Tharimmune, Inc. announced the first patient dosed in the Company's Phase 1 clinical trial with TH104, utilizing a proprietary oral thin film. TH104 is a proprietary transmucosal buccal film embedded with the approved, active compound nalmefene onto a thin film which easily adheres inside of the mouth on the cheek and biodegrades within minutes. Tharimmune's lead clinical-stage asset, TH104, is designed as an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions, by avoiding the first-pass metabolism usually in traditional oral formulations.

The molecule has a dual mechanism of action affecting both the mu and kappa opioid receptors, while emerging data suggests inhibition of interleukin-17, a pro-inflammatory cytokine. The well-known mu and kappa receptors, when stimulated and/or inhibited by the body's endogenous ligands, have been implicated in the body's itch circuitry for certain conditions, specifically cholestatic or dysregulated bile acid-related liver conditions. The Phase 1 clinical trial currently recruiting is a pharmacokinetic bridging study in the U.S. designed as a single-dose, single-center, open-label, randomized 2-way crossover study of TH104 and an intravenous dose of nalmefene administered under fasting conditions, with a 7-day washout period between doses.

Sixteen normal healthy volunteers are anticipated to participate and complete the study. The primary objective is to evaluate the absolute bioavailability of TH104 as well as assess safety and tolerability. Topline data is expected in 2Q24 with a full data readout shortly thereafter.

Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease with debilitating symptoms, including pruritus or "unrelenting itching" and fatigue. Pruritus is a common clinical feature seen in liver diseases but particularly frequent in cholestatic liver disease. A recent study found that pruritus in PBC is under-treated in clinical practice in the United States.

Current treatment options may only be partially effective or poorly tolerated and are not FDA-approved for cholestatic pruritus in patients with PBC, therefore effective solutions for this significant problem are a high unmet need. Multiple ex-US human studies have been completed with TH104 which showed reliable and predictable delivery of nalmefene in healthy subjects using proprietary drug embedded transmucosal oral film applied to the inside of the cheek. Another previously disclosed study of an open-label trial using TH104 in chronic liver disease patients showed a 33.3% decline in 24-hour itch intensity when administered a single low-dose.

Safety and tolerability in these studies were consistent with published studies in the literature with nalmefene, the active ingredient in TH104. TH104 is embedded with nalmefene onto a proprietary transdermal buccal film which easily adheres to the inside of the mouth. This endows TH104 with key features making it an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions.

The molecule has a dual mechanism of action affecting both the µ-opioid receptor and the kappa opioid receptor as well as inhibiting IL-17 inflammatory cytokine expression. These opioid receptors when stimulated and/or inhibited by the body's natural ligands have been known to be involved in the body's itch circuitry.