PH102: A GPC3-targeted IT-ACTS Therapy for Liver Cancer

GPC3 is an attractive target for immunotherapy due to its high expression in liver cancer and low expression in normal tissues. However, targeting solid tumors with CAR T-cell therapies has been challenging, as solid tumors often evade immune killing through multiple mechanisms of resistance.

Our lead candidate harnesses the power of IT-ACTS in a GPC3-targeted chimeric antigen receptor (CAR) T-cell therapy specifically designed to tackle multiple critical pathways of immunotherapy resistance in hepatocellular carcinoma. By actively enhancing the activation and persistence of T-cells, natural killer (NK) cells, and dendritic cells within the hostile tumor microenvironment—while simultaneously reducing immunosuppressive signals and boosting tumor infiltration—this triple-action platform maximizes the anti-tumor potential of CAR T-cells. At the same time, it minimizes off-target effects and improves tolerability, targeting novel mechanisms never before explored in solid tumor therapies.

In preclinical models of the most aggressive and lethal cancer subtypes, this IT-ACTS-based cell therapy has demonstrated exceptional efficacy, showing robust and durable anti-tumor responses across multiple solid tumor settings. Its unprecedented persistence, deep tumor infiltration, and ability to resist immunosuppressive pathways result in enhanced efficacy and improved safety—even from a single dose. To date, we have observed no off-target effects and only minimal on-target, off-tumor effects, setting the stage for a confident transition into clinical trials.

A First-In-Class Approach

Although many CAR T-cell therapies encounter difficulties in addressing solid tumors—often due to immunosuppression and insufficient tumor infiltration—our IT-ACTS-based candidate has been specifically engineered to overcome these hurdles by directly targeting the key mechanisms of immune evasion. Unlike conventional CAR T therapies that suffer from limited persistence and immune exhaustion, this next-generation approach employs unique targeting and activation strategies that support sustained responses in hard-to-treat cancers.

The versatile design of our IT-ACTS-based therapy also lends itself to a range of solid tumor indications, whether used as a standalone treatment or in combination with immune checkpoint inhibitors, vaccines, and other immunotherapy approaches. By employing a triple-action mechanism, this therapy transcends the limitations of traditional CAR T-cell treatments, offering a compelling new avenue for combating solid tumors.