Onvansertib Phase 2 results move Cardiff Oncology (NASDAQ: CRDF) toward Phase 3
Rhea-AI Filing Summary
Cardiff Oncology, Inc. shared updated Phase 2 CRDF-004 data for its PLK1 inhibitor onvansertib in first-line RAS-mutated metastatic colorectal cancer and outlined plans for a registrational Phase 3 trial. The 30 mg onvansertib + FOLFIRI/bevacizumab arm showed a 72% objective response rate, about 30% higher than standard FOLFIRI/bevacizumab. Median progression-free survival has not yet been reached in key onvansertib arms, while standard-of-care FOLFIRI/bevacizumab showed a median PFS of 12.22 months by investigator assessment. The company completed a successful End-of-Phase 2 FDA meeting and is proposing a ~640-patient pivotal trial with dual primary endpoints of objective response rate and progression-free survival, designed to allow accelerated approval based on response and full approval based on PFS. Safety data indicate no unexpected or new toxicities when onvansertib is added to existing chemotherapy and bevacizumab regimens.
Positive
- Strong Phase 2 efficacy signal: 30 mg onvansertib + FOLFIRI/bevacizumab achieved a 72% objective response rate, about 30% higher than standard FOLFIRI/bevacizumab in first-line RAS-mutated metastatic colorectal cancer, with median progression-free survival not yet reached in key onvansertib arms.
Negative
- None.
Insights
Phase 2 data support moving onvansertib into a large Phase 3 trial.
Cardiff Oncology reports that adding 30 mg onvansertib to FOLFIRI/bevacizumab achieved a 72% objective response rate, about 30% higher than standard FOLFIRI/bevacizumab in first-line RAS-mutated metastatic colorectal cancer. Median progression-free survival has not yet been reached in key onvansertib combinations, while standard FOLFIRI/bevacizumab showed a median PFS of 12.22 months by investigator assessment.
The company has completed an FDA End-of-Phase 2 meeting and proposes a pivotal Phase 3 trial enrolling about 640 patients, with dual primary endpoints of objective response rate and progression-free survival. The design is intended to support accelerated approval via response and full approval via PFS, if results are favorable.
Safety tables show frequent but expected chemotherapy-related adverse events and no unexpected, overlapping, or new toxicities when onvansertib is combined with FOLFIRI/bevacizumab or FOLFOX/bevacizumab. Subsequent company filings may provide more detail on regulatory interactions and the timing of Phase 3 trial initiation.
8-K Event Classification
Key Figures
Key Terms
objective response rate financial
progression free survival financial
FOLFIRI/bev medical
End-of-Phase 2 meeting regulatory
accelerated approval regulatory
PLK1 inhibitor medical
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
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Item 7.01 Regulation FD Disclosure.
Cardiff Oncology, Inc. prepared an investor presentation reviewing its Phase 2 CRDF-004 data and registrational study plans for onvansertib. A copy of the presentation materials is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference..
The information in this report, including the investor presentation furnished as Exhibit 99.1 hereto, shall not be deemed to be “filed” for purposes of Section 18 of the Securities and Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, and shall not be incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing. In addition, the exhibit furnished herewith contain statements intended as “forward-looking statements” that are subject to the cautionary statements about forward-looking statements set forth in such exhibit.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
99.1 |
Cardiff Oncology, Inc. Corporate Presentation |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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CARDIFF ONCOLOGY, INC. |
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June 3, 2026 |
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/s/ Mani Mohindru |
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Mani Mohindru |
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June 3, 2026 Interim Results from the Randomized, Controlled Phase 2 CRDF-004 Trial Onvansertib + SoC Chemo/Bevacizumab in First-Line RAS-Mutated mCRC
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 similar terms or expressions that concern our expectations, strategy, plans or intentions. These forward-looking statements are based on our current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidate; results of preclinical studies or clinical trials for our product candidate could be unfavorable or delayed; our need for additional financing; ; uncertainty as to the outcome of pending litigation against Nerviano Medical Sciences S.r.l. with respect to our license agreement with Nerviano; risks related to business interruptions, including the outbreak of COVID-19 coronavirus and cyber-attacks on our information technology infrastructure, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that our product candidate will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that our product candidate will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in our Form 10-K for the year ended December 31, 2025, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and we do not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.
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 Medicine of USC. He serves as Co-Leader of the Gastrointestinal Cancers Program and Co-Director of the USC Center for Cancer Drug Development Josep Tabernero, MD, PhD, 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 Q&A AGENDA Mani Mohindru, PhD President and CEO GI ONCOLOGY KOLS: CARDIFF LEADERSHIP: Heinz-Josef Lenz, MD Josep Tabernero, MD, PhD
Program Overview CRDF-004 Clinical Update Path Forward FIRST-LINE RAS-MUTATED mCRC ONVANSERTIB
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-mutated mCRC, is an area of high unmet need and limited innovation Practice-changing potential in large, underserved populations Opportunity for market expansion, including in rare RAS-driven cancers such as CMML Large Commercial Opportunity Successful End-of-Phase 2 meeting: aligned on the registrational trial in first-line RAS-mutated mCRC Dose and chemo regimen selected: 30 mg onvansertib + FOLFIRI/bev Ph 3 designed to allow for Accelerated Approval (ORR) and full approval (PFS) Clear Registrational Path 72% ORR in randomized Phase 2 trial, +30% over SoC; median PFS not reached vs 12.2 months in SoC* Synergy with FOLFIRI/bev in first-line RAS-mut mCRC with a favorable safety profile Confirms earlier efficacy shown in Ph 1b/2 trial in second-line KRAS-mut mCRC in bev-naïve patients Strong Efficacy in RAS-mutated mCRC
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 Decades Chemotherapy (FOLFOX/FOLFIRI/FOLFOXIRI) Bevacizumab (Avastin®) No approvals specific to panRAS-mut mCRC 15% 5-year relative OS Less than 12 months median PFS For patients with mCRC *American Cancer Society; NCI SEER database CRC, colorectal cancer; mCRC, metastatic colorectal cancer
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 45% vs 35% 43% vs 41% 10.6 vs 6.2 9.3 vs 5.5 0.54 p<0.0001 0.41 FOLFOXIRI/bev (TRIBE trial) FOLFOXIRI/bev vs FOLFIRI/bev Chemo RAS WT or mutant All ITT patients Mutant only1 508 236 65% vs 54% 66% vs 55% 12.3 vs 9.7 12.0 vs 9.5 0.77 p=0.006 0.78 Data from positive first-line mCRC chemo/bev Phase 3 clinical trials by RAS-mutated status* * Source: bevacizumab: USPI from accessdata.fda.gov, Hurwitz H, et al. The Oncologist 2009. FOLFOXIRI: Cremolini C, et al. Lancet Oncol 2015. 1. RAS mutation was evaluated retrospectively and tumor samples for RAS analysis were not available for all patients.
Program Overview CRDF-004 Clinical Update (Data cut-off Mar 18, 2026) Path Forward FIRST-LINE RAS-MUTATED mCRC ONVANSERTIB
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 SoC: Chemo + bevacizumab First-line SoC: Chemo + bevacizumab 28 DAY CYCLE 6 7 8 9 10 11 12 13 14 20 21 22 23 24 25 26 27 28 ONVANSERTIB ONVANSERTIB ENROLLMENT CRITERIA ENDPOINTS* Primary: Secondary: ORR DoR and PFS First-line mCRC KRAS+/NRAS+ No BRAF-V600 or MSI-H/dMMR Unresectable No prior bev ITT=110 R Onv 30mg + Onv 20mg + SoC alone 6 RANDOMIZATION ARMS * Assessed by blinded independent central review (BICR) Patient’s tumors are scanned every 8 weeks 1. FOLFIRI/bev 2. FOLFOX/bev 3. FOLFIRI/bev 4. FOLFOX/bev 5. FOLFIRI/bev 6. FOLFOX/bev
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) Median (Min, Max) 53 (32, 81) 52 (30, 78) 60 (34, 81) 57 (34, 82) 66 (34, 79) 59.5 (39, 86) ECOG 0 6 (31.6%) 13 (72.2%) 11 (61.1%) 7 (38.9%) 10 (55.6%) 11 (57.9%) 1 11 (57.9%) 4 (22.2%) 7 (38.9%) 10 (55.6%) 7 (38.9%) 7 (36.8%) Stage at initial diagnosis* STAGE IV 9 (47.4%) 10 (55.6%) 14 (77.8%) 9 (50.0%) 11 (61.1%) 13 (68.4%) STAGE III 4 (21.1%) 4 (22.2%) 2 (11.1%) 6 (33.3%) 2 (11.1%) 3 (15.8%) STAGE II 3 (15.8%) 2 (11.1%) 2 (11.1%) 2 (11.1%) 3 (16.7%) 1 (5.3%) STAGE I 0 1 (5.6%) 0 0 1 (5.6%) 1 (5.3%) Side of tumor RIGHT 5 (26.3%) 8 (44.4%) 6 (33.3%) 8 (44.4%) 7 (38.9%) 7 (36.8%) LEFT 6 (31.6%) 7 (38.9%) 6 (33.3%) 5 (27.8%) 8 (44.4%) 4 (21.1%) BILATERAL 6 (31.6%) 2 (11.1%) 6 (33.3%) 4 (22.2%) 2 (11.1%) 7 (36.8%) Liver metastasis at study entry Yes 10 (52.6%) 10 (55.6%) 14 (77.8%) 10 (55.6%) 12 (66.7%) 14 (73.7%) No 7 (36.8%) 7 (38.9%) 4 (22.2%) 7 (38.9%) 5 (27.8%) 4 (21.1%) Liver only disease No 15 (78.9%) 15 (83.3%) 11 (61.1%) 14 (77.8%) 16 (88.9%) 15 (78.9%) Yes 2 (10.5%) 2 (11.1%) 7 (38.9%) 3 (16.7%) 1 (5.6%) 3 (15.8%) Number of metastatic organs Multiple 11 (57.9%) 9 (50.0%) 9 (50%) 9 (50.0%) 13 (72.2%) 15 (78.9%) Single 6 (31.6%) 8 (44.4%) 9 (50%) 8 (44.4%) 4 (22.2%) 3 (15.8%) Prior adjuvant or neo-adjuvant chemo No 13 (68.4%) 12 (66.7%) 14 (77.8%) 12 (66.7%) 12 (66.7%) 16 (84.2%) Yes 4 (21.1%) 5 (27.8%) 4 (22.2%) 5 (27.8%) 5 (27.8%) 2 (10.5%) *Missing in one patient
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 March 18, 2026 cut-off: 13 of 14 remaining patients are on onvansertib + SOC chemo/bev
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 surgery * Residual non-target disease (Non-CR/Non-PD) Patients that are not-evaluable or do not have target lesions are not shown in the plots PR Stable Disease Progressive Disease CR Confirmed ORR (n) Onv 20 mg + FOLFIRI/bev (n=18) 44.4% (8/18) FOLFIRI/bev (n=19) 42.1% (8/19) Onv 30 mg + FOLFIRI/bev (n=18) 72.2% (13/18) Best % Change from Baseline > On 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 Adverse Event To Pursue Surgery Progressive Disease (Investigator) Other Patient Decision Death First Response Scan > On Treatment Time on Trial by Best Confirmed Response Partial Response Stable Disease Complete Response > > > > > > > > > > > Some patients on treatment for >18+ months
% 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) (n=18) > > > > > > > > > > Best Confirmed Response Stable Disease Partial Response Complete Response > On Treatment
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 NR* HR (95% CI) 0.44 (0.15, 1.25) FOLFIRIbev + FOLFOX/bev Onv (20 & 30mg) + FOLFIRI/bev N 37 36 Median PFS 10.97 NR* HR (95% CI) 0.53 (0.25, 1.15) HR: hazard ratio; PFS: Progression Free Survival; BICR: Blinded Independent Central Review; * Nine patients still on study Onv (30mg & 20mg) + FOLFIRI/bev Combined SoC (FOLFIRI/bev & FOLFOX/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) *Discordance in median PFS in FOLFIRI/ bev arm due to investigator-assessed progressive disease (PD) and discontinuation prior to BICR confirmation of progression **Four patients still on study Onv 30 mg + FOLFIRI/bev FOLFIRI/bev BICR Assessment Investigator Assessment Onv 30 mg + FOLFIRI/bev FOLFIRI/bev
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 treatment group Favors control group
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 diagnosis excluded due to too few patients to meaningfully analyze.
