The anti-GPC3 targeted therapies market is experiencing significant momentum as pharmaceutical companies advance novel treatment approaches for hepatocellular carcinoma (HCC) and other GPC3-expressing malignancies. According to DelveInsight's analysis, the total market size of anti-GPC3 targeted therapies in the 7MM is expected to surge significantly by 2040, driven by increasing cancer incidence, clinical pipeline activity, and anticipated regulatory approvals.
GPC3 Emerges as Promising Therapeutic Target
Glypican-3 (GPC3), a cell surface heparan sulfate proteoglycan, has emerged as an attractive tumor-specific antigen due to its minimal expression in normal adult tissues. This distinct expression pattern makes GPC3 particularly suitable for HCC-specific therapies, allowing for precise drug delivery while minimizing unintended effects on normal liver cells. GPC3 is notably overexpressed in cancerous liver cells but shows minimal or no expression in healthy liver tissue, with the antigen present in over 70% of hepatocellular carcinoma cells.
The specificity of GPC3 has sparked considerable interest from biotech and pharmaceutical companies in developing antibody-drug conjugates (ADCs), CAR T-cell therapies, bispecific antibodies, and vaccines targeting this antigen. Key indications contributing to the anti-GPC3 therapy landscape include hepatocellular carcinoma, non-small cell lung cancer, gastric cancer, and potentially other GPC3-expressing tumors.
Recent Clinical Developments
AstraZeneca's Novel T Cell Engager
In May 2025, AstraZeneca presented data at ASCO 2025 from the RHEA-1 first-in-human study evaluating AZD9793, a first-in-class CD8-guided T cell engager (TCE) targeting GPC3-positive advanced or metastatic HCC. This milestone highlighted AstraZeneca's innovation in TCE platform development.
AZD9793 is a first-in-class trispecific IgG1 monoclonal antibody engineered as a CD8-directed T-cell engager. It links CD8+ T cells with GPC3-positive tumor cells to initiate T cell-mediated tumor killing and promote T cell proliferation. The antibody selectively activates CD8+ T cells while limiting CD4+ T cell engagement and minimizing cytokine release. Its novel mode of action combines dual GPC3 binding, CD8-biased targeting, and low-affinity TCR interaction to enhance tumor cytotoxicity and reduce the likelihood of cytokine release syndrome compared to conventional TCEs.
Bayer's Radiopharmaceutical Approach
In April 2025, Bayer announced the initiation of a Phase I clinical trial for 225Ac-GPC3 (BAY 3547926), an investigational targeted alpha radiopharmaceutical designed to treat GPC3-expressing tumors in patients with advanced HCC. This represents a novel approach utilizing targeted radiation therapy.
225Ac-GPC3 (BAY 3547926) is an investigational alpha-emitting radiopharmaceutical aimed at treating advanced HCC tumors that express GPC3. It comprises a high-affinity GPC3-specific antibody conjugated to the alpha-emitting radionuclide actinium-225. This targeted delivery of alpha radiation to GPC3-positive cancer cells can cause DNA double-strand breaks, potentially decreasing cell viability and exerting anti-tumor effects.
Pipeline Therapies Show Promise
Eureka Therapeutics' ARTEMIS Platform
ECT204, developed by Eureka Therapeutics, is an experimental ARTEMIS T-cell therapy designed to target glypican-3. This therapy incorporates Eureka's proprietary tumor infiltration platform, which has shown enhanced penetration into solid tumors in preclinical animal studies, potentially translating into greater clinical effectiveness. ECT204 is currently under evaluation in the ongoing ARYA-3 clinical trial, a multi-center, open-label, Phase I/II dose-escalation study involving adult patients with GPC3-positive HCC. The therapy has also received Orphan Drug Designation for HCC treatment.
Expanding Pipeline Activity
Other key anti-GPC3 targeted therapies in the pipeline include RPCAR01 from CRISPR Therapeutics, BGB-B2033, and Anti-GPC3 in vivo CAR-M Therapy from Carisma Therapeutics and Moderna. Leading companies such as Eureka Therapeutics, AstraZeneca, Bayer, CRISPR Therapeutics, BeOne Medicines, Carisma Therapeutics, and Moderna are developing novel anti-GPC3 targeted therapies expected to become available in the coming years.
Market Dynamics and Challenges
The competitive landscape remains fragmented but is becoming increasingly crowded as GPC3 garners attention beyond HCC. Emerging evidence of GPC3 expression in other solid tumors, like ovarian clear cell carcinoma and lung squamous cell carcinoma, is encouraging companies to broaden their development strategies. This potential expansion across multiple indications could significantly widen the market opportunity and drive further investment in GPC3-targeted platforms.
However, the market faces challenges including the complexity of treating solid tumors, tumor heterogeneity, immunosuppressive microenvironments, and antigen escape, which continue to hinder the efficacy of cellular therapies. Manufacturing complexities, regulatory hurdles, and high costs associated with personalized therapies like CAR-Ts may limit widespread adoption. In contrast, ADCs and bispecific antibodies may offer more scalable solutions, but will require careful optimization to avoid off-target toxicities and achieve durable responses.
Future Outlook
Although anti-GPC3 monotherapies have demonstrated limited success in hepatocellular carcinoma, this has been attributed to the requirement for extensive tumor saturation to elicit a meaningful therapeutic response. As a result, there is growing interest in next-generation approaches, such as CAR-T cell and TCR-engineered T cell therapies, that may be better equipped to address these challenges.
The anti-GPC3 therapies market is positioned for long-term growth, driven by scientific validation, technological innovation, and the increasing prioritization of precision oncology. As data from ongoing clinical trials mature, particularly those evaluating combination strategies or novel formats, GPC3-targeted therapies have the potential to reshape the treatment paradigm for GPC3-expressing tumors, especially in HCC, where treatment options remain limited.
