• Collaboration allows Hillstream to enter the rapidly growing Immuno-oncology therapeutics market
• By capitalizing on the long half-life of tumor targeting Quatramers™ combined with OmniTaur™-derived Picobodies™, the lead program, HSB-1940, is being developed to target PD-1
• Picobodies are the smallest known antibody fragment, comprised of ultra-long CDR H3 sequences of 30-40 amino acids rich with cysteines that create tightly folded structures capable of binding recessed epitopes

BRIDGEWATER, N.J., Dec. 01, 2022 (GLOBE NEWSWIRE) -- Hillstream BioPharma, Inc. (Nasdaq: HILS) (“Hillstream”, the “Company”) today announced the development of proprietary targeted biologics, Knob Quatrabodies™ (HSB-1940) against PD-1. Hillstream signed separate collaboration agreements with a subsidiary of OmniAb, Inc. (Nasdaq: OABI) (“OmniAb”) and with Minotaur Therapeutics, Inc. (“Minotaur”) to advance Picobodies against novel, unreachable and undruggable epitopes in high-value validated targets starting with PD-1.

The technologies of Hillstream and Minotaur will be combined under a previously disclosed license from OmniAb to discover, develop and advance biotherapeutics against high-value validated targets. 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, Hillstream believes it could more efficiently target novel epitopes with greater binding affinity than approved biologics. Targeting PD-1 is a step toward enabling Hillstream to enter the rapidly growing Immuno-oncology (IO) therapeutics market with additional IO targets after PD-L1.

Dr. Vaughn Smider, Founder and Chief Executive Officer of Minotaur, stated, “We are excited to contribute our expertise to help in combining OmniAb’s OmniTaur-derived ultralong CDR H3 antibody fragments and Hillstream’s tumor-targeting Quatramers to discover and develop novel next-generation targeted cancer therapeutics.”

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.

Randy Milby, Chief Executive Officer of Hillstream, stated, “The Picobodies which OmniAb brings to this collaboration combined with our Quatramers to create a novel and disruptive Knob Quatramer platform will be a great addition to our portfolio starting with HSB-1940. We are doubly excited that Dr. Vaughn Smider, a pioneer in the discovery, engineering and understanding of these unique proteins, will be leading Minotaur’s services. The Quatramer is a key Hillstream platform which is now poised to create novel therapeutics using “smart carriers” with multiple approaches for enhancing targeted cancer immunotherapy.”

About Hillstream BioPharma, Inc.

Hillstream BioPharma, Inc. is a biotechnology company developing novel therapeutic candidates targeting ferroptosis, an emerging new anti-cancer mechanism resulting in iron mediated cell death 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 and epithelial carcinomas. Hillstream intends to initiate IND discussions with the FDA in first half of 2023. Hillstream uses Quatramer™, our proprietary tumor targeting platform, to enhance the uptake of HSB-1216 in the tumor microenvironment with an extended duration of action and minimal off-target toxicity. 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 is expert in the use of the novel ultralong CDR H3 scaffold of OmniAb’s OmniTaur bovine antibodies which allows unique targeting properties. Minotaur has licensing and partnership arrangements with The Applied Biomedical Science Institute and OmniAb on this emerging therapeutic class and its underlying technologies.

About OmniAb, Inc.

OmniAb, Inc.’s discovery platform provides pharmaceutical industry partners access to diverse antibody repertoires and high-throughput screening technologies to enable discovery of next-generation therapeutics. At the heart of the OmniAb platform is the Biological Intelligence™ (BI) of our proprietary transgenic animals, including OmniRat^®, OmniChicken^® and OmniMouse^®, that have been genetically modified to generate antibodies with human sequences to facilitate development of human therapeutic candidates. OmniFlic^® (transgenic rat) and OmniClic^® (transgenic chicken) address industry needs for bispecific antibody applications though a common light chain approach, and OmniTaur™ (obtained in the acquisition of Taurus Biosciences) features unique structural attributes of cow antibodies for complex targets. We believe the OmniAb animals comprise the most diverse host systems available in the industry and they are optimally leveraged through computational antigen design and immunization methods, paired with high-throughput single B cell phenotypic screening and mining of next-generation sequencing datasets with custom algorithms to identify fully human antibodies with superior performance and developability characteristics. An established core competency focused on ion channels and transporters further differentiates our technology and creates opportunities in emerging target classes. OmniAb antibodies have been leveraged across modalities, including bispecific antibodies, antibody-drug conjugates and others. The OmniAb suite of technologies span from BI-powered repertoire generation to cutting edge antibody discovery and optimization offering a highly efficient and customizable end-to-end solution for the growing discovery needs of the global pharmaceutical industry.

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, including the outbreak of COVID-19 coronavirus, 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 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, 2021 and our periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. 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.