C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Investor Presentation (December 2024)
37 slides from C4 Therapeutics's investor presentation, Dec 9, 2024
Slide 1: Protein degraded. Disease targeted. Lives transformed.
December 2024 Protein degraded. Disease targeted. Lives transformed.
Slide 2: Forward-looking Statements and Intellectual Property
Forward-looking Statements and Intellectual Property 2 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,
Slide 3: C4T Is a Recognized Leader in Delivering on the Promise of Targeted Protein Degradation
C4T Is a Recognized Leader in Delivering on the Promise of Targeted Protein Degradation 3 WORLD-CLASS DEGRADER PLATFORM Robust patent portfolio of novel cereblon binders; Demonstrated ability to design orally bioavailable, catalytically efficient degraders Our Mission To deliver on the promise of ta
Slide 4: Advancing a Broad Pipeline to Deliver Near-Term Value
Advancing a Broad Pipeline to Deliver Near-Term Value Discovery Stage Programs Various Cancers Collaboration Programs Autoimmune & Cancer Cancer Cancer Autoimmune & Neurological Program Target Indications Cemsidomide IKZF1/3 Multiple Myeloma & Non-Hodgkin’s Lymphoma CFT1946 BRAF V600 Mutant V600 Mut
Slide 5: C4T Has Delivered a Steady Flow of Clinical Updates and Innovative Collaborations
C4T Has Delivered a Steady Flow of Clinical Updates and Innovative Collaborations Over the Past 12 Months… Cemsidomide Collaborations Have Further Validated TORPEDO Platform CFT1946 CFT8919 Significant Progress Across Clinical Programs 5 ✓ Compelling activity in both multiple myeloma and non-Hodgkin
Slide 6: Which Set the Stage to Unlock Value
…Which Set the Stage to Unlock Value C4T is positioned to become a fully integrated biotechnology company focused on orally bioavailable degraders KEY CATALYSTSVALUE DRIVERS Cemsidomide IKZF1/3 Further development in multiple myeloma and non- Hodgkin’s lymphoma positions cemsidomide to potentially b
Slide 7: Cemsidomide Targeting IKZF1/3: Multiple Myeloma & Non-Hodgkin's Lymphoma
Cemsidomide Targeting IKZF1/3 Multiple Myeloma (MM) & Non-Hodgkin’s Lymphoma (NHL)
Slide 8: IKZF1/3 Are Key Promoters of Myeloma and Lymphoma Cell Survival
IKZF1/3 Are Key Promoters of Myeloma and Lymphoma Cell Survival and Will Remain Important Therapeutic Targets in MM and NHL Key Roles of IKZF1/3 Physiological Functions: • IKZF1/3 are key transcriptional regulators of hematopoietic stem cell differentiation • IKZF1/3 directly regulate the activity o
Slide 9: Cemsidomide First-in-Human Phase 1 Trial Continues to Progress
R/R NHL Monotherapy Dosing: MWF & QD 14 days on/ 14 days off N=~25 Status: Enrolling R/R MM Dex Combo Dosing: MWF & QD 14 days on/ 14 days off N=~40 Status: Enrolling R/R MM Monotherapy Dosing: MWF & QD 14 days on/ 14 days off N=22 Status: Complete Cemsidomide First-in-Human Phase 1 Trial Continues
Slide 10: Clinical Evidence of Immune T-cell Activation With Cemsidomide Monotherapy
TEMRA TEM 0 20 40 60 80 100 % positive cells (C1D21 vs C1D1) % p o s it iv e c e ll s C1D1 C1D21 Clinical Evidence of Immune T-cell Activation With Cemsidomide Monotherapy ** **** TEMRA: Terminally differentiated T-cells TEM: Effector memory T-cells Peripheral Blood Mononuclear Cells (PBMCs); Daily
