Entolimod (CBLB502) Biodefense

Entolimod (CBLB502) is in development as a countermeasure against death following total body irradiation. Acute radiation syndrome (ARS) results from radiation exposure, for which there are currently no FDA-approved treatments.

Entolimod (CBLB502) is a recombinant protein that induces a spectrum of protective effects upon direct interaction and signaling via toll-like receptor 5 (TLR5), an innate immune system receptor. It has multiple advantages compared to agonists of other TLRs, including those that are currently under development for oncology applications, stemming from its unique mechanism of action.

The FDA established the Animal Rule in 2002 to permit the approval of certain drugs and biologics that are intended to reduce or prevent serious or life threatening conditions based on evidence of safety from trial in healthy subjects and effectiveness from appropriate animal studies when human efficacy studies are not ethical or feasible.

Efficacy of Entolimod (CBLB502) as a radiation countermeasure has been assessed in animal models. These studies demonstrate that a single administration of Entolimod (CBLB502) given either before or after lethal total body irradiation leads to significant improvement in animal survival. We showed that Entolimod (CBLB502) reduces radiation damage to both hematopoietic (HP) and gastrointestinal (GI) tissues and improves tissue regeneration.

We completed two clinical studies that involved administration of a range of doses of Entolimod (CBLB502) in 150 healthy human volunteers. Both studies demonstrated that administration of Entolimod (CBLB502) appears to be safe within a certain dose range. The most frequent adverse event associated with Entolimod (CBLB502) administration was a transient flu-like syndrome, which is consistent with the mechanism of action of the compound. Ongoing studies will enable accurate definition of the projected human efficacious dose based on comparison of biomarker responses in humans and in animals.

A few additional animal and human studies need to be completed prior to submitting a Biological License Application (BLA) for licensure with the FDA. The protocols for these remaining studies are being discussed with the FDA. The FDA granted Entolimod (CBLB502) both Fast Track and Orphan Drug status for reducing the risk of death following a potentially lethal dose of total body irradiation during or after a radiation disaster.

The U.S. government provides funding to conduct biodefense research and support the development of drugs and vaccines as medical countermeasures against potential terrorist attacks. Both the Department of Health and Human Services and the Department of Defense procure and maintain medical stockpiles to respond to bioterrorist and emerging infectious disease outbreaks. Under a declared state of emergency, countermeasures may be procured for the Strategic National Stockpile under an Emergency Use Authorization prior to their full FDA licensure approval.