Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (August 2021)
48 slides from Cardiff Oncology's investor presentation, August 2021
Slide 1: Turning the Tide on Cancer
Turning the Tide on Cancer August 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: 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
Cardiff Oncology At-A-Glance Exchange Nasdaq: CRDF Clinical-stage biotech company developing onvansertib, an oral, Cash, Cash Equivalents and Investments* $140.1M highly-selective Polo-like Kinase 1 (PLK1) inhibitor, to treat cancers Net Cash used in Operating Activities in 1H 2021 $10.2M with the g
Slide 5: Investment Highlights and Strategy
Investment Highlights and Strategy Fully leverage onvansertib in combination with targeted therapeutics and chemotherapies across multiple cancer indications The only oral and highly selective PLK1 inhibitor. Optimized product profile overcomes the shortcomings of Onvansertib prior PLK inhibitors. B
Slide 6: 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 James Levine Katherine Ruffner, MD Brigitte Lindsay Chief Executive Officer Chief Operating Officer Chief Financial Officer Chief Medical Officer Vice President of Finance 2021 Corpo
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 Function Throughout the Cell Cycle
PLK1 Function Throughout the Cell Cycle G2 G2 G2 M M PLK1 promotes G2/M DNA damage M PLK1 promotes mitotic progression PLK1 facilitates DNA repair S S S G1 checkpoint recovery G1 G 1 Stage of cell Stage of cell Stage of cell cycle affected cycle affected cycle affected Stalled replication forks, DNA
Slide 9: PLK1 Function Throughout the Cell Cycle in Relation to Cancer Treatment
PLK1 Function Throughout the Cell Cycle in Relation to Cancer Treatment G2 PLK1 promotes the repair of G2 PLK1 promotes G2 PLK1 promotes M DNA double-strand breaks caused by M S M mitotic progression despite S S DNA repair and G2/M checkpoint recovery after topoisomerase-I inhibitors or PARP inhibit
Slide 10: Synergistic Effect of Onvansertib in Combination with Standard-of-Care Cancer Treatment
Synergistic Effect of Onvansertib in Combination with Standard-of-Care Cancer Treatment G2 M Onvansertib synergizes with G2 M Onvansertib synergizes with G2 M Onvansertib synergizes with S S genotoxic stress agents microtubule-targeting agents S topoisomerase-I inhibitors & PARP inhibitors G (e.g. i
Slide 11: Onvansertib Overcomes the Shortcomings of Prior PLK Inhibitors
Onvansertib Overcomes the Shortcomings of Prior PLK Inhibitors Prior generation PLK inhibitors demonstrated clinical activity but had less than optimal drug properties Onvansertib Prior PLK Inhibitors Selectivity for PLK1 ✓ ✕ Oral dosing ✓ ✕ Flexible dose and scheduling ✓ ✕ Safety and Tolerability ✓
Slide 12: KRAS-Focused Clinical Programs
KRAS-Focused Clinical Programs Leveraging the synergy of onvansertib when combined with irinotecan and/or 5-FU
Slide 13: Targeted Therapies for KRAS-mutant Patients is an Unmet Need
Targeted Therapies for KRAS-mutant Patients is an Unmet Need • KRAS Targeted drugs in development: Targeting the Ras Pathway4 – Two KRAS G12C inhibitors are currently in clinical development Receptor Stimulation • Sotorasib (AMG510, Amgen) • Adagrasib (MRTX849, Miriati Therapeutics) KRASG12C Inhibit
Slide 14: Cells with KRAS Mutations are Hypersensitive to Inhibition of PLK1
Cells with KRAS Mutations are Hypersensitive to Inhibition of PLK11 Cell Viability in Onvansertib-Treated KRAS Mutant and Wild Type Isogenic CRC Cells • RAS activates PLK1 through a MEK/ERK- independent mechanism • Downstream target CRAF interacts with PLK1 and promotes PLK1 activation, leading to m
Slide 15: Onvansertib is Synergistic in Combination with Irinotecan and 5-FU
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 2021 Corporation Presentation I 15
Slide 16: Early Decreases in Plasma KRAS Mutational Burden are Associated with Clinical Benefit
Early Decreases in Plasma KRAS Mutational Burden are Associated with Clinical Benefit Patient: 61-year-old female with KRAS 8-week CT 16-week CT Baseline CT G12V metastatic sigmoid colon Scan Scan Scan cancer (EAP Participant) Treatment: Onvansertib + FOLFIRI (irinotecan + 5-FU) + Bevacizumab Early
