Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Trovagene — Investor Presentation (July 2018)
57 slides from Cardiff Oncology's investor presentation, Jul 17, 2018
Slide 1: Using Our Precision Medicine Strategy to Develop Oncology Drugs That Target Mitosis
Using Our Precision Medicine Strategy to Develop Oncology Drugs That Target Mitosis July 2018 Exhibit 99.1
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: Strategy for Oncology Drug Development
Strategy for Oncology Drug Development Taking a precision medicine approach to developing PCM-075 by integrating a highly-selective antimitotic drug with a biomarker strategy Leveraging a proven cancer target, PLK1, that is highly expressed in tumor cells and integral to cell division (mitosis) Deve
Slide 4: Our PCM-075 Oncology Pipeline
Our PCM-075 Oncology Pipeline Opportunities in Solid Tumors and Leukemias/Lymphomas Preclinical Phase 1 Phase 2 Solid Tumor Cancers Leukemias & Lymphomas Metastatic Castration-Resistant Prostate Phase 2 trial in combination with with abiraterone acetate (Zytiga®)/prednisone Lung Colon Ovarian Others
Slide 5: Trovagene's Management Team
Trovagene’s Management Team Proven Leadership in Oncology Tom Adams, PhD Chairman of the Board Interim CEO Mark Erlander, PhD Chief Scientific Officer George Samuel, Esq. VP, General Counsel Vicki Kelemen VP, Corporate Communications Sandra Silberman, MD, PhD Chief Medical Advisor
Slide 6: Scientific Advisors
Scientific Advisors Principal Investigators and Collaborators Jorge Cortes, MD – MD Anderson Deputy Chair, Professor of Medicine, Department of Leukemia and Director of CML and AML programs Glenn Bubley, MD – Beth Israel Deaconess Medical Center Director, Multidisciplinary Genitourinary Cancer Progr
Slide 7: Licensed Drug Candidate from NMS
Licensed Drug Candidate from NMS PCM-075 – Polo-like Kinase 1 (PLK1) Inhibitor Largest oncology research and development company in Italy Developed anthracycline class of drugs (doxorubicin) Leader in protein kinase drug development (Polo-like Kinase Inhibitors) Identification and validation of mole
Slide 8: Leveraging Proven Cancer Target
Leveraging Proven Cancer Target
Slide 9: PLK1: Established Target for Cancer Therapy
PLK1: Established Target for Cancer Therapy PLK1 Plays a Critical Role in Initiation, Maintenance and Completion of Mitosis PLK1 belongs to a family of kinases (PLK1, 2,4,4 and 5) Dysfunction of PLK1 promotes cancerous formation and drives cancer progression PLK1 is over-expressed in dividing cells
Slide 10: PLK1 is Over-Expressed in Multiple Cancers
PLK1 is Over-Expressed in Multiple Cancers “In our view, combined therapies targeting other relevant pathways together with Plk1 may be vital to combat issues observed with monotherapy, especially resistance.” July 2016 PLK1 Inhibitors in Cancer Therapy: From Laboratory to Clinics Randomized, Phase
Slide 11: Developing First-in-Class 3rd Generation PLK1 Inhibitor
Developing First-in-Class 3rd Generation PLK1 Inhibitor
Slide 12: PLK Inhibitor Landscape
PLK Inhibitor Landscape 1st Generation PLK inhibitors: BI-2536, TAK-960, GW843682 Pan inhibitors: No selectivity between PLK1, 2, & 31 TAK-960, GW843682 (toxicity issues) Phase 1 & 2 results (BI-2536) Tolerable and reversible hematological toxicities2-4 Limited efficacy as single agent in AML3, lymp
Slide 13: PCM-075: 3rd Generation PLK1 Best-in-Class Attributes
PCM-075: 3rd Generation PLK1 Best-in-Class Attributes Highly Selective Favorable Safety and Tolerability Orally Available Synergistic in Combination Ideal Pharmacokinetics
Slide 14: PCM-075: Characteristics
PCM-075: Characteristics PCM-075 is a small molecule, selective PLK1 inhibitor (MW 650 Daltons)1 Half-life of ~24 hours Formulated as 5 mg and 20 mg hard gelatin capsules 4-year shelf-life when stored at 5°C ± 3°C (36°F to 46°F) Nerviano manufacturer for GMP API and finished goods ADME Profile2 High
Slide 15: PCM-075 Intellectual Property
PCM-075 Intellectual Property Four worldwide patent families Genus, Compound, Combinations, Salt Mature portfolio Granted in most major jurisdictions Patent term 2030 plus up to 5 years extension
Slide 16: PCM-075: Selective 3rd Generation PLK1
PCM-075: Selective 3rd Generation PLK1 Tested against >260 kinases and PLK1 was the only active target (IC50 of 2nM) Selectivity driven by polar interaction with the carboxyl side chain of Glutamate 140 position of PLK11 1Data on File, Trovagene, Inc. Selective PLK1 Inhibitor Induces tumor cell deat
Slide 17: Phase 1 Safety Trial in Solid Tumors
Phase 1 Safety Trial in Solid Tumors1 Favorable First-in-Human Data Phase 1 Trial Design PCM-075 Trial Results Included: colorectal, pancreatic, lung, sarcomas, hepatocellular, ampullary, prostate, ovarian, skin Established safety of PCM-075 and identified a recommended Phase 2 dose of 24 mg/m2/day
Slide 18: Benefiting From Drug Class Experience
Benefiting From Drug Class Experience
Slide 19: 2nd Generation PLK Inhibitor (BI-6727) Randomized Phase 2 Trial in AML
2nd Generation PLK Inhibitor (BI-6727) Randomized Phase 2 Clinical Trial in AML LDAC 2 x 20 mg/day sc, Days 1–10 Every 28 days Adults with previously untreated AML Ineligible for intensive therapy LDAC 2x20 mg/day sc, Days 1–10 + BI 6727 50 mg Days 1 + 15 Every 28 days n=45 n=42 4-week cycles until
Slide 20: 2nd Generation PLK Inhibitor (BI-6727) Phase 3 Trial in AML
2nd Generation PLK Inhibitor (BI-6727) Randomized Phase 3 Clinical Trial in AML Primary analysis for efficacy included 371 of a total 666 patients randomized Results: BI-6727 + LDAC vs placebo + LDAC Increase in remission rate (CR + CRi): 25.2% vs 16.8% (central assessment) – Overall Response 1.659;
Slide 21: PCM-075 Clinical Development Benefiting From Class Experience
PCM-075 Clinical Development Benefiting From Class Experience Product Attributes 1st and 2nd Generation PLK Inhibitors 3rd Generation PCM-075 Selectivity for PLK1 panPLK inhibition of PLK1,2,3* Highly-selective only for PLK1 Antileukemic Activity Phase 2 & 3 trial results indicate activity Improved
Slide 22: Combination Therapy Approach
Combination Therapy Approach
Slide 23: PCM-075: Combination Therapy Strategy
PCM-075: Combination Therapy Strategy Combination therapy is considered the cornerstone of precision cancer medicine Demonstrated synergy in combination with chemotherapies and targeted therapeutics Enhances efficacy compared to monotherapy approach because it targets key pathways in a characteristi
Slide 24: PCM-075: Synergistic in Combination
PCM-075: Synergistic in Combination High PLK1 expression is associated with the most aggressive forms of solid tumor cancers, leukemias and lymphomas Synergistic activity of PCM-075 may enhance efficacy of standard-of-care therapies 1Alphabetical order. 2Preclinical data on file with PCM-075 and the
Slide 25: Rationale for Combination with DNA Damaging Agents
