Neumora Therapeutics Announces Clinical Hold of Phase 1 NMRA-266 Study
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- The Phase 1 trial of NMRA-266 has been placed on clinical hold due to safety concerns in rabbits, potentially impacting the Company's pipeline and future developments.
Insights
The announcement of a clinical hold by the FDA on Neumora Therapeutics' Phase 1 NMRA-266 study has immediate ramifications for the company's stock performance and investor confidence. This news interrupts the usual trajectory of drug development, whereby successful phase trials are critical milestones that typically bolster market valuations. The fact that NMRA-266 is a positive allosteric modulator of the M4 muscarinic receptor, a target potentially significant in the treatment of brain diseases, further heightens interest in the drug's journey through the clinical process.
Investors are likely to react to the halt in the study with caution, as the safety of NMRA-266 is now under scrutiny. Given the innovative nature of the company's M4 PAM franchise, setbacks like these could have a chilling effect on both short-term and long-term prospects if the issues are not swiftly and satisfactorily resolved.
From a portfolio diversification standpoint, the mention of Neumora's other novel compounds within the M4 franchise is a mitigating factor. The advancement of these other compounds and upcoming milestones in different programs could provide alternative paths for growth, potentially offsetting the negative impact of NMRA-266's clinical hold.
The FDA's decision to impose a clinical hold based on pre-clinical data showing convulsions in rabbits is a serious safety concern and reflects the rigorous regulatory environment governing clinical trials. It speaks to the scrutiny over novel pharmacological treatments, particularly in the realm of brain diseases where the therapeutic window is often narrow.
In discussing the safety profile of NMRA-266, it's important to highlight that while no convulsions were observed in the 30 participants dosed, pre-clinical animal studies are a important component of safety assessment. They can often predictive of potential adverse effects in humans. Without available details on the convulsions seen in rabbits and the degree of translatability to humans, the long-term impact on NMRA-266's development timeline is difficult to ascertain, but it is likely to be delayed.
The company's engagement with the FDA to resolve this hold indicates a proactive approach, which may mitigate some concerns from stakeholders. However, the reversal of the hold and continuation of the study will depend on the ability to demonstrate that the benefits outweigh the risks, which may involve additional studies or modifications to the trial protocol.
Positive allosteric modulators, like NMRA-266, enhance the activity of receptors such as the M4 muscarinic receptor, which is implicated in numerous central nervous system disorders. The specificity and potential therapeutic advantages of targeting the M4 muscarinic receptor make this a promising area of drug development. However, the occurrence of convulsions in animal models is a substantial concern, as it suggests potential central nervous system toxicity that could pose serious risks to patients.
Despite no evidence of convulsions in human subjects to date, the FDA's conservative stance is consistent with its mandate to ensure public safety. This event underscores the importance of rigorous pre-clinical testing and could prompt a review of the safety profiles of similar compounds within the M4 PAM franchise.
The clinical hold serves as a reminder of the complexity and unpredictability inherent to drug development, particularly within the CNS therapeutic area, where side effects can be particularly severe. Ensuring the safety of the compounds through further pre-clinical safety and toxicology work is paramount for Neumora, as it remains committed to an IND submission in 2025 for other compounds in its portfolio.
WATERTOWN, Mass., April 15, 2024 (GLOBE NEWSWIRE) -- Neumora Therapeutics, Inc. (Nasdaq: NMRA), a clinical-stage biopharmaceutical company with a therapeutics pipeline consisting of seven clinical and pre-clinical brain disease programs, today announced that the Phase 1 trial of NMRA-266 has been placed on clinical hold by the U.S. Food and Drug Administration (FDA). NMRA-266 is a positive allosteric modulator (PAM) of the M4 muscarinic receptor and is part of the Company’s M4 PAM franchise. The clinical hold determination follows recently available pre-clinical data showing convulsions in rabbits.
Following this action, the Phase 1 single ascending dose / multiple ascending dose study with NMRA-266 has been paused. Approximately 30 participants have been dosed in the Phase 1 study, with no evidence of convulsions observed in any participant.
Neumora is working with the FDA to evaluate the potential to resolve the clinical hold. While these discussions with the Agency are ongoing, the Company’s prior guidance regarding NMRA-266 is no longer applicable. Neumora will provide an update on NMRA-266 when available.
Neumora’s M4 franchise includes multiple novel compounds beyond NMRA-266 that each have different properties and chemical composition. These compounds demonstrated robust activity in preclinical efficacy models, as well as high selectivity for the M4 receptor subtype and the potential for an oral once-daily dosing profile. Neumora is advancing pre-clinical safety and toxicology work with these compounds and expects to submit an IND in 2025.
“We are disappointed with the unanticipated safety findings in rabbits and are discussing next steps with the FDA,” said Henry Gosebruch, president and chief executive officer, Neumora. “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. 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.”
About Neumora
Neumora Therapeutics, Inc. is a clinical-stage biopharmaceutical company founded to confront the global brain disease crisis by taking a fundamentally different approach to the way treatments for brain diseases are developed. Our therapeutic pipeline currently consists of seven clinical and preclinical neuroscience programs that target novel mechanisms of action for a broad range of underserved neuropsychiatric disorders and neurodegenerative diseases. Our work is supported by an integrated suite of translational, clinical, and computational tools to generate insights that can enable precision medicine approaches. Neumora’s mission is to redefine neuroscience drug development by bringing forward the next generation of novel therapies that offer improved treatment outcomes and quality of life for patients suffering from brain diseases.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements about Neumora Therapeutics, Inc. (the “Company,” “we,” “us,” or “our”) within the meaning of the federal securities laws, including statements related to: Neumora’s intention to redefine neuroscience drug development by bringing forward the next generation of novel therapies that offer improved treatment outcomes and quality of life for patients suffering from brain diseases; the timing, progress and plans for its therapeutic development programs, including the timing of initiation and data read outs for its programs and studies, as well as its clinical trial and development plans; Neumora’s ability to work with the FDA to resolve the clinical hold; the potential for Neumora to advance other compounds in its M4 portfolio; the oral one-daily dosing potential of any M4 compounds; the timing and potential for any INDs in Neumora’s M4 portfolio; and; other statements identified by words such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negatives of those terms. Other than statements of historical facts, all statements contained in this press release, are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These statements are subject to risks and uncertainties that could cause the actual results or to be materially different from the information expressed or implied by these forward-looking statements, including, among others: the risks related to the inherent uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals; risks related to the timely initiation and enrollment in our clinical trials; risks related to our reliance on third parties, including CROs; risks related to serious or undesirable side effects of our therapeutic candidates; risks related to our ability to utilize and protect our intellectual property rights; and other matters that could affect sufficiency of capital resources to fund operations. For a detailed discussion of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Neumora’s business in general, please refer to the risk factors identified in the Company’s filings with the Securities and Exchange Commission (SEC), including but not limited to its Annual Report on Form 10-K for the year ended December 31, 2023 that was filed with the SEC on March 7, 2024. Forward-looking statements speak only as of the date hereof, and, except as required by law, Neumora undertakes no obligation to update or revise these forward-looking statements.
Neumora Contact:
Helen Rubinstein
315-382-3979
Helen.Rubinstein@neumoratx.com
FAQ
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