Syndeio Biosciences emerged from stealth mode with $90 million in startup funding to advance what the company calls the first synapse-targeted therapeutics platform for treating neurological and psychiatric disorders. The clinical-stage biotech, led by former Karuna Therapeutics and Naurex executives, aims to address synaptopathies—diseases characterized by weakened or lost synaptic connections that affect more than one billion people globally.
The Indianapolis-based company was founded by CEO Derek Small, former chief executive at Naurex, alongside former Karuna executives Steve Brannan and Anantha Shekhar, and Nobel Laureate Thomas Südhof. The Series A funding round was led by Catalio Capital Management and Innoviva, with strategic investments from AbbVie and Eli Lilly.
Targeting Synaptic Dysfunction
Syndeio's approach centers on restoring balance to synaptic function, which becomes disrupted in conditions like Alzheimer's disease, major depressive disorder, and schizophrenia. According to Small, while targeting synapses has been attempted before, the understanding of the pharmacology hasn't been sufficient until now.
"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," Small said. "Targeting the synapse offers a powerful but underexplored pharmacological approach to treating these conditions."
The company's scientific foundation builds on discoveries by Südhof, who won the 2013 Nobel Prize for uncovering how signals instruct vesicles to release their cargo with precision. Südhof and Syndeio's other founders have since "uncovered critical nuances in translating the biology of synaptic plasticity into effective therapeutics," according to the company.
Proprietary Platform and Lead Program
Syndeio's drug development is driven by its proprietary Boost synapse pharmacology platform, originally developed at Stanford University in Südhof's laboratory. The platform combines molecular, functional, and behavioral models to predict treatment outcomes and dosing strategies for synaptogenic agents, integrating electrophysiological, behavioral, and human neuronal network assays.
"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," said Südhof, who co-chairs the company's Scientific Advisory Board.
The company's lead candidate, zelquistinel, is currently in Phase II trials for major depressive disorder, targeting a patient population with significant unmet need. At least 30% of people with MDD fail to respond to two or more antidepressants, leaving substantial therapeutic gaps.
First-of-Kind Alzheimer's Trial
Syndeio plans to initiate what it claims will be the first Alzheimer's disease trial using synaptic function biomarkers as endpoints. Prior clinical studies of zelquistinel have demonstrated rapid and durable enhancement of synaptic plasticity, with measurable biomarker effects.
The company employs quantitative EEG, brain wave analysis, machine learning, and other advanced technologies to refine patient targeting and optimize treatment strategies. Syndeio partners with Beacon Biosignals to incorporate wearable devices into clinical protocols, enabling real-time capture of neurological biomarkers and improving trial precision.
Strategic Vision and Market Position
Small noted that Syndeio follows a "very similar" path to Karuna Therapeutics, which was acquired by Bristol Myers Squibb for $14 billion in December 2023. Like Karuna's registrational Phase II approach with KarXT (now Cobenfy), zelquistinel's Phase II program is designed to enable moving "right into a Phase III registration strategy."
However, Small emphasized a different long-term vision for Syndeio. "Our goal is not to get taken out," he said. "Our goal is to actually have a really long-term advantaged synapse modulating-focused company."
The company represents a decade-long effort, with Small revealing that Syndeio has been in development since he pivoted his investment firm Luson Bioventures to focus on neuroscience in 2015, driven by personal experience as a caregiver to his father with early-onset dementia.
"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 from Catalio Capital Management. "This is a world-class team with unmatched expertise in translating synaptic biology into impactful therapies."
