SP-624

Study to Leverage Firefly’s BNA™ Technology for Biomarker Identification, with Potential Applications for Broader Neurological ResearchTORONTO, Oct. 15, 2024 (GLOBE NEWSWIRE) -- Firefly Neuroscience, Inc. (“Firefly,” or the “Company”) (NASDAQ: AIFF), an Artificial Intelligence (“AI”) company developing innovative solutions that improve brain health outcomes for patients with neurological and mental disorders, today announced that its FDA-510(k) cleared Brain Network Analytics (BNA™) biomarker discovery AI platform will be used to support Arrivo Bioventures’ (“Arrivo”) Phase 1 exploratory study of its first-in-class SIRT6 activator, SP-624, in healthy volunteers and patients with major depressive disorder (MDD). The study, which has enrolled its first subject, is designed to evaluate the impact of the epigenetic mechanism of action of SP-624 on neurological pathways and assess changes in various cognitive domains. SP-624 is also currently being studied in a large Phase 2b study in patients diagnosed with MDD, with efficacy in females as the primary endpoint. “We believe that utilizing Firefly’s BNA™ technology in the SP-624 study will help Arrivo better understand SP-624’s activity and uncover critical biomarkers that may inform future research across neurological conditions,” said Jon Olsen, CEO of Firefly. “Together with Arrivo, this study underscores our shared commitment to advancing targeted treatments for women with major depressive disorder, which continues to be an unmet medical need in mental health.” In an earlier Phase 2 study of SP-624, Arrivo explored efficacy over placebo during a four week treatment period. In a post-hoc analysis, the company found statistically significant improvement versus placebo consistent across both investigator and patient measures of MDD in female subjects, which was achieved as early as week 2. In male subjects, there were no statistically significant changes detected. While differences in MDD between males and females have long been discussed, these results support recent published literature citing differences in gene expression between males and females with MDD. Using Firefly’s BNA™ technology, Arrivo will also identify target engagement and biomarkers in the Phase 1 study that can be used in future studies across a variety of neurological conditions, including MDD. “There is a growing body of literature suggesting that targeting SIRT6 can play an important role in multiple neuropsychiatric, neurodegenerative, inflammatory, and metabolic diseases,” said Steve Butts, CEO of Arrivo. “This study should help us in our ongoing efforts to characterize the activity of SP-624 and look for potential biomarkers.” The Phase 1, single-center, double-blind, randomized, placebo-controlled study is being conducted at Alivation Research with Walt Duffy, M.D., founder, CEO and Chief Medical Officer, as the Principal Investigator. About FireflyFirefly (NASDAQ: AIFF) is an Artificial Intelligence (“AI”) company developing innovative solutions that improve brain health outcomes for patients with neurological and mental disorders. Firefly’s FDA-510(k) cleared Brain Network Analytics (BNA™) technology revolutionizes diagnostic and treatment monitoring methods for conditions such as depression, dementia, anxiety disorders, concussions, and ADHD. Over the past 15 years, Firefly has built a comprehensive database of brain wave tests, securing patent protection, and achieving FDA clearance. The Company is now launching BNA™ commercially, targeting pharmaceutical companies engaged in drug research and clinical trials, as well as medical practitioners for clinical use. Brain Network Analytics was developed using artificial intelligence and machine learning on Firefly’s extensive proprietary database of standardized, high-definition longitudinal electroencephalograms (EEGs) of over 17,000 patients representing twelve disorders, as well as clinically normal patients. BNA™, in conjunction with an FDA-cleared EEG system, can provide clinicians with comprehensive insights into brain function. These insights can enhance a clinician’s ability to accurately diagnose mental and cognitive disorders and to evaluate what therapy and/or drug is best suited to optimize a patient’s outcome. Please visit https://fireflyneuro.com/ for more information. About Arrivo BioVentures Arrivo BioVentures is propelled forward by its insatiable curiosity and drive to solve complex problems and help millions of patients globally. Working in partnership with investors, innovators, and pharmaceutical companies, Arrivo is always seeking solutions for unmet medical needs. Arrivo has a portfolio of diverse drug candidates with the potential to be first-in-class or best-in-class. Arrivo is based in Morrisville, N.C., on the edge of Research Triangle Park. For more information, visit www.arrivobio.com. Forward-Looking StatementsCertain statements in this press release and the information incorporated herein by reference may constitute “forward-looking statements” for purposes of the federal securities laws concerning Firefly. These forward-looking statements include express or implied statements relating to Firefly’s management teams’ expectations, hopes, beliefs, intentions, or strategies regarding the future. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs concerning future developments and their potential effects. There can be no assurance that future developments affecting Firefly will be those that have been anticipated. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond Firefly’s control) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to development and commercialization of BNA™ technology; risks related to Firefly’s ability to recognize the anticipated benefits of the merger (the “Merger”) with WaveDancer, Inc. (“WaveDancer”); risks related to Firefly’s ability to correctly estimate its operating expenses and expenses associated with the Merger and other events and unanticipated spending and costs that could reduce Firefly’s cash resources; the ability of Firefly to protect its intellectual property rights; competitive responses to the business combination; unexpected costs, charges or expenses resulting from the Merger; potential adverse reactions or changes to business relationships resulting from the completion of the Merger; legislative, regulatory, political and economic developments; and those factors described under the heading “Risk Factors” in the in the registration statement on Form S-4 filed by WaveDancer with the Securities and Exchange Commission on January 22, 2024, as amended, and declared effective on February 6, 2024. Should one or more of these risks or uncertainties materialize, or should any of Firefly’s assumptions prove incorrect, actual results may vary in material respects from those projected in these forward-looking statements. It is not possible to predict or identify all such risks. Forward-looking statements included in this press release only speak as of the date they are made, and Firefly does not undertake any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. Arrivo Bio Media ContactICR HealthcareAlexis Feinberg, Vice PresidentAlexis.feinberg@westwicke.com Firefly Neuroscience Investor ContactsKCSA Strategic CommunicationsValter Pinto / Jack Perkins(212) 896-1254Firefly@KCSA.com Firefly Neuroscience Media ContactKCSA Strategic CommunicationsRaquel Cona, Vice President(516) 779-2630Rcona@KCSA.com

Pictured: A vibrant collage with layered mind and keyhole/Nicole Bean for BioSpace The psychiatric space is drawing significant interest as late-stage readouts for novel depression treatments glitter just on the horizon—with many experts hoping that a precision medicine approach is on the cusp of proving its worth. Though the market is saturated with generic selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs—the go-to treatments for depression—studies show that a large portion of the population is depressed. An estimated 21 million, or 8.3% of adults in the U.S. had at least one major depressive episode in 2021. Yet, according to Amit Etkin, CEO of Alto Neuroscience, there is hope ahead. “We’re in this period of a lot of readouts, new drugs and the potential for a very different set of antidepressants [on the market] five years from now,” he told BioSpace. Etkin noted that assets now in development rely on different mechanisms and targets than the antidepressants currently on the market. “There’s no appetite for developing things that are similar to what we’ve had before,” he said. Some of these novel therapies are tested on only a subset of patients within a given diagnosis, moving forward a precision approach that experts say could move the needle on the standard of care. “While there are lots of medications out there, we have not solved depression,” Steve Butts, CEO of Arrivo BioVentures, told BioSpace. Many recent approvals in the psychiatric space have been “polished up versions of older medications. We are getting closer to personalized medicine with this”—something he noted is crucial for both the industry and patients. Precision Psychiatry Comes Into Focus The success rate for psychiatric drugs is the lowest among non-oncology indications with a 6.2% chance of approval. Even successful drugs in the category have a small effect size, and according to Etkin, solely employing novel mechanisms has so far not improved things on that front. He’s hoping precision medicine will. Etkin sees a stark division between a “traditional all-comer” strategy and a precision approach to psychiatric drug development. Historically, trials have included all patients within a diagnosis, such as major depressive disorder (MDD). With a precision approach, companies have the opportunity to understand the underlying biology of psychiatric disorders, “using something other than just the diagnosis” to select patients for trials and targeting the patient population expected to respond better to the therapeutic. Both Alto and Johnson & Johnson’s Janssen are taking a precision approach to depression. Janssen is sectioning out its trial participants based on specific symptoms. Its orexin antagonist, seltorexant, is in a Phase III study for MDD patients suffering from insomnia, while aticaprant, a kappa-opioid receptor (KOR) antagonist, is in a Phase III study targeting MDD patients with anhedonia. Both studies are projected to read out this year. Alto is using clinical biomarkers to select patients for trial participation. Depending on the trial, the biotech chooses participants based on cognitive tests or EEG measures to indicate the underlying biology of each patient’s brain. In December 2023, the company shared a positive readout from ALTO-300 in patients bearing a specific EEG-based biomarker. Results from the trial showed that patients with the biomarker saw a greater drop in their Montgomery–Åsberg Depression Rating Scale (MADRS) score than patients without the biomarker profile. In January 2023, a study of another candidate, ALTO-100, showed 61% of biomarker-defined patients had a clinical response to the treatment versus only 33% of comparators without the biomarker. Meanwhile, Arrivo is developing a novel therapeutic for depression with an epigenetic mechanism. Its SP-624 activates SIRT6, an enzyme that works through several inflammatory pathways and is essential to epigenetic regulation of gene expression, mitochondrial health and DNA repair. In a Phase I trial, the company realized its asset alleviates depression symptoms preferentially in females. Butts said this discovery is a strong step forward toward understanding the underlying biological basis for why this psychiatric disorder manifests so differently in males and females. New Mechanisms Drive Investments The neuropsychiatric space has been gaining traction as “success builds on success,” Butts said, pointing to the recent $14 billion acquisition of Karuna Therapeutics and its schizophrenia asset, KarXT, by Bristol Myers Squibb. BMS is already seeing a return on its investment as Phase III data in April showed significant and sustained symptom improvement in patients taking KarXT. If approved, KarXT would be the first new class of medicine for schizophrenia in over 50 years, Karuna founder and Chief Operating Officer Andrew Miller told BioSpace in a previous interview. The M1/M4-preferring muscarinic agonist is being reviewed by the FDA with an action date of September 26. Another recent deal in the schizophrenia space came last December, when AbbVie dropped $8.7 billion to acquire Cerevel Therapeutics, picking up its late-stage, next-generation antipsychotic emraclidine. The asset is a positive allosteric modulator of the muscarinic M4 receptor being tested in schizophrenia and Alzheimer’s disease psychosis. “Those kinds of [deals] help the rest of our industry,” Butts said. On the depression front, Neurocrine Biosciences revealed positive data from a Phase II study of a Takeda-partnered asset targeting the AMPA receptor in patients who don’t benefit from current antidepressants. Graig Suvannevejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, told BioSpace that while the Phase II data were good, the effect will now need to be repeated in a larger Phase III study. KOR antagonists have also caught the eye of pharma. In addition to Janssen’s aticaprant, Neumora Therapeutics’ navacaprant is in a Phase III study for MDD. Navacaprant is being tested as a monotherapy, potentially making it a good option for patients who want to avoid the “troublesome side effects” of current antidepressants, Suvannavejh said. Finding the right novel targets for each unique patient population is going to end up being one of the “more productive tensions in our field as we see these readouts happening,” Alto’s Etkin said. “New mechanisms and a new approach in orientation—other areas of medicine have done quite a bit, but we’ve just not seen that historically in psychiatry.” Novel mechanisms also stand a better chance for reimbursement, Suvannevejh noted. With multiple generic SSRI and SNRI drugs available, insurers are less likely to cover the cost of a drug with a similar mechanism, he said. “The worst thing that can happen is that you spend 10 years getting your drug approved,” only to have insurance refuse to pay for it, Suvannevejh explained. “Payers will pay for novelty and innovation.” Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.