Slide 1: Interim Results from the Randomized, Controlled Phase 2 CRDF-004 Trial
June 3, 2026 Interim Results from the Randomized, Controlled Phase 2 CRDF-004 Trial Onvansertib + SoC Chemo/Bevacizumab in First-Line RAS-Mutated mCRC
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: Agenda
Program Overview Mani Mohindru, PhD, President and CEO CRDF-004 Clinical Update & Path Forward Mani Mohindru, PhD, President and CEO KOL Perspectives Heinz-Josef Lenz, MD, University Professor of Medicine, Population and Public Health Sciences and Cancer Biology; Professor of Medicine and Preventive
Slide 4: Program Overview
Program Overview CRDF-004 Clinical Update Path Forward FIRST-LINE RAS-MUTATED mCRC ONVANSERTIB
Slide 5: Highly selective PLK1 inhibitor with practice-changing potential in first-line RAS-mutated mCRC
Highly selective PLK1 inhibitor with practice-changing potential in first-line RAS-mutated metastatic colorectal cancer *ORR reflects BICR. PFS reflects Investigator Assessment* ORR: Objective Response Rate; PFS: Progression Free Survival; BICR: Blinded Independent Central Review First-line RAS-muta
Slide 6: Positioned to address the first-line RAS-mutated mCRC market
RAS Wild Type G12C ~4% RAS-mutated ~50% ~50% Positioned to address the first-line RAS-mutated mCRC market Blockbuster potential: Onvansertib targets All RAS-mut mCRC ~150,000 newly diagnosed CRC patients in U.S.; 20% present metastatic disease* 1st Line Standard-of-Care Remains Unchanged for Two De
Slide 7: Large unmet need in first-line mCRC: efficacy data from existing therapies
Large unmet need in first-line mCRC: efficacy data from existing therapies Targeted agent Trial Mechanism of action Trial population Sample size ORR Exp. vs Ctrl. PFS (months) Exp. vs Ctrl. Hazard ratio bevacizumab IFL/bev vs IFL Antiangiogenic KRAS WT or mutant All ITT patients Mutant only1 813 78
Slide 8: CRDF-004 Clinical Update (Data cut-off Mar 18, 2026)
Program Overview CRDF-004 Clinical Update (Data cut-off Mar 18, 2026) Path Forward FIRST-LINE RAS-MUTATED mCRC ONVANSERTIB
Slide 9: CRDF-004: dose-finding, randomized, controlled Phase 2 trial design
mCRC: metastatic colorectal cancer; ORR: objective response rate; DoR: duration of response; PFS: progression free survival; SoC: standard of care; onv: onvansertib; bev: bevacizumab CRDF-004: dose-finding, randomized, controlled Phase 2 trial in first-line patients with RAS-mutated mCRC First-line
Slide 10: Demographics and baseline characteristics
Demographics and baseline characteristics FOLFIRI/bev (N=19) Onv 20 mg + FOLFIR/bev (N=18) Onv 30 mg + FOLFIRI/bev (N=18) FOLFOX/bev (N=18) Onv 20 mg + FOLFOX/bev (N=18) Onv 30 mg + FOLFOX/bev (N=19) Age (years) Mean (SD) 55.41 (14.34) 52.41 (13.13) 59.67 (12) 56.24 (12.04) 59.41 (14.5) 60.11 (14.1)
Slide 11: Patient populations and trial status
Population, n FOLFIRI/bev Onv 20mg + FOLFIRI/bev Onv 30mg + FOLFIRI/bev FOLFOX/bev Onv 20mg + FOLFOX/bev Onv 30mg + FOLFOX/bev Total Intent-to-treat (ITT) 19 18 18 18 18 19 110 Safety population (dosed) 17 17 18 17 17 18 104 Patients still on study treatment 1 5 4 0 3 1 14 Trial is ongoing as of Mar
Slide 12: Onv 30 mg + FOLFIRI/bev delivers superior ORR and depth of response
Onv 30 mg + FOLFIRI/bev delivers superior ORR & depth of response: 30% improvement in ORR over FOLFIRI/bev Onv 20 mg/Onv 30 mg + FOLFIRI/bev (n=36) Combined ORR: 58.3% (21) Objective Response Rate (per BICR) - ITT Analysis ** CR at last assessment; unconfirmed due to discontinuation for curative sur
Slide 13: Onv 30 mg + FOLFIRI/bev demonstrates longer duration of treatment
Onv 30 mg + FOLFIRI/bev demonstrates longer duration of treatment 9 of 10 remaining patients on onv + FOLFIRI/bev Onv 30 mg + FOLFIRI/bev Onv 20 mg + FOLFIRI/bev Control Arm (FOLFIRI/bev) Patients that are not evaluable are not shown in the plots (n=19) (n=18) (n=18) Reason For Discontinuation Adver
Slide 14: Deep and durable tumor shrinkage over time
% Change in target lesions from baseline Patients that are not-evaluable or do not have target lesions are not shown in the plots. Onv 30 mg + FOLFIRI/bev demonstrates deep and durable tumor shrinkage over time Control Arm (FOLFIRI/bev) Onv 20 mg + FOLFIRI/bev Onv 30 mg + FOLFIRI/bev (n=19) (n=18) (
