Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Trovagene — Investor Presentation (September 2017)
26 slides from Cardiff Oncology's investor presentation, Sep 21, 2017
Slide 1: 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 2: Company Overview
Company Overview Precision Cancer Therapeutics Clinical stage biotechnology company developing treatments for hematologic and solid tumor malignancies Core DNA/RNA Technology Expertise Proprietary technology in tumor genomics and CLIA/CAP-accredited laboratory for drug development programs Lead Ther
Slide 3: Lead Drug Candidate PCM-075 Investment Highlights
Lead Drug Candidate PCM-075 Investment Highlights Progressing Pipeline Broad clinical applications in hematologic and solid tumor malignancies Hematologic: Acute Myeloid Leukemia, Non-Hodgkin Lymphoma Solid Tumors: Adrenocortical Carcinoma (ACC), Castrate-Resistant Prostate cancer CRPC), Small Cell
Slide 4: PCM-075 Expanding Pipeline
PCM-075 Expanding Pipeline Indication (Target) Preclinical Phase 1 Phase 2 Non-Hodgkin Lymphoma Acute Myeloid Leukemia - Phase 1b/2 combination FDA approved IND / protocol – active Indication (Target) Preclinical Phase 1 Phase 2 Phase 1 Advanced Solid Tumors Completed and published Castration-Resist
Slide 5: PLK1: Target for Cancer Therapy
PLK1: Target for Cancer Therapy PLK1, PLK2, PLK3 are members of a family of serine/threonine kinases that are important regulators of cell-cycle progression1–6 PLK1 is a master regulator of mitotic progression and is the only family member expressed exclusively in dividing cells1-6 Other members of
Slide 6: PLK1: As a Cancer Target
PLK1: As a Cancer Target Higher Expression of PLK1 is Associated with Shorter Overall Survival2 Overexpression of PLK1 Observed in Numerous Cancer Types1 Adrenocortical Carcinoma 1Data derived from The Tumor Genome Atlas, https://tcga-data.nci.nih.gov/docs/publications/tcga; 2Bussey et al. Clin Tran
Slide 7: PCM-075 Attributes
PCM-075 Attributes Highly Selective Short Half-Life Acceptable Safety Profile Broad Applicability Orally Available
Slide 8: PCM-075 Biochemical Profile
PCM-075 Biochemical Profile Selective, adenosine triphosphate (ATP) competitive PLK1 inhibitor Selectivity driven by polar interaction with the carboxyl side chain of Glutamate 140 position of PLK1 Polo-like kinase 1 (PLK1) inhibitor PLK Member PCM-075 IC50 (nM)1 PLK1 2 PLK2 > 10,000 PLK3 > 10,000 1
Slide 9: PCM-075 Mechanism of Action
PCM-075 Mechanism of Action Induces a cellular phenotype of G2/M, leading to cell death Clear evidence of in-vitro pathway modulation in AML Mitotic inhibitor demonstrating anti-proliferative activity* AML-NS8 Patient-Derived Cells Treated with 200 nM PCM-075 for 24 Hrs1 * In numerous human cel line
Slide 10: Phase 1 Study Completed in Solid Tumors
Phase 1 Study Completed in Solid Tumors* Phase 1 Study Design 19 of 21 patients enrolled administered PCM-075 orally, once daily for 5 consecutive days, every 3 weeks PCM-075 Study Results Included: colorectal, pancreatic, lung, sarcomas, hepatocellular, ampullary, prostate, ovarian, skin Open-label
Slide 11: Acute Myeloid Leukemia Market Opportunity
Acute Myeloid Leukemia Market Opportunity1 AML: aggressive hematologic malignancy Incidence: 20,000* new cases and 10,400 deaths annually in the U.S. Prognosis: 5 year survival rate is 25% Treatment options vary based on patient condition / age, but can include: Chemotherapy Radiation Stem cell tran
Slide 12: PLK Inhibition in AML
PLK Inhibition in AML Pan-PLK inhibitor demonstrated increased response rates, improvements in event-free survival, and overall survival benefit in combination with low-dose cytarabine (LDAC)1 Adverse events observed in Phase 3 study, potentially due to drug accumulation and pan-PLK inhibitor activi
Slide 13: PCM-075 In-Vivo Activity
PCM-075 In-Vivo Activity Response observed in various xenograft models as a single agent and in combination1 Compound Median Survival Time (days) %TGI Placebo 28 Cytarabine 38 128.6 PCM-075 62 221.4 In Vivo Disseminated Leukemia Model (AML-NS8 Cells) Treatment with PCM-075 Started 20 Days Post-Inocu
