Neflamapimod

Frontotemporal dementia is an uncommon type of dementia that causes problems with behaviour and language. Credit: Azurhino via Shutterstock. The US Food and Drug Administration (FDA) has granted orphan drug designation to CervoMed ’s lead investigational therapy neflamapimod for the treatment of frontotemporal dementia, a rare neurodegenerative disease. Following the announcement, CervoMed’s stock price rose by 14.6%, climbing from $7.98 at the market close on 26 November to $9.15 at the close of trading on 27 November. While neflamapimod’s orphan designation is specific to frontotemporal dementia , the drug is currently being studied in treating early-stage dementia with Lewy bodies. The ongoing RewinD-LB Phase IIb study (NCT05869669) is evaluating the oral therapy in 159 patients with early-stage Lewy body dementia, with topline results expected next month. CervoMed’s CEO John Alam noted that the company anticipates advancing neflamapimod to a Phase III trial in mid-2025, with data readout and regulatory submission targeted for 2027 , assuming positive topline results in the RewinD-LB trial. In earlier trials, neflamapimod demonstrated promising results. In the AscenD-LB Phase IIa trial (NCT04001517), the drug candidate improved clinical dementia severity scores – assessed by clinical dementia rating sum-of-boxes (CDR-SB) – and functional mobility, as measured using the timed up and go test (TUG), compared to placebo. Notably, patients with early-stage Lewy body dementia without tau pathology showed a strong response. The FDA’s orphan drug designation offers financial incentives to developers for rare diseases, including tax credits for clinical trial costs, a waiver of marketing application fees, and seven years of US market exclusivity upon approval. While there are approved treatments such as acetylcholinesterase inhibitors to help symptoms of Lewy body dementia, there are no approved treatments that target the cause of the condition. Neflamapimod is an oral p38MAP kinase alpha (p38a) inhibitor that has the potential to treat synaptic dysfunction. It is the reversible aspect of the underlying neurodegenerative processes in dementia with Lewy bodies. Frontotemporal dementia – which affects fewer than 200,000 people in the US – also currently has no approved treatments. “We are pleased to have received orphan drug designation as it implicitly recognises the scientific rationale and potential for neflamapimod to treat this debilitating condition,” said Alam. He emphasised the heavy burden the disease places on patients and caregivers. CervoMed’s progress has been supported by a robust financial foundation. In March 2024, the company secured up to $149.4m in private placement funding led by RA Capital Management, with participation from Armistice Capital, Special Situations Funds and Soleus Capital. These funds are expected to facilitate the ongoing and future clinical development of neflamapimod.

- Reported last patient, last visit in its RewinD-LB Phase 2b clinical trial evaluating neflamapimod in patients with early-stage dementia with Lewy bodies (DLB) in October 2024; topline data expected in December 2024 – - Hosted a virtual key opinion leader event in July 2024 highlighting neflamapimod’s potential for patients with early-stage DLB – BOSTON, Nov. 12, 2024 (GLOBE NEWSWIRE) -- CervoMed Inc. (NASDAQ: CRVO), a clinical stage company focused on developing treatments for age-related neurologic disorders (CervoMed or the Company), today reported its financial results for the third quarter ended September 30, 2024. “In the third quarter, we conducted the final patient visits in RewindD-LB, our Phase 2b trial evaluating neflamapimod in patients with early-stage DLB and began to prepare for database lock in the fourth quarter. We remain on track to report topline data from the study in December 2024,” said John Alam, MD, Chief Executive Officer of CervoMed. “Additionally, we carried out important chemistry, manufacturing and controls (CMC) activities to prepare for Phase 3 trial initiation in mid-2025 after a planned end-of-Phase 2 meeting with the FDA. While our core focus remains on the opportunity in DLB, we also plan to initiate a Phase 2a trial to evaluate neflamapimod’s potential to promote recovery from ischemic stroke in the first quarter of 2025, for which we recently obtained ethics committee approval.” Recent Highlights and Anticipated Milestones In November 2024, CervoMed was selected as “Best Startup” in the 2024 Prix Galien USA Award by the Galien Foundation, a premier global institution dedicated to honoring innovators in life sciences.Delivered two oral presentations at the recent Clinical Trials on Alzheimer’s Disease Conference (CTAD) showing neflamapimod demonstrated a treatment effect on plasma glial fibrillary acid protein, a robust measure of neurogenerative disease activity in DLB, and that the RewinD-LB study enrolled a population that is optimized to show the treatment effect. Full details on the CTAD presentation can be found here.Reported last patient, last visit had occurred in the Phase 2b RewinD-LB clinical trial evaluating oral neflamapimod in patients with early-stage DLB in October 2024 and remain on track to report topline data from the study in December 