Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Trovagene — IPO Roadshow (June 2018)
38 slides from Cardiff Oncology's IPO roadshow presentation, Jun 4, 2018
Slide 1: Transforming Patient Care with Targeted Cancer Therapeutics
Issuer Free Writing Prospectus dated June 4, 2018 Relating to Prospectus dated June 4, 2018 Filed Pursuant to Rule 433 Registration Statement No. 333-224808 Transforming Patient Care with Targeted Cancer Therapeutics june, 2018
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: Free Writing Prospectus
Free Writing Prospectus This presentation highlights basic information about Trovagene, Inc. and the offering. Trovagene, Inc. has filed a registration statement on Form S-1 (Registration No. 333-224808) (including a prospectus) with the U.S. Securities and Exchange Commission (“SEC”) for the offeri
Slide 4: Public Offering Summary
Issuer Trovagene, Inc. Listing / Symbol NASDAQ: TROV Expected Offering Size Approximately $15,000,000 (100% Primary) Over-Allotment Option 15% (100% Primary) Securities Offered Class A Unit of Common Stock and Warrants Class B Unit, for 4.99% or greater shareholders, of Preferred Stock and Warrants
Slide 5: Trovagene Snapshot
Trovagene Snapshot Oncology Focus Clinical-stage therapeutics company developing therapies for hematologic and solid tumor cancers Lead drug candidate, PCM-075, a highly-selective Polo-like Kinase 1 (PLK1) inhibitor Phase 1 safety trial in advanced/metastatic solid tumor cancers published in 2017 Tw
Slide 6: Key Advisors and Collaborators
Key Advisors and Collaborators Jorge Cortes, MD – MD Anderson Cancer Center 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 Program David Einstein
Slide 7: PCM-075 Pipeline Assets
PCM-075 Pipeline Assets Indication (Target) Preclinical Phase 1 Phase 2 Non-Hodgkin Lymphoma Phase 1 Advanced or Metastatic Solid Tumors Published in Investigational New Drugs Metastatic Castration-Resistant Prostate Phase 2 open-label clinical trial in combination with abiraterone acetate (Zytiga®)
Slide 8: PCM-075 – Polo-like Kinase (PLK1) Inhibitor Lead Drug Candidate
PCM-075 – Polo-like Kinase 1 (PLK1) Inhibitor Lead Drug Candidate
Slide 9: PLK1 – Established Cancer Target
PLK1 – Established Cancer Target PLK1 belongs to a family of kinases (PLK1,2,3,4 and 5) PLK1 is the master regulator of the cell-cycle and only with expression of PLK1 are cells able to pass-through the last checkpoint (G2Mitosis) and divide1-6 PLK2-PLK5 have properties more consistent with tumor su
Slide 10: PLK1 – Overexpressed in Numerous Cancers
PLK1 – Overexpressed in Numerous 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 2
Slide 11: Clinical Development Program
Clinical Development Program Hematologic and Solid Tumor Cancers PCM-075 in combination with either low-dose cytarabine or decitabine Lead Investigator: Dr. Jorge Cortes – MD Anderson Study to include up to 10 clinical trial sites Phase 1b/2 Open-Label Trial in Acute Myeloid Leukemia (AML) - Ongoing
Slide 12: PCM-075 – Highly Selective PLK1 Inhibitor
PCM-075 – Highly Selective PLK1 Inhibitor 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 d
Slide 13: PCM-075 – Oral Administration and Half Life
PCM-075 – Oral Administration and Half Life 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) NerPharMa Inc. – contract manufacturer for GMP API a
Slide 14: PCM – Synergistic in Combination
PCM 075 – Synergistic in Combination High PLK1 expression is associated with the most aggressive forms of hematologic and solid tumor cancers PCM-075’s synergistic activity may enhance the efficacy of numerous standard-of-care therapies 1Alphabetical order. 2Preclinical data on file with PCM-075 and
Slide 15: 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 16: 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 17: Synergy: PCM-075 + Abiraterone (Zytiga)
Synergy: PCM-075 + Abiraterone (Zytiga®) Metastatic Castration-Resistant Prostate Cancer (mCRPC) 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 mitosi
Slide 18: PCM-075 Summary
PCM-075 Summary Characteristic Benefit PCM-075 Oral; 24-Hour Half-Life Enables sustaining drug levels without compromising safety Selective for PLK1 Provides highly-targeted therapy for G2/M cell-cycle division checkpoint Reversible, on-target side effects, consistent with the expected mechanism of
Slide 19: PCM-075 Clinical Trials
