In dose-ranging studies for Larimar Therapeutics’ experimental treatment for the rare neuromuscular disorder Friedreich’s ataxia, no problems were observed in patients other than mild to moderate reactions at the injection site. But an undisclosed number of monkeys have died in an ongoing toxicology study, and the FDA has placed a clinical hold on the entire program until the agency gets answers why.
The clinical hold means that Bala Cynwyd, Pennsylvania-based Larimar can’t proceed with further tests of the drug, CTI-1601, in humans, including a study designed that was expected to start in the second half of this year to gather more long-term data about the therapy. It also scuttles an agreement for a $95 million private financing, which the publicly traded company announced last week to fund that clinical research.
In a prepared statement, President and CEO Carole Ben-Maimon said Larimar believes there is a path forward for CT1-1601, the company’s only program. But she added that responding to the clinical hold could push resumption of clinical testing into next year.
Shares of Larimar opened Wednesday at $7.90 apiece, down 41.5% from Tuesday’s closing stock price.
Friedreich’s ataxia is an inherited disorder caused by a mutation to the gene that codes for frataxin, a protein that is essential for the proper function of mitochondria, the energy-producing components of cells. Without sufficient frataxin, nerve and heart cells begin to degenerate. The disease, which leads to lack of muscle coordination and heart problems, has no FDA-approved therapies.
CTI-1601 is a fusion protein engineered to deliver human frataxin into the mitochondria of Friedreich’s ataxia patients. Larimar has advanced the program to Phase 1 tests that evaluated a single dose and multiple ascending doses of the drug over the course of about 10 weeks. Larimar said that the dose-ascending study showed that daily subcutaneous injections of CTI-1601, at 50 mg and 100 mg doses, produced frataxin levels in peripheral tissues that were at the same levels or greater than what would be expected in those who appear to be normal.
At the same time that Larimar conducted the Phase 1 tests of CTI-1601, the company was also testing its drug in a non-human primate toxicology study. The 180-day study was designed to support extended dosing of patients. Larimar had previously notified the FDA of the monkey deaths, which the company said occurred at the highest dose. According to Larimar, the FDA’s clinical hold letter said that the agency needs to see a full study report from that monkey study. Furthermore, Larimar may not start additional clinical research of its drug until the FDA has reviewed that report and cleared the company to resume testing.
CTI-1601 employs proprietary Larimar technology that enables a therapeutic molecule to cross a cell membrane in order to reach targets inside of a cell. That technology is based on research licensed from Indiana University and Wake Forest University. Though CTI-1601 is the only drug currently in the Larimar pipeline, the company has said it plans to use the platform technology to deliver frataxin or other molecules to targets inside of cells as a way of treating more rare diseases. But that ambition is tempered by a caveat stated in Larimar’s 2020 annual report.
“If CTI-1601 proves to be ineffective, unsafe or commercially unviable, it is possible that our platform and pipeline would have little, if any, value, which would substantially harm our business, financial condition, results of operations and prospects,” the company said.
Larimar was initially named Chondrial Therapeutics. That company went public in 2018 by combining operations with Zafgen, a Boston-based biotech that had its own stumbles, including clinical holds, before exploring the strategic alternatives that led to the reverse merger. The combined company took the name Larimar Therapeutics, a reference to the rare larimar gemstone that Ben-Maimon said was a fitting name for a rare disease company.
With Larimar’s private financing agreement now terminated, the company must continue operations with the cash it has on hand. As of the end of the first quarter of this year, Larimar reported having $81.4 million in cash and investments, which it estimates should last through the first half of next year.
Photo: Streeter Lecka, Getty Images
