Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (February 2021)
48 slides from Cardiff Oncology's investor presentation, February 2021
Slide 1: Turning the Tide on Cancer
Turning the Tide on Cancer February 2021
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: Investment Highlights
Investment Highlights 3rd Generation, 1st-in-class, Strong Lead Program in Diversified Pipeline Across Integrated Biomarker Oral PLK1 Inhibitor KRAS-mutated mCRC Numerous Cancers Strategy Onvansertib overcomes the Supported by compelling preliminary Clinical data from ongoing trials Circulating Tumo
Slide 4: Experienced Management Team With Drug Development and Biomarker Technology Expertise
Experienced Management Team With Drug Development and Biomarker Technology Expertise Mark Erlander, PhD Vicki Kelemen Chief Executive Officer Chief Operating Officer Brigitte Lindsay Vice President of Finance 2021 Corporation Presentation I 4
Slide 5: Onvansertib
Onvansertib 3rd generation, 1st in class, oral and highly selective PLK1 inhibitor addressing unmet needs across a broad range of cancer indications
Slide 6: PLK1 is a Proven Therapeutic Target that is Overexpressed in Most Cancers
PLK1 is a Proven Therapeutic Target that is Overexpressed in Most Cancers • PLK1 is a serine/threonine kinase and master regulator of cell-cycle progression • PLK1 controls G2/mitosis (G2/M) checkpoint • Inhibition of PLK1 causes mitotic arrest and subsequent cell death • Emerging data demonstrate t
Slide 7: PLK1-Specific ATP Competitive Inhibitor
PLK1-Specific ATP Competitive Inhibitor1 Biochemical Profile Profile Characteristics Co-crystal of Onvansertib with PLK1 Enzyme IC50 (μM) Small Molecule MW 648.60 Daltons PLK1 0.002 Formulation 5mg and 20mg oral gelcaps Plasma Protein 95% at 10μM and 91% at 50μM PLK2 >10 Binding PLK3 >10 Moderate in
Slide 8: Onvansertib has Optimal Drug Properties and Synergistically Combines with Standard-of-Care Therapies
Onvansertib has Optimal Drug Properties and Synergistically Combines with Standard-of-Care Therapies Synergistic in Combination with Standard-of- Optimal Drug Properties Care Chemo and Targeted Therapies High Selectivity Zytiga® For PLK1 (abiraterone) Taxol® Avastin® (paclitaxel) (bevacizumab) Demon
Slide 9: Second-Line Treatment of KRAS-Mutated mCRC
Second-Line Treatment of KRAS-Mutated mCRC Phase 1b/2 open-label trial of onvansertib + FOLFIRI/bevacizumab Trial Sites: USC Norris Comprehensive Cancer Center; Mayo Clinics (Arizona, Minnesota, Florida), Kansas University Medical Center, CARTI Cancer Center, Inova Schar Cancer Institute Principal I
Slide 10: New Second-Line Therapies are Needed to Improve Response and Increase Progression-Free Survival
New Second-Line Therapies are Needed to Improve Response and Increase Progression-Free Survival 50% of patients with mCRC Prognosis is poor with a five- Other drugs currently in development have a KRAS mutation year survival rate of 10% do not address the most prevalent KRAS mutations in mCRC 4% Res
Slide 11: KRAS is a Pivotal Diagnostic Biomarker in the CRC Treatment Paradigm
KRAS is a Pivotal Diagnostic Biomarker in the CRC Treatment Paradigm • KRAS-mutated patients do not benefit from anti-EGFR agents: – No increase in OS, PFS and ORR was observed in KRAS mutant patients treated with EGFR inhibitors vs control arm1,2 – The use of anti-EGFRs is therefore limited to KRAS
Slide 12: Second-line Treatment: Real World Utilization in the US
Second-line Treatment: Real World Utilization in the US Flatiron Health Data 255 Cancer clinics representing 1.7 million active cancer patients 14,315 Colorectal cancer patients 7,034 Denotes combination Colorectal cancer patients who with bevacizumab receive second line therapy Denotes combination
Slide 13: FDA Approved Standard-of-Care, FOLFIRI + Bev, has an ORR of 5% and PFS of 5.7 Months
