Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (June 2021)
49 slides from Cardiff Oncology's investor presentation, Jun 1, 2021
Slide 1: Turning the Tide on Cancer
Turning the Tide on Cancer June 2021
Slide 2: Forward-looking statements
2021 Corporation Presentation I 2 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 ot
Slide 3: Corporate Overview
Corporate Overview Clinical stage biotech company developing onvansertib, an oral and highly-selective PLK1 inhibitor, to treat cancers with the greatest medical needs for new therapeutic options
Slide 4: Cardiff Oncology At-A-Glance
2021 Corporation Presentation I 4 Clinical-stage biotech company developing onvansertib, an oral, highly-selective Polo-like Kinase 1 (PLK1) inhibitor, to treat cancers with the greatest medical needs for new treatment options Cardiff Oncology At-A-Glance Exchange Nasdaq: CRDF Cash, Cash Equivalents
Slide 5: Investment Highlights and Strategy
2021 Corporation Presentation I 5 Investment Highlights and Strategy Fully leverage onvansertib in combination with targeted therapeutics and chemotherapies across multiple cancer indications MOA: Mechanism of action; mCRC: Metastatic colorectal cancer; ORR: Objective response rate; mPFS: Median pro
Slide 6: Experienced Management Team
2021 Corporation Presentation I 6 Mark Erlander, PhD Chief Executive Officer Vicki Kelemen Chief Operating Officer Experienced Management Team With Drug Development and Biomarker Technology Expertise Brigitte Lindsay Vice President of Finance
Slide 7: Onvansertib
Onvansertib Oral and highly selective PLK1 inhibitor in clinical development across multiple indications: KRAS-mutated metastatic colorectal cancer (mCRC); metastatic pancreatic ductal adenocarcinoma (mPDAC) and metastatic castrate-resistant prostate cancer (mCRPC)
Slide 8: PLK1 is a Proven Therapeutic Target Overexpressed in Most Cancers
2021 Corporation Presentation I 81Zitouni et al., Nat Rev Mol Cell Biol. 2014 Jul;15(7):433-52; PLK1 is a Proven Therapeutic Target that is Overexpressed in Most Cancers Inhibition of PLK1 Causes Mitotic Arrest and Subsequent Cell Death1 • PLK1 is a serine/threonine kinase and master regulator of ce
Slide 9: Onvansertib Overcomes the Shortcomings of Prior PLK Inhibitors
2021 Corporation Presentation I 9 Prior generation PLK inhibitors demonstrated clinical activity but had less than optimal drug properties Onvansertib Overcomes the Shortcomings of Prior PLK Inhibitors Onvansertib Prior PLK Inhibitors Selectivity for PLK1 ✓ ✕ Oral dosing ✓ ✕ Flexible dose and schedu
Slide 10: Summary of Onvansertib Safety and Tolerability Findings
2021 Corporation Presentation I 10 Summary of Onvansertib Safety and Tolerability Findings Combination regimens have been well-tolerated in clinical trials across multiple indications mCRC: Metastatic colorectal cancer; Transient / reversible hematological toxicities (grade 3 or 4; typically resolve
Slide 11: Onvansertib Synergistically Combines with Standard-of-Care Therapies
2021 Corporation Presentation I 11 Onvansertib Synergistically Combines with Standard-of-Care Therapies Zytiga® (abiraterone) Lynparza® (Olaparib)Taxol® (paclitaxel) Venclexta® (venetoclax) Cytarabine DoxorubicinCamptosar ® (irinotecan) Beleodaq® (belinostat) Cisplatin Gemzar® (gemcitabine) 5-FU Vel
Slide 12: Mechanism of Therapeutic Synergy with DNA Damaging Agents
2021 Corporation Presentation I 12 Mechanism of Therapeutic Synergy Between DNA Damaging Agents and Onvansertib DNA Damaging Agents promote cell-cycle arrest in tumors by promoting DNA damage PLK1 promotes the repair of DNA damage DNA Damaging Agents (i.e., irinotecan) Onvansertib Induces Cell Death
Slide 13: KRAS-Focused Clinical Programs
KRAS-Focused Clinical Programs Leveraging the synergy of onvansertib when combined with irinotecan and/or 5-FU
Slide 14: Targeting the Ras Pathway
