Aphasia, Primary Progressive

Results from the first patient cohort (N=5) of an open-label proof of concept academic study with low-dose IL-2 and CTLA4-Ig demonstrated a rapid and durable statistically significant increase in the number and suppressive function of Tregs compared to baseline values. Clinically, patients with Frontotemporal Dementia (FTD) demonstrated minimal to no cognitive decline throughout the study period. Treatment was well tolerated, no serious adverse events were reported, and all 5 patients completed the study. HOUSTON--(BUSINESS WIRE)-- Coya Therapeutics, Inc. (NASDAQ: COYA) (“Coya” or the “Company”), a clinical-stage biotechnology company developing biologics intended to enhance regulatory T cell (Treg) function announced positive interim results of an investigator-initiated proof of concept open-label study with low-dose IL-2 and CTLA4-Ig combination treatment in patients with Frontotemporal Dementia (FTD). The study is led by Dr. Alireza Faridar and Dr. Stanley Appel at the Houston Methodist Neurological Institute (Houston, TX) with funding from The Peggy and Gary Edwards Endowment Fund. Study patients received subcutaneously administered CTLA4-Ig, followed by a 5-day course of low-dose IL-2 every four weeks, for a total of 22 weeks of dosing and follow-up. The study aims to enroll up to 10 patients, and these interim results include data from the first 5 patients with mild to moderate FTD who have completed the full course of treatment. Dr. Arun Swaminathan, Coya’s Chief Executive Officer followed: “The results thus far are consistent with previously published encouraging data from an open-label investigator-initiated study of patients with ALS treated with low-dose IL-2/CTLA4-Ig. This interim data in FTD provides us further confidence of our approach to target and enhance Treg biology to address devastating neurodegenerative diseases including ALS and FTD.” Previous biomarker data presented by the Company demonstrated that FTD patients exhibit a compromised immunosuppressive function of regulatory T cells (Tregs), along with increased peripheral levels of inflammatory cytokines and chemokines, dysregulation of monocytes, and systemic activation of the inflammatory cascade, supporting the critical role of the immune system in the pathophysiology of FTD. One previous study showed that a cohort of 68 patients with FTD worsened by an average of 3.57 points over a 12-month period per the Clinical Dementia Rating - Frontotemporal Lobar Degeneration (CDR‐FTLD) scale (Knopman et al. Brain 2008; 131(11): 2957-2968). In addition, patients with FTD typically have shorter survival times and more rapid rates of cognitive and functional decline compared to patients with Alzheimer’s disease (Rascovsky et al. Neurology 2005; 65(3): 397-403). Dr. Fred Grossman, Coya’s Chief Medical Officer stated: “We are excited with the results observed in this initial group of patients with this proof-of-concept study. We believe that the increase in Treg numbers and suppressive function, with subsequent anti-inflammatory biological activity still to be evaluated, underscores the potential for this low-dose IL-2/CTLA4-Ig combination to be further studied as a therapy for FTD, for which there are no currently approved treatments.” Summary of Interim Study Results Overall, treatment with low-dose IL-2 and CTLA4-Ig was well tolerated. All 5 patients enrolled in the first cohort completed the study and received the investigational treatment as planned. The most common adverse events were mild injection site reactions. No serious adverse events were reported. Treg numbers and suppressive function increased after the first treatment cycle (p < 0.01 and p < 0.05, respectively), and remained at higher significant levels throughout the treatment period. Clinical functional assessments were performed in all patients at pre-specified timepoints over the course of the study using validated tools, including the Clinical Dementia Rating - Frontotemporal Lobar Degeneration (CDR‐FTLD) scale, the Montreal Cognitive Assessment (MoCA) scale, and the Progressive Aphasia Severity Scale (PASS). Results of the functional tests show that, on average, these five FTD patients treated with low-dose IL-2 and CTLA4-Ig combination exhibited minimal to no cognitive decline over the course of the study, compared to pre-treatment values. The Company intends to publish and/or present more comprehensive data in a future peer-reviewed meeting and/or publication. About Frontotemporal Dementia Frontotemporal dementia (FTD) refers to a group of neurodegenerative disorders characterized by altered behavior and language, with a progressive decline in executive function.1 FTD affects an estimated 30,000 Americans.2 FTD is categorized