CervoMed, Inc.

—Neflamapimod did not demonstrate statistically significant effects versus placebo on primary and secondary endpoints at 16 weeks— —Favorable safety and tolerability results with no new safety signal identified— —Target plasma drug concentrations not achieved during 16-week double-blind phase of the trial— —Trial participants continue to receive neflamapimod during open-label extension— Dec. 10, 2024 -- CervoMed Inc. (NASDAQ: CRVO) (“CervoMed” or the “Company”), a clinical-stage company focused on developing treatments for age-related neurologic disorders, today announced topline data from the RewinD-LB Phase 2b clinical trial evaluating neflamapimod for the treatment of patients with dementia with Lewy bodies (DLB). The trial did not meet statistical significance thresholds for its primary endpoint of change in the Clinical Dementia Rating Sum of Boxes (CDR-SB) or any of its key secondary endpoints – change from baseline in Timed Up and Go (TUG) test, change from baseline in a Neuropsychological Test Battery (NTD) and the Clinician’s Global Impression of Change (CGIC). Initial analysis shows that target plasma drug concentrations were not achieved during the double-blind phase of the trial, which may have adversely impacted trial results. “Obviously, we are disappointed with these results, particularly given our prior clinical experience with neflamapimod in patients with early-stage DLB and we are investigating the reasons for the lower-than-expected plasma drug concentrations. We continue to believe neflamapimod may have potential as a treatment for DLB, and we will thoroughly analyze the clinical and pharmacokinetic data from the trial to better understand its outcome and potential future development paths for the drug. This includes data expected to be available in the first half of 2025 from the first 16 weeks of the open label extension trial which we believe may be valuable to our investigation. In the meantime, we are pausing all preparations for our previously planned Phase 3 trial in early-stage DLB until the full analysis is complete,” said John Alam, MD, Chief Executive Officer of CervoMed. In the RewinD-LB Phase 2b trial, neflamapimod demonstrated a favorable safety and tolerability profile that is consistent with prior clinical studies, with no new safety signal identified. “We are grateful to the entire DLB community, including trial participants, their caregivers and families, and all of our investigators, sites and coordinators,” said Kelly Blackburn, CervoMed’s SVP of Clinical Development. The full data set from the double-blind phase of the RewinD-LB trial is expected to be available to the Company in January 2025 and the data from the first 16 weeks of the open label extension portion of the trial are expected to be available in the late second quarter of 2025. CervoMed will announce the timing of any presentation of additional data from the RewinD-LB trial at a later date upon completion of the first 16 weeks of the open label extension portion of the trial and CervoMed’s analysis of all such data. DLB is the third most common degenerative disease of the brain (after Alzheimer’s disease and Parkinson’s disease), with approximately 700,000 individuals affected in each of the United States (U.S.) and European Union. Patients with this disease accumulate protein deposits, called Lewy bodies, in the brain’s nerve cells. This negatively affects cognitive ability, including attention, judgement, and reasoning, along with motor function. Patients with DLB incur higher healthcare costs, have longer hospitalizations, report lower quality of life, and have caregivers with higher levels of distress when compared to patients with Alzheimer’s disease. No treatments for DLB have been approved by the U.S. Food and Drug Administration (FDA) or European Medicines Agency, and there are few drugs in development. The current standard of care is cholinesterase inhibitor therapy, which is approved for use in Alzheimer’s disease, but in DLB patients typically improves cognition transiently, and does not impact the motor component of the disease. Neflamapimod is an investigational, orally administered small molecule brain penetrant drug designed to inhibit alpha isoform of the p38MAP kinase. Following preclinical studies in which neflamapimod reversed synaptic dysfunction, results from CervoMed’s AscenD-LB Phase 2a clinical trial demonstrated that, compared to placebo, treatment with neflamapimod 40 mg TID significantly improved dementia severity, functional mobility and performance on a cognitive test battery, with the treatment response most substantial among patients with early-stage DLB. With a design guided by learnings from AscenD-LB, CervoMed’s RewinD-LB trial was the first trial to successfully enroll an exclusively early-stage DLB patient population. CervoMed’s Phase 2b trial, RewinD-LB, is a randomized, 16-week, double-blind, placebo-controlled clinical trial evaluating oral neflamapimod (40mg TID) in 159 patients with early-stage DLB. In early-stage DLB patients – who are estimated to comprise more than 50% of the total diagnosed DLB patient population at any given time – the disease has not progressed to a point where the patient has significant neuronal loss in the hippocampus. Patients with advanced DLB – in whom there is a significant, irreversible neuronal loss in the hippocampus and associated Alzheimer’s Disease co-pathology – were excluded from the trial. The primary endpoint in the trial is a change in CDR-SB, and secondary endpoints include the TUG test, a cognitive test battery, and the CGIC. The RewinD-LB trial is funded by a $21.3 million grant from the National Institutes of Health’s National Institute on Aging, which is being disbursed over the course of the trial as costs are incurred. The trial includes 43 sites across the United States, the United Kingdom, and the Netherlands. CervoMed Inc. is a clinical-stage company focused on developing treatments for age-related neurologic disorders. The Company is currently developing neflamapimod, an investigational, orally administered small molecule brain penetrant designed to inhibit p38 mitogen-activated protein kinase alpha. Neflamapimod has the potential to treat synaptic dysfunction, the reversible aspect of the underlying neurodegenerative processes that causes disease in certain major neurological disorders. The content above comes from the network. if any infringement, please contact us to modify.

