A Phase 2a, Randomized, Double-blind, Placebo-controlled Pilot Study to Evaluate the Effects of Oral NMRA-335140 Versus Placebo in Participants With a Major Depressive Episode Associated With Bipolar II Disorder

This is a randomized, double-blind, placebo-controlled pilot study aiming to evaluate the effects of NMRA-335140 on symptoms of major depression in adults with Bipolar (BP) II disorder. The study design consists of a Screening Period (up to 28 days), a 6-week Treatment Period (during which participants will receive either NMRA-335140 or placebo), and a 6-week Safety Follow-up Period.

Start Date13 May 2024

Sponsor / Collaborator

Neumora Therapeutics, Inc.

NCT06058039 / RecruitingPhase 3

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Oral NMRA-335140 Versus Placebo in Participants With Major Depressive Disorder

This randomized, double-blind, placebo-controlled, multicenter study will evaluate the effects of NMRA-335140 (formerly BTRX-335140) on symptoms of depression in participants with Major Depressive Disorder (MDD). The study design consists of a Screening Period (up to 35 days), and a 6-week Treatment Period (during which participants will receive either NMRA-335140 or placebo). At the completion of the 6-week Treatment Period, participants who complete the study, provide informed consent, and meet the eligibility criteria may enter an open-label extension study (NMRA-335140-501).

Start Date21 Dec 2023

Sponsor / Collaborator

Neumora Therapeutics, Inc.

NCT06058013 / RecruitingPhase 3

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Oral NMRA-335140 Versus Placebo in Participants With Major Depressive Disorder

This is a randomized, double-blind, placebo-controlled, multicenter study to evaluate the effects of NMRA-335140 (formerly BTRX-335140) on symptoms of depression in participants with Major Depressive Disorder (MDD). The study design consists of a Screening Period (up to 28 days), and a 6-week Treatment Period (during which participants will receive either NMRA-335140 or placebo). At the completion of the 6-week Treatment Period, participants who complete the study, provide informed consent, and meet the eligibility criteria may enter an open-label extension study (NMRA-335140-501).

Start Date20 Dec 2023

Sponsor / Collaborator

Neumora Therapeutics, Inc.

100 Clinical Results associated with Navacaprant

100 Translational Medicine associated with Navacaprant

100 Patents (Medical) associated with Navacaprant

Literatures (Medical) associated with Navacaprant

01 Oct 2024·JOURNAL OF AFFECTIVE DISORDERS

Preclinical and clinical efficacy of kappa opioid receptor antagonists for depression: A systematic review

Review

Author: Kwan, Angela T H ; Rosenblat, Joshua D ; Meshkat, Shakila ; Choi, Hayun ; Vasudeva, Shreya ; Ho, Roger ; Cao, Bing ; McIntyre, Roger S ; Teopiz, Kayla M ; Le, Gia Han ; Rhee, Taeho Greg ; Wong, Sabrina ; Phan, Lee

BACKGROUND:

Approximately 30 % of persons with Major Depressive Disorder (MDD) inadequately respond to conventional antidepressants. Kappa opioid receptor (KOR) antagonists, aticaprant and navacaprant, are in development as treatments for MDD. Herein, we aim to comprehensively evaluate the safety, efficacy and pharmacology of aticaprant and navacaprant for MDD.

METHODS:

We performed a systematic review of primary research investigating aticaprant and navacaprant on PubMed, OVID, and Scopus databases from inception to April 2024. Studies that reported on the pharmacological profile and/or safety and efficacy of aticaprant and navacaprant were included.

RESULTS:

Navacaprant monotherapy and aticaprant adjunctive therapy are in development for MDD. Navacaprant exhibits 300-fold selectivity for the KOR compared to the mu-opioid receptor, while aticaprant exhibits 30-fold selectivity. At clinically-relevant doses, navacaprant and aticaprant occupy 87-95 % and 73-94 % of KORs, respectively. Clinical trials of the foregoing agents (navacaprant as monotherapy and actiprant as adjunctive therapy) reported significant improvement in depressive symptoms and may clinically benefit measures of anhedonia. Both agents appear well-tolerated, with most adverse events mild and no known safety concerns.

LIMITATIONS:

Aticaprant and navacaprant treatment for MDD are in early stages of clinical trials and results from Phase 3 pivotal trials are not yet available.

