Onxeo to Present New Preclinical Data at AACR 2021 - Seite 2

Session:		PO.ET03.05 - Reversal of Drug Resistance		E-poster:		1433
Date/ Time:		April 10, 2021 – 8:30 AM - 11:59 PM (U.S. Eastern Daylight Time -EDT)

To read the abstract: Acquired resistance to KRAS^G12C inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNA.

Recent progress has been made in the development of therapeutics against KRAS^G12C mutated tumors, which represent approximately 15% of lung adenocarcinoma. However, therapeutic resistance to KRASG12C inhibition is still a clinical hurdle. As we have previously shown with PARP inhibitors, we describe in these new data that resistance to KRAS^G12C inhibitors could also emerge, at least in part, from drug-tolerant persister cells, a specific cell population that undergo “dormancy” during treatment and accumulate mutations enabling the development of resistance to KRASG12C inhibitors. AsiDNA can target specifically this source of resistance and therefore prevents the emergence of acquired resistance to KRAS^G12C inhibitors, pointing to the therapeutic opportunity of combining AsiDNA and KRAS^G12C to overcome tumor progression or relapse.

Session:		PO.CL06.07 - Immunomodulatory Agents and Interventions		E-poster:		527
Date/ Time:		April 10, 2021 - 8:30 AM – 11:59 PM (U.S. Eastern Daylight Time -EDT)

To read the abstract: A new generation of PARP interfering drug candidates for cancer treatment.

Onxeo pioneered a new approach of anti-cancer treatment to tackle acquired drug resistance: the decoy agonist mechanism of action. Drugs based on this mechanism hijack and hyperactivate therapeutic targets leading to an impairment of their physiological function. Our first compound using this breakthrough decoy agonist action, AsiDNA, has already shown target engagement, excellent safety profile in humans and importantly, lack of acquired resistance. We now describe the mechanism of action of our OX400 molecules, designed to trap PARP proteins. We show that these molecules, by interfering with PARP signaling, display immunomodulatory properties and metabolic effects. Our results provide a preclinical rationale for using OX400 molecules as immunomodulatory and “metabolic exhauster” agents, especially in appropriately molecularly selected patients with tumors showing metabolic deficiencies.