SYT-510: First-in-Class Inhibitor Targets Endocannabinoid System to Improve Mental Health Outcomes

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Synendos Therapeutics today announced topline results for its lead asset, SYT-510, a first-in-class inhibitor that modulates a newly identified drug target in the endocannabinoid system (ECS) that helps restore healthy brain functions.¹

SYT-510 belongs to a novel class of ECS modulators called selective endocannabinoid reuptake inhibitors (SERIs), which represent first-in-class, new chemical entities that modulate the ECS through a self-limiting mode of action. This novel mode of action has the potential to combine treatment of a range of symptoms with sustained efficacy in large patient populations alongside the potential to address chronic tolerability, a key unmet need; this represents an innovative and potentially safer therapeutic approach to multiple CNS disorders such as anxiety, mood, and stress-related conditions, and more. Furthermore, SERIs could allow more patients remain treatment adherent and achieve an improved quality of life.

Synendos successfully completed its phase 1 clinical program in 60 healthy volunteers, following the preclinical development of SYT-510, and regulatory approval received from the EMA and MHRA. Participants were dosed in the single and multiple ascending dose studies with no drug-related safety concerns. Key findings from this phase 1 program include (1) plasma and central nervous system exposure reached the anticipated pharmacological levels for activity, and (2) the effect of SYT-510 on electroencephalograms (EEG) showed an effect on the brain consistent with that seen with anxiolytic medicines used successfully to control anxiety symptoms.

“SYT-510 is the first selective endocannabinoid reuptake inhibitors (SERIs) candidate that has advanced into humans and not only demonstrated an excellent safety and tolerability profile, but also promising pharmacokinetic properties and penetration into the central nervous system,” said Andrea Chicca, PhD, cofounder and CEO of Synendos Therapeutics. “Furthermore, the EEG data provide first evidence of an effect on the brain. Overall, this clinical result is very encouraging for our upcoming phase 2 trial where we plan to demonstrate the validity of the first-in-class SERI mode of action in patients.”

The completed preclinical and phase 1 studies provide a strong foundation and rationale for advancing Synendos’ clinical program to evaluate the efficacy of SERI molecules across a spectrum of symptoms commonly observed in psychiatric and neurological disorders.

“Our planned phase 2 study in anxiety symptoms represents a critical step toward unlocking the therapeutic potential of SERIs across psychiatric and neurological disorders,” said George Garibaldi, MD, CMO at Synendos. “By rigorously evaluating both symptom reduction and the restoration of daily function, our program is designed to generate clinically meaningful evidence and address what matters most to patients: the ability to regain their lives and achieve their full potential.”

Investigators first discovered endocannabinoids 30 years ago, identifying anandamide (N-arachidonoyl-ethanolamine). Since then, distinct elements of the ECS have been the target of drug design programs aimed at treating and managing several diseases.² Through this dual focus on innovation and real-world impact, Synendos aims to expand this knowledge and set a new benchmark in how disabling symptoms are treated and managed.

References

1. Synendos Therapeutics reports positive and highly promising topline results from phase 1 trials, paving the way for phase 2 in mental health. News release. September 24, 2025. Accessed September 24, 2025. https://www.biospace.com/press-releases/synendos-therapeutics-reports-positive-and-highly-promising-topline-results-from-phase-1-trials-paving-the-way-for-phase-2-in-mental-health

2. Maccarrone M, Di Marzo V, Gertsch J, et al. Goods and bads of the endocannabinoid system as a therapeutic target: lessons learned after 30 years. Pharmacol Rev. 2023;75(5):885-958.