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 ENZYME IC50 (µM) • Oral dosing PLK1-selective inhibitor PLK1 0.002 • 24-hour half-life PLK2 >10.000 PLK3 >10.000 CK2 0.
Slide 5: We designed the CRDF-004 trial to address four objectives
We designed the CRDF-004 trial to address four objectives CRDF-004 Ph2 trial RAS-mut mCRC shift from 2nd line to 1st line INTENT Aug 7, 2023 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
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 mCRC, metastatic colorectal cancer; Mut, mutant; ORR, objective response rate; PFS, progression free survival 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 3 rd 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 meta
Slide 10: 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 1st line mCRC Chemo/bev Phase 3 Clinical Trials by RAS-mut Status* PFS Mechanism Trial Sample ORR ORR (months) Hazard Targeted agent Trial of action population size Exp. vs Ctrl. delta Exp. vs Ctrl. ratio Bevacizuma
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 Unresectable R Onv 20mg + 3. FOLFIRI/bev 4. FOLFOX/bev
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 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 13: Dose-dependent increase in objective response rates observed 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 ORR1 30% 42% 49% 19% n, [95% CI] n=11 [16-47]
Slide 14: Dose-dependent increase in objective response rates observed 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 ORR1 30% 42% 49% 19% n, [95% CI] n=11 [16-47]
Slide 15: Deeper tumor regression observed with onvansertib+SoC
Deeper tumor regression observed with onvansertib+SoC Intent-to-treat Control Onv 20mg Onv 30mg Best Radiographic Response BY ONVANSERTIB DOSE* (ITT) (SoC alone) + SoC + SoC Confirmed ORR1 30% 42% 49% ORR2 43% 50% 59% Control rm oC erimental rms oC onvansertib Control rm oC oC onvansertib mg oC onva
Slide 16: Deeper tumor regression over time observed with onvansertib+SoC
Deeper tumor regression over time observed with onvansertib+SoC Control rm oC oC onvansertib mg oC onvansertib mg Radiographic Response over Time* Control Arms Experimental Arms SoC Onvansertib 20mg plus SoC Onvansertib 30mg plus SoC Best Response Change in target lesions from baseline Complete Resp
Slide 17: Deeper tumor regression 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 Best Radiographic Response BY CHEMO BACKBONE* Intent-to-treat (ITT) Control SoC + Onv Control SoC + Onv Confirmed ORR1 26% 44% 33% 46% Control rms oC Control Control rms rms oC oC Controlrms
Slide 18: Higher number of 30mg onvansertib patients remain on trial vs. control
Higher number of 30mg onvansertib patients remain on trial vs. control Radiographic Response over Time* Time on Trial by Best Response O CR/PR Control Onv 20mg Onv 30mg O O SD Safety Population (Dosed) (SoC alone) + SoC + SoC Control arms O O PD O > On treatment O Patients on treatment 18 (53%) 19 (
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 Any Adverse Events 33 ( 97.1) 21 ( 61.8) 34 (100.0) 24 ( 70.6) 36 (100.0) 28 ( 77
Slide 22: Dose intensity is similar and high across all trial arms
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* FOLFIRI/bev FOLFIRI/bev/onv 20 FOLFIRI/bev/onv 30 FOLFOX/bev FOLFOX/bev/onv 20 FOLFOX/bev/onv 30 Safety Population (Do
Slide 23: Agenda
1st line RAS-mut mCRC program update 1. ORR efficacy and safety AGENDA 2. PFS analyses 3. Registrational program path forward mCRC, metastatic colorectal cancer; mut, mutant; ORR, objective response rate; PFS, progression free survival 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 Progression Free Survival – Median PFS Not Reached* 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 PFS Probability Strata Control vs. onv 30m
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- TRIBE Tumor Shrinkage (ETS) term Outcome in mCRC Patients FOLFOXIRI+bev Cremolini, et. al. vs. FOLFIRI+bev Treated with 1st-line Chemo+bev ≥20%
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 % of patients TRIBE CRYSTAL OPUS CRDF-004 with ETS RAS WT/mut. RAS WT RAS WT RAS mut. Early Tumor Control Shrinkage (ETS) 52% 49% 46% 41% Arm (11/27) ≥20% reduction Onv 20mg Onv 30mg in
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 Control rm oC oC onvansertib mg oC onvansertib mg Radiographic Response over Time* Control Arms Experimental Arms SoC Onvansertib 20mg plus SoC Onvansertib 30mg plus SoC nova, Best Response lesions from baseline Complete Response B
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 % Tumor TRIBE CRYSTAL OPUS CRDF-004 Shrinkage RAS WT/mut. RAS WT RAS WT RAS mut. Depth of Control Response (DpR) Arm 38% 33% 31% 32% Maximum tumor Experimental Onv 20mg Onv 30mg shrinkage at Arm 43% 51% 58% 41%
Slide 29: Agenda
1st line RAS-mut mCRC program update 1. ORR efficacy and safety AGENDA 2. PFS analyses 3. Registrational program path forward mCRC, metastatic colorectal cancer; Mut, mutant; ORR, objective response rate; PFS, progression free survival 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 CRDF-004 Ph2 trial Progress to date 1st line RAS-mut mCRC INTENT Data supports focus on 1. Select a Ph3 dose – per FDA’s Project Optimus onvansertib 30mg dose 2. Assess efficacy signal 3. Characterize safety profile in first-line setting 4. B
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 CRDF-004 Ph2 trial Progress to date 1st line RAS-mut mCRC INTENT ORR: meaningful deltas in 1. Select a Ph3 dose – per FDA’s Project Optimus context of 1st line mCRC PFS: early PFS separation 2. Assess efficacy
Slide 32: Onvansertib in combination with SoC is generally well-tolerated
Onvansertib in combination with SoC is generally well-tolerated CRDF-004 Ph2 trial Progress to date 1st line RAS-mut mCRC INTENT 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 3. Cha
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 Seek FDA Agreement CRDF-004 Ph2 trial Progress for Ph3to date CRDF-005 1st line RAS-mut mCRC registrational protocol INTENT Totality of data supports 1. Select a Ph3 dose – per FDA’s Project Optimus moving forward with FDA interaction
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 PHASE 2 DOSE-CONFIRMATION TRIAL PHASE 3 REGISTRATIONAL TRIAL Designed for accelerated and full-approval Endpoint
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 Initial Control rm oC oC onvansertib mg oC onvansertib mg Radiographic Response over Time* – as of November 26, 2024 30 patients data disclosed Control Arms Experimental Arms Dec 10, 2024 SoC Onvansert
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 Initial Control rm oC oC onvansertib mg oC onvansertib mg Radiographic Response over Time* – as of July 8, 2025 30 patients data disclosed Control Arms Experimental Arms July 29, 2025 SoC Onva
Slide 38: Swimmer Plot for Stable Disease patients still on trial
Swimmer Plot for Stable Disease patients still on trial Radiographic Response over Time* > On Treatment Control arms Best Response O # Stable Disease O O # indicates % change from baseline Chemotherapy Backbone onths FOLFIRI FOLFOX Onv 20mg + SoC O O onths O Onv 30mg + SoC O O onths * Radiographic r
Slide 39: No baseline characteristic has a significant impact on ORR
No baseline characteristic has a significant impact on ORR Forest Plot of the Treatment Effect on ORR by Baseline Characteristic* atients Odds atios by ose Control rm oC oC onvansertib mg oC onvansertib mg CO O O C O CO O CO O esion Count ingle ulti le ets es iver o Characteristic iver Only es o Org
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