Zelquistinel

INDIANAPOLIS--(BUSINESS WIRE)--Syndeio Biosciences today announced its launch to pioneer precision neurotherapeutics focused on repairing and enhancing synaptic function in central nervous system (CNS) diseases. The company’s clinical-stage pipeline and proprietary R&D platform are built on cutting-edge discoveries in synapse biology and translational biomarkers, with a mission to transform treatment for patients suffering from major depressive disorder (MDD), Alzheimer’s disease, schizophrenia, and other synaptopathies. Syndeio is building from over $90 million raised to date from a syndicate of leading life science investors, including Catalio Capital Management and Innoviva, and participation from Tenmile, Luson Bioventures, and Palo Santo, with AbbVie and Lilly as strategic shareholders. The funds will back a world-class team of entrepreneurs, clinicians, and scientists with deep experience in neural drug development, including: Derek Small, Co-founder & Chief Executive Officer : Founder of Luson Bioventures; Founding CEO of Monument Biosciences, Naurex, Inc. (acquired by Allergan), Assembly Biosciences (Nasdaq: ASMB), and other biotech companies Michael G. McCully, President & Chief Operating Officer: Founding President and CEO of Gate Neurosciences; former CEO of Anagin; and other executive roles John Donello, Ph.D., Chief Science Officer : Vice President of External Innovation at Allergan (acquired by AbbVie); Co-founder, President & CSO of Boost Neuroscience Thomas C. Südhof, M.D., Co-chair of Scientific Advisory Board : Nobel Laureate; Avram Goldstein Professor in the School of Medicine at Stanford University; HHMI Investigator Anantha Shekhar, M.D., Ph.D., Chief Scientific Advisor : Founding Advisor of Karuna Therapeutics; Dean of the University of Pittsburgh School of Medicine Steve Brannan, M.D., Chief Medical Advisor : Former CMO at Karuna Therapeutics; former VP of Clinical Development at Takeda Pharmaceuticals; former Senior Medical Director at Novartis; former Clinical Research Professional at Eli Lilly and Company Robert Berman, M.D., Senior Clinical Advisor : Founding CMO at Biohaven Pharmaceuticals; Adjunct Professor of Psychiatry at Yale University School of Medicine Joseph R. Moskal, Ph.D., Co-chair of Scientific Advisory Board: Founder and former CSO at Naurex, Inc.; Professor of Biomedical Engineering at Northwestern University; Director of the Falk Center for Molecular Therapeutics “Synaptopathies – diseases rooted in synaptic dysfunction – including major depressive disorder, Alzheimer’s disease, schizophrenia, and others, affect more than a billion people globally and represent a pressing public health crisis,” said Derek Small, Co-founder and CEO of Syndeio Biosciences. “Targeting the synapse offers a powerful but underexplored pharmacological approach to treating these conditions. Our scientific founders have uncovered critical nuances in translating the biology of synaptic plasticity into effective therapeutics. With these proprietary insights, Syndeio is building a robust pipeline of clinical- and discovery-stage programs aimed at optimizing synaptic function. We are pioneering a new generation of neurotherapeutics that we believe have the potential to transform outcomes for patients with neuropsychiatric and cognitive disorders.” Syndeio’s lead candidate, zelquistinel, is currently being evaluated in a Phase 2 study for MDD, which is enrolling across nearly 30 sites in the US (NCT06547489). It will soon enter a first-of-its-kind synaptic function biomarker trial in Alzheimer’s disease. Zelquistinel harnesses a potential best-in-class novel mechanism for rapidly and durably enhancing synaptic strength and plasticity and has demonstrated promising clinical activity and mechanistic biomarker effects in prior trials. The program is the subject of a recently-published review article in Pharmaceuticals1 and will be featured in both an oral presentation and a pipeline session this week at the ASCP Annual Meeting (details below). The company is additionally advancing apimostinel, an investigational therapy for acute treatment of MDD, in an investigator-led Phase 2a clinical study in collaboration with the University of Pittsburgh (NCT06400121). Syndeio’s clinical programs are powered by its proprietary Boost™ Synapse Pharmacology Platform, which integrates molecular, functional, and behavioral models to predict treatment outcomes and dosing strategies for synaptogenic agents. The platform is rooted in the groundbreaking work of scientific founders from Stanford University, Northwestern University, and Boost Neuroscience, including Nobel Laureate Thomas C. Südhof, M.D., Joseph R. Moskal, Ph.D., Jeffrey Burgdorf, Ph.D., and Syndeio Chief Science Officer John Donello, Ph.D. “The strength of Syndeio’s scientific platform and clinical pipeline has the potential to reshape the landscape of synapse-targeted drug development,” said Jacob Vogelstein, Ph.D., Managing Partner at Catalio Capital Management and Syndeio Board member. “This is a world-class team with unmatched expertise in translating synaptic biology into impactful therapies.” “The fields of neurology and psychiatry are converging on an understanding of synaptic function as one of the most important drivers of brain health,” said Thomas C. Südhof, M.D., Co-chair of Syndeio’s Scientific Advisory Board. “Still, a lack of high-quality preclinical models has long impeded neurology drug development. The preclinical models of Syndeio’s Boost™ Platform provide translatable data predicting clinical outcomes across numerous