Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (November 2023)
59 slides from Cardiff Oncology's investor presentation, November 2023
Slide 1: Company Overview: The Onvansertib Opportunity
Company Overview The Onvansertib Opportunity N OV E M B E R 2 0 2 3
Slide 2: Forward-looking statements
Forward-looking statements CERTAIN STATEMENTS IN THIS PRESENTATION ARE FORWARD-LOOKING within the meaning of the Private Securities Litigation Reform Act of 1995, These statements may be identified by the use of words such as “anticipate,” "believe," "forecast," "estimated" and "intend" or other sim
Slide 3: First-in-class PLK1 inhibitor with robust clinical data
First-in-Class Robust clinical data in FDA Pfizer PLK1 inhibitor 2L KRAS-mut mCRC • Onvansertib • 73% • FDA • Pfizer ~25% • 15 month • Pfizer • ~8 month We expect clinical data from our 1st line RAS-mutated mCRC trial in mid-2024 Runway with current cash extends into 2025
Slide 4: Line of therapy and trials
Line of Therapy Trial IIT* Ph2 Ph3 Combination with:
Slide 5: Fighting mCRC through PLK1 inhibition
Fighting mCRC through PLK1 inhibition Robust data in lead mCRC program Path forward to accelerated approval
Slide 6: Onvansertib properties and specificity
Onvansertib PROPERTIES SPECIFICITY • • •
Slide 7: 350 140
350 140 300 120 250 100 200 80 150 60 100 40 50 20 0 0
Slide 8: mCRC standard of care leaves a significant unmet need
mCRC standard of care leaves a significant unmet need Standard of Care for 1st / 2"4 line RAS-mutated mCRC includes chemo + bevacizumab FOLFOX (approved 1996) Chemotherapy FOLFIRI (approved 2002) oo . Bevacizumab Antiangiogenic (Avastin”) (approved 2004) Targeted therapy None
Slide 9: Other mCRC programs leave a significant unmet need
Other mCRC development programs leave a significant unmet need KRAS G12C therapies would address a small part of the need" 4% G12C G12D G12V Normal (WT) G13D G12S G12A Q61H NRAS G13C Onvansertib js targeting all RAS-mutated mCRC' G12C G12D 52% RAS-mutated G12V | G13D G12S G12A Q61H NRAS G13C
Slide 10: Multiple onvansertib MOAs underlie focus on RAS-mutated mCRC
Multiple onvansertib MOAs underlie our focus on RAS-mutated mCRC Onvansertib attacks RAS-mutated mCRC in three ways Synthetic RAS-mut mCRC tumor cells are lethality hypersensitive to onvansertib Inhibit Onvansertib inhibits repair of DNA repair chemo-induced DNA damage Inhibit tumor Onvansertib inhi
Slide 11: Annual eligible U.S. patients by target
Annual eligible U.S. patients (’000s)* Targets with Targets without oncogenic oncogenic alterations alterations 50 48 50 15 12 3 5 * ROS1 estimated eligible patients presented in mCRC estimated population includes 1st line, Turning Point Therapeutics’ corporate KRAS- and NRAS-mutated cancers. mPDAC
Slide 12: Robust data in lead mCRC program
Fighting mCRC through PLK1 inhibition Robust data in lead mCRC program Path forward to accelerated approval
Slide 13: 1st line and 2nd line RAS-mutated trials
Normal 1st LINE 2nd LINE RAS Mutated
Slide 14: 1st line and 2nd line RAS-mutated trials
Normal 1st LINE 2nd LINE RAS Mutated
Slide 15: Trial design: enrollment criteria and endpoints
ENROLLMENT CRITERIA EFFICACY ENDPOINTS 1 2 28 DAY CYCLE 3
Slide 16: Bev exposed vs bev naive patients
Bev exposed vs bev naïve patients 1st LINE 2nd LINE
Slide 17: Bev naive patients achieved higher response rate with onvansertib+SoC
