Avistone Announces Preclinical Results for ANS014004, a Type II c-Met Tyrosine Kinase Inhibitor (TKI) at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

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Aberrant MET oncogenic alterations include: MET exon 14 skipping (MET∆ex14) mutations; activating mutations in the kinase domain; MET gene amplification; MET fusions; and MET protein overexpression.

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Business Wire, Inc.Business Wire, Inc.
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Saturday, October 14, 2023
Information
Tags: 
Biotechnology, Health, Pharmaceutical, Clinical Trials, Oncology, European Organisation for Research and Treatment of Cancer, Treatment, NSCLC, RTK, AACR, Therapy, Capmatinib, EORTC, Wound healing, National Cancer Institute, American Association for Cancer Research, NCI, Research, Immunomodulation, Poster, HGF, Hepatocyte growth factor, MET, Patient, TKI, Pharmaceutical industry, Cancer
Geotags: 
CHINA, ASIA PACIFIC, MASSACHUSETTS, US, AVISTON, ILLINOIS, BOSTON
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AVISTONE BIOTECHNOLOGY, AVISTONE BIOTECHNOLOGY CO. LTD.
Summary
Key Points: 
  • Aberrant MET oncogenic alterations include: MET exon 14 skipping (MET∆ex14) mutations; activating mutations in the kinase domain; MET gene amplification; MET fusions; and MET protein overexpression.
  • Presently, type I c-Met inhibitors such as Capmatinib are used as monotherapies in patients with locally advanced or metastatic NSCLC with MET∆ex14 mutations.
  • However, development of post-treatment resistance to type I c-Met inhibitors occurs clinically, including through acquired mutations in codons D1228 and Y1230.
  • Next generation MET inhibitors are thus needed to treat patients harboring various MET oncogenic alterations beyond MET∆ex14, including post-treatment acquired mutations.


Avistone Biotechnology Co., Ltd (“Avistone” or “the Company”), a clinical-stage biotechnology company focused on precision oncology therapeutics, today announced results from its China and US IND enabling nonclinical studies for ANS014004 (“ANS01”), a novel small-molecule type II c-Met tyrosine kinase inhibitor (TKI). The data were presented today (Poster# C145) at the AACR-NCI-EORTC meeting hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC) in Boston, Massachusetts USA.

Mesenchymal epithelial transition (MET) proto-oncogene receptor tyrosine kinase (RTK) is a cell surface receptor selective for hepatocyte growth factor (HGF), and is involved in embryogenesis regulation, wound healing, organ regeneration, angiogenesis, and immunomodulation. Aberrant MET oncogenic alterations include: MET exon 14 skipping (MET∆ex14) mutations; activating mutations in the kinase domain; MET gene amplification; MET fusions; and MET protein overexpression. These oncogenic alterations occur in a wide range of human solid cancers.

Presently, type I c-Met inhibitors such as Capmatinib are used as monotherapies in patients with locally advanced or metastatic NSCLC with MET∆ex14 mutations. However, development of post-treatment resistance to type I c-Met inhibitors occurs clinically, including through acquired mutations in codons D1228 and Y1230. No drugs have been approved globally for MET alteration indications other than MET∆ex14 mutations. Next generation MET inhibitors are thus needed to treat patients harboring various MET oncogenic alterations beyond MET∆ex14, including post-treatment acquired mutations.

Overall, the non-clinical studies of ANS014004 demonstrated it is a potent, orally-bioavailable type II c-Met inhibitor with activity against various pathogenetic MET alterations and with favorable absorption, distribution, pharmacokinetic, efficacy, and tolerability profiles in vivo. The molecule will enter Phase 1 clinical studies in both China and the US soon.

“Avistone is a science-driven, innovative biotechnology company committed to the discovery and clinical development of first-in-class and best-in-class drugs,” said Dr. Hepeng Shi, Chairman, CEO, and Founder of Avistone. “We are proud to share these preclinical data for ANS014004 at this year’s AACR-NCI-EORTC meeting for which has promise for patients with c-MET aberrations in NSCLC.”

Electronic copies of the poster presented at the AACR-NCI-EORTC annual meeting are available upon request.

About Avistone Biotechnology Co. Ltd.

Avistone is an oncology company focused on developing innovative therapies for patients with significant unmet medical needs globally. Avistone has an extensive pipeline of targeted therapies including two clinical-stage drug candidates and several ongoing programs in the pre-clinical development stage. The Company’s lead asset is PLB1001, a small-molecule inhibitor that targets MET tyrosine kinase activity, including aberrant activity observed with METexon14 skipping (genetic) alterations in NSCLC tumors and in other solid tumors. The company's second clinical asset is PLB1004, a potent inhibitor of EGFR tyrosine kinases (TKI), including aberrant activity observed with EGFR exon20 insertion (genetic) mutations in NSCLC tumors.

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