Eureka Therapeutics Granted FDA Orphan Drug Designation for Two T-Cell Therapies, ET140203 and ECT204, for Hepatocellular Carcinoma

On February 8, 2022, Eureka Therapeutics announced that the U.S. FDA had granted Orphan Drug Designation to the investigational T-cell therapies ET140203 and ECT204 for the treatment of hepatocellular carcinoma (HCC). Both T-cell candidates are developed based on the company’s proprietary ARTEMIS technology platform, targeting specific liver cancer antigens. Eureka Therapeutics is currently recruiting patients in three Phase 1/2 clinical trials to evaluate their safety and potential efficacy separately.

Liver Cancer: A Leading Cause of Cancer-Related Deaths WorldwideLiver cancer is one of the leading causes of cancer-related deaths globally. It was estimated that there were over 905,000 new cases of liver cancer worldwide in 2020, with more than 830,000 deaths attributed to the disease. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for approximately 75% to 90% of primary liver cancer cases. Globally, the main risk factors for HCC are chronic hepatitis B and chronic hepatitis C, alcohol consumption, and metabolic syndrome.

The ARTEMIS platform has two core functional components: an antibody-based antigen-binding domain and an effector domain. The receptor design of ARTEMIS enables it to utilize the activation and regulation pathways typically employed by endogenous T-cell receptors (TCR). Since this strategy does not directly link the intracellular signaling domain with the co-stimulatory domain, it is expected to eliminate cytokine release syndrome (CRS) caused by excessive T-cell activation.

The treatment process of ET140203 involves collecting T cells from patients, engineering them to express Eureka Therapeutics' proprietary ARTEMIS cell receptor, and then infusing them back into the patient. The receptor expressed by the modified ET140203 T cells targets the alpha-fetoprotein (AFP)-peptide/HLA-A2 complex expressed on liver cancer cells. In addition, ET140203 T cells incorporate Eureka Therapeutics’ proprietary tumor infiltration technology, which has been shown in animal models to enhance the drug’s ability to infiltrate solid tumors, potentially improving patient outcomes. This therapy is currently being evaluated in two open-label, dose-escalation, multi-center Phase 1/2 clinical trials: one in adult patients with AFP-positive HCC, and the other in pediatric subjects with AFP-positive recurrent/refractory hepatoblastoma (HB), hepatocellular neoplasm-not otherwise specified (HCN-NOS), and HCC.

ECT204 Targets GPC3 Expressed on Hepatocellular Carcinoma Cells, a Promising HCC Antigen Present in Over 70% of HCC Cells. ECT204 T Cells Also Incorporate Eureka Therapeutics' Proprietary Tumor Infiltration Technology. It is Currently Being Evaluated in a Phase 1/2 Clinical Trial for the Treatment of Adult Patients with GPC3-Positive HCC.

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