Positive safety/tolerability profile achieved with TH104 showing self-resolving, mild side effect profile aligned with previous studies
Phase 1 clinical trial compared oral transmucosal delivery of TH104 to injectable reference approved drug completed
Company fully funded into 2025 with Phase 2 moderate-to-severe chronic pruritus in primary biliary cholangitis (PBC) study on-track and expected to initiate in 2024
Tharimmune, Inc. (NASDAQ:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates for inflammation and immunology announced today 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.
"We are pleased with the completion of our Phase 1 study of TH104 and our expectations for a safe and tolerable transmucosal film delivery have been met," said Randy Milby, Chief Executive Officer of Tharimmune. "We would like to thank the Trial subjects for participating in this program where the data generated are a critical step forward to continue our momentum and remain on-track to initiate a Phase 2 program this year."
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.
Earlier, we announced data from several ex-US human studies with TH104 showing consistent and predictable delivery of nalmefene in healthy subjects using our proprietary drug embedded transmucosal buccal film. Another previously disclosed study of an open-label trial using TH104 in cholestatic 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 and are aligned with the profile from the most recent study announced today.
Tharimmune announced last quarter the closing of an $11 million public offering which 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.
About 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 and kappa opioid receptors. 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.
About Pruritus and Primary Biliary Cholangitis
According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, PBC, is a chronic disease where the bile ducts in the liver eventually become dysfunctional and cause the buildup of bile which causes liver damage. The disease, believed to be an autoimmune condition, affects an estimated 58 out of every 100,000 U.S. women and about 15 out of every 100,000 U.S. men. Pruritus is one of the most common symptoms associated with PBC affecting up to 75% of individuals at some point during their disease course. It has a negative impact on health-related quality of life with limited treatment options.Published survey data of PBC respondents suffering from pruritus described their itch as "bugs crawling under the skin". More than 65% of patients reported that the itch was worse at night, known as nocturnal pruritus, a high unmet need.
About Tharimmune
Tharimmune, Inc. is a clinical-stage biotechnology company developing a portfolio of therapeutic candidates for inflammation and immunology. The Company's lead clinical-stage asset, TH104 is known to suppress chronic, debilitating pruritus or "uncontrollable itching" in PBC, a rare and orphan liver disease with no known cure. The Company's early-stage immunology pipeline includes novel multi-specific antibodies targeting unique epitopes with novel mechanisms of action against well-known, validated targets in multiple solid tumors, including PD-1, HER2 and HER3. Tharimmune has a license agreement with OmniAb, Inc. to access the company's antibody discovery technology platform against these and other specified targets.
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