CONCLUSIONS:

Kappa opioid receptor antagonists may serve as mechanistically-novel treatments for MDD and persons who inadequately respond to index conventional antidepressants. Anhedonia is debilitating and insufficiently treated with conventional antidepressants. Future research vistas should establish the efficacy and safety of KORAs in phase 3 studies in both acute and maintenance paradigms.

01 Oct 2024·NEUROPHARMACOLOGY

Navacaprant, a novel and selective kappa opioid receptor antagonist, has no agonist properties implicated in opioid-related abuse

Article

Author: Zeitz, Karla ; Van Orden, Lori Jean ; Morrison, Filomene G ; Wallace, Tanya L ; Kuijer, Eloise J ; Heal, David J ; Smith, Sharon L

Kappa opioid receptors (KORs) are implicated in the pathophysiology of various psychiatric and neurological disorders creating interest in targeting the KOR system for therapeutic purposes. Accordingly, navacaprant (NMRA-140) is a potent, selective KOR antagonist being evaluated as a treatment for major depressive disorder. In the present report, we have extended the pharmacological characterization of navacaprant by further demonstrating its selective KOR antagonist properties and confirming its lack of agonist activity at KORs and related targets involved in opioid-related abuse. Using CHO-K1 cells expressing human KOR, mu (MOR), or delta (DOR) opioid receptors, navacaprant demonstrated selective antagonist properties at KOR (IC₅₀ = 0.029 μM) versus MOR (IC₅₀ = 3.3 μM) and DOR (IC₅₀ > 10 μM) in vitro. In vivo, navacaprant (10-30 mg/kg, i.p.) dose-dependently abolished KOR-agonist induced analgesia in the mouse tail-flick assay. Additionally, navacaprant (10, 30 mg/kg, p.o.) significantly reduced KOR agonist-stimulated prolactin release in mice and rats, confirming KOR antagonism in vivo. Navacaprant showed no agonist activity at any opioid receptor subtype (EC₅₀ > 10 μM) in vitro and exhibited no analgesic effect in the tail-flick assays at doses ≤100 mg/kg, p.o. thereby confirming a lack of opioid receptor agonist activity in vivo. Importantly, navacaprant did not alter extracellular dopamine concentrations in the nucleus accumbens shell of freely-moving rats following doses ≤100 mg/kg, p.o., whereas morphine (10, 20 mg/kg, i.p.) significantly increased dopamine levels. These results demonstrate that navacaprant is a KOR-selective antagonist with no pharmacological properties implicated in opioid-related abuse.

01 Feb 2024·Anesthesiology

Opposing Effects on Descending Control of Nociception by µ and κ Opioid Receptors in the Anterior Cingulate Cortex

Article

Author: Neugebauer, Volker ; Roberts, Edward ; Navratilova, Edita ; Guerrero, Miguel ; Ji, Guangchen ; Rosen, Hugh ; Porreca, Frank ; Qu, Chaoling

Background:

The efficiency of descending pain modulation, commonly assessed with the conditioned pain modulation procedure, is diminished in patients with chronic pain. The authors hypothesized that the efficiency of pain modulation is controlled by cortical opioid circuits.

Methods:

This study evaluated the effects of µ opioid receptor activation in the anterior cingulate cortex on descending control of nociception, a preclinical correlate of conditioned pain modulation, in male Sprague-Dawley rats with spinal nerve ligation–induced chronic pain or in sham-operated controls. Additionally, the study explored the consequences of respective activation or inhibition of κ opioid receptor in the anterior cingulate cortex of naive rats or animals with neuropathic pain. Descending control of nociception was measured as the hind paw withdrawal response to noxious pressure (test stimulus) in the absence or presence of capsaicin injection in the forepaw (conditioning stimulus).

Results:

Descending control of nociception was diminished in the ipsilateral, but not contralateral, hind paw of rats with spinal nerve ligation. Bilateral administration of morphine in the anterior cingulate cortex had no effect in shams but restored diminished descending control of nociception without altering hypersensitivity in rats with neuropathic pain. Bilateral anterior cingulate cortex microinjection of κ opioid receptor antagonists, including nor-binaltorphimine and navacaprant, also re-established descending control of nociception in rats with neuropathic pain without altering hypersensitivity and with no effect in shams. Conversely, bilateral injection of a κ opioid receptor agonist, U69,593, in the anterior cingulate cortex of naive rats inhibited descending control of nociception without altering withdrawal thresholds.

