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ES104

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ES104, a bispecific antibody was composed of the C-terminal of anti-VEGF IgG backbone linked with a single chain Fv targeting DLL4. ES104 is currently being evaluated in Ph1 dose escalation study.


MOA:

1. Anti-VEGF therapy has proven survival benefits and a mainstay in various tumors;
2. Resistance to current VEGF drugs creates the need for alternative anti-angiogenic regimens;
3. DLL4 mediated NOTCH1 signaling represents an essential pathway for vascular development of tumors and cancer stem cells;
4. Simultaneously blocking both VEFG and DLL4 is the next frontier of angiogenic therapy as this mechanism has been shown to overcome multi-VEGF resistance.


Onging Clinical Trial: 

Data from ongoing Phase 1 Dose Escalation/Expansion Monotherapy and Phase 1B Combination studies (n~60 patients) demonstrate 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 in combination with irinotecan or paclitaxel, have also shown deep and sustained partial responses in difficult to treat 3rd/ 4thline Intrahepatic Cholangiocarcinoma (Biliary Tract Cancer) and Non-Small Cell cancer patients that have failed multiple lines of chemo, biological therapy, and anti-PD-1. ES104 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 ES104 has not been hampered by pulmonary hypertension or other cardiac toxicities.