Abstract Dual-payload antibody drug conjugates (ADCs) have achieved increasing traction as a next-generation ADC technology to improve the therapeutic window of single-payload ADCs. By integrating two different payloads having distinct modes of actions, dual-payload ADC platforms can offer opportunities to counter tumor heterogeneity, or to reduce the likelihood of resistance that often emerges with the single-payload ADCs. We have pursued novel dual-payload ADC formats that can provide synergistic activity as well as minimal overlapping toxicity due to complementary acting mechanisms from two different payloads. A few combinations of payloads have been found to demonstrate synergistic cytotoxicity, which have been successfully incorporated into ADCs to confirm the novel dual-payload ADC(AD2C) concept. Although folate receptor-alpha (FRα) represents a clinically validated antigen as highlighted by the approval of Elahere, clinical benefit is yet to remain limited due to dose-limiting toxicities and suboptimal response durability. To address these shortcomings, we have generated dual-payload FRα ADC (AD2C) designed to enhance anti-tumor activity without exacerbating systemic toxicity. This presentation covers a comprehensive characterization of FRα AD2C including in vitro cytotoxicity for cancer cells with different levels of FRα expression, in vivo anti-tumor activities in FRα-positive CDX models, in vivo stability of FRα AD2C via pharmacokinetic assessment in rats, and preliminary safety evaluation in mice. We are currently advancing dual-payload FRα ADC(AD2C) toward PDX efficacy studies and GLP toxicology studies in order to proceed to Ph1 IND filing in due course. Citation Format: Soyeon Lim, Myeong Joo Kim, Junho Ha, Heegoo Jun, Jongchan Lee, So Hee Im, Seo Ha Kim, Young Sang Kim, Seung Chan Kim, Hyo Jin Kang, Chang-Sun Lee. A novel synergistic dual-payload FRα ADC (CTPH-08) that can potentially offer benefits for low IHC+ ovarian cancer patients by improving MTD and MED abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1698.
Lim et al. (2026) studied this question.