Abstract 7336: B7-H7 is a novel ADC target for solid tumors and shows potent activity with multiple payload-linker technologies

Abstract Introduction: B7-H7 is a member of the B7 family, with strong expression in multiple cancer indications in addition to its known role as an immune regulator. B7-H7 upregulation is correlated with poor patient outcomes. Furthermore, its normal tissue expression is limited making B7-H7 very attractive for targeting tumors. NextPoint has therefore explored B7-H7 as a novel antigen to target antibody drug conjugates (ADCs) to solid tumors. Antibodies previously raised against distinct B7-H7 epitopes, with cross-reactivity to the cynomolgus protein, were produced as ADCs and multiple distinct payload-linker technologies were applied. These were tested for in vitro and in vivo activity, and for their developability characteristics enabling lead selection of the most potent compounds. Methods: ADC binding efficacy was assessed by flow cytometry on endogenous B7-H7+ and overexpressing B7-H7 cell lines. Internalization was tracked with Fabfluor-pH reporter conjugated to ADCs using Incucyte® imaging. In vitro cytotoxicity was evaluated by luminescence-based cell viability assays with CellTiter-Glo® to detect ATP in the media. The pharmacokinetics of each ADC was assessed in rats by measurement of both total and drug-conjugated antibody. The in vivo activity was tested against B7-H7-expressing xenograft tumors in immunodeficient mice. Results: The majority of B7-H7-targeted ADCs had similar on-cell binding capacities as parental antibodies. Internalization analyses showed that after 4h, over 50% of cells had internalized the compounds with an optimal concentration of 0.3 nM ADCs. Multiple B7-H7 targeted ADCs demonstrated cytotoxicity against tumor cell lines, with an in vitro EC50 under 0.3 nM on average and under 0.1 nM for the most potent compounds. Rat pharmacokinetics demonstrated half-lives above 7 days for the lead compounds and acceptable payload stability across technologies. In vivo, ADC leads were tested in several in vivo tumor models that cover a wide range ofB7-H7 protein expression. Selected ADC leads with distinct linker-payload technologies demonstrated tumor activity in multiple in vivo tumor models. Body weight changes were minimal following dosing of the most active ADCs in these mouse systems. Conclusions: Collectively, these preclinical studies establish B7-H7 as an attractive ADC targeting antigen and demonstrate its activity with multiple clinically relevant payload-linker technologies. These data support further development of lead compounds as a promising treatment for patients with B7-H7-expressing tumors. Citation Format: Emilien Loeuillard, Bijan A. Etemad-Gilbertson, Susannah L. Hewitt, Jamie L. Strand, Riale T. Gilligan, Silvia Ferrati, Tatiana I. Novobrantseva, Matthew Rausch. B7-H7 is a novel ADC target for solid tumors and shows potent activity with multiple payload-linker technologies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7336.