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

July 20, 2023

Collaboration adds multiple modular swappable antigen recognition regions to lead program, HSB-3215, a bispecific antibody targeting novel epitopes on HER2/HER3 receptors

Capitalizes on “Knob” biologics (Picobodies TM ) for tumor targeting, extends partnership to include validated target, HER3

IND filing for HSB-3215 planned in 2024

BRIDGEWATER, N.J., July 20, 2023 (GLOBE NEWSWIRE) — Hillstream BioPharma, Inc. (“Hillstream”, the “Company”) today announced the expansion of its collaboration with Minotaur Therapeutics, Inc. (“Minotaur”) and its license agreement with OmniAb, Inc. (“OmniAb”) to advance the development of next generation targeted Knob biologics (Picobodies TM ) against HER3 and a new undisclosed oncology target. Hillstream will collaborate with Minotaur using OmniAb’s “OmniTaur™” technology to discover targeted biotherapeutic Picobodies complementing Hillstream’s most advanced program, HSB-3215, a HER2/HER3 bispecific antibody (BsAb).

As a diverse group of molecules, BsAbs recognize distinct epitopes on two different antigens, in the case of HSB-3215, HER2 and HER3. These validated targets, belong to the ERBB receptor tyrosine kinase family and are exploited by cancer cells to promote oncogenesis. HER2 is an extensively validated target, and emerging evidence suggests that HER3 plays a key role as well. While HER3 has little to no tyrosine kinase activity on its own, its activation promotes tumors through dimerization or locking into place with HER2, which is believed to intensify its cancer-causing potential.

Hillstream’s lead program, HSB-3215, is designed as a BsAb targeting the extracellular domains of HER2 and HER3. HSB-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. HSB-3215 and HER3 associated novel Picobodies offer the potential to target previously undruggable epitopes of these clinically validated targets, distinguishing them from earlier generations of antibodies.

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

Picobodies, which are a characteristic of antibodies in bovine animals, are 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” 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 TM could more efficiently target multiple cell surface portions compared to known or existing biologics. Hillstream aims to develop both HSB-3215 and other antibodies using this framework to interchange antigen-recognition sites designed to fit distinct portions of the HER2/HER3 heterodimer complex potentially effecting both ligand-dependent and independent signaling pathways into tumor cells. The Company intends to develop its lead program, HSB-3215 and file an IND application with the US FDA late next year.

Dr. Vaughn Smider, Founder and Chief Executive Officer of Minotaur, stated “We are excited to continue Minotaur’s collaboration with Hillstream to progress novel next-generation targeted cancer biologics.”

Randy Milby, Chief Executive Officer of Hillstream, stated, “We are extremely pleased with the progress made to date. The Knob biologics program continues to be a great addition to our portfolio as we rapidly progress our lead asset HSB-3215 towards an IND. Hillstream is now poised to develop a novel technology for creating multiple proteins to enhance targeted cancer immunotherapy.”

About Hillstream BioPharma, Inc.
Hillstream BioPharma, Inc. is a biotechnology company developing a focused portfolio of therapeutic candidates targeting drug resistant and devastating cancers. The Company’s emerging immuno-oncology pipeline is led by HSB-3215, a novel anti-HER2 monoclonal antibody targeting unique epitopes with a novel mechanism of action. The erbB/HER family of cell surface proteins include well-known and validated drug targets including HER2 and HER3 found in multiple solid tumors, including breast, lung, GYN, endocrinological and CNS. Hillstream has a license agreement with OmniAb, Inc. to access the company’s antibody discovery technology platform. For more information about Hillstream, please visit: hillstreambio.com .

About Minotaur Therapeutics
Minotaur Therapeutics is a private biotechnology company developing unique biotherapeutics for oncology and immunology. Minotaur uses the novel ultralong CDR3 scaffold of bovine antibodies which allows unique targeting properties. Minotaur has licensing and partnership arrangements with The Applied Biomedical Science Institute on this emerging therapeutic class and its underlying technologies.

Forward Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified using words such as “anticipate,” “believe,” “forecast,” “estimated” and “intend” or other similar terms or expressions that concern Hillstream’s expectations, strategy, plans or intentions. These forward-looking statements are based on Hillstream’s current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidates; risks related to business interruptions which could seriously harm our financial condition and increase our costs and expenses; dependence on key personnel; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain Food and Drug Administration (“FDA”) clearances or approvals and noncompliance with FDA regulations. Investors should read the risk factors set forth in our Form 10-K for the year ended December 31, 2022, and our periodic reports filed with the Securities and Exchange Commission. However, these risks are not exhaustive and new risks and uncertainties emerge from time to time and it is not possible for us to predict all risks and uncertainties that could have an impact on the forward-looking statements contained in this press release. Forward-looking statements included herein are made as of the date hereof, and Hillstream does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances, except as may be required by law.

Investor Contact : Investor Contact: investorrelations@hillstreambio.com

Source: Hillstream BioPharma, Inc.

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