Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Trovagene — Investor Presentation (November 2017)
32 slides from Cardiff Oncology's investor presentation, Nov 28, 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: Castrate-Resistant Prostate cancer CRPC), Adrenocortical Carcinoma (ACC), 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 – Orphan Drug Designation Phase 1b/2 open-label clinical trial in combination with standard-of-care ongoing Indication (Target) Preclinical Phase 1 Phase 2 Phase 1 Advanced Solid Tu
Slide 5: PLK1: Targeted Therapy for Cancer
PLK1: Targeted Therapy for Cancer PLK1, a serine/threonine kinase, is a master regulator of cell-cycle progression1-6 Depletion of PLK1 induces cell death in tumor cells; in striking contrast, normal cells were much less sensitive to PLK1 depletion7 Normal cells are 10-fold less sensitive than tumor
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 Tested against over 260 kinases and PLK1 was the only active target with IC50 of 2nM All other kinase
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 cell lin
Slide 10: 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 11: 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 12: 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 13: 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 We believe that the adverse events observed in Phase 3 study were due to drug accumulation and pan-PLK inhi
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: PCM-075 Phase 1b/2 AML Clinical Trial Endpoints
PCM-075 Phase 1b/2 AML Clinical Trial Primary Endpoints Safety: characterization of does-limiting toxicities (DLTs), adverse events (AEs) by type, incidence, severity, seriousness and relationship to treatment effects on vital signs and laboratory parameters Efficacy: Rate of complete response (CR +
Slide 16: 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 by assessing inhibition of TCTP phosphorylation Blockage of cell division (G2/M arrest) Tumor DNA biomarkers Blood sample (baseline) AML Patie
Slide 17: PLK1 Enzymatic Activity Biomarker for PCM-075 inhibition
PLK1 Enzymatic Activity Biomarker for PCM-075 inhibition1 PCM-075 (µM): 0 .01 .032 .1 .32 1 3 10 pTCTP Total TCTP 1Trovagene, data on file PLK1 activity: as measured by pTCTP (Translationally Controlled Tumor Protein) which is activated by PLK1 1Trovagene Data on file Vehicle (DMSO) PCM-075 Positive
Slide 18: Molecular Profiling and Patient Response
Molecular Profiling and Patient Response AML Genomic Subgroup Frequency of Patients Most Frequently Mutated Genes (%) DNA Panel RNA Panel NPM1 mutation 27% NPM1(100), DNMT3A(54), FLT3(39), NRAS(19), TET2(16), PTPN11(15) Mutated chromatin, RNA-splicing genes, or both 18% RUNX1(39), MLLPTD(25), SRSF2(
Slide 19: 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 20: AML Combination of PCM-075 with FLT3 Inhibitor
Acute Myeloid Leukemia (AML) Combination of PCM-075 with FLT3 Inhibitor Evaluation of 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 Trovagene,
Slide 21: Synergistic Combinations
Synergistic Combinations PCM-075 may be 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 22: Metastatic Castration-Resistant Prostate Cancer Market Opportunity
Metastatic Castration-Resistant Prostate Cancer (mCRPC) Market Opportunity 25,000 men progress to metastatic prostate cancer resistant to standard androgen-deprivation therapy, anually1 Five-year survival rate of 37%2 Risk of metastases increases as the disease progresses; most common metastases are
Slide 23: PCM-075 + Abiraterone Synergy
PCM-075 + Abiraterone Synergy PCM-075 plus abiraterone suggested increased sensitivity when compared to abiraterone alone, showing decreased viability of mCRPC tumor cells1 Combination appears to enhance the PCM-075 mechanism of action of arresting cells during mitosis1 There continues to be a large
Slide 24: mCRPC Path Forward
mCRPC Path Forward Active IND for PCM-075 in solid tumors Recommended Phase 2 (RP2) study dose of 24 mg/m2 Dosing Schedule: 21 day cycle, 5 days on and 16 days off Engaging key opinion leaders in metastatic castration resistant prostate cancer (mCRPC) to develop Phase 2 clinical trial protocol Combi
Slide 25: PCM-075 Value Proposition
Established Drug Class PCM-075 Value Proposition Demonstrated Safety PLK1-selective inhibitor in clinical development and Orphan Drug Designation for the treatment of acute myeloid leukemia (AML) Demonstrated synergy across multiple chemo and targeted therapies Clinical Activity Drug class demonstra
Slide 26: 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 27: Thank you
Thank you for more information, please email: ir@trovagene.com
Slide 28: Thank you
|. TS a a Thank you help” for more information, please email: ir@trovagene.com
Slide 29: Non-Hodgkin Lymphoma: Combination of PCM-075 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 30: Adrenocortical Carcinoma 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 31: 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 in one patient
Slide 32: Adrenocortical Carcinoma
nocortical Carcinoma > Super-responder observed had high phospho-PLK1 expression prior to therapy; 5 of 8 patients had stable disease > Post-therapy biopsy in one patient indicated complete tumor necrosis € trovagene Copyright(C) 2017 Trovagene, In. 32