On October 11, 2021 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported that it has entered into a collaborative partnership agreement with Eucure Biopharma, a subsidiary of Biocytogen Pharmaceuticals (Beijing) Co., Ltd. (Biocytogen), and a China-based clinical stage biopharmaceutical company primarily focused on the research and development of biologics, for the development of YH001, a CTLA-4 antibody with enhanced ADCC and CDC effector functions, for development in multiple oncology indications, including soft tissue sarcoma, in North America (Press release, Tracon Pharmaceuticals, OCT 11, 2021, View Source [SID1234591070]).
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Under the terms of the agreement, TRACON will be responsible for the clinical development and commercialization of YH001 in multiple oncology indications in North America, with the majority of the development activities expected to occur in the U.S. TRACON will bear the costs of clinical trials and Eucure Biopharma will supply YH001. TRACON will be responsible for commercializing YH001 in multiple oncology indications in North America and will owe Eucure Biopharma escalating double digit royalties on net sales.
YH001 was developed to potently inhibit CTLA-4 binding to the CD80/CD86 receptors and deplete regulatory T cells through enhanced ADCC and CDC effector functions. YH001 demonstrated superior activity in vitro and in transgenic syngeneic tumor models compared to ipilimumab (Yervoy), both as a single agent and when combined with a PD-(L)1 antibody.
"We are focused on advancing a dual checkpoint inhibitor strategy focused on the PD-(L)1 and CTLA-4 pathways, that we expect to leverage in sarcoma by combining YH001 with envafolimab, our novel, single-domain PD-L1 antibody, in sarcoma. Going forward, we intend to use YH001 rather than Yervoy in our future dual checkpoint inhibition trials in sarcoma, which we anticipate will result in meaningful cost savings from not needing to purchase Yervoy at retail prices," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "Moreover, we expect to study YH001 in other solid tumors in combination with PD-(L)1 antibodies, including in patients who have progressed on prior PD-(L)1 treatment."
"We believe that this collaboration with TRACON has potential to provide cancer patients in the United States with a best-in-class CTLA-4 checkpoint inhibitor. YH001 was optimized using Biocytogen’s discovery labs and proprietary transgenic mouse models to inhibit CTLA-4 binding and to deplete regulatory cells. In our ongoing Phase 1 clinical trials, YH001 has been tolerable as a single agent and in combination with the PD-1 antibody toripalimab," said Dr. Yuelei Shen, CEO of Biocytogen and Eucure Biopharma.
About YH001
YH001 is an IgG1 antibody against CTLA-4 that has shown enhanced antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) in vitro. In preclinical studies YH001 demonstrated superior T cell activation and superior tumor growth inhibition activity compared to ipilimumab. YH001 also demonstrated superior activity compared to ipilimumab in human transgenic mouse tumor models when combined with a PD-(L)1 antibody. In these models, single agent YH001 depleted regulatory T cells and increased CD8+ T cells in tumor tissue. YH001 is being dosed as a single agent in a Phase 1 trial in China (NCT04699929) and in combination with the PD-1 antibody toripalimab in a Phase 1 trial in Australia (NCT04357756). In July 2021, the U.S. Food and Drug Administration (FDA) approved the Investigational New Drug application to initiate multiple phase II clinical trials for YH001 in the United States.
About Envafolimab
Envafolimab (KN035), a novel, single-domain antibody against PD-L1, is the first subcutaneously injected PD-(L)1 inhibitor to be studied in pivotal trials. Envafolimab is currently being studied in the ENVASARC Phase 2 pivotal trial in the U.S. sponsored by TRACON, as well as in a Phase 2 pivotal trial as a single agent in MSI-H/dMMR advanced solid tumor patients and a Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China sponsored by TRACON’s corporate partners, Alphamab Oncology and 3D Medicines. Alphamab Oncology and 3D Medicines submitted an NDA to the NMPA in China for envafolimab in MSI-H/dMMR cancer that was accepted for review in December 2020 and granted priority review in January 2021. In the Phase 2 MSI-H/dMMR advanced solid tumor trial, the confirmed objective response rate (ORR) by blinded independent central review in MSI-H/dMMR colorectal cancer (CRC) patients treated with envafolimab who failed a fluoropyrimidine, oxaliplatin and irinotecan was 32%, which was similar to the 28% confirmed ORR reported in the Opdivo package insert in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin, and irinotecan and the 33% confirmed ORR reported for Keytruda in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin and irinotecan in cohort A of KEYNOTE-164.