Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (January 2026)
68 slides from Cardiff Oncology's investor presentation, January 2026
Slide 1: Company Overview: The Onvansertib Opportunity
Company Overview The Onvansertib Opportunity
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: Unlocking a high-value oncology market: First-in-class PLK1 inhibitor
Unlocking a high-value oncology market: First-in-class PLK1 inhibitor with blockbuster potential in first-line RAS-mutated mCRC 0% 0° Onvansertib: Highly selective PLK1 inhibitor Strong efficacy signal in RAS-mutant mCRC + PLK1: recognized cancer target that drives tumor cell division, * Robust acti
Slide 4: Colorectal cancer 1st line standard of care
COLORECTAL CANCER 1st LINE STANDARD of CARE 3rd 150,000 50,000 1996 2004 2002 2014 15% Less than 12 months
Slide 5: Positioned to address the first-line RAS-mutated mCRC market
Positioned to address the first-line RAS-mutated mCRC market ~150,000 newly diagnosed CRC patients in U.S. Onvansertib targets ALL RAS-mutated mCRC OScaraitt Oncology” Blockbuster potential: = ro) of first-line © mCRC market - G12C ~4% CRC, colorectal cancer; mCRC, metastatic colorectal cancer
Slide 6: Onvansertib: First-line RAS-mutated mCRC
ONVANSERTIB FIRST-LINE RAS-MUTATED mCRC O O O00 a Mechanism Supports First-Line Treatment @) Ongoing Phase 2 CRDF-004 Trial Next Steps
Slide 7: A novel discovery from our second-line mCRC trial
We had a novel discovery from our second-line mCRC trial Ph 1b/2 trial CRDF-004 trial second-line KRAS-mut mCRC first-line RAS-mut mCRC Discovered synergy with First-line trial with bevacizumab support of FDA Sep 2022 Aug 2023 Preclinical research identifies novel MOA: Onvansertib likely more effect
Slide 8: 28 day cycle trial design
ENROLLMENT CRITERIA 28 DAY CYCLE ENDPOINTS
Slide 9: Ph 1b/2 trial added onvansertib to SoC in 2nd line
Ph 1b/2 trial added onvansertib to SoC in the 2" line setting Patients who came to our second-line trial not having received bev in first-line are called, “bev naive” 1st LINE Standard of Care FOLFOX chemotherapy Bev (optional) Yes No “bev naive" - Qnd LINE Cardiff Oncology Phase 1b/2 trial FOLFIRI
Slide 10: Bev-naive patients achieved higher response rates
Ph 1b/2 trial (274 line): Bev-naive patients achieved higher response rates Best Radiographic Response and Duration of Response* Historical controls** 66 evaluable patients (as of June 16, 2023) Bev Bev . naive exposed Bev naive: 15 of 66 patients (23%) Bev exposed: 51 of 66 (77%) 73% ORR 16% ORR OR
Slide 11: Bev-naive patients achieved higher mPFS
Ph 1b/2 trial (second-line): Bev-naive patients achieved higher mPFS Progression-free survival* . Historical controls** 66 evaluable patients (as of June 16, 2023) _ Bev Bev = 1.005 naive exposed ra 3 et mPFS (mo) 6.9-8.5 4.5-6.7 Pan] = 0.755 2 o 2 2 a 050} -+-------------f------------4 Hh Bev naive
Slide 12: Tumor growth, hypoxia, bevacizumab and onvansertib
Tumor growth Hypoxia HIF1α onvansertib α α bevacizumab
Slide 13: Multiple onvansertib MOAs underlie our focus on RAS-mutated mCRC
Multiple onvansertib MOAs underlie our focus on RAS-mutated mCRC Onvansertib attacks RAS-mutated mCRC in three ways l Synthetic lethality in RAS-mut background ? Synergy with chemo 3 Synergy with bevacizumab RAS-mut mCRC tumor cells are hypersensitive to onvansertib Onvansertib inhibits repair of ch
Slide 14: Ongoing Phase 2 CRDF-004 Trial
ONVANSERTIB FIRST-LINE RAS-MUTATED mCRC Mechanism Supports First-Line Treatment @) O ae Ongoing Phase 2 CRDF-004 Trial O00 © Next Steps
Slide 15: Prior first-line Ph3 mCRC trials provide benchmarks for current SoC
Prior First-line Ph3 mCRC trials provide benchmarks for current SoC Data from Positive first-line mCRC Chemo/bev Phase 3 Clinical Trials by RAS-mut Status* Targeted agent Bevacizumab FOLFOXIRI/bev (TRIBE trial) Trial IFL/bev vs IFL FOLFOXIRI/bev vs FOLFIRI/bev Mechanism of action Antiangiogenic Chem
Slide 16: CRDF-004 trial design
ENROLLMENT CRITERIA 6 RANDOMIZATION ARMS 28 DAY CYCLE ENDPOINTS*
Slide 17: Majority of CRDF-004 patients remain on treatment
As of July 8, 2025, a majority of CRDF-004 patients remain on treatment Study Populations as of July 8, 2025* Population, n Control (SoC alone) Onv 20mg + SoC Onv 30mg + SoC Total Intent-to-treat (ITT) 37 36 37 110 Safety population (dosed) 34 34 36 104 Patients still on trial 18 19 23 60 Patients w
Slide 18: Dose-dependent increase in ORR
CRDF-004 shows dose-dependent increase in ORR with onvansertib+SoC in ongoing Phase 2 trial Objective Response Rates per RECIST 1.1* Intent-to-treat (ITT) Control (SoC alone) Onv 20mg + SoC Onv 30mg + SoC Onv 30mg vs. (N=110) (n=37) (n=36) (n=37) Control Confirmed ORR' 30% 42% 49% 19% n, [95% Cl] n=
Slide 19: Deeper tumor regression with onvansertib+SoC
Deeper tumor regression observed with onvansertib+SoC Best Radiographic Response BY ONVANSERTIB DOSE* freretotreat Contre! Onw 20mg Onv some (ITT) (SoC alone) + SoC + SoC Confirmed ORR! 30% 42% 49% ORR? 43% 50% 59% > Control Arm + Experimental Arms SoC Onvansertib 20mg + SoC Onvansertib 30mg + SoC .
Slide 20: Best response and scan response
Best Response Complete Response Partial Response Stable Disease Progressive Disease Scan Response Complete Response Partial Response Stable Disease Progressive Disease
Slide 21: Deeper regression with either chemo backbone
Deeper tumor regression observed when adding onvansertib to either chemo backbone vs SoC alone FOLFIRI \ FOLFOX. Best Radiographic Response BY CHEMO BACKBONE* Intent-to-treat ( Y (7T]) Control SoC + Onv Control SoC + Onv Confirmed ORR" 26% 44% 33% 46% ORR? 47% 50% 39% 59% co FOLFIRI Arms r FOLFOX Ar
Slide 22: Patient scan examples
47-year-old female 69-year-old male 49-year-old male 62-year-old male
Slide 23: PFS shows initial separation between 30mg onv and control
PFS as of July 8, 2025 data cutoff shows initial separation between 30mg onv and control arms Progression Free Survival - Median PFS Not Reached* 1.00 Hazard Ratio (HR) HR 95% Cl Control vs. all onv arms 0.69 0.25, 1.90 0.75. 2 Control vs. onv 20mg + SoC 0.89 0.28, 2.77 Strat me Control vs. onv30mg+
Slide 24: Early proof-of-principle and depth of response
Ph3 TRIAL DATA* Early Proof-of-Principle Depth Meta Analysis Validation
Slide 25: CRDF-004 treatment emergent adverse events data
CRDF-004 treatment emergent adverse events (TEAE) data* All Control Arms Safety Population (Dosed) (N=34) N (% of total) All Grades Gr >=3 Any Adverse Events 33 (97.1) 21 (61.8) Fatigue 16 (47.1) 2( 59) Nausea 17 (50.0) 1(29) Diarthoea 17 (50.0) 1(29) Neutrophil count decreased 18 (52.9) 11(32.4) Hy
Slide 26: First-line RAS-mutated mCRC clinical development program
First-line RAS-mutated mCRC clinical development program Agreed with FDA June 2023 Type C meeting CRDF-00 4 CRDF-00 5
Slide 27: Next Steps
ONVANSERTIB FIRST-LINE RAS-MUTATED mCRC Mechanism Supports First-Line Treatment Ongoing Phase 2 CRDF-004 Trial Next Steps
Slide 28: Upcoming milestones including CRDF-004 update in Q1 2026
First-in-Class 2nd line KRAS-mut. Clinical signal from Clinical update Shift to first-line PLK1 inhibitor mCRC program CRDF-004 trial in Q1 2026 • • • • •
Slide 29: Pfizer Breakthrough Growth Initiative
PFIZER PFIZER BREAKTHROUGH GROWTH INITIATIVE Ignite
Slide 30: Line of therapy, trials and combinations
Line of Therapy Trial IIT* Ph2 Ph3 Combination with:
Slide 31: Appendix: mCRC Mechanism of Action Data
Appendix mCRC Mechanism of Action Data
Slide 32: Onvansertib: Cardiff Oncology's lead development asset
Cardiff Oncology’s lead development asset is onvansertib Onvansertib PROPERTIES SPECIFICITY • • •
Slide 33: A novel discovery from our second-line mCRC trial
We had a novel discovery from our second-line mCRC trial Ph 1b/2 trial CRDF-004 trial second-line KRAS-mut mCRC first-line RAS-mut mCRC Discovered synergy with First-line trial with bevacizumab support of FDA Aug 2023 Preclinical research identifies novel MOA: Onvansertib likely more effective in fi
