Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (November 2020)
45 slides from Cardiff Oncology's investor presentation, November 2020
Slide 1: Turning the Tide on Cancer
Turning the Tide on Cancer November 2020
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 Integrated Biomarker Diversified Pipeline Across Oral PLK1 Inhibitor KRAS-mutated mCRC Strategy Numerous Cancers Onvansertib overcomes the Supported by compelling preliminary Circulating Tumor DNA: changes in Clinical data fr
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 2020 Corporation Presentation I 4
Slide 5: Pipeline and Upcoming Catalysts
Pipeline and Upcoming Catalysts Indication Preclinical Phase 1b Phase 2 Next Milestone Onvansertib + FOLFIRI/Avastin® in Second-Line KRAS- Q1 2021 mCRC Mutated Metastatic Colorectal Cancer ASCO-GI Onvansertib Solid Tumor Programs Onvansertib + Zytiga® (abiraterone)/prednisone in Zytiga-Resistant Q1
Slide 6: Onvansertib
Onvansertib 3rd generation, 1st in class, oral and highly selective PLK1 inhibitor addressing unmet needs across a broad range of cancer indications
Slide 7: 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 8: 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 9: 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® (paciltaxel) (bevacizumab) Demon
Slide 10: 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 Clinic Cancer Centers Principal Investigator: Dr. Heinz-Josef Lenz
Slide 11: 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 12: 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 13: 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 Colorectal cancer patients who Denotes combination receive second line therapy with bevacizumab Denotes combination
Slide 14: New Second-line mCRC Treatment is an Unmet Need
New Second-line mCRC Treatment is an Unmet Need Outcomes for patients in the 2nd line setting is poor • Efficacy of FOLFIRI: 4% ORR and 2.5 months PFS1 • Addition of bevacizumab to FOLFIRI improves outcomes2 • However, while KRAS WT patients benefit from the addition of bevacizumab, there was no sta
Slide 15: Magnitude of Response with Other Antiangiogenic Therapy
Magnitude of Response with Other Antiangiogenic Therapy The anti-angiogenic agents aflibercept and ramucirumab have been approved in combination with chemotherapy in 2nd-line treatment, although they are used to a much lesser extent than bevacizumab Trial Agent/ARM Patients ORR 95% CI of ORR (%) VEL
Slide 16: 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 17: 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 18: 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) Synergy in Combination with Irinotecan Synergy in Combination with 5-FU 2020 Corporation Presentation I 18
Slide 19: PLK1 Regulates DNA Damage Response
PLK1 Regulates DNA Damage Response1,2 DNA Damaging Mitosis G2/M Arrest Agents 1. Checkpoint adaptation DNA Damage 2. PLK1 inhibits DDR, induces Response mitotic entry for tumor cells (DDR) arrests cells & cell division at G2/M checkpoint Cell Death • Irinotecan 1. Keeps tumor cells in G2/M arrest le
Slide 20: 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 21: Response to Treatment Confirmed by Radiographic Scan
Response to Treatment Confirmed by Radiographic Scan Compelling Preliminary Efficacy Data Best Radiographic Response • 10 of 11 (91%) patients had clinical benefit: - 5 (45%) patients achieved a partial response (PR) - 4 patients had a confirmed PR (≥ 30% tumor shrinkage) with 1 patient going on to
Slide 22: Response to Treatment Confirmed by Progression-Free Survival
Response to Treatment Confirmed by Progression-Free Survival Durability of Response Response Appears Durable ks ks ks s ks ASCO data ks ee ee ee ek ee wee w w w 0 we w • 8 (73%) patients had durable 01-006 8 16 24 32 4 48 ASCO to present 01-007 Treatment ongoing responses of >6 months (range 6 01-00
Slide 23: Serial Monitoring of KRAS is Predictive of Radiographic Scan Response
Serial Monitoring of KRAS is Predictive of Radiographic Scan Response Monitoring KRAS mutations in plasma ctDNA may % KRAS MAF Changes % KRAS MAF Changes After Cycle 1 enable rapid predictions of therapeutic response After Cycle 1 • KRAS mutant allelic frequency (MAF) was measured by PR SD PD digita
Slide 24: KRAS-Mutated mCRC Expanded Access Program (EAP)
KRAS-Mutated mCRC Expanded Access Program (EAP) • Program initiated in June 2020 • 15 sites participating across the US as of October 30 • Eligibility criteria includes: – Patients not meeting clinical trial inclusion criteria – Patients who have received 2 or more lines of prior treatment – Patient
Slide 25: Catalysts and Milestones: KRAS-Mutated mCRC
Catalysts and Milestones: KRAS-Mutated mCRC Positive Phase 1b/2 results may provide an opportunity for a Phase 2b registrational trial Q1 2021: FDA meeting to May 2020: Fast Track September 2020: ESMO January 2021: ASCO-GI discuss regulatory path Designation presentation data presentation (planned)