Bev naive patients achieved higher response rate with onvansertib+SoC Best Radiographic Response and Duration of Response* - 66 evaluable patients (as of June 16, 2023) All Bev patients naive N 66 15 ORR 29% (19) 73% (11) 95% Cl (18-41%) (45-92%) mDoR = 12.0mo_ 13.0mo 95% Cl (8.9,-) | (12.0, -) Dise
Slide 18: Response by KRAS variant
KRAS G12C Variant CR+PR SD PD Total G12D G12V G13D G12S G12A Q61H G13C
Slide 19: PFS exceeds historical controls for SoC
PFS exceeds historical controls for SoC, particularly in bev naive patients Progression free survival* — 66 evaluable patients (as of June 16, 2023) 3 1.00 3 1.004 g 5 a a ° 8 Bojs. Bors, . iad I O76 — Bev naive 8 — All patients 4 £ P & — Bev exposed 050) - 22-22 eee- eee 77 ee ieee 0.25: 0.25- 5.0
Slide 20: Scientific basis for clinical findings
Scientific basis for clinical findings
Slide 21: Combination had superior anti-tumor activity compared to single agents
The combination had significant superior anti-tumor activity compared to the single agents SW620 (KRAS G12V) 2500 2000 Tumor volume (mm3) 1500 1000 500 0 0 10 20 30
Slide 22: Tumors from onv + bev mice smaller and less vascularized
• • • KRAS-mut tumors from mice treated with onv + bev appear smaller and pale (less vascularized)
Slide 23: New MOA inhibits a survival switch of tumorigenesis
This new MOA, which inhibits a “survival switch” of tumorigenesis, may underlie the increased efficacy observed clinically
Slide 24: Path forward to accelerated approval
Fighting mCRC through PLK1 inhibition Robust data in lead mCRC program Path forward to accelerated approval
Slide 25: mCRC clinical program agreed with FDA at June 2023 Type C meeting
mCRC clinical development program agreed with FDA at June 2023 Type C meeting • • • • • • •
Slide 26: Enrollment criteria and endpoints
ENROLLMENT CRITERIA ENDPOINTS Primary Secondary Benchmark of success PFIZER IGNITE
Slide 27: 2nd line and 1st line mCRC trials
2nd Line mCRC 1st line mCRC 2nd Line mCRC 1st line mCRC
Slide 28: Pfizer Breakthrough Growth Initiative and Ignite
PFIZER BREAKTHROUGH GROWTH INITIATIVE PFIZER Ignite • • • • •
Slide 29: Summary: first-in-class PLK1 inhibitor, data expected mid-2024
First-in-Class Robust clinical data in FDA Pfizer PLK1 inhibitor 2L KRAS-mut mCRC • Onvansertib • 73% • FDA • Pfizer ~25% • 15 month • Pfizer • ~8 month We expect clinical data from our 1st line RAS-mutated mCRC trial in mid-2024
Slide 30: Appendix: Additional mCRC Data
Appendix Additional mCRC Data
Slide 31: Bev naive patients experienced more durable responses
Bev naive patients experienced more durable responses Swimmer plot* - 66 evaluable patients (as of June 16, 2023) ; All Bev Bev patients naive exposed Pursued surgery / ablation 18% 12/60) 53% (g/15) 8% 4/51) Initial PR at 8 week scan 9 8 1 Initial PR at 16+ week scan 10 3 7 o e@ eee ee eo ew ew 8 l
Slide 32: No single patient characteristic explains difference in response rates
No single patient characteristic explains the difference in response rates by prior bev status
Slide 33: Treatment-emergent adverse events
• TEAE GR1 GR2 GR3 GR4 TOTAL TEAE GR1 GR2 GR3 GR4 TOTAL Fatigue 24 22 7 0 53 78% Cough 11 0 0 0 11 16% • Neutropenia 1 18 23 7 49 72% Pyrexia 8 1 1 0 10 15% Nausea 29 13 4 0 46 68% Dyspnea 7 3 0 0 10 15% • Diarrhea 21 13 4 0 38 56% AST Increase 7 2 1 0 10 15% Leukopenia 9 14 5 1 29 43% Lymphocytopen
Slide 34: Hypoxia: a hallmark of cancer
