Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (November 2024)
82 slides from Cardiff Oncology's investor presentation, November 2024
Slide 1: Company Overview: The Onvansertib Opportunity
Company Overview The Onvansertib Opportunity
Slide 2: dependence upon third parties; and risks related to failure to obtain FDA clearances or
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: Onvansertib: 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 • FDA • Pfizer • 73% ~25% • Pfizer • • 15 month ~8 month validates We expect initial clinical data from our 1st line RAS-mutated mCRC trial in Q4 2024 Runway with current cash extends into Q1 2026
Slide 4: Onvansertib and bevacizumab combination reduces tumor size in mice
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 properties and specificity
Onvansertib PROPERTIES SPECIFICITY • • •
Slide 9: 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 RAS Wild-Type 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: Fighting mCRC through PLK1 inhibition
Fighting mCRC through PLK1 inhibition Robust data in lead mCRC program Path forward to accelerated approval
Slide 13: Our mCRC journey 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 KRAS-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 discontinued
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: Our mCRC journey: Phase 1b/2 and ONSEMBLE
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: RAS wild-type and mutated, 1st and 2nd line
RAS Wild-Type 1st LINE 2nd LINE RAS Mutated
Slide 19: RAS wild-type and mutated, 1st and 2nd line
RAS Wild-Type 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: 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: Phase 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 difference in response
No single patient characteristic explains the difference in response rates by prior bev status
Slide 26: Univariable and multivariable analysis
Univariable analysis Multivariable Analysis
Slide 27: Scientific basis for clinical findings
Scientific basis for clinical findings
Slide 28: Combination had superior anti-tumor activity vs 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 29: Tumors from mice treated with onv + bev appear smaller and pale
• • • KRAS-mut mCRC tumors from mice treated with onv + bev appear smaller and pale (less vascularized)
Slide 30: Tumor growth, hypoxia, HIF1α
α Tumor growth Hypoxia HIF1α HIF1a α
Slide 31: Tumor growth, hypoxia, HIF1α, onvansertib, bevacizumab
Tumor growth Hypoxia HIF1α onvansertib α α bevacizumab
Slide 32: 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 33: Tumor biopsy samples identified
135 tumor biopsy samples identified
Slide 34: Our mCRC journey: ONSEMBLE 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) 34
Slide 35: ONSEMBLE trial design
ENROLLMENT CRITERIA 28 DAY CYCLE PRIMARY ENDPOINT
Slide 36: ONSEMBLE bev naive patients achieved deeper responses than SoC
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 37: Change in tumor size, bev naive patients
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 38: Change in tumor size, onvansertib arm
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 39: Fighting mCRC through PLK1 inhibition
Fighting mCRC through PLK1 inhibition Robust data in lead mCRC program Path forward to accelerated approval
Slide 40: Annual eligible US patients and CRDF-004
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 development program agreed with FDA at June 2023 Type C meeting
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 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
PFIZER BREAKTHROUGH GROWTH INITIATIVE PFIZER Ignite • • • • •
Slide 45: Onvansertib summary and Q4 2024 data expectation
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 initial clinical data from our 1st line RAS-mutated mCRC trial in Q4 2024
Slide 46: Appendix: Additional mCRC Data
Appendix Additional mCRC Data
Slide 47: Phase 1b/2 patient demographics
Ph 1b/2 trial’s patient demographics reflect 2"¢ line mCRC population Enrollment* Number of Patients (N) Phase 1b, Dose Level 0 Phase 1b, Dose Level +1 Phase 1b, Dose Level +2 Phase 2 RP2D Total Patients Onvansertib 12 mg/m? Onvansertib 15 mg/m? Onvansertib 18 mg/m? Onvansertib 15 mg/m? All Doses Tr
Slide 48: 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: 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: Onvansertib 30mg arm TEAEs
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 TEAEs
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: Tumor growth, hypoxia, HIF1α
Tumor growth Hypoxia HIF1α onvansertib α α bevacizumab
Slide 57: Gene expression changes under hypoxia
Hx_DMS0_4h vs Nx_DMSO_4h: HCT116 and SW620 cells Hx_ONV2_4h vs Hx_DMSO_4h: HCT116 and SW620 cells 4 1 DDIT4 SLC2A3 ADM BHLHE40 PLAUR KDM3A 2 0 SAP30 INHA CDKN1C XPNPEP1 log2FoldChange in SW620 log2FoldChange in SW620 PNRC1 ANGPTL4 STBD1 PFKP NFIL3 PFKFB3 STC2 BNIP3L SLC25A1 AK4 GBE1 PDK1 CCNG2 HOXB9
Slide 58: Tumor response by treatment: vehicle, bev, onv
Vehicle Bev – Onv Onv+Bev – Bev+Irin *** Onv+Irin ** Onv+Bev+Irin *
Slide 59: Combination reduces tumor vascularization
The combination of onvansertib and bev reduces tumor vascularization marker CD31 vascularization - 20 O 15 8 % 10 oO a Oo 5 0 we $W620 xenograft model is shown. CD31 scoring: for each sample 5 fields of view at 100 um magnification were randomly selected in the tumor area. CD Mean score SEM for each
Slide 60: KRAS G12D and G12C models treatment
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 61: KRAS G12C, G12D and G13D models treatment
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 62: Appendix: Metastatic Pancreatic Adenocarcinoma (mPDAC)
Appendix: Metastatic Pancreatic Adenocarcinoma (mPDAC)
Slide 63: 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 64: 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 65: CRDF-001 trial design
ENROLLMENT CRITERIA OBJECTIVE PRIMARY ENDPOINT 14 DAY SECONDARY ENDPOINT CYCLE
Slide 66: Onvansertib+SoC has higher efficacy than 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 67: Stable disease patients converted to partial responses
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 68: 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 69: 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 70: 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 71: Biomarker trial enrollment criteria and objectives
ENROLLMENT CRITERIA OBJECTIVES • •
Slide 72: Tumor responder vs non-responder patients
• • Patient 28 (tumor responder) Patient 33 (tumor non-responder)
Slide 73: 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 74: Appendix: Investigator-Initiated Trial Small Cell Lung Cancer
Appendix: Investigator-Initiated Trial Small Cell Lung Cancer (SCLC)
Slide 75: 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 76: SCLC trial design
ENROLLMENT CRITERIA OBJECTIVE PRIMARY ENDPOINT 21 DAY CYCLE SECONDARY ENDPOINTS
Slide 77: SCLC preliminary safety and efficacy
ENROLLMENT CRITERIA PRELIMINARY SAFETY (N=6) PRELIMINARY EFFICACY (N=7)
Slide 78: 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 79: Appendix: Investigator-Initiated Trial Triple Negative Breast Cancer
Appendix: Investigator-Initiated Trial Triple Negative Breast Cancer (TNBC)
Slide 80: Onvansertib + paclitaxel superior to single agent therapy
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 81: TNBC trial design
ENROLLMENT CRITERIA PRIMARY ENDPOINTS − 28 DAY CYCLE
Slide 82: TNBC trial endpoints
ENROLLMENT CRITERIA PRIMARY ENDPOINTS − 28 DAY CYCLE SECONDARY ENDPOINT
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