BK channel

LONDON, UK I July 25, 2024 I Kaerus Bioscience Ltd. (www.kaerusbio.com), a clinical-stage biotechnology company focused on developing therapeutics for rare genetic syndromes of neurodevelopment, today announced that it has initiated a Phase 1 clinical trial of KER-0193, its lead BK channel modulator being developing for Fragile X syndrome. Fragile X syndrome is the most common inherited cause of autism and intellectual disability globally, affecting over 1.5 million individuals globally. There are currently no approved treatments for Fragile X. “Kaerus’ BK modulator program is a potential game-changer in field of therapeutics development for Fragile X syndrome,” declared Ring, adding that, “Our lead BK modulator KER-0193 was developed to specifically address a breakdown in brain function uniquely tied to the genetics of Fragile X syndrome.” “The start of our Phase 1 program for KER-0193 represents an exciting milestone for Kaerus, culminating over 5 years of R&D investment in BK channel modulator discovery and enabled by strong partnerships with academic collaborators, clinical experts and research foundations such as FRAXA,” said Robert Ring, PhD, Chief Executive Officer, Kaerus Bioscience. Michael Tranfaglia, MD, Co-founder of the FRAXA Research Foundation notes: “We are very excited about the therapeutic strategy of targeting BK channels, and believe it can make a significant difference in the lives of people with fragile X,” adding that, “Kaerus’ lead molecule KER-0193 is in an excellent position to address this well-validated treatment target in Fragile X. I am also quite convinced that this treatment approach may be of value in a great many other neurodevelopmental disorders. FRAXA has funded an enormous amount of research over many years focused on the hypo-function of BK channels in fragile X, and the potential value of BK channel modulators to treat this condition.” The Phase 1 clinical trial, being conducted in Belgium, will investigate the safety and tolerability of KER-0193 in healthy volunteers and is expected to complete in 2025. Ring added, “The BK modulator program of Kaerus has also provided the company with a platform to further develop treatments for a variety of additional indications, with clear opportunities in a range of genetic epilepsies.” About KER-0193 KER-0193 is a novel, proprietary, and orally-bioavailable small molecule modulator of BK channels discovered by Kaerus. KER-0193 has already demonstrated broad effects on improving syndrome-relevant behavioral, sensory and cognitive deficits observed in genetic animal models of Fragile X. SOURCE: Kaerus Bioscience

U.S. FDA has granted Orphan Drug Designation to SPG601 for the Treatment of Fragile X Syndrome SPG601 is a novel small molecule that works by correcting specific synaptic dysfunctions in the brain to address core symptoms of Fragile X Syndrome LOS ANGELES, July 23, 2024 (GLOBE NEWSWIRE) -- Spinogenix, Inc., a clinical-stage biopharmaceutical company pioneering first-in-class therapeutics that restore synapses to improve the lives of patients worldwide, today announced that enrollment is now open for their Phase 2 clinical trial evaluating SPG601 for the treatment of adult men with Fragile X Syndrome (FXS), the leading inherited form of intellectual disability and a known cause of autism. The U.S. Food and Drug Administration (FDA) recently cleared the Investigational New Drug (IND) application and granted Orphan Drug Designation for SPG601 for the treatment of people with FXS. "Fragile X patients and their families compose an incredible, yet still underserved community. That is why, during this year’s National Fragile X Awareness Month, we are especially excited to announce that we have begun recruiting for our Phase 2 trial evaluating SPG601 for the treatment of individuals with this difficult condition. This aligns with our commitment to advancing research and treatment options to help people with this condition live better-quality lives, as there are currently no FDA-approved drugs available for those with FXS," said Craig Erickson, M.D., Spinogenix Chief Medical Advisor. “Notably, SPG601 is a novel once-a-day pill that works by binding to BK channels and increasing their activation to correct specific synaptic dysfunctions, a therapeutic approach that we believe can bring much needed hope to individuals and families struggling with FXS.” Stella Sarraf, Ph.D., Spinogenix Chief Executive Officer and Founder, added, "People with FXS and their families face immense challenges every day. This milestone marks a significant step forward in our mission to bring new hope to the people and families affected by this condition. At Spinogenix, we are passionately working to develop first-in-class therapeutics that restore synapses to improve the lives of people worldwide and we are accomplishing this through our trials evaluating SPG601 in FXS and SPG302 in ALS and Alzheimer’s disease. We look forward to exploring the potential of our small molecule platform to address a range of diseases involving synapse loss and dysfunction." This study is a Phase 2 randomized, double blind, placebo-controlled, cross over, single dose of SPG601 and matching placebo in patients with Fragile X syndrome. Enrollment is currently open at the Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio, United States. Additional information on the Phase 2 trial is available on ClinicalTrials.gov (NCT06413537). FXS results from the silencing of the Fmr1 gene which leads to changes in mRNA and protein expression that results in abnormalities in synaptic function. Some of these abnormalities have been shown to be a result of a reduction in the amount and activity of large-conductance, calcium-activated potassium (“BK”) channels. Many core symptoms of FXS have been linked to deficient activity of BK channels. In addition to FXS, BK channel expression and activity have been linked to a range of other conditions including neurodegenerative, vascular, and sensory disorders. SPG601 is a novel small molecule BK channel activator that works by binding to BK channels and increasing their activation to correct specific synaptic dysfunctions that underlie these conditions. About Fragile X SyndromeFragile X Syndrome (FXS) is the leading inherited form of intellectual disability and a known cause of autism that results from the silencing of the Fmr1 gene. FXS is an orphan disease affecting approximately 1 in 4-5000 men and 1 in 6-8000 women globally. In addition to intellectual disability, FXS patients endure a wide range of disabling symptoms, including severe anxiety, social aversion, hyperactivity and attention deficit, sensory hypersensitivity, aggression, developmental seizures, and others. Providing care for individuals with FXS often becomes a full-time commitment for at least one parent and imposes significant financial strain, with direct family healthcare costs totaling $4.1 billion annually in the United States alone. Despite the considerable impact of FXS, there are currently no FDA-approved drugs available for those with the condition. About Spinogenix Spinogenix is dedicated to developing transformative therapeutics for conditions involving the loss or dysfunction of synapses. Our lead clinical-stage synaptic regenerative candidate is a first-in-class therapeutic designed to reverse synapse loss and improve cognitive and motor functions in neurodegenerative and neuropsychiatric diseases such as ALS, Alzheimer’s disease, and schizophrenia. In parallel, we are also developing a synaptic function therapeutic designed to improve behavior in Fragile X Syndrome. More information on Spinogenix can be found at www.spinogenix.com or follow us on LinkedIn. Spinogenix Contact info@spinogenix.com Media Contact Kristin Politi, Ph.D.LifeSci Communicationskpoliti@lifescicomms.com(646) 876-4783

