microbiome diagnostics platform for microbiome health and colon cancer prevention

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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

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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

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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%

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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%

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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

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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.

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Saves Time by Eliminating Ligation Step The elimination of the extra ligation step saves 1-2 hours per run.

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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.

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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)

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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

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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

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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

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Human Gut

Microbiome health & disease

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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