PCM-075: Rationale for Combination with DNA Damaging Agents1,2 Active PLK1 PLK1 Inhibited 1van Vugt & Yaffe, Cell Cycle 2010 9:2097-2101; 2van Vugt et al., 2010, PLoS 8:1-19 DNA Damaging Agents Cytarabine Doxorubicin Cisplatin DNA Damage Response (DDR) arrests cells at G2/M checkpoint G2/M Arrest Mi
Slide 26: Synergy: PCM-075 + Cytarabine
Synergy: PCM-075 + Cytarabine Acute Myeloid Leukemia (AML) Cell Line (HL-60) 1 10 100 1000 Concentration [nM] Combination Index (CI) 0.67 PCM-075 IC50 60.40 nM Cytarabine IC50 37.40 nM Combination IC50 30.09 nM Expected Combination IC50 46.40 nM Data: Nerviano Medical Sciences Greatest Synergy Obser
Slide 27: Synergy: PCM-075 + FLT3 Inhibitor
Synergy: PCM-075 + FLT3 Inhibitor Acute Myeloid Leukemia (AML) 1Kindler et al, Blood 2010; 116:5089-10. 2Stone et al, N Engl J Med 2017; 377:454-64. 3Data on File at Trovagene, Inc. 30% of AML patients harbor a FLT3 mutation1 Midostaurin (FDA approved); 3 additional FLT3 inhibitors, including quizar
Slide 28: Synergy: PCM-075 + HDAC Inhibitor
Synergy: PCM-075 + HDAC* Inhibitor Non-Hodgkin Lymphoma (NHL) Aggressive NHL progresses rapidly; accounts for 60% of cases in the U.S. Subtypes: Diffuse large B-cell lymphoma (DLBCL), including double-hit Mantle cell lymphoma Peripheral T-cell lymphoma (PTCL) Demonstrated synergy of PCM-075 in comb
Slide 29: Synergy: PCM-075 + Abiraterone (Zytiga)
Synergy: PCM-075 + Abiraterone (Zytiga®) Metastatic Castration-Resistant Prostate Cancer PCM-075 in combination with abiraterone demonstrated synergy with decreased viability of mCRPC tumor cells1 Combination appears to enhance the PCM-075 mechanism of action of arresting cells during mitosis1 Medic
Slide 30: PCM-075 Clinical Trials
PCM-075 Clinical Trials Phase 1b/2 in Acute Myeloid Leukemia (AML) Phase 2 in metastatic Castration-Resistant Prostate Cancer (mCRPC)
Slide 31: Acute Myeloid Leukemia: Significant Need for New Treatment Options
Acute Myeloid Leukemia1 Significant Need for New Treatment Options AML: aggressive hematologic malignancy of immature blood cells 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 ca
Slide 32: Scientific Rationale for PCM-075 Clinical Development in AML
in-vitro studies1 High sensitivity of hematological tumor cell lines to PCM-075 (IC50 < 200nM in 38 out of 42 tested cell lines) in-vitro and in-vivo mode of action (MoA) studies2 Cell lines studies indicated G2/M arrest within cell cycle with dose dependent increase in 4N DNA after 24hrs Xenograft
Slide 33: PCM-075: in-vivo efficacy in AML Models
PCM-075: in-vivo efficacy in AML Models1 PCM-075 is efficacious in subcutaneously implanted promyelocytic leukemia (HL60) PCM-075 is active in AML patient derived disseminated primary cells (AML-PS) and showed increased survival in comparison with vehicle 1Valsasina et al. (2012), Mol Cancer Ther 11
Slide 34: PCM-075: Comparative and Combination with Cytarabine in AML Models
PCM-075: Comparative and Combination with Cytarabine in AML Models1,2 1Casolaro et al. (2013) PLOS One 8(3); 2Valsasina et al. (2012), Mol Cancer Ther 11(4) *p = 0.001 Vehicle PCM-075 60 mg/kg BID Cytarabine 75 mg/kg Vehicle PCM-075 60 mg/kg BID Cytarabine 75 mg/kg Vehicle PCM-075 60 mg/kg BID Cytar
Slide 35: PCM-075: Positioning in AML Patient Selection Algorithm
PCM-075: Positioning in AML Patient Selection Algorithm AML Diagnosis 18,3761 cases/year Eligible for Induction Treatment ~11,000 Relapsed & Refractory 30-50% 3,300 to 5,500 PCM-075 in combination with standard-of care chemotherapy and/or targeted therapeutics2 Responders 50-70% Ineligible for Induc