FDA Approved Standard-of-Care, FOLFIRI + Bev, has an ORR Rate of 5% and PFS of 5.7 months in Pivotal Trial Used for Registration Outcomes for patients in the 2nd line setting is poor • Addition of bevacizumab to FOLFIRI improves outcomes1 • While KRAS WT patients benefit from the addition of bevaciz
Slide 14: Synthetic Lethality: Cells with KRAS Mutations are Hypersensitive to Inhibition of PLK1
Synthetic Lethality: Cells with KRAS Mutations are Hypersensitive to Inhibition of PLK1 The output of the RAS-mutated pathway activates PLK1, which is inhibited by onvansertib Onvansertib Addresses KRAS Mutation Cell Viability in Onvansertib-Treated KRAS Mutant Subtypes in mCRC and Wild Type Isogeni
Slide 15: PLK1 and RAS Cooperative Relationship
PLK1 and RAS Cooperative Relationship RAS RAS activates PLK1 through a MEK/ERK-independent mechanism RAF Onvansertib P P The downstream target of KRAS, pCRAF, localizes to the mitotic P CRAF PLK1 spindle poles at mitosis where it interacts with PLK1 and promotes MEK PLK1 activation, leading to mitos
Slide 16: Synergy: Onvansertib in Combination with SOC Irinotecan and 5-FU
Synergy: Onvansertib in Combination with SOC Irinotecan and 5-FU Onvansertib works synergistically in combination with standard-of-care FOLFIRI (irinotecan and 5-FU) HCT-116 (with G13D KRAS mutation) Synergy in Combination with Irinotecan Synergy in Combination with 5-FU 2021 Corporation Presentatio
Slide 17: PLK1 Regulates DNA Damage Response
PLK1 Regulates DNA Damage Response1,2 DNA Damaging Mitosis G2/M Arrest Agents 1. Checkpoint adaptation 2. PLK1 inhibits DDR, induces DNA Damage mitotic entry for tumor cells Response & cell division (DDR) arrests cells at G2/M checkpoint Cell Death • Irinotecan 1. Keeps tumor cells in G2/M arrest le
Slide 18: Phase 1b/2 Open Label Trial of Onvansertib + FOLFIRI/bevacizumab
Phase 1b/2 Open Label Trial of Onvansertib + FOLFIRI/bevacizumab Trial Design 1 CYCLE = 28 Days Treatment Course = 14 Days Treatment Course = 14 Days 1 2 3 4 5 6 - 14 1 2 3 4 5 6 - 14 Onvansertib Onvansertib FOLFIRI + bevacizumab FOLFIRI + bevacizumab Efficacy Endpoints What is Clinical Trial Succes
Slide 19: Phase 1b Enrollment and Patient Baseline Characteristics
Phase 1b Enrollment and Patient Baseline Characteristics Dose Escalation Patient Cohorts Total Patients N=18 Median [range] or n (%) Age (years) 59 [37-83] (as of 06-Jan-2021) Sex Dose Level 0 Dose Level +1 Dose level +2 Male 8 (44%) Number of Female 10 (56%) Onvansertib Onvansertib Onvansertib Pati
Slide 20: Phase 1b Safety Assessment
Phase 1b Safety Assessment Most Common Treatment-Emergent AEs Adverse Events (AEs) Grade Grade Grade Grade All • 5 patients had G4 adverse events: 1 2 3 4 Grades – 1 patient had a G4 neutropenic fever at dose level 12 mg/m2 Fatigue 4 7 1 0 12 – 1 patient had a G4 neutropenia at dose level 15 mg/m2 N
Slide 21: Phase 1b Preliminary Efficacy
Phase 1b Preliminary Efficacy Treatment Response and Duration Changes in Tumor Size From Baseline (as of 06-Jan-2021) 01-003 ks → Treatment ongoing ks ks ks eeks eks ks 100 ks ee wee wee ee wee w 0 w we w wee 02-004 8 16 24 32 4 48 56 64 80 Reason for discontinuation lesions from baseline 01-007 PD
Slide 22: KRAS Mutant Allelic Frequency (MAF) Biomarker Analyses
KRAS Mutant Allelic Frequency (MAF) Biomarker Analyses % KRAS MAF Decrease Following 1 Cycle of Treatment • KRAS MAF was measured by digital droplet PCR (ddPCR) at baseline (Cycle 1 Day 1, pre-dose) and on-treatment PR SD PD (Day 1 of Cycles 2 to 9) 0 Cycle 2 Day 1 from baseline % change in KRAS MAF
Slide 23: Conclusions
Conclusions • Safety Assessment: – The combination of onvansertib and FOLFIRI/Bev is well-tolerated – Onvansertib RP2D was established at 15 mg/m2 • Preliminary Efficacy: – 12 of 14 (86%) patients evaluable for efficacy achieved a clinical benefit (SD + PR) – 5 (36%) patients achieved a partial resp
Slide 24: Catalysts and Milestones: KRAS-Mutated mCRC
