Tharimmune, Inc. announces positive phase 1 data with TH104, a proprietary transmucosal buccal film which easily adheres to the inside of the mouth. The Phase 1 trial was a single-dose, single-center, open-label, randomized, study of TH104 transmucosal buccal film conducted in India in two different cohorts. The primary outcome measure was to determine the safety and tolerability of a buccal dose of TH104 in chronic liver disease patients, while a secondary objective included establishing its' response for clinical efficacy studies for pruritus or "debilitating itching" using a validated endpoint, the Worst Itch-Numerical Rating Scale (WI-NRS).

This study enrolled 2 types of chronic liver disease patients including subjects with cholestatic liver disease categorized as Child-Pugh A (Cohort A) and cholestatic liver disease categorized as Child-Pugh B (Cohort B). The Child-Pugh score is a system for assessing the prognosis and necessity of transplant in chronic liver disease. It provides a forecast of the increasing severity of a patient's liver disease and expected survival rate.

The score is determined by scoring clinical measures of liver disease and the possibility of eventual liver failure. Class A refers to the least severe liver disease with a one to five-year survival rate of 95% and Class B refers to moderately severe liver disease with a one to five-year survival rate of 75%. There were no patients in this study enrolled with a very severe Child-Pugh C classification.

Pruritus is a common clinical feature seen in most liver diseases but particularly frequently in cholestatic liver disease. The WI-NRS is a validated numerical rating scale with 11 numbers anchored at 0 representing "no itch" to 10 representing "worst imaginable itch" which are displayed, and patients are asked to pick the number corresponding to the intensity of their pruritus. Results from multiple large studies support the usefulness and validity of WI-NRS for evaluating change over time in the clinical trial setting.

This study incorporated this relevant clinical outcome assessment for pruritus in chronic liver disease patients administered one 2 mg dose of TH104 applied as a transmucosal buccal film and assessed patient itch intensity over a 24-hour period. A total of 12 cholestatic liver disease patients with a known history of persistent chronic pruritus for at least 4 weeks prior to screening were randomized in this study with 6 subjects each in Cohorts A and B. The mean baseline WI-NRS scores in Groups A and B were 4.33 and 6.17, respectively, translating to moderate-to-severe chronic pruritus at the start of the study. The mean baseline itch score for all 12 subjects was 5.25.

At 1-hour post dosing with TH104, Group A and Group B had a mean decline in WI-NRS scores by 26.8% and 19.0% and continuing to decline 2-hours post-dose by 42.3% and 21.7%, respectively. All 12 subjects had a mean decline of 30.1% in WI-NRS scores at 1-hour and 2-hours post-dose. Both Cohorts continued to improve in mean itch scores at the 4-hour and 8-hour time points including the combined total subjects.

At 24-hours post dosing, Group A and Group B achieved a mean decline of 30.7% and 35.2%, respectively in pruritus scores. All 12 subjects had a mean decline of 33.3% in itch scores after a single dose at 24-hours post dosing of TH104. There were no deaths, other serious adverse events, or other significant adverse events reported during the entire study.

There were no new adverse events during the entire study with events correlated with previous studies and a safety profile consistent in the literature with nalmefene, the active ingredient in TH104. Further analysis including bioanalytical, pharmacokinetic, biomarker, safety and tolerability are currently ongoing, and the Company plans to announce the full data set in 1Q24. The Company intends to provide topline data in 2024 for a phase 1 pharmacokinetic bridging study in the United States designed as a single-dose, single-center, open-label, randomized 2-way crossover study of TH104 transmucosal buccal film and an intravenous dose of drug administered under fasting conditions, with a 7-day washout period between doses.

Sixteen normal healthy volunteers will participate in the study. The primary objective is to evaluate the absolute bioavailability of TH104 as well as assess safety and tolerability of the formulation. The Company plans to engage the US and EU Regulatory Authorities and expects to launch a 28-day Phase 2a trial in the coming months which is currently planned as a multiple ascending dose trial to assess the safety and tolerability of TH104 which will also assess the change from baseline in WI-NRS to evaluate chronic pruritus in PBC patients, with a topline data readout expected in fourth quarter of 2024.