Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (November 2021)
51 slides from Cardiff Oncology's investor presentation, November 2021
Slide 1: Company Overview: The Onvansertib Opportunity
Company Overview The Onvansertib Opportunity TURNING THE TIDE ON CANCER NOVEMBER 2021
Slide 2: Forward-Looking Statements
Forward-Looking Statements competition; uncertainties of patent protection and litigation; dependence upon CERTAIN STATEMENTS IN THIS PRESENTATION ARE third parties; regulatory, and risks related to failure to obtain FDA clearances or FORWARD-LOOKING within the meaning of the Private Securities appr
Slide 3: PLK1 is hijacked by tumor cells, allowing uncontrolled growth
PLK1 is hijacked by tumor cells, allowing uncontrolled growth DNA Further synthesis S G2 cell growth TUMOR CELL CYCLE Initial Mitosis cell growth G1 M (cell division) PL K 1 3
Slide 4: PLK1 repairs damaged DNA, enabling tumor cells to proliferate
PLK1 repairs damaged DNA, enabling tumor cells to proliferate Molecular Cell, March 4, 2021 PLK1 repairs dsDNA breaks at broken replication forks PLK1 S G2 TUMOR CELL CYCLE G1 M PL K 1 4
Slide 5: Onvansertib positions Cardiff Oncology to effectively target PLK1
Onvansertib positions Cardiff Oncology to effectively target PLK1 SPECIFICITY PROPERTIES OPPORTUNITY Exquisitely specific for PLK1 • Small molecule PLK1 is over-expressed • Oral dosing in many cancer types1 ENZYME IC50 (µM) • 24-hour half-life PLK1 0.002 Breast PLK2 >10.000 Colorectal PLK3 >10.000 L
Slide 6: We believe Pfizer relationship validates onvansertib as platform molecule
We believe Pfizer relationship validates onvansertib as platform molecule Pfizer BREAKTHROUGH GROWTH INITIATIVE SUMMARY TERMS Announced November 18, 2021 • Onvansertib program validation • Pfizer will invest a total of $15M at $6.22 per share (a 19% premium over prior • Scientific Advisory Board exp
Slide 7: WHAT Onvansertib has achieved
WHAT Onvansertib has achieved WHY Onvansertib works WHERE Cardiff Oncology can go 7
Slide 8: WHAT Onvansertib has achieved
WHAT Onvansertib has achieved WHY Onvansertib works WHERE Cardiff Oncology can go 8
Slide 9: Our lead program is in KRAS-metastatic colorectal cancer (mCRC)
Our lead program is in KRAS-metastatic colorectal cancer (mCRC) Preclinical IND En. Ph 0/1 Ph 2 Status mCRC FOLFIRI/bev Enrolled mPDAC Onivyde/5-FU Enrolling mCRPC Abiraterone Enrolling PDAC Biomarker Target Q4, ’21 TNBC Combo w/ Paclitaxel Development SCLC Single agent Development CMML Single agent
Slide 10: Gaps in current mCRC therapies leave a significant unmet need
Gaps in current mCRC therapies leave a significant unmet need 1st LINE 2nd LINE FOLFOX (chemo) + bevacizumab KRAS Wild Type + EGFR inhibitor FOLFIRI (chemo) + bevacizumab KRAS Mutant FOLFOX (chemo) + bevacizumab KRAS KRAS Normal1 Mutant 57.1% 42.9% 1. Jones R et al. Br J Cancer. 2017 Mar 28;116(7):9
Slide 11: The prognosis for second-line mCRC therapies is poor
The prognosis for second-line mCRC therapies is poor 2nd LINE 5-year survival: 10% Drugs in development do not address FOLFIRI (chemo) + bevacizumab most prevalent KRAS mutations HISTORICAL ORR 5% 2006 – 2008 ML18147 Phase 3 Registrational Trial FOLFIRI + bev in second-line1 Systematic Literature-Ba
Slide 12: Gaps in KRAS-mutated mCRC therapies leave a significant unmet need
