On April 19, 2024 The Crossfire team reported that it has attended this year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting with three posters (Press release, Crossfire Oncology, APR 19, 2024, View Source [SID1234642182]).
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On Tuesday the Crossfire team unveiled its highly innovative degrader-based payload targeting an essential cell cycle kinase. Its sophisticated design is expected to dramatically reduce off-tumor related toxicity observed with classical payloads. This will increase the therapeutic window for this novel Degrader Antibody Conjugate technology versus currently approved ADCs (see poster link).
On the same day, Crossfire’s proprietary EPriL platform was presented, that enables rapid identification of potent kinase degraders. EPriLs contain a unique macrocyclic scaffold that binds the ATP-binding pocket of kinases and which have several exit vectors suitable for attachment of E3 ligase binders. In this way, potent BTK degraders were established with potent activity on all clinically relevant BTK inhibitor resistance mutants (see poster link).
The day before, our best-in-class non-covalent BTK inhibitor (CFON-026) was presented. The macrocyclic nature of CFON-026 endows it with high potency, not only on BTK wild-type, but also BTK[C481S] and BTK[T474I], making it a unique non-covalent BTK inhibitor with cytotoxicity to all clinically relevant BTK mutant variants. Because of Crossfire’s strategic decision to fully focus on the development of Degrader Antibody Conjugates, an out-licensing process was recently initiated for this exciting program that is mid-way preclinical development (see poster link).