Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Corporate Update (July 2025)
41 slides from Cardiff Oncology's corporate update, Jul 29, 2025
Slide 1: CRDF-004 Trial Update
CRDF-004 Trial Update 1st Line RAS-mutated mCRC J U LY 2 9 , 2 0 2 5
Slide 2: Forward-looking statements
Forward-looking statements CERTAIN STATEMENTS IN THIS PRESENTATION ARE FORWARD-LOOKING within the meaning of the Private dependence upon third parties; and risks related to failure to obtain FDA Securities Litigation Reform Act of 1995. These statements may be identified clearances or approvals and
Slide 3: Mark Erlander, PhD, Chief Executive Officer
Mark Erlander, PhD Chief Executive Officer 3
Slide 4: Onvansertib specifically targets PLK1, a well-established cancer target
Onvansertib specifically targets PLK1, a well-established cancer target Onvansertib PROPERTIES SPECIFICITY Exquisitely specific for PLK1 • Small molecule First oral, well-tolerated • Oral dosing PLK1-selective inhibitor • 24-hour half-life PLK2 >10.000 PLK3 >10.000 CK2 0.400 FLT3 0.400 CDK1/CycB >10
Slide 5: We designed the CRDF-004 trial to address four objectives
We designed the CRDF-004 trial to address four objectives shift from 2nd line to 1st line 1. Select a Ph3 dose – per FDA’s Project Optimus 2. Assess efficacy signal 3. Characterize safety profile in 1st line setting 4. Basis for meeting with FDA to agree Ph3 trial 2023 2024 2025 5
Slide 6: Dr. Sidhu brings a wealth of clinical development experience
Dr. Sidhu brings a wealth of clinical development experience Deep Expertise in mCRC CAREER and Drug Development Dr. Sidhu served as Executive Vice President and Chief Medical Officer at Roivant Sciences. He was also the Chief Medical Officer at Eterna Therapeutics, Inc. PRACTICAL EXPERIENCE AT AMGEN
Slide 7: Roger Sidhu, MD, Chief Medical Officer
Roger Sidhu, MD Chief Medical Officer 7
Slide 8: Agenda
1st line RAS-mut mCRC program update 1. ORR efficacy and safety AGENDA 2. PFS analyses 3. Registrational program path forward 8
Slide 9: CRC: High unmet need with limited therapies for RAS-mut mCRC
CRC: High unmet need with limited therapies for RAS-mut mCRC COLORECTAL CANCER 1st LINE STANDARD of CARE 3rd most common cancer worldwide RAS-mutated mCRC 1990 2000 2010 2020 Annually in the United States 150,000 50,000 1996 FOLFOX 2004 Bevacizumab (Avastin®) new cases deaths For patients with metas
Slide 10: Prior 1st line Ph3 mCRC trials provide benchmarks for current SoC
Prior 1st line Ph3 mCRC trials provide benchmarks for current SoC * PFS Mechanism Trial Sample ORR ORR (months) Hazard Targeted agent Trial of action population size Exp. vs Ctrl. delta Exp. vs Ctrl. ratio Bevacizumab IFL/bev Antiangiogenic KRAS WT or All ITT patients 813 45% vs 35% 10.6 vs 6.2 0.54
Slide 11: Trial design of CRDF-004: 1st line RAS-mutated mCRC Phase 2 trial
Trial design of CRDF-004: 1st line RAS-mutated mCRC Phase 2 trial O N VA N S E R T I B ENROLLMENT CRITERIA 6 RANDOMIZATION ARMS 28 27 1. FOLFIRI/bev 26 First-line mCRC SoC alone 2. FOLFOX/bev 25 1st line SoC: 24 6 KRAS+/NRAS+ Chemo + bevacizumab 3. FOLFIRI/bev Onv 20mg + 23 7 4. FOLFOX/bev Unresecta
Slide 12: 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 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 with only a 2-month scan 3 2 1 6 and re
Slide 13: Dose-dependent increase in objective response rates observed with onvansertib+SoC
Dose-dependent increase in objective response rates observed with onvansertib+SoC 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 ORR1 30% 42% 49% 19% n, [95% CI] n=11 [16-47] n=15 [26–59] n=18 [32–66] p=0.018 22% 33
Slide 14: Dose-dependent increase in objective response rates observed with onvansertib+SoC
Dose-dependent increase in objective response rates observed with onvansertib+SoC 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 ORR1 30% 42% 49% 19% n, [95% CI] n=11 [16-47] n=15 [26–59] n=18 [32–66] p=0.018 22% 33
Slide 15: Deeper tumor regression observed with onvansertib+SoC
Deeper tumor regression observed with onvansertib+SoC Intent-to-treat Control Onv 20mg Onv 30mg (ITT) (SoC alone) + SoC + SoC Confirmed ORR1 30% 42% 49% ORR2 43% 50% 59% SoC plus SoC plus SoC Best % Change from Baseline Best Response CR PR SD PD Confirmed CR Confirmed PR Unconfirmed PR > On treatmen
Slide 16: Deeper tumor regression over time observed with onvansertib+SoC
Deeper tumor regression over time observed with onvansertib+SoC SoC plus SoC plus SoC Best Response Complete Response Partial Response Stable Disease Progressive Disease Scan Response Complete Response Best Response Partial Response CR Stable Disease PR Progressive Disease SD PD 16
Slide 17: Deeper tumor regression observed when adding onvansertib to either chemo backbone vs SoC alone
Deeper tumor regression observed when adding onvansertib to either chemo backbone vs SoC alone FOLFIRI FOLFOX Intent-to-treat (ITT) Control SoC + Onv Control SoC + Onv Confirmed ORR1 26% 44% 33% 46% ORR2 47% 50% 39% 59% / bev / bev / onvansertib / bev / bev / onvansertib (Control) (Experimental) (Co
Slide 18: Higher number of 30mg onvansertib patients remain on trial vs. control
Higher number of 30mg onvansertib patients remain on trial vs. control Time on Trial by Best Response CR/PR Control Onv 20mg Onv 30mg SD Safety Population (Dosed) (SoC alone) + SoC + SoC PD > On treatment Patients on treatment 18 (53%) 19 (56%) 23 (64%) On follow up First response scan Patients disc
Slide 19: Several patients in onvansertib arms achieved deep responses, CR, and surgery referrals
Several patients in onvansertib arms achieved deep responses, CR, and surgery referrals* 47-year-old female Achieved CR and went 69-year-old male Achieved CR of target Metastatic disease on enrollment. to curative surgery after Adjuvant FOLFOX for stage 3 lesions and confirmed Right sided colon canc
Slide 20: CRDF-004 demographics and baseline characteristics
CRDF-004 demographics and baseline characteristics* FOLFIRI/bev FOLFIRI/bev/onv 20 FOLFIRI/bev/onv 30 FOLFOX/bev FOLFOX/bev/onv 20 FOLFOX/bev/onv 30 Total Safety Population (Dosed) (n=17) (n=17) (n=18) (n=17) (n=17) (n=18) (n=104) Age (years) Median 53 (32, 81) 52 (30, 78) 60 (34, 81) 57 (34, 82) 66
Slide 21: CRDF-004 treatment emergent adverse events (TEAE) data
CRDF-004 treatment emergent adverse events (TEAE) data* All Control Arms Onv 20mg + SoC Onv 30mg + SoC Safety Population (Dosed) (N=34) (N=34) (N=36) N (% of total) All Grades Gr >=3 All Grades Gr >=3 All Grades Gr >=3 21
Slide 22: Dose intensity is similar and high across all trial arms
Dose intensity is similar and high across all trial arms actual amount of study drug a patient receives over time compared to the planned dose and schedule* FOLFIRI/bev FOLFIRI/bev/onv 20 FOLFIRI/bev/onv 30 FOLFOX/bev FOLFOX/bev/onv 20 FOLFOX/bev/onv 30 Safety Population (Dosed) (n=17) (n=17) (n=18)
Slide 23: Agenda
1st line RAS-mut mCRC program update 1. ORR efficacy and safety AGENDA 2. PFS analyses 3. Registrational program path forward 23
Slide 24: PFS as of July 8, 2025 data cutoff 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 Hazard Ratio (HR) HR 95% CI Control vs. all onv arms 0.69 0.25, 1.90 Control vs. onv 20mg + SoC 0.89 0.28, 2.77 Strata Control vs. onv 30mg + SoC 0.52 0.15,1.83 Control arm Onv 20mg + SoC Onv 30mg + SoC Med
Slide 25: In 1st line mCRC, two response metrics predict PFS and OS
In 1st line mCRC, two response metrics predict PFS and OS Ph3 TRIAL DATA* Early Proof-of-Principle Early Tumor Shrinkage and Depth of Response Predict Long- Tumor Shrinkage (ETS) term Outcome in mCRC Patients FOLFOXIRI+bev Cremolini, et. al. vs. FOLFIRI+bev Treated with 1st-line Chemo+bev ≥20% reduc
Slide 26: Greater number of onvansertib 30mg dose patients achieved Early Tumor Shrinkage
Greater number of onvansertib 30mg dose patients achieved Early Tumor Shrinkage Previous Ph3 1st Line mCRC Trials1 RAS WT/mut. RAS WT RAS WT RAS mut. Early Tumor Control Shrinkage (ETS) 52% 49% 46% 41% Arm (11/27) ≥20% reduction in tumor size at Experimental Arm 63% 62% 69% 63% 69% 2-month scan. (19
Slide 27: Tumor regression vs. baseline is deeper over time with onv 30mg dose
