Cochlear Diseases

10 February 2025 marie.peytavy Cilcare takes a major step forward with the launch of SAPHIR, a groundbreaking study on the link between hearing disorders and neurodegenerative diseases. A pioneering observational clinical study conducted in partnership with the University Hospitals of Gui de Chauliac (Montpellier) and Carémeau (Nîmes). Recruitment of 309 participants, divided into three groups: Mild Cognitive Impairment (MCI), Parkinson’s Disease, and an age-matched control group. A cutting-edge approach combining advanced auditory testing and biological biomarkers to uncover specific auditory signatures. Hearing impairment is a growing global health challenge, affecting over 20% of the population and expected to impact nearly 900 million people by 2050 (WHO, 2021). Among hearing disorders, sensorineural hearing loss is the most common, with various underlying causes, including cochlear synaptopathy. This form of hearing loss is particularly difficult to detect in its early stages using standard audiometry, making early diagnosis a significant challenge. In Europe, 40% of dementia cases are linked to modifiable risk factors, with hearing loss among the most critical (Livingston et al., 2020). These findings highlight the essential role of auditory health in preventing cognitive decline, reinforcing the need for earlier detection and intervention strategies. The SAPHIR study aims to achieve key breakthroughs in auditory and neurodegenerative research by: Investigating the prevalence of cochlear synaptopathy, a hearing disorder that is challenging to diagnose, in patients with mild cognitive impairment or Parkinson’s disease. Developing distinct auditory signatures through advanced testing, including audiometry, tympanometry, electrophysiology, and speech-in-noise assessment. Examining the link between hearing disorders and biological biomarkers, with a special focus on plasma-based indicators, to better understand the interplay between auditory dysfunction and neurodegeneration. The protocol includes questionnaires, biological analyses, and detailed auditory assessments across three groups of 103 participants each: With 9 million people affected by Alzheimer’s and Parkinson’s in Europe, the SAPHIR study could pave the way for innovative diagnostic and prognostic tools, leading to: The identification of early markers to support preventive care. A deeper understanding of the link between hearing disorders and neurological diseases. Improved quality of life for patients and a reduction in healthcare costs. “Our observational studies help ensure the right treatments reach patients at the right time while providing solid evidence of drug effectiveness through objective biomarkers recognized by health authorities. By exploring the link between hearing and neurocognitive disorders, we aim to push auditory science forward and protect this essential sense.” Celia Belline, CEO of Cilcare. Expected by mid-2026, the SAPHIR study results will help refine Phase 2a trial protocols for CIL001, a drug candidate targeting cochlear synaptopathy, while also advancing the preclinical development of CIL003. As part of an innovative clinical strategy, these observational studies use artificial intelligence to identify and stratify patient groups most likely to respond to treatment, paving the way for more targeted and effective therapies. Press contact Saman Charlotte; csaman@jin.fr; +33 7 67 80 13 97 About the SAPHIR Study The SAPHIR study is a multicenter, prospective, and cross-sectional study, classified as RIPH2, conducted on three groups of participants aged 50 to 85: a group with amnestic mild cognitive impairment (MCI) of neurodegenerative origin (e.g., Alzheimer’s disease), a group of Parkinson’s disease patients, and an age-matched control group. Participants will follow a protocol that includes blood tests, cognitive assessments, and auditory evaluations across three visits, with an optional visit to review their hearing assessment with an ENT specialist. The primary objective is to compare the prevalence of cochlear synaptopathy among the three groups, identified by speech-in-noise deficits despite a normal or slightly altered pure-tone audiogram. Secondary objectives include comparing other hearing disorders (sensorineural hearing loss, auditory neuropathy, and speech comprehension deficits) across groups, as well as studying asymmetric hearing loss in Parkinson’s patients and its link to motor symptoms. The study will also assess the prevalence of hearing disorders across different frequencies and explore associations between auditory profiles—including cochlear synaptopathy—and Alzheimer’s disease, in relation to plasma biomarkers. About Cilcare Cilcare is a biotechnology company specializing in auditory sciences, developing cutting-edge solutions for the characterization, diagnosis, and treatment of hearing disorders and associated diseases. Founded by three visionary entrepreneurs, the company now employs a team of 45 international collaborators, supported by a scientific advisory board. Since its creation in 2014, Cilcare has dedicated itself to addressing these global challenges by combining an advanced R&D platform, a promising drug candidate portfolio, and the use of artificial intelligence and machine learning to characterize various forms of hearing loss. For the past 10 years, Cilcare has also made its technology available to industry leaders and researchers in Europe, the United States, and Asia to accelerate the development of drugs, gene and cell therapies, and medical devices for hearing disorders. Link to Press Release (French Version) Link to Press Release (English version) About cilcare External innovation Therapeutics Auditory Analytics Resources Partners News Contact About cilcare External innovation Therapeutics Auditory Analytics Resources Partners News Contact

