The FDA has placed a phase 1 trial of Neumora Therapeutics’ schizophrenia therapy on hold after preclinical data revealed rabbits dosed with the drug had experienced convulsions.
So far, 30 healthy adult humans have been dosed with NMRA-266, a positive allosteric modulator of the M4 muscarinic receptor, as part of the single and multiple-ascending-dose phase 1 study. None of these patients have shown any evidence of convulsions, Neumora stressed.
The biotech said it’s “working with the FDA to resolve the clinical hold” and will provide an update when available.
The company has been developing NMRA-266 as a potential treatment for schizophrenia and other neuropsychiatric disorders. A readout from the phase 1 trial had been penciled in for 2024, while a separate phase 1b study in patients with schizophrenia had been expected to kick off in the second half of the year.
“We are disappointed with the unanticipated safety findings in rabbits and are discussing next steps with the FDA,” CEO Henry Gosebruch said in the April 15 release. “In parallel, we’re continuing to make significant progress across the rest of our portfolio as we seek to fulfill our mission to develop medicines for serious brain diseases.”
Neumora may have been one of the few biotech IPO success stories of 2023, but this isn’t first time that its therapies have run into trouble with the FDA. The company previously culled its obstructive sleep apnea prospect NMRA-094, which it acquired in its Alairion takeover, based on FDA feedback.
A phase 1 trial of its V1aR antagonist NMRA-511 was also initially placed on partial clinical hold by the regulator over dose-limiting toxicities including tremor and convulsions.
NMRA-511 is now in the clinic, and Gosebruch name-checked the drug in today’s release along with the company’s lead asset, navacaprant, which is in a late-stage trial for major depressive disorder.
“We anticipate several important milestones including phase 3 data in major depressive disorder and the initiation of a phase 2 study in bipolar depression with navacaprant, our kappa opioid receptor antagonist, and the initiation of a phase 1b study in agitation in Alzheimer’s disease with NMRA-511, our vasopressin 1a receptor antagonist,” the CEO said in this morning’s statement.
Despite Gosebruch’s promise of more positive news to come, investors sent Neumora’s stock down 13% to $11.84 in premarket trading Monday from a Friday closing price of $13.56.
The company brought in $250 million from its IPO back in September 2023, when it debuted at $17 per share.
William Blair analysts said the hold would set NMRA-266 even further behind Karuna’s much-hyped schizophrenia treatment KarXT—which was recently acquired by Bristol Myers Squibb—and Neurocrine’s M4 agonist NBI-1117568.
“While the hold may be addressable and the company has backup compounds in the event it is not, ultimately the largest area of investor focus remains the company’s lead program navacaprant,” the analysts added in an April 15 note.