Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (August 2024)
80 slides from Cardiff Oncology's investor presentation, August 2024
Slide 1: Company Overview: The Onvansertib Opportunity
Company Overview The Onvansertib Opportunity A U G U ST 2 0 2 4
Slide 2: Forward-looking statements
dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. risks related to business interruptions, including the outbreak of COVID-19 coronavirus and cyber- attacks on our information technology infrastructure, which cou
Slide 3: First-in-class PLK1 inhibitor with robust mCRC clinical data
First-in-Class Robust clinical data in FDA Pfizer PLK1 inhibitor 2L KRAS-mut mCRC • Onvansertib • FDA • Pfizer • 73% ~25% • Pfizer • • 15 month ~8 month validates We expect clinical data from our 1st line RAS-mutated mCRC trial in H2 2024 Runway with current cash extends through the end of Q3 2025
Slide 4: Onvansertib and bevacizumab combination reduces tumor size and vascularization
Human metastatic colorectal cancer (mCRC) tumors grown in mice (KRAS G12V) The combination of onvansertib and bevacizumab shows dramatically reduced • tumor size and • • vascularization
Slide 5: Annual eligible U.S. patients by target
Annual eligible U.S. patients (’000s)* Targets with Targets without oncogenic oncogenic alterations alterations Announced acquisition 48 50 for $4.8 billion by BMS 29 3 5 5 * ROS1 estimated eligible patients presented in KRAS G12C estimated eligible patients includes Turning Point Therapeutics’ corp
Slide 6: Line of therapy and trials
Line of Therapy Trial IIT* Ph2 Ph3 Combination with:
Slide 7: Fighting mCRC through PLK1 inhibition
Fighting mCRC through PLK1 inhibition Robust data in lead mCRC program Path forward to accelerated approval
Slide 8: Onvansertib
Onvansertib PROPERTIES SPECIFICITY • • •
Slide 9: Our lead program targets RAS-mutated metastatic colorectal cancer
Our lead program targets RAS-mutated metastatic colorectal cancer mCRC is BOTH common... 2023 new US cases (’000s)* Breast Prostate Lung Colorectal Melanoma Bladder Renal N-H Lymph. Uterus Pancreas 0 100 200 300 400 153k * American Cancer Society Cancer Facts and Figures 2024. ...and challenging to
Slide 10: 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) a /= oo . Bevacizumab Antiangiogenic (Avastin”) (approved 2004) Targeted therapy None
Slide 11: Other mCRC development 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 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: Our mCRC journey led us from second-line to first-line
Our mCRC journey of discovery led us from second-line to first-line FIRST LINE SECOND LINE * ONSEMBLE e Both patients CRDF-004 RAS-mutated mCRC 90 patients, randomized, _—......_ 3 2d ENROLLING 2 aime 2 Gases Pfizer Ignite Ph 1 b/2 KRAS-mutated mCRC CRDF-003 RAS-mutated mCRC 7 66 evaluable patients,
Slide 14: Our mCRC journey: Phase 1b/2 trial
Our mCRC journey of discovery led us from second-line to first-line FIRST LINE Provided initial signal of efficacy in second-line RAS-mutated mCRC SECOND Ph 1 b/2 KRAS-mutated mCRC 66 evaluable patients, LINE (TROV-054) : single arm COMPLETED
Slide 15: Our mCRC journey: ONSEMBLE second-line trial
Our mCRC journey of discovery led us from second-line to first-line FIRST Randomized second-line trial LINE designed to show onvansertib’s contribution to SoC that was discontinued SECOND LINE CRDF-003 © ONSEMBLE mCRC Clinical Trial DISCONTINUED RAS-mutated mCRC 23 patients”, randomized, blinded, 3
Slide 16: Shift to first-line setting
Our mCRC journey of discovery led us from second-line to first-line FIRST Shift to 1s+line setting based on: 1. Phase 1b/2 clinical data LINE 2. New mechanism of action 3. FDA recommendation 4. ONSEMBLE validation CRDF-004 ENROLLING RAS-mutated mCRC 90 patients, randomized, 3 arms (2 doses + control