PCM-075 Clinical Trials Phase 1 Advanced/Metastatic Solid Tumors Phase 1b/2 Acute Myeloid Leukemia (AML) Phase 2 metastatic Castration-Resistant Prostate Cancer (mCRPC)
Slide 20: Phase 1 Safety Trial Completed in Solid Tumors
Phase 1 Safety Trial1 Completed in Solid Tumors 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 16 of the 19 patient
Slide 21: Acute Myeloid Leukemia
Acute Myeloid Leukemia1 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 can include: Chemotherapy Radiation Stem cell
Slide 22: Pre-Clinical Data in AML
Pre-Clinical Data in AML Compound Median Survival Time (days) Placebo 28 Cytarabine 36 PCM-075 62* Treatment Started 20 Days Post-Inoculation PCM-075 60 mg/kg BID (Days 1-2 with 5-day rest) + cytarabine 75 mg/kg IP Injection (Days 1-5 with 5-day rest) 1Casolaro et al (2013) PLOS One *p = 0.001 Vehic
Slide 23: Previous PLKi Clinical Experience in AML
Previous PLKi Clinical Experience in AML Volasertib (Boehringer Ingelheim) Volasertib demonstrated clinical activity in AML Phase 2 and Phase 3 clinical trials Phase 2 trial: Increased response rate (31.0%) vs control (13.3%) and significant survival benefit in elderly patients ineligible for intens
Slide 24: PCM-075 attributes
PCM-075 Highly Selective Short Half-Life Synergistic in Combination Broad Applications Orally Available
Slide 25: Treatment Pathway in Acute Myeloid Leukemia
Treatment Pathway in Acute Myeloid Leukemia AML Diagnosis 20,0001 cases/year Eligible for Induction Treatment 12,000 Relapse & Refractory 30-50% 4,000 to 6,000 Phase 1b/2 AML Trial: To assess the safety and efficacy of PCM-075 in combination with cytarabine or decitabine Responders 50-70% Ineligible
Slide 26: Ongoing Phase 1b/2 Clinical Trial in AML
Ongoing Phase 1b/2 Clinical Trial in AML Current Clinical Trial Sites MD Anderson Yale Cancer Center University of California Los Angeles Kansas University Cancer Center PCM-075 in Combination with Either Low-Dose Cytarabine (LDAC) or Decitabine in Patients with Acute Myeloid Leukemia (AML) Seattle
Slide 27: Ongoing Phase 1b/2 Clinical Trial in AML
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 28: Biomarker Assessment in AML
Biomarker Assessment in AML Biomarkers will be measured and correlated with pharmacokinetic drug levels to assess: Inhibition of PLK1 Changes in blast cells in blood and bone marrow Underlying tumor genetics Blood sample (baseline) AML Patient + PCM-075 Blood sample (post PCM-075) Pre- and Post-Dose
Slide 29: 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 30: 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 31: PLK1 Sensitivity of AR-Driven Tumors
PLK1 Sensitivity of AR-Driven Tumors PLK1 dependent microtubule dynamics promotes androgen receptor (AR) signaling in prostate cancer1 PLK1 is upregulated in androgen insensitive prostate cancer cells and its inhibition leads to necroptosis2 PLK1 inhibition improves abiraterone acetate efficacy3 Inh
Slide 32: 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 33: Planned Phase 2 Clinical Trial in mCRPC
Planned Phase 2 Clinical Trial in mCRPC Efficacy Endpoints Effect of PCM-075 in combination with Zytiga®/prednisone on disease control assessed by prostate-specific antigen (PSA) decline or stabilization pre- and post-treatment Safety Endpoint Safety of PCM-075 in combination with Zytiga®/prednisone
Slide 34: Looking Ahead
Looking Ahead trovagene
Slide 35: 2018 Goals
2018 Goals Completion of dose escalation cohorts in Phase 1b trial1 Safety and preliminary clinical activity (pharmacodynamic markers) Recommended Phase 2 dose1 Initiation of Phase 2 continuation trial1; possible preliminary data Activation of Beth Israel, Dana Farber and Massachusetts General and f
Slide 36: Takeaways
Takeaways PLK1 is an established cancer target; the PLK inhibitor drug class has demonstrated clinical activity in AML PCM-075 is the only oral, highly-selective PLK1 inhibitor in clinical trials Synergy demonstrated with PCM-075 in combination with chemotherapies and targeted therapeutics 2 clinica
Slide 37: Financial Summary and Capitalization
Financial Summary and Capitalization Capitalization Table as of April 30, 20181 Common Shares2 4,953,442 70% Warrants Outstanding 1,489,488 21% Options Outstanding3 630,061 9% Restricted stock units 30,919 0% Fully Diluted Shares4 7,103,910 100% 1Q 2018 Financial Summary Cash: $6.7 M Repayment of Eq
Slide 38: For additional information or questions please contact
For additional information or questions please contact: ir@trovagene.com