Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (October 2025)
70 slides from Cardiff Oncology's investor presentation, October 2025
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: Onvansertib properties and specificity
Onvansertib PROPERTIES SPECIFICITY • • •
Slide 4: We shifted our RAS-mutated mCRC program to the first-line
We shifted our RAS-mutated mCRC program to the first-line Ph 1b/2 trial KRAS-mut. 24 line mCRC Unexpected clinical finding Sep 12, 2022 Pre-clinical research identifies novel MOA: Onvansertib likely more SECOND-LINE effective in 1% line nt I | I I | I 2022 2023 2024 2025
Slide 5: We are encouraged by the initial clinical data from CRDF-004
We are encouraged by the initial clinical data from CRDF-004 6 Announced shift from (4 ) nd |i st |j | 2" line to 15 line (CRDF-004) CRDF-004: supported by FDA and Pfizer Ignite data release Aug 7, 2023 July 29, 2025 FIRST-LINE — l l 4 2024 2025
Slide 6: Our shift to first-line RAS-mutated mCRC
OUR SHIFT TO FIRST-LINE RAS-MUTATED mCRC The strength of our 1st-line program The rationale for our shift from 2nd-line The coming catalysts
Slide 7: Colorectal cancer: first-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 8: Onvansertib's MOA allows us to target ALL RAS-mutated mCRC
Onvansertib’s MOA allows us to target ALL RAS-mutated mCRC KRAS G12C therapies would address a small part of the need" G12Cc G12D G12V RAS Wild-Type G13D G12S G12A Q61H NRAS G13C ONVANSERTIB addresses 52% of mCRC cases are RAS-mutated! RAS LN ) Wild-Type
Slide 9: Prior 1st line Ph3 mCRC trials provide benchmarks for current SoC
Prior 1st line Ph3 mCRC trials provide benchmarks for current SoC Data from Positive 1% 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 Chemo Tri
Slide 10: CRDF-004 trial design
ENROLLMENT CRITERIA 6 RANDOMIZATION ARMS 28 DAY CYCLE ENDPOINTS*
Slide 11: As of July 8, 2025, a 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 12: Dose-dependent increase in objective response rates with onvansertib+SoC
Dose-dependent increase in objective response rates observed with onvansertib+SoC 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% Cll] n=11 [16-47
Slide 13: Dose-dependent increase in objective response rates with onvansertib+SoC
Dose-dependent increase in objective response rates observed with onvansertib+SoC 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=11 [16-47]
Slide 14: Deeper tumor regression observed 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 plus SoC Onvansertib 30mg plus
Slide 15: Best Response / Scan Response
Best Response Complete Response Partial Response Stable Disease Progressive Disease Scan Response Complete Response Partial Response Stable Disease Progressive Disease
Slide 16: Deeper tumor regression with either chemo backbone vs SoC alone
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 17: Higher number of 30mg onvansertib patients remain on trial
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 0 2 a é | | Time on Trial by Best Response mmm CR/PR mm SD mmm PD On treatment On follow up First response sca
Slide 18: Patient case scans
47-year-old female 69-year-old male 49-year-old male 62-year-old male
Slide 19: PFS shows initial separation between 30mg onv and control arms
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 20: Ph3 trial data: early proof-of-principle, depth, validation
Ph3 TRIAL DATA* Early Proof-of-Principle Depth Meta Analysis Validation
Slide 21: Early Tumor Shrinkage (ETS)
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 22: Best Response / Scan Response
Best Response Complete Response Partial Response Stable Disease Progressive Disease Scan Response Complete Response Partial Response Stable Disease Progressive Disease
