In short
CSX-1004 is an investigational monoclonal antibody being developed to prevent and reverse respiratory depression caused by fentanyl and related opioids. It is not yet an authorised medicine. One Phase 2 clinical trial is currently authorised in the EU to study CSX-1004 in 24 healthy adults and people with opioid use disorder.
Key points
- CSX-1004 is a fully human monoclonal antibody that binds fentanyl and related analogs.
- It is being developed for prophylaxis against fentanyl overdose and reversal of fentanyl-induced respiratory depression.
- One Phase 2 trial is authorised in the EU, enrolling 24 participants.
- The trial includes healthy adults and people with opioid use disorder.
- The main measure is change in minute ventilation after fentanyl challenge.
- Preclinical studies in non-human primates showed protection from fentanyl-induced respiratory depression for 3–4 weeks after a single dose.
What is CSX-1004?
CSX-1004 is a fully human monoclonal antibody of the IgG1 type. It is an investigational substance, meaning it has no marketing authorisation in the product records and is still being studied in clinical trials. The substance is a protein-based product, given as a solution for injection by intravenous infusion. It is developed by Cessation Therapeutics, Inc. CSX-1004 is specific for fentanyl and structurally related fentanyl analogs, which are potent synthetic opioids.
How does CSX-1004 work?
CSX-1004 binds fentanyl and related analogs with picomolar affinity, meaning it attaches very tightly to these opioid molecules in the blood. By binding fentanyl, the antibody prevents the opioid from reaching its targets in the brain, thereby blocking the respiratory depression that fentanyl can cause. In non-human primate studies, a single intravenous dose of CSX-1004 produced durable and selective blockade of fentanyl-induced respiratory depression for at least one month. Importantly, CSX-1004 does not affect non-fentanyl opioids such as oxycodone, which means its action is selective for fentanyl and structurally similar compounds.
Which conditions is CSX-1004 studied for?
- Fentanyl-induced respiratory depression — a life-threatening slowing or stopping of breathing caused by fentanyl or fentanyl analogs. CSX-1004 is being studied to prevent and reverse this effect.
- Opioid use disorder — a condition in which a person has difficulty controlling opioid use. The authorised Phase 2 trial includes participants with this diagnosis.
How is CSX-1004 given?
In the authorised clinical trial, CSX-1004 is given as a solution for injection by intravenous infusion. The developer's stated target product profile is a fixed-dose subcutaneous injection that could be deployed rapidly in healthcare settings. A planned bioavailability study will compare subcutaneous and intravenous administration.
What do the clinical trials show?
One Phase 2 clinical trial is authorised in the EU under the number 2025-524133-33-00. The trial is interventional and plans to enrol 24 participants, including healthy adults and people with opioid use disorder. The primary outcome is the peak change in minute ventilation, which measures how much air a person breathes in one minute. The trial will evaluate the effect of CSX-1004 on fentanyl-induced respiratory depression compared with a sodium chloride infusion.
Preclinical data support the clinical development of CSX-1004. In a first-in-human pharmacokinetic and safety study, intravenous CSX-1004 was well tolerated and showed a multi-week half-life with predictable exposure across the dose range tested. In mice, CSX-1004 reversed fentanyl antinociception and the respiratory depression caused by the ultrapotent opioid carfentanil. In non-human primates, treatment with CSX-1004 produced up to a 15-fold potency reduction of fentanyl in respiration assays, with protection lasting 3–4 weeks.
What side effects are known?
In a repeat-dose rat study and a human tissue cross-reactivity study, CSX-1004 showed a favourable pharmacokinetic profile with no safety-related issues. A first-in-human pharmacokinetic and safety study indicated that intravenous CSX-1004 was well tolerated. No specific side effects are reported in the available registry or supplementary sources at this stage of development.