OSAKA, Japan, June 6, 2024 - Shionogi & Co., Ltd. (Head Office: Osaka, Japan; Chief Executive Officer: Isao Teshirogi, Ph.D.; hereafter "Shionogi") announced that Shionogi has entered into an option agreement with Cilcare DEV SAS (Head Office: Montpellier, France; Chief Executive Officer: Celia BELLINE, hereafter “Cilcare”) to acquire the exclusive license for the development, manufacturing, and commercialization of CIL001 and/or CIL003, the hearing loss treatment drug candidates worldwide. In conjunction with the signing of the agreement, Shionogi will make an upfront payment of Euros 15 million to Cilcare. If Shionogi exercises its option for both compounds and development and commercialization proceeds successfully, the total of the option payments and development, regulatory, and sales milestones may reach approximately Euros 400 million, plus royalties on net sales. Cilcare has been developing CIL001, a novel candidate drug for hearing loss treatment with auditory nerve protective effects. Currently, preparatory activities are underway to collect auditory data in patients with type 2 diabetes or mild cognitive impairment. From the fiscal year 2025, Phase 2a studies are planned to evaluate the safety and efficacy of CIL001 in patients with type 2 diabetes who have cochlear synaptopathy. Additionally, preclinical studies for CIL003 are currently underway. Shionogi will decide whether to exercise the option right based on the results of the Phase 2a studies of CIL001 and preclinical study data of CIL003, both to be conducted by Cilcare. Hearing loss is a major global health issue affecting around 1.5 billion people worldwide. Its incidence is rapidly increasing, with predictions that, by 2050, a quarter of the global population will experience varying degrees of hearing deficiency1. Hearing loss, particularly when it primarily affects the cochlear synapses*1 in the inner ear, is known as cochlear synaptopathy. This condition is also known to increase the risk of dementia in the elderly and is also an important complication of diabetes2. However, there are no effective treatments available, making it a condition with a high unmet need. The economic loss due to unaddressed hearing loss is said to be around 1 trillion dollars annually, and there is a demand for new therapeutic drugs3. Shionogi has identified Contributing to a Healthy and Prosperous Life as a material focus. We are committed to creating a society where everyone can lead a longer, more vibrant life, realizing their goals. Shionogi continues to strive to deliver innovative treatments for diseases with high unmet medical needs, including hearing loss, to patients as quickly as possible. Reference: 1: Hearing Loss Disease Treatment Market Size & Growth to 2028　(kbvresearch.com) 2: Livingston G. et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 2020; 396: 413-416 3: Estimating the global costs of hearing loss About Cilcare Development Cilcare is a biotech established in 2014, dedicated to harnessing auditory sciences to reshape the future of care via early diagnosis and targeted treatment. Cilcare’s mission is to ensure hearing impairments are addressed earlier and with precision, as they are often associated with chronic diseases from their very early stages. As a catalyst in the development of pharmaceuticals, medical devices, gene therapies, and cell therapies for hearing loss and tinnitus, Cilcare is driving transformative breakthroughs. For more information, please visit Cilcare’s website. About CIL001 CIL001 is a novel candidate drug for hearing loss treatment with auditory nerve protective effect, licensed by Sanofi to Cilcare in 2020. In preclinical studies to date, CIL001 has been confirmed to have an organic effect that repairs inner ear cochlear synapses, and a functional effect that improves the first wave of the auditory brainstem response (ABR)*2. About Hearing loss Hearing loss is a major global health issue affecting around 1.5 billion people worldwide. The significant surge in its incidence is attributed to the growing global population and an increase in the elderly demographic. If this trend continues, it will result in higher health insurance costs, social isolation, poverty, and a decrease in productivity, leading to substantial losses for society. One of the challenges with hearing loss is its gradual onset, making it difficult for patients to recognize and leading to low diagnosis rates. It is known to hinder various social activities, including communication with others, and is also considered a risk factor for central nervous system diseases. *1 Cochlear synapse: The site of information transmission in the cochlea of the inner ear, connecting sensory cells (hair cells) and nerve cells. *2 Auditory brainstem response (ABR) Wave I: The first electrical signal generated by cochlear nerve cells in response to an auditory stimulus, believed to reflect the function of the cochlear synapse. For Further Information, Contact: SHIONOGI Website Inquiry Form : https://www.shionogi.com/global/en/contact.html

