Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Technical Presentation (April 2021)
53 slides from Cardiff Oncology's technical presentation, Apr 12, 2021
Slide 1: Key Opinion Leader Webinar: Onvansertib for KRAS-Mutated Metastatic Colorectal Cancer
Key Opinion Leader Webinar Onvansertib for the Treatment of KRAS-Mutated Metastatic Colorectal Cancer
Slide 2: Forward-Looking Statements
2020 Corporation Presentation I 220 Corporation Pr sentation I 2 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 "anticipa
Slide 3: Phase 1b/2 Trial of Onvansertib + FOLFIRI/Bevacizumab in Second-Line mCRC
Phase 1b/2 Trial of Onvansertib + FOLFIRI/Bevacizumab for Second-Line Treatment of KRAS-Mutated mCRC Daniel H. Ahn, D.O., M.S. Assistant Professor in the Division of Hematology/Medical Oncology Mayo Clinic Arizona
Slide 4: Today's Discussion
April 12, 2021 KOL Webinar I 4 Today’s Discussion Putting the Second-Line mCRC Landscape into Perspective – Benchmarking 2nd line standard-of-care: response rates, progression-free survival and overall response – KRAS Targeted Therapies Scientific Rationale for Onvansertib in mCRC – Synthetic Lethal
Slide 5: Benchmarking for Second Line Treatment of mCRC
Benchmarking for Second Line Treatment of mCRC
Slide 6: Second-Line mCRC Treatment is an Unmet Need
April 12, 2021 KOL Webinar I 1Giessen et al., Acta Oncologica, 2015, 54: 187-193; 2Cremolini et al., Lancet Oncol 2020, 21: 497–507; 3Antoniotti et al., Correspondence Lancet Oncol June 2020; 4Bennouna et al., Lancet Oncol 2013; 14: 29–37 6 Objective Response Rate (ORR) Progression-Free Survival (PF
Slide 7: KRAS Targeted Drugs in Development
April 12, 2021 KOL Webinar I 1Hong et al., NEJM 2020; 2Johnson et al., ENA 2020, #LBA-04; 3https://www.revmed.com/pipeline/rmc-4630 7 • KRAS Targeted Drugs in Development: – Two KRAS G12C inhibitors are currently in clinical development • Sotorasib (AMG510, Amgen) and Adagrasib (MRTX849, Miriati The
Slide 8: Flatiron Health Data: Second-line Treatment
April 12, 2021 KOL Webinar I Source: Hess, L. International Journal of Colorectal Disease; 2019. Data is limited to limited to second-line regimens used in >1% of the cohort. FOLFOX: fluoropyrimidine, leucovorin, oxaliplatin. FOLFIRI: fluoropyrimidine, leucovorin, irinotecan, FOLFOXIRI: fluoropyrimi
Slide 9: Scientific Rationale: Synthetic Lethality and Synergy
Scientific Rationale: Synthetic Lethality and Synergy
Slide 10: KRAS Mutant CRC Cells are More Sensitive to Onvansertib
April 12, 2021 KOL Webinar I 101Luo et al, Cell. 2009; 137 835-48; PLK1: Polo-like Kinase 1; mCRC: Metastatic colorectal cancer KRAS Mutant CRC Cells are More Sensitive to Onvansertib than KRAS Wild-Type CRC Cells • A genome-wide RNAi screen was performed in KRAS-mutant and wild-type isogenic CRC ce
Slide 11: RAS Activates PLK1 via CRAF through a MEK-ERK Independent Pathway
April 12, 2021 KOL Webinar I RAS activates PLK1 through a MEK/ERK-independent mechanism 1Mielgo et al., Nat. Med. 2011; 17(12):1641-5 RAS Activates PLK1 via CRAF through a MEK-ERK Independent Pathway 11 The downstream target of KRAS, pCRAF, localizes to the mitotic spindle poles at mitosis where it
Slide 12: Onvansertib is Synergistic with Irinotecan and 5-FU
April 12, 2021 KOL Webinar I Onvansertib works synergistically in combination with standard-of-care FOLFIRI (irinotecan and 5-FU) HCT-116 (with G13D KRAS mutation) 12 Onvansertib is Synergistic in Combination with Irinotecan and 5-FU Synergy in Combination with Irinotecan Synergy in Combination with
Slide 13: Phase 1b/2 Clinical Study in KRAS-mutated Metastatic Colorectal Cancer
Phase 1b/2 Clinical Study in KRAS- mutated Metastatic Colorectal Cancer
Slide 14: Phase 1b/2 Open Label Trial Design
April 12, 2021 KOL Webinar I 14 Phase 1b/2 Open Label Trial of Onvansertib + FOLFIRI/bevacizumab Trial Design Efficacy Endpoints • Overall response in patients who receive ≥1 cycle (2 courses) of treatment • Progression-free survival (PFS) and duration of response (DOR) • Decreases in KRAS mutation
Slide 15: Phase 1b/2 Enrollment and Patient Baseline Characteristics
April 12, 2021 KOL Webinar I Phase 1b/2 Enrollment and Patient Baseline Characteristics Enrollment (as of 04-Apr-2021) Number of Patients (N) Phase 1b Dose Level 0 Onvansertib 12 mg/m2 Phase 1b Dose Level +1 Onvansertib 15 mg/m2 Phase 1b Dose level +2 Onvansertib 18 mg/m2 Phase 2 RP2D Onvansertib 15
Slide 16: Phase 1b/2 Safety Assessment
April 12, 2021 KOL Webinar I Phase 1b/2 Safety Assessment Adverse Events (AEs) Grade 1 Grade 2 Grade 3 Grade 4 All Grades Nausea 13 5 2 0 20 Fatigue 10 8 1 0 19 Neutropenia 3 4 5 4 16 Abdominal pain 8 5 1 0 14 Diarrhea 7 5 0 0 12 Alopecia 8 2 0 0 10 WBC Decreased 3 5 1 1 10 Vomiting 4 4 1 0 9 Anemia
Slide 17: Phase 1b/2 Preliminary Efficacy Assessment
April 12, 2021 KOL Webinar I • Of the 18 patients evaluable for efficacy*, 7 (39%) achieved a partial response (PR) representing KRAS mutations G12D (n=2), G13D (n=1), G12V (n=1), G12A (n=2) and A146T (n=1) – 4 patients had a confirmed PR; 1 patient went on to have curative surgery – 1 patient (02-0
Slide 18: Median Progression-free Survival
April 12, 2021 KOL Webinar I 1Giessen et al, Acta Oncologica, 2015; 54:187-193; 2Bennouna et al., Lancet Oncol. 2013; 14(1):29-37 18 Median Progression-free Survival (PFS) Median PFS (95% CI) = 9.40 months (7.85, not reached) Median Progression-Free Survival (mPFS) • mPFS for patients treated to-dat
Slide 19: KRAS Mutant Allelic Frequency Biomarker Analyses
April 12, 2021 KOL Webinar I KRAS Mutant Allelic Frequency (MAF) Biomarker Analyses PR: partial response, SD: stable disease, PD: progressive disease % KRAS MAF Decrease Following 1 Cycle of Treatment 19 02 -0 04 04 -0 23 01 -0 10 01 -0 19 02 -0 05 01 -0 07 01 -0 13 01 -0 18 02 -0 16 02 -0 12 01 -0
Slide 20: Phase 1b/2 Summary
April 12, 2021 KOL Webinar I 20 • Safety Assessment: – The combination of onvansertib and FOLFIRI/bev is well-tolerated – In patients experiencing hematologic toxicities, eliminating the 5-FU bolus from the regimen led to resolution of associated AEs – Onvansertib MTD was established at 15 mg/m2 • P
Slide 21: Patient Case Report
Patient Case Report OC) os OS carditt Oncology”
Slide 22: Case Report – Patient 01-019
April 12, 2021 KOL Webinar I – 83-year-old woman with KRAS G12D metastatic colon cancer Case Report – Patient 01-019 Background Oxaliplatin + 5-FU Patient Overview Treatment History 22 Dec 2018 – Jul 2019 Jul – Dec 2019 5-FU + Bev Dec 2019 – Sept 2020 5-FU Nov 2020 – TROV-054 Jul 2020 Disease Progre
Slide 23: Case Report – Patient 01-019 Response
April 12, 2021 KOL Webinar I 23 Case Report – Patient 01-019 Response – January 2021 (8-week scan): stable disease (-16%) with decrease in size of metastatic lesions – March 2021 (16-week scan): partial response (-39%) with further decrease in size of metastatic lesions Baseline Scan 05-Nov-2020 16-
Slide 24: Expanded Access Program of Onvansertib with FOLFIRI/Bevacizumab
Expanded Access Program (EAP) of Onvansertib in Combination with FOLFIRI/Bevacizumab for Treatment of Patients with KRAS-mutated Metastatic Colorectal Cancer Manish R. Sharma, M.D. Associate Director of Clinical Research START Midwest
Slide 25: Today's Discussion
April 12, 2021 KOL Webinar I 25 Today’s Discussion Putting the Heavily Pre-Treated mCRC Landscape into Perspective EAP Program Design Safety and Clinical Benefit Assessment KRAS Response Biomarker Patient Case Report
Slide 26: Effective Treatment Options for Heavily Pre-Treated Patients are Needed
April 12, 2021 KOL Webinar I 26 Effective Treatment Options for Heavily Pre-Treated Patients are Needed • Third- or later-lines of treatment have poor outcomes: – Approved therapies for KRAS mutant patients are Stivarga® (regorafenib) and Lonsurf® [trifluridine/tipiracil (TAS-102)] • These agents ha
Slide 27: EAP Provides Access to Onvansertib in Combination with FOLFIRI/bevacizumab
April 12, 2021 KOL Webinar I 27 EAP Provides Access to Onvansertib in Combination with FOLFIRI/bevacizumab for Patients with KRAS-mutant mCRC 1 CYCLE = 28 Days Treatment Course = 14 Days Treatment Course = 14 Days 2 3 4 5 6 - 141 2 3 4 5 6 - 141 Onvansertib FOLFIRI + bevacizumab FOLFIRI + bevacizuma
Slide 28: Safety and Clinical Benefit Assessed in EAP Participants
April 12, 2021 KOL Webinar I 28 Safety and Clinical Benefit Assessed in EAP Participants CI = confidence interval Baseline Characteristics (n=20) Median [range] or N (%) Participant age 50 [35-74] Prior lines of therapy 3 [1-6] Participants who received irinotecan- based regimen as last therapy 15 (
Slide 29: Changes in Plasma KRAS-mutant Stratify Participant Outcomes
April 12, 2021 KOL Webinar I 29 Changes in Plasma KRAS-mutant Stratify Participant Outcomes CI= confidence interval; NR= not-reached 0 100 200 300 0 50 100 Days P ro gr es si on F re e S ur vi va l >50% <50% Decrease in KRAS MAF after 1st cycle p=0.014 Decrease in KRAS MAF Median PFS (95% CI) ≥50% N
Slide 30: Patient Case Report
Patient Case Report OC) os OS carditt Oncology”
Slide 31: Participant Case Report
April 12, 2021 KOL Webinar I 31 Participant Case Report • Participant received several prior lines of treatment including FOLFIRI + Bev • Oct 2020 – progressed on investigational drug and had increase in size of lung metastases • Nov 2020 – enrolled in EAP and received onvansertib 15 mg/m2 + FOLFIRI
Slide 32: Clinical Benefit Demonstrated
April 12, 2021 KOL Webinar I 32 Clinical Benefit Demonstrated • 8-week CT scan: decrease in size of numerous lung metastases; many appearing necrotic • 16-week CT scan: further decrease in size of lung metastases; many continuing to appear necrotic Clinical Benefit / Response to Onvansertib + FOLFIR
Slide 33: Summary
April 12, 2021 KOL Webinar I • Treatment with onvansertib + FOLFIRI + Bevacizumab in the EAP has been well tolerated with no SAEs reported to-date • At the AACR cutoff date of March 10, 2021, 20 participants with a median of 3 or more prior therapies, were evaluated for clinical benefit – Median pro
Slide 34: Corporate Update and Outlook for 2021
Corporate Update and Outlook for 2021 Mark Erlander, Ph.D. Chief Executive Officer
Slide 35: Cardiff Oncology Strategy – Transforming to Lead the Way
April 12, 2021 KOL Webinar I 35 Cardiff Oncology Strategy – Transforming to Lead the Way Undergoing Corporate Transformation to Position Cardiff for Long-term Success Maximizing Our Clinical Development Capabilities Leading with Research and Data o Accelerating corporate governance best practices, s
Slide 36: Cardiff Oncology At-A-Glance
April 12, 2021 KOL Webinar I 36 Cardiff Oncology At-A-Glance Clinical-stage biotech company, developing onvansertib, an oral, highly-selective Polo-like Kinase 1 (PLK1) inhibitor, to treat cancers with the greatest medical need for new effective therapies Exchange Nasdaq: CRDF Cash & Cash Equivalent
Slide 37: Timeline of Key Anticipated Catalysts for the Balance of 2021
April 12, 2021 KOL Webinar I 37 Timeline of Key Anticipated Catalysts for the Balance of 2021 June - July FDA EOP1b Meeting mCRC Regulatory Path June 1-4 Jeffries Healthcare Conference Sept 17-21 ESMO mCRC Phase 2 data May PDAC First Patient Enrolled Oct 28-30 Prostate Cancer Foundation (PCF) Scient
Slide 38: Phase 1b/2 Ongoing Trial: Patient Accrual and Anticipated Timing of Results
April 12, 2021 KOL Webinar I 38 Phase 1b/2 Ongoing Trial: Patient Accrual and Anticipated Timing of Results • Increased the number of trial sites from 2 to 7 going into Phase 2 • Accrual and enrollment is ahead of expectations: – First patient enrolled in Phase 2 – February 2021 – 16 patients enroll
Slide 39: Scenario 1: Trial Design Option for Regulatory Approval Pathway
April 12, 2021 KOL Webinar I 39 Scenario 1: Trial Design Option for Regulatory Approval Pathway • Expand current Phase 2 trial [onvansertib + FOLFIRI/bevacizumab] from 29 to 87 evaluable patients to obtain accelerated (conditional) approval based on primary endpoints of ORR and DOR • Follow with a r
Slide 40: Scenario 2: Trial Design Option for Regulatory Approval Pathway
April 12, 2021 KOL Webinar I 40 Scenario 2: Trial Design Option for Regulatory Approval Pathway Primary Endpoints 1. Progression-Free Survival (PFS) 2. Overall Survival (OS) Randomized Trial for Second Line Treatment of KRAS- Mutated mCRC Treatment Arm Onvansertib + FOLFIRI/bevacizumab Comparative A
Slide 41: 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 42: New Therapeutic Options are Needed to Overcome Resistance to SOC ARSi
April 12, 2021 KOL Webinar I 1Antonarakis, Emmannel – Current Understanding of Resistance to Abiraterone and Enzalutamide in Advanced Prostate Cancer; Clinical Advances in Hematology & Oncology – May 2016 – Volume 14, Issue 5; 2Armstrong et al., 2019, JCO 37: 1120-1129; SOC: Standard-of-care; mCRPC:
Slide 43: Phase 2 Trial Design, Objectives and Enrollment
April 12, 2021 KOL Webinar I Phase 2 Trial Design, Objectives and Enrollment (NCT03414034) 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 with either enzalutamide or
Slide 44: Efficacy Assessment
April 12, 2021 KOL Webinar I • Nineteen (53%) patients had at least 1 AR alteration associated with abiraterone-resistance (AR-V7 expression, AR mutation T878A and/or amplification of AR)1: – 5 (26%) patients had disease control at 12 weeks – 8 (42%) patients had radiographic stable disease at 12 we
Slide 45: Identifying an Onvansertib-Abiraterone Response Gene Signature
April 12, 2021 KOL Webinar I Identifying an Onvansertib-Abiraterone Response Gene Signature 45 Onvansertib/Abiraterone Abiraterone induces expression of mitotic genes in prostate cancer cells synergistic for Onv+Abi • Synergy study • RNA-sequencing Transcriptome analysis of 32,000 prostate cancer sp
Slide 46: Metastatic Pancreatic Ductal Adenocarcinoma
Metastatic Pancreatic Ductal Adenocarcinoma Phase 2 open-label trial of onvansertib + nanoliposomal irinotecan + 5-FU
Slide 47: New Second-Line Therapies are Needed for Metastatic PDAC Patients
April 12, 2021 KOL Webinar I 47 New Second-Line Therapies are Needed for Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Patients Second-line treatment with SOC irinotecan + 5-FU/leucovorin offers a mOS benefit of only 6.1 months2 • Mutant KRAS contributes to treatment resistance and metastases a
Slide 48: Trial Design: Onvansertib + Nanoliposomal Irinotecan + 5-FU in PDAC
April 12, 2021 KOL Webinar I Trial Design (~45 patients): Phase 2 Open Label Trial of Onvansertib + Nanoliposomal Irinotecan + 5-FU in Metastatic PDAC Eligibility Criteria • Prior abraxane/gemcitabine and no prior irinotecan, nanoliposomal irinotecan or investigational PLK1 inhibitor Primary Efficac
Slide 49: Leading with Research and Data
Leading with Research and Data
Slide 50: Identifying Novel Effective Combinations of Onvansertib in CRC
April 12, 2021 KOL Webinar I 50 Identifying Novel Effective Combinations of Onvansertib in CRC • PDX models from CRC patient biopsies with clinical and molecular features available “Preclinical trial” PDX models Oxaliplatin + 5FU KRAS MUTANT TUMORS KRAS WILD TYPE TUMORS Proposed Combinations SHP2 in
Slide 51: Combining Onvansertib and PARP Inhibitors
April 12, 2021 KOL Webinar I 51 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 • M
Slide 52: PLK1 Inhibition Sensitizes Cancer Cells to PARP Inhibitors
April 12, 2021 KOL Webinar I 52 PLK1 Inhibition Sensitizes Cancer Cells to PARP Inhibitors 1Yata et al. Mol. Cell 45, 371-383, 2012; 2Chabalier-Taste et al., Oncotarget 2016 Jan 19; 7(3): 2269-83; 3Data on file • In vitro preclinical studies showed that PLK1 inhibition sensitized cells to genotoxic
Slide 53: Thank You
2020 Corporation Presentation I 53 Thank You
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