Gaps in KRAS-mutated mCRC therapies leave a significant unmet need KRAS Mutations in mCRC1 3.8% G12C Current therapies (Amgen; Mirati) G12D address the G12C KRAS mutation only G12V KRAS Wild Type G13D G12S G12A Q61H G13C 1. Jones R et al. Br J Cancer. 2017 Mar 28;116(7):923-929 12
Slide 13: Gaps in KRAS-mutated mCRC therapies leave a significant unmet need
Gaps in KRAS-mutated mCRC therapies leave a significant unmet need KRAS Mutations in mCRC1 91.1% G12C G12D of patients with KRAS mutations miss out on G12V targeted therapy KRAS Wild Type G13D G12S G12A Q61H G13C 1. Jones R et al. Br J Cancer. 2017 Mar 28;116(7):923-929 13
Slide 14: Gaps in KRAS-mutated mCRC therapies leave a significant unmet need
Gaps in KRAS-mutated mCRC therapies leave a significant unmet need KRAS Mutations in mCRC1 Cell nucleus DOWNSTREAM G12C G12D Onvansertib S G2 Addresses all KRAS PLK1 mutations because PLK1 G1 M activation is downstream CRAF G12V of RAS P KRAS Wild Type G13D RAS RAF MEK ERK G12S MUTATIONS G12A P P P
Slide 15: Our Ph 1b/2 trial in KRAS-mutated mCRC combines onvansertib w/ SoC
Our Ph 1b/2 trial in KRAS-mutated mCRC combines onvansertib w/ SoC 2nd-Line SoC: FOLFIRI + bevacizumab One Cycle = 28 Days WEEKS 1−2 6 7 8 9 10 11 12 13 14 O N VA N S E R T I B 2nd-Line SoC: FOLFIRI + bevacizumab WEEKS 3−4 20 21 22 23 24 25 26 27 28 O N VA N S E R T I B 15
Slide 16: End-points measured tumor response and KRAS mutations
End-points measured tumor response and KRAS mutations 2nd-Line SoC: FOLFIRI + bevacizumab One Cycle = 28 Days WEEKS 1−2 6 7 8 9 10 EFFICACY END POINTS 11 12 13 14 O N VA N S E R T I B Objective Response Rate (ORR) in 2nd-Line SoC: FOLFIRI 1 patients who receive ≥1 cycle of treatment + bevacizumab Pr
Slide 17: End-points measured tumor response and KRAS mutations
End-points measured tumor response and KRAS mutations 2nd-Line SoC: FOLFIRI + bevacizumab One Cycle = 28 Days WEEKS 1−2 6 7 8 9 10 11 SUMMARY AT JULY 2, 20211 12 13 14 O N VA N S E R T I B PHASE 1b PHASE 2 2nd-Line SoC: FOLFIRI JAN APR JUL + bevacizumab 12 mg/m2 5 WEEKS 3−4 1520 212 mg/m 22 23 16 RP
Slide 18: End-points measured tumor response and KRAS mutations
End-points measured tumor response and KRAS mutations 2nd-Line SoC: FOLFIRI HISTORICAL ORR* + beacizumab One Cycle = 28 Days 5% 2006 – 2008 WEEKS 1−2 6 7 8 PROOF OF CONCEPT CRITERIA 9 10 11 12 13 14 O N VA N S E R T I B 11.4% 2000 – 2013 13% 2015 – 2017 2nd-Line SoC: FOLFIRI + beacizumab 20% ORR WEE
Slide 19: End-points measured tumor response and KRAS mutations
End-points measured tumor response and KRAS mutations 2nd-Line SoC: FOLFIRI HISTORICAL ORR* + beacizumab One Cycle = 28 Days 5% 2006 – 2008 WEEKS 1−2 6 7 8 9 RESULTS AT JULY 2, 2021 10 11 12 13 14 O N VA N S E R T I B 11.4% 2000 – 2013 13% 2015 – 2017 2nd-Line SoC: FOLFIRI + beacizumab 20% 31% 37% O
Slide 20: Our clinical data indicates that onvansertib is well tolerated
Our clinical data indicates that onvansertib is well tolerated GRADE GRADE No unexpected toxicities TEAEs* All 1 2 3 4 TEAEs* All 1 2 3 4 • Of all TEAEs, only 10% (49/490) Fatigue 28 12 3 13 0 Hypertension 8 2 4 2 0 were G3/G4 • Only 2/16 had neutropenia after Neutropenia 25 1 11 8 5 Vomiting 8 4 3
Slide 21: In the clinic, onvansertib safely and effectively raised response rates
In the clinic, onvansertib safely and effectively raised response rates HISTORICAL ORR SoC ORR* vs. Onvansertib+SoC over time 40% 37% RP2D 7 of 19 5% 2006 – 2008 ALL DOSES 31% 10 of 32 30 11.4% 2000 – 2013 20 13% 11.4% 10 13% 2015 – 2017 5% 2008 ‘09 ‘10 ‘11 ‘12 ‘13 ‘14 ‘15 ‘16 ‘17 ‘18 ‘19 ‘20 2021 2
Slide 22: Across all doses we observe initial PRs up to six months on treatment
Across all doses we observe initial PRs up to six months on treatment SoC vs. Onvansertib+SoC* 31% ALL DOSES 10 of 32 13% 11.5% 5% 2008 ‘13 ‘17 ‘21† †confirmed PRs as of 08-Sept-21 * 2008: Bennouna et al., Lancet Oncol 2013; 14: 29–37; 2013: Giessen et al., Acta Oncologica, 2015, 54: 187-193; 2017:
Slide 23: Across all doses we observe initial PRs up to six months on treatment
Across all doses we observe initial PRs up to six months on treatment KRAS Mutations in mCRC1 Onvansertib responses across KRAS mutations KRAS G12C Variant PR SD PD Total G12D G12D 3 4 1 8 G12V 1 5 6 G13D 2 2 4 G12V G12A 3 1 4 A146T 2 2 4 G13D G12S 3 3 G12S G12A G12C 1 1 2 Q61H G13C Q61H 1 1 Total 1
Slide 24: Onvansertib's median PFS nearly doubles historical SoC
Onvansertib’s median PFS nearly doubles historical SoC Progression-Free Survival SoC vs. Onvansertib+SoC* Months 0 5 10 2008 5.7 Median PFS 2013 4.5 2017 5.6 9.4 Onvansertib 9.4 * 2008: Bennouna et al., Lancet Oncol 2013; 14: 29–37; 2013: Giessen et al., Acta Oncologica, 2015, 54: 187-193; 2017: Cre
Slide 25: At RP2D we observe initial responses up to six months on treatment
At RP2D we observe initial responses up to six months on treatment SoC vs. Onvansertib+SoC* 37% RP2D 7 of 19† 13% 11.5% 5% 2008 ‘13 ‘17 ‘21 † confirmed RP2D PRs as of 08-Sept-21 * 2008: Bennouna et al., Lancet Oncol 2013; 14: 29–37; 2013: Giessen et al., Acta Oncologica, 2015, 54: 187-193; 2017: Cre
Slide 26: Onvansertib's response rate has been consistent over time
Onvansertib’s response rate has been consistent over time Onvansertib+SoC ORR, Sep 8, 2020−Jul 2, 2021 36% 37% ALL DOSES 33% RP2D 7 of 19† 4 of 11 6 of 18 31% ALL DOSES 10 of 32 Historical SoC* ORR 13% 11.5% 5% Sep 8 Apr 4 July 2 2008 ‘13 ‘17 Oct Jan Apr Jul Oct DETAIL 2020 2021 † confirmed PRs as o
Slide 27: WHY Onvansertib works
WHAT Onvansertib has achieved WHY Onvansertib works WHERE Cardiff Oncology can go 27
Slide 28: To date, toxicity has prevented regulatory approval of PLK1 inhibitors
To date, toxicity has prevented regulatory approval of PLK1 inhibitors Onvansertib Volasertib1 Onvansertib’s Pan-inhibitor for Selectivity for PLK1 Exclusive safety profile PLK1, 2, and 3 eclipses that of its most Dosing Oral IV promising predecessor Half-life 1 day ~5 days Safety and tolerability W
Slide 29: Onvansertib's PLK1 inhibition is a two-pronged attack of tumor cells
Onvansertib’s PLK1 inhibition is a two-pronged attack of tumor cells KRAS HYPERSENSITIVITY1 SYNERGY WITH CHEMO Cells with KRAS mutation are Inhibiting PLK1 increases the hypersensitive to inhibition of PLK1 efficacy of chemotherapy drugs PLK1 S G2 KRAS KRAS Wild-type Mutant 57.1% 42.9% G1 M 1. Jones
Slide 30: Onvansertib's PLK1 inhibition is a two-pronged attack of tumor cells
Onvansertib’s PLK1 inhibition is a two-pronged attack of tumor cells KRAS HYPERSENSITIVITY1 120 Cell viability relative to DMSO Cells with KRAS mutation are hypersensitive to inhibition of PLK1 100 P<0.0001 80 60 KRAS KRAS Wild-type Mutant KRAS 40 wild-type 57.1% 42.9% 20 KRAS mutant 0 0 25 50 100 2