clinically into various subtypes; the main three include behavioral-variant frontotemporal dementia and two language variants, semantic dementia (also known as semantic variant primary progressive aphasia) and progressive non-fluent aphasia (also known as non-fluent variant primary progressive aphasia). It's a presenile dementia, meaning it can occur in younger individuals, often between the ages of 45 and 64. The average age of onset is 58, with an average survival time of 7.5 years.1,2 References About Coya Therapeutics, Inc. Headquartered in Houston, TX, Coya Therapeutics, Inc. (Nasdaq: COYA) is a clinical-stage biotechnology company developing proprietary treatments focused on the biology and potential therapeutic advantages of regulatory T cells (“Tregs”) to target systemic inflammation and neuroinflammation. Dysfunctional Tregs underlie numerous conditions, including neurodegenerative, metabolic, and autoimmune diseases, and this cellular dysfunction may lead to sustained inflammation and oxidative stress resulting in lack of homeostasis of the immune system. Coya’s investigational product candidate pipeline leverages multiple therapeutic modalities aimed at restoring the anti-inflammatory and immunomodulatory functions of Tregs. Coya’s therapeutic platforms include Treg-enhancing biologics, Treg-derived exosomes, and autologous Treg cell therapy. COYA 302 is a combination treatment comprised of low-dose IL-2 and CTLA4-Ig is an investigational therapy with a dual immunomodulatory mechanism of action intended to enhance the anti-inflammatory function of Tregs and suppress the inflammation produced by activated monocytes and macrophages. Coya is developing COYA 302 for the treatment of fatal neurogenerative diseases characterized by chronic inflammation and Treg dysfunction. For more information about Coya, please visit www.coyatherapeutics.com Forward-Looking Statements This press release contains “forward-looking” statements that are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our current and future financial performance, business plans and objectives, current and future clinical and preclinical development activities, timing and success of our ongoing and planned clinical trials and related data, the timing of announcements, updates and results of our clinical trials and related data, our ability to obtain and maintain regulatory approval, the potential therapeutic benefits and economic value of our product candidates, competitive position, industry environment and potential market opportunities. The words “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” and similar expressions are intended to identify forward-looking statements. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors including, but not limited to, those related to risks associated with the success, cost and timing of our product candidate development activities and ongoing and planned clinical trials; our plans to develop and commercialize targeted therapeutics; the progress of patient enrollment and dosing in our preclinical or clinical trials; the ability of our product candidates to achieve applicable endpoints in the clinical trials; the safety profile of our product candidates; the potential for data from our clinical trials to support a marketing application, as well as the timing of these events; our ability to obtain funding for our operations; development and commercialization of our product candidates; the timing of and our ability to obtain and maintain regulatory approvals; the rate and degree of market acceptance and clinical utility of our product candidates; the size and growth potential of the markets for our product candidates, and our ability to serve those markets; our commercialization, marketing and manufacturing capabilities and strategy; future agreements with third parties in connection with the commercialization of our product candidates; our expectations regarding our ability to obtain and maintain intellectual property protection; our dependence on third party manufacturers; the success of competing therapies or products that are or may become available; our ability to attract and retain key scientific or management personnel; our ability to identify additional product candidates with significant commercial potential consistent with our commercial objectives; ; and our estimates regarding expenses, future revenue, capital requirements and needs for additional financing. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy, short-term and long-term business operations and objectives, and financial needs. Moreover, we operate in a very competitive and rapidly changing environment, and new risks may emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed herein may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Although our management believes that the expectations reflected in our forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances described in the forward-looking statements will be achieved or occur. We undertake no obligation to publicly update any forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Investor Contact David Snyder, CFO david@coyatherapeutics.com CORE IR Bret Shapiro brets@coreir.com 561-479-8566 Media Contacts For Coya Therapeutics: Kati Waldenburg media@coyatherapeutics.com 212-655-0924