Catalysts and Milestones: KRAS-Mutated mCRC Fast Track Designation enables more frequent interaction with the FDA and facilitates an accelerated clinical development pathway May 2020: Fast Track January 2021: ASCO-GI Q2 2021: FDA End of Phase ESMO 2021: ESMO mCRC Designation Granted by FDA virtual p
Slide 25: Second-Line Treatment of Metastatic PDAC
Second-Line Treatment of Metastatic PDAC Phase 2 open label trial of onvansertib + nanoliposomal irinotecan, 5-FU and leucovorin Trial Sites: Mayo Clinics (Arizona, Minnesota, Florida), Emory University, Kansas University Medical Center and Inova Schar Cancer Institute Principal Investigator: Dr. Da
Slide 26: New Second-Line Therapies are Needed for Metastatic PDAC Patients
New Second-Line Therapies are Needed for Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Patients Second-line treatment with SOC Second-line treatment with SOC Mutant KRAS contributes to irinotecan + 5-FU/leucovorin has a irinotecan + 5-FU/leucovorin offers treatment resistance and metastases res
Slide 27: Phase 2 Open Label Trial of Onvansertib + Nanoliposomal Irinotecan + 5-FU in Metastatic PDAC
Phase 2 Open Label Trial of Onvansertib + Nanoliposomal Irinotecan + 5-FU in Metastatic PDAC Trial Design (~45 patients): 1 CYCLE = 14 Days Treatment Course (Days) 1 2 3 4 5 6 7 8 9 10 11 - 14 Onvansertib 12 mg/m2 Onvansertib to be administered on Days 1-10 (12 mg/m2) based on safety lead-in of 6 pa
Slide 28: Projected Catalysts and Milestones: Metastatic PDAC
Projected Catalysts and Milestones: Metastatic PDAC January 2021: Received January 2022: ASCO-GI April 2022: AACR September 2022: ESMO FDA “Study May Proceed” Phase 2 data presentation biomarker data presentation Phase 2 data presentation 2021 Corporation Presentation I 28
Slide 29: Metastatic Castration-Resistant Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer Phase 2 open-label trial of onvansertib + abiraterone Trial Sites: Beth Israel Deaconess, Dana Farber, Mass General Hospital Principal Investigator: Dr. David Einstein
Slide 30: New Therapeutic Options are Needed to Overcome Resistance to SOC ARSi
New Therapeutic Options are Needed to Overcome Resistance to SOC Androgen Receptor Signaling Inhibitors (ARSi) Resistance develops to treatment with standard ARSi’s offer a median overall survival No effective treatment options are of care ARSi’s within 9-15 months1 (mOS) benefit of only ~4 months1
Slide 31: Onvansertib Extends the Response to Androgen Receptor Signaling Inhibitors
Onvansertib Extends the Response to Androgen Receptor Signaling Inhibitors Onvansertib works synergistically in combination with abiraterone (Zytiga®) and significantly increases mitotic arrest Onvansertib + Abiraterone (Zytiga®) Demonstrate Onvansertib + Abiraterone (Zytiga®) Significantly Synergy
Slide 32: Clinical Trial Background and Rationale
Clinical Trial Background and Rationale • PLK1 - a promising target for prostate cancer: – PLK1 is overexpressed in prostate cancer and linked to higher tumor grades1 – PLK1 inhibition and abiraterone demonstrated synergy in CRPC in vitro and in vivo Synergy In Vitro in C4-2 Cells models: the combin
Slide 33: Phase 2 Trial Design, Objectives and Enrollment (NCT03414034)
Phase 2 Trial Design, Objectives and Enrollment (NCT03414034) Key Eligibility Criteria: Treatment Schedules for Each Study Arm • Initial signs of abiraterone resistance defined as 2 rising Arm A (n=24) Arm B (n=32) Arm C (n=32) PSAs; one rise of ≥0.3 ng/mL (21-day cycle) + Abi (14-day cycle) + Abi (
Slide 34: Baseline Characteristics and Safety
Baseline Characteristics and Safety Baseline Characteristics Safety Assessment Median [range] • Most frequent Grade 3 and 4 adverse events (AEs) were expected, Total patients N=51 on-target, reversible hematological (anemia, neutropenia, or n (%) thrombocytopenia and WBC decrease), associated with t
Slide 35: Efficacy Assessment
