Tharimmune Reports Positive Phase 1 Results for TH104 in Primary Biliary Cholangitis Pruritus

Tharimmune, Inc., a biotechnology company specializing in inflammation and immunology treatments, has announced promising results from its Phase 1 clinical trial of TH104. TH104 is a novel transmucosal buccal film embedded with nalmefene, an approved active compound, which adheres to the inside of the mouth and biodegrades within minutes. This film aims to provide a new route of administration that bypasses the liver's first-pass metabolism, potentially offering advantages for treating liver-related and pruritogenic inflammatory conditions.

The Phase 1 trial, designed as a single-dose, single-center, open-label, randomized 2-way crossover study, involved 20 healthy subjects. The study compared a 16mg dose of TH104 with a 1mg intravenous dose of nalmefene under fasting conditions. Each subject received both treatments with a 7-day washout period between doses. The primary objectives were to evaluate the absolute bioavailability of TH104 and to assess its safety and tolerability.

Results showed that the pharmacokinetic profiles of TH104 via buccal and intravenous administration were consistent. The absolute bioavailability of TH104 was 45.9%, with the median time to maximum concentration (Cmax) occurring at 2.0 hours. Concentrations began to rise within minutes of administration, and the mean half-life (T1/2) of TH104 was 14 hours compared to 9 hours for the intravenous dose of nalmefene. These findings align with published data from other Phase 1 studies involving nalmefene.

Safety and tolerability were comparable between the two administration routes. Treatment emergent adverse events (TEAEs) were reported in 40% of subjects in the TH104 group and 36.8% in the intravenous group, with all TEAEs rated as mild. The most common TEAEs for both groups were dizziness, reported by 20% of subjects taking TH104 and 36.8% of those receiving the intravenous dose. Other frequently reported TEAEs included nausea and somnolence, each occurring in 15% of subjects in both groups. No serious adverse events were noted, and no participants discontinued the study due to adverse events.

The study's data suggests TH104's pharmacokinetics are consistent with those of oral and intravenous nalmefene formulations. This consistency, along with its safety profile, indicates that TH104 could be suitable for once-daily dosing in patients with moderate-to-severe chronic pruritus associated with primary biliary cholangitis (PBC).

Tharimmune is preparing to advance TH104 to a Phase 2 trial in 2024, targeting moderate-to-severe chronic pruritus in PBC patients. This progress is seen as a significant step in developing effective treatments for conditions with limited therapeutic options.

About TH104, it operates with a dual mechanism affecting both the μ-opioid and kappa opioid receptors, which are implicated in the body's itch circuitry, especially relevant to cholestatic liver conditions. Bypassing the liver's first-pass metabolism makes TH104 an attractive candidate for treating liver-related and inflammatory conditions.

Tharimmune, Inc., continues to engage with the FDA regarding its Phase 2 program and maintains its focus on developing a portfolio of therapeutic candidates for inflammation and immunology. The company's efforts include innovative approaches such as multi-specific antibodies targeting well-known receptors like PD-1, HER2, and HER3 in various solid tumors.

Tharimmune's ongoing research and development endeavors reflect its commitment to addressing unmet medical needs in inflammation and immunological disorders, leveraging advanced biotechnological solutions to improve patient outcomes.