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 preferred term are counted only once in that preferred term. For subjects reporting more than one AE within a preferred term, the AE with maximum grade is included in the table. FOLFIRI/bev (N=17) Onv 20 mg + FOLFIRI/bev (N=17) Onv 30 mg + FOLFIRI/bev (N=18) FOLFOX/bev (N=17) Onv 20 mg + FOLFOX/bev (N=17) Onv 30 mg + FOLFOX/bev (N=18) Number (%) of Participants: by Preferred Term Any Grade n (%) Gr ≥ 3 n (%) Any Grade n (%) Gr ≥ 3 n (%) Any Grade n (%) Gr ≥ 3 n (%) Any Grade n (%) Gr ≥ 3 n (%) Any Grade n (%) Gr ≥ 3 n (%) Any Grade n (%) Gr ≥ 3 n (%) Participants with events 17 (100.0) 15 (88.2) 17 (100.0) 13 (76.5) 18 (100.0) 15 (83.3) 16 (94.1) 11 (64.7) 17 (100.0) 12 (70.6) 18 (100.0) 16 (88.9) Nausea 9 (52.9) 1 (5.9) 13 (76.5) 1 (5.9) 12 (66.7) 0 11 (64.7) 1 (5.9) 12 (70.6) 0 11 (61.1) 0 Fatigue 9 (52.9) 0 12 (70.6) 0 11 (61.1) 0 10 (58.8) 2 (11.8) 12 (70.6) 1 (5.9) 10 (55.6) 0 Diarrhea 11 (64.7) 1 (5.9) 13 (76.5) 2 (11.8) 9 (50.0) 0 8 (47.1) 1 (5.9) 7 (41.2) 1 (5.9) 7 (38.9) 0 Neutrophil count decreased 9 (52.9) 5 (29.4) 5 (29.4) 2 (11.8) 7 (38.9) 3 (16.7) 5 (29.4) 5 (29.4) 7 (41.2) 4 (23.5) 7 (38.9) 4 (22.2) Peripheral sensory neuropathy 5 (29.4) 0 2 (11.8) 0 3 (16.7) 0 6 (35.3) 0 10 (58.8) 2 (11.8) 11 (61.1) 1 (5.6) Vomiting 6 (35.3) 1 (5.9) 8 (47.1) 0 7 (38.9) 0 5 (29.4) 1 (5.9) 7 (41.2) 1 (5.9) 4 (22.2) 0 Hypertension 6 (35.3) 2 (11.8) 8 (47.1) 3 (17.6) 7 (38.9) 3 (16.7) 3 (17.6) 0 5 (29.4) 1 (5.9) 7 (38.9) 5 (27.8) Constipation 3 (17.6) 1 (5.9) 6 (35.3) 0 5 (27.8) 0 2 (11.8) 0 10 (58.8) 0 8 (44.4) 0 Abdominal pain 5 (29.4) 2 (11.8) 4 (23.5) 1 (5.9) 7 (38.9) 1 (5.6) 4 (23.5) 0 6 (35.3) 1 (5.9) 7 (38.9) 1 (5.6) Decreased appetite 7 (41.2) 1 (5.9) 5 (29.4) 0 7 (38.9) 1 (5.6) 4 (23.5) 0 7 (41.2) 0 3 (16.7) 0 Epistaxis 4 (23.5) 0 9 (52.9) 0 7 (38.9) 0 4 (23.5) 0 5 (29.4) 0 4 (22.2) 0 Anemia 4 (23.5) 1 (5.9) 7 (41.2) 1 (5.9) 5 (27.8) 1 (5.6) 3 (17.6) 0 4 (23.5) 1 (5.9) 8 (44.4) 4 (22.2) Platelet count decreased 2 (11.8) 1 (5.9) 4 (23.5) 0 3 (16.7) 1 (5.6) 7 (41.2) 1 (5.9) 7 (41.2) 0 8 (44.4) 2 (11.1) Weight decreased 7 (41.2) 2 (11.8) 2 (11.8) 1 (5.9) 6 (33.3) 0 2 (11.8) 0 3 (17.6) 0 5 (27.8) 1 (5.6) Alopecia 5 (29.4) 0 4 (23.5) 0 6 (33.3) 0 2 (11.8) 0 5 (29.4) 0 2 (11.1) 0 Dizziness 3 (17.6) 0 4 (23.5) 0 2 (11.1) 0 3 (17.6) 0 5 (29.4) 0 7 (38.9) 0 Headache 4 (23.5) 0 7 (41.2) 0 2 (11.1) 0 4 (23.5) 0 6 (35.3) 0 1 (5.6) 0 Hypokalemia 4 (23.5) 1 (5.9) 3 (17.6) 2 (11.8) 5 (27.8) 2 (11.1) 5 (29.4) 1 (5.9) 3 (17.6) 0 4 (22.2) 1 (5.6) Insomnia 0 0 5 (29.4) 0 4 (22.2) 0 3 (17.6) 0 6 (35.3) 0 6 (33.3) 0 Stomatitis 3 (17.6) 1 (5.9) 7 (41.2) 0 3 (16.7) 0 6 (35.3) 0 3 (17.6) 0 1 (5.6) 0 White blood cell count decreased 5 (29.4) 1 (5.9) 5 (29.4) 0 5 (27.8) 0 6 (35.3) 2 (11.8) 0 0 2 (11.1) 1 (5.6) Dysgeusia 2 (11.8) 0 1 (5.9) 0 4 (22.2) 0 5 (29.4) 0 5 (29.4) 0 5 (27.8) 0