Efficacy Assessment Arm A Arm B Arm C (5+16) (5+9) (14+7) s s s Evaluable for efficacy* 17 12 8 th th th ar on on on ar ye 3 m 6 m 9 m ye 1. 5 1 Completed at least 12 weeks of treatment 14 8 6 03-043 → → Ongoing Arm C (14+7) 01-044 → Had radiographic or clinical progression 02-045 → 3 4 2 02-046 → M
Slide 36: Onvansertib-Induced Circulating Tumor Cell Decrease is Associated with Progression-Free Survival
Onvansertib-Induced Circulating Tumor Cell Decrease is Associated with Progression-Free Survival Circulating tumor cell (CTC) count, reported as favorable or unfavorable (<5 versus ≥5 CTC/7.5mL of blood, respectively) is a prognostic factor for survival in CRPC – conversion from unfavorable to favor
Slide 37: Biomarker Analyses
Biomarker Analyses ctDNA Genomic Profiling 33 Patients Analyzed Analysis of Genes Differentially Mutated in SD and PD Patients Mutation profiling of circulating A total of 379 somatic variants 15 patients had PD at or before 18 patients had SD at 12 weeks tumor DNA (ctDNA) isolated from were identif
Slide 38: Identifying an Onvansertib-Abiraterone Response Gene Signature
Identifying an Onvansertib-Abiraterone Response Gene Signature Onvansertib/Abiraterone Abiraterone induces • Synergy study Identification of an expression of mitotic genes • RNA-sequencing Abi/Onv synergy gene signature in prostate cancer cells synergistic for Onv+Abi Identified 4 molecular subtypes
Slide 39: Conclusions
Conclusions • Safety: – Onvansertib + abiraterone demonstrated safety across 3 different dosing schedules: Arm A ( 5 days ON, 16 days OFF), Arm B (5 days ON, 9 days OFF), Arm C (14 days ON, 7 days OFF) • Efficacy: – Arms A (n=17) and B (n=12) showed similar efficacy with 29% and 25% of patients achi
Slide 40: Catalysts and Milestones: mCRPC
Catalysts and Milestones: mCRPC October 2020: Prostate February 2021: ASCO- April 2021: AACR October 2021: Prostate Cancer Foundation (PCF) GU presentation Preclinical data presentation Cancer Foundation (PCF) 2021 Corporation Presentation I 40
Slide 41: New Clinical Programs Planned
New Clinical Programs Planned Chronic Myelomonocytic Leukemia (CMML)
Slide 42: Phase 2 Study of Onvansertib in RAS-Pathway Mutant CMML
Phase 2 Study to Evaluate the Safety and Efficacy of Onvansertib in RAS- Pathway Mutant CMML Study Rationale • Proliferative CMML is enriched for activating RAS Activating RAS Pathway Can Be Therapeutically pathway mutations such as NRAS, KRAS, CBL, PTPN11 Targeted with PLK1 Inhibitors and NF1, all
Slide 43: Phase 2 Two-Arm Randomized Trial of Onvansertib +/- Decitabine in RAS-Pathway Mutated CMML
Phase 2 Two-Arm Randomized Trial of Onvansertib +/- Decitabine in RAS-Pathway Mutated CMML Determine the safety and efficacy of onvansertib, a novel oral PLK1 inhibitor in RAS-pathway mutant chronic myelomonocytic leukemia Trial Design: Dosing Schedule Duration Efficacy Endpoint Two Arms: 3 cycles m
Slide 44: Corporate
Q5 Cardiff Oncology” Corporate
Slide 45: Strong Patent Portfolio
Strong Patent Portfolio Core Technology: 3 Issued Patents Evergreening: Combination Evergreening: Biomarkers to 2030 in US, Europe and Asia, Therapy with anticipated extension to 2035 Method for assessing PLK1 target Exclusive license from MIT for 2 US issued phosphorylation status for identifying C
Slide 46: Cardiff Oncology At-A-Glance
Cardiff Oncology At-A-Glance Exchange Nasdaq: CRDF Clinical-stage biotech company, Cash & Cash Equivalents (as of 10/31/20) $131.8M developing onvansertib, an oral, highly-selective Polo-like Kinase 1 Q1 – Q3, 2020 Average Quarterly Cash Burn $3.8M (PLK1) inhibitor, to treat cancers with the greates
Slide 47: Investment Highlights
Investment Highlights 3rd Generation, 1st-in-class, Strong Lead Program in Diversified Pipeline Across Integrated Biomarker Oral PLK1 Inhibitor KRAS-mutated mCRC Numerous Cancers Strategy Onvansertib overcomes the Supported by compelling preliminary Clinical data from ongoing trials Circulating Tumo
Slide 48: Thank You
Thank You for more information contact: ir@cardiffoncology.com
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