2021 Corporation Presentation I 14 Targeting the Ras Pathway Targeted Therapies for KRAS-mutant Patients is an Unmet Need 1Hong et al., NEJM 2020; 2Johnson et al., ENA 2020, #LBA-04; 3https://www.revmed.com/pipeline/rmc-4630; mCRC: Metastatic colorectal cancer; ORR: Objective response rate; CRC: Col
Slide 15: Cells with KRAS Mutations are Hypersensitive to PLK1 Inhibition
2021 Corporation Presentation I 15 Cells with KRAS Mutations are Hypersensitive to Inhibition of PLK11 1Luo et al, Cell. 2009; 137 835-48; 2Mielgo et al., Nat. Med. 2011; 17(12):1641-5; PLK1: Polo-like Kinase 1; CRC: Colorectal cancer • RAS activates PLK1 through a MEK/ERK- independent mechanism • D
Slide 16: Onvansertib is Synergistic with Irinotecan and 5-FU
2021 Corporation Presentation I 16 Onvansertib is Synergistic in Combination with Irinotecan and 5-FU Synergistic in combination with Standard-of-Care FOLFIRI (irinotecan and 5-FU) in HCT-116 (with G13D KRAS mutation) Synergy in Combination with Irinotecan Synergy in Combination with 5-FU
Slide 17: Early Decreases in Plasma KRAS Mutational Burden
2021 Corporation Presentation I 17 Patient: 61-year-old female with KRAS G12V metastatic sigmoid colon cancer (EAP Participant) Treatment: Onvansertib + FOLFIRI (irinotecan + 5-FU) + Bevacizumab Early KRAS Decrease: Decrease in KRAS mutational burden following 1 cycle of treatment correlates with su
Slide 18: 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 19: New Second-Line Therapies are Needed
2021 Corporation Presentation I 19 50% of patients with mCRC have a KRAS mutation Prognosis is poor with a five-year survival rate of 10% Other drugs currently in development do not address the most prevalent KRAS mutations in mCRC Historically, second-line SOC treatment in KRAS-mutated mCRC has had
Slide 20: Standard-of-Care Second Line mCRC Benchmarks
2021 Corporation Presentation I 20 13% 11.5 months Not Reported for Second-line 11.2 months Overall Survival (OS) 4.5 months 5.6 months 5.7 months Progression-Free Survival (PFS) 11.4% 5% Objective Response Rate (ORR) Systematic Literature-Based Analysis of 23 Randomized Trials (10,800 Patients) in
Slide 21: KRAS is a Pivotal Diagnostic Biomarker in the CRC Treatment Paradigm
2021 Corporation Presentation I 211Karapetis et al., NEJM 2008;359:1757-1765; 2Amado et al., JCO 2008, 26:1626-1634; CRC: Colorectal cancer; OS: Overall survival; PFS: Progression free survival; ORR: Objective response rate; mCRC: Metastatic CRC; WT: Wild-type KRAS is a Pivotal Diagnostic Biomarker
Slide 22: Trial Design: Phase 1b/2 Onvansertib + FOLFIRI/bevacizumab
2021 Corporation Presentation I 22 Trial Design: Phase 1b/2 Open Label Study of Onvansertib + FOLFIRI/bevacizumab Trial Design Efficacy Endpoints • Objective response rate (ORR) in patients who receive ≥1 cycle of treatment • Progression-free survival (PFS) and duration of response (DOR) • Decreases
Slide 23: Trial Enrollment and Patient Baseline Characteristics
2021 Corporation Presentation I 23mCRC: Metastatic colorectal cancer; RP2D: Recommended Phase 2 dose; ECOG: Eastern Cooperative Oncology Group, Phase 1b/2 KRAS-mutated mCRC Trial Enrollment and Patient Baseline Characteristics Enrollment (as of 04-Apr-2021) Number of Patients (N) Phase 1b, Dose Leve
Slide 24: Trial Safety Assessment
2021 Corporation Presentation I 24n=number of patients (total N=30); mCRC: Metastatic colorectal cancer; AE: Adverse events; WBC=white blood cells; RP2D: Recommended Phase 2 dose; ALT= alanine aminotransferase Phase 1b/2 KRAS-mutated mCRC Trial Safety Assessment Most Common Treatment-Emergent AEs (a
Slide 25: Assessment of Preliminary Efficacy and Duration of Response
2021 Corporation Presentation I 25ORR: Objective response rate; PR: Partial response; PFS: Progression free survival; mPFS: Median PFS; SOC: standard-of-care Assessment of Preliminary Efficacy and Duration of Response 39% (7/18 evaluable patients) ORR 7 PRs observed across 5 different KRAS mutations