Plus, news about Lava Therapeutics, Recursion and Aqemia: CervoMed’s dementia drug disappoints in Phase 2: The drugmaker’s neflamapimod missed both the primary and key secondary endpoints in a mid-stage trial of 159 patients with dementia with Lewy bodies. The drug didn’t hit target plasma concentrations, which “may have” contributed to the failure, the biotech said. Its shares $CRVO plunged about 73% in premarket trading on Tuesday. — Ayisha Sharma UK changes mind about Santhera’s Duchenne muscular dystrophy drug: NICE, the cost-effectiveness watchdog, has now recommended Agamree for Duchenne patients aged 4 and older. It previously ruled against reimbursing the drug in a provisional decision because its “relative effectiveness compared with other corticosteroids was highly uncertain.” — Ayisha Sharma Lava Therapeutics reprioritizes its pipeline: The Dutch and Philadelphia biotech is ending work on LAVA-1207 after it failed to reach the biotech’s “internal benchmarks” in a Phase 1 trial. The drug was being studied in certain forms of prostate cancer. The discontinuation was “not due to safety concerns.” — Kyle LaHucik Recursion shares early results for CDK7 inhibitor: The Salt Lake City-based biotech’s REC-617 produced a partial response in one patient with metastatic, platinum-resistant ovarian cancer, according to interim Phase 1 data. The treatment was well-tolerated with mostly low-grade side effects and no safety-related discontinuations. — Ayisha Sharma Aqemia’s $38M raise: The Paris-based techbio startup has now raised a total of $100 million. It also plans to open a London office in January. — Kyle LaHucik

Designation underscores significant unmet need in frontotemporal dementia and the potential role of neflamapimod in multiple neurologic disorders On track to report topline data from the RewinD-LB Phase 2b clinical trial in early-stage dementia with Lewy bodies (DLB) in December 2024 Nov. 27, 2024 -- CervoMed Inc. (NASDAQ: CRVO), a clinical-stage company focused on developing treatments for age-related neurologic disorders, today announced that its oral investigational drug neflamapimod has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of frontotemporal dementia (FTD). “We are pleased to have received Orphan Drug Designation as it implicitly recognizes the scientific rationale and potential for neflamapimod to treat this debilitating condition. Patients diagnosed with frontotemporal dementia have no available treatment options, and this rare condition is extremely burdensome to patients and caregivers alike,” said John Alam, MD, Chief Executive Officer of CervoMed. “Within this year, there have been multiple scientific presentations and publications that indicate neflamapimod targets specific pathogenic mechanisms associated with FTD. We are in active discussions with clinical thought leaders regarding the design of a proof-of-principle study in FTD, while continuing to prepare to advance neflamapimod into a Phase 3 trial in DLB in mid-2025.” FDA Orphan Drug Designation is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. Importantly, the FDA also requires sufficient preclinical and/or clinical data to establish a medically plausible basis for expecting the drug to be effective in the rare disease for which orphan drug status is granted. Orphan Drug status provides benefits to drug developers, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees and seven years of post-approval marketing exclusivity. FTD is a rare neurodegenerative disease, but it is one of the most common causes of early onset dementia. It affects an estimated 50,000 to 60,000 people in the United States and roughly 110,000 in the European Union, with potentially higher prevalence in Asia and Latin America. Pathologically FTD is characterized by significant neuronal loss (i.e. atrophy by MRI or at autopsy) in the frontal and temporal regions of the cortex. The pathogenic drivers underlying the neuronal loss are in most cases, in roughly equal proportions, intraneuronal inclusions in those two regions of the brain containing either the protein tau or TDP-43 (transactive response DNA binding protein); intranuclear inclusions of fused in sarcoma (FUS) are also seen, but in fewer than 10% of patients. Patients with FTD frequently develop symptoms such as behavioral changes, lapses in judgment, and diminished language skills when they are in their 40s and 50s with the disease running its course in 7-10 years. There are no FDA- or EMA-approved treatment options available for any form of FTD. Neflamapimod is an investigational, orally administered small molecule brain penetrant drug that inhibits alpha isoform of the p38MAP kinase. In preclinical studies, neflamapimod reversed synaptic dysfunction, including and particularly within the part of the brain most impacted in DLB – the basal forebrain cholinergic system. In Phase 1 and Phase 2 clinical studies involving more than 300 participants, neflamapimod has been shown to be generally well tolerated. Results from the AscenD-LB Phase 2a clinical study demonstrated that neflamapimod significantly improved dementia severity (assessed by Clinical Dementia Rating Sum-of-boxes, or CDR-SB) compared to placebo and significantly improved functional mobility (assessed by Timed Up and Go Test, or TUG test) compared to placebo. At the highest dose evaluated, neflamapimod also improved results on a cognitive test battery. The treatment response in AscenD-LB in patients with early-stage DLB (i.e., those without biomarker evidence of tau pathology in the brain) was substantial (effect size > 0.7) and greater than the overall patient population. Neflamapimod is currently being evaluated in the ongoing RewinD-LB Phase 2b study, a randomized, 16-week, double-blind, placebo-controlled clinical trial evaluating oral neflamapimod (40mg TID) in 159 patients with early-stage DLB. Topline results from the RewinD-LB study are expected in December 2024. CervoMed Inc. (the “Company”) is a clinical-stage company focused on developing treatments for age-related neurologic disorders. The Company is currently developing neflamapimod, an investigational, orally administered small molecule brain penetrant that inhibits p38 mitogen-activated protein kinase alpha. Neflamapimod has the potential to treat synaptic dysfunction, the reversible aspect of the underlying neurodegenerative processes that causes disease in DLB and certain other major neurological disorders. Neflamapimod is currently being evaluated in a Phase 2b study in patients with early-stage DLB. 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