Phase 1 clinical trial dosing of first patient complete; primary objective to assess safety/tolerability and absolute bioavailability of TH104
Phase 1 study expected to be completed in 1Q24 with topline readout in 2Q24
Company fully funded into 2025 with full readouts of Phase 1 and 2 in moderate-to-severe chronic pruritus in PBC expected in 4Q24/1Q25
Tharimmune, Inc. (NASDAQ:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates in inflammation & immunology announced today the first patient dosed in the Company's Phase 1 clinical trial with TH104, utilizing a proprietary oral thin film. TH104 is a proprietary transmucosal buccal film embedded with the approved, active compound nalmefene onto a thin film which easily adheres inside of the mouth on the cheek and biodegrades within minutes.
Tharimmune's lead clinical-stage asset, TH104, is designed as an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions, by avoiding the first-pass metabolism usually in traditional oral formulations. The molecule has a dual mechanism of action affecting both the mu and kappa opioid receptors, while emerging data suggests inhibition of interleukin-17, a pro-inflammatory cytokine. The 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 Phase 1 clinical trial currently recruiting is a pharmacokinetic bridging study in the U.S. designed as a single-dose, single-center, open-label, randomized 2-way crossover study of TH104 and an intravenous dose of nalmefene administered under fasting conditions, with a 7-day washout period between doses. Sixteen normal healthy volunteers are anticipated to participate and complete the study. The primary objective is to evaluate the absolute bioavailability of TH104 as well as assess safety and tolerability. Topline data is expected in 2Q24 with a full data readout shortly thereafter.
"The dosing of the first patient in our Phase 1 study of TH104 marks the initiation of our vision of becoming a patient-focused clinical development organization," said Randy Milby, Chief Executive Officer of Tharimmune. "Along with the recently disclosed human studies conducted outside the US, and a focused effort to complete this ongoing trial, we are dedicated to advance TH104, which has the potential to bring meaningful patient benefit. We aim to continue our momentum in the clinic 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.
Multiple ex-US human studies have been completed with TH104 which showed reliable and predictable delivery of nalmefene in healthy subjects using our proprietary drug embedded transmucosal oral film applied to the inside of the cheek. Another previously disclosed study of an open-label trial using TH104 in chronic 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.
The Company previously announced the closing of an $11 million public offering which it believes is sufficient to extend its cash runway into early 2025 for both clinical readouts of its lead program, TH104. Tharimmune 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 receptor and the kappa opioid receptor as well as inhibiting IL-17 inflammatory cytokine expression. 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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