Page 1

888C4 Therapeutics C4 Therapeutics Presents Pre - clinical Data on CFT8919 , A Selective Degrader of EGFR L858R , at Keystone Symposium on Targeted Protein Degradation June 7 , 2021 - CFT8919 Induces Tumor Regression in Pre - clinical Models Resistant to First- and Third - generation EGFR Inhibitors - - CFT8919 Demonstrates Intracranial Activity Pre - clinically , Indicating the Potential to be Effective Against CNS Metastases - - Pre - clinical Data Support Plans to Advance CFT8919 to Clinical Development with IND Submission Expected in mid - 2022 and Clinical Trial Initiation Expected by YE 2022 - - Conference Call and Webcast at 8:00 am ET Today - WATERTOWN , Mass . , June 07 , 2021 ( GLOBE NEWSWIRE ) -- C4 Therapeutics , Inc. ( C4T ) ( Nasdaq : CCCC ) , a biopharmaceutical company pioneering a new class of small - molecule medicines that selectively destroy disease - causing proteins through degradation , today presented new pre - clinical data on CFT8919 , a novel mutant - selective degrader of epidermal growth factor receptor ( EGFR ) in non - small cell lung cancer ( NSCLC ) at the Keystone Symposium on Targeted Protein Degradation . The poster presentation shares pre - clinical data that suggests CFT8919 may be active as a single agent in patients with resistance to EGFR inhibitors due to secondary mutations in EGFR , including T790M and C797S , as well as in the front - line setting with the potential to avoid the emergence of resistance - causing secondary EGFR mutations seen with currently approved EGFR inhibitors . " We are excited to share strong preclinical data that establishes CFT8919 as a potent and selective degrader of EGFR L858R , a mutation responsible for more than a third of mutant EGFR lung cancer diagnoses . Patients with this mutation are commonly treated with approved EGFR inhibitor therapies , but often have worse clinical outcomes than individuals diagnosed with other driver mutations such as Exon19del , " said Adam Crystal , M.D. , Ph.D. , chief medical officer of C4 Therapeutics . " Across our portfolio , we see the potential for targeted protein degradation to transform patient care . We believe our decision to advance CFT8919 recognizes promising early data that indicate CFT8919 may have the potential to treat patients who develop resistance to first - line EGFR inhibitors as well as a path to inclusion in front - line therapeutic regimens . We look forward to learning more about CFT8919 as we advance the program into IND - enabling studies and initiate the Phase 1 clinical trial in 2022. " Summary of CFT8919 Pre - clinical Results C4T conducted in vitro and in vivo studies that show CFT8919 is a potent and highly selective orally bioavailable degrader of EGFR L858R with broad coverage of on - target resistance mutations as well as intracranial activity . Notable observations include : • In cancer cell lines , CFT8919 induces degradation of EGFR L858R at low nanomolar concentrations while no degradation of wild type is induced up to 10 μM . • CFT8919 demonstrates equipotent activity against EGFR mutations resistant to EGFR inhibition , including L858R - C797S , L858R - T790M , and L858R - T790M - C797S compared to L858R single mutation in Ba / F3 cell models in vitro . • Kinome profiling and global proteomic evaluation did not identify any significant off - target activity of CFT8919 . CFT8919 does not induce degradation of known cereblon neo - substrates SALL4 or GSPT1 , indicating that the potential associated toxicities will not be liabilities . Additionally , in vivo data demonstrates the following : • CFT8919 degrades and inhibits mutant EGFR in tumors upon oral administration . In the NCI - H1975 EGFR - L858R - T790M xenograft model , after a single oral dose of CFT8919 , up to 85 percent of mutant EGFR was degraded in tumors accompanied with near - complete inhibition of phospho - EGFR . o In this model , twice - daily oral administration of CFT8919 showed dose - dependent anti - tumor activity and regressions comparable to osimertinib . • In BaF3 allograft model expressing EGFR - L858R - T790M - C797S , CFT8919 demonstrates anti - tumor activity resulting in tumor regression , while osimertinib is inactive . • CFT8919 demonstrates rapid and significant reductions in tumor burden in the H1975 - LUC ( EGFR L858R - T790M ) brain metastasis model after oral dosing , indicating its potential to be active in the central nervous system . This promising pre - clinical data supports the Company's decision to advance CFT8919 into investigational new drug ( IND ) -enabling studies this year . C4T anticipates filing an IND for CFT8919 by mid - 2022 , with the goal to initiate a Phase 1 clinical trial by year - end 2022 . C4T will host an investor event and webcast today , June 7 , 2021 , at 8 am E.T. to further discuss the pre - clinical data . Details of this event are included below .