Slide 23: Depth of Response is deeper for the onv 30mg dose 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 24: 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 Safety Population (Dosed) (n=17) (n=17) (n=18) (n=17) (n=17) (n=18) ‘Age (years) Median 53 (32, 81) 52 (30, 78) 60 (34, 81) 57 (34, 82) 66 (34,79)
Slide 25: CRDF-004 treatment emergent adverse events (TEAE) 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: 1st line RAS-mutated mCRC clinical development program
1st line RAS-mutated mCRC clinical development program Agreed with FDA June 2023 Type C meeting CRDF-00 4 CRDF-00 5
Slide 27: Our shift to first-line RAS-mutated mCRC
OUR SHIFT TO FIRST-LINE RAS-MUTATED mCRC The strength of our 1st-line program The rationale for our shift from 2nd-line The coming catalysts
Slide 28: Our second-line phase 1b/2 trial generated a novel finding
Our second-line phase 1b/2 trial generated a novel finding Ph 1b/2 trial KRAS-mut. 24 line mCRC Unexpected clinical finding Sep 12, 2022 SECOND-LINE | I I I 2022 2023 2024 2025 28
Slide 29: Phase 1b/2 trial design
ENROLLMENT CRITERIA EFFICACY ENDPOINTS 1 2 28 DAY CYCLE 3
Slide 30: Our Ph1b/2 trial added onvansertib to SoC in the 2nd line
Our Ph1b/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 FOLFI
Slide 31: 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* r Historical controls** 66 evaluable patients (as of June 16, 2023) s—<— Bev Bev . naive exposed Bev naive: 15 of 66 patients (23%) Bev exposed: 51 of 66 (77%) 73% ORR 16% ORR ORR 23-
Slide 32: Ph 1b/2 trial mPFS exceeds historical controls for SoC
Ph 1b/2 trial mPFS exceeds historical controls for SoC Progression-free survival* Historical controls** 66 evaluable patients (as of June 16, 2023) Bev Bev naive exposed $ 1.00 § et mPFS (mo) 6.9-8.5 4.5-6.7 Pal = 0754 re} o 2 e oa 0.505 cH Bev naive 0.25+ Bev exposed 0,00- 25 Months et al,, 2007, J
Slide 33: Univariable and multivariable analysis
n ORR (Odds Ratio) p-value PFS (Hazard Ratio) p-value Univariable analysis of baseline characteristics for ORR and PFS indicate superior clinical benefit for bev naïve patients and for patients without metastatic disease at time of diagnosis Multivariable Analysis was performed with these two charac
Slide 34: Unexpected clinical findings prompted new pre-clinical research
Unexpected clinical findings prompted new pre-clinical research Ph 1b/2 trial KRAS-mut. 2" line mCRC Unexpected clinical finding Sep 12, 2022 Pre-clinical research identifies novel MOA: Onvansertib likely more SECOND-LINE effective in 1% line et I | I I | I 2022 2023 2024 2025
Slide 35: Onvansertib + bev inhibits tumor growth greater than either agent 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 36: Onvansertib + bev inhibits tumor growth greater than either agent alone
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 37: 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 38: Tumor growth, hypoxia, HIF1α
α Tumor growth Hypoxia HIF1α HIF1a α
Slide 39: Tumor growth, hypoxia, bevacizumab
Tumor growth Hypoxia HIF1α α bevacizumab
Slide 40: Tumor growth, hypoxia, onvansertib, bevacizumab
Tumor growth Hypoxia HIF1α onvansertib α α bevacizumab
Slide 41: PLK1 inhibition in LoVo RAS-mutant CRC cell lines
α PLK1 inhibition in LoVo RAS-mutant CRC cell lines1 α α α β α β α
Slide 42: Onvansertib inhibits hypoxia signaling by downregulating HIF1a
Onvansertib inhibits the hypoxia signaling pathway by downregulating HIF 1a expression In 4 RAS-mutant CRC cell lines', onvansertib inhibited hypoxia-induced HIF 1a expression PLK1 inhibition using siRNA against PLK1 (siPLK1)2 prevented hypoxia-induced HIF 1a expression LoVo HCT-116 SW-620 DLD1 0, 2
Slide 43: HIF1α, onvansertib, bevacizumab 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 44: Proposed MOA of onv+bev therapy in bev naive / exposed tumors
Proposed MOA of onv+bev therapy in bev naive / bev exposed tumors Journal of Clinical Oncology’ MOA Onvansertib’s inhibition of the hypoxia response pathway (A) In bev naive tumors, the combination of onvansertib and bev effectively inhibits cell survival, proliferation, and angiogenesis (8) In bev
