, FDA, biotechnology, rare disease, open-label extension