-Reported positive 16-week results from the extension phase of the Phase 2b RewinD-LB trial of neflamapimod in dementia with Lewy bodies (DLB), including improvement on the trial’s primary outcome measure- -Plan to initiate Phase 3 trial in mid-2026 following meeting with regulatory authorities- -Awarded 2024 Prix Galien USA Award as “Best Startup” by the Galien Foundation- BOSTON, March 17, 2025 (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 fourth quarter and full year ended December 31, 2024. “Following the highly encouraging 16-week extension results from our Phase 2b RewinD-LB trial, we believe we have established proof-of-concept for neflamapimod as a potential treatment for DLB. Our team is now focused on reporting the results from the 32-week extension phase in the second half of 2025 and discussing next steps on Phase 3 trial design with regulatory authorities,” said John Alam, MD, Chief Executive Officer of CervoMed. Recent Highlights and Anticipated Milestones The 16-week results from the extension phase of the Phase 2b RewinD-LB trial have been accepted as an oral presentation at the 19th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurologic Disorders (AD/PD™) in Vienna, Austria, April 1-5, 2025. In March 2025, CervoMed reported positive 16-week results from the extension phase of the RewinD-LB trial in which patients who were administered a new batch of neflamapimod capsules had higher plasma drug concentration levels and demonstrated improvements on the primary outcome measure, Clinical Dementia Rating Sum of Boxes (p<0.001 v. old capsules; p=0.003 v. placebo), and a key secondary endpoint. The full details on these results can be found here. The Company expects to report 32-week results from the extension phase of the RewinD-LB trial in the second half of 2025. Initial safety, biomarker and pharmacokinetic data from an ongoing trial in patients with mild-to-moderate DLB being treated with a twice daily regimen (80mg BID) of neflamapimod is expected to be available in the fourth quarter of 2025. In January 2025, the Company presented at the 8th International Lewy Body Dementia Conference (ILBDC) in Amsterdam, the Netherlands. During 2025, CervoMed plans to also advance neflamapimod development in additional diseases: In November 2024, the U.S. Food and Drug Administration (FDA) granted neflamapimod Orphan Drug designation for the treatment of frontotemporal dementia (FTD) and CervoMed plans to initiate a Phase 2a trial evaluating neflamapimod in the nonfluent/agrammatic variant of primary progressive aphasia – a subtype of FTD – in mid-2025. In the second quarter of 2025, CervoMed plans to initiate the Phase 2 Restore Trial to evaluate neflamapimod in patients recovering from ischemic stroke. Fourth Quarter 2024 Highlights: CervoMed added to its leadership team with the appointments of Claudia Ordonez, MD, as Senior Vice President, Medical Science, and Mark De Rosch, Ph.D., FRAPS, as Senior Vice President, Regulatory and Government Affairs and Program Management. CervoMed was awarded the 2024 Prix Galien USA 2024 prize in the “Best Startup” category by the Galien Foundation, a premier global institution dedicated to honoring innovators in life sciences. The Company expects to report 32-week results from the extension phase of the RewinD-LB trial in the second half of 2025. Initial safety, biomarker and pharmacokinetic data from an ongoing trial in patients with mild-to-moderate DLB being treated with a twice daily regimen (80mg BID) of neflamapimod is expected to be available in the fourth quarter of 2025. In November 2024, the U.S. Food and Drug Administration (FDA) granted neflamapimod Orphan Drug designation for the treatment of frontotemporal dementia (FTD) and CervoMed plans to initiate a Phase 2a trial evaluating neflamapimod in the nonfluent/agrammatic variant of primary progressive aphasia – a subtype of FTD – in mid-2025. In the second quarter of 2025, CervoMed plans to initiate the Phase 2 Restore Trial to evaluate neflamapimod in patients recovering from ischemic stroke. CervoMed added to its leadership team with the appointments of Claudia Ordonez, MD, as Senior Vice President, Medical Science, and Mark De