Slide 1: CFT8919 Pre-Clinical Data Investor Call
CFT8919 Pre-Clinical Data Investor Call June 7, 2021 Exhibit 99.2
Slide 2: Forward-looking Statements and Intellectual Property
Forward-looking Statements The following presentation contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “loo
Slide 3: Today's Agenda
7 Today’s Agenda Introductions Kendra Adams, SVP Communications & Investor Relations Andrew Hirsch, President and CEO Adam Crystal, M.D., Ph.D., CMO Andrew Hirsch, Adam Crystal and Stew Fisher, CSO Opening Remarks CFT8919 Pre-clinical Data Overview Q&A Session ose $33 C4 i herapeutics, Ine. $88 C4 T
Slide 4: What You Will Hear Today
What You Will Hear Today 4 CFT8919 is an orally bioavailable, selective, allosteric degrader of EGFR L858R Active in vitro and in vivo in models with secondary EGFR mutations Demonstrates intracranial activity indicating potential to prevent or treat brain metastases in patients with EGFR L858R-driv
Slide 5: TORPEDO Platform Has Delivered a Robust Degrader Pipeline
TORPEDO Platform Has Delivered a Robust Degrader Pipeline; Four Clinical Programs Expected by End of 2022 Nine Additional Undisclosed Collaborator Programs in Discovery 5
Slide 6: Updated 2021 Milestones Continue to Support Progress Toward Goal of Four Clinical-Stage Programs
Updated 2021 Milestones Continue to Support Progress Toward Goal of Four Clinical-Stage Programs by Year-End 2022 6 Phase 1/2 Initiation IND Submission Lead Optimization IND Enabling Studies IND Enabling Studies Phase 1 Top-line Safety & Efficacy Proof of Mechanism Phase 1 Initiation IND Submission
Slide 7: Preclinical Evaluation of CFT8919 as a Mutant Selective Degrader of EGFR with L858R
Preclinical Evaluation of CFT8919 as a Mutant Selective Degrader of EGFR with L858R Activating Mutations for the Treatment of Non-Small Cell Lung Cancer
Slide 8: Mutations in EGFR Drive Oncogenesis and Resistance in Non-Small Cell Lung Cancer
Mutations in EGFR Drive Oncogenesis and Resistance in Non-Small Cell Lung Cancer 8 10-15% of Non-Small Cell Lung Cancer has Mutant EGFR 30-40% of Mutant EGFR NSCLC Patients will Develop Brain Metastases 25-45% of Mutant EGFR NSCLC is Driven by L858R Activating Mutation This rises to nearly 40% in As
Slide 9: Despite Three Generations of Approved EGFR Inhibitors, L858R Patients Have Poorer Prognosis
L858R mutation predicts less durable response to EGFR inhibitors No evidence that L858R is a more aggressive disease Despite Three Generations of Approved EGFR Inhibitors, L858R Patients Have Poorer Prognosis L858R Patients are Underserved by Current EGFR Inhibitor Therapies 9 Source: Soria, J.-C. e
Slide 10: Selectively Targets EGFR-L858R in Human Cancer Cell Lines
CFT8919 Selectively Targets EGFR-L858R in Human Cancer Cell Lines and is Not Impacted by EGFR T790M or C797S EGFR Degradation Phospho-EGFR Inhibition Degradation and Inhibition Potency 10 C B A
Slide 11: Active in Ba/F3 Models Expressing Secondary Mutations Resistant to Approved EGFR Inhibitors
CFT8919 is Active in Ba/F3 Models Expressing Secondary Mutations Resistant to Approved EGFR Inhibitors Viability of Ba/F3 Cells Expressing the Indicated EGFR Variant Ba/F3 Cell Growth Inhibition Potency 11 B A
Slide 12: Highly Selective Against Kinase Targets and Known Cereblon Neo-Substrates
CFT8919 is Highly Selective Against Kinase Targets and Known Cereblon Neo-Substrates Kinome Binding Specificity Evaluation Against Known CRBN Neo-substrates 12 No SALL4 degradation No GSPT1 degradation B A
Slide 13: Shows Excellent Proteome-Wide Selectivity
CFT8919 Shows Excellent Proteome-Wide Selectivity Global Proteomic Evaluation 13 *p-value < 0.001 +Likely due to the biological effect of EGFR suppression; similar change observed upon osimertinib treatment
Slide 14: Degrades and Inhibits Mutant EGFR in Tumors Upon Oral Administration
CFT8919 Degrades and Inhibits Mutant EGFR in Tumors Upon Oral Administration 14 Tumor PD in H1975 EGFR-L858R-T790M xenograft model
Slide 15: Induces Tumor Regression in Mouse Models Resistant to First and Third-Generation EGFR Inhibitors
CFT8919 Induces Tumor Regression in Mouse Models Resistant to First and Third-Generation EGFR Inhibitors 15 3rd-Generation EGFRi Resistant Ba/F3 (L858R-T790M-C797S) Allograft 1st-Generation EGFRi Resistant H1975 (L858R-T790M) Xenograft
Slide 16: Demonstrates Activity in H1975-LUC Brain Metastasis Model
CFT8919 Demonstrates Activity in H1975-LUC (EGFR-L858R-T790M) Brain Metastasis Model Mean Plasma & Tumor Concentration In vivo Efficacy In vivo Body Weight Change 16 Plasma clearance t1/2 = 3.1 hrs
Slide 17: CFT8919 is a Potent, Oral, Allosteric, Mutant-selective Degrader of EGFR L858R
Active in vitro and in vivo in models with secondary mutations (such as T790M, C797S, T790M-C797S) that cause acquired resistance to 1st-, 2nd-, and 3rd-generation EGFR inhibitors Demonstrates intracranial activity indicating potential to prevent or treat brain metastases in patients with EGFR L858R
Slide 18: Q&A Session
Q&A Session
Slide 19: Thank You
ee C4 Therapeutics Thank You