ReST Therapeutics, a clinical-stage biopharmaceutical company with operations in New Haven has announced that the U.S. Food and Drug Administration has accepted its Investigational New Drug (IND) application for RST-101, an investigational therapeutic candidate targeting the early treatment of post-traumatic stress disorder.

The IND acceptance clears the way for a first-in-human clinical trial evaluating RST-101 in healthy volunteers. The trial will assess the safety, tolerability, pharmacokinetics, and food effect characteristics of the candidate. PTSD affects approximately 300 million people globally, with roughly 2 million new cases each year. Current treatments, primarily psychotherapy and antidepressant medications, are typically initiated months after a traumatic event, missing what the company identifies as a critical early intervention window.

"We are very pleased with the FDA acceptance of our IND application, which allow us to initiate the First-In-Human clinical trial to evaluate the safety, tolerability, pharmacokinetics and food effect characteristics of RST-101 in healthy volunteers, a pivotal step in our clinical development program to address early PTSD and potentially avoid debilitating long-term symptoms, a profound unmet medical need in mental health," said Reina Benabou, MD, PhD, ReST Therapeutics Chief Medical Officer.

RST-101 is a small molecule NMDA antagonist designed to modulate NMDAR 2C/2D during the early period following trauma exposure. Rather than managing established PTSD symptoms, the therapeutic targets the neurobiological processes involved in trauma memory consolidation and stress response dysregulation, with the goal of preventing the development of chronic PTSD, including associated conditions such as depression, anxiety disorders, and substance abuse.

"This is quite an achievement for ReST therapeutics and a tribute to the commitment of our team and partners. What started with a conviction that we could quench the consolidation of Traumatic Events into a chronic PTSD plaguing the life of millions of civilians and veterans now enters clinical phase," said Founder and Chief Innovation Officer, Gilles Rubinstenn, PhD, MBA.

The ReST Therapeutics milestone arrives at a moment of significant unmet need in PTSD treatment. No new drug has received FDA approval for PTSD in over two decades, and the two medications currently approved target depressive symptoms rather than the underlying trauma response. Even the most widely used therapies leave a substantial portion of patients without meaningful relief, and dropout rates from treatment remain high. RST-101's approach, targeting trauma biology in the hours and days immediately after a traumatic event rather than treating symptoms that may take months or years to become entrenched, represents a meaningfully different strategy from anything currently available.