Microbiome Diagnostics Platform for Microbiome Health and Colon Cancer Prevention
-
Upload
laura-berry -
Category
Science
-
view
27 -
download
0
Transcript of Microbiome Diagnostics Platform for Microbiome Health and Colon Cancer Prevention
Metabiomics Safe Harbor Statement: This slide deck contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the potential results and future outcomes our clinical
research and business plan; ability to discover biomarkers and diagnostic tests. including the ability of the company’s tests to impact clinical practice. Forward-looking
statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of
future performance. These risks and uncertainties include, but are not limited to: the results of clinical and developmental studies and any resulting products and services; the regulation of our tests by the FDA and other agencies abroad; and the other risks set forth in the company’s business plans and presentations. These forward- looking
statements speak only as of the date hereof. Metabiomics disclaims any obligation to update these forward-looking statements.
Microbiome MDx Platform Overview
1
mission and vision
2Confidential and Proprietary Information - Not For Distribution
Our vision is to continuously advance our patented MultiTag™ DNA sequencing technology and metagenomics discovery platform to pursue innovative molecular systems biology, biomarker discovery, and clinical research aimed at developing diagnostics and therapeutics for the prevention of colon cancer and other gastrointestinal cancerous, autoimmune, and infectious diseases.
Our mission is to Eliminate Colon Cancer
Worldwide with a Low-CosT, Easy-to-use, Non-Invasive,
Screening test for precancerous adenomas
colon cancer is a major global killer
121kChina23%
56kNorth America
11%
31kSouth America
6%
Europe34%
More than 1.5 million people around the world are diagnosed with colon cancer each year, more than 600k die.
Colon cancer is the 3rd-most common cancer in the world, and causes the 2nd-most number of deaths.
122kAsia23%
CRC creates $14 Billion in healthcare costs in the US annually.
187k
In the US, there are 137,000 new cases every year, 56,000 deaths. 3Confidential and Proprietary Information - Not For Distribution
but it shouldn’t beColon cancer is the most preventable, yet least prevented cancer
4
47% of Americans do not adhere to public health screening guidelines
60% of Cancers are not detected until later stages 3 and 4
14M Colonoscopies are performed annually
3%Since 1998 there has been a 3% annual decline in CRC deaths due to the detection and removal of adenomas
Early Detection Saves Lives
5Confidential and Proprietary Information - Not For Distribution
It can take 10 years for a polyp to develop into cancer
100% 10-year survival rate with detection of pre-cancer
Stage 1 cancer rapidly advances to stage 4 in a few years
Chances of survival fall drastically in late stage cancers
Healthcare costs for patients with stage 4 cancer is $140k
0%
25%
50%
75%
100%
$0
$35,000
$70,000
$105,000
$140,000
Pre-Cancer Stage 1 Stage 2 Stage 3 Stage 4
CRC Management Costs Survival Rate
intercepting colon cancer is Possible
6Confidential and Proprietary Information - Not For Distribution
Metabiomics Microbiome MDx is only test with high sensitivity to hyperplastic polyps and adenomas
hyperproliferation hyperplastic polyps adenomatous polyps
Severe dysplasia precancerous polyp
adenocarcinoma malignant
invasive cancer malignant
existing non-invasive Tests Miss Pre-Cancerous Polyps
7Confidential and Proprietary Information - Not For Distribution
Non-Advanced Adenomas
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
FOBT-low
FOBT-high
FIT-Low
FIT-Mid
Fit-High
EXAS < 5 m
m
EXAS < 5-9 m
m
Specificity Sensitivity
FOBT and FIT tests detect blood in fecal samples
Many adenomas do not bleed, FOBT and FIT have low sensitivity
FOBT & FIT tests have utility due to high specificity and low cost
Exact Sciences adds methylation/mutation markers + FIT
Epi ProColon blood test claims no sensitivity to adenomas
Advanced Adenomas
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
FOBT-low
FOBT-high
FIT-Low
FIT-Mid
FIT-High
FIT-Dee
pCEXAS
Stage I-IV Cancer
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
FOBT-low
FOBT-high
FIT-Low
FIT-Mid
Fit-High
FIT-Dee
pCEXAS
Epi ProColon
Colorectal Cancer Screening for Average-Risk North Americans: An Economic Evaluation, Cologuard Exec Summary
We Have A Solution
8
Highest Accuracy Metabiomics MultiTagDx screening test can detect the smallest precancerous adenomas
Earliest Detection Microbiome disruption/dysbiosis provides the earliest warning signs of polyps and carcinogenesis
Non-Invasive and Easy-to-Use Low-cost, easy-to-use, stool collection kits require no stool contact and can be mailed to our centralized testing facility
Cost-Effective Leveraging Next-Generation DNA Sequencing (NGS) and our patented MultiTag process will reduce cost to less than $200 per test
A game-changing Pre-Cancerous Adenoma Screening Test for Colon Cancer Prevention
After detection, colon polyps will be removed via a follow-up colonoscopy and polypectomy
88% - 96% Sensitivity
92% - 96% Specificity
Adenoma (119) vs Healthy (112) 10-fold cross-validation test pre-publication, subject to change
metabiomics Team
9Confidential and Proprietary Information - Not For Distribution
Visionary Entrepreneur and Inventor, Systems Engineer, Data Scientist
Thomas J. Kuehn, PHD Chairman and CEO
Co-founder, Business Dev, Marketing, Finance, R&D Management
Gregory J. Kuehn, MBA President and COO
Experienced Executive, Sales Reimbursement for Healthcare
Products + Services
Chris Metz Business Development and Sales
Co-Founder, Pioneering molecular ecologist, inventor, Former Director of
Harvard Genome Laboratory
Patrick Gillevet, PHD Chairman Science Advisory Board
CEO COO VP AB
Tom Soriano - DOCRO Regulatory Bob Thiel, PHD - DOCRO Statistics
Jim Linfield. JD - Cooley LLP Erich Veitenheimer, JD PHD Cooley LLP
Lila Hope, JD PHD Cooley LLP Sandy Sterrett, Jr. JD Rimon P.C.
Mark Hayman, JD PHD;
Se Jin Song PHD Masi Sikaroodi, PHD
Bob Brown, PHD Tiffany Weir, PHD
Paul DeRidder, MD, PHD
Advisors and Consultants
Leading Gastroenterology Practitioner, Crohns and Colitis Fdn, Am. Soc.
Gastrointestinal Endoscopy
Louis Korman, MD VP and Chief Medical Officer
Gastroenterology & Internal Medicine National Board Crohn’s and Colitis Fdn,
President, APCR Clinical Research
Robert Hardi, MD VP Clinical Research Director
Board Certified Pathologist, Anatomic, clinical, cytopathology Founder of
Capital Digestive Care CAP /CLIA Lab
Jeff Baybick, MD VP Pathology and Lab Operations
CMO VP VP
MB-01 Colorectal Neoplasia Clinical studyMB-01 is the largest and most rigorous human microbiome diagnostics clinical study to date producing breakthrough protocols and predictive modeling results.