Conclusions:

Anterior cingulate cortex κ opioid receptor activation therefore diminishes descending control of nociception both in naive animals and as an adaptive response to chronic pain, likely by enhancing net descending facilitation. Descending control of nociception can be restored by activation of μ opioid receptors in the anterior cingulate cortex, but also by κ opioid receptor antagonists, providing a nonaddictive alternative to opioid analgesics. Navacaprant is now in advanced clinical trials.

Editor’s Perspective:

What We Already Know about This Topic:

What This Article Tells Us That Is New:

News (Medical) associated with Navacaprant

16 Sep 2024

·www.fiercepharma.com

Bridging research and clinical care in a new era of psychiatry

None By Dr. L. Alison McInnes and Jimmy QianWe’re finally moving towards a causality-based nosology for psychiatry: specific symptoms with defined biological underpinnings can now be targeted by new therapies. But how do we bridge clinical development with real-world care? How do we ensure trial endpoints are synchronized with real-world measures, payer requirements, and clinical society guidelines? Below, we dig into the widening gap between research and clinical care. No consensus on how to measure transdiagnostic symptomsExcitingly, researchers have been able to characterize underlying neural circuitry for certain symptoms. The NIMH Fast-Fail Trials initiative, which stipulated that a drug candidate should alter a biomarker in an objectively measurable fashion, accelerated this movement. For anhedonia, investigators identified ventral striatum abnormalities during reward anticipation that normalized in response to kappa opioid receptor (KOR) antagonists. Despite this advancement, there has yet to be consensus on how to measure anhedonia in the clinic. Many clinicians do not practice measurement-based care, and even amongst those who do, measurement of anhedonia is typically confined to the first question of the PHQ-9. Moreover, anhedonia is a transdiagnostic symptom that should be measured across multiple diagnoses, not just depression.Progress has also been made in elucidating the neurocircuitry of cognition in depression. Leanne Williams’ group has identified biotypes with distinct fMRI signatures and associated cognitive abnormalities that may predict differential response to treatment. Meanwhile, Alto Neuroscience is developing cognitive profiling tools to subtype patients for enriched response to its pipeline agents. However, there is no consensus approach to measure cognition in the real-world. Furthermore, tools for characterizing cognitive deficits in depression do not necessarily capture the deficits observed in other disorders. Today, real-world clinicians often miss subtle but disabling cognitive symptoms for lack of appropriate measurement tools.Researchers have made additional advancements in precision measurement spanning EEG, fMRI, digital phenotyping, proteomics, and more. Yet as research progresses, the gap to real-world care widens. New mechanisms of action require more from cliniciansNovel mechanisms of action are also being developed, often enabling precise targeting of pharmacotherapies to specific symptoms. Continuing the anhedonia example, the phase 3 KOR antagonists aticaprant and navacaprant leverage the fact that elevated levels of dynorphin, which activates KORs, are associated with stress, anhedonia, and dysregulation of reward processing.Seltorexant, a selective orexin-2 receptor antagonist, is being studied specifically for depression with insomnia symptoms. Xanomeline-trospium, a dual M1/M4 muscarinic agonist, has shown promise in treating positive, negative, and cognitive symptoms of schizophrenia, with scientists speculating that dual agonism confers broad activity while M1 agonism may be more involved in cognitive improvements.Additional novel mechanisms are being studied or have been recently approved, spanning NMDA and AMPA receptor modulators, dual orexin receptor antagonists, 5HT2a receptor antagonists, GABAA receptor modulators, digital therapeutics, and more. New treatment options coupled with the complexity of treatment pathways and symptom clusters mean clinicians will need to know how to prioritize different mechanisms, measure success, and monitor side effects.Most patients have constellations of symptoms, so how are clinicians to make decisions about which to treat first with these targeted therapies? A hospitalist has objective physiological measures to help prioritize interventions to stabilize an inpatient; similarly, psychiatrists need novel objective measures to select the best treatment pathway for individual patients. Diagnosing and measuring previously untreatable conditions is a challengeIt is wonderful to see therapies for hitherto untreatable indications. Tardive dyskinesia is an example of a historically-neglected condition as there were no effective therapeutics. Why should clinicians and patients spend time measuring symptoms if there is no solution? Though valbenazine and deutetrabenazine have recently been approved for tardive dyskinesia, it is under-diagnosed in the real-world. The symptom measures used in trials are not typically used – or even known – by real-world clinicians. Similar dynamics exist for negative symptoms of schizophrenia, cognitive impairment, and other conditions. Our solution: a Learning Health SystemWe appreciate an analogy by one of the leaders of precision psychiatry, “You wouldn't want to launch electric vehicles without building an EV charging network first.” With breakthroughs in drug development comes an increased need for connectivity across biopharma, regulators, clinicians, payers, and clinical societies.At Osmind, our Learning Health System approach lowers barriers between research and patient care. By building consensus around the same precision measurements, we align evidence goalposts and generate cohorts of well-characterized patients for research. We deploy these measures directly at the point of care through our technology and EHR. Our collaboration with the American Psychiatric Association is an example of this approach.“As we advance in understanding the biological underpinnings of mental illness, an important challenge – and opportunity – will be to ensure that these insights translate into improvements in patient care,” says Husseini Manji, MD, a Strategic Advisor at Osmind. “We must work collaboratively across sectors to create a seamless integration of precision diagnostics and targeted therapeutics into everyday practice and real-world outcomes.”

