On April 8, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported new preclinical data demonstrating proof-of-concept for its differentiated HER3-ADC program (Press release, Elevation Oncology, APR 8, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-presents-preclinical-proof-of-concept-data-for-her3-adc-program-at-aacr-annual-meeting-2024 [SID1234641864]). The data will be presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, being held April 5-10 in San Diego, California.
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"We are pleased to share the first preclinical proof-of-concept data for our HER3-ADC program, reinforcing our commitment to advancing a portfolio of differentiated ADC-based therapies that may deliver better outcomes for patients," said David Dornan, Ph.D., Chief Scientific Officer of Elevation Oncology. "With our HER3-ADC program, we set out to design a differentiated ADC which selectively binds to HER3 and is internalized to potentially attack HER3-expressing cancerous cells while minimizing systemic exposure. Preclinical data with our proof-of-concept HER3-ADC shows HER3-dependent cell killing and robust anti-tumor activity in vivo where HER3 is expressed at high levels. We look forward to nominating a development candidate from our HER3 program later this year and, subsequently, advancing our program closer to the clinic."
HER3 is a clinically validated oncology and antibody-drug conjugate (ADC) target, which is overexpressed in a range of solid tumors, including breast cancer, EGFR-mutant non-small cell lung cancer and pancreatic cancer, and is often associated with poor clinical outcomes. Elevation Oncology’s HER3-ADC program conjugated seribantumab, its anti-HER3 monoclonal antibody, with a cleavable valine-citrulline linker and monomethyl auristatin E (MMAE) payload to yield HER3-ADC1, a proof-of-concept molecule with an average drug-antibody ratio (DAR) of 4.
In a poster titled, "Therapeutic potential of a HER3 antibody-drug conjugate for the treatment of HER3-expressing cancers," Elevation Oncology scientists presented in vitro and in vivo data of a seribantumab-based ADC for patients with HER3-expressing cancers. The data showed:
HER3-ADC1 binding to cancer cells, endocytosis, MMAE release and inhibition of proliferation were dependent on HER3 expression.
In cytotoxicity assays, HER3-ADC1 displayed HER3-dependent cell killing and outperformed a benchmark HER3-ADC with a deruxtecan payload, which is currently in clinical development.
In a patient derived xenograft (PDX) model of pancreatic cancer with high HER3 expression, HER3-ADC1 induced tumor regression, whereas an isotype-MMAE control and a benchmark HER3-ADC with a deruxtecan payload had only a modest effect.
The poster presentation is now available in the "Publications" section of Elevation Oncology’s website: View Source