Tharimmune releases pharmacokinetic, metabolism data from TH104 study

Tharimmune (THAR) released pharmacokinetic and metabolism data from its Phase 1 study of TH104, a buccal film formulation of nalmefene, in healthy subjects. Tharimmune recently highlighted the advancement of TH104 for the proposed indication of temporary prophylaxis against respiratory and/or central nervous system depression in military personnel and chemical incident responders exposed to high-potency opioids, following recent positive feedback from the FDA. The Phase 1 study presented this week at Digestive Disease Week taking place in San Diego, California evaluated the pharmacokinetics and metabolism of a single dose of TH104 compared to an intravenous dose of nalmefene injection in healthy volunteers. The study successfully demonstrated that buccal administration of TH104 achieves systemic exposure to nalmefene while offering a distinct metabolic profile compared to IV administration. Phases of drug metabolism denote the “breaking down” and “tagging” of drugs, generally into molecules known as metabolites, by the liver to prepare them for removal. The key difference with drugs taken by mouth is the “first-pass effect,” where the drug goes through the liver’s processing immediately after being absorbed from the gut, before the drug circulates throughout the body. Drugs injected into the bloodstream bypass this initial liver processing generally leading to more drug circulating in the body before being metabolized. Key findings from the pharmacokinetic study presented at the Digestive Disease Week 2025 included: Buccal administration of TH104 resulted in slower absorption compared to IV administration. The ratio of the area under the curve of nalmefene glucuronide, a metabolite, compared to nalmefene was significantly higher for TH104 versus IV administration. Pharmacokinetics of nalmefene sulfate and nornalmefene, 2 other metabolites, were significantly delayed with TH104 compared to IV administration. Both formulations showed early phase 2 metabolism, but importantly, TH104 demonstrated delayed phase 1 metabolism, which is mainly catalyzed by enzymes such as cytochrome P450 oxidases in the liver. By attenuating the burden on hepatic metabolic pathways, TH104 may represent a novel therapeutic candidate for individuals with impaired liver function. The altered pharmacokinetic profile, particularly the delayed onset of phase 1 metabolism observed with buccal administration may confer a potential advantage in populations with impaired hepatic function, and may be important in patients with primary biliary cholangitis. PBC is a rare cholestatic liver disease frequently associated with intractable pruritus. Tharimmune is also advancing TH104 as a therapeutic agent for the management of moderate-to-severe chronic pruritus in PBC patients. The Phase 1 results in healthy subjects also demonstrated comparable safety and tolerability between TH104 and IV nalmefene, with only mild adverse events reported. Building on the favorable pharmacokinetic and safety profile, Tharimmune is advancing TH104 as a critical medical countermeasure product. Following positive feedback from the FDA, Tharimmune is pursuing a 505(b)(2) regulatory pathway for TH104 for the temporary prophylaxis of respiratory and/or CNS depression in military personnel and chemical incident responders who may encounter environments contaminated with high-potency opioids, including weaponized fentanyl and its analogues. The FDA has indicated that no additional clinical trials appear to be necessary prior to the submission of a new drug application for this indication, allowing Tharimmune to leverage existing safety and efficacy data for nalmefene along with the pharmacokinetic data generated with the TH104 buccal film. This expedited pathway underscores the urgent need for such a prophylactic solution, particularly for chemical incident responders operating in high-risk environments where exposure to highly potent opioids is a potential threat to national security. The buccal film formulation offers a distinct advantage for rapid and convenient administration, even when personnel are wearing protective gear.