Slide 17: Phase 1b/2 and ONSEMBLE trials
Our mCRC journey of discovery led us from second-line to first-line FIRST LINE SECOND Ph 1 b/2 KRAS-mutated mCRC 66 evaluable patients, LINE (URONHOY single arm COMPLETED * ONSEMBLE enrolle
Slide 18: Phase 1b/2 trial: 1st and 2nd line
Normal 1st LINE 2nd LINE RAS Mutated
Slide 19: Phase 1b/2 trial: 1st and 2nd line
Normal 1st LINE 2nd LINE RAS Mutated
Slide 20: Phase 1b/2 trial design
ENROLLMENT CRITERIA EFFICACY ENDPOINTS 1 2 28 DAY CYCLE 3
Slide 21: Bev exposed vs bev naive patients
Bev exposed vs bev naïve patients 1st LINE 2nd LINE
Slide 22: Ph 1b/2 bev naive patients achieved higher response rates
Ph 1b/2 trial bev naive patients achieved higher response rates 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, -) Disease Co
Slide 23: Response by KRAS variant
KRAS G12C Variant CR+PR SD PD PR SD PD Total G12D G12V G13D G12S G12A Q61H G13C
Slide 24: Ph 1b/2 mPFS exceeds historical controls for SoC
Ph 1b/2 trial mPFS exceeds historical controls for SoC Progression free survival* — 66 evaluable patients (as of June 16, 2023) Probability of Survival 1.00 075+ — All patients OB] aaceaceecccenns nd 0.25 0.00 3 6 3 io 5 20 2 Months Characteristic N EventN mPFS (95%C!) 9.3 (78, 14) Overall 66 42 8 P
Slide 25: No single patient characteristic explains response difference by prior bev status
No single patient characteristic explains the difference in response rates by prior bev status
Slide 26: Scientific basis for clinical findings
Scientific basis for clinical findings
Slide 27: Combination had superior anti-tumor activity versus 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 28: Tumors from onv + bev mice appear smaller and less vascularized
• • • KRAS-mut mCRC tumors from mice treated with onv + bev appear smaller and pale (less vascularized)
Slide 29: Tumor growth, hypoxia and HIF1α
α Tumor growth Hypoxia HIF1α HIF1a α
Slide 30: Onvansertib and bevacizumab mechanism
Tumor growth Hypoxia HIF1α onvansertib α α bevacizumab
Slide 31: Onvansertib inhibited hypoxia-induced HIF1α expression
α In 4 RAS-mutant CRC cell lines1, onvansertib inhibited hypoxia-induced HIF1α expression α α α α PLK1 inhibition using siRNA against PLK1 (siPLK1)2 prevented hypoxia-induced HIF1α expression α α β β α
Slide 32: Tumor biopsy samples identified
135 tumor biopsy samples identified
Slide 33: ONSEMBLE second-line trial discontinued
Our mCRC journey of discovery led us from second-line to first-line FIRST LINE SECOND LINE CRDF-003 @ONSEMBLE mCRC Clinical Trial DISCONTINUED RAS-mutated mCRC 23 patients”, randomized, blinded, 3 arms (2 doses + control) 33
Slide 34: ONSEMBLE trial design
ENROLLMENT CRITERIA 28 DAY CYCLE PRIMARY ENDPOINT
Slide 35: ONSEMBLE bev naive patients achieved deeper responses than SoC alone
ONSEMBLE bev naive patients treated with onvansertib + SoC achieved deeper responses than SoC alone Best Radiographic Response* — @ONSEMBLE patients (as of February 26, 2024) mCRC Clinical Trial Bev Naive Bev Exposed Onvansertib + FOLFIRI / bev Onvansertib + FOLFIRI / bev FOLFIRI / bev alone FOLFIRI
Slide 36: ONSEMBLE bev naive change in tumor size
ONSEMBLE bev naive patients treated with onvansertib + SoC achieved deeper responses than SoC alone Change in tumor size from baseline* — QONSEMBLE bev naive patients (as of February 26, 2024) mCRC Clinical Trial Bev naive: onvansertib + FOLFIRI/bev arm Bev naive: FOLFIRI/bev (control) arm 100+ 100+
Slide 37: ONSEMBLE bev naive change in tumor size by patient
ONSEMBLE bev naive patients treated with onvansertib + SoC achieved deeper responses than SoC alone Change in tumor size from baseline* — QONSEMBLE bev naive patients (as of February 26, 2024) mCRC Clinical Trial Bev naive: onvansertib + FOLFIRI/bev arm 100+ Best response of: Lesion was later biopsy
