Crossfire Oncology to present best-in-class macrocyclic BTK inhibitor CFON-026 and novel Degrader Antibody Conjugate technology at AACR 2024

The Crossfire team will present 3 posters at the American Association for Cancer Research (AACR) annual meeting 2024. We will highlight the latest data on our best-in-class macrocyclic BTK inhibitor CFON-026, our novel Degrader Antibody Conjugate (DAC) technology, and our proprietary EPriL platform, which sits at the heart of both CFON-026 and our DACs.

On Monday April 8, we will present our clinical candidate CFON-026, a best-in-class non-covalent macrocyclic BTK inhibitor that has potent activity towards BTK wild-type and all its clinically relevant mutant variants. The macrocycle structure of CFON-026 ensures a unique covalent-like binding mode based on β-sheet complementation. This not only allows for targeting BTK wild-type and BTK[C481S], often acquired following treatment with covalent BTK inhibitors, but also BTK[T474I] which arises with high incidence following pirtobrutinib treatment. CFON-026 is currently in preclinical development and expected to enter the clinic H2 2025.

On Tuesday April 9, we will present our EPriL (Energetically Privileged Ligands) macrocycle platform and how its chemical versatility was used to create a library of kinase degraders. Applying a screening cascade, novel degraders were discovered with high kinase selectivity and excellent potency.

On Tuesday April 9, we will present the opportunities that our EPriL platform provides for the generation of DACs. EPriL-based degraders have intrinsic properties that make them extraordinarily suitable for conjugation to antibodies. This will overcome the physicochemical challenges observed with degraders and increase the therapeutic window, thus improving their clinical potential. Our internal conjugation and in vitro testing platform enable the rapid exploration of powerful new degrader-antibody combinations for the treatment of cancer.

CFON-026 is a potent non-covalent BTK inhibitor suitable for combination therapy with covalent BTK inhibitors for early eradication of resistance mutations

Experimental and Molecular Therapeutics, abstract no. 1960
Monday Apr 8, 2024 9:00 AM – 12:30 PM
Presenter: Jos de Man

EPriL: A platform for the rapid identification of degraders of inhibitor-resistant kinases

Experimental and Molecular Therapeutics, abstract no. 6044
Tuesday Apr 9, 2024 1:30 PM – 5:00 PM
Presenter: Michelle Muller

EPriL macrocycles as a platform for the rapid generation of effective kinase degrader antibody conjugates (DACs)

Experimental and Molecular Therapeutics, abstract no. 5814
Tuesday Apr 9, 2024 1:30 PM – 5:00 PM
Presenter: Joost Uitdehaag