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

July 10, 2023

Lead bispecific antibody, HSB-3215 designed to target novel conformational epitopes on high value validated targets, HER2 and HER3

Focus on optimizing ADCs to generate a more potent Bystander Effect and proprietary novel bovine-derived biologic platform, PicoKnob TM , targeting undruggable epitopes on PD-1 and TROP2

Experienced biopharmaceutical executive joins as Chief Operating Officer to spearhead execution of ADC and biologic strategy

BRIDGEWATER, N.J., July 10, 2023 (GLOBE NEWSWIRE) —  Hillstream BioPharma (Nasdaq: HILS) a biotechnology company developing innovative therapeutic candidates targeting drug resistant and devastating cancers that can make a difference in patients’ lives, today announced a strategic reprioritization of its pipeline and provided a corporate update. The strategic assessment took into account, the pipeline’s near-term value creation opportunity and other factors. Hillstream will focus its pipeline on advancing novel oncology assets with the greatest potential and strong competitive profiles to address unmet needs across multiple solid tumors, such as bispecific antibodies and ADCs targeting novel conformational epitopes on high value validated targets, HER2 and HER3, with a more potent Bystander Effect .

Bispecific antibodies (BsAbs) refer to a diverse group of molecules that recognize distinct epitopes on two different antigens, such as 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 and validated target, has multiple approved therapeutics for solid tumors. Meanwhile, emerging evidence suggests that HER3 plays a central role through interacting with neighboring receptors. While HER3 has little to no tyrosine kinase activity on its own, its activation to promote tumors depends on heterodimerization or locking into place with HER2 and EGFR, which is believed to unlock its cancer-causing potential.

Hillstream’s lead asset, HSB-3215 is designed as a bispecific humanized immunoglobulin containing two arms targeting the extracellular domains of HER2 and HER3. HSB-3215 binds to both overlapping and different epitopes on HER2 when compared to trastuzumab, the first approved antibody against HER2, while adhering to novel epitopes on HER3, thus creating novel conformational epitopes. The Company intends to develop this novel BsAb and file an IND application with the US FDA late next year.

By exploiting the “ Bystander Effect ”, a key aspect of ADCs which has been recently highlighted by the improved clinical efficacy of Daiichi Sankyo/AstraZeneca’s ENHERTU ® (trastuzumab deruxtecan), the Company plans to optimize its BsAb pipeline with BiSpecific ADCs, i.e. BiSpecific antibodies conjugated with novel toxin payloads which are optimized to generate a more powerful Bystander Effect . ADCs are comprised of a targeting antibody chemically conjugated via a proprietary linker to a powerful, cancer-killing compound/toxin (payload). With a BsAb backbone utilizing HSB-3215, the Company intends to develop novel ADCs, targeting HER2/HER3 and better direct a payload to cancer cells overexpressing these receptors, while healthy cells don’t take up the unwanted compound.

Hillstream also intends to further enhance its previously announced collaborations with Applied Biomedical Science Institute (ABSI) and Minotaur to develop novel bovine-derived biologics in multiple formats against highly validated targets, including PD-1, HER2 and TROP-2, referred to as PicoKnobs TM . An update regarding these collaborations will be announced during an R&D Day in the third quarter.

“Our recently announced collaborations with ABSI are transforming Hillstream into a focused and targeted cancer biologics company,” said Randy Milby, Chairman and CEO of Hillstream. “With the HER2 and HER3 platform, we are building a diverse foundation of targeted biologics which can be utilized for our current portfolio as well for future in-licensed assets. We are confident that our focused approach and experienced management team best positions us for success.”

The Company also announced the appointment of Sireesh Appajosyula, Pharm.D.as as Chief Operating Officer (COO). Sireesh brings over 20 years of experience in creating and advising biotechnology companies such as 9 Meters Biopharma Inc. through targeted transactions thus creating a pipeline as well as accessing the public capital markets. He was responsible for corporate development including portfolio strategy, in-licensing transactions and alliances for 9 Meters’s core assets as well as monetization of non-core assets. Previously, he spent eight years at Salix Pharmaceuticals, Inc. in various roles including medical & clinical affairs, product commercialization and business development culminating in Salix’s acquisition for $16 billion by Bausch Health. Prior to Salix, Sireesh held increasing roles and responsibilities at Amgen, Chiesi (Critical Therapeutics) and Sanofi S.A. (Aventis). Sireesh holds a Doctor of Pharmacy degree from the Ernest Mario College of Pharmacy at Rutgers University in New Jersey.

“I am thrilled to join Hillstream and look forward to working alongside the team as we further our development programs. I believe the Company’s precision oncology strategy with the current HER2/HER3 antibody programs and pipeline have the potential to bring much needed treatments to cancer patients,” said Dr. Appajosyula.

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. For more information, please visit: 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. 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.

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