Fragile X Syndrome typically affects males more severely compared to females and is a significant cause of inherited intellectual disability and autism. Credit: bangoland via Shutterstock. Spinogenix has received approval from the US Food and Drug Administration (FDA) for a Phase II clinical trial of SPG601 for Fragile X Syndrome (FXS), the same week that the European Commission gave orphan drug status to Shionogi’s zatolmilast (BPN14770). FXS is a rare genetic condition that causes a range of developmental problems, including learning disabilities and cognitive impairment. The disorder typically affects males more severely than females and is a significant cause of inherited intellectual disability and autism. These issues arise from the silencing of the Fmr1 gene, leading to impaired BK channel function, which is essential for neuron communication. Spinogenix’s SPG601 is a novel small molecule BK channel activator that works by binding to BK channels and increasing their activation to restore synaptic function. The Phase IIa trial will assess the neurophysiological and clinical impacts of SPG601, a once-a-day pill, in adult men diagnosed with FXS. This trial aims to determine how effective the drug is in altering disease markers and alleviating symptoms compared to a placebo. CEO of Spinogenix Stella Sarraf emphasised the gap in effective and patient-friendly solutions for neurodevelopmental conditions such as FXS: “Like many other conditions, loss of synaptic function remains a key driver of disease, and for that reason, we are excited to launch our first US trial to address this unmet need in FXS.” This development follows the 11 April announcement that the European Commission has granted orphan medicinal product designation for Shionogi’s FXS drug, zatolmilast, a cAMP-specific 3′,5’ cyclic phosphodiesterase 4D inhibitor. Zatolmilast is developed by Tetra Therapeutics, a Shionogi Group company. Shionogi acquired Tetra in 2020 as part of its efforts to develop medications for unmet medical needs. Zatolmilast received orphan drug designation for FXS in the US in September 2023. See Also: FDA grants orphan drug status to NovelMed’s PNH treatment Norgine seeks approval for high-risk neuroblastoma treatment In a Phase II clinical trial assessing zatolmilast, cognitive assessments using the NIH Toolbox revealed significant benefits in oral reading recognition, picture vocabulary, and cognition crystallised composite score (NCT03569631), in males aged 18 to 45 years. The drug is forecast to generate $64m in sales in 2030, according to GlobalData. GlobalData is the parent company of Pharmaceutical Technology. There are currently no approved treatments for FXS, and prescribed treatment consists exclusively of off-label drugs that target individual symptoms of the disease, such as SSRIs for depressive symptoms and anxiety, and stimulants that include methylphenidate for hyperactivity, inattention, and impulsivity. According to a report on the GlobalData Pharma Intelligence Center, the FXS market across two major markets (US and Germany) was valued at $21.9m in 2020 and is projected to grow at a compound annual growth rate of 7.6% reaching $45.8m by 2030.