Slide 26: Significant Decreases in KRAS Mutational Burden
2021 Corporation Presentation I 26 % KRAS MAF Decrease Following 1 Cycle of Treatment Significant Decreases in KRAS Mutational Burden in Cycle 1 are Predictive of Subsequent Tumor Shrinkage on Radiographic Scan • Clinical responses were observed across KRAS mutations, including the 3 most prevalent
Slide 27: Patient Case Report – Patient 01-019
2021 Corporation Presentation I 27DLT: Dose-limiting toxicity Patient Overview: 83-year-old woman with KRAS G12D metastatic colon cancer Phase 1b/2 Trial Patient Case Report – Patient 01-019 Background Additional Details C1D15 – G4 neutropenia (DLT); treatment was held C3D1 – G3 neutropenia; treatme
Slide 28: Patient Case Report Summary
2021 Corporation Presentation I 28MAF: Mutant Allelic Frequency; SD: Stable disease; PR: Partial response Summary Phase 1b/2 Trial Patient Case Report – Patient 01-019 Response • January 2021 (8-week scan): stable disease [SD] (-16%) with decrease in size of metastatic lesions • March 2021 (16-week
Slide 29: Recent and Upcoming Milestones: KRAS-Mutated mCRC
2021 Corporation Presentation I 29 3 10 17 24 31 4 11 18 25 5 12 19 26 6 13 20 27 7 14 21 28 1 8 15 22 29 2 9 16 23 30 S May 2020 M T W T F S 3 10 17 24 31 4 11 18 25 5 12 19 26 6 13 20 27 7 14 21 28 1 8 15 22 29 2 9 16 23 30 S January 2021 M T W T F S 5 12 19 26 6 13 20 27 7 14 21 28 1 8 15 22 29 4
Slide 30: 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), Kansas University Medical Center, Inova Schar Cancer Institute, University of Nebraska Medical Center Principal In
Slide 31: New Second-Line Therapies Needed for Metastatic PDAC
2021 Corporation Presentation I 31 1Onyvide Package Insert: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207793lbl.pdf; 2Wang-Gillam A, Li C-P, Bodoky G, et al. Lancet 2016;387:545-57. 3Waters AM, Der CJ. Cold Spring Harb Perspect Med 2018;8(9). SOC: Standard-of-care; mOS: Median overal
Slide 32: Trial Design: Phase 2 Onvansertib in Metastatic PDAC
2021 Corporation Presentation I 32PDAC: Pancreatic ductal adenocarcinoma Trial Design: Phase 2 Open Label Study of Onvansertib + Nanoliposomal Irinotecan + 5-FU in Metastatic PDAC Trial Design (~45 patients): Eligibility Criteria • Prior abraxane/gemcitabine and no prior irinotecan, nanoliposomal ir
Slide 33: Upcoming Milestones: Metastatic PDAC
2021 Corporation Presentation I 33PDAC: Pancreatic adenocarcinoma Upcoming Milestones: Metastatic PDAC S Q2/3’2021 M T W T F S Dose first patient 5 12 19 26 6 13 20 27 7 14 21 28 1 8 15 22 29 S September 2022 M T W T F S ESMO Phase 2 data 2 9 16 23 30 3 10 17 24 4 11 18 25 3 10 17 24 31 4 11 18 25 5
Slide 34: Metastatic Castrate-Resistant Prostate Cancer
Metastatic Castrate-Resistant Prostate Cancer Phase 2 open-label trial of onvansertib + abiraterone in abiraterone-resistant mCRPC Trial Sites: Beth Israel Deaconess, Dana Farber, Mass General Hospital Principal Investigator: Dr. David Einstein
Slide 35: New Therapeutic Options Needed to Overcome ARSi Resistance
2021 Corporation Presentation I 35 New treatment options are needed to extend the duration of response to ARSi’s and increase overall survival Limited options for patients once resistant to abiraterone New Therapeutic Options are Needed to Overcome Resistance to SOC Androgen Receptor Signaling Inhib
Slide 36: Onvansertib Extends Response to Androgen Receptor Signaling Inhibitors
2021 Corporation Presentation I 361Patterson & Yaffe, 2019, MIT; 2Weichert et al., Prostate 2004;60(3):240-5; Abi: Abiraterone; CRPC: Castrate-resistant prostate cancer Onvansertib Extends Response to Androgen Receptor Signaling Inhibitors Onvansertib + Abiraterone (Zytiga®) Significantly Increases
Slide 37: Identifying an Onvansertib-Abiraterone Response Gene Signature
