On January 7, 2020 Hummingbird Bioscience, an innovative biotherapeutics company pioneering the discovery and development of new breakthrough precision antibody therapeutics for difficult-to-treat conditions, reported the publication of preclinical data for its lead candidate, HMBD-001, an anti-HER3 antibody, in Molecular Cancer Therapeutics, a high-impact peer-reviewed American Association of Cancer Research journal (Press release, Hummingbird Bioscience, JAN 7, 2020, View Source [SID1234552813]).
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HMBD-001 is a unique anti-HER3 antibody with a novel mechanism of action and favorable safety profile. HER3 is a member of the EGFR tyrosine kinase receptor family, which is responsible for driving cancer cell division and growth, and is expressed in over half of colorectal and gastric cancers, at least a third of breast cancers, as well as significant sub-populations of many other indications.[1] HER3 activation is implicated in cancer progression as well as in acquired resistance to drugs against other tyrosine kinase receptor family members such as EGFR (e.g. cetuximab or Erbitux) and HER2 (e.g. trastuzumab or Herceptin). HMBD-001 was developed using Hummingbird Bioscience’s proprietary Rational Antibody Discovery Platform to specifically bind to and inhibit a difficult-to-access region of the HER3 protein that is essential for activation.
The published findings show that HMBD-001 (also known as 10D1F) is superior at tumor growth inhibition, regardless of how HER3 is activated, compared to previous anti-HER3 drugs with different binding sites and mechanisms of action. HMBD-001 demonstrated potent efficacy in a broad panel of in vitro and in vivo tumor models that had high HER3 activity and oncogenic downstream signaling.
"Previous attempts to target HER3 with other drugs failed as they could not inhibit activation of HER3 effectively. The highly specific binding of HMBD-001 to a difficult-to-target region on HER3 allows us to completely shut off activation of this important cancer-associated protein," said Dr Jerome Boyd-Kirkup, Chief Scientific Officer and co-founder, Hummingbird Bioscience. "This preclinical data provides proof-of-concept and represents exciting therapeutic opportunities for us as we look to develop HMBD-001 in hard-to-treat conditions such as gastric, colorectal, lung and pancreatic cancers."
Hummingbird Bioscience, in partnership with Cancer Research UK, will be advancing HMBD-001 into clinical trials for the treatment of HER3 driven cancers. Manufacturing of the material for the Phase 1 clinical trial of HMBD-001 is underway and is expected to be completed in the second half of 2020.
The paper titled 10D1F, An Anti-HER3 Antibody that Uniquely Blocks the Receptor Dimerization Interface, Potently Inhibits Tumor Growth Across a Broad Panel of Tumor Models can also be accessed online at View Source
About HMBD-001
HMBD-001 represents a unique, highly-specific, anti-HER3 neutralizing antibody with a novel mechanism of action that offers significant potential for broad clinical benefit. Previous attempts to block the HER3 receptor, a key player in the signaling pathway that promotes cell division and tumor growth in cancer, have not proven to be efficacious. HER3 is activated by the binding of neuregulin (NRG1), which stabilizes a transient open conformation to allow it to form heterodimers with HER2/EGFR. In the presence of abundant HER2/EGFR, heterodimers can form without NRG1.
Preclinical models have shown that HMBD-001 is able to effectively and uniquely bind to a
difficult-to-target region on HER3, blocking the heterodimerization of HER3 with HER2/EGFR independent of NRG1 binding. This potently inhibits the activation of the signaling pathway – and consequently, stops tumor growth.
Cancer Research UK has partnered with Hummingbird Bioscience to advance this novel antibody drug into clinical trials for the treatment of HER3 driven cancers. The clinical trial of this investigational candidate is expected to commence following the completion of manufacturing and the subsequent submission of regulatory approval.