Slide 31: Onvansertib's PLK1 inhibition is a two-pronged attack of tumor cells
Onvansertib’s PLK1 inhibition is a two-pronged attack of tumor cells KRAS HYPERSENSITIVITY1 SYNERGY WITH CHEMO Cells with KRAS mutation are Inhibiting PLK1 increases the hypersensitive to inhibition of PLK1 efficacy of chemotherapy drugs PLK1 S G2 KRAS KRAS Wild-type Mutant 57.1% 42.9% G1 M 31
Slide 32: Chemotherapy drugs damage tumor DNA to prevent cell proliferation
Chemotherapy drugs damage tumor DNA to prevent cell proliferation FOLFIRI induces DNA damage DNA REPLICATION PHASE PLK1 Irinotecan S G2 PL K1 TUMOR CELL CYCLE G1 M 32
Slide 33: PLK1's "virtuous" repair of DNA interferes with chemotherapy drugs
PLK1’s “virtuous” repair of DNA interferes with chemotherapy drugs FOLFIRI induces DNA damage DNA REPLICATION PHASE CELL GROWTH PHASE PLK1 Irinotecan S G2 PL K1 PLK1 repairs DNA enabling progression to G2 TUMOR CELL CYCLE G1 M 33
Slide 34: Inhibiting PLK1 prevents DNA repair and halts the cell cycle
Inhibiting PLK1 prevents DNA repair and halts the cell cycle Onvansertib inhibits PLK1 preventing DNA repair CELL GROWTH PHASE PLK1 S G2 PL K1 TUMOR CELL CYCLE G1 M 34
Slide 35: Inhibiting PLK1 prevents DNA repair and halts the cell cycle
Inhibiting PLK1 prevents DNA repair and halts the cell cycle Onvansertib inhibits PLK1 preventing DNA CELL GROWTH PHASE repair and progression from G2 to M PLK1 S G2 PL K1 TUMOR G2/M CELL CYCLE CHECKPOINT G1 M 35
Slide 36: Combined, onvansertib and irinotecan are profoundly more effective
Combined, onvansertib and irinotecan are profoundly more effective Onvansertib + Irinotecan in HCT116 model 3 Tumor volume (cm3) 2.5 Vehicle 2 Onvansertib (45 mg/kg) 1.5 Irinotecan (10 mg/kg) 1 Onvansertib 0.5 + Irinotecan 0 TREATMENT 14 0 10 20 30 40 Days 36
Slide 37: Combined, onvansertib and 5-FU are profoundly more effective
Combined, onvansertib and 5-FU are profoundly more effective Onvansertib + 5-FU in HCT116 model Vehicle Tumor volume (mm3) 1600 Onvansertib (45 mg/kg) 1200 5-FU (40 mg/kg) 800 Onvansertib + 5-FU 400 0 TREATMENT 12 0 10 20 30 Days 37
Slide 38: WHERE Cardiff Oncology can go
WHAT Onvansertib has achieved WHY Onvansertib works WHERE Cardiff Oncology can go 38
Slide 39: Onvansertib's MOA allows combinations with current therapies
Onvansertib’s MOA allows combinations with current therapies DNA DAMAGING AGENTS Inhibit the ability of PLK1 to repair DNA CHEMOTHERAPY PARP INHIBITORS mCRC Phase 1b/2 Trial mPDAC Phase 2 Trial S G2 mCRPC TUMOR Ovarian CELL CYCLE Breast SCLC G1 M Medulloblastoma = Cardiff Oncology potential 39
Slide 40: Onvansertib's MOA allows combinations with current therapies
Onvansertib’s MOA allows combinations with current therapies DNA DAMAGING AGENTS Inhibit the ability of PLK1 to promote progression to M phase RADIATION mCRC mPDAC S G2 mCRPC TUMOR PLK1 Ovarian CELL CYCLE Breast SCLC G1 M Medulloblastoma = Cardiff Oncology potential 40
Slide 41: Onvansertib's MOA allows combinations with current therapies
Onvansertib’s MOA allows combinations with current therapies MICROTUBULE TARGETING AGENTS Inhibit the ability of PLK1 to promote cell division DISRUPT FREEZE DISCONNECT S G2 mCRC TUMOR CELL CYCLE mPDAC mCRPC Phase 2 Trial G1 M Ovarian Disrupt Breast Freeze SCLC Disconnect PLK1 Medulloblastoma Facili