Slide 14: PCM-075 Phase 1b/2 AML Clinical Trial
PCM-075 Phase 1b/2 AML Clinical Trial PCM-075 in Combination with Standard-of-Care (SOC) in Subjects with Acute Myeloid Leukemia (AML) Principal Investigator – Dr. Jorge Cortes, MD Anderson Open-label trial to evaluate safety and anti-leukemic activity Phase 1b: dose escalation in combination with S
Slide 15: Phase 1b/2 Biomarker Assessment
Phase 1b/2 Biomarker Assessment1 Biomarkers will be measured and correlated with pharmacokinetic drug levels to assess: Inhibition of PLK1 enzymatic activity Blockage of cell division (G2M arrest) Tumor cell death Blood sample (baseline) AML Patient + PCM-075 Blood sample (post PCM-075) Pre- and Pos
Slide 16: Combination Therapy Opportunities
Combination Therapy Opportunities High PLK1 expression is associated with the most aggressive forms of hematologic malignancies and solid tumor cancers PCM-075 may be synergistic and enhance the efficacy of current and future standard-of-care therapies 1Alphabetical order. 2Preclinical data on file
Slide 17: PCM-075 is Synergistic in Combination
PCM-075 is Synergistic in Combination PCM-075 is synergistic with both targeted drugs and chemotherapeutics CI > 1.0 Antagonistic CI < 1.0 Synergy CI = 1.0 Additive *Data on File at Trovagene, Inc..
Slide 18: AML: Combination of PCM-075 with FLT3 Inhibitor
Acute Myeloid Leukemia (AML) Combination of PCM-075 with FLT3 Inhibitor Evaluation of the Efficacy of PCM-075 for MV-4-11 Human Acute Myeloid Leukemia (AML) Xenograft Model in NOD.SCID Mice 1Kindler et al, Blood 2010; 116:5089-10. 2Stone et al, N Engl J Med 2017; 377:454-64. 3Data on File at Trovage
Slide 19: Non-Hodgkin Lymphoma: Combination with HDAC inhibitor
Non-Hodgkin Lymphoma (NHL) Combination of PCM-075 with Histone deacetylase (HDAC) inhibitor Aggressive NHL progresses rapidly and accounts for 60% of cases in the U.S. No standard-of-care regimen for relapse/refractory patients Subtypes: Diffuse large B-cell lymphoma (DLBCL), including double-hit Ma
Slide 20: Sensitivity to PCM-075 in Breast Cancer
Sensitivity to PCM-075 in Breast Cancer Driven by Triple-Negative Cell Lines Triple-negative breast cancer (TNBC) represents a significant challenge: aggressive clinical course, resistance to chemo, lack of effective targeted therapies PLK1 is significantly over expressed (p < 0.0001) in TNBC compar
Slide 21: Adrenocortical Carcinoma (ACC) Market Opportunity
Adrenocortical Carcinoma (ACC) Market Opportunity Adrenocortical carcinoma (ACC) is a rare cancer with significant unmet clinical needs Incidence: 0.7 to 2 cases per 1 million population per year1,2 Prognosis: 5-year survival in patients with metastatic disease is <15%3-7 40-70% of patients present
Slide 22: PLK1 Inhibition in Adrenocortical Carcinoma
PLK1 Inhibition in Adrenocortical Carcinoma Therapeutic Opportunity 1Demeure et al.; ASCO-2016 Tumor Prior to Treatment Tumor Necrosis Following Treatment Super-responder observed had high phospho-PLK1 expression prior to therapy; 5 of 8 patients had stable disease Post-therapy biopsy indicated comp
Slide 23: PCM-075 Value Proposition
Established Drug Class PCM-075 Value Proposition Demonstrated Safety Only company with a PLK1-selective inhibitor in clinical development and demonstrated synergy across multiple chemo and targeted therapies Clinical Activity Drug class demonstrated 25-30% response in Phase 2 studies in acute myeloi
Slide 24: PCM-075 Value Inflection Points
PCM-075 Value Inflection Points Acute Myeloid Leukemia Phase 1b/2 Trial Initiate patient enrollment and dose escalation in Q4’17 Data release of Phase 1b results in Q2’18 with subsequent Phase 2 trial initiated (pending number of dose escalation cohorts studied) Publication of pharmacokinetic and ph
Slide 25: Thank you
Thank you for more information, please email ir@trovagene.com
Slide 26: Thank you
» Thank you Sa for more information, please email ir@trovagene.com