Cardiff Oncology, Inc. · NASDAQ:CRDF
Cardiff Oncology — Trovagene — Investor Presentation (July 2013)
33 slides from Cardiff Oncology's investor presentation, Jul 23, 2013
Slide 1: A better clinical pathway for cancer monitoring
A better clinical pathway for cancer monitoring Antonius Schuh, Ph.D. | Chief Executive Officer July 2013
Slide 2: Forward-Looking Statements
Forward-Looking Statements DISCLAIMER Statements in this presentation about the Company's expectations, applications of its technology, markets, launch of tests and other statements that are not historical facts are "forward-looking statements" within the meaning of Section 27A of the Securities Act
Slide 3: Our goal: Towards better treatment for cancer
Our goal: Towards better treatment for cancer INTRODUCTION A better clinical pathway for cancer monitoring Novel clinical utility: non-invasive, near real-time detection of oncogene mutations for any tumor type
Slide 4: Welcome to Trovagene, Inc.
Welcome to Trovagene, Inc. INTRODUCTION INTRODUCTION Addresses a high unmet need in cancer by enabling easier, more frequent monitoring of emergence of oncogene mutation status, disease progression and recurrence Unique IP around cell-free DNA in urine creates a powerful core diagnostic platform for
Slide 5: Trovagene Core Team
TROVAGENE CORE TEAM Antonius Schuh PhD CEO CEO Sorrento Therapeutics, AviaraDx, Arcturus Biosciences, Sequenom PhD Pharm. Chem Stephen Zaniboni CFO Mark Erlander PhD CSO Keith McCormick VP, Comm. Ops Michael Terry VP, Corp. Devel. Thomas Adams, PhD (Chair) John P. Brancaccio, CPA Gary S. Jacob, PhD
Slide 6: Understanding cell-free DNA for cancer monitoring
Understanding “cell-free” DNA for cancer monitoring THE CLINICAL UTILITY OF CELL-FREE DNA FROM URINE Cell-free DNA is released by dying cells in the human body Cells in the body die continuously in a process known as “apoptosis” , releasing DNA/RNA into the bloodstream This “cell-free” DNA, detectab
Slide 7: Why not simply use a blood specimen?
Why not simply use a blood specimen? THE CLINICAL UTILITY OF CELL-FREE DNA FROM URINE Blood Draw Sample quantity is limited Sample frequency is limited Inconvenient for patient – requires an appointment Painful and perceived as threatening Requires a medical professional Specimen is a biohazard Requ
Slide 8: Kidneys filter cell-free DNA from blood into the urine
Kidneys filter cell-free DNA from blood into the urine THE CLINICAL UTILITY OF CELL-FREE DNA FROM URINE By isolating cell-free DNA from urine, Trovagene eliminates the need for the cost, complexity and inconvenience of a blood sample Truly non-invasive Patient can self-sample at home or clinic No me
Slide 9: Enabled by a confluence of emerging technologies
Enabled by a confluence of emerging technologies Ability to detect single DNA molecules in a urine sample Trovagene IP Next gen sequencing Digital PCR THE CLINICAL UTILITY OF CELL-FREE DNA FROM URINE RainDance Droplet Digital PCR up to 5,000,000 target sequences Oncogene mutations are rare events Tu
Slide 10: Why Cell-free DNA?