10Confidential and Proprietary Information - Not For Distribution
Specific Aims Determine the sensitivity and specificity for detection of colorectal neoplasia based on 16S rRNA microbiome analysis and clinical risk factors
Study Design cross-sectional, observational, case-controlled study, IRB Approved, ClinicalTrials.gov: NCT02141945, 2 colonoscopy center sites in metro DC area, Capital Digestive Care
Patient Population 260 patients undergoing CRC screening by colonoscopy with collection of three samples per patient including rectal swab, home stool sample and biopsy
Classification and Metadata Clinically relevant classes were defined by gastroenterologists and pathologists including: Hyper-plastic Polyp, Adenomas, Advanced Adenoma, Age, Gender, BMI, Race, History of Polyps
microbiome diagnostics workflowMetabiomics is developing and end-to-end pipeline for microbiome diagnostics
11Confidential and Proprietary Information - Not For Distribution
02. Automated Sample Prep Nucleic Acid Extraction
16S PCR
01. Sampling Kits Patient and physician friendly
sampling kits, proper preservation of samples
03. MultiTag Sequencing Primer Kits
Patented 16S Library Preparation kits enabling multiplexing of 96 - 384 samples/run (see MultiTag
Sequencing slide)
05. Computational Diagnostics
Automated software algorithm for diagnostics based on multivariate
statistics and machine learning technology
Physician Report 1. Qualitative detection of colorectal
polyps and adenomas, 2. Qualitative detection and
classification of colorectal hyperplastic polyps,
adenomatous polyps, and/or advanced adenomas
04. NGS Sequencing MiSeqDx, Ion Torrent PGM,
HiSeqDx (future)
MultiTagDx Process
Sample-to-insight, 96X, 192X, 384x high-
throughput, multiplexing
Microbiome Sampling methods and kitsInnovative sampling standards and kits that can be used by the patient at home or by the physician during an examination
12Confidential and Proprietary Information - Not For Distribution
Puritan Hydraflock® Swabs Origin Sciences - OriCol
Use as rectal swab or home stool sampling direct from toilet paper
Patient and physician friendly
Validated by MB-01 study, 500+ samples with minimal PCR failures
No bowel preparation required
Biomarker-rich samples human and microbiome DNA, RNA, proteins, antibodies
Large sampling surface contact and volume
Significant reduction of stool contamination
Quantitative sample reproducibility
OriCol™ is an innovative device for the convenient and
effective sampling of mucocellular material that has migrated along the entire colon to the rectum.
Advanced Puritan Hydraflock® swabs and RNA/DNA
preservative for transport at ambient temperatures,
Use as rectal swab or home stool sampling direct from
toilet paper to the swab with no stool contact
patented Tagged Fusion Primers multitag SequencingAwarded in the US in 2013 (US Patent No, 8603749) and Europe (EP 2082063) in 2014, awarded in Canada in 2016. Divisional “MultiTag Primer Kit” patents allowed in EU and awarded in US in 2016. Priority date of 11/15/2006.
13Confidential and Proprietary Information - Not For Distribution
Simplifies Library Preparation MTS supports pooling and sample handling for multiplexing, managing and optimizing throughput of NGS process.
04
Saves Time by Eliminating Ligation Step The elimination of the extra ligation step saves 1-2 hours per run.
05
Provides Patent Protection & FTO for MDx Assays The Mayo vs. Prometheus decision limits the ability to patent a correlation with a measurement of a natural process.
06
Cost-Effective Sample Barcoding and Multiplexing 3-piece Fusion Primer contains: 1) Patient/Sample Barcode - unique oligonucleotide 2) Target Primer - i.e. 16S variable regions 3) Sequencing Adapter for MiSeqDX, Ion Torrent PGM, ect…
01
Minimizes PCR Amplification Bias A critical feature because the ligation of sample barcodes in 2-step process has been proven to distort microbial community profiling (relative abundance OTU tables)
02
Yields Accurate/Reproducible Quantification of Relative Abundances Essential for molecular diagnostics, MultiTag (barcoded fusion primers) are the gold-standard in leading microbiome labs around the world. Other primer designs have been shown to negatively impact the reproducibility of microbiome studies.
03
Jones, MB, Library preparation methodology can influence genomic and functional predictions in human microbiome research, pnas (2015) Binladen J, Gilbert MTP, Bollback JP, Panitz F, Bendixen C (2007) The Use of Coded PCR Primers Enables High-Throughput Sequencing of
Multiple Homolog Amplification Products by 454 Parallel Sequencing. PLoS ONE 2(2): e197. doi:10.1371/journal.pone.0000197 Sikaroodi 2015- Quality control in multi-tag pyrosequencing of microbial communities MultiTag Sequencing Ecogenomics Analysis US Patent No 8,603,749 B2
Platform Independent Protocol for
MultiTag Next-Generation sequenCing
14
Patented solution for sample multiplexing and barcoding with a fusion primer designed to minimize library preparation, cost per sample/run, and PCR amplification bias while providing accurate quantification of amplicon abundances.
