Tharimmune, Inc. is set to launch a Phase 2 clinical trial in 2025 to investigate TH104 as a treatment for moderate-to-severe pruritus (severe itching) linked to primary biliary cholangitis (PBC), a rare and chronic liver disease. This follows encouraging outcomes from their Phase 1 study of TH104 and constructive feedback from both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).
Phase 2 Trial Design
The planned Phase 2 trial is a multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and efficacy of TH104 in reducing itch in PBC patients. Approximately 40 patients will be enrolled at sites across the U.S., Europe, and the UK. Participants will receive escalating doses of TH104 over a nine-week period, encompassing both treatment and observation phases. Efficacy will be assessed by changes in patient-reported itch scores using the Worst-Itch Numerical Rating Scale (WI-NRS), a clinically relevant outcome measure for pruritus, alongside other quality-of-life metrics. Additional trial details are available on ClinicalTrials.gov (NCT06733519).
TH104: Mechanism and Prior Data
TH104 incorporates nalmefene within a proprietary transdermal buccal film designed for easy adherence inside the mouth. This delivery system aims to provide key advantages for treating liver-related and other pruritogenic inflammatory conditions. TH104 features a dual mechanism of action, impacting both the μ-opioid and kappa-opioid receptors, and potentially inhibiting IL-17 inflammatory cytokine expression. These opioid receptors are known to be involved in the body’s itch circuitry.
PBC and Pruritus: Unmet Needs
According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), PBC is a rare, chronic condition characterized by dysfunctional bile ducts, leading to bile buildup and liver damage. Pruritus affects up to 75% of PBC patients, significantly impairing their quality of life, with limited effective treatment options. Surveys indicate that many patients describe the itch as feeling like “bugs crawling under the skin,” with over 65% experiencing nocturnal pruritus, highlighting a significant unmet medical need.
Corporate Updates
In addition to the Phase 2 trial announcement, Tharimmune reported several corporate achievements, including:
- Validation and manufacturing of TH104 supply for the Phase 2 clinical study.
- Positive regulatory feedback from the FDA and EMA regarding the TH104 clinical program.
- A licensing agreement with Intract Pharma to develop oral biologics, including an oral formulation of infliximab.
- A licensing agreement with OmniAb to access their antibody discovery technology.
- The appointment of David Jones, Professor of Liver Immunology at Newcastle University, to Tharimmune’s Scientific Advisory Board.
- The completion of private placement financings, raising over $4 million to support clinical development.
Tharimmune also announced the appointment of Sanam Parikh to its Board of Directors, bringing expertise in clinical trial management and regulatory submissions.