Rosch, Ph.D., FRAPS, as Senior Vice President, Regulatory and Government Affairs and Program Management. CervoMed was awarded the 2024 Prix Galien USA 2024 prize in the “Best Startup” category by the Galien Foundation, a premier global institution dedicated to honoring innovators in life sciences. Full Year 2024 Financial Results Cash Position: As of December 31, 2024, CervoMed had approximately $38.9 million in cash, cash equivalents and marketable securities, as compared to $7.8 million as of December 31, 2023. The increase in cash on-hand compared to 2023 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 December 31, 2024, will enable the Company to fund its planned operating expenses and capital expenditure requirements into mid-2026. Grant Revenue: In January 2023, CervoMed was awarded a $21.0 million grant from the National Institute on Aging of the National Institutes of Health (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 $9.7 million for the twelve months ended December 31, 2024, compared to approximately $7.1 million for the same period in 2023. This increase was related to an increase in services performed during the twelve months ended December 31, 2024, as a result of, among other things, a larger number of trial sites being active in the RewinD-LB trial during 2024. Research and Development (R&D) Expenses: R&D expenses for the twelve months ended December 31, 2024, were approximately $18.8 million, compared to approximately $8.4 million 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 $9.2 million during the twelve months ended December 31, 2024, versus approximately $6.5 million in the same period in 2023. The increases were primarily due to outsourced legal costs, insurance costs, headcount costs, investor/public relations costs, and stock-based compensation expense as a result of, among things, increased headcount and a full-year of public company expenses in the current year period. Operating Loss: Operating loss was approximately $18.2 million for the twelve months ended December 31, 2024, compared to approximately $7.8 million for the same period in 2023. Net Loss: Net loss was approximately $16.3 million for the twelve months ended December 31, 2024, compared to net loss of approximately $2.2 million for the same period in 2023. The lower net loss in 2023 was driven by a noncash gain recognized for the conversion of the convertible notes upon the closing of the Company’s reverse merger, which was based on the stock price on the date of the transaction. About the RewinD-LB Phase 2b Trial in Dementia with Lewy Bodies The initial phase of RewinD-LB is a randomized, 16-week, double-blind, placebo-controlled clinical trial evaluating oral neflamapimod (40mg TID) in 159 patients with DLB. Patients with Alzheimer’s disease (AD) co-pathology, as assessed by plasma ptau181 levels, were excluded from the trial. Compared to patients with “pure” DLB – who may comprise up to 50% of the total diagnosed DLB patient population at any given time – DLB patients with AD co-pathology have significant, irreversible neuronal loss in the hippocampus. The primary endpoint in the trial is change in the Clinical Dementia Rating Sum of Boxes, and secondary endpoints include Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change, the Timed Up and Go test, and a cognitive test battery. The RewinD-LB trial is funded primarily by a $21.3 million grant from the NIA, which is expected to be disbursed over the course of the trial as costs are incurred. The trial includes 43 sites across in the United States, the United Kingdom, and the Netherlands). Participants completing the 16-week initial phase of the trial were able to continue in the trial while receiving neflamapimod treatment for an additional 32-week extension phase, which includes a pre-specified data readout after the first 16 weeks. About CervoMed CervoMed 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 trial in patients with DLB. Forward-Looking Statements This 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 the RewinD-LB Phase 2b clinical trial and the Company’s announcement of additional data therefrom, 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, and the timing of the initiation of any potential future trials or interactions with regulatory authorities, including the Company’s need to acquire sufficient funding prior to initiating any Phase 3 trial of neflamapimod in DLB. 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 FDA; 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, 2024 filed with the U.S. Securities and Exchange Commission (SEC) on March 17, 2025, 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 Kelleher LifeSci Advisors Investors@cervomed.com 617-430-7579 Source: CervoMed Inc.