Slide 38: Two independent trials demonstrate the bev naive finding
Two independent clinical trials demonstrate the bev naive finding Objective Response Rate (ORR) by Cohort* N Bev Naive Bev Exposed QONSEMBLE Onvansertib 15 50% 0% coysomd + S0C ota oot Control 6 0% 0% (SoC alone) (0 of 3) (0 of 3) Phase 1b/2 Onvansertib 66 73% 16% Single-arm + SoC (11 of 15) (8 of 5
Slide 39: Path forward to accelerated approval
Fighting mCRC through PLK1 inhibition Robust data in lead mCRC program Path forward to accelerated approval
Slide 40: CRDF-004 first-line trial and eligible patients
Our mCRC journey of discovery led us from second-line to first-line FIRST LINE SECOND LINE Annual eligible US patients* First-line Second-line , All bev naive 9.5k | bev naive ( mCRC RAS-mut * Company estimates of firstline and second-line mCRC population with KRAS- and NRAS-mutated cancers. CRDF-00
Slide 41: mCRC clinical development program agreed with FDA
mCRC clinical development program agreed with FDA at June 2023 Type C meeting • • • • • • •
Slide 42: CRDF-004 trial design
ENROLLMENT CRITERIA 6 RANDOMIZATION ARMS 28 DAY CYCLE ENDPOINTS *
Slide 43: Historical controls include RAS-mut and RAS wild-type cancers
2nd Line mCRC 1st line mCRC 2nd Line mCRC 1st line mCRC Given the design of prior trials, historical controls include RAS-mut and RAS wild-type cancers
Slide 44: Pfizer Ignite collaboration
PFIZER BREAKTHROUGH GROWTH INITIATIVE PFIZER Ignite • • • • •
Slide 45: Summary: first-line data expected H2 2024
First-in-Class Robust clinical data in FDA Pfizer PLK1 inhibitor 2L KRAS-mut mCRC • Onvansertib • FDA • Pfizer • 73% ~25% • Pfizer • • 15 month ~8 month ONSEMBLE We expect clinical data from our 1st line RAS-mutated mCRC trial in H2 2024
Slide 46: Appendix: Additional mCRC Data
Appendix Additional mCRC Data
Slide 47: Ph 1b/2 patient demographics
Ph 1b/2 trial’s patient demographics reflects 2"4 line mCRC population Enrollment* Number of Patients (N) Treated Total Patients N=68 Age (years) Sex Male Female ECOG 0) 1 Primary tumor site Colon Rectum Other * Data are interim as of June 16, 2023 from an ongoing trial and unlocked EDC d Phase 1b,
Slide 48: Ph 1b/2 bev naive patients experienced more durable responses
Ph 1b/2 trial 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% (12/66) 53% (8/15) 8% 4/51) Initial PR at 8 week scan 9 8 1 Initial PR at 16+ week scan 10 3 7 a | oo 0 0
Slide 49: Ph 1b/2 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 50: ONSEMBLE patient demographics
ONSEMBLE’s patient demographics reflect second-line mCRC population Enrollment* Number of Patients (N) FOLFIRI and bev Intent to Treat 8 Treated (included in safety evaluable patients) 7 Evaluable for efficacy 6 Total Patients N=22 Median [range] or n (%) Age (years) 53 [35-81] Sex Male 12 (54%) Fem
Slide 51: ONSEMBLE swimmer plot
ONSEMBLE swimmer plot Bev Naive Bev Naive Bev Exposed Bev Exposed lung lesion, which was later biopsy- Swimmer plot* — ONSEMBLE mCRC Clinical Trial patients (as of February 26, 2024) fe] fe] e ie) ° e te) e e io] oO oO oO o e o fo) e a 0 10 12 Months fe] fe} fe} ° ° ce) Ke} fe} fe] > fe] (0) fe} fe)
Slide 52: ONSEMBLE bev exposed patients showed no responses
ONSEMBLE bev exposed patients, with or without onvansertib, showed no responses Change in tumor size from baseline* — @ONSEMBLE bev exposed patients (as of February 26, 2024) mCRC Clinical Trial Bev exposed: onvansertib + FOLFIRI/bev arm Bev exposed: FOLFIRI/bev (control) arm 100+ 100+ © Best respon
Slide 53: ONSEMBLE control arm adverse events
ONSEMBLE Control Arm: Treatment Emergent Adverse Effects (TEAEs) N (% of total) Grade 1 Grade 2 Grade 3 Grade 4 Total Control arm Any Adverse Events 6 (85.7) 6 (85.7) 3 (42.9) 0( 0.0) 6 (85.7) Diarrhea 3 (42.9) 1 (14.3) 0( 0.0) 0( 0.0) 4 (57.1) (N=7) Nausea 2 ( 28.6) 1 (14.3) 1 (14.3) 0( 0.0) 4 (57.