Slide 11: Cemsidomide Combined With Novel MM Agents Demonstrated Enhanced Immune Cell Lysis
Cemsidomide Combined With Novel MM Agents Demonstrated Enhanced Immune Cell Lysis in Non-clinical Translational Models Notes: Daratumumab combos performed using an Antibody-Dependent Cell-Mediated Cytotoxicity Assay (ADCC) and the teclistamab and talquetamab combos used a T-cell Dependent Cellular C
Slide 12: Cemsidomide + Dexamethasone Dose Escalation Trial in MM Continues to Progress
Cemsidomide + Dexamethasone Dose Escalation Trial in MM Continues to Progress; Have Not Exceeded the Maximum Tolerated Dose DOSE ESCALATION CEMSIDOMIDE 14/14 + DEX* Utilizing a Bayesian logistic regression model until determination of the MTD and/or RP2D 50 µg MWF Back-fill cohort; N=1 37.5 µg QD Ba
Slide 13: Cemsidomide Is Well-Tolerated With Manageable Neutropenia
Cemsidomide Is Well-Tolerated With Manageable Neutropenia and No Treatment Emergent Adverse Events Lead to Dose Reductions Common (>20% All Grades) TEAEs and Events of Interest, n (%) All Grades (N=47) Grade 3 (N=47) Grade 4 (N= 47) Grade 5 (N=47) Neutropenia 22 (47) 6 (13) 12 (26) 0 Infections Pneu
Slide 14: Compelling Safety Profile With Low Rates of Neutropenia and Infections
Compelling Safety Profile With Low Rates of Neutropenia and Infections With Limited G-CSF Use 28% 26% 6% 5% 13% 0% 14% 0% 8% 7% 3% 5% 0% 0% 0% 0% 11% 19% 6% 0% 13% 0% 14% 0% 0% 25% 50% 75% 100% Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 Cycle 7 Cycle 8 P ts w it h G ra d e ≥ 3 A E s o r G -C S
Slide 15: 40% of MM Patients With Elevated Light Chains Showed at Least 50% dFLC Decrease
Across Doses, 40% (14/35) of Multiple Myeloma Patients With Elevated Light Chains Demonstrated at Least a 50% Decrease in dFLC Best Change in dFLC from Baseline (Cemsidomide + Dex) Multiple Myeloma Patients w/ Elevated Light Chain Disease (N=35)* Data cutoff: 10/11/24 0 6 12 18 24 30 36 42 48 0.00 0
Slide 16: Cemsidomide 75 µg Dose Level or Greater Drives Sufficient Exposure
Exposure (AUC) Quartiles <Q1 (N=9) Q1-Q2 (N=8) Q2-Q3 (N=8) >Q3 (N=9) Mean AUC0-28d (ng*h/mL) 14.6 28.8 37.9 65.2 Mean Change in dFLC from Baseline +10% -12% -20% -53% Cemsidomide + Dex Dose ~17 μg QD ~35 μg QD ~45 μg QD ~78 μg QD Data cutoff: 10/11/24 Cemsidomide 75 µg Dose Level or Greater Drives S
Slide 17: Cemsidomide Demonstrated Anti-Myeloma Activity Across Dose Levels
a Cemsidomide Demonstrated Anti-Myeloma Activity Across Dose Levels Data cutoff: 10/11/24 As of the data cutoff: • 26% ORR and 40% clinical benefit rate across all dose levels evaluated • At the two highest dose levels evaluated to date (62.5 μg and 75 μg), 62% of all patients remain on treatment1 b
Slide 18: 75 µg Dose Level Resulted in 36% ORR and 45% CBR
75 µg Cemsidomide Dose Level Resulted in Compelling Anti-Myeloma Activity With a 36% ORR and 45% CBR 33% (2) 8% (1) 18% (2) 12% (5) 50% (3) 58% (7) 46% (6) 36% (4) 48% (20) 17% (2) 23% (3) 9% (1) 14% (6) 17% (1) 8% (1) 15% (2) 36% (4) 19% (8) 8% (1) 8% (1) 5% (2)8% (1) 2% (1) 0% 25% 50% 75% 100% 50
Slide 19: Dose Exploration Continues for Cemsidomide Monotherapy Trial in R/R NHL
Dose Exploration Continues for the Cemsidomide Monotherapy Dose Escalation Trial in R/R NHL KEY INCLUSION CRITERIA • Adults with NHL, R/R to prior therapy • PTCL patients must have received at least 1 prior alkylator-based chemotherapy • ALCL patients must have also received a CD-30 mAb • Nonrespons
