Abstract 3051: DiaXCIP3M: A new small drug molecules conjugate displaying a strong antiproliferative in vitro and in vivo activity against human small cell lung cancer

Abstract The high medical need for new, original therapeutic molecules remains clear for all those fighting small cell lung cancer (SCLC). DiaXCIP3M based on patented technology belongs to a new class of small drug molecules conjugates (SDMCs). Traditional chemotherapy mostly relies on the use of a cocktail of several anticancer drugs. However, two different drugs display two different pharmacokinetics and two different tissue biodistributions meaning that it is very challenging to anticipate the ratio of these two drugs in the tumor or normal cells. Small molecule drug conjugates (SMDCs) are a promising strategy to reduce these limits by coupling two distinct cytotoxic molecules in one new drug therefore inducing only one pharmacokinetic and one biodistribution. The inter-variability of the drug exposure between patients is thus expected to be reduced compared to the cocktail approach. Reduction of the variability allows a better definition of the recommended dose to actively and safely treat the cancer patients. Preclinical studies performed today indicate that DiaXCIP3M has a strong product profile for further development with 1/ a patented chemical structure, 2/ an original mechanism of action that involves simultaneously inhibition of two validated anticancer targets, resulting in activity in a large range of cancer subtypes, 3/ a powerful in vitro antitumor activity at low nM against human SCLCs, 4/ a suitable in vivo plasma stability assessed by iv route in mouse superior to 2 hrs, and 5/ an induction of in vivo tumor reduction at safe dose in human SCLC xenografted model in mice.DiaXCIP3M has the potential to become an integral part of the therapeutic landscape for ES-SCLC, particularly as a second-line alternative to the currently validated chemotherapy, topotecan, or as a third-line treatment after topotecan failure. Citation Format: Gregoire Pierre Prevost, Gwenaël Forcher, Anne-Caroline Chany, Laurent Fontaine. DiaXCIP3M: A new small drug molecules conjugate displaying a strong antiproliferative in vitro and in vivo activity against human small cell lung cancer [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 3051.