Phase 3Phase 2

14 Aug 2024

·www.globenewswire.com

Neumora Therapeutics to Host Key Opinion Leader Roundtable to Discuss the Potential of Navacaprant in Neuropsychiatric Disorders

Roundtable discussion to take place on Thursday, September 12 at 8:00 a.m. ETWATERTOWN, Mass., Aug. 14, 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 Company will host a roundtable discussion on the neuropsychiatric treatment landscape and role of kappa opioid receptor antagonists (KORAs) in neuropsychiatry. The discussion will feature leading experts in neuropsychiatry and will take place on Thursday, September 12 at 8:00 a.m. ET. “We look forward to an engaging discussion with our panel of distinguished medical experts and to providing an overview of the potential for navacaprant to make a difference for patients,” said Henry Gosebruch, chief executive officer, Neumora. “It is clear that there is significant excitement among the scientific community regarding the potential of KORAs across many neuropsychiatric indications. We share their enthusiasm and are pleased to be executing the comprehensive Phase 3 KOASTAL program with navacaprant in MDD in the monotherapy setting and a Phase 2 study in bipolar depression. We believe navacaprant has the potential to reshape the treatment of these serious brain disorders. We look forward to reporting topline data from our first Phase 3 study, KOASTAL-1, in the fourth quarter.” The program agenda will feature the following topics and speakers: Global Brain Disease: Neumora’s Mission and Pipeline Josh Pinto, Ph.D., Chief Financial Officer The Role of Kappa Opioid Receptors in MDD and Overview of Navacaprant Phase 2 Data Bill Aurora, Pharm.D., Chief Strategy Officer Indication Opportunities for Navacaprant: MDD, BPD, and Beyond Rob Lenz, M.D., Ph.D., Head of Research and Development Fireside Chat: A Discussion on the Neuropsychiatric Treatment Landscape and Opportunity for Navacaprant Roger McIntyre, M.D., University of TorontoSanjay Mathew, M.D., Baylor College of MedicineJohn Krystal, M.D., Yale University School of Medicine Company Outlook: A Look Ahead Henry Gosebruch, Chief Executive Officer Webcast InformationThe event will begin at 8:00 a.m. ET on Thursday, September 12, 2024. Participants can register for the live webcast here. In addition, the live webcast of the event will be available on the events and presentations section of the Company’s website at www.neumoratx.com. A replay of the webcasts will be available following the completion of the event and will be archived for up to 30 days. About Navacaprant Clinical Development ProgramNavacaprant (NMRA-140) is a highly selective, novel, once-daily kappa opioid receptor (KOR) antagonist being developed as a potential monotherapy treatment for major depressive disorder (MDD) and other neuropsychiatric disorders. The KOR antagonist approach has been clinically validated in three independent studies. Neumora is currently enrolling the registrational Phase 3 KOASTAL program, which is designed to evaluate the efficacy and safety of navacaprant monotherapy for the treatment of MDD. KOASTAL-1, KOASTAL-2, and KOASTAL-3 are replicate Phase 3, randomized, placebo-controlled, double-blind studies in adult patients with MDD. Neumora is also evaluating the potential of navacaprant for the treatment of bipolar depression (BPD) in a Phase 2 study initiated in May 2024. Neumora expect to report data from KOASTAL-1 study in the fourth quarter of 2024, topline data from the KOASTAL-2 and KOASTAL-3 studies in the first half of 2025 and topline data from the Phase 2 BPD study in the second half of 2025. About NeumoraNeumora 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 StatementsThis 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; Neumora’s goal to make navacaprant available for MDD patients; the timing, progress and plans for its therapeutic development programs, including the timing of patient enrollment, initiation and data read outs for its programs and studies, as well as its clinical trial and development plans 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 Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 that was filed with the SEC on or about the date hereof. 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. Our results for the quarter ended June 30, 2024 are also not necessarily indicative of our operating results for any future periods. Neumora Contact:Helen Rubinstein315-382-3979Helen.Rubinstein@neumoratx.com