2024.Plasma biomarker data from the AscenD-LB Phase 2a trial of neflamapimod in patients with DLB were featured in a poster presentation at the Alzheimer's Association International Conference®, held in Philadelphia on July 29, 2024. A PDF copy of the poster presentation is available on the “Presentations and Publications” section of the CervoMed website.Hosted a virtual key opinion leader event on clinical disease expression of DLB, the role of the cholinergic system and neflamapimod’s potential for patients with early-stage DLB in July 2024. The call featured presentations from John-Paul Taylor, MBBS (hons), MRCPsych, PhD (Newcastle University) and Ralph A. Nixon, MD, PhD (New York University Grossman School of Medicine). A replay is accessible on CervoMed’s website.On July 1, 2024, CervoMed was added to the Russell 2000® and Russell 3000® Indexes as part of the 2024 Russell U.S. Indexes annual reconstitution. Third Quarter 2024 Financial Results Cash Position: As of September 30, 2024, CervoMed had approximately $46.7 million in cash, cash equivalents and marketable securities, as compared to approximately $50.9 million and $7.8 million as of June 30, 2024, and December 31, 2023, respectively. The increase in cash on-hand compared to year-end was primarily attributable to the upfront proceeds received in CervoMed’s private placement completed in April 2024. Based on its current operating plan, CervoMed believes its cash, cash equivalents and marketable securities on hand as of September 30, 2024, along with the remaining funds to be received from its National Institute on Aging of the National Institutes of Health (NIA) grant, will enable the Company to fund its operating expenses and capital expenditure requirements through 2025. Grant Revenue: In January 2023, CervoMed was awarded a $21.0 million grant from the NIA to support the RewinD-LB trial and, in August 2024, CervoMed was awarded an additional $0.3 million under the grant. Grant revenue was approximately $1.9 million for the three months ended September 30, 2024, compared to approximately $1.5 million for the same period in 2023. This increase was related to an increase in services performed during the nine months ended September 30, 2024, as a result of, among other things, a larger number of trial sites being active in the RewinD-LB trial during the current year period. Research and Development (R&D) Expenses: R&D expenses for the three months ended September 30, 2024, were approximately $5.1 million, compared to approximately $1.8 million in the same period in 2023. This increase was primarily attributable to an increase in outsourced contract research organization costs and related site expenses related to the RewinD-LB trial, services for which ramped up progressively between initiation in the third quarter of 2023 and the completion of enrollment in June 2024. General and Administrative (G&A) Expenses: G&A expenses were approximately $2.2 million during the three months ended September 30, 2024, versus approximately $2.4 million in the same period in 2023. The slight decrease of $0.2 million was primarily due to fewer one-time professional fee costs incurred related to the Company’s reverse merger in August 2023, including D&O insurance, public relations, and accounting services. Operating Loss: Operating loss was approximately $5.4 million for the three months ended September 30, 2024, compared to approximately $2.7 million for the same period in 2023. Net Loss: Net loss was approximately $4.8 million for the three months ended September 30, 2024, compared to net income of approximately $2.2 million for the same period in 2023. The net income in the prior year period was driven primarily by a non-cash fair value adjustment to previously outstanding convertible notes, which converted into shares of CervoMed common stock in connection with the reverse merger in August 2023. About the RewinD-LB Phase 2b Study in Dementia with Lewy BodiesCervoMed’s ongoing Phase 2b study, 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 approximately 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 significant, irreversible neuronal loss in the hippocampus and associated Alzheimer’s Disease co-pathology – as assessed by a blood biomarker (plasma ptau181), were excluded from the study. The primary endpoint in the study is change in the Clinical Dementia Rating Sum of Boxes, and secondary endpoints include the Timed Up and Go test, a cognitive test battery, and the Clinician’s Global Impression of Change. The RewinD-LB study is funded by a $21.3 million grant from the NIA, which is being disbursed over the course of the study as costs are incurred. The study includes 43 sites (32 in the United States, eight in the United Kingdom, and three in the Netherlands) and completed enrollment in June 2024, with topline data expected in December 2024. Patients completing the 16-week placebo-controlled study period will be able to continue in the study while receiving open label neflamapimod treatment for an additional 32 weeks. More information on the RewinD-LB study, including contact information on active clinical trial sites, is available at clinicaltrials.gov. About CervoMedCervoMed 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. Forward-Looking StatementsThis press release includes express and implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, regarding the intentions, plans, beliefs, expectations or forecasts for the future of the Company, including, but not limited to, the Company’s financial position and cash runway, the therapeutic potential of neflamapimod, the anticipated timing and achievement of clinical and development milestones, including the completion and achievement of primary endpoints of the RewinD-LB Phase 2b clinical trial and the Company’s announcement of topline and other data therefrom, and any other expected or implied benefits or results, including that any initial clinical results observed with respect to neflamapimod in the AscenD-LB trial or RewinD-LB trial will be replicated in later trials, as well as the timing of the initiation of any potential future trials. Terms such as “believes,” “estimates,” “anticipates,” “expects,” “plans,” “aims,” “seeks,” “intends,” “may,” “might,” “could,” “might,” “will,” “should,” “approximately,” “potential,” “target,” “project,” “contemplate,” “predict,” “forecast,” “continue,” or other words that convey uncertainty of future events or outcomes (including the negative of these terms) may identify these forward-looking statements. Although there is believed to be reasonable basis for each forward-looking statement contained herein, forward-looking statements by their nature involve risks and uncertainties, known and unknown, many of which are beyond the Company’s control and, as a result, actual results could differ materially from those expressed or implied in any forward-looking statement. Particular risks and uncertainties include, among other things, those related to: the Company’s available cash resources and the availability of additional funds on acceptable terms; the results of the Company’s clinical trials, including RewinD-LB; the likelihood and timing of any regulatory approval of neflamapimod or the nature of any feedback the Company may receive from the U.S. Food and Drug Administration; the ability to implement business plans, forecasts, and other expectations in the future; general economic, political, business, industry, and market conditions, inflationary pressures, and geopolitical conflicts; and the other factors discussed under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023 filed with the U.S. Securities and Exchange Commission (SEC) on March 29, 2024, and other filings that the Company may file from time to time with the SEC. Any forward-looking statements in this press release speak only as of the date hereof (or such earlier date as may be identified). The Company does not undertake any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except to the extent required by law. Investor Contact: PJ KelleherLifeSci AdvisorsInvestors@cervomed.com617-430-7579 CervoMed Inc. Condensed Consolidated Balance Sheets (unaudited) September 30, December 31, 20242023Assets Current assets: Cash and cash equivalents $7,743,667 $7,792,846 Marketable securities, current 38,913,236 — Prepaid expenses and other current assets 1,888,879 1,256,501 Grant receivable 264,148 915,404 Total current assets 48,809,930 9,964,751 Other assets 73,937 7,770 Total assets $48,883,867 $9,972,521 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $1,082,435 $662,471 Accrued expenses and other current liabilities 2,163,936 1,933,276 Total liabilities 3,246,371 2,595,747 Commitments and Contingencies (Note 10) Stockholders’ Equity: Common stock, $0.001 par value: 1,000,000,000 shares authorized: 8,253,741 and 5,674,520 shares issued and outstanding at September 30, 2024 and December 31, 2023, respectively 8,253 5,674 Additional paid-in capital 109,531,651 61,811,889 Accumulated other comprehensive income 123,162 — Accumulated deficit (64,025,570) (54,440,789)Total stockholders' equity 45,637,496 7,376,774 Total liabilities and stockholders' equity $48,883,867 $9,972,521 CervoMed Inc. Condensed Consolidated Statements of Operations and Comprehensive Loss (unaudited) Three Months Ended Nine Months Ended September 30,September 30, 2024 2023 2024 2023 Grant revenue $1,939,751 $1,526,482 $7,575,972 $4,654,294 Operating expenses: Research and development 5,125,097 1,791,487 11,711,746 5,583,149 General and administrative 2,210,927 2,410,124 6,850,536 4,403,590 Total operating expenses 7,336,024 4,201,611 18,562,282 9,986,739 Loss from operations (5,396,273) (2,675,129) (10,986,310) (5,332,445)Other income (expense): Other income (expense) (3,440) 4,777,824 (3,717) 5,422,192 Interest income 646,172 47,667 1,405,246 100,778 Total other income, net 642,732 4,825,491 1,401,529 5,522,970 Net (loss) income $(4,753,541) $2,150,362 $(9,584,781) $190,525 Per share information: Net (loss) income per share of common stock, basic and diluted $(0.55) $0.65 $(1.22) $0.13 Weighted average shares outstanding, basic and diluted 8,702,764 3,308,302 7,861,757 1,458,415 Net loss per share of common stock, diluted $(0.55) $(0.70) $(1.22) $(2.37)Weighted average shares outstanding, diluted 8,702,764 3,766,700 7,861,757 2,209,407 Comprehensive (loss) income: Net unrealized gain on marketable securities 142,864 — 123,162 — Total comprehensive (loss) income $(4,610,677) $2,150,362 $(9,461,619) $190,525