Language-processing difficulties are more of an indicator than memory loss of amnestic mild cognitive impairment (aMCI), a risk factor for dementia due to Alzheimer's disease, according to a new study. Individuals with mild cognitive impairment, especially of the "amnestic subtype" (aMCI), are at increased risk for dementia due to Alzheimer's disease relative to cognitively healthy older adults. Now, a study co-authored by researchers from MIT, Cornell University, and Massachusetts General Hospital has identified a key deficit in people with aMCI, which relates to producing complex language. This deficit is independent of the memory deficit that characterizes this group and may provide an additional "cognitive biomarker" to aid in early detection -- the time when treatments, as they continue to be developed, are likely to be most effective. The researchers found that while individuals with aMCI could appreciate the basic structure of sentences (syntax) and their meaning (semantics), they struggled with processing certain ambiguous sentences in which pronouns alluded to people not referenced in the sentences themselves. "These results are among the first to deal with complex syntax and really get at the abstract computation that's involved in processing these linguistic structures," says MIT linguistics scholar Suzanne Flynn, co-author of a paper detailing the results. The focus on subtleties in language processing, in relation to aMCI and its potential transition to dementia such as Alzheimer's disease is novel, the researchers say. "Previous research has looked most often at single words and vocabulary," says co-author Barbara Lust, a professor emerita at Cornell University. "We looked at a more complex level of language knowledge. When we process a sentence, we have to both grasp its syntax and construct a meaning. We found a breakdown at that higher level where you're integrating form and meaning." The paper, "Disintegration at the syntax-semantics interface in prodromal Alzheimer's disease: New evidence from complex sentence anaphora in amnestic Mild Cognitive Impairment (aMCI)," appears in the Journal of Neurolinguistics. The paper's authors are Flynn, a professor in MIT's Department of Linguistics and Philosophy; Lust, a professor emerita in the Department of Psychology at Cornell and a visiting scholar and research affiliate in the MIT Department of Linguistics and Philosophy; Janet Cohen Sherman, an associate professor of psychology in the Department of Psychiatry at Massachusetts General Hospital and director of the MGH Psychology Assessment Center; and, posthumously, the scholars James Gair and Charles Henderson of Cornell University. Anaphora and ambiguity To conduct the study, the scholars ran experiments comparing the cognitive performance of aMCI patients to cognitively healthy individuals in separate younger and older control groups. The research involved 61 aMCI patients of Massachusetts General Hospital, with control group research conducted at Cornell and MIT. The study pinpointed how well people process and reproduce sentences involving "anaphora." In linguistics terms, this generally refers to the relation between a word and another form in the sentence, such the use of "his" in the sentence, "The electrician repaired his equipment." (The term "anaphora" has another related use in the field of rhetoric, involving the repetition of terms.) In the study, the researchers ran a variety of sentence constructions past aMCI patients and the control groups. For instance, in the sentence, "The electrician fixed the light switch when he visited the tenant," it is not actually clear if "he" refers to the electrician, or somebody else entirely. The "he" could be a family member, friend, or landlord, among other possibilities. On the other hand, in the sentence, "He visited the tenant when the electrician repaired the light switch," "he" and the electrician cannot be the same person. Alternately, in the sentence, "The babysitter emptied the bottle and prepared the formula," there is no reference at all to a person beyond the sentence. Ultimately, aMCI patients performed significantly worse than the control groups when producing sentences with "anaphoric coreference," the ones with ambiguity about the identity of the person referred to via a pronoun. "It's not that aMCI patients have lost the ability to process syntax or put complex sentences together, or lost words; it's that they're showing a deficit when the mind has to figure out whether to stay in the sentence or go outside it, to figure out who we're talking about," Lust explains. "When they didn't have to go outside the sentence for context, sentence production was preserved in the individuals with aMCI whom we studied." Flynn notes: "This adds to our understanding of the deterioration that occurs in early stages of the dementia process. Deficits extend beyond memory loss. While the participants we studied have memory deficits, their memory difficulties do not explain our language findings, as evidenced by a lack of correlation in their performance on the language task and their performances on measures of memory. This suggests that in addition to the memory difficulties that individuals with aMCI experience, they are also struggling with this central aspect of language." Looking for a path to treatment The current paper is part of an ongoing series of studies that Flynn, Lust, Sherman, and their colleagues have performed. The findings have implications for potentially steering neuroscience studies toward regions of the brain that process language, when investigating MCI and other forms of dementia, such as primary progressive aphasia. The study may also help inform linguistics theory concerning various forms of anaphora. Looking ahead, the scholars say they would like to increase the size of the studies as part of an effort to continue to define how it is that diseases progress and how language may be a predictor of that. "Our data is a small population but very richly theoretically guided," Lust says. "You need hypotheses that are linguistically informed to make advances in neurolinguistics. There's so much interest in the years before Alzheimer's disease is diagnosed, to see if it can be caught and its progression stopped." As Flynn adds, "The more precise we can become about the neuronal locus of deterioration, that's going to make a big difference in terms of developing treatment." Support for the research was provided by the Cornell University Podell Award, Shamitha Somashekar and Apple Corporation, Federal Formula Funds, Brad Hyman at Massachusetts General Hospital, the Cornell Bronfenbrenner Center for Life Course Development, the Cornell Institute for Translational Research on Aging, the Cornell Institute for Social Science Research, and the Cornell Cognitive Science Program.