Hypoxia: a hallmark of cancer In response to hypoxia, cancer cells activate the hypoxia- inducible factor (HIF) pathway, which can promote tumorigenesis through multiple means: ° Angiogenesis Cell proliferation and survival Highly immunosuppressive and invasive tumor microenvironment * Hypoxia-induc
Slide 35: Onvansertib inhibited hypoxia-induced HIF1a expression
In 4 RAS-mutant CRC cell lines*, onvansertib inhibited hypoxia-induced HIF1a expression PLK1 inhibition using siRNA against PLK1 (siPLK1) prevented hypoxia-induced HIF1a expression
Slide 36: Prior bev treatment modulates gene pathways conferring resistance
Prior bev treatment modulates gene pathways that can confer resistance to bev and onvansertib Aim: to identify potential mechanisms of treatment resistance in bev exposed KRAS-mutant mCRC patients Method: KRAS-mutant mCRC patients 1* line treatment fe) . FOLFOX (n=71) 7 . Analysis of genes and pathw
Slide 37: Tumor response in KRAS G12D and G12C models
C1143 (KRAS G12D) 600 Vehicle 400 Onvansertib Irinotecan 200 200 Onv+Irino 150 100 *** 50 ** 0 0 5 10 15 20 -50 Treatment time (days) C1144 (KRAS G12C) 250 200 **** 150 100 ** 50 0 0 5 10 15 20 Treatment time (days)
Slide 38: Tumor response in KRAS G12C, G12D and G13D models
B8239 (KRAS G12C) C1143 (KRAS G12D) 800 300 600 200 400 *** 100 200 **** *** * 0 0 5 10 15 20 0 5 10 15 20 Treatment time (days) Treatment time (days) C1138 (KRAS G13D) 300 200 *** 100 ** 0 0 5 10 15 20 Treatment time (days)
Slide 39: Onvansertib inhibits vascularization in vitro
Onvansertib inhibits vascularization in vitro Tube formation assay: HUVEC endothelial cells seeded onto a 3D extracellular matrix form tube-like structures upon stimulation with the angiogenic factor VEGFA, simulating the formation of new blood vessels Treatment with onvansertib (25, 100 and 400nM)
Slide 40: Appendix: Metastatic Pancreatic Adenocarcinoma (mPDAC)
Appendix: Metastatic Pancreatic Adenocarcinoma (mPDAC)
Slide 41: Path forward: Move to 1st line mPDAC
mPDAC mPDAC CRDF-001 Ph 2 Second-Line Trial Biomarker Discovery Trial (IIT) • • Path forward: Move to 1st line mPDAC •
Slide 42: Path forward: Move to 1st line mPDAC
mPDAC mPDAC CRDF-001 Ph 2 Second-Line Trial Biomarker Discovery Trial (IIT) • • Path forward: Move to 1st line mPDAC •
Slide 43: CRDF-001 trial design
ENROLLMENT CRITERIA OBJECTIVE PRIMARY ENDPOINT 14 DAY SECONDARY ENDPOINT CYCLE
Slide 44: Onvansertib+SoC has higher efficacy than 2nd line historical controls
Onvansertib+SoC has higher efficacy than 2"9 line historical controls Best Radiographic Response - 21 evaluable patients (as of September 13, 2023)* 400 ve ® Historical controls! £ 3 50 . ' 3 24 \ine 15 line 4 CRDF-001 mPDAC mPDAC 6 = Best Response é a 9 5 PD ORR is 77% 23% $8 0 OO @ O (4/21) 2 | %
Slide 45: Stable disease patients converted to partial responses over time
Stable disease patients have converted to partial responses over time Swimmer plot — 23 evaluable patients (as of September 13, 2023)* Q oO ie} 085 te} e e Reason for Discontinuation (o} [e) Adverse Event — — 7 Death Disease Progression (} e e @ Withdrawal of Informed Consent Response oO @ Progressi
Slide 46: Patient responses can deepen over time
Patient responses to onvansertib+SoC can deepen over time Spider plot - 21 evaluable patients (as of September 13, 2023)* 100+ ( mPFS for SoC is 3.1 months } A T = i} 3 ! i} 6 1 - 2 20+ i} Best Response co} 2 of ! — Partial Response 3 — Progressive Disease 5 — Stable Disease © 20+ @ Confirmed PR ° !