Slide 17: 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 18: 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 have a Prognosis is poor with a five-year Other drugs currently in development KRAS mutation survival rate of 10% do not address the most prevalent KRAS mutations in mCRC ~5-13%
Slide 19: New Second-Line mCRC Treatment Options are an Unmet Need
New Second-Line mCRC Treatment Options are an Unmet Need Standard-of-Care Second Line mCRC Benchmarks for Median ORR, PFS and OS Objective Response Progression-Free Overall Rate (ORR) Survival (PFS) Survival (OS) Systematic Literature-Based Analysis of 23 Randomized Trials 11.4% 4.5 months 11.5 mont
Slide 20: 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-EGFRs agents: Metastatic CRC – No increase in OS, PFS and ORR was observed in KRAS mutant patients treated with EGFR inhibitors vs control arm1,2 KRAS Mutant KRAS Wild Type – The use
Slide 21: Trial Design: Phase 1b/2 Open Label Study of Onvansertib + FOLFIRI/bevacizumab
Trial Design: Phase 1b/2 Open Label Study 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 Criteria for Cl
Slide 22: Phase 1b/2 KRAS-mutated mCRC Trial Enrollment and Patient Baseline Characteristics
Phase 1b/2 KRAS-mutated mCRC Trial Enrollment and Patient Baseline Characteristics Enrollment (as of 04-Apr-2021) Phase 1b, Dose Level 0, Phase 1b, Dose Level +1 Phase 1b, Dose level +2 Phase 2, RP2D Number of Patients (N) Onvansertib 12 mg/m2 Onvansertib 15 mg/m2 Onvansertib 18 mg/m2 Onvansertib 15
Slide 23: Phase 1b/2 KRAS-mutated mCRC Trial Safety Assessment
Phase 1b/2 KRAS-mutated mCRC Trial Safety Assessment Most Common Treatment-Emergent AEs (as of 04-Apr-2021) • 5 patients had G4 adverse events: Adverse Events (AEs) Grade 1 Grade 2 Grade 3 Grade 4 All Grades Nausea 13 5 2 0 20 – G4 neutropenic fever (n=1); G4 neutropenia (n=4); Fatigue 10 8 1 0 19 D
Slide 24: Assessment of Preliminary Efficacy and Duration of Response
Assessment of Preliminary Efficacy and Duration of Response Treatment Response and Duration Progression Free Survival (PFS) ks eeks ek s ek s ek s ek s s ek eeks Median PFS (95% CI) = 9.40 months (7.85, not-reached) wee w 4 we 2 we 0 we 8 we 6 we w 8 16 2 3 4 4 5 64 01-007 → Treatment ongoing 12 mg/
Slide 25: Significant Decreases in KRAS Mutational Burden Predictive of Tumor Shrinkage
Significant Decreases in KRAS Mutational Burden in Cycle 1 are Predictive of Subsequent Tumor Shrinkage on Radiographic Scan % KRAS MAF Decrease Following 1 Cycle of Treatment • Clinical responses were observed across KRAS PR SD PD mutations, including the 3 most prevalent in CRC (G12D, G12V, G13D)
Slide 26: Phase 1b/2 Trial Patient Case Report – Patient 01-019 Background
Phase 1b/2 Trial Patient Case Report – Patient 01-019 Background Patient Overview: 83-year-old woman with KRAS G12D metastatic colon cancer Treatment History Dec 2018 – Jul 2019 Jul 2019 – Dec 2019 Dec 2019 – Sept 2020 Nov 2020 – TROV-054 Oxaliplatin + 5-FU 5-FU + Bev 5-FU FOLFIRI + Bev + onvanserti
Slide 27: Phase 1b/2 Trial Patient Case Report – Patient 01-019 Response
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 Summary • March 2021 (16-week scan): partial response [PR] (-39%) with further decrease in size of metastatic lesions 16.1 mm 15.0 mm Ch
Slide 28: Recent and Upcoming Milestones: KRAS-Mutated mCRC
Recent and Upcoming Milestones: KRAS-Mutated mCRC Fast Track Designation enables more frequent interaction with the FDA and may facilitate an accelerated regulatory path May 2020 January 2021 September 2021 January 2022 S M T W T F S S M T W T F S S M T W T F S S M T W T F S 1 2 1 2 1 2 3 4 1 3 4 5
Slide 29: 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 30: 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 31: Trial Design: Phase 2 Open Label Study of Onvansertib + Nanoliposomal Irinotecan + 5-FU
Trial Design: Phase 2 Open Label Study 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 l
Slide 32: Upcoming Milestones: Metastatic PDAC
Upcoming Milestones: Metastatic PDAC June 2021 January 2022 September 2022 S M T W T F S S M T W T F S S M T W T F S 1 2 3 4 5 1 1 2 3 6 7 8 9 10 11 12 2 3 4 5 6 7 8 4 5 6 7 8 9 10 13 14 15 16 17 18 19 9 10 11 12 13 14 15 11 12 13 14 15 16 17 20 21 22 23 24 25 26 16 17 18 19 20 21 22 18 19 20 21 22
Slide 33: 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 34: 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 35: Onvansertib Extends Response to Androgen Receptor Signaling Inhibitors