Library Preparation with Fusion Primers Involves the preparation of a DNA Library comprising a high-throughput NGS adapter, a sample-specific barcode sequence and a target primer sequence that are fused by PCR.
Pool Samples / Multiplex Primer kits can include 96, 192, 384 or any number of unique barcoded primers for multiplexing samples.
NGS Sequencing Platform-independent primers can be customized for Illumina or Life Technologies adapters or any sequencing-by-synthesis instrument.
Data Processing and De-multiplexing Sequences are assigned to samples during bioinformatics processing using the sample-specific tags/barcodes.
Confidential and Proprietary Information - Not For Distribution
01
02
03
04 5’
5’3’
3’
Barcoded Amplicon flanked by NGS Sequencing Adapters
16S or 18S Amplicon flanked by linker sequences
+ MultiTag sequencing fusion primersGene TargetBarcodeNGS Adapter
3’
5’
5’5’
PCR amplification with barcoded/tagged forward and reverse primers
microbiome diagnostics
18
The human gut microbiome provides the earliest warning of precancerous colon polyps and carcinogenesis.
Disruption/Dysbiosis of the microbiome has been linked to inflammatory responses and metabolic processing alterations
Chronic inflammation is known to be an important feature in CRC progression, linked to oxidative DNA damage
Bacterial mutagens can also damage genomic DNA
16S rRNA Microbial DNA sequencing platform
Metabiomics assays begin with microbial nucleic acid extraction and next-generation sequencing
Sources: McAllister 2014, Dulal 2014, O’Keefe 2015, Arthur et al 2012, Boleij 2012, Bongers et al 2014
01
02
03
04
Human Gut
Microbiome health & disease
19
The microbiome co-evolved with the human host and is an important player in human health and disease. Nature Review - A microbial perspective of human developmental biology Nature Review - Diet-microbiota interactions as moderators of human metabolism
The microbiome activates and regulates the immune system. Nature Review - The microbiome and innate immunity Nature Review - The microbiota in adaptive immune homeostasis and disease Cancer J Author Manuscript - Microbiota and Immune Responses in Colon Cancer
The healthy microbiome is the first line of defense by fighting off pathogenic bacteria. Nature Review - Interactions between the microbiota and pathogenic bacteria
10 to 1 trillions of microbial cells vs human cells, microbial cells weighs ~3 pounds
100 to 1 1M+ microbial genes vs 23k human genes
Dysbiosis of the microbiome has been linked to a broad range of human diseases. Nature Review - Microbiome-wide association studies link dynamic microbial consortia to disease
Microbiome MDX pipeline
20Confidential and Proprietary Information - Not For Distribution
Biomarker Discovery
Clinical Trials
Diagnostic Modeling
Clinical Validation
Service Launch
MultiTag 16S rRNA Primer Kits Microbiome Health Assays
Colorectal Adenoma LDT
IBD/IBS LDT
Colorectal Adenoma and Carcinoma FDA Cleared IVDs
Microbiome Health, Metabolic Disease, Obesity & Diabetes
Therapeutic and Pharmabiomic Discovery
Our Microbiome NGS Diagnostics Platform and NGS Microbiome Sequencing Solutions supports a pipeline of MDx services
Contact UsMetabiomics currently has a “virtual office” but is planning on expanding in the Fitzsimmons Technology Park on the Anschutz medical campus in Aurora, Colorado
Confidential and Proprietary Information - Not For Distribution
Email & Website http://metabiomics.com [email protected]
Phone & Fax Phone: 571-354-6171 Fax: 720-367-5071
Social Media facebook twitter @metabiomics