Undisclosed masked antibodies / Adagene, Sanofi - LARVOL DELTA

Safety and efficacy of ADG126 (an anti-CTLA-4 masking antibody) in combination with pembrolizumab: Updated results of phase 1b/2 study in advanced MSS CRC. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05405595 Background: ADG126 is an anti-CTLA-4 IgG1 masked antibody that is preferentially activated in the tumor upon cleavage of masking peptides in the tumor microenvironment... Dose-dependent ORR has been observed for ADG126/Pembro IO doublet across multiple dose levels/regimens of ADG126 (10 mg/kg Q6W to 20 mg/kg LD) that is associated with well-tolerated to acceptable safety profile, which is enabled by a relatively large therapeutic window. The overall performance of ADG126/Pembro IO doublet warrants further clinical development including combination with SOCs targeting earlier lines/broader populations, such as MSS CRC with liver metastasis. Key efficacy results from MSS CRC patients.120 mg/kg LD: ADG126 20 mg/kg x1 cycle followed by 10 mg/kg Q3W."

Clinical • Combination therapy • Metastases • P1/2 data • Colorectal Cancer

Update of phase 1b/2 study of muzastotug (ADG126, an anti-CTLA-4 SAFEbody) in combination with pembrolizumab in advanced/metastatic MSS CRC. (ASCO-GI 2025) - P1/2 | "Funded by No funding sources reported Clinical Trial Registration Number: NCT05405595 Background: ADG126 is an anti-CTLA-4 IgG1 masked antibody with cleavable masking peptides that is preferentially activated in the tumor microenvironment, which in turn binds to a unique epitope to block CTLA-4 function, prime T cells and deplete Tregs. Extensive effort on ADG126 dose optimization, aided by PK-informed dosing strategy, suggested that ADG126 10 mg/kg Q6W and Q3W are appropriate dose/regimen for the IO doublet; this is supported by the well-balanced safety and efficacy (ORR, PFS and OS) profile observed in MSS CRC. ADG126 20 mg/kg Q3W appears to have reached safety ceiling for the IO doublet. The totality of the data further verifies that ADG126 possesses potential best-in-class therapeutic index, and provides basis for continued development of the IO doublet in MSS CRC and for additional exploration of the IO doublet in combination with SOCs/other anti-cancer..."

Combination therapy • Metastases • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer

Increased therapeutic index of muzastotug (ADG126), a masked anti-CTLA-4 antibody, in combination with pembrolizumab (pembro) enables significant clinical benefits and supports further clinical development in patients with metastatic MSS CRC (ESMO 2024) - P1/2 | "Muza up to 10mpk Q3W in combination with Pembro is well-tolerated with a comparable G3 TRAE rate as Pembro monotherapy. Meaningful clinical benefit and durability have been observed as demonstrated by significantly better ORR and mPFS compared to SOCs in 3L MSS CRC. These data support further evaluation of this combination therapy in the clinic, including with a 20 mpk loading dose regimen, in a randomized Ph2 study in MSS CRC without liver metastasis."

Clinical • Combination therapy • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ADG153, a novel masked anti-CD47 IgG1 SAFEbody, demonstrates strong in vivo anti-tumor activities in preclinical solid tumor models and preferential CD47 target engagement in the tumor microenvironment (AACR 2023) - "In normal tissues, the SAFEbody masking moiety is expected to shield ADG153 from binding to CD47; however, in the presence of highly upregulated CD47 in protease-rich tumor microenvironment (TME), the masked antibody can engage dynamically with highly expressed CD47 and can be cleaved, enabling efficient binding to CD47, blocking CD47/SIRPα signaling, and triggering strong anti-tumor activities in solid tumors. The in vivo anti-tumor efficacy of ADG153 or magrolimab analog (magrolimab) was assessed across several solid tumor xenograft models. ADG153 demonstrates significantly reduced antigen sink liabilities and favorable CD47 engagement in the TME, which are highly differentiated from other anti-CD47 agents. ADG153 is locally enriched and efficiently cleaved in tumors, engages its target, and elicits potent anti-tumor activities in multiple solid tumor xenograft models. These results indicate that the ADG153 SAFEbody is a novel anti-CD47 IgG1 antibody prodrug with..."

Preclinical • Tumor microenvironment • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • CD47 • SIRPA

ADG153-G1, a highly differentiated anti-CD47 IgG1 SAFEbody, demonstrates potent in vivo anti-tumor activities with enhanced ADCC/ADCP effects and significantly reduced RBC-related and antigen sink liabilities (AACR 2022) - "Next, our SAFEbody® technology for precision masking enables us to mask the CD47 binding sites to create the masked antibody in active IgG1 isotype called ADG153-G1 SAFEbody, which can be conditionally activated to bind and inhibit CD47 on tumor cells for potent tumor killing with much improved safety and pharmacokinetic profiles.In vitro studies showed that the activated ADG153-G1 SAFEbody blocked CD47 binding to SIRPα, bound to the CD47 protein, CD47+ tumor cell lines, and human RBCs, and induced strong ADCC/ADCP activities. Consistent with a reduced antigen sink effect due to lower RBC binding, the ADG153-G1 SAFEbody had more favorable pharmacokinetic properties than the Hu5F9 analog (~8× longer t1/2 and ~5× higher AUC) at 10 mg/kg. Taken together, these results indicate that the ADG153-G1 SAFEbody is a differentiated anti-CD47 IgG1 antibody prodrug with strong ADCC/ADCP potential and significantly reduced anemia-related and antigen sink liabilities,..."

Preclinical • Hematological Malignancies • Oncology • SIRPA

ADG206, an anti-CD137 agonistic POWERbodyTM with tailor-made efficacy and safety profiles by strong crosslinking and tumor selective activation for single and combinational cancer immunotherapy (AACR 2022) - "Utomilumab appears safe but has modest efficacy, while urelumab is more efficacious but causes severe dose-dependent liver toxicity...In normal tissues, the CD137 antigen binding interfaces of ADG206 are masked using a covalently linked designer peptide to limit on-target off-tumor toxicities, whereas in the tumor microenvironment (TME), the masked antibody can be activated to selectively bind CD137, promoting costimulatory signaling in situ...These results demonstrate that ADG206 POWERbody acquires a tailor-made product profile toward a best-in-class anti-CD137 immunotherapeutic agent that combines conditional activation in the TME with strong agonistic activity through heightened FcγR-mediated crosslinking. Further clinical development of ADG206 POWERbody may hold promises for achieving the long-awaited desirable tolerability and efficacy outcome of an anti-CD137 immunotherapy in either single agent or combination regimens."

Clinical • IO biomarker • Oncology