Slide 36: Ongoing Phase 1b/2 Clinical Trial in AML
Ongoing Phase 1b/2 Clinical Trial in AML PCM-075 in Combination with Either Low-Dose Cytarabine (LDAC) or Decitabine in Patients with Acute Myeloid Leukemia (AML) Study Design: Dose escalation to assess safety and identify recommended Phase 2 dose Patient Population: Patients who are Ineligible for
Slide 37: Ongoing Phase 1b/2 Clinical Trial in AML: Phase 2
Ongoing Phase 1b/2 Clinical Trial in AML Phase 2: Assess safety and preliminary antitumor activity Efficacy Endpoints: Rate of complete response (CR + CRi) defined as morphologic leukemia-free state (MLF) Exploratory Endpoints: Evaluation of pharmacodynamic and correlative biomarkers PCM-075 in Comb
Slide 38: Biomarker Strategy in AML
Biomarker Strategy in AML Biomarkers will be measured and correlated with pharmacokinetic drug levels to assess: Inhibition of PLK1 by PCM-075 (Target Engagement) Monitoring treatment effects by measuring % blast cells in blood and bone marrow Correlating underlying tumor genetics with treatment res
Slide 39: Immuno-Profiling: Monitoring Leukemic Cells in Response to Treatment
Immuno-Profiling: Monitoring Leukemic Cells in Response to Treatment Cytarabine PCM-075 Blasts as % of leukocytes Days of cycle PCM-075 + Cytarabine PCM-075 + Decitabine % of Leukemic Cells in Blood Cytarabine PCM-075 Decitabine PCM-075 % of Leukemic Cells in Bone Marrow 3 of 6 patients treated with
Slide 40: Target Engagement: Monitoring PLK1 Inhibition Upon Treatment
Target Engagement: Monitoring PLK1 Inhibition Upon Treatment TCTP PLK1 TCTP P No PCM-075 P PCM-075 PLK1 TCTP TCTP PCM-075 P PCM-075 inhibits PLK1 kinase activity resulting in reduction in PLK1 substrates phosphorylation; Translational Control Tumor Protein (TCTP) is phosphorylated by PLK1 Inhibition
Slide 41: Correlation of Target Engagement and Treatment Response
Correlation of Target Engagement and Treatment Response % of Leukemic Cells in Blood PCM-075 + LDAC 01-002 0h 3h D1 D5 0h 07-004 07-010 0h 3h D1 D5 0h 0h 3h D1 D5 0h pTCTP TCTP PCM-075 12mg/m2 + LDAC PCM-075 + Decitabine % of Leukemic Cells in Blood 07-013 07-009 0h 3h D1 D5 0h 07-011 0h 3h D1 D5 0h
Slide 42: Summary of Target Engagement and Correlation to Treatment Response
Summary of Target Engagement and Correlation to Treatment Response PCM-075 12mg/m2 + Cytarabine PCM-075 12mg/m2 + Decitabine 0h 3h D1 D5 0h pTCTP TCTP 0h 3h D1 D5 0h 0h 3h D1 D5 0h 0h 3h D1 D5 0h 0h 3h D1 D5 0h 0h 3h D1 D5 0h Response % Blasts Response Response
Slide 43: Predictive Response Strategy
Predictive Response Strategy Patient receives single dose PCM-075 AML Patient Assess target engagement of PLK1 by PCM-075 Pre-dose 3hr post-dose Target Engagement Eligible Patient NO Target Engagement Non-Eligible Patient Determining which Patients are Eligible for AML Trial
Slide 44: Molecular Profiling and Patient Response in AML
Molecular Profiling and Patient Response in AML1 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) X Mutated chromatin, RNA-splicing genes, or both 18% RUNX1(39), MLLPTD(2
Slide 45: Genomic Profiling: Correlation of Mutation Detected in Blood and % Leukemic Cells
Genomic Profiling: Correlation of Mutation Detected in Blood and % Leukemic Cells Genomic analysis was performed on bone marrow and blood samples Mutations detected in bone marrow and blood were identical for all patients examined The mutation allelic frequencies detected in blood correlates with %
Slide 46: Metastatic Castration-Resistant Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer 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 adrenal gland, bone, and l
Slide 47: PCM-075 + Abiraterone Combination
PCM-075 + Abiraterone Combination Opportunity to Extend Response to Abiraterone 1Yadi, Li et al; An Investigative Approach for Sequencing Therapies in Metastatic Prostate Cancer - AJHO. 2017;13(12):26-31 A All treatment options should include androgen deprivation therapy (surgical/medical orchiectom
Slide 48: PLK1, Abiraterone and Castration-Resistant Prostate Cancer
PLK1, Abiraterone and Castration-Resistant Prostate Cancer All metastatic prostate cancer patients become castration-resistant PLK1 dependent microtubule dynamics promotes androgen receptor (AR) signaling in prostate cancer1,2 PLK1 inhibition improves abiraterone acetate efficacy3 Inhibition of PLK1
Slide 49: PSA Tracks Tumor Response in mCRPC
PSA Tracks Tumor Response in mCRPC1 Tumor volume was significantly reduced in mice treated with the combination of PLK inhibitor and abiraterone versus either drug alone 1Zhang et al, Cancer Res 2014; 74(22) Vehicle PLK inhibitor Abiraterone PLKi + Abi Vehicle PLK inhibitor Abiraterone PLKi + Abi Pa
Slide 50: Ongoing Phase 2 Clinical Trial in mCRPC
Ongoing Phase 2 Clinical Trial in mCRPC Patient Population: Patients on abiraterone showing early signs of disease progression Treatment Cycle: PCM-075 administered orally on Days 1-5 in a 21-day cycle Efficacy Endpoints: Effect of PCM-075 in combination with Zytiga®/prednisone on disease control as
Slide 51: PSA: NCCN Recommended Biomarker for mCRPC
PSA: NCCN Recommended Biomarker Trial Eligibility and Efficacy for mCRPC1 Prostate Specific Antigen (PSA) is a validated biomarker that shows breakthrough in treatment Prostate Cancer Clinical Trials Working Group (PCWG)1 has set criteria for the use of blood PSA levels for both trial eligibility (p
Slide 52: Biomarker Strategy in mCRPC
Biomarker Strategy in mCRPC PSA Asses disease progression and stabilization CTCs Assess gene expression and response to treatment Tissue Predict synergy of PCM-075 and abiraterone PBMC’s Assess PLK1 inhibition ctDNA Assess dynamic changes associated with treatment
Slide 53: Biomarker Assessment Schedule
Biomarker Assessment Schedule PCM abiraterone/ prednisone Cycle 3 EOS Cycle 2 Cycle 4 PCM PCM PCM D1 D8 D15 PSA CTCs ctDNA Cycle 1 Week: 3 6 9 12 D1 D8 D1 D1 D1 5 pTCTP Pre 1h Baseline, Pre-dose/cycle 1 Pre-dose to cycle 2 Pre 1h Pre-dose to cycle 3 … … Pre-dose to cycle 5 Primary Endpoint: Proporti
Slide 54: Summary
Summary trovagene
Slide 55: Milestones: Significant Value Creation in 2018
Milestones Significant Value Creation in 2018 Q1 18 Q2 18 Q3 18 Q4 18 AML Phase 1bTrial Enrolling AACR Data Presentation Successful completion of 1st dosing cohort in AML trial (Arm B) ASH Data Presentation First Patient Successfully Completes Cycle 1 in AML Trial Successful completion of 1st dosing
Slide 56: Summary
Summary Precision Medicine Approach Developing PCM-075 by integrating a highly-selective antimitotic drug with a biomarker strategy Leveraging a proven cancer target PLK1 is highly expressed in tumor cells and integral to mitosis PCM-075 – first-in-class, 3rd generation PLK1 inhibitor Benefiting fro
Slide 57: For additional information or questions please contact
For additional information or questions please contact: ir@trovagene.com