Tharimmune, Inc. is a biotechnology company developing a portfolio of therapeutic candidates for rare immune, inflammatory, and oncologic diseases. The Company is progressing towards acquiring a clinical-stage asset, known to suppress chronic, debilitating pruritis or “uncontrollable itching” in primary biliary cholangitis (PBC), a rare orphan liver disease with no known cure. The Company’s early-stage immuno-oncology pipeline includes novel multi-specific antibodies targeting unique epitopes with novel mechanisms of action against well-known, validated targets in multiple solid tumors. Tharimmune has a license agreement with OmniAb, Inc. to access the company’s antibody discovery technology platform against specified targets.

Anticipate completion of Phase 1 & Phase 2 clinical trials in chronic pruritis over the next approximately 12 months

Seeking first approval in an orphan disease, PBC, for the treatment of moderate to severe chronic pruritis in which more than 70% of patients suffer from chronic pruritis

BRIDGEWATER, N.J., Sept. 11, 2023 (GLOBE NEWSWIRE) — Hillstream BioPharma, Inc. (Nasdaq: HILS) (“Hillstream” or the “Company”), a biotechnology company developing therapeutic candidates targeting drug resistant and devastating cancer announces an exclusive option agreement to acquire a clinical stage asset, AV104, with a recently approved IND. AV104 has a dual mechanism of action by affecting multiple receptors, known to suppress chronic, debilitating pruritis or “uncontrollable itching”. The Company intends to first seek approval in an orphan disease for the treatment of moderate to severe cholestatic pruritis in patients with primary biliary cholangitis (PBC), a rare form of liver disease with no known cure in which more than 70% of patients suffer from chronic pruritis.

Embedded onto a proprietary transdermal buccal film which easily adheres to the inside of the mouth, AV104’s key features make it an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions. AV104’s active molecule, nalmefene, has a dual mechanism of action by 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.

When the itch circuitry is imbalanced in diseased conditions, pharmacological intervention can help suppress this phenomenon which occurs in patients suffering from chronic pruritis. Nalmefene crosses into the circulation via a proprietary buccal delivery by adhering the drug-coated film inside the cheek where the film biodegrades in minutes and the drug is absorbed. The buccal delivery of the drug bypasses the liver’s first-pass metabolism thus creating high drug concentrations in the skin, an added benefit for treating conditions in which the liver may be impaired. The Company intends to complete a bridging pharmacokinetic phase 1 trial and a phase 2 proof-of-concept in PBC patients over approximately the next 12 months after alignment with the US FDA.

Hillstream believes AV104 has expansion opportunities in treating chronic pruritogenic conditions associated with cholestatic liver disease as well as other liver related and as non-liver related diseases including fatty and alcoholic liver diseases, non-alcoholic liver diseases and certain types of hepatitis. Chronic pruritis is significant in liver diseases as well as chronic kidney diseases, hemodialysis and atopic dermatitis.

“The past year has been a period of transformational change for our company,” said Randy Milby, CEO of Hillstream. “This exclusive option allows the company to bring a clinical-stage asset into the organization as we shift into a patient-focused biotechnology organization. This signifies our next step as we grow into a business model focused on clinical development.”

The THARIMMUNE Biopharma Pipeline

HSB-3215: anti-HER2/HER3 bispecific Ab

The ErbB family of cell surface proteins are some of the most well-known and validated oncology drug targets including ErbB2 or HER2 (human epidermal growth factor receptor) and Erb3 or HER3. The family of antibodies and biologics against HER2 starting with HERCEPTIN® (trastuzumab) approved in 1998 for breast cancer, one of the first few anti-cancer antibodies, as well as PERJETA®, KADCYLA® and PHESGO® totaled $8.4 billion in 2022 sales for Roche/Genentech. Antibodies against HER2 and HER3 bind to different domains of the extracellular portion of the proteins or epitopes with trastuzumab binding domain IV of HER2 primarily. HER2 is also one of the most utilized targeting antigens for antibody drug conjugates to treat HER2 positive cancers with two approved antibodies, Roche/Genentech’s PERJETA® and Daiichi Sankyo/AstraZeneca’s ENHERTU®.

The Applied Biomedical Science Institute has developed technology to target unique functional epitopes of the cancer targets HER2 and HER3.   Monoclonal antibodies being developed at ABSI are unique from the currently approved anti-HER2 antibodies. ABSI has granted under an exclusive option agreement to Hillstream, certain of its proprietary technology which if converted to an exclusive license agreement, will allow Hillstream to develop HER2 and HER3 antibodies, including multi-specific and Quatramer- based therapeutics incorporating portions of the antibodies.

HSB-0059: Bispecific ADC

Antibody Drug Conjugates (ADCs) are a class of newly emerging therapeutics which may serve as “magic bullets” to treat certain cancers. They consist of a 1) a cancer killing chemotherapeutic payload, 2) an antibody-targeting a cancer cell and 3) a linker connecting the antibody to the payload. The problem with some ADCs targeting HER2 and/or HER3 essentially target the same epitopes as trastuzumab based domains. Our solution based on data an HSB-3215 (HER2/HER3) mAb backbone with HSB-0059 targets novel epitopes on HER2 while blocking natural ligands to HER3 and/or preventing heterodimers. ADCs can also have a potential “bystander effect” of its’ toxin payload. We intend to design ADCs whereby the toxin delivered to surrounding non-antigenic cancer tissue can be killed and maximize antitumor potential for this novel compound.

HSB-1940: Anti-PD-1 (Undruggable Epitopes)

Picobodies are antibody “knob” domains comprised of cysteine-rich ultralong complementary determining region (CDR) H3 sequences of 30-40 amino acids, which have the potential to access challenging epitopes better than full size antibodies can. By combining Quatramers with their long half-life coated with a PD-1 Picobody™ to create HSB-1940, we intend to efficiently target novel epitopes with greater binding affinity than approved biologics. Antibodies derived from mouse or human sources use the surface formed by complementarity determining regions (CDRs) on the variable regions of the heavy chain/light chain heterodimer, which typically forms a relatively flat binding surface. Alternative species, particularly camelids and bovines, provide a paradigm for antigen recognition through novel domains which form the antigen binding site. However, for camelids, heavy chain antibodies bind antigen with only a single heavy chain variable region, in the absence of light chains. Meanwhile, in bovines, ultralong CDR-H3 regions form an independently folding mini-domain, which protrudes far out from the surface of the antibody and forms a “stalk and knob” structure which is diverse in both its sequence and disulfide patterns. The “knob” (Picobody) component can be expressed as an independent antigen binding domain. At ~4-6 kDa, these are three times smaller than a camelid “nanobody”, and are the smallest known antibody fragment. These atypical antigen binding sites of bovines potentially provide the ability to interact with different antigenic determinants, particularly recessed or concave surfaces, compared to traditional antibodies.

Fri Sep 22nd, 2023

• Hillstream BioPharma Progressing Towards Acquiring Clinical Stage Asset and Announces Corporate Name Change to Tharimmune, Inc.

Thu Sep 21st, 2023

• Dawson James Securities Announces October Date for 8th Annual Small Cap Growth Conference

Mon Sep 11th, 2023

• Hillstream Enters into an Exclusive Option Agreement to Acquire a Clinical Stage Asset for Chronic Pruritis

Fri Sep 8th, 2023

• Hillstream BioPharma to Present at H.C. Wainwright 25th Annual Global Investment Conference September 11-13

Wed Aug 9th, 2023

• Hillstream BioPharma to Present at the Sidoti Micro-Cap Virtual Conference on August 16-17, 2023

Thu Jul 20th, 2023

• Hillstream Advances Next-Gen Multispecific Antibodies for Solid Tumors with Lead HER2/HER3 Program, HSB-3215

Mon Jul 10th, 2023

• Hillstream BioPharma Announces Strategic Reprioritization of Pipeline to Targeting HER2/HER3 Solid Tumors via Bispecific and ADC Antibodies and Biologics

Thu Jul 6th, 2023

• Hillstream BioPharma Licenses Technology to Develop Proprietary HER2 and HER3 Antibody Drug Conjugates against Drug-Resistant Breast, Lung, Gastric, and Ovarian Cancers

Mon May 15th, 2023

• Hillstream BioPharma Strengthens its Board of Directors with Appointment of Kelly Anderson

Tue May 2nd, 2023

• Hillstream BioPharma Announces Closing of Public Offering of Common Stock