Slide 54: ONSEMBLE onvansertib 30mg arm adverse events
ONSEMBLE onvansertib 30mg Arm TEAEs: Onvansertib in combination with FOLFIRI+bev is well-tolerated N (% of total) Grade 1 Grade 2 Grade 3 Grade 4 Total . Any Adverse Events 7 (100.0) 7 (100.0) 4 (57.1) 0( 0.0) 7 (100.0) Experimental arm Diarrhea 1 (143) 1(143) 2( 28.6) 0( 0.0) 4(57.1) Onv 30mg (N=7)
Slide 55: Onvansertib 20mg arm adverse events
Onvansertib 20mg Arm TEAEs: Onvansertib in combination with FOLFIRI+bev is well-tolerated Thrombocytopenia N (% of total) Grade 1 Grade 2 Grade 3 Grade 4 Total : Any Adverse Events 8 (100.0) 7 (87.5) 2 (25.0) 2(25.0) 8 (100.0) Experimental arm Diarrhea 4 (50.0) 3 (37.5) 0 ( 0.0) 0( 0.0) 7 (87.5) Onv
Slide 56: Preclinical tumor growth by treatment
Vehicle Bev – Onv Onv+Bev – Bev+Irin *** Onv+Irin ** Onv+Bev+Irin *
Slide 57: Combination of onvansertib and bev reduces tumor vascularization
The combination of onvansertib and bev reduces tumor vascularization Vascularization was quantified using the endothelial marker CD31 Onvansertib and bev monotherapies reduced tumor vascularization The combination treatment of onvansertib and bev resulted in further decrease in vascularization SW620
Slide 58: Patient-derived xenografts: KRAS G12D and G12C
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 59: Patient-derived xenografts: KRAS G12C, G12D, G13D
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 60: Appendix: Metastatic Pancreatic Adenocarcinoma (mPDAC)
Appendix: Metastatic Pancreatic Adenocarcinoma (mPDAC)
Slide 61: 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 62: 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 63: CRDF-001 trial design
ENROLLMENT CRITERIA OBJECTIVE PRIMARY ENDPOINT 14 DAY SECONDARY ENDPOINT CYCLE
Slide 64: Onvansertib+SoC has higher efficacy than 2nd line historical controls
Onvansertib+SoC has higher efficacy than 2" line historical controls Best Radiographic Response - 21 evaluable patients (as of September 13, 2023)* 100 a © Historical controls! £ 2 50 24 \ine 15 line 4 CRDF-001 mPDAC mPDAC Best Response : | 9, 6 PD ORR is 77% 23% $8 0 O 0 @ O (4/21) 2 | ia 2 is 8 Su
Slide 65: 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)* [e) {e) fe} io} ie] (o} ® o} [e} oO fe} fo} e e@ fe] [o} fe) o fe} [e} fe} oO fo} fo} e ry fe} [e} t fe) oe te) 1 e e (eo) e Oo 0 4 8 12 Months an ongoing trial and
Slide 66: 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 I - 2 20+ i} Best Response 2 of — Partial Response a — Progressive Disease 5 — Stable Disease © 20+ @ Confirmed PR 3, ! © Wa
Slide 67: Onvansertib+SoC has longer median PFS than 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 1% line mPDAC 5.5 mos 48% 1,004 Probabil
Slide 68: 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 69: Biomarker discovery trial design
ENROLLMENT CRITERIA OBJECTIVES • •
Slide 70: Patient 28 responder versus Patient 33 non-responder
• • Patient 28 (tumor responder) Patient 33 (tumor non-responder)
Slide 71: 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 72: Appendix: Investigator-Initiated Trial, Small Cell Lung Cancer (SCLC)
Appendix: Investigator-Initiated Trial Small Cell Lung Cancer (SCLC)
Slide 73: 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 (mm?) SCLC * Mice were implanted with SCLC PDX and treated with vehicle, 2000 1500 7 1000 | 500 4 0
Slide 74: SCLC trial design
ENROLLMENT CRITERIA OBJECTIVE PRIMARY ENDPOINT 21 DAY CYCLE SECONDARY ENDPOINTS
Slide 75: SCLC preliminary safety and efficacy
ENROLLMENT CRITERIA PRELIMINARY SAFETY (N=6) PRELIMINARY EFFICACY (N=7)
Slide 76: Radiographic scans for patient with confirmed PR in SCLC
Radiographic scans for patient with a confirmed PR in SCLC IIT Baseline Scan Restaging after Cycle 2
Slide 77: Appendix: Investigator-Initiated Trial, Triple Negative Breast Cancer (TNBC)
Appendix: Investigator-Initiated Trial Triple Negative Breast Cancer (TNBC)
Slide 78: Preclinical: Onvansertib + paclitaxel superior to single agent
Preclinical: 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) =) 2 8004 |
Slide 79: TNBC trial design
ENROLLMENT CRITERIA PRIMARY ENDPOINTS − 28 DAY CYCLE
Slide 80: TNBC trial design and endpoints
ENROLLMENT CRITERIA PRIMARY ENDPOINTS − 28 DAY CYCLE SECONDARY ENDPOINT
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