2021 Corporation Presentation I 37Onv: Onvansertib; Abi: Abiraterone; CRPC: Castrate-resistant prostate cancer Identifying an Onvansertib-Abiraterone Response Gene Signature Onvansertib/Abiraterone Abiraterone induces expression of mitotic genes in prostate cancer cells synergistic for Onv+Abi Syner
Slide 38: mCRPC Trial Design and Enrollment
2021 Corporation Presentation I 38mCRPC: Metastatic castrate-resistant prostate cancer; PSA: Prostate specific antigen Key Eligibility Criteria: • Initial signs of abiraterone resistance defined as 2 rising PSAs; one rise of ≥0.3 ng/mL separated by one week Key Exclusion Criteria: • Prior treatment
Slide 39: mCRPC Safety and Patient Characteristics
2021 Corporation Presentation I 39 • Most frequent Grade 3 and 4 adverse events (AEs) were expected, on-target, reversible hematological (anemia, neutropenia, thrombocytopenia and WBC decrease), associated with the mechanism of action of onvansertib • Hematological AEs were reversible and effectivel
Slide 40: Treatment Response and Duration
2021 Corporation Presentation I 40*Completed at least 12 weeks of treatment or had radiographic/clinical progression within 12 weeks; **Defined as prostate specific antigen (PSA) stabilization or decline (PSA rise <25% over baseline); SD: Stable disease; DCR: Disease control rate; AR: Androgen recep
Slide 41: Recent and Upcoming Milestones: mCRPC
2021 Corporation Presentation I 41 7 14 21 28 1 8 15 22 2 9 16 23 3 10 17 24 4 11 18 25 5 12 19 26 6 13 20 27 S February 2021 M T W T F S 4 11 18 25 5 12 19 26 6 13 20 27 7 14 21 28 1 8 15 22 29 2 9 16 23 30 3 10 17 24 S April 2021 M T W T F S 3 10 17 24 4 11 18 25 5 12 19 26 6 13 20 27 2 9 16 23 30
Slide 42: Expanding Target Indications
Expanding Target Indications
Slide 43: Preclinical Programs to Expand Onvansertib Indications
2021 Corporation Presentation I 43 SCLC: Small cell lung cancer; TNBC: Triple negative breast cancer; PANC: Pancreatic cancer; CRC: Colorectal cancer; WT: Wild-type Preclinical Programs to Expand Onvansertib Pipeline of Indications TNBC PARP Inhibitors, Paclitaxel Ovarian PARP Inhibitors CRC Erbitux
Slide 44: Onvansertib is a Platform Molecule
2021 Corporation Presentation I 44 Onvansertib is a Platform Molecule PLK1 Function to Inhibit DNA Repair PLK1 Function to Inhibit Mitosis DNA Damaging Agent Microtubule (MT) Targeting Agents (Disruption of Mitosis) Cancer Indication Chemo: Irinotecan & 5-FU PARP Inhibitors Radiation Paclitaxel-MT S
Slide 45: Identifying Novel Effective Combinations of Onvansertib in CRC
2021 Corporation Presentation I 45CRC: Colorectal cancer; PDX: Patient derived xenograft Identifying Novel Effective Combinations of Onvansertib in CRC PDX models from CRC patient biopsies with clinical and molecular features available“Preclinical trial” PDX models Proposed Combinations KRAS WILD TY
Slide 46: PARP Inhibitors and PLK1 in DNA Repair
2021 Corporation Presentation I 461Yata et al. Mol. Cell 45, 371-383, 2012; 2Chabalier-Taste et al., Oncotarget 2016 Jan 19; 7(3): 2269-83 PARP Inhibitors • PARP inhibitors are approved for BRCA1/2 mutant ovarian, breast, prostate and pancreatic cancer patients • Although initial response to PARP in
Slide 47: PLK1 Inhibition Sensitizes Cancer Cells to PARP Inhibitors
2021 Corporation Presentation I 471Yata et al. Mol. Cell 45, 371-383, 2012; 2Chabalier-Taste et al., Oncotarget 2016 Jan 19; 7(3): 2269-83; 3Data on file; PDX: Patient derived xenograft PLK1 Inhibition Sensitizes Cancer Cells to PARP Inhibitors • In vitro preclinical studies showed that PLK1 inhibit
Slide 48: Investment Highlights and Strategy
2021 Corporation Presentation I 48 Investment Highlights and Strategy Fully leverage onvansertib in combination with targeted therapeutics and chemotherapies across multiple cancer indications MOA: Mechanism of action; mCRC: Metastatic colorectal cancer; ORR: Objective response rate; mPFS: Median pr
Slide 49: Thank You
Thank You for more information contact: ir@cardiffoncology.com