On February 25, Junshi Biosciences announced a strategic collaboration with Antengene Corporation to jointly explore the synergistic potential of the combination therapy involving Junshi Biosciences’ independently developed JS207 (anti-PD-1/VEGF bispecific antibody) and Antengene’s ATG-037 (oral small-molecule CD73 inhibitor) in cancer patients in Chinese Mainland.JS207 is a recombinant humanized anti-PD-1 and VEGF bispecific antibody independently developed by Junshi Biosciences. It has demonstrated encouraging anti-tumor activity and a manageable safety profile in both preclinical and clinical studies. Preclinical studies have validated its prominent anti-tumor efficacy in multiple tumor models and supported its differentiated mechanism of action. Studies have shown that VEGFA can enhance the antigen-binding activity, T-cell activation potency, and endocytosis of cell-surface PD-1 by JS207.
In a poster presentation at the European Society for Medical Oncology Asia (ESMO Asia) 2025, JS207 monotherapy exhibited promising efficacy across multiple solid tumors. Among 62 PD-L1-positive non-small cell lung cancer (NSCLC) patients receiving first-line treatment, the objective response rate (ORR) reached 58.1% and the disease control rate (DCR) reached 87.1%. In addition, clinical activity of JS207 was also observed in other tumor types including hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), further supporting the potential value of the dual PD-1/VEGF targeting strategy across multiple tumor settings.
To date, a total of 11 Phase 2 clinical trials of JS207 are ongoing, exploring combinations with chemotherapy, monoclonal antibodies, antibody-drug conjugates (ADCs) and other agents in tumor types including NSCLC, colorectal cancer, triple-negative breast cancer and liver cancer, with nearly 500 patients enrolled in total. Based on the accumulated data, the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application for JS207, authorizing Junshi Biosciences to initiate an open-label, two-arm, randomized, active-controlled Phase 2/3 study comparing JS207 versus nivolumab as neoadjuvant therapy in patients with Stage Ⅱ/Ⅲ resectable alterable genomic alteration (AGA)-negative NSCLC.
ATG-037 is an oral small-molecule CD73 inhibitor under development by Antengene, with distinct advantages over anti-CD73 monoclonal antibodies. Preclinical studies have shown that ATG-037 more potently inhibits cell-surface CD73 enzymatic activity and overcomes the “hook effect” commonly seen with antibody-based agents. Furthermore, ATG-037 exhibits superior tissue penetration compared to antibodies, facilitating complete CD73 inhibition at the cellular level.
According to the latest data presented by Antengene at its R&D Day in November 2025, the combination of ATG-037 and anti-PD-1 therapy demonstrated encouraging clinical activity in patients with immune checkpoint inhibitor (CPI)-resistant melanoma and NSCLC. In the ongoing Phase 1/1b STAMINA-01 study, the combination achieved an ORR of 33.3% and a DCR of 100% in patients with CPI-resistant melanoma, and an ORR of 21.4% and a DCR of 71.4% in patients with CPI-resistant NSCLC. The data were derived from Australian patients with CPI-refractory solid tumors, whose prior anti-PD-1 monoclonal antibody treatment was mainly pembrolizumab and/or nivolumab. Among melanoma patients, over 70% were dual-resistant to both anti-PD-1 and anti-CTLA-4 (ipilimumab) therapies. These findings indicate that ATG-037 holds clinically meaningful therapeutic potential across multiple tumor types, particularly in patients with prior resistance to immunotherapy.
Meanwhile, ATG-037 demonstrated favorable overall safety and tolerability in combination regimens, with no new or unexpected safety signals observed, and no new safety concerns identified in patients on long-term treatment. The incidence of treatment-related adverse events (TRAEs) of Grade 3 or higher was only 7.9%. In addition, durable responses were observed: one patient achieved complete response (CR) with more than three years of follow-up in the study, remains on ATG-037 monotherapy for over one year, and multiple other patients had a duration of response (DoR) exceeding 12 months. These data further support the value of ATG-037 as a potential backbone agent in next-generation immuno-oncology combination regimens.
The scientific rationale for this collaboration lies in the complementarity and potential synergy between CD73 inhibition and dual PD-1/VEGF targeting. CD73 is recognized as a key regulator of immunosuppression and angiogenesis in the tumor microenvironment, exerting its effects through the generation of adenosine and thereby attenuating anti-tumor immune responses.
CD73 inhibitors have demonstrated significant synergy with anti-PD-1 monoclonal antibodies in clinical and preclinical studies. Furthermore, studies have shown that CD73 activity promotes angiogenesis, including via upregulation of the VEGF signaling pathway, and may contribute to resistance to anti-VEGF therapy. Given the widespread involvement of immunosuppression, angiogenesis and adenosine signaling across multiple solid tumors, this combination strategy holds promise for broad applicability across various tumor types. Collectively, the combination of CD73 blockade with PD-1/VEGF targeting is expected to enhance and sustain therapeutic efficacy.
In a press release, Junshi Biosciences stated that the combination of ATG-037 and JS207 constitutes a potential “tri-axis” strategy, simultaneously modulating immune checkpoint signaling, angiogenesis and the adenosine pathway. With a favorable safety profile, this combination regimen is expected to further boost efficacy and improve the durability of clinical benefit, potentially translating into superior long-term outcomes including overall survival (OS) benefit.