Why Cell-free DNA? Tumors are heterogeneous in their tumor mutational make-up Would need multiple tissue/tumor biopsies to determine heterogeneity and optimal therapy Cell-free DNA from tumors is released into the blood plasma after cell-death Previously established that cell-free DNA increases with
Slide 11: Detecting & monitoring cancer mutations key to effective therapy
Healthy Subject Oncogenic Mutation DRUG A CYCLE 1 CYCLE 2 CYCLE 3 CYCLE 4 SURVIVAL TUMOR MUTATION#1 Selective pressure of targeted drugs enrich tumor tissue with new mutant cells that are drug resistant Match up targeted drugs with mutation profile Treatment SURVIVAL DRUG B DRUG C DRUG D SURVIVAL CE
Slide 12: Opportunity to implement monitoring of tumor dynamics, demonstrated in plasma
Opportunity to implement monitoring of tumor dynamics, demonstrated in plasma High signal consistent with metastatic patient CLINICAL DEVELOPMENT PROGRAM Patient responds to therapy Disease progression Patients responds to therapy switch Hormonal therapy No response to hormonal RX 1Dawson et al., NE
Slide 13: Building value through clinical validation
Building value through clinical validation PHASE 1 Initial studies demonstrating concordance with the existence of cancer mutations between tumor, blood and urine. Opportunity for diagnosis when a biopsy is not an option for example. Diagnostic PHASE 2 Tracking cancer mutation trends quantitatively
Slide 14: Clinical Study: Detecting & Monitoring Tumor Mutations in Urine
Clinical Study: Detecting & Monitoring Tumor Mutations in Cell-free DNA from Urine in Metastatic Cancer Patients Title: KRAS and BRAF Mutational Analysis of Cell-free DNA from Urine in Patients with Advanced Cancers Principal Investigator: Filip Janku MD PhD; Investigational Cancer Therapeutics (Pha
Slide 15: Development of optimal DNA extraction methodology
Development of optimal DNA extraction methodology CLINICAL DEVELOPMENT PROGRAM For small target purification - detection of 50 bp target spiked into identical 10 mL urine samples. First Elution First and Second Elutions Combined Total Number of Copies Yields >95% recovery
Slide 16: Two-Step Assay Design for 28-30 bp footprint
STEP ONE Pre-amplification with wild-type suppression DNA template with mutation (“M”; Patient DNA) A B STEP TWO Amplification with A,B primers, digital droplet PCR (Raindance) DNA template with no mutation (Wild Type (“WT”; Patient DNA) WT Blocker of A,B primers M WT A B M M TAQMAN Probe Amplificat
Slide 17: High sensitivity for mutation detection
0.03% mutant in WT Healthy Control (WT) G12V mutation confirmed MDJ#23 MDJ#9-P1 V600E mutation confirmed MDJ#14 G12D mutation confirmed 0.03% mutant in WT Healthy Control (WT) 0.03% mutant in WT Healthy Control (WT) Template Control 0.03% MDJ#23 #molecules/25ul 44 319 1083 Template Control 0.03% MDJ
Slide 18: Detection sensitivity: BRAF V600E mutation
06-13-2013 30ng DNA input in 1st round PCR Detection sensitivity: BRAF V600E mutation CLINICAL DEVELOPMENT PROGRAM #WT molecules/25 ul 517380 545319 552052 #mut molecules/25ul 50439 5065 2493 %mut detect in WT 9.75% 0.93% 0.45%
Slide 19: Healthy Controls Have Low Background
06-13-2013 30ng DNA input in 1st round PCR Detection sensitivity: BRAF V600E mutation CLINICAL DEVELOPMENT PROGRAM Healthy Controls Have Low Background Lane A B C D G H Assay VIC/FAM V600E-FAM V600E-FAM V600E-FAM V600E-FAM V600E-FAM V600E-FAM Template KR005 pool ID003 pool TRGD001 pool 1 0.03%V600E
Slide 20: Metastatic cancer patients with KRAS and BRAF mutations: 95% concordance
ID Mutation Tumor Staging Cancer Type Results DNA mutation fragments 14 G12D IV Colon 489 15 G12D IV Colon 563 16 G12D IV Appendiceal Adenocarcinoma 1231 17 G12D IV Colon 1935 18 G12D IV Colon 2825 19 G12V IV Adenocarcinoma/upper lobe lung 1083 20 G12V IV Colorectal 1168 G12D Healthy Control 234 20
Slide 21: Next Gen Sequencing: content rich, higher throughput, lower cost
Content Rich Ability to detect multiple mutations in a single run and any nucleotide at each position 9 KRAS mutations in a single assay: G12A, G12C, G12D, G12F, G12R, G12S, G12V, G13C, G13D Target Multiplexing Multiple Genes and multiple sites per gene can be interrogated The potential to monitor d
Slide 22: Anatomy of a KRAS Next Gen Sequencing Assay
CLINICAL DEVELOPMENT PROGRAM ...and provides generic assay design for all mutations Anatomy of a KRAS Next Gen Sequencing Assay Enables unsupervised query for any mutation, eliminating the need for the creation of individual assays for specific mutations.