Phase 2Phase 3

06 Aug 2024

·www.globenewswire.com

Neumora Therapeutics Reports Second Quarter 2024 Financial Results and Provides Business Update

Phase 3 data from KOASTAL-1 study of navacaprant in MDD expected in fourth quarter of 2024 Progressing clinical studies in MDD, bipolar depression and Alzheimer’s disease agitation, providing opportunity for multiple value-creating catalysts over next 18 months Strong financial position with $371.6 million in cash, cash equivalents and marketable securities expected to support operations into 2026 WATERTOWN, Mass., Aug. 06, 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 financial results for the second quarter ended June 30, 2024, and provided a business update. “The first half of the year was marked by considerable progress across our robust clinical development pipeline as we seek to pioneer a new era in brain diseases,” said Henry Gosebruch, president and chief executive officer, Neumora. “We are excited for the topline data readout from our pivotal Phase 3 KOASTAL-1 study of navacaprant to treat major depressive disorder (MDD), which we continue to expect in the fourth quarter. We are committed to bringing navacaprant to the millions of patients suffering with MDD as expeditiously as possible.” “Additionally, we’re making significant progress across the rest of our pipeline with the recent initiations of a Phase 2 study of navacaprant as a treatment for bipolar depression and a Phase 1b study of NMRA-511 in Alzheimer's disease agitation, as well as narrowing guidance to submit an IND for an additional M4 compound in the first half of 2025. These are areas of substantial unmet medical need, and we are confident that our novel mechanisms have strong rationales with the potential for favorable benefit-risk profiles,” added Mr. Gosebruch. KEY PIPELINE HIGHLIGHTS Neumora is advancing a therapeutic pipeline of seven clinical and preclinical neuroscience programs that target novel mechanisms of action for a broad range of underserved neuropsychiatric disorders and neurodegenerative diseases. Navacaprant (NMRA-140): Phase 3 Data from KOASTAL-1 Study in Major Depressive Disorder (MDD) Expected in Fourth Quarter of 2024 Navacaprant (NMRA-140) is a highly selective, novel, once-daily kappa opioid receptor (KOR) antagonist being developed as a potential monotherapy treatment for MDD and other neuropsychiatric disorders. The KOR antagonist approach has been clinically validated in three independent studies. Neumora is currently enrolling the registrational Phase 3 KOASTAL program, which is designed to evaluate the efficacy and safety of navacaprant monotherapy for the treatment of MDD. KOASTAL-1, KOASTAL-2, and KOASTAL-3 are replicate Phase 3, randomized, placebo-controlled, double-blind studies in adult patients with MDD. Neumora remains on-track to report data from the KOASTAL studies within previously guided timeframes. The Company expects to report topline data from the KOASTAL-1 study in the fourth quarter of 2024, and topline data from the KOASTAL-2 and KOASTAL-3 studies in the first half of 2025. Beyond MDD, Neumora recently initiated a Phase 2 clinical trial evaluating the potential of navacaprant as treatment for bipolar depression. The randomized, double-blind, placebo-controlled, Phase 2 clinical trial is designed to evaluate the safety and efficacy of navacaprant in people with depression associated with bipolar II disorder. Neumora expects to report topline data from this trial in the second half of 2025. NMRA-511: Ongoing Phase 1b Study in Alzheimer’s Disease (AD) Agitation NMRA-511 is a highly selective, novel antagonist of the vasopressin 1a receptor (V1aR) being developed for the treatment of agitation associated with dementia due to AD and other neuropsychiatric disorders. In June 2024, the Company initiated a Phase 1b study in investigating NMRA-511 initially in healthy elderly adult participants and then people with agitation associated with dementia due to AD. The Company expects to report data from this study in the second half of 2025. M4 Positive Allosteric Modulator (PAM) Franchise: Advancing Preclinical Work Across Compounds, with IND expected in the first half of 2025 Neumora’s M4 franchise is comprised of multiple novel compounds that each have different properties and chemical composition, including NMRA-266. The Phase 1 single ascending dose / multiple ascending dose study with NMRA-266 is currently paused following a clinical hold determination by the U.S. Food and Drug Administration (FDA). Neumora is working with the FDA to evaluate the potential to resolve the clinical hold and will provide an update when available. Beyond NMRA-266, additional compounds in Neumora’s M4 PAM franchise also 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 