Epilepsy, Partial, Sensory

Bsense Bio Therapeutics Ltd., a preclinical-stage biopharmaceutical company developing innovative small molecule drug candidates for sensory hyperexcitability disorders, today announced the clinical candidate nomination of their drug candidate, BSEN760, a dual Kv7.2/3 and TRPV1 ion-channel modulator, which heralds a potential breakthrough in the treatment of chronic pain by potentially providing efficacy for a broad spectrum of chronic pain conditions devoid of side effects associated with current standard-of-care (SOC) treatments. BSEN760 is a novel potent and selective, orally active, investigational small molecule drug that simultaneously activates Kv7.2/3 and inhibits TRPV1. The dual mechanism of action (MOA) of BSEN760 underlies the compound’s exquisite potency and synergistic activity in dampening sensory neuron hyperexcitability. Kv7.2/3 and TRPV1 are highly validated therapeutic targets for modulation of sensory hyperexcitability, specifically for pain alleviation; however, significant CNS, renal and thermal side effects have limited successful translation of numerous Kv7.2/3 and TRPV1 drug development programs. The Company’s novel MOA, targeting dual ion-channel modulation, is particularly advantageous compared to current SOC drugs due to its efficacy in models of chronic pain at low (sub-nanomolar) exposures that translate to a wide therapeutic window avoiding side effects. As such, BSEN760 may enter the market with comparable, potentially better, efficacy vs. SOC, and a much improved safety profile. Preclinical studies of BSEN760 demonstrate dose-proportional efficacy in neuropathic and osteoarthritis pain models. Moreover, BSEN760 shows no evidence of motoric impairment/sedation (rotarod) nor effects on core body temperature and thermal sensation, side effects that have precluded clinical development of drugs targeting either Kv7.2/3 or TRPV1. These, and other data, support the Company’s efforts toward full preclinical development of BSEN760 and IND submission by Q1 2025. Haim Belinson PhD., Chief Scientific Officer of Bsense, commented: “The nomination of our dual Kv7.2/3-TRPV1 ion-channel modulator drug candidate, BSEN760, is an exciting step forward for Bsense Bio Therapeutics and the treatment of chronic pain conditions in general. With its unique features of modulating sensory nervous system hyperexcitability by two well validated pain MOAs but without class-related side effects, this asset shows unmatched potential to provide a superior, non-addictive treatment option for chronic pain. We look forward to bringing BSEN760 to the clinic in Q1, 2025 as we work to complete IND-enabling studies.” Alan Brown, Director, AD Brown Medchem Consulting Limited, added: “The exciting pharmacological profile and medicinal chemistry development behind BSEN760 suggest that this compound represents a significant step forward in the development of new pain therapeutics.” Vladimir Skljarevski M.D., Clinical consultant, Principal of VS Biopharma Consulting Inc.: “This novel and unique mechanism of action, involving modulation of two co-located ion-channels, has a potential to provide significant clinical analgesia across a broad range of chronic pain conditions with no addiction/abuse potential.” Sensory hyperexcitability translates to an increase in sensory stimuli, such as proprioception, vision, sound, and touch, as unpleasantly heightened sensations. Pathophysiology could arise from nerve damage, inflammation, and metabolic diseases, all of which may alter the normal function of sensory neurons. Sensory hyperexcitability is observed in a wide variety of neurological disorders, including Epilepsy, Anxiety, Autism, Pain, Tinnitus, and Pruritus to name a few. Sensory hyperexcitability related disorders impact millions of people worldwide. Moreover, these conditions have a profound negative effect on the quality of life of patients and place a significant operational and economic burden on healthcare systems. The multitude of patients suffering from sensory hyperexcitability disorders emphasizes a significant unmet medical need that ranges from a lack of effective pharmacological treatment (i.e., Tinnitus, various Pruritic conditions) to those, in particular chronic pain, with multiple available pharmacological treatments but that demonstrate less-than optimal efficacy often associated with significant side effects as well as, for some, the potential for drug abuse and addiction. In each case, the spatial and mechanistic emergence of sensory hyperexcitability may lead to different and varied clinical manifestations; however, in all cases, the sensory neuronal system’s excessive activity is the hallmark of the disorder. Importantly, the anatomical positioning of dorsal root ganglia (DRG) outside the CNS blood-nerve barrier has made signal transmission and transduction by afferent sensory neurons a prime target for modulating pain signaling to the spinal cord and higher brain centers. As such, modulation of hyperexcitability at the level of DRG neurons where Kv7.2/3 and TRPV1 are predominantly, and mutually, expressed represents a unique, synergistic approach toward providing significant relief coupled with superior tolerability to sensory hyperexcitability disorders. Bsense Bio Therapeutics is developing dual cationic channel small molecule modulators for the treatment of sensory hyperexcitability-related disorders. The goal of the Company’s novel, pioneering approach of targeting multiple neuronal excitability-related mechanisms using a single compound is to achieve greater efficacy and safety compared to current therapeutic approaches that focus on modulation of a single target. Bsense Bio’s approach is based on the targeting of two cation channels, TRPV1 and Kv7.2/3, a ligand-gated and a voltage-gated potassium channel, respectively, which are co-localized on sensory neurons and are widely recognized as prominent players in controlling neuronal excitability. Bsense Bio was established based on the initial discovery and identification by Prof. Bernard Attali and Dr. Asher Peretz from Tel-Aviv University of small molecule compounds demonstrating dual ion-channel activity. Bsense Bio was founded in September 2018 at the FutuRx biotech incubator and is financed by RMGP, OrbiMed Israel Partners, Johnson & Johnson Innovation – JJDC, Takeda Ventures Inc., and the Israeli Innovation Authority (IIA). The content above comes from the network. if any infringement, please contact us to modify.