Slide 45: Biopsies: bev naive vs bev exposed
135 biopsies: Bev naïve Bev exposed
Slide 46: Our shift to first-line RAS-mutated mCRC
OUR SHIFT TO FIRST-LINE RAS-MUTATED mCRC The strength of our 1st-line program The rationale for our shift from 2nd-line The coming catalysts
Slide 47: We expect additional clinical data from our 1st line trial
First-in-Class 2nd line KRAS-mut. Clinical signal from Shift to 1st line PLK1 inhibitor mCRC program CRDF-004 1st trial • • • • • We expect additional clinical data from our 1st line RAS-mutated mCRC trial in H1 2025
Slide 48: Line of therapy, trial, IIT, Ph2, Ph3
Line of Therapy Trial IIT* Ph2 Ph3 Combination with:
Slide 49: Pfizer Ignite
PFIZER BREAKTHROUGH GROWTH INITIATIVE PFIZER Ignite • • • • •
Slide 50: Appendix: Additional mCRC Data
Appendix Additional mCRC Data
Slide 51: CRDF-004 Dec 2024: initial data showed deeper tumor shrinkage
CRDF-004 Dec 2024: Initial data showed deeper tumor shrinkage with onvansertib that appeared dose-dependent Initial : Radiographic Response over Time* — as of November 26, 2024 30 patients data disclosed r Control Arms \¢ Experimental Arms Dec 10, 2024 SoC Onvansertib 20mg plus SoC Onvansertib 30mg
Slide 52: CRDF-004 July 2025: deeper dose-dependent responses
CRDF-004 July 2025: Data for same 30 patients continued to show deeper dose-dependent responses in onvansertib arms Initial 30 patients data disclosed July 29, 2025 Radiographic Response over Time* — as of July 8, 2025 > Control Arms \r Experimental Arms SoC! Onvansertib 20mg plus SoC? Onvansertib 3
Slide 53: No baseline characteristic has a 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 54: CRDF-004 treatment emergent adverse events (TEAE) 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 55: CRDF-004 dose intensity is similar across all trial 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 56: Tumor growth, hypoxia, onvansertib, bevacizumab
Tumor growth Hypoxia HIF1α onvansertib α α bevacizumab
Slide 57: log2FoldChange in HCT116 and SW620 cells
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: Vehicle, Bev, Onv combinations
Vehicle Bev – Onv Onv+Bev – Bev+Irin *** Onv+Irin ** Onv+Bev+Irin *
Slide 59: 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 60: C1143 (KRAS G12D) and C1144 (KRAS G12C) 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: B8239, C1143 and C1138 treatment time
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: Investigator-Initiated Trial Small Cell Lung Cancer (SCLC)
Appendix: Investigator-Initiated Trial Small Cell Lung Cancer (SCLC)
Slide 63: 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 64: SCLC trial design
ENROLLMENT CRITERIA OBJECTIVE PRIMARY ENDPOINT 21 DAY CYCLE SECONDARY ENDPOINTS
Slide 65: SCLC preliminary safety and efficacy
ENROLLMENT CRITERIA PRELIMINARY SAFETY (N=6) PRELIMINARY EFFICACY (N=7)
Slide 66: Radiographic scans for patient with a confirmed PR in SCLC
Radiographic scans for patient with a confirmed PR in SCLC Baseline Scan Restaging after Cycle 2
Slide 67: Appendix: Investigator-Initiated Trial Triple Negative Breast Cancer (TNBC)
Appendix: Investigator-Initiated Trial Triple Negative Breast Cancer (TNBC)
Slide 68: Onvansertib + paclitaxel is superior to single agent therapy
Preclinical: Onvansertib + paclitaxel is superior to single agent therapy TRIAL RATIONALE The combination of onvansertib + paclitaxel showed significant synergy TNBC In vivo efficacy of onvansertib in combination with paclitaxel Tp53-Mutant SUM159 xenografts* 1200 5 1000 800 ~ 600 + Tumor volume (mm
Slide 69: TNBC trial design
ENROLLMENT CRITERIA PRIMARY ENDPOINTS − 28 DAY CYCLE
Slide 70: TNBC trial endpoints
ENROLLMENT CRITERIA PRIMARY ENDPOINTS − 28 DAY CYCLE SECONDARY ENDPOINT
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