Hillstream BioPharma and Minotaur Therapeutics Sign Term Sheet to Advance Next-Generation Targeted Knob Biologics for Undruggable Targets

Development partnership expected to capitalize upon tumor targeting Quatramers

and novel "Knob" biologics

Knob biologics with ultra-long CDRs could be effective against undruggable targets

BRIDGEWATER, NJ / ACCESSWIRE / August 5, 2021 / Hillstream BioPharma, Inc. ("Hillstream", the "Company") today announced the signing of a non-binding term sheet with Minotaur Therapeutics ("Minotaur") to advance the development of the next generation targeted Knob biologics for undruggable targets including c-MYC combined with Hillstream's tumor-targeting Quatramers™.

The technologies of Hillstream and Minotaur will be combined to advance the creation and clinical advancement of targeted biotherapeutics. The Knobs biologics feature ultra-long complementary determining region 3 (CDR3) domains to access heretofore hidden or highly inaccessible epitopes in traditional antibody development. With a much smaller size compared to antibodies combined with a novel genetic and structural diversity, the Knobs enable binding to conformational or linear or discontinuous epitopes in undruggable targets. Further, using Quatramers coated with "multi-specific" Knobs, Hillstream believes it could more efficiently target complex, glycosylated cell surface targets than the known or existing biologics.

Dr. Vaughn Smider, Founder and Chief Executive Officer of Minotaur, stated "We are excited to combine Minotaur's bovine antibody Knob biologics with Hillstream's tumor-targeting Quatramers to discover and develop a novel next-generation of targeted biologics."

Recent evidence suggests that 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. 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.

Randy Milby, Chief Executive Officer of Hillstream, stated, "The Knob biologics will be a great addition to our portfolio and Dr. Vaughn Smider is a pioneer in the discovery, engineering and understanding of antibodies. Quatramer is a key Hillstream platform which is now poised to create a novel technology creating "smart carriers" with multiple possibilities for enhancing targeted cancer immunotherapy."

About Hillstream BioPharma, Inc.

Hillstream BioPharma, Inc. (Hillstream) is a biotechnology company developing novel therapeutic candidates targeting ferroptosis, an emerging new anti-cancer mechanism resulting in iron mediated cell death ("IMCD") for drug resistant and devastating cancers. Hillstream's most advanced candidate is HSB-1216, an IMCD modulator, targeting a variety of solid tumors. The active drug in HSB-1216 was found to be efficacious in a clinical pilot study in Germany in devastating cancers, including triple negative breast cancer (TNBC) and epithelial carcinomas. Hillstream intends to start a clinical study with HSB-1216 in 2022 to expand upon the existing early clinical proof-of-concept. Hillstream uses Quatramer™, our proprietary tumor targeting platform, to enhance the uptake of HSB-1216 in the tumor microenvironment ("TME") with an extended duration of action and minimal off-target toxicity. In addition, Trident Artificial Intelligence ("TAI" or "Trident"), Hillstream's artificial intelligence precision medicine platform, is used to identify biomarkers in our clinical programs to target a specific patient segment most likely to benefit. For more information, please visit www.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
This press release includes forward-looking statements including, but not limited to, statements related to the development of drug candidates, our operations and business strategy, our expected financial results, and corporate updates. The forward-looking statements contained in this press release are based on management's current expectations and are subject to substantial risks, uncertainty and changes in circumstances. Actual results may differ materially from those expressed by these expectations due to risks and uncertainties, including, among others, those related to our ability to obtain additional capital on favorable terms to us, or at all, including, without limitation, to fund our current and future preclinical studies and clinical trials and the success, timing and cost of our drug development program and our ongoing or future preclinical studies and clinical trials, including, without limitation, the possibility of unfavorable new clinical and preclinical data and additional analyses of existing data, that the risks that prior clinical and preclinical results may not be replicated, and risks associated with the current coronavirus pandemic. Forward-looking statements speak only as of the date of this press release, and we undertake no obligation to review or update any forward-looking statement except as may be required by applicable law.

Hillstream BioPharma, Inc.

Randy Milby
President & CEO
Hillstream Biopharma, Inc.
Tel: +1-908-955-3140
Email: rmilby@hillstreambio.com

Investor Contact:

Jennifer K. Zimmons, Ph.D.
Investor Relations

Zimmons International Communications, Inc.
Tel : +1-917-214-3514
Email : jzimmons@zimmonsic.com

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SOURCE: Hillstream BioPharma, Inc.