Slide 26: 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 Principal Investigator: Dr. David Einstein
Slide 27: New Therapeutic Options are Needed to Overcome Resistance to SOC Androgen Receptor Signaling Inhibitors
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 28: 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 29: Phase 2 Open Label Trial of Onvansertib + Abiraterone
Phase 2 Open Label Trial in of Onvansertib + Abiraterone Disease Control Assessed by PSA Stabilization Trial Design: Dosing Schedule Duration Efficacy Endpoint Cohort A (n = 24) Disease Control Onvansertib 24mg/m2 Days 1-5 (21-day cycle) + Zytiga® (Abiraterone) 4 Cycles = 12 Weeks Cohort Closed (PSA
Slide 30: Patient Baseline Characteristics and Enrollment Status
Patient Baseline Characteristics and Enrollment Status Patient Baseline Characteristics Enrollment as of October 16th, 2020 Total patients N=39 Median [range] or n (%) Number of patients (N) Arm A Arm B Arm C Age in Years 72 [54-87] Treated 24 11 4 Nonwhite Ethnicity 5 (13%) Currently on Treatment 1
Slide 31: Phase 2 Data Demonstrate the Safety and Efficacy of Onvansertib in mCRPC
Phase 2 Data Demonstrate the Safety and Efficacy of Onvansertib in mCRPC Safety Assessment Efficacy Evaluation at 12-Weeks Adverse events Grade 1 Grade 2 Grade 3 Grade 4 All grades Total Patients Evaluable N=29 Arm A Arm B Arm C Total Patients N=39 Anemia 10 5 1 16 Evaluable for efficacy* 17 9 3 Thr
Slide 32: Phase 2 Data Demonstrate the Efficacy and Durability of Response Including Patients with AR Alterations
Phase 2 Data Demonstrate the Efficacy of Onvansertib and and Durability of Response Including Patients with AR Alterations Treatment Response and Duration for Patients Completing 12 Weeks of Treatment hs hs hs a r ont ont ont ar ye Arm C (14+7) Efficacy in patients with AR alterations: 3 m 6 m 9 m 1
Slide 33: 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 34: Identifying an Onvansertib-Abiraterone Response Gene Signature
Identifying an Onvansertib-Abiraterone Response Gene Signature Onvansertib/Abiraterone • Synergy study Abiraterone induces expression of Identification of an • RNA-sequencing mitotic genes in prostate cancer Abi/Onv synergy gene signature cells synergistic for Onv+Abi Identified 4 molecular subtypes
Slide 35: Catalysts and Milestones: mCRPC
Catalysts and Milestones: mCRPC Positive Phase 2 results may provide an opportunity for a Phase 2b registrational trial October 2020: Prostate February 2021: ASCO-GU April 2021: AACR Q3 2021: FDA meeting to Cancer Foundation (PCF) presentation (planned) presentation (planned) discuss regulatory path
Slide 36: New Clinical Programs Planned
New Clinical Programs Planned Chronic Myelomonocytic Leukemia (CMML) Pancreatic Ductal Adenocarcinoma (PDAC)
Slide 37: Phase 2 Study to Evaluate the Safety and Efficacy 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 pathway Activating RAS Pathway Can Be Therapeutically mutations such as NRAS, KRAS, CBL, PTPN11 and NF1, Targeted with PLK1 Inhibitors all o
Slide 38: 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 overall response rate (ORR) of onvansertib, a novel oral PLK1 inhibitor in RAS- pathway mutant chronic myelomonocytic leukemia Trial Design: Dosing Schedule Duration Efficacy Endpoint
Slide 39: Phase 2 Study of Onvansertib in Combination with 5-FU and Nal-IRI for Second Line Treatment of KRAS-Mutated PDAC
Phase 2 Study of Onvansertib in Combination with 5-FU and Nal-IRI for Second Line Treatment of KRAS-Mutated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Study Rationale • KRAS is the most common oncogene mutated in Mutant KRAS is Essential for PDAC Growth – Activated RAS Proteins Contribute to
Slide 40: Phase 2 Open Label Trial of Onvansertib + 5-FU and Nanoliposomal Irinotecan in KRAS-Mutated PDAC
Phase 2 Open Label Trial of Onvansertib + 5-FU and Nanoliposomal Irinotecan in KRAS-Mutated PDAC Trial Design (~40 patients): 1 CYCLE = 14 Days Treatment Course (Days) 1 2 3 4 5 6 - 14 Onvansertib 15 mg/m2 5-FU + Nanoliposomal Irinotecan (nal-IRI) Eligibility Criteria • Prior abraxane/gemcitabine an
Slide 41: Corporate
OS cardiff Oncology: Corporate
Slide 42: 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 43: 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 44: Investment Highlights
Investment Highlights 3rd Generation, 1st-in-class, Strong Lead Program in Integrated Biomarker Diversified Pipeline Across Oral PLK1 Inhibitor KRAS-mutated mCRC Strategy Numerous Cancers Onvansertib overcomes the Supported by compelling preliminary Circulating Tumor DNA: changes in Clinical data fr
Slide 45: Thank You
Thank You for more information contact: ir@cardiffoncology.com
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