preclinical safety and toxicology work with its additional M4 PAM compounds and has narrowed the guidance for bringing an additional M4 PAM compound into the clinic from its prior guidance of 2025. The Company now expects to submit an IND in the first half of 2025. SECOND QUARTER 2024 FINANCIAL RESULTS Cash Position: As of June 30, 2024, Neumora had cash, cash equivalents and marketable securities of $371.6 million.Financial Guidance: The Company expects that its cash, cash equivalents and marketable securities as of June 30, 2024, will enable it to fund its operating plan into 2026.R&D Expense: Research and development expenses for the second quarter of 2024 were $48.6 million, as compared to $32.8 million for the same period in 2023. This increase was primarily due to advancement of clinical and preclinical programs and related activities for Phase 3 clinical trials evaluating navacaprant as a monotherapy treatment for MDD.G&A Expense: General and administrative expenses for the second quarter of 2024 were $15.2 million, as compared to $9.3 million for the same period in 2023. This increase was primarily due to personnel-related costs, including stock-based compensation and professional services to support the continued expansion of administrative functions.Net Loss: The Company reported a net loss of $58.7 million for the second quarter of 2024, as compared to $38.5 million for the same period in 2023. About NeumoraNeumora 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 StatementsThis 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; Neumora’s goal to make navacaprant available as expeditiously as possible for MDD patients; the timing, progress and plans for its therapeutic development programs, including the timing of patient enrollment, initiation and data read outs for its programs and studies, as well as its clinical trial and development plans and the potential for Neumora’s clinical pipeline to create value; timing and expectations related to regulatory filings and interactions; expectations and projections regarding future operating results and financial performance, including the sufficiency of its cash resources and expectation of the timing of its cash runway; 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 Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 that was filed with the SEC on or about the date hereof. 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. Our results for the quarter ended June 30, 2024 are also not necessarily indicative of our operating results for any future periods. Financial Tables NEUMORA THERAPEUTICS, INC.Unaudited Consolidated Statements of Operations and Comprehensive Loss (in thousands, except per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Operating expenses: Research and development $48,628 $32,769 $94,385 $62,254 General and administrative 15,194 9,293 29,511 18,976 Total operating expenses 63,822 42,062 123,896 81,230 Loss from operations (63,822) (42,062) (123,896) (81,230) Other income (expense): Interest income 5,271 3,558 11,636 7,127 Other expense, net (24) (39) (36) (65) Total other income 5,247 3,519 11,600 7,062 Net loss before income taxes (58,575) (38,543) (112,296) (74,168) Provision for income taxes 125 — 125 — Net loss (58,700) (38,543) (112,421) (74,168) Other comprehensive income (loss): Unrealized gain (loss) on marketable securities (39) (150) (111) 326 Comprehensive loss $(58,739) $(38,693) $(112,532) $(73,842) Net loss per share, basic and diluted $(0.37) $(1.28) $(0.71) $(2.50) Weighted-average shares outstanding, basic and diluted 158,984 30,125 158,464 29,704 Neumora Therapeutics, Inc. Unaudited Condensed Consolidated Balance Sheets (in thousands) June 30, 2024 December 31, 2023 Cash, cash equivalents and marketable securities $371,639 $463,827 Total assets $404,473 $496,195 Total liabilities $23,214 $27,119 Total stockholders’ equity $381,259 $469,076 Neumora ContactHelen Rubinstein+1 (315) 382-3979Helen.Rubinstein@neumoratx.com

Phase 2Phase 1Financial StatementPhase 3

100 Deals associated with Navacaprant

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 3	US	Neumora Therapeutics, Inc.	20 Sep 2023
Depressive Disorder	Phase 2	-	Neumora Therapeutics, Inc.	14 May 2024
Bipolar II disorder	Phase 2	US	Neumora Therapeutics, Inc.	13 May 2024

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04221230 (BusinessWire) Manual	Phase 2	Depressive Disorder, Major	171	navacaprant	ykjgxicoyr(qrzbezyctw): difference = -1.7, P-Value = 0.121 View more	Positive	18 Jul 2023
				placebo

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Understand key drug designations in just a few clicks with Synapse.

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Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis