Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Investor Presentation (October 2021)
48 slides from Cardiff Oncology's investor presentation, October 2021
Slide 1: Turning the Tide on Cancer
Turning the Tide on Cancer October 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: 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 4: Cardiff Oncology is Well-Positioned
Cardiff Oncology is Well-Positioned Fully leverage onvansertib in combination with targeted therapeutics and chemotherapies across multiple cancer indications Onvansertib A platform molecule with broad indication opportunities Lead program: KRAS-mutated mCRC ORR demonstrating >2-fold improvement ove
Slide 5: 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 6: 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 7: Onvansertib Targets Key Functions of PLK1 Throughout the Cell Cycle
Onvansertib Targets Key Functions of PLK1 Throughout the Cell Cycle G2 G2 G2 Cell cycle S M M M S S G1 G1 G1 DNA Damaging Agents Microtubule Targeting Agents Topoisomerase-I inhibitors (Irinotecan, Topotecan) MT stabilizing agents: paclitaxel, docetaxel, cabazitaxel Radiation, MT destabilizing agent
Slide 8: 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 9: Onvansertib is a Platform Molecule
Onvansertib is a Platform Molecule Combination IND Sponsor or Indication Agent(s) Preclinical Enabled Phase 1 Phase 2 Collaborator Status mCRC FOLFIRI/bev Fully Enrolled mPDAC Onivyde/5-FU Enrolling Onvansertib Zytiga® mCRPC Enrolling (Abiraterone) Oral PLK1 Inhibitor Ovarian PARP Inhibitors Preclin
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 Clinics (Arizona, Minnesota, Florida), Kansas University Medical Center, CARTI Cancer Center, Inova Schar Cancer Institute Principal I
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 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 12: 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) ML18147 Phase 3 Registrational Trial of FOLFIRI + bev in second- 5% 5.7 months 11.2 mon
Slide 13: 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 14: Current KRAS Inhibitors Target G12C, a Small Subset of CRC Patients
Current KRAS Inhibitors Target G12C, a Small Subset of CRC Patients Onvansertib is agnostic to the KRAS mutation subtype Somatic Mutations N (%) G12D 49 (29.2%) G12V 41 (24.4%) G13D 26 (15.5%) G12S 16 (9.5%) G12A 15 (8.9%) G12C 15 (8.9%) Q61H 4 (2.4%) G13C 2 (1.2%) G12F 1 (0.6%) 1 Janakiraman M et a
Slide 15: 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 16: RAS Activates PLK1 through a MEK/ERK-independent mechanism
RAS Activates PLK1 through a MEK/ERK-independent mechanism RAS • The downstream target of KRAS, pCRAF localizes RAF Onvansertib to the mitotic spindle poles at mitosis where it P interacts with PLK1 and promotes PLK1 activation, P leading to mitosis and tumor progression1 P CRAF PLK1 MEK PLK1 Activi
Slide 17: 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 17
Slide 18: PLK1 Promotes Cancer Cell Survival by Facilitating DNA Repair of Irinotecan-induced DNA Damage
PLK1 Promotes Cancer Cell Survival by Facilitating DNA Repair of Irinotecan-induced DNA Damage Onvansertib has the potential to sensitize cancer cells to irinotecan by preventing PLK1-mediated DNA repair PLK1 Promotes Survival by Facilitating • Topoisomerase I inhibitors such as irinotecan induce DN
Slide 19: 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 20: 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 02-Jul-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 m
Slide 21: Phase 1b/2: Safety and Tolerability of Onvansertib Demonstrated
Phase 1b/2: Safety and Tolerability of Onvansertib Demonstrated Most Common Treatment-Emergent AEs (as of 02-Jul-2021) – N=45 Patients TEAEs* Grade 1 Grade 2 Grade 3 Grade 4 All Grades Fatigue 12 3 13 0 28 • 8 patients had a total of 10 G4 adverse events: Neutropenia 1 11 8 5 25 – Neutropenia (n=6);
Slide 22: Efficacy Data Remain Consistent as Patient Numbers Increase
Efficacy Data Remain Consistent as Patient Numbers Increase Data Cutoff Date: SEPT 8, 2020 APRIL 4, 2021 JULY 2, 2021 All Doses All Doses All Doses Phase 2 Dose (12, 15 and 18 mg/m2) (12, 15 and 18 mg/m2) (12, 15 and 18 mg/m2) (15 mg/m2) Number of 11 18 32 19 Evaluable Patients Initial PRs as 5 of 1
Slide 23: Phase 1b/2: Efficacy and Duration of Response (as of 02-Jul-21)
