Tharimmune Announces Initiation of Phase 1 Clinical Trial of TH104 and Provides Business Update

January 29th, 2024

Phase 1 trial initiated to assess safety/tolerability and absolute bioavailability of TH104 with topline data expected in 2Q24

Planning well underway for Phase 2 of TH104 in primary biliary cholangitis (PBC) patients suffering from moderate-to-severe chronic pruritus

Company outlines near-clinical pipeline of novel antibody technology for multiple immuno-oncology targets and plans an R&D day in 2024

Company fully funded into 2025 with full readouts of Phase 1 and Phase 2 results for moderate-to-severe chronic pruritus in PBC expected in 4Q24/1Q25

BRIDGEWATER, NJ / ACCESSWIRE / January 29, 2024 / Tharimmune, Inc. (NASDAQ:THAR) (“Tharimmune” or the “Company”), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates in inflammation & immunology announces initiation of a Phase 1 trial with TH104, utilizing a proprietary oral thin film. TH104 is a proprietary transmucosal buccal film embedded with the active compound nalmefene onto a thin film which easily adheres inside of the mouth on the cheek and biodegrades within minutes. This provides key features making TH104 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 with emerging data showing inhibition of interleukin-17, a pro-inflammatory cytokine. These well-known opioid receptors when stimulated and/or inhibited by the body’s endogenous ligands have been shown to be involved in the body’s itch circuitry for certain conditions, including cholestatic or dysregulated bile acid-related liver conditions.

TH104/Tharimmune Clinical-Stage Program Update

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 Company plans to engage both U.S. and European Regulatory Authorities to gain agreement on launching a 28-day Phase 2 trial in 2024 which is currently anticipated as a multiple ascending dose study to assess the safety and tolerability of TH104 while also evaluating the change from baseline for moderate-to-severe chronic pruritus or “debilitating itching” using a validated endpoint, in PBC patients. A topline data readout is anticipated in late ‘24/early ’25, post regulatory discussions, anticipated in 2024. The Company believes the Phase 2 program may establish TH104’s response for clinical efficacy studies in moderate-to-severe pruritus using this potential endpoint for future registrational trials.

Pruritus is a common clinical feature seen in liver diseases but particularly frequent in cholestatic liver disease. A previous open-label study with TH104 in chronic liver disease patients administered a single low-dose of TH104 and assessed itch intensity over a 24-hour period, with topline data showing a decline by 33.3%. Safety and tolerability correlated with previous studies consistent in the literature with nalmefene, the active ingredient in TH104.

TH-3215 and TH-1940/ Tharimmune Non Clinical-Stage Program Update

Tharimmune is advancing TH-3215 designed as a bispecific antibody (BsAb) targeting the extracellular domains of HER2 and HER3. These validated targets have been extensively studied and belong to the ERBB receptor tyrosine kinase family and are exploited by cancer cells to promote tumorigenesis and metastasis. HER2, an extensively studied target, has multiple approved therapeutics for solid tumors. Evidence suggests that HER3 plays a central role through interacting with neighboring receptors. While TH-3215 binds to both overlapping and different epitopes on HER2 in contrast to approved therapies, with ligand-blocking and potential complementary fit to HER3, affecting novel conformational epitopes thought to be important in intracellular downstream signaling in tumor cells.

Furthermore, the Company also is advancing novel Picobodies, which are antibodies in bovine animals or cows, and derived from ultra-long complementary determining region 3 (CDR3) domains which potentially enable access to epitopes that had previously been hidden or highly inaccessible in traditional antibody development. With a much smaller size compared to traditional antibodies, combined with structural diversity, Picobodies can bind to conformational, linear or discontinuous epitopes in “undruggable” areas of validated targets. Picobodies are derived from bovines, which unlike other species, express ultralong CDR-H3 regions forming an independently folding mini-domain, that protrudes far out from the surface of the antibody and is diverse in both its sequence and disulfide patterns. These atypical antigen binding sites of bovines potentially provide the ability to interact with different antigenic determinants capable of eliciting an immune response, particularly recessed or concave surfaces, compared to traditional antibodies. This conceivable “multi-specific” capacity of Picobodies , which is the basis of developing TH-1940, could more efficiently target multiple cell surface portions compared to known or existing biologics. Tharimmune aims to develop both TH-3215 and TH-1940 using this framework to interchange antigen-recognition sites designed to fit distinct portions of the HER2/HER3 heterodimer complex and other validated cancer targets, such as programmed cell death protein 1 or PD-1 potentially effecting both ligand-dependent and independent signaling pathways into tumor cells.

The Company announced in 4Q23 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.

“We are pleased with the progress we’ve made at Tharimmune including the initiation of our Phase 1 clinical trial with TH104 using our proprietary nalmefene embedded transmucosal delivery system which can easily be applied to the inside of the cheek,” said Randy Milby, CEO of Tharimmune. “The data we aim to obtain coupled with our plans to engage regulators in a timely manner will aid in potentially bringing this much needed treatment strategy to people suffering from chronic pruritis in PBC. As we continue to transform into a clinical company, we hope to engage shareholders, patients and all stakeholders on the progress of our pipeline over the coming months.”

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 has acquired an exclusive worldwide license for a clinical-stage asset, TH104 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. For more information please visit: www.tharimmune.com.

Forward Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, contained in this press release, including statements regarding Tharimmune’s strategy, future operations, future financial position, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “depends,” “estimate,” “expect,” “intend,” “may,” “ongoing,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “will,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements. Factors that may cause such differences, include, but are not limited to, those discussed under Risk Factors set forth in our Annual Report on Form 10-K/A for the year ended December 31, 2022 and other periodic reports filed by the Company from time to time with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date of this release. Subsequent events and developments may cause the Company’s views to change; however, the Company does not undertake and specifically disclaims any obligation to update or revise any forward-looking statements to reflect new information, future events or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this release.

Investor Relations Contact

ir@tharimmune.com
www.tharimmune.com

SOURCE: Tharimmune, Inc.