Slide 20: Heavily Pre-Treated Population Where Majority Were Diagnosed With PTCL
Heavily Pre-Treated Population Where Majority of Patients Were Diagnosed With PTCL, Reflecting High Unmet Need 20 Data cutoff: 10/11/24 Characteristics Safety Population (N=23) Age, median (range) 68 (28-85 years) Male, n (%) 14 (61) Years since initial diagnosis, median (range) 2 (0.4-21) ECOG perf
Slide 21: Cemsidomide Is Well-tolerated With Manageable On-target Neutropenia
Cemsidomide Is Well-tolerated With Manageable Incidents of On-target Neutropenia Common (>20% All Grades) TEAEs and Events of Interest*, n (%) All Grade (N=23) Grade 3 (N=23) Grade 4 (N=23) Infections Upper respiratory tract infection Sepsis Bacteremia Pneumonia 15 (65) 4 (17) 1(4) 1(4) 2 (9) 4 (17)
Slide 22: Cemsidomide Clinical Responses Were Observed Across a Broad Range of Doses
Cemsidomide Clinical Responses Were Observed Across a Broad Range of Doses 22 a a b b a Both patients were not evaluable based on PET-CT but were considered progressive disease due to CT scan. b Both patients dose reduced to 62.5 ug following DLTs. Anaplastic large cell lymphoma (ALCL); adult T-cell
Slide 23: PET-CT–based Assessment of PMR or Better by PTCL Subtype
19% (1) 25% (1) 20% (1) 20% (1) 25% (3) 75% (3) 50% (1) 0% 25% 50% 75% 100% All PTCL (N=16) AITL (N=4) ALCL (N=2) ATLL (N=5) PTCL-NOS (N=5) B e st R e sp o n se % ( N ) CMR PMR PET-CT–based Assessment of PMR or Better by PTCL Subtype* (N=16) ORR 20% ORR 20% ORR 100% ORR 50% Data cutoff: 10/11/24 ORR
Slide 24: Cemsidomide Is Positioned to Potentially Be a Best-in-Class Therapy
Cemsidomide Is Positioned to Potentially Be a Best-in-Class Therapy in Two Distinct Indications With Opportunities Across Multiple Lines of Therapy IKZF1/3 is a fundamental target for MM and NHL and data supports cemsidomide as a potential backbone therapy within the evolving treatment landscape Com
Slide 25: CFT1946 Targeting BRAF V600 Mutant Melanoma, CRC & NSCLC
CFT1946 Targeting BRAF V600 Mutant Melanoma, Colorectal (CRC) & Non-Small Cell Lung Cancer (NSCLC)
Slide 26: CFT1946 Has the Potential to Overcome Several Shortcomings of BRAF V600X Inhibitors
CFT1946 Has the Potential to Overcome Several Shortcomings Seen With Inhibitors for BRAF V600X Cancers 26 Potential Advantages of CFT1946, a Novel, Oral, BRAF V600 Mutant BiDAC degrader: ✓ Prevents BRAF V600 mutant mono/heterodimer formation1 ✓ Avoids paradoxical activation seen with approved inhibi
Slide 27: CFT1946 Ability to Cross the Blood-Brain Barrier
Kpu,u Results Demonstrate CFT1946’s Ability to Cross the Blood-Brain Barrier and Support Activity in Preclinical Intercranial Metastatic Models 27 These results demonstrate the ability of CFT1946 to cross the blood-brain barrier and highlight the potential for drug delivery to CNS tumors Survival Lu
Slide 28: CFT1946 Phase 1/2 Dose Escalation Trial Continues to Progress
PRIMARY ENDPOINTS • Safety and tolerability • Determine RP2D/MTD CFT1946 Phase 1/2 Dose Escalation Trial Continues to Progress Across BRAF V600 Mutant Driven Solid Tumors 28 KEY INCLUSION CRITERIA1 • Evidence of BRAF V600 mutation obtained from tumor tissue or liquid biopsy • BRAF V600 mutant measur
