Hillstream BioPharma announces strategic reprioritization of pipeline

Hillstream BioPharma 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 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, 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. 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 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. An update regarding these collaborations will be announced during an R&D Day in the third quarter.