Cessation Therapeutics Presents Preliminary First-in-Human Study Results of Anti-Fentanyl Antibody CSX-1004

Cessation Therapeutics, Inc., a clinical-stage biotechnology firm, has presented initial data from its Phase 1a first-in-human study of CSX-1004. This investigational monoclonal antibody is aimed at preventing fentanyl-related overdose. The data was shared as an oral presentation at the annual College on Problems of Drug Dependence (CPDD) meeting in Montreal. The results indicated that CSX-1004 is safe and well-tolerated within the tested dose range, showing no dose-limiting toxicities.

The study, titled "First-in-Human Study of the Safety, Tolerability and Pharmacokinetics of CSX-1004," included authors B. Vince, A. Barrett, N. Jacob, P. Bremer, and S. Hull. Presented on June 19, 2024, the preliminary findings from the study revealed that CSX-1004 was generally well-tolerated. Among the 17 recorded adverse events (AEs), 16 were classified as mild, and none were serious. There were no significant laboratory abnormalities, changes in vital signs, or electrocardiogram (ECG) anomalies. Furthermore, the pharmacokinetic profile of CSX-1004 was consistent with other IgG monoclonal antibodies, featuring a rapid distribution phase and a slower elimination phase, resulting in a multi-week half-life.

For at least a month post-dosing, serum concentrations of CSX-1004 remained above levels necessary to block fentanyl-induced respiratory depression, as demonstrated in nonhuman primates. No evidence of immunogenicity, such as the development of anti-drug antibodies, was detected in blood samples thus far.

Andy Barrett, PhD, President and Chief Scientific Officer at Cessation Therapeutics, expressed optimism about the findings, emphasizing the molecule's potential to maintain effective serum concentrations over an extended period. This facilitates the progression of CSX-1004 into Phase 2 clinical development. Dr. Brad Vince, CEO & Chief Medical Officer of Dr. Vince Clinical Research, highlighted the ongoing opioid crisis in America, particularly due to illegally manufactured fentanyl and its analogs. He emphasized the potential of CSX-1004 to offer healthcare providers an additional tool to combat this epidemic, owing to its extended half-life.

The Phase 1a study was a randomized, placebo-controlled, single ascending dose trial (NCT06005402) involving 32 healthy participants. Four doses of CSX-1004 were tested sequentially, starting from the lowest dose: 1.0, 3.0, 10, and 30 mg/kg. Each cohort had eight subjects randomized in a 3:1 ratio to receive either CSX-1004 or a placebo. A Safety Monitoring Committee (SMC) reviewed blinded data after each cohort completed dosing to approve escalation to the next dose level. The trial took place at Dr. Vince Clinical Research in Overland Park, Kansas.

A Phase 2a proof-of-concept study is planned to evaluate the capacity of CSX-1004 to block the respiratory depressant effects of fentanyl through repeated challenges over 28 days in both healthy volunteers and patients with Opioid Use Disorder.

CSX-1004 is a recombinant human immunoglobulin G (IgG)1λ monoclonal antibody specifically targeting fentanyl and related synthetic opioids. It neutralizes fentanyl in the bloodstream, preventing it from affecting the brain’s respiratory centers. CSX-1004 has received FDA Fast Track designation as of October 2023 and is being developed for prophylaxis against fentanyl-related overdose.

Cessation Therapeutics, established in 2018 by Mark Pearson and John D. Harkey, Jr., is focused on creating novel immunobiologics aimed at preventing and protecting against overdoses. Initially targeting fentanyl, the company's monoclonal antibodies can be adapted to address future synthetic opioids and other substances. Backed by Altamont Pharmaceutical Holdings, LLC, JDH Investment Management, LLC, and grant support from the National Institute on Drug Abuse (NIDA), Cessation Therapeutics aims to treat various substance use disorders and improve the lives of individuals and families impacted by addiction.