Slide 29: CFT1946 Monotherapy Data Demonstrated Proof of Mechanism and Early Proof of Degrader Concept
CFT1946 Monotherapy Phase 1 Data Demonstrated Proof of Mechanism and Provided Early Evidence of Proof of Degrader Concept 29 CFT1946 has the potential to disrupt the treatment landscape and become an important option for patients with BRAF V600 mutant driven solid tumors Proof of Mechanism Well tole
Slide 30: Well-Tolerated Monotherapy Safety Profile of CFT1946
Preferred Term Grade 1 n (%) Grade 2 n (%) Grade 3 n (%) Grade 4 n (%) Grade 5 n (%) Total (n=36) n (%) Patients with any TEAEs^ 3 (8) 14 (39) 11 (31) 2 (6) 1 (3)# 31 (86) Anemia 1 (3) 4 (11) 2 (6) 0 0 7 (19) Abdominal pain 4 (11) 1 (3) 2 (6) 0 0 7 (19) Peripheral edema 5 (14) 1 (3) 0 0 0 6 (17) Pyr
Slide 31: Early Signs of CFT1946 Anti-tumor Activity
PR PD PRSD SD SDV 60 0K V 60 0K V 60 0R PR PD PRSD SD SD # 31 Source: ESMO Congress 2024; C4T data on file as of 7/19/2024 Early Signs of CFT1946 Anti-tumor Activity: 59% of Patients Demonstrated Target Lesion Tumor Reductions * 1 2 3 4 5 *Other tumor types include cholangiocarcinoma, non-small cell
Slide 32: CFT1946 Potential to Address Multiple Tumor Types With BRAF V600X Mutations
CFT1946 Has the Potential to Address Multiple Tumor Types With BRAF V600X Mutations Where BRAF Inhibitors Are Insufficient 32 BRAF V600X Mutation Rate 2023 U.S. Incidence of BRAF V600X Patients4 Approved BRAF Inhibitors BRAF Inhibitor Regimen mPFS5 Melanoma ~35% ~35,000 • Dabrafenib • Encorafenib •
Slide 33: CFT8919 Targeting EGFR L858R Non-Small Cell Lung Cancer
CFT8919 Targeting EGFR L858R Non-Small Cell Lung Cancer (NSCLC)
Slide 34: Potential for CFT8919 to Improve Outcomes for NSCLC Patients With EGFR L858R
Potential for CFT8919 to Improve Outcomes for NSCLC Patients With EGFR L858R Mutations 34 Market Size • ~$6B approved EGFR inhibitor market 1 Osimertinib and other inhibitors provide suboptimal responses in L858R mutant NSCLC compared to other mutations of NSCLC Strong Rationale for an EGFR L858R De
Slide 35: CFT8919 is a Potent, Oral, Allosteric, Mutant-selective Degrader of EGFR L858R
CFT8919 is a Potent, Oral, Allosteric, Mutant-selective Degrader of EGFR L858R 35 • CFT8919 exploits allosteric binding site, close to L858R activating mutation Allosteric binding avoids resistance mutations, wild-type activity, and is combinable with orthosteric inhibitors CFT8919 Orthosteric Inhib
Slide 36: CFT8919 is Selective for EGFR L858R and Active in Osimertinib Resistance
CFT8919 is Selective for EGFR L858R and Active in a Setting of Osimertinib Resistance in Preclinical Models 36 Source: C4T data on file; Keystone Symposium 2021 Investigational New Drug Application (IND) Specific for EGFR Exon 21 Mutants EGFR-L858R EGFR-L861Q Active in setting of EGFR C797S 0 5 10 1
Slide 37: C4T Is Progressing Multiple Clinical and Preclinical Programs
C4T Is Progressing Multiple Clinical and Preclinical Programs Cemsidomide IKZF1/3 ASH 2024 (Dec.): Presented updated data from Phase 1 dose escalation +dex trial in R/R MM ASH 2024 (Dec.): Presented data from Phase 1 dose escalation monotherapy trial in R/R NHL CFT1946 BRAF V600 Mutant ESMO Congress
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