Slide 42: Onvansertib's MOA allows combinations with current therapies
Onvansertib’s MOA allows combinations with current therapies EPIGENETICS Inhibit PLK1’s promotion to M and increase tumor cell’s vulnerability to G2/M arrest LSD1 INHIBITORS mCRC mPDAC S G2 mCRPC TUMOR PLK1 Ovarian CELL CYCLE Breast SCLC G1 M Medulloblastoma = Cardiff Oncology potential 42
Slide 43: Collectively, Cardiff Oncology has many attractive options
Collectively, Cardiff Oncology has many attractive options DNA DAMAGING AGENTS MICROTUBULE TARGETING EPIGENETICS PARP CHEMOTHERAPY INHIBITORS RADIAT’N DISRUPT FREEZE DISCONNECT LSD1 INHIBITORS mCRC Phase 1b/2 Trial mPDAC Phase 2 Trial mCRPC Phase 2 Trial Ovarian Breast SCLC Medullo- blastoma = Cardi
Slide 44: Our pipeline opens many attractive opportunities for onvansertib
Our pipeline opens many attractive opportunities for onvansertib Preclinical IND En. Ph 0/1 Ph 2 Status mCRC FOLFIRI/bev Enrolled mPDAC Onivyde/5-FU Enrolling mCRPC Abiraterone Enrolling Partners PDAC Biomarker Target Q4, ’21 TNBC Combo w/ Paclitaxel Development SCLC Single agent Development CMML Si
Slide 45: Catalysts over the next twelve months
Catalysts over the next twelve months 2022 CLINICAL PROGRAMS Early 2022 OTHER COMBINATIONS mCRC Phase 2 data release • Ovarian cancer with PARPi • Breast cancer with paclitaxel Mid 2022 • Medulloblastoma with mCRC Launch pivotal trial radiation (pediatric) PDAC Phase 2 data release mCRPC Phase 2 dat
Slide 46: Cardiff Oncology at a glance
Cardiff Oncology at a glance Clinical-stage biotech Exchange Nasdaq: CRDF company developing onvansertib, an oral, highly- Cash, Cash Equivalents and Investments1 $134.0M selective Polo-Like Kinase 1 (PLK1) inhibitor, to treat Cash used in Operating Activities1 (9/30/21 YTD) $15.7M cancers with the
Slide 47: Appendix
APPENDIX 47
Slide 48: Most common Treatment-Emergent Adverse Events (TEAEs)
Most common Treatment-Emergent Adverse Events (TEAEs) GRADE GRADE TEAEs* All 1 2 3 4 TEAEs* All 1 2 3 4 Fatigue 28 12 3 13 0 Hypertension 8 2 4 2 0 Neutropenia 25 1 11 8 5 Vomiting 8 4 3 1 0 Nausea 22 15 5 2 0 Headache 6 6 0 0 0 Abdominal pain 16 9 5 2 0 Neuropathy 6 5 1 0 0 Diarrhea 16 8 6 2 0 ALT
Slide 49: Progression-Free- and Overall-Survival has ranged from 4.5-5.7 mo.
Progression-Free- and Overall-Survival has ranged from 4.5−5.7 mo. HISTORICAL REFERENCE PFS OS PROOF OF CONCEPT CRITERIA 5.7 11.2 ML18147 Phase 3 Registrational Trial FOLFIRI + bev in second-line1 4.5 11.5 Systematic Literature-Based Analysis of 23 Randomized Trials (10,800 Patients) in Second-Line
Slide 50: Progression-Free- and Overall-Survival has ranged from 4.5-5.7 mo.
Progression-Free- and Overall-Survival has ranged from 4.5−5.7 mo. HISTORICAL REFERENCE PFS OS ML18147 Phase 3 Registrational Trial FOLFIRI RESULTS AT JULY 2, 2021 5.7 11.2 + bev in second-line1 4.5 11.5 Systematic Literature-Based Analysis of 23 Randomized Trials (10,800 Patients) in Second-Line mC
Slide 51: Onvansertib's response rate has been consistent over time
Onvansertib’s response rate has been consistent over time PRs at and after Cutoff Dates Onvansertib ORR, Sep 8, 2020−Jul 2, 2021 2020 2021 36% 37% ALL DOSES 33% Sep 8 Apr 4 Jul 2 Jul 2 31% All Doses All Doses All Doses P2RD 5 of 11 7 of 18 12 of 32 8 of 191 Initial 45% 39% 38% 42% 4 of 11 4 of 18 6
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