Tumor regression vs. baseline is deeper over time with onv 30mg dose SoC plus SoC plus SoC Best Response Complete Response Best Response Partial Response CR Stable Disease PR Progressive Disease SD PD Scan Response Complete Response Partial Response Stable Disease Progressive Disease Control Onv Onv
Slide 28: Depth of Response is deeper for the onv 30mg dose arm
Depth of Response is deeper for the onv 30mg dose arm Previous Ph3 1st Line mCRC Trials1 RAS WT/mut. RAS WT RAS WT RAS mut. Depth of Control Response (DpR) Arm 38% 33% 31% 32% Maximum tumor Experimental shrinkage at Arm 43% 51% 58% 41% 48% nadir on trial Interim data: p-value 0.066 0.011 Patients on
Slide 29: Agenda
1st line RAS-mut mCRC program update 1. ORR efficacy and safety AGENDA 2. PFS analyses 3. Registrational program path forward 29
Slide 30: Current CRDF-004 trial data are supportive of a 30mg dose
Current CRDF-004 trial data are supportive of a 30mg dose Progress to date 1st line RAS-mut mCRC Data supports focus on onvansertib 30mg dose 2. Assess efficacy signal 3. Characterize safety profile in first-line setting 4. Basis for meeting with FDA to agree Ph3 trial 2024 2025 2026 30
Slide 31: Dose response observed across ORR, ETS and DpR efficacy signals and may predict longer PFS
Dose response observed across ORR, ETS and DpR efficacy signals and may predict longer PFS Progress to date 1st line RAS-mut mCRC ORR: meaningful deltas in 1. Select a Ph3 dose – per FDA’s Project Optimus context of 1st line mCRC PFS: early PFS separation and correlative response 3. Characterize saf
Slide 32: Onvansertib in combination with SoC is generally well-tolerated
Onvansertib in combination with SoC is generally well-tolerated Progress to date 1st line RAS-mut mCRC Onvansertib is generally well- 1. Select a Ph3 dose – per FDA’s Project Optimus tolerated in combination with both chemo backbones and 2. Assess efficacy signal bev 4. Basis for meeting with FDA to
Slide 33: We intend to discuss our registrational trial protocol with FDA for Ph3
We intend to discuss our registrational trial protocol with FDA 4 Progress for Ph3to date CRDF-005 1st line RAS-mut mCRC registrational protocol Totality of data supports 1. Select a Ph3 dose – per FDA’s Project Optimus moving forward with FDA interactions on the 2. Assess efficacy signal registrati
Slide 34: We believe CRDF-004 data positions onvansertib for registrational trial
We believe CRDF-004 data positions onvansertib for registrational trial 1st line RAS-mutated mCRC clinical development program Agreed with FDA June 2023 Type C meeting CRDF-00 4 CRDF-00 5 Designed for accelerated and full-approval Endpoint for accelerated approval: - ORR with DoR Endpoint for full a
Slide 35: Appendix
APPENDIX 35
Slide 36: Dec 2024: Initial data showed deeper tumor shrinkage with onvansertib that appeared dose-dependent
Dec 2024: Initial data showed deeper tumor shrinkage with onvansertib that appeared dose-dependent – as of November 26, 2024 30 patients SoC plus SoC plus SoC Best Response CR PR SD PD 36
Slide 37: July 2025: Data for same patients continued to show deeper dose-dependent responses
July 2025: Data for same 30 patients continued to show deeper dose- dependent responses in onvansertib arms – as of July 8, 2025 30 patients SoC plus SoC plus SoC Best Response CR PR SD PD 37
Slide 38: Swimmer Plot for Stable Disease patients still on trial
Swimmer Plot for Stable Disease patients still on trial > On Treatment Best Response # Stable Disease # indicates % change from baseline Chemotherapy Backbone FOLFIRI FOLFOX + SoC + SoC 38
Slide 39: No baseline characteristic has a significant impact on ORR
No baseline characteristic has a significant impact on ORR 39
Slide 40: Baseline measures of tumor burden (by sum of longest diameters)
Baseline measures of tumor burden (by sum of longest diameters) The mean and median sum of the longest diameters was similar (not significantly different) for control, onvansertib 20mg and onvansertib 30mg arms Safety population - Baseline Sum of Longest Dimensions* (SLD) Control Arm (SoC) SoC + onv
Slide 41: 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=18) (n=17) (n=17) (n=18) (n=34) (n=70) N (% of total) All