Slides
Page 1
Company OverviewThe Onvansertib Opportunity
Page 3
•••• ••••
Page 4
COLORECTAL CANCER3rd150,000 50,000 15%Less than 12months1stLINE STANDARD of CARE1996200220042014
Page 8
28 DAY CYCLE ENROLLMENT CRITERIAENDPOINTS
Page 9
2ndLINE1stLINE
Page 10
Bev naïve: Bev exposed:
Page 12
HIF1αTumor growthHypoxiaα bevacizumabonvansertibα
Page 13
213
Page 16
28 DAY CYCLE ENROLLMENT CRITERIAENDPOINTS*6 RANDOMIZATION ARMS
Page 20
Best ResponseProgressive Disease Stable Disease Partial Response Complete Response Progressive DiseaseStable DiseasePartial ResponseComplete ResponseScan Response
Page 22
47-year-old female69-year-old male49-year-old male62-year-old male
Page 24
EarlyDepthProof-of-PrincipleMeta Analysis Validation Ph3 TRIAL DATA*
Page 26
CRDF-005CRDF-004First-line RAS-mutated mCRC clinical development programAgreed with FDA June 2023 Type C meeting
Page 28
Clinical update in Q1 2026First-in-Class PLK1 inhibitorShift to first-line•••2ndline KRAS-mut.mCRC programClinical signal from CRDF-004 trial••
Page 29
BREAKTHROUGH GROWTH INITIATIVEPFIZERIgnitePFIZER
Page 30
Line of Therapy Ph2 Ph3Combination with: TrialIIT*
Page 31
AppendixmCRC Mechanism of Action Data
Page 32
Cardiff Oncology’s lead development asset is onvansertibOnvansertibSPECIFICITY PROPERTIES•••
Page 37
α HIF1aHIF1αTumor growthHypoxiaα
Page 38
HIF1αTumor growthHypoxiaα bevacizumab
Page 39
HIF1αTumor growthHypoxiaα bevacizumabonvansertibα
Page 40
α αsiPLK1β α02 + +− − αα β αOnv02+ +− −PLK1 inhibition in LoVo RAS-mutant CRC cell lines1
Page 41
siPLK1β α02 + +− − β αOnv02+ +− −α αOnv02+ +− −siPLK102+ +− − Onv02+ +− − Onv02+ +− − αα
Page 42
HIF1αbevacizumabonvansertibα•• Patent No.:Date of Patent:Expiration:US 12,263,173 B2Apr. 1, 2025Not before 2043United States PatentRidinger et al.Patent No.:Date of Patent:Expiration:US 12,144,813 B2Nov. 19, 2024Not before 2043United States PatentRidinger et al.
Page 43
MOAOnvansertib’s inhibition of the hypoxia response pathway
Page 44
May drive tumor resistance to bevMay drive tumor resistance to onvansertib 135 biopsies:Bev naïve Bev exposed
Page 45
AppendixAdditional mCRC Clinical Data
Page 48
Early Tumor Shrinkage (ETS)
Page 49
Best ResponseProgressive Disease Stable Disease Partial Response Complete Response Progressive DiseaseStable DiseasePartial ResponseComplete ResponseScan Response
Page 50
Depth of Response (DpR)
Page 54
AppendixAdditional mCRC Preclinical Data
Page 55
•––•
Page 56
PIM1MXI1EFNA1CXCR4TMEM45AVLDLRPFKFB3INHAAK4EFNA3MAFFP4HA1STC2ANKZF1BNIP3LKDM3APDK1PNRC1ALDOCSLC2A3ADMCCNG2BHLHE40DDIT4ANGPTL4−20240 2 4log2FoldChange in HCT116log2FoldChange in SW620Significant in BothSignificant in HCT116Significant in SW620Hx_DMS0_4h vs Nx_DMSO_4h: HCT116 and SW620 cellsANGPTL4CDKN1CSLC25A1STBD1SAP30STC2KLF6PLAURPFKPXPNPEP1PNRC1PDK1VEGFAEFNA1KDM3APFKFB3BHLHE40SLC2A1VLDLRCCNG2GCNT2PGK1MAFFAK4GBE1NFIL3ALDOCDDIT4EFNA3SLC2A3HOXB9P4HA1ENO2BNIP3LERRFI1ANKZF1ADMPGM1LDHA−2−101−2 −1 0 1 2 3log2FoldChange in HCT116log2FoldChange in SW620Significant in BothSignificant in HCT116Significant in SW620Hx_ONV2_4h vs Hx_DMSO_4h: HCT116 and SW620 cellsGenes induced by hypoxia in two mCRC cell lines Adding onvansertib inhibits adaptation to hypoxia Hypoxia vs normoxia gene expression in HCT116 and SW620 cellsWith vs without onvansertib gene expression in hypoxic HCT116 and SW620 cells
Page 57
••• CD31
Page 58
••• 0 510 15 20-50050100150200200400600Treatment time (days) C1143 (KRAS G12D)***** 0 510 15 20050100150200250Treatment time (days) C1144 (KRAS G12C)******VehicleOnv+IrinoOnvansertibIrinotecan
Page 59
•••• 0 510 15 200100200300Treatment time (days) C1138 (KRAS G13D)***** 0 510 15 200200400600800Treatment time (days) B8239 (KRAS G12C)****** 510 15 200100200300Treatment time (days) C1143 (KRAS G12D)*****
Page 60
Appendix:Investigator-Initiated TrialSmall Cell Lung Cancer (SCLC)
Page 61
TRIAL RATIONALE
Page 62
ENROLLMENT CRITERIA 21 DAY CYCLEPRIMARY ENDPOINTSECONDARY ENDPOINTSOBJECTIVE
Page 63
ENROLLMENT CRITERIA PRELIMINARY EFFICACY (N=7)PRELIMINARY SAFETY (N=6)
Page 65
Appendix:Investigator-Initiated TrialTriple Negative Breast Cancer (TNBC)
Page 66
TRIAL RATIONALE
Page 67
PRIMARY ENDPOINTS 28 DAY CYCLE TRIPLE NEGATIVE BREAST CANCER
Page 68
TRIPLE NEGATIVE BREAST CANCER ••