Singapore — HER3 activation is implicated in tumor progression and in acquired resistance to EGFR and HER2 therapies
Study, published in Molecular Cancer Therapeutics, found HMBD-001 to be able to uniquely block HER3 dimerization interface and potently inhibit tumor growth
Hummingbird Bioscience, an innovative biotherapeutics company pioneering the discovery and development of new breakthrough precision antibody therapeutics for difficult-to-treat conditions, today announced 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.
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. 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 http://mct.aacrjournals.org/content/early/2020/01/06/1535-7163.MCT-19-0515.
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.
About Hummingbird Bioscience
Hummingbird Bioscience is an innovative biotherapeutics company pioneering the discovery and development of new breakthrough precision antibody therapies for difficult-to-treat conditions. Leveraging its proprietary rational antibody discovery platform and deep experience in systems biology, Hummingbird Bioscience is able to accurately identify novel disease targets enabling it to engineer and generate antibodies to precisely hit these difficult targets. The company is developing a broad pipeline of first and best-in-class drug candidates across multiple indications, including: HMBD-001, an anti-HER3 antibody, and HMBD-002, an anti-VISTA antibody, for the treatment of cancer. Hummingbird Bioscience has established strategic collaborations with Cancer Research UK and Amgen, and has been awarded a product development grant from the Cancer Prevention and Research Institute of Texas.
Hummingbird Bioscience is located in Singapore, Houston, Texas and South San Francisco, California. To learn more about its science, pipeline assets, and team, please visit: www.hummingbirdbioscience.com or follow the company on LinkedIn and Twitter at @Hummingbirdbio.
Li Q., Zhang R., Yan H., Zhao P., Wu L., Wang H., Li T., Cao B. Prognostic significance of HER3 in patients with malignant solid tumors. Oncotarget. 2017; 8: 67140-67151. Retrieved from http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=18007&path%5B%5D=57679
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