Slide 23: NGS has the required detection sensitivity
Actual Mutation Frequency Observed Frequency 50.00% 91.14% 12.50% 86.74% 3.13% 72.26% 0.78% 41.32% 0.20% 16.59% 0.05% 5.72% 0.01% 2.24% 0% 0.30% CLINICAL DEVELOPMENT PROGRAM NGS has the required detection sensitivity % Mutant Total Input (ng) WT Genomes Mutant Genomes Total Reads Expected Read Count
Slide 24: Next steps for a first NGS-based offering
53 initial targets: can be assessed using 9 designs multiplexed in a single well. The largest amplicon fragment is only 34bp. Another control set can be added for quantification purposes 1 KRAS assay 9 mutations 1 NRAS assay 7 mutations 1 BRAF 4 mutations 2 PIK3CA assay 4 mutations 2 EGFR assays 3 m
Slide 25: Core IP extends into assay detection and development
Core IP extends into assay detection and development
Slide 26: Trovagene's Proprietary HPV Test
Trovagene’s Proprietary HPV Test
Slide 27: HPV in Urine: market dynamics
HPV in Urine: market dynamics Market Opportunity Estimated 11-12M HPV tests run annually (US) 1 Represents only about 35% market penetration 8.7 – 14.2% of cases come back as positive2 Repeat HPV testing often performed at 6 and 12 months HPV 1. McEvoy and Farmer – Licensed Market Research Report –
Slide 28: Validating analytical performance of our HPV assay
Validating analytical performance of our HPV assay Europe (UK) Queen Mary University of London PREDICTORS 4 Study - 500 patient cohort - samples currently being processed HPV Brazil Barretos Cancer Hospital – largest cancer hospital in Brazil 350 patient cohort - enrollment underway India Simbiosys
Slide 29: 2012 achievements
2012 achievements Acquired CLIA Laboratory CLIA-certified, CAP-accredited high complexity molecular diagnostic lab Strengthened Patent Portfolio Issued U.S. Patent for NPM Mutants to Diagnose and Monitor Acute Myeloid Leukemia Issued European Patent for Detection of Pathogenic Infections Improved Li
Slide 30: 2013 achievements
2013 achievements Demonstrated Proof of Concept for Tumor Mutation Detection from Urine Samples of Medistatic Cancer Patients Validated the presence of BRAF, KRAS in multiple cancer types Initiated R&D Partnership with PerkinElmer Collaborate to develop test to determine liver cancer risk Initiated
Slide 31: PerkinElmer R&D agreement
PerkinElmer R&D agreement Research & Development agreement with PerkinElmer to develop a test to determine the risk for developing liver cancer TROV will develop the test TROV and PKI will jointly validate the test The Companies will collaborate on potential automation for TROV’s DNA isolation techn
Slide 32: Illumina R&D agreement
Illumina R&D agreement Goal – POC to develop library for NGS (next generation sequencing) from cell-free DNA isolated from urine Strategic imperative to establish TrNAs on NGS NGS will become a platform standard in the industry TROV to gain significant domain knowledge from market leader in NGS Illu
Slide 33: For further information
For further information Please contact: Antonius Schuh, CEO aschuh@trovagene.com Stephen Zaniboni, CFO szaniboni@trovagene.com