Kv3.1

Topline results are expected in Q3 2025 ADELAIDE, Australia and CAMBRIDGE, Mass., July 18, 2024 (GLOBE NEWSWIRE) -- Bionomics Limited (Nasdaq: BNOX) (Bionomics or Company), a biotechnology company developing novel, potential first-in-class, allosteric ion channel modulators to treat patients suffering from serious central nervous system (CNS) disorders with high unmet medical need, today announced the initiation of patient screening for the Phase 3 AFFIRM-1 trial evaluating the safety and efficacy of BNC210 for the acute, as-needed treatment of social anxiety disorder (SAD). “AFFIRM-1 trial initiation marks a major achievement for Bionomics as we enter the Phase 3 clinical stage, made possible by our recent capital raise and our expert clinical development team that has a proven track record of executing high quality trials on time and within budget.”, said Spyros Papapetropoulos, M.D., Ph.D., President and CEO of Bionomics. “The Phase 3 study expands on the findings of the Phase 2 PREVAIL trial and brings us closer to potentially transforming the treatment paradigm for the millions of individuals who lack safe and effective acute, as-needed treatment options to assist them in facing anxiety-inducing situations.” AFFIRM-1 targets enrollment of 330 adult patients with SAD at clinical sites in the United States (U.S.). It is a multi-center, double-blind, two-arm, parallel group, placebo-controlled trial. Participants will be randomized 1:1 to receive a single dose of 225 mg BNC210 or matched placebo about one hour before speaking in public. The primary endpoint will compare BNC210 to placebo using the Subjective Units of Distress Scale (SUDS) to measure self-reported anxiety levels during a public speaking task. Secondary efficacy endpoints include the Clinical and Patient Global Impression (CGI and PGI, respectively) scales and the State-Trait Anxiety Inventory (STAI). BNC210 is an α7 nicotinic receptor small molecule with a unique and differentiating profile that is fast-acting, non-sedating, non-addictive and non-cognition impairing, and is suitable for both acute and chronic administration in neuropsychiatric disorders. The Phase 3 initiation of AFFIRM-1 follows results from the full data analysis of the Phase 2 PREVAIL study and the End-of-Phase 2 (EoPh2) meeting with the U.S. Food and Drug Administration (FDA) in Q3 2023 during which agreement was reached on the roadmap for a future NDA submission. Beyond SAD, BNC210 has demonstrated effects in reducing panic symptoms in pharmacologically induced panic attacks, in reducing anxiety levels in general anxiety disorder, and in reducing in total symptom severity in post-traumatic stress disorder (PTSD). Dr Papapetropoulos added, “We remain committed to advancing BNC210, a potential first- and best-in-class candidate with FDA Fast Track designation for both SAD and PTSD and look forward to sharing an update about our PTSD program following the recently completed EoPh2 meeting with the FDA.” About AFFIRM-1 The AFFIRM-1 trial aims to enroll approximately 330 adult patients diagnosed with SAD and who rate ≥60 on the Liebowitz Social Anxiety Scale (LSAS). Study participants are randomized 1:1 to receive a single acute dose of either 225 mg BNC210 or a matched placebo. Approximately 1 hour after dosing, participants are introduced to the public speaking challenge and have 2 minutes to prepare for the speech (anticipation phase). Participants are then required to give a 5-minute speech in front of a small audience (performance phase). The primary endpoint of the trial is the change from baseline to the average of the performance phase of the public speaking challenge in Subjective Units of Distress Scale (SUDS) scores. Secondary endpoints include change in SUDS score from baseline to the average of the anticipation phase, changes in the Clinical Global Impression – Severity (CGI-S) scale, and self-assessment with the State-Trait Anxiety Inventory (STAI, State subscale) and the Patient-Global Impression - Improvement (PGI-I) scale. A follow-up visit occurs 1 week after the public speaking challenge. About Social Anxiety Disorder (SAD) SAD is a significant and persistent fear of social and performance-related situations. As one of the most common mental disorders in the United States, an estimated 31 million Americans will suffer from SAD at some point in their lives. SAD can interfere with a person’s ability to work, make it difficult to maintain friendships, family relationships, and romantic partnerships, cause a person to avoid lifestyle activities like dining out and traveling, and make normal parts of everyday life such as grocery shopping, calling a handyman, or picking up coffee challenging. About BNC210 Formulated as an oral solid tablet BNC210 is a negative allosteric modulator of the α7 nicotinic acetylcholine receptor under development for the treatment of social anxiety disorder (SAD) and post-traumatic stress disorder (PTSD). BNC210 has been given FDA Fast Track designation for acute treatment of SAD and other anxiety related disorders, and for treatment of PTSD and other trauma and stressor related disorders. FOR FURTHER INFORMATION PLEASE CONTACT: GeneralRajeev Chandra Company SecretaryCoSec@bionomics.com.auInvestor RelationsKevin Gardnerkgardner@lifesciadvisors.comInvestor RelationsChris Calabreseccalabrese@lifesciadvisors.com About Bionomics LimitedBionomics (NASDAQ: BNOX) is a clinical-stage biotechnology company developing novel, potential first-in-class, allosteric ion channel modulators to treat patients suffering from serious central nervous system (CNS) disorders with high unmet medical need. Bionomics is advancing its lead drug candidate, BNC210, an oral, proprietary, selective negative allosteric modulator of the α7 nicotinic acetylcholine receptor, for the acute treatment of social anxiety disorder (SAD) and chronic treatment of post-traumatic stress disorder (PTSD). Beyond BNC210, Bionomics has a strategic partnership with Merck & Co., Inc. (known as MSD outside the United States and Canada) with two drugs in early-stage clinical trials for the treatment of cognitive deficits in Alzheimer’s disease and other CNS conditions. Bionomics’ pipeline also includes preclinical assets that target Kv3.1/3.2 and Nav1.7/1.8 ion channels being developed for CNS conditions of high unmet need.www.bionomics.com.au Forward-Looking StatementsBionomics cautions that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as “may,” “could,” “will,” “would,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “intend,” “predict,” “seek,” “contemplate,” “potential,” “continue” or “project” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: the closing of each tranche of the Company’s private placement financing, the achievement of certain milestones for the various tranches, the timely funding to the Company by each investor in the private placement, the timing, size and expectation of the closing of the private placement; and expectations regarding market conditions, the satisfaction of customary closing conditions related to the private placement and the anticipated use of proceeds therefrom; and the Company’s expectation that its current cash, cash equivalents, and marketable securities will fund our operations into the third quarter of 2025. The inclusion of forward-looking statements should not be regarded as a representation by Bionomics that any of its plans will be achieved. Actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in the Company’s business and other risks described in the Company’s filings with the Securities and Exchange Commission (SEC), including, but not limited to, the Company’s Annual Report on Form 20-F filed with the SEC, and its other reports. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Bionomics undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks, uncertainties and other factors is included in Bionomics’ filings with the SEC, copies of which are available from the SEC’s website (www.sec.gov) and on Bionomics’ website (www.bionomics.com.au) under the heading “Investor Center.” All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995. Bionomics expressly disclaims all liability in respect to actions taken or not taken based on any or all the contents of this press release.

The discovery of a physical interaction between two proteins in brain cells that can be traced in mice to control of movement, anxiety and memory could one day open the door to development of new schizophrenia treatment strategies, researchers say. The discovery of a physical interaction between two proteins in brain cells that can be traced in mice to control of movement, anxiety and memory could one day open the door to development of new schizophrenia treatment strategies, researchers say. The research group is the first to determine that the two proteins, both among the dozens of proteins related to risk for the development of schizophrenia, bind to each other under normal conditions in multiple regions of the brain, and that their connection was found in mice to be key to maintaining normal movement, memory function and anxiety regulation. When that connection doesn't happen as it should, they found, behavior can be negatively affected -- in mice, disruption to the proteins' ability to interact increased hyperactivity, reduced risk avoidance and impaired memory. Though delusions and hallucinations are hallmark symptoms of schizophrenia, the condition also encompasses additional symptoms, including movement and memory problems. "These two proteins are seemingly unrelated, and our study has provided a link between them that wasn't recognized before," said lead author Chen Gu, associate professor of biological chemistry and pharmacology in The Ohio State University College of Medicine. "There are more than 100 genes that have been identified as risk genes for schizophrenia, but we still don't know the real mechanisms behind those risks," Gu said. "We're hopeful that getting a better understanding of this mechanism could help in the long run to find a new treatment that could benefit patients with schizophrenia." The study was published recently in the journal Molecular Psychiatry. Previous post-mortem studies have identified risk genes for schizophrenia based on signs of protein dysfunction detected in brain tissue. Among them are the proteins in this study: MAP6, which has a role in supporting a neuron's cytoskeleton or, more specifically, microtubules, and Kv3.1, which helps control the maximal frequency of electrical signaling by neurons. Gu's lab has studied Kv3.1 for many years, often working with genetically altered mice lacking its gene. As the team began exploring a connection between Kv3.1 and MAP6, first study author Di Ma, a graduate student in the lab, found that mice lacking the genes for both proteins experienced similar behavior changes. "That's how we started looking at their relationship in more detail," Gu said. In this study, Ma and her lab mates took a more nuanced look at how the proteins' connection relates to behavior by disrupting their ability to bind to each other in specific brain regions in mice: the hippocampus, which governs learning and memory, and the nearby amygdala, where emotions are processed. The researchers found that disruption to the proteins' connection in the amygdala led to a reduction in risk avoidance -- shown in mice as a lack of fear of height. Blocking the proteins' attachment in the hippocampus resulted in hyperactivity and lower recognition of a familiar object. Though some behavior changes in these experiments differed from the longer list of changes seen in mice completely lacking one or both genes, the finding provided important insights about where the proteins' interactions, or lack thereof, have the strongest effect on behavior. "Different physiological functions we are engaged in daily are governed by different brain regions," Gu said. "That's an advance provided by our study -- because previously we only knew global knockout mice had these behavioral alterations, we didn't really know what brain region was responsible for them." The next step in Gu's lab will be exploring any links between social behavior in mice and these proteins' functions in the prefrontal cortex, a brain region important to decision making and planning. In a series of biochemistry and cell biology experiments, the researchers also determined how the proteins bind and how that connection affects their positioning inside neurons. Results showed MAP6 stabilizes the Kv3.1 channel in a specific type of interneurons, where it helps these cells keep brain signals at an even keel. A drop in the expression of MAP6, on the other hand, dramatically decreased the level of Kv3.1 in those interneurons. The combined findings suggest that when the proteins don't bind properly, there isn't enough Kv3.1 available to maintain interneurons' signal-control function, leading to an imbalance of neural inhibition and excitation in affected brain regions -- and related negative behavioral symptoms. This type of interneurons, capable of generating nerve impulses in high frequencies, represent a key therapeutic target for schizophrenia. "Our study further provides a link between the MAP6 dysfunction and the interneuron signal dysfunction, and we now know that there are two proteins that interact and that one could alter the other," Gu said. "That opens up potential new directions for treatment strategies." This work was supported by grants from the National Institutes of Health.

Research targeted at identifying novel inhibitors or activators of Kv3.1 mutation CAMBRIDGE, England & TORONTO, Canada--(BUSINESS WIRE)-- Metrion Biosciences Limited (“Metrion”), the specialist ion channel contract research and drug discovery company, and The KCNC1 Foundation, a not-for-profit organisation focused on the development of a treatment for an ultra rare genetic disorder, today announced a collaboration to progress a hit identification research project for small molecule modulators of the potassium ion channel Kv3.1, targeting KCNC1-related disorders. Variants of the KCNC1 gene impact Kv3.1 potassium channel function, resulting in neurodevelopmental disorders which can include progressive myoclonic epilepsy (PME) and developmental epileptic encephalopathy (DEE). Symptoms of KCNC1 disorder include seizures during infancy, vision impairment, developmental delay, intellectual disability and many others. The collaboration is focused on the identification of small molecule modulators of the variant potassium ion channel, Kv3.1 as a potential therapeutic strategy for KCNC1-related disorders, identified as being the cause of KCNC1 related DEE. Metrion will develop cell lines for both wild type and variant Kv3.1, to establish a fluorescence-based screen using FLIPR® Penta, a high-throughput cellular screening system. The high-throughput screen will then be used to identify novel inhibitors or activators of Kv3.1 mutant channels. The KCNC1 Foundation was created by the parents of a child diagnosed with KCNC1-related DEE to support research aimed at accelerating the development of a cure, as well as to raise awareness to identify and connect patients and provide support for families. ““We are very excited to collaborate with Metrion on the possibility of identifying a potential therapeutic for children with KCNC1-related disorder. This is our first step of many to address the pathophysiology of the disorder, to give individuals suffering the opportunity to reach their full potential.” Stephanie Telesca, Co-Founder of The KCNC1 Foundation, commented. “We welcome any contributions toward The KCNC1 Foundation as we work hard to pave a path towards a cure.” Dr Andrew Southan, Metrion’s Chief Executive, said: “I would like to thank The KCNC1 Foundation for choosing Metrion to progress this discovery research programme. Our team looks forward to helping the Foundation accomplish its goal to deliver efficacious treatments to patients as quickly as possible.” For more information, please visit and . Donations to The KCNC1 Foundation can be made through gofundme or, for those in the USA, through the organisation’s fiscal sponsor The Rare Village. View source version on businesswire.com: Contacts Media contact: Katie Odgaard Zyme Communications E-mail: katie.odgaard@zymecommunications.com Tel: +44 (0)7787 502 947 Source: Metrion Biosciences View this news release online at: