Fentanyl Phase 2 Trial met all endpoints; Phase 3 planned for H1 2027

CAMBRIDGE, Mass., Oct. 1, 2026 /PRNewswire/ — Clear Scientific, Inc. today announced positive top-line results from its Phase 2 trial of CS-1103, a small-molecule sequestrant that immediately binds and inactivates fentanyl, subsequently accelerating its removal from the body into urine. The results provide validation of CS-1103’s novel mechanism of action. The trial met all endpoints, with CS-1103 accelerating the removal of fentanyl in human subjects and showing a favorable safety profile.

To reflect the real-world scenarios in which people overdose on fentanyl and are subsequently treated with naloxone, all participants received both fentanyl and naloxone, then followed by CS-1103 or placebo. CS-1103 accelerated fentanyl excretion into urine 25-fold vs control, significantly reducing fentanyl body burden. Critically, CS-1103 did not interfere with the action of naloxone. All results were consistent with non-clinical findings, which have also demonstrated that CS-1103 rapidly reverses respiratory depression caused by synthetic opioids. 

The single-site, double-blind, randomized, inpatient pharmacokinetic and clearance study enrolled 16 healthy adults. A single intravenous dose of CS-1103 was well tolerated, with no serious adverse events reported. All 16 participants completed the study.

“Fentanyl in the body makes rescue and transition to treatment significantly more challenging, said Shekar Shetty, Chief Executive Officer of Clear Scientific. “By removing fentanyl from the plasma and brain rather than replacing it, as with receptor antagonists, CS-1103 could help prevent potentially fatal re-narcotization and reduce or eliminate precipitated withdrawal enabling faster, safer transitions to addiction treatment, such as buprenorphine and methadone. “

About CS-1103

CS-1103 is a first-in-class injectable small molecule sequestrant that binds and inactivates target compounds, rapidly reversing their effects and accelerating their clearance into urine. The Company is initially targeting methamphetamine, fentanyl and cocaine, which are present in close to 95% of all US drug related fatalities. Clear Scientific’s pipeline includes indications in central nervous system (CNS), metabolic diseases, amongst others. 

About Clear Scientific

Clear Scientific was co-founded in March 2019 by Professor George M. Whitesides of Harvard University with technology licensed from Massachusetts General Hospital and the University of Maryland.

Clear Scientific is pioneering a new paradigm for treatment of conditions and diseases that involve an excess of specific compounds in the body. The company is developing highly selective, small molecule sequestrants that bind, inactivate, and rapidly clear these excess compounds from the body. Clear Scientific receives funding from the National Institutes of Health (NIH) / National Institute on Drug Abuse (NIDA) and is working with their network of medical and academic professionals. 

About the Crisis

 In 2024, synthetic opioids were associated with approximately 1 million emergency department visits and more than 55,000 fatalities. These events place a significant burden on healthcare systems, costing hospitals more than $30 billion annually and contributing to overcrowded emergency departments and prolonged patient boarding.

While naloxone successfully reverses opioid-induced respiratory depression, it faces increasing treatment limitations because of the presence of fentanyl in the body:

• re-narcotization, a dangerous situation in which the fentanyl poisoning lasts longer than the naloxone blockade
• polydrug situations, in which naloxone is less effective when other drugs of abuse are present along with fentanyl (e.g., methamphetamine, xylazine, cocaine, etc.)
• precipitated withdrawal, a sudden, severe onset of withdrawal symptoms caused when a receptor antagonist rapidly displaces an opioid from its receptors, before natural withdrawal would have occurred, making transition to medications for opioid user disorder, including buprenorphine, difficult and potentially dangerous

According to the White House, the fentanyl-fueled opioid crisis cost the U.S. economy nearly $2.7 trillion in 2023 —impacting healthcare, criminal justice, and productivity in every community.

CS-1103 is investigational and has not been approved by any health authority. Research reported in this press release was supported by the National Institute on Drug Abuse of the National Institutes of Health under award number UG3DA059286-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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SOURCE Clear Scientific, Inc.