Slide 34: Onvansertib + bev inhibits tumor growth greater than either alone
Onvansertib + bev inhibits tumor growth greater than either agent alone HCT-116 (KRAS G13D) 2500 2000 — Vehicle E Bev only 1500 10005 Onv only E | The combination had significant = 500 as: ‘ Onv + bev superior anti-tumor activity ee aa ee | compared to the single agents | o- T 0 10 20 30 Onv: 45mg/k
Slide 35: Onvansertib + bev inhibits tumor growth in three KRAS-mutant models
Onvansertib + bev inhibits tumor growth greater than either agent alone HCT-116 (KRAS G13D) * 0 10 20 30 Days Onv: 45mg/kg PO, QD : Bev: 10mg/kg, IP, BIW — Vehicle — Bev only — Onv only — Onv + bev hree KRAS-mutant mCR' the difference in tumor ve 2500 2000 » 1500 > 1000 500 0 LoVo (KRAS G13D) t 1) 1
Slide 36: Onvansertib's independent role in antiangiogenesis complements bev
Onvansertib’s independent role in antiangiogenesis complements bev LoVo (KRAS G13D)* SW620 (KRAS G12V)* Control (vehicle) 4 Roche drug Avastin” Bevacizumab 8 largest global drug in 2019 ($7.1B sales) Onvansertib <4 KRAS-mut mCRC tumors from mice Onv + bev treated with onv + bev appear smaller and pa
Slide 37: Tumor growth, hypoxia, HIF1α
α Tumor growth Hypoxia HIF1α HIF1a α
Slide 38: Tumor growth, hypoxia, bevacizumab
Tumor growth Hypoxia HIF1α α bevacizumab
Slide 39: Hypoxia pathway with onvansertib and bevacizumab
Tumor growth Hypoxia HIF1α onvansertib α α bevacizumab
Slide 40: PLK1 inhibition in LoVo RAS-mutant CRC cell lines
α PLK1 inhibition in LoVo RAS-mutant CRC cell lines1 α 02 02 α siPLK1 − + − + Onv − + − + α β α β α
Slide 41: PLK1 inhibition cell line data
α 02 02 02 02 Onv − + − + Onv − + − + Onv − + − + Onv − + − + α α β 02 02 siPLK1 − + − + siPLK1 − + − + α α β α
Slide 42: HIF1α pathway and patents
HIF1α onvansertib α • • bevacizumab United States Patent Patent No.: US 12,144,813 B2 Ridinger et al. Date of Patent: Nov. 19, 2024 Expiration: Not before 2043 United States Patent Patent No.: US 12,263,173 B2 Ridinger et al. Date of Patent: Apr. 1, 2025 Expiration: Not before 2043
Slide 43: Onvansertib's inhibition of the hypoxia response pathway
MOA Onvansertib’s inhibition of the hypoxia response pathway
Slide 44: Biopsies: bev naive vs bev exposed
135 biopsies: Bev naïve Bev exposed May drive tumor resistance to bev May drive tumor resistance to onvansertib
Slide 45: Appendix: Additional mCRC Clinical Data
Appendix Additional mCRC Clinical Data
Slide 46: CRDF-004 demographics and baseline characteristics
CRDF-004 demographics and baseline characteristics* ; FOLFIRI/bev FOLFIRV/bev/onv 20 FOLFIRI/bev/onv30 FOLFOX/bev —- FOLFOX/bev/onv 20 FOLFOX/bev/onv 30 Total Safety Population (Dosed) (o=17) (o=17) (o=18) (o=17) (o=17) (0=18) (o=104) ‘Age (years) Median 53 (32, 81) 52 (30, 78) 60 (34, 81) 57 (34, 8
Slide 47: Higher number of 30mg patients remain on trial vs control
Higher number of 30mg onvansertib patients remain on trial vs. control Radiographic Response over Time* 2 E E o gi 5 c o v ae Onv 20mg + SoC f Onv 30mg + SoC HH ( * Radiograph patients discon | Time on Trial by Best Response mmm CR/PR mm SD mmm PD On treatment On follow up First response scan @c PR
Slide 48: Early tumor shrinkage
Greater number of onvansertib 30mg dose patients achieved Early Tumor Shrinkage % of patients with ETS Early Tumor Control Shrinkage (ETS) en >20% reduction in tumor size at Experimental 2-month scan. Arm Final data: All ETS Delta patients on trial p-value have had a 2- month scan. Hazard Ratio Impr
Slide 49: Best response and scan response
Best Response Complete Response Partial Response Stable Disease Progressive Disease Scan Response Complete Response Partial Response Stable Disease Progressive Disease
Slide 50: Depth of response deeper for onv 30mg arm