compounds, increasing our confidence in the potential therapeutic benefits of each of Syndeio’s current and future programs.” Details of Syndeio’s presence at ASCP are as follows: Event: Syndeio Biosciences “Launch & Lunch” Date & time: Tuesday, May 27, 12:30 pm MST Location: Castille 5 Oral Presentation: Pharma Pipeline Presentation on Lead Oral Program Zelquistinel Date & time: Tuesday, May 27, 2:00 pm MST Presenter: Anantha Shekhar, M.D., Ph.D. Location: Princess Ballroom Poster Presentation: “Development of Zelquistinel, an Orally Bioavailable Positive Allosteric Modulator of the NMDA Receptor, to Treat Major Depressive Disorder in Subjects with Comorbid Insomnia and Anxiety” Date & time: Thursday, May 29, 11:15 am MST Presenter: Ronald M. Burch, M.D., Ph.D. Location: Palomino Ballroom References Donello, J.E.; McIntyre, R.S.; Pickel, D.B.; Stahl, S.M. Demystifying the Antidepressant Mechanism of Action of Stinels, a Novel Class of Neuroplastogens: Positive Allosteric Modulators of the NMDA Receptor. Pharmaceuticals 2025 , 18 , 157. https://doi-org.libproxy1.nus.edu.sg/10.3390/ph18020157 About Syndeio Biosciences Syndeio Biosciences (derived from Ancient Greek and meaning “to connect”) is a clinical-stage biotechnology company developing therapies to restore and enhance synaptic health in CNS disorders. The company’s proprietary Boost™ Synapse Pharmacology Platform combines electrophysiology, behavior, and human neuronal network assays to predict clinical outcomes with unprecedented accuracy. Originally developed at Stanford and now expanded through proprietary IP and data systems, Boost™ de-risks new synaptic agents and guides effective treatment strategy. Syndeio’s clinical pipeline includes lead asset, zelquistinel, currently in Phase 2 development for major depressive disorder and will soon be entering an industry-first biomarker study in Alzheimer’s disease, and apimostinel, currently in an investigator-led phase 2 study for acute depression. The company is headquartered in Indianapolis, IN with research laboratories in Menlo Park, CA & Evanston, IL focused on advancing the Boost™ Synapse Pharmacology Platform. Visit us at http://www.syndeio.bio.

Syndeio Biosciences' precision neurotherapeutics are fundamentally differentiated from existing treatments for psychiatric and neurodegenerative disorders, co-founder and CEO Derek Small told FirstWord, because they're designed to "directly modulate synaptic structure and function — targeting the root cause of circuit dysfunction."The startup emerged from stealth on Tuesday with $90 million in funding and two assets in Phase II testing. Its investor syndicate includes Catalio Capital Management, Innoviva, Tenmile, Luson Bioventures and Palo Santo, while AbbVie and Eli Lilly are strategic shareholders.Syndeio's purview includes central nervous system (CNS) disorders that involve synaptic dysfunction, such as major depressive disorder (MDD), Alzheimer’s disease and schizophrenia.Traditional antipsychotics for MDD rely on neurotransmitter blockade, such as dopamine or serotonin antagonists, "which dull symptoms but fail to repair circuits," Small said. He added that, along the same lines, targeting amyloid or tau in Alzheimer’s has "limited cognitive impact unless synaptic integrity is restored."Syndeio is betting that its lead candidate, zelquistinel, can overcome those pitfalls in both diseases. The N-methyl-D-aspartate receptor (NMDAR) positive allosteric modulator (PAM), designed to enhance activity-dependent signaling and plasticity, is in Phase II testing for MDD, and is slated to shortly begin a synaptic function biomarker trial for Alzheimer's – a first-of-its-kind, according to the company."Our goal is not just to manage symptoms, but to repair the machinery of cognition and emotion," Small said. The biotech is also advancing a second NMDAR PAM, dubbed apimostinel, as an acute treatment of MDD. The candidate is being evaluated in an investigator-led Phase IIa study in collaboration with the University of Pittsburgh.Giving synapse repair a BoostWhile NMDAR is a well-known target, Small believes that the company's approach to modulating the receptor is unique, thanks to its Boost Synapse Pharmacology Platform. "We not only utilise scientifically-validated mechanisms, but we’ve also established the translational discipline needed to convert biological promise into therapeutic impact," Small said. "We’ve invested significant amounts to rigorously de-risk both our clinical and non-clinical programmes — not just to advance compounds, but to build a robust translational platform."Syndeio's platform integrates electrophysiology, behavioural assays, biomarker readouts such as EEG and polysomnography, as well as retrospective validation from past CNS programmes to predict treatment outcomes and dosing strategies for synaptogenic agents. According to Small, the Boost platform helps inform the company's asset selection, pipeline prioritisation, clinical trial design, patient selection and dose optimisation. Along with NMDAR, Syndeio is also exploring whether fine-tuning other synaptic targets, such as AMPAR, mGluR, 5HT2A, can restore synaptic plasticity. "Importantly, while these targets are not new, the field has historically applied outdated pharmacologic frameworks, primarily receptor occupancy and chronic exposure models," Small said. "This has overlooked the dynamic nature of synaptic potentiation and depotentiation, which has been well established since the 1970s. Sustained stimulation can paradoxically shut down synaptic function, negating therapeutic effects."