Supports the development of a novel, non-hallucinogenic neuroplastogen to restore hearing by stimulating cochlear synaptic growth Reinforces the potential of Delix’s proprietary neuroplasticity platform to identify neuroplastogens to treat a wide range of synapse-related disorders, beyond those associated with mental health conditions BEDFORD, Mass.--(BUSINESS WIRE)-- Delix Therapeutics, a clinical-stage neuroscience company developing novel disease-modifying therapeutics for psychiatric and neurological conditions by targeting neuroplasticity, today announced it has been awarded a $825,000 grant from the United States Department of Defense (DOD), to support the advancement of a neuroplastogen for hearing loss treatment. Delix is pursuing the use of a novel, first-in-class, non-toxic, neuroplastogen that has been found to repair cochlear synaptopathy, or loss of synapses, that contribute to hidden hearing loss (HHL). One of the predominant mechanisms responsible for HHL is the loss of connections between hair cells and auditory nerve fibers, which results in a deficit of signaling from the inner ear to the central nervous system (CNS). Preliminary data has demonstrated that Delix’s compound can safely and effectively repair and restore cochlear neuronal synapses. By repairing these lost connections, there is promise to reverse auditory deficits, as well as prevent loss of hair cells and permanent hearing loss. “Our understanding of the root causes of hearing loss has advanced significantly and we have observed that when damaged synaptic connections within inner hair cells are restored through rapid neuroplasticity, hearing loss can potentially be reversed,” said Delix Chief Scientific Officer, Kurt Rasmussen, PhD. “There are unfortunately no FDA-approved therapies for hearing restoration in adults and, with this important funding, we look forward to advancing a promising neuroplastogen and exploring its potential further in this indication.” The grant will support further evaluation of optimal neuroplastogen dosing in various models of hearing loss, including both temporary and permanent, and observe the role synapses play in functional recovery of hearing after damage. "Over 48 million Americans suffer from hearing loss in at least one ear, with particular prevalence among active duty and retired military personnel. Not only does hearing loss have a significant impact on a patient’s quality of life, but it has been associated with an increased risk of cognitive decline and neurodegeneration,” said Delix CEO Mark Rus. “We are grateful for the DOD's support, as we work to identify and develop non-hallucinogenic neuroplastogens from our neuroplasticity platform to treat a variety of neurological disorders, in the CNS and beyond, including hearing loss, harnessing the body’s ability to repair and restore itself at the level of synapses." Delix is rapidly advancing its library of thousands of novel compounds into scalable, orally bioavailable, take-home therapies. The Company recently presented additional data from its ongoing Phase 1 trial evaluating the safety, tolerability, and pharmacokinetic profiles of lead candidate and novel neuroplastogen, DLX-001, at the Society of Biological Psychiatry (SOBP) Annual Meeting and the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting. Delix compounds have demonstrated the ability to promote fast-acting and long-lasting neural circuitry repair of synapses associated with neuropsychological and neurodegenerative conditions, without the costly in-clinic care, safety issues, and abuse potential inherent to first- and second-generation neural plasticity-promoting compounds such as LSD, ketamine, psilocybin, and MDMA. About Neuroplastogens Neuroplastogens are a novel class of potentially disease-modifying therapeutics for psychiatric and neurological conditions. These compounds promote rapid and sustained neuroplasticity in select neural circuits resulting in fast-acting therapeutic effects. Neuroplastogens are novel chemical entities inspired by compounds that are proving to be beneficial across a range of therapeutic areas including mood, anxiety, cognitive, and neurodegenerative disorders in addition to other synaptopathies. Leveraging our phenotypic drug discovery engine to generate distinct compounds, Delix seeks to bring to market a pipeline of neuroplastogens that will be the faster, stronger, and more effective therapies of the future. About Delix Therapeutics Delix Therapeutics is a clinical-stage neuroscience company focused on harnessing the power of novel neuroplasticity-promoting therapeutics to better treat patients struggling with difficult-to-treat neuropsychiatric and neurological disorders. The company's compounds are easily manufactured small molecules capable of rapidly inducing structural and functional neural changes in targeted areas of the brain. Through its novel Neuroplastogen Platform, Delix is pioneering a new class of fast-acting outpatient pharmacotherapies and rapidly advancing through preclinical and clinical development to bring patients FDA-approved, take-home medicines that will serve several unmet needs and enhance the psychiatric treatment paradigm for patients and providers.