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=19) 47.4 (9) > On Treatment Best % Change from Baseline Progression Free Survival FOLFOX/bev (n=18) Onv 20 mg + FOLFOX/bev (n=18) Onv 30 mg + FOLFOX/bev (n=19) Median (95% CI) Median (95% CI) Hazard Ratio (95% CI) Median (95% CI) Hazard Ratio (95% CI) BICR only 11.07 (10.18-NR) 14.13 (10.94-NR) 1.14 (0.32, 4.04) 11.37 (9.4-NR) 2.2 (0.67, 7.28) Investigator only 9.89 (9.23-NR) 12.78 (7.39-NR) 1.02 (0.39, 2.64) 11.37 (8.15-NR) 1.81 (0.64, 5.08) Objective Response Rate (per BICR)a - ITT Analysis > > > >
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 double stranded breaks (DSBs) rely on PLK1-dependent Homologous Recombination repair Oxaliplatin + Onvansertib Oxaliplatin has low impact on HIF1a suppression — no shared antiangiogenic effect Oxaliplatin induced DNA damage uses Nucleotide Excision Repair mechanism — limited/no role of PLK1 HCT116_SN38 HIF1α B-Actin Nx Hypoxia (1%O2) (-) (-) 5 50 500 (nM) HCT116_OXALIPLATIN HIF1α B-Actin Nx Hypoxia (1%O2) (-) (-) 5 500 5000 (nM) SN38 decreases HIF1α in a dose-dependent manner; HIF1α less sensitive to oxaliplatin Onvansertib & irinotecan both cause HIF1α suppression (anti-angiogenic effects) Onvansertib may inhibit DNA-repair pathway activated upon irinotecan-induced DNA damage
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 + FOLFIRI/bev demonstrated improvement in ORR compared to SoC Median PFS not yet reached vs SoC 9 of 14 patients remain on onvansertib + FOLFIRI/bev treatment; median PFS not reached but reached in SoC
Program Overview CRDF-004 Clinical Update Path Forward FIRST-LINE RAS-MUTATED mCRC ONVANSERTIB
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 two arms Potential for accelerated approval based on ORR and durability of responses FDA feedback received, EMA feedback pending Onvansertib 30 mg + FOLFIRI/bevacizumab Randomize 1:1 CRDF-005 FOLFIRI/bevacizumab First-line mCRC KRAS+/NRAS+ No BRAF-V600 or MSI-H/dMMR Unresectable No prior bev
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 FOLFIRI/bev Two clinical studies demonstrate improved outcomes in bev-naïve patients, validating combination synergy No meaningful treatment advances in first-line RAS-mutated mCRC in over 20 years Advancement to Registrational Trial Improved Efficacy in 1L RAS-mut mCRC Phase 2 CRDF-004 data show 72% ORR at 30mg, +30% over SoC; median PFS not reached with some patients on treatment > 18 months 30 mg dose selected; Phase 3 designed for accelerated approval via ORR and full approval via PFS Clean Safety Profile No added safety signals — side effects consistent with background therapy
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 University Professor of Medicine, Population and Public Health Sciences and Cancer Biology; Professor of Medicine and Preventive Medicine of USC. He serves as Co-Leader of the Gastrointestinal Cancers Program and Co-Director of the USC Center for Cancer Drug Development.
Heinz-Josef Lenz, MD Mani Mohindru, PhD President & CEO Joshua Muntner CFO Josep Tabernero, MD, PhD Q&A GI ONCOLOGY KOLS: CARDIFF LEADERSHIP: