Tharimmune, Inc. announced the completion of the Company's Phase 1 clinical trial with TH104. TH104 is a proprietary transmucosal buccal film embedded with the approved, active compound nalmefene which easily adheres inside of the mouth on the cheek and biodegrades within minutes. TH104, is designed to avoid the liver's first pass metabolism seen in oral formulations and may be an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions.

The molecule has a dual mechanism of action affecting both the mu and kappa opioid receptors. These 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 completed Phase 1 clinical trial was a pharmacokinetic bridging study in the U.S. and was designed as a single-dose, single-center, open-label, randomized 2-way crossover study with 16 mg of TH104 compared to an intravenous 1 mg dose of nalmefene administered under fasting conditions, with a 7-day washout period between doses.

Sixteen subjects were planned and pre-specified to complete both doses of the crossover design per the study protocol. Twenty normal healthy volunteers participated, and 19 subjects completed the study. The primary objective was to evaluate the absolute bioavailability of TH104 as well as assess safety and tolerability.

The Phase 1 pharmacokinetic analysis is ongoing and topline readout and full data are expected to be achieved in the second quarter of 2024. The Phase 1 study demonstrated that TH104 had a comparable safety and tolerability profile to the FDA approved nalmefene reference intravenous formulation of the drug. In the preliminary analysis of the completed trial safety results, all adverse events reported in the clinical trial were categorized as mild and were evenly reported between TH104 and intravenous injection.

One patient did not return for the second dose of the study after a 7-day washout post the first dose which was unrelated to the study. There were no deaths, serious adverse events, or other significant adverse events reported during the entire study with events consistent with the safety profile of marketed formulations as well as those described in the literature including self-resolving nausea, dizziness, and drowsiness per previous reports with nalmefene. 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. Earlier, announced data from several ex-US human studies with TH104 showing consistent and predictable delivery of nalmefene in healthy subjects using proprietary drug embedded transmucosal buccal Film. Safety and tolerability in these studies were consistent with published studies in the literature with nalmefene, the active ingredient in TH104 and are aligned with the profile from the most recent study announced.

Tharimmune announced last quarter the closing of an $11 million public offering which it believes it believes is sufficient to extend its cash runway into early 2025 for clinical readouts of its lead program, TH104. The Company plans to advance both its clinical and non-clinical programs and announce an R&D Day in 2Q24 to update stakeholders and patients. TH104 is embedded with nalmefene onto a proprietary transdermal buccal film which easily adheres to the inside of the mouth.

More than 65% of patients reported that the itch was worse at night, known as noctogenic inflammatory conditions.