Slide 15: Onv + FOLFIRI/bev shows improved PFS vs SoC
No. at risk No. at risk Onv (20 & 30 mg) + FOLFIRI/bev shows improved PFS vs SoC (FOLFIRI/bev & FOLFOX/bev) BICR Assessment Investigator Assessment Onv (30mg & 20mg) + FOLFIRI/bev Combined SoC (FOLFIRI/bev & FOLFOX/bev) FOLFIRI/bev + FOLFOX/bev Onv (20 & 30mg) + FOLFIRI/bev N 37 36 Median PFS 11.07
Slide 16: Onv 30 mg + FOLFIRI/bev shows improved PFS vs FOLFIRI/bev
Onv 30 mg + FOLFIRI/bev shows improved PFS vs FOLFIRI/bev BICR Assessment Investigator Assessment FOLFIRI/bev Onv 30 mg + FOLFIR/bev N 19 18 Median PFS 18.89* NR** HR (95% CI) 0.55 (0.15, 2.09) FOLFIRI/bev Onv 30 mg + FOLFIR/bev N 19 18 Median PFS 12.22* NR** HR (95% CI) 0.57 (0.2, 1.65) *Discordanc
Slide 17: Forest plot of ORR by baseline characteristics
STAGE I at initial diagnosis excluded due to too few patients to meaningfully analyze. Forest plot of ORR (BICR) by baseline characteristics demonstrates consistent benefit across subgroups with Onv 30 mg + FOLFIRI/bev Onv 30 mg + FOLFIRI/bev vs FOLFIRI/bev N Difference in ORR (95% CI) Level Favors
Slide 18: Forest plot of PFS by baseline characteristics
Forest plot of PFS* by baseline characteristics demonstrates trends in benefit across subgroups with Onv 30 mg + FOLFIRI/bev * Progressive disease events were based on events of BICR and Investigator assessments. The earliest reported date was used for a conservative estimate STAGE I at initial diag
Slide 19: Onvansertib shows no unexpected, overlapping, or new toxicities
Onvansertib shows no unexpected, overlapping, or new toxicities when added to FOLFIRI/bev or FOLFOX/bev *Data cut-off March 18, 2026, from an ongoing trial and unlocked EDC database. events shown occurred in ≥20% of total patients; Subjects reporting more than one adverse event (AE) within a preferr
Slide 20: Onvansertib adds no consistent meaningful benefit to FOLFOX/bev
Patients that are not evaluable are not shown in the plots Onvansertib adds no consistent meaningful benefit to FOLFOX/bev Best confirmed Response PR Stable Disease Progressive Disease CR Confirmed ORR (n) FOLFOX/bev (n=18) 44.4% (8) Onv 20 mg + FOLFOX/bev (n=18) 55.6% (10) Onv 30 mg + FOLFOX/bev (n
Slide 21: Mechanistic rationale for onvansertib's synergy with FOLFIRI but not FOLFOX
Mechanistic rationale for onvansertib's synergy with FOLFIRI but not FOLFOX HCT116 is a human colorectal cell line; Irinotecan, a component of FOLFIRI, is a prodrug of SN38 Topoisomerase I inhibitors (Irinotecan/SN38) + Onvansertib Both suppress HIF1α → dual anti-angiogenic effect Irinotecan-induced
Slide 22: CRDF-004 Phase 2 trial: key goals/endpoints achieved
CRDF-004 Phase 2 trial: key goals/endpoints achieved Primary Endpoint: ORR Secondary Endpoint: PFS Primary Goal: DOSE + CHEMO SELECTION 30 mg onvansertib + FOLFIRI/bev Selected the efficacious and safe dose of onvansertib + SoC for the registrational program 30% improvement in ORR 30 mg onvansertib
Slide 23: Path Forward
Program Overview CRDF-004 Clinical Update Path Forward FIRST-LINE RAS-MUTATED mCRC ONVANSERTIB
Slide 24: Proposed pivotal trial design in first-line RAS-mutated mCRC
Proposed pivotal trial design in first-line RAS-mutated mCRC FDA End-of-Phase 2 meeting completed in 2Q 2026 ENROLLMENT CRITERIA ENDPOINTS Dual Primary Endpoints: Secondary: ORR and PFS DoR and OS Design details: Proposed sample size ~ 640 patients >90% power to detect PFS and ORR difference in the
Slide 25: Key takeaways for onvansertib
Key takeaways for onvansertib mCRC, metastatic colorectal cancer; bev, bevacizumab; ORR, objective response rate; PFS, progression-free survival; PLK1, polo-like kinase 1; SoC, standard of care Onvansertib: highly selective, oral, small molecule inhibitor of PLK1 Large Unmet Need Proven Synergy with
Slide 26: KOL perspectives: mCRC market and therapeutic landscape
KOL perspectives: mCRC market and therapeutic landscape Josep Tabanero, M.D., PhD., is Head of the Medical Oncology Department at Vall d’Hebron University Hospital, Professor of Medicine at the Universitat de Vic and Director of the Vall d’Hebron Institute of Oncology. Heinz Josef-Lenz, M.D., is a U
Slide 27: Q&A
Heinz-Josef Lenz, MD Mani Mohindru, PhD President & CEO Joshua Muntner CFO Josep Tabernero, MD, PhD Q&A GI ONCOLOGY KOLS: CARDIFF LEADERSHIP: