NAYA Biosciences has announced the initiation of a Phase 1/2a clinical trial to evaluate NY-303, a GPC3-targeting NK Engager bispecific antibody, for the treatment of hepatocellular carcinoma (HCC) in patients who have not responded to first-line immunotherapy. The trial received regulatory approval from the Israeli Ministry of Health in July 2024 and institutional review board clearance to begin patient enrollment across multiple academic centers in Israel.
The Phase 1 portion of the trial will be a dose-escalation study, where patients showing a response to treatment will continue weekly administration as long as no disease progression is observed. Key endpoints include safety, pharmacokinetics, activity markers, preliminary clinical efficacy, and time-to-progression. Patient recruitment is planned to commence in early 2025 at leading medical centers in Israel, including Hadassah Hospital, Sheba Medical Center, and Sourasky Medical Center.
The Phase 2a part of the trial is anticipated to expand to the United States and Europe, pending further regulatory approvals. This phase will evaluate NY-303 at two dose levels selected during Phase 1. The primary efficacy endpoints will be objective response rate and progression-free survival.
Addressing Unmet Needs in HCC Treatment
Hepatocellular carcinoma is a significant global health challenge, with over 900,000 new cases diagnosed annually, making it the sixth most common cancer worldwide. According to NAYA Therapeutics Chief Medical Officer Dan Chiche, MD, less than 30% of patients treated with the current standard of care respond to immunotherapy, with a mean progression-free survival of less than 7 months. The five-year survival rate for liver cancer in the United States is around 20%, underscoring the critical need for more effective therapies.
NY-303: A Novel Approach
NY-303 is a first-in-class therapeutic candidate designed to engage and activate natural killer (NK) cells. It utilizes a bispecific antibody that targets both GPC3, an oncofetal protein uniquely expressed on liver cancer cells, and NKp46, a cell surface receptor on NK cells that plays a central role in NK cell activation and target cell elimination. This mechanism aims to transform tumors from "cold" to "hot," making liver cancer cells more susceptible to immunotherapy. This approach is particularly promising for HCC patients who have limited treatment options and poor survival rates, as well as for other GPC3-expressing tumors such as lung squamous cell carcinoma, ovarian cancer, and pediatric cancers.
Current Treatment Landscape
Current liver cancer therapies include surgery, liver transplantation, targeted drugs, and immunotherapies like checkpoint inhibitors. However, the prognosis remains poor, especially for advanced-stage disease. NY-303 represents a new opportunity by harnessing the body’s immune system to specifically attack tumor cells and engage NK cells, potentially offering a safer profile with reduced side effects compared to traditional treatments.
