On January 6, 2021 TRIGR Therapeutics, Inc. ("TRIGR"), a clinical stage biopharmaceutical company focused on the development of multi-targeted angiogenic and immunomodulatory bispecific antibodies for oncology and certain ischemic indications, reported the publication of a manuscript in the International Journal of Molecular Sciences, highlighting the pre-clinical development of TR009, the Company’s investigational dual angiogenic bispecific antibody targeting VEGF/DLL4 (Press release, TRIGR Therapeutics, JAN 6, 2021, View Source [SID1234573589]).
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TRIGR Therapeutics holds the global rights to TR009 (a.k.a ABL001/NOV1501), outside of the Republic of Korea. ABL Bio (KOSDAQ: 298380), a premier biotechnology company focused on cancer and neurodegenerative diseases, licensed the worldwide rights to TRIGR in November 2018.
As described in the paper "ABL001 [TR009], a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models" the authors report that TR009 demonstrates more potent in vitro and in vivo biological activity compared to VEGF or DLL4 targeting monoclonal antibodies alone. Further, TR009, in combination with paclitaxel and irinotecan in human gastric and colon cancer xenograft models synergistically inhibited tumor progression as compared to each monotherapy. Tumor vessel regression and apoptotic tumor cell induction were noted along with TR009’s mechanistic effect on tumor vessel normalization. Immunohistochemical analysis of tumor blood vessels showed marked reduction of expression levels of VEGFR-2 and DLL4, dual targets of TR009, in tumor endothelial cells after TR009 treatment. Consistent with previous studies, the data strongly support that VEGF/VEGFR signaling interacts with DLL4/Notch signaling in the tumor vasculature; the facilitation of immune cell infiltration via dual blockade of VEGF and DLL4 also suggests a rationale for TR009 in combination therapy with immune checkpoint inhibitors.
These pre-clinical findings are consistent with preliminary data from TR009 ongoing Phase 1 Dose Escalation/Expansion Monotherapy and Phase 1B Combination studies (n~60 patients). As a single agent, TR009 has demonstrated a 67% Clinical Benefit Rate, with deep and sustained partial responses per RECIST criteria in heavily pre-treated colorectal and gastric cancer patients that have failed at least 3 lines of prior therapy and become resistant to multi-VEGF (Avastin, Stivarga, Cyramza), EGFR, anti-PD-1/PD-L1 and chemotherapies. The Phase 1B results testing the safety of TR009 in combination with irinotecan or paclitaxel, have also shown deep and sustained partial responses in difficult to treat 3rd / 4th line Intrahepatic Cholangiocarcinoma (Biliary Tract Cancer) and Non-Small Cell Lung Cancer patients that have failed multiple lines of chemo, biological therapy, and anti-PD-1. TR009 has been safety administered up to 17.5mg/kg dose with no dose limiting toxicities (DLT). In contrast to historical DLL4 and other Notch targeted therapies, the administration of TR009 has not been hampered by pulmonary hypertension or other cardiac toxicities. Further updates on these studies will be provided later in 2021.