Cambridge, Massachusetts, U.S., October 5, 2026
Clear Scientific, Inc. has reported positive top-line Phase 2 results for CS-1103, an investigational small-molecule sequestrant designed to rapidly bind and inactivate fentanyl and accelerate its removal from the body. The clinical findings provide important human validation for the therapeutic’s novel mechanism of action and demonstrate its potential to address challenges associated with fentanyl overdose and opioid treatment. In the randomized Phase 2 study, CS-1103 met all prespecified endpoints, accelerated fentanyl clearance, and demonstrated a favorable safety profile. The company is developing CS-1103 as a potential new approach that could complement existing emergency treatments by reducing the amount of fentanyl remaining in the body.
CS-1103 Accelerates Fentanyl Clearance 25-Fold
The Phase 2 study was designed to reflect a real-world fentanyl overdose treatment scenario, in which patients receive naloxone to reverse opioid-induced respiratory depression. All study participants received fentanyl and naloxone before being administered either CS-1103 or placebo. Results showed that CS-1103 accelerated fentanyl excretion into urine by 25-fold compared with control, significantly reducing fentanyl body burden. Importantly, the investigational therapy did not interfere with the action of naloxone, supporting the potential for CS-1103 to be used alongside established opioid overdose interventions. The findings were also consistent with previous non-clinical research showing that CS-1103 can rapidly reverse respiratory depression associated with synthetic opioids. By directly targeting fentanyl in the body rather than relying solely on receptor antagonism, the investigational therapy represents a distinct therapeutic strategy for managing opioid exposure.
Phase 2 Study Shows Favorable Safety Profile
The single-site, double-blind, randomized inpatient Phase 2 pharmacokinetic and clearance study enrolled 16 healthy adults. Participants received a single intravenous dose of CS-1103 and were monitored to assess fentanyl clearance, pharmacokinetic effects, and safety. According to Clear Scientific, the treatment was well tolerated, with no serious adverse events reported during the study. All 16 participants completed the trial. The company said the results validate CS-1103’s proposed mechanism of action and support continued clinical development. Because the study was conducted in healthy volunteers and involved a relatively small participant population, additional clinical research will be needed to determine how the treatment performs in people experiencing actual fentanyl overdose and other relevant clinical situations.
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Novel Approach Targets Fentanyl Body Burden
CS-1103 is being developed as a first-in-class injectable small-molecule sequestrant that binds target compounds, inactivates them, and promotes their rapid clearance into urine. Clear Scientific is initially investigating the technology against fentanyl, methamphetamine, and cocaine, with the broader platform designed to address conditions associated with excessive concentrations of specific compounds in the body. The company believes removing fentanyl from plasma and other tissues could potentially help address challenges such as re-narcotization, in which opioid effects return after naloxone activity declines, and precipitated withdrawal, which can complicate transitions to medications such as buprenorphine and methadone. CS-1103 remains investigational and has not been approved by any health authority. The company was co-founded in 2019 by Professor George M. Whitesides of Harvard University and has developed its sequestrant technology using licensed research from Massachusetts General Hospital and the University of Maryland. The Phase 2 findings represent a significant clinical development milestone for the program and provide a basis for further investigation of CS-1103 in opioid-related emergencies and other therapeutic applications.
Source: Clear Scientific press release
