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
Presenter: Chang-Sun Lee, PhD Session: Antibody-Drug Conjugates and Linker Engineering 1 Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
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 Celltrion Pharm, Inc., Incheon, Korea, Republic of
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(AD 2 C) 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 (AD 2 C) designed to enhance anti-tumor activity without exacerbating systemic toxicity. This presentation covers a comprehensive characterization of FRα AD 2 C 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 AD 2 C via pharmacokinetic assessment in rats, and preliminary safety evaluation in mice. We are currently advancing dual-payload FRα ADC(AD 2 C) toward PDX efficacy studies and GLP toxicology studies in order to proceed to Ph1 IND filing in due course.
Disclosure
S. Lim, None.. M. Kim, None.. J. Ha, None.. H. Jun, None.. J. Lee, None.. S. Im, None.. S. Kim, None.. Y. Kim, None.. S. Kim, None.. H. Kang, None.. C. Lee, None.
Cited in
Control: 5625 · Presentation Id: 5370 · Meeting 21436