Depth of Response is deeper for the onv 30mg dose arm % Tumor Shrinkage Depth of Control Response (DpR) Arm Maximum tumor Experimental shrinkage at Arm nadir on trial , DpR Delta Interim data: P Patients on trial may achieve Hazard Ratio deeper tumor regression Improvement in PFS Previous Ph3 1t Lin
Slide 51: No baseline characteristic has significant impact on ORR
CRDF-004 No baseline characteristic has a significant impact on ORR Forest Plot of the Treatment Effect on ORR by Baseline Characteristic* ITT patients | Odds Ratios by Dose ‘Control ($00) ‘SoC 4 onvansemb 20 mq SOC + onvanserto 30 m9 ae | of * $ NOT REPORTED a a a | NOT HISPANIC OR LATINO HISPANIC
Slide 52: CRDF-004 treatment emergent adverse events data
CRDF-004 treatment emergent adverse events (TEAE) data* Safety Population (Dosed) FOLFIRI/bev FOLFIRI/bev/onv 20mg FOLFIRI/bev/onv 30mg FOLFOX/bev FOLFOX/bev/onv 20mg FOLFOX/bev/onv 30mg All Control Arms All Experimental Arms (n=17) (n=17) (n=17) (n=70) N06 of total AllGrades Gr>=3 AllGrades Gr>=3 A
Slide 53: CRDF-004 dose intensity similar and high across arms
CRDF-004 dose intensity is similar and high across all trial arms Relative Dose Intensity: actual amount of study drug a patient receives over time compared to the planned dose and schedule* Safety Population (Dosed) Relative dose intensity (%) Mean (Std) Median FOLFIRI/bev (n=17) 91.84 (12.8) 96.93
Slide 54: Appendix: Additional mCRC Preclinical Data
Appendix Additional mCRC Preclinical Data
Slide 55: Onvansertib, bevacizumab and irinotecan combination showed greater potency
The combination of onvansertib, bevacizumab and irinotecan showed greater potency than each individual or doublet therapy * The combination of onvansertib, bevacizumab and irinotecan was potent in the HCT116 xenograft model, resulting in: — tumor regression in all treated mice (8/8), including 1 CR
Slide 56: Genes induced by hypoxia; onvansertib inhibits adaptation
Genes induced by hypoxia in two mCRC cell lines Adding onvansertib inhibits adaptation to 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 log2FoldC
Slide 57: Onvansertib and bev reduce 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
Slide 58: Onvansertib with irinotecan in KRAS-mutant models
• 600 C1143 (KRAS G12D) 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: Onvansertib in KRAS G12C, G12D, G13D models
B8239 (KRAS G12C) • 800 C1143 (KRAS G12D) 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: Investigator-Initiated Trial Small Cell Lung Cancer
Appendix: Investigator-Initiated Trial Small Cell Lung Cancer (SCLC)
Slide 61: Onvansertib demonstrates single-agent activity in SCLC
Onvansertib demonstrates single-agent activity in SCLC TRIAL RATIONALE Onvansertib monotherapy showed significant tumor - 2000 growth inhibition against = platinum-sensitive and " -resistant models — 1500 ze} > 6 1000 4 € =) e SCLC 500 | 0 * Mice were implante red with SCLC PDX and treated with vehi
Slide 62: SCLC trial design
ENROLLMENT CRITERIA OBJECTIVE PRIMARY ENDPOINT 21 DAY CYCLE SECONDARY ENDPOINTS
Slide 63: Preliminary safety and efficacy in SCLC
ENROLLMENT CRITERIA PRELIMINARY SAFETY (N=6) PRELIMINARY EFFICACY (N=7)
Slide 64: Radiographic scans for patient with confirmed PR in SCLC
Radiographic scans for patient with a confirmed PR in SCLC Baseline Scan Restaging after Cycle 2
Slide 65: Appendix: Investigator-Initiated Trial Triple Negative Breast Cancer
Appendix: Investigator-Initiated Trial Triple Negative Breast Cancer (TNBC)
Slide 66: Onvansertib + paclitaxel superior to single agent therapy
Preclinical: Onvansertib + paclitaxel is superior to single agent therapy TRIAL RATIONALE The combination of onvansertib + paclitaxel showed significant synergy in preclinical models TNBC In vivo efficacy of onvansertib in combination with paclitaxel Tp53-mutant SUM159 xenografts* 1200 5 1000 800 ~
Slide 67: TNBC trial design
TRIPLE NEGATIVE BREAST PRIMARY ENDPOINTS CANCER 28 DAY CYCLE
Slide 68: Triple negative breast cancer
TRIPLE NEGATIVE BREAST CANCER • •
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