Onvansertib Extends Response to Androgen Receptor Signaling Inhibitors Onvansertib + Abiraterone (Zytiga®) Demonstrate Onvansertib + Abiraterone (Zytiga®) Significantly Synergy in Abi-Resistant Model (LVCaP2CR)1 Increases Apoptotic Cell Death1 • PLK1 is overexpressed in prostate cancer and linked to
Slide 36: Identifying an Onvansertib-Abiraterone Response Gene Signature
Identifying an Onvansertib-Abiraterone Response Gene Signature Onvansertib/Abiraterone Abiraterone induces expression of mitotic genes in Identification of an Synergy study prostate cancer cells Abi/Onv synergy gene signature RNA-sequencing synergistic for Onv+Abi Identified 4 molecular subtypes: Ab
Slide 37: Trial Design: Phase 2 Open Label Study of Onvansertib + Abiraterone in mCRPC
Trial Design: Phase 2 Open Label Study of Onvansertib + Abiraterone in Metastatic Castrate-Resistant Prostate Cancer 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
Slide 38: Phase 2 mCRPC Trial Baseline Characteristics and Safety
Phase 2 mCRPC Trial Baseline Characteristics and Safety Baseline Characteristics Safety Assessment • Most frequent Grade 3 and 4 adverse events (AEs) were expected, on-target, Total patients N=51 Median [range] or n (%) reversible hematological (anemia, neutropenia, thrombocytopenia and WBC Age, yea
Slide 39: Assessment of Preliminary Efficacy and Duration of Response
Assessment of Preliminary Efficacy and Duration of Response Preliminary Data Summary for Evaluable Patients Treatment Response and Duration Arm A Arm B Arm C on th s on th s on th s ar ye ar m m m ye 5 (5+16) (5+9) (14+7) 03-043 3 6 9 1 1. → Ongoing → Arm C (14+7) 01-044 → 02-045 → 02-046 → Met PSA
Slide 40: Recent and Upcoming Milestones: mCRPC
Recent and Upcoming Milestones: mCRPC February 2021 April 2021 October 2021 February 2022 S M T W T F S S M T W T F S S M T W T F S S M T W T F S 1 2 3 4 5 6 1 2 3 1 2 1 2 3 4 5 7 8 9 10 11 12 13 4 5 6 7 8 9 10 3 4 5 6 7 8 9 6 7 8 9 10- 11 12 14 15 16 17 18 19 20 11 12 13 14 15 16 17 10 11 12 13 14
Slide 41: Expanding Target Indications
Expanding Target Indications
Slide 42: Preclinical Programs to Expand Onvansertib Pipeline of Indications
Preclinical Programs to Expand Onvansertib Pipeline of Indications Prostate CRC TNBC PANC PARP Inhibitors Erbitux (EGFR) KRAS WT PARP Inhibitors, Onvansertib single agent Onvansertib G12C Inhibitors KRAS Paclitaxel Exploratory combinations Ovarian Pediatric SCLC PARP Inhibitors Medulloblastomas Irin
Slide 43: Onvansertib is a Platform Molecule
Onvansertib is a Platform Molecule Inhibit Ability of PLK1 to Repair DNA Inhibit Ability of PLK1 to Promote Cell Division (Mitosis) DNA Damaging Agent Microtubule (MT) Targeting Agents (Disruption of Mitosis) Chemo: Paclitaxel-MT DM4-MT Cancer Indication Irinotecan & 5-FU PARP Inhibitors Radiation S
Slide 44: Identifying Novel Effective Combinations of Onvansertib in CRC
Identifying Novel Effective Combinations of Onvansertib in CRC PDX models PDX models from CRC patient biopsies with “Preclinical clinical and molecular features available trial” Proposed Combinations KRAS MUTANT TUMORS KRAS WILD TYPE TUMORS Oxaliplatin + 5-FU G12C Irinotecan-resistant mutant EGFR in
Slide 45: Combining Onvansertib and PARP Inhibitors
Combining Onvansertib and PARP Inhibitors PARP Inhibitors • PARP inhibitors are approved for BRCA1/2 mutant ovarian, breast, prostate and pancreatic cancer patients • Although initial response to PARP inhibitors is high, patients will eventually develop resistance • Mechanisms of resistance to PARP
Slide 46: PLK1 Inhibition Sensitizes Cancer Cells to PARP Inhibitors
PLK1 Inhibition Sensitizes Cancer Cells to PARP Inhibitors • In vitro preclinical studies showed that PLK1 inhibition sensitized cells to genotoxic stresses (i.e. radiation) and to PARP inhibitors through impairment of HR1,2 • Onvansertib sensitizes tumor cells to PARP inhibition in vivo: – In an ov
Slide 47: Investment Highlights and Strategy
Investment Highlights and Strategy Fully leverage onvansertib in combination with targeted therapeutics and chemotherapies across multiple cancer indications The only oral and highly selective PLK1 inhibitor. Optimized product profile overcomes the shortcomings of Onvansertib prior PLK inhibitors. B
Slide 48: Thank You
Thank You for more information contact: ir@cardiffoncology.com
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