Slide 47: Longer median PFS than 2nd line historical controls
Onvansertib+SoC has longer median PFS than 2"9 line historical controls Progression-free survival — 23 evaluable patients (as of September 13, 2023)* Historical controls! 2r9 line CRDF-001 mPDAC mPFS 5.0mos 3.1 mos 16 week progression- 56% van free? available mber 13, 2023 from 1% line mPDAC 5.5 mos
Slide 48: Path forward: Move to 1st line mPDAC
mPDAC mPDAC CRDF-001 Ph 2 Second-Line Trial Biomarker Discovery Trial (IIT) • • Path forward: Move to 1st line mPDAC •
Slide 49: Biomarker trial enrollment criteria and objectives
ENROLLMENT CRITERIA OBJECTIVES • •
Slide 50: Tumor responder vs non-responder patients
• • Patient 28 (tumor responder) Patient 33 (tumor non-responder)
Slide 51: Path forward: Move to 1st line mPDAC
mPDAC mPDAC CRDF-001 Ph 2 Second-Line Trial Biomarker Discovery Trial (IIT) • • Path forward: Move to 1st line mPDAC •
Slide 52: 1st line mPDAC trial design
SUBSEQUENT CHEMO + ENROLLMENT CRITERIA TWO LEAD-IN COHORTS ONVANSERTIB TREATMENT* • • PRIMARY ENDPOINT 28 DAY CYCLE SECONDARY ENDPOINTS
Slide 53: Appendix: Investigator-Initiated Trial Small Cell Lung Cancer
Appendix: Investigator-Initiated Trial Small Cell Lung Cancer (SCLC)
Slide 54: Onvansertib demonstrates single-agent activity in SCLC
Onvansertib demonstrates single-agent activity in SCLC TRIAL RATIONALE Onvansertib monotherapy showed significant tumor growth inhibition against platinum-sensitive and -resistant models Tumor volume (mm3) 2, cisplatin 3mg/kg IP weekly, or In vivo efficacy of onvansertib monotherapy (SCLC xenografts
Slide 55: SCLC trial design
ENROLLMENT CRITERIA OBJECTIVE PRIMARY ENDPOINT 21 DAY CYCLE SECONDARY ENDPOINTS
Slide 56: Appendix: Investigator-Initiated Trial Triple Negative Breast Cancer
Appendix: Investigator-Initiated Trial Triple Negative Breast Cancer (TNBC)
Slide 57: Onvansertib + paclitaxel superior to single agent therapy
Onvansertib + paclitaxel is superior to single agent therapy TRIAL RATIONALE In vivo efficacy of onvansertib in combination with paclitaxel Tp53-Mutant SUM159 xenografts* The combination of onvansertib + paclitaxel = 1200- showed significant synergy S e 1000 + control (n=8) =) re 800 | a So 600-1 Lo
Slide 58: TNBC trial design
ENROLLMENT CRITERIA PRIMARY ENDPOINTS − 28 DAY CYCLE
Slide 59: TNBC trial design endpoints
ENROLLMENT CRITERIA PRIMARY ENDPOINTS − 28 DAY CYCLE SECONDARY ENDPOINT
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