Neurogenic detrusor overactivity

STAMFORD, Conn.--(BUSINESS WIRE)-- Imbrium Therapeutics L.P. (“Imbrium”), a subsidiary of Purdue Pharma L.P. (“Purdue”), achieved last patient last visit in its Phase 1b study of the investigational drug sunobinop as a potential treatment for overactive bladder syndrome (OAB)*. Sunobinop is an investigational, novel and potential first-in-class oral compound discovered by Imbrium Therapeutics and that is currently in clinical development. Sunobinop is designed to bind to and activate the nociceptin/orphanin-FQ peptide receptor (NOP), a protein that is widely expressed in the central and peripheral nervous system1 and involved in a range of biological functions, including bladder function.2,3 Fifty-one female patients suffering from OAB were enrolled in this multicenter, randomized, double-blind, placebo-controlled crossover study. The study was designed to test the effects of sunobinop at bedtime on key disease symptoms, such as urinary urgency, frequency, incontinence, and nocturia in subjects with OAB compared to placebo. OAB is a life-long urologic disorder that reduces patients’ quality of life. The condition affects 14% of men and women in the U.S.4 "Millions of patients with overactive bladder are in need of additional treatment options for the disruptive, distressing symptoms. This study will help us learn more about sunobinop’s potential to be a new treatment option,” said Dr. Julie Ducharme, Vice President and Chief Scientific Officer. “We look forward to reviewing and analyzing the results later this year.” “We are pleased to achieve last patient last visit in the sunobinop Phase 1b study,” said Craig Landau, MD, President and CEO of Purdue. “Our continued progress in this work demonstrates our ongoing commitment to innovation through research and development.” In addition to OAB, Imbrium is also evaluating sunobinop as a potential treatment for interstitial cystitis/bladder pain syndrome (IC/BPS) and separately for alcohol use disorder. *This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that sunobinop will successfully complete development or gain FDA approval. About Imbrium Therapeutics L.P. Imbrium is a clinical-stage biopharmaceutical company dedicated to advancing medical science through the development of important new therapeutics. We are pursuing treatments for genitourinary disorders, disorders of the central nervous system, oncology chemotherapeutics, and non-opioid approaches to the management of pain. As a subsidiary of Purdue Pharma L.P., Imbrium strives to develop new medicines that serve the unmet needs of patients, physicians, and health systems worldwide. We have built a robust and diversified pipeline of investigational drug candidates, and we seek to actively collaborate with industry and academic partners to identify and advance future impactful medicines. For more information, please visit . References 1. Zaveri, N. The nociceptin opioid receptor (NOP) as a therapeutic target: Progress in translation from preclinical research to clinical utility. J Med Chem. 2016; 59(15): 7011-7028. 2. Lambert, D. The nociception/orphanin FQ receptor: a target with broad therapeutic potential. Nat. Rev. 2008 Aug;7(8):694-710. 3. Lazzeri, M., Calò, G., Spinelli, M., et al. Daily intravesical instillation of 1 mg nociceptin/orphanin FQ for the control of neurogenic detrusor overactivity: a multicenter, placebo controlled, randomized exploratory study. J Urol. 2006 Nov;176(5):2098-102. 4. Reynolds, W., Fowke, J., & Dmochowski, R. The burden of overactive bladder on US public health. Current Bladder Dysfunct Rep. 2016 Mar;11(1):8-13. MR-08567

PARIS, France I June 24, 2024 I EG 427, a biotechnology company leading the development of pinpoint DNA medicines for prevalent diseases in neurology based on its unique non-replicative HSV-1 vector platform, announces today that it has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for EG110A, a gene therapy for the treatment of Neurogenic Detrusor Overactivity (NDO) in Spinal Cord Injury (SCI) patients. The phase 1b/2a study is being initiated in 2 leading US institutions. EG110A is a non-replicating HSV-1 vector that has been designed to selectively silence the signals of key bladder sensory neurons responsible for the bladder muscle overactivity, whilst preserving motor neuron and retaining normal bladder function. NDO is a common urinary bladder dysfunction caused mainly by SCI and other neurodegenerative diseases, such as Multiple Sclerosis or Parkinson’s disease. NDO causes uncontrolled urinary incontinence, risk of kidney damage as well as urinary tract infections than can lead to death in 5-10% of the SCI population. NDO affects most (70-84%) patients with SCI 1 , an estimated total of 300,000-400,000 worldwide. It has a significant impact on their quality of life. The European Association of Urology recently estimated that incontinence caused by NDO and other indications, such as overactive bladder, represents a growing economic burden of over €40 billion per year in Europe 2 . “NDO is a serious bladder condition, for whom treatment options are limited,” said Cornelia Haag-Molkenteller, MD, PhD, Chief Medical Officer of EG 427. “Preclinical results have shown clear evidence that suggests EG110A could offer significant medical improvement over existing therapies. These data have shown that one course of treatment with EG110A can potentially lead to long-lasting efficacy without affecting the bladder function. We are excited to move this promising product into the clinic.” “This IND clearance for our first product is a major milestone for EG 427, opening the way for clinical development of EG110A across a series of medically important but neglected neuro-urology pathologies. It is a step forward in bringing the potential benefits of gene therapy to large disease populations in neurology. Non-replicative HSV-1 vectors are truly unique in their ability to deliver therapeutic solutions in a potentially safe, redosable and cost-effective way,” said Philippe Chambon, MD, PhD, Chief Executive Officer at EG 427. Neurological diseases affect some 3 billion people, or about 1 in 3 worldwide, and their medical needs are underserved, a study by The Lancet Neurology 3 found. EG 427 is building a pipeline of products to address these diseases, based on its proprietary non-replicative HSV vector platform, uniquely suited to target neural cells in a safe and long-lasting manner. About EG 427 EG 427 is the second company to bring a non-replicating HSV-1 (nrHSV-1) vector into clinical development, with an Investigational New Drug (IND) cleared by the US Food and Drug Administration (FDA) in June 2024. It will be the first human trial of such a vector, targeting sensory neuron-based diseases. The product, EG110A, addresses multiple severe bladder diseases, such as neurogenic bladder (NDO) and overactive bladder (OAB), and has the potential to be a major improvement over existing therapies, resulting in better care for patients and lower costs for healthcare systems. The company’s unique platform delivers pinpoint neurotherapeutics to treat prevalent diseases of the peripheral and central nervous system. Its vectors can achieve focal transduction in specific regions and then selective expression of transgenes in targeted subsets of neurons thanks to the control of sophisticated regulatory elements. With demonstrated clinical safety and possible repeated dosing, the large payload capacity of nrHSV-1 vectors allows either for long-term gene therapy, or all-in-one gene editing approaches. 1 Hamid, R., Averbeck, M.A., Chiang, H. et al. Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury. World J Urol 36, 1517–1527 (2018). https://doi-org.libproxy1.nus.edu.sg/10.1007/s00345-018-2301-z 2 https://uroweb.org/press-releases/incontinence-costs-european-society-over-40-billion-euros-per-year 3 Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. https://www-thelancet-com.libproxy1.nus.edu.sg/journals/laneur/article/PIIS1474-4422(24)00038-3/fulltext#seccestitle210 SOURCE: EG 427

EG427 Announces New Preclinical Results from Multiple Studies of EG110A in Neurogenic Detrusor Overactivity (NDO) and Overactive Bladder (OAB) In a non-clinical pharmacology study in an OAB model, EG110A showed similar efficacy and a strong safety profile compared to botulinum toxin A, notably without the increase in post-void residual urine volume, a known adverse reaction in NDO and OAB with botulinum toxin AIn a long-term non-clinical kinetic study, EG110A demonstrated persistent transgene expression in the dorsal root ganglia in animals of at least six monthsFirst-in-human phase 1b/2a trial of non-replicative HSV1-based gene therapy on track to start in H1 2024 Paris, France, January 4, 2023 – EG 427, a biotechnology company leading the development of pinpoint DNA medicines for neurology, based on its unique non-replicative HSV-1 vector platform, today reports positive preclinical results from two studies of its gene therapy product EG110A for the treatment of neurogenic detrusor overactivity (NDO) and overactive bladder (OAB). In the first non-clinical pharmacology study comparing bladder injections of EG110A to botulinum toxin A in OAB, EG110A showed comparable efficacy, and further showed no increase in post-void residual urine volume. The increase of residual urine volume is known to lead in humans to an increased frequency of urinary infections, that can be difficult to treat in these patients. In the second study, which evaluated EG110A transgene expression over time in the dorsal root ganglia of treated animals, EG110A demonstrated persistent gene expression out to the final six-month time point. These results strongly support the potential for EG110A to provide long-term relief for patients suffering from NDO and OAB. “These exciting preclinical results demonstrate that EG 427 is on-track to establish proof of concept for first product, EG110A, in its initial indication, a major step toward validating the potential of our broad platform in neurology" said Philippe Chambon, MD, Chief Executive Officer at EG 427. These data offer compelling preclinical evidence for proof-of-concept for EG110A in NDO and OAB, with potential significant medical improvement over existing therapies, as one course of treatment could lead to long lasting efficacy without negative impact on residual volume. EG 427 will be filing an Investigational New Drug (IND) application for EG110A in the first quarter of this year. About EG 427 EG 427 is the second company to bring a non-replicating HSV-1 vector into clinical development, filing an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) in early 2024. It will be the first human trial of such a vector, targeting sensory neuron-based diseases. The product, EG110A, addresses multiple severe bladder diseases, such as neurogenic bladder (NDO) or overactive bladder (OAB), and has the potential to be a major improvement over existing therapies, resulting in better care for patients and lower costs for healthcare systems. The company’s unique platform delivers pinpoint neurotherapeutics to treat prevalent diseases of the peripheral and central nervous system. Its vectors can achieve focal transduction in specific regions and then selective expression of transgenes in targeted subsets of neurons thanks to the control of sophisticated regulatory elements. With demonstrated clinical safety and possible repeated dosing, the large payload capacity of nrHSV-1 vectors allows either for long-term gene therapy, or all-in-one gene editing approaches. For more information: check our website at www.eg427.com follows us on at www.linkedin.com/company/eg427/ Contacts: EG427Philippe Chambon, M.D., Ph.D.Founder and CEOpchambon@eg427.com Global Media Relations Sophie BaumontCohesion Bureausophie.baumont@cohesionbureau.com+33 6 27 74 74 49 Attachment 20240104_Comparison and Persistence_EN_final