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 (PicobodiesTM) for tumor targeting, extends partnership to include validated target, HER3
IND filing for HSB-3215 planned in 2024
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.
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 PicobodiesTM 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
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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
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
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Hillstream Advances Next-Gen Multispecific Antibodies for Solid Tumors with Lead HER2/HER3 Program, HSB-3215
Hillstream Advances Next-Gen Multispecific Antibodies for Solid Tumors with Lead HER2/HER3 Program, HSB-3215
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