Phase 1b/2: Efficacy and Duration of Response (as of 02-Jul-21) Treatment Response and Duration Progression Free Survival (PFS (Onvansertib All Doses) (All Evaluable Patients - N=32) ks s ks eeks ks ek s s ek eeks ee ek ee ee we 6 we w 6 we 24 w 32 w 40 w 8 w Median PFS (95% CI) = 9.40 months (7.85,
Slide 24: Efficacy at the RP2D of Onvansertib 15 mg/m2 (as of 02-Jul-21)
Efficacy at the RP2D of Onvansertib 15 mg/m2 (as of 02-Jul-21) 19 of 22 patients treated per protocol* with onvansertib at the RP2D (15 mg/m2) were evaluable for efficacy:** • 8 (42%) achieved a partial response (PR) • 3 confirmed and 5 unconfirmed PRs as of 02-Jul-21 • Further follow-up: 7 confirme
Slide 25: Best Radiographic Response (as of 02-Jul-21)
Best Radiographic Response (as of 02-Jul-21) Best Radiographic Response Best Radiographic Response All Doses RP2D – 15 mg/m2 Best Radiographic Response _All Doses _ 2JUL2021 Best Radiographic Response _15mg/m2 _ 2JUL2021 100 Partial Response Stable Disease Partial Response Stable Disease 50 Confirme
Slide 26: 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 was measured by digital droplet PCR (ddPCR) at % KRAS MAF Decrease Following baseline (Cycle 1 Day 1, pre-dose) and on-treatment (Day 1 of 1%Change Cycle ofinTreatm
Slide 27: KRAS Mutations Variants in Treated Patients
KRAS Mutations Variants in Treated Patients • 7 different variants were detected by targeted next-generation sequencing (NGS) in circulating tumor DNA (ctDNA) isolated from patient plasma at baseline • Clinical responses were observed across different KRAS variants, including the 3 most common (G12D
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 September 2021 January 2022 S M T W T F S S M T W T F S 1 2 3 4 1 5 6 7 8 9 10 11 2 3 4 5 6 7 8 12 13 14 15 16 17 18 9 10 11 12 13
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 Study of Onvansertib + Nanoliposomal Irinotecan + 5-FU in Metastatic PDAC
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: 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 33: 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 34: 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 35: Trial Design: Phase 2 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 36: 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 37: Assessment of Preliminary Efficacy and Duration of Response as of 02-Jul-21
Assessment of Preliminary Efficacy and Duration of Response as of 02-Jul-21 Preliminary Data Summary for Evaluable Patients Treatment Response and Duration Arm A Arm B Arm C hs hs hs nt nt nt ar (5+16) (5+9) (14+7) mo mo mo ye 3 6 9 1 01-044 Evaluable for efficacy* 17 20 13 02-045 Arm C (14+7) 02-04
Slide 38: mCRPC (TROV-053 Trial) PFS as of 02-Jul-21
mCRPC (TROV-053 Trial) PFS as of 02-Jul-21 Comparison of PFS in arm B and C mCRPC (TROV-053) PFS (as of 02-Jul-21) TROV053_PFS_July2nd, 2021 Probability of Progression 100 Arm B (5+9) Arm C (14+7) Arm Median Survival Lower 95% CI Upper 95% CI Median PFS 50 B 5.98 2.76 NA Arm B: 6 months ns Arm C: no
Slide 39: Identifying an Onvansertib-Abiraterone Response Gene Signature
Identifying an Onvansertib-Abiraterone Response Gene Signature Onvansertib/Abiraterone Abiraterone induces expression of mitotic genes Identification of an Synergy study in prostate cancer cells Abi/Onv synergy gene signature RNA-sequencing synergistic for Onv+Abi Identified 4 molecular subtypes: Ab
Slide 40: Recent and Upcoming Milestones: mCRPC
Recent and Upcoming Milestones: mCRPC February 2021 April 2021 February 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 6 1 2 3 1 2 3 4 5 7 8 9 10 11 12 13 4 5 6 7 8 9 10 6 7 8 9 10- 11 12 14 15 16 17 18 19 20 11 12 13 14 15 16 17 13 14 15 16 17 18 19 21 22 23 24 25 26 27 18 19 20 21 22 23
Slide 41: Expanding Target Indications
Expanding Target Indications
Slide 42: 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 Irinotecan & 5-FU PARP Inhibitors Radiation Stabilizer Abirater
Slide 43: 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 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: Cardiff Oncology is Well-Positioned
Cardiff Oncology is Well-Positioned Fully leverage onvansertib in combination with targeted therapeutics and chemotherapies across multiple cancer indications Onvansertib A platform molecule with broad indication opportunities Lead program: KRAS-mutated mCRC ORR demonstrating >2-fold improvement ove
Slide 48: Thank You
Thank You for more information contact: [email protected]
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