Corporate OverviewDecember 2016

2

BioNano Is the Key to Unlocking the $100+ Billion Potential of the Genomics Market

BioNano’s Irys reveals genome structure, enables precision medicine and untethers the genomics market potential

Market Size Growth Catalyst Key Driver Bottleneck

$40B-$170B

Precision Medicine

PrecisionGenomes

GenomeStructure

Sequencing (Genomics) Mkt.:JPM: $20B (’14) → $170B (’16)

Application of genomics to precision medicine is the growth

catalyst

Current genome analysis is not comprehensive enough to make

precision medicine effective

Current tools fail to reveal the structure of a genome at the

chromosome level

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$0$20$40$60$80

$100$120$140$160$180

Revealing True Genome Structure Unlocks Genome Biology and the $100+ Genomics Market – Bionano Is a Significant Catalyst

$50B - $170B

$40B - $40B

Average $45B - $105B

$8B

$2B

Average $5B

$5B

Up to

$170B

Genomics Also Broadly Used As a Clinical Tool

Genomics Used As a Research Tool

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Genome Structure Drives Biology … Structural Variation Drives Disease

• Genome structure is the order, orientation and quantity of genes and other functional elements in the genome

• Structural variations (SVs) involve rearrangement or replication of thousands, and sometimes millions, of base pairs

• Hundreds of human diseases are already known to be caused by SVs

• No tool, prior to BioNano’s, existed to comprehensively and cost efficiently reveal a genome’s structure

− By systematically elucidating SVs, BioNano can cause a flood of new diagnostics and drug discovery, unlocking the promise of precision medicine

SVs Involving One Chromosome SVs Involving TwoChromosomes

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The Problem with Using Next-Gen Sequencing to Study Genome Structure Is the Lack of True Long-Range Genomic Information

Repeated Sequence

Unique Sequences

TruthCh 1

Ch 4

Ch 1

Ch 4

Problem• How many ‘s (repeated sequences)

go next to each other?• Which chromosome do the ‘s go on?

Solution• BioNano sequence maps

− Span nearly all repeats to enable accurate and complete assemblies

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Bionano Delivers the Long-Range Genomic Information to Reveal Structural Variation on a Scale that Works for Population Studies

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

Gig

abas

ses

per r

un (l

og s

cale

)

HiSeq MiSeq PacBio MinION Sanger Ion Torrent 454 SOLID

Th

rou

gh

pu

t“Read” Length

Bionano

1 Kbp 1 MbpLength (log scale)

10X

2016

2014

2017

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Our Economic Engine Is the Irys System for Genome Mapping

IrysView®IrysPrep®

IrysSolve®

IrysChip®

Irys®

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Irys Has Become a Global Leader in Mapping for Basic and Translational Research

Bionano Irys systems installed

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The Alliance with Berry Genomics Enables BioNano to Next Transform Clinical Cytogenetics

GeneticDisorders

Cancer

Develop Submit Market

Together, BioNano and Berry can revolutionize the very rapidly expanding market in China for karyotyping, FISH and microarrays

Applications & Markets

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Structural Variation Discovery & Detection

Hybrid Scaffolding

Two Main Applications for Irys: Structural Variation and Scaffolding

• Translational research• Clinical

− Known content Dx− New content Dx− Drug discovery

• Platinum genomes• Reference genomes• Plant & animal

− Basic research− Molecular breeding

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Structural Variation Detection & Discovery: BioNano Sees What Illumina Misses

Oct. ‘15 BioNano Customer Presentation: This graph depicts the density of SVs found (y axis) relative to the size of the SV found (x axis) for NGM (solid lines) against NGS (dotted lines). For SVs greater than 2,000bp, NGS has very significant drop in detection. NGM’s ability to see SVs picks up where NGS drops off.

NGS

Variation Type

SNPs & Indels(<2kb)

NGM

Variation Type

SVs(>2kb)

All SNPs, Indels & SVs

Size of Variant

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Irys Is the Only System that Systematically Finds the SVs that NGS Misses

January 2016 Genetics Publication, UCSF

7.3x215

1,570

SVs Found (>5kb)

NGS

BioNano Genomics

Improvement in Sensitivity for SVs over NGS

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Background

Institution

Principal Investigator

Eric Vilain, M.D., Ph.D.

Area Pediatric Disorders (e.g. DMD)

Technologies to be Replaced or

AugmentedNGS

Sample Types Blood

Proving the Importance of SV Detection: Ongoing UCLA Pediatric Developmental Delay & Autism Spectrum Disorder Study

• Dr. Vilain previously investigated 814 pediatric cases with presumed genetic disorders that predominantly remained undiagnosed despite exhaustive testing efforts

− This study mainly focused on sequencing the protein coding regions of a patient's genome

− The study showed a 26% diagnostic yield (was unsuccessful in identifying the cause of genetic disorders in 74% of the study patient population)

• Dr. Vilain is using multiple Irys systems in his lab to conduct research on samples obtained from 80 undiagnosed patients

Highlights of the Collaboration

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BioNano’s Irys Is the Driver of New Prostate Cancer ResearchThe BioNano Irys ran prostate cancer samples at the Garvan Institute and found novel SVs, nearly all of which were undetectable using Illumina instruments

1/10of BioNano’s SVs

detected with NGS

Only one-tenth of the large SVs found by BioNano were detectable using high-coverage Illumina runs and automated five-tooled bioinformatic analyses

94%of BioNano-called SVs

were verified

While less than 0.5% of Illumina-called variations showed oncogenic potential, over 50% of the BioNano-called variations directly impact a gene or gene region

100xgreater likelihood of

oncogenic potential in BioNano-found SVs

With BioNano-derived target regions identified, manual inspection of corresponding NGS reads and de novo assembled scaffolds allowed for 94% of BioNano-called SVs to be verified

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Examples of Human Clinical Samples Run on Irys

• Human samples are being run on Irys to either:

− Confirm SV detection as a proof of principle and/or

− Begin to show a path to a better, faster and/or cheaper method relative to a standard of care

• Selected examples of human clinical samples run on Irys:

− DMD – proof of principle shows that Irys detects the disease-causing heterozygous deletion

− FSHD – improved quantification by Irys of the D4Z4 repeat array occurring at chr 4q

− DiGeorge Syndrome – proof of principle shows that Irys detects the heterozygous 22q11 microdeletion

− Multiple Myeloma – confirms detection of three hallmark variations (2 translocations and 1 deletion)

− CML – confirmatory study shows that Irys detects the chr 9-13 translocation; also discovered a unique deletion on chr 13

− CLL – confirms detection of chr 9-22 translocation resulting in the BCR-ABL fusion protein (Philadelphia chromosome)

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The First Clinical Application is SV Detection As a Replacement for Karyotyping and FISH

Disease SVs Dual Method Test

AML del(5q)

inv(3)

inv (16)

t(8,21)

t(15,17)

t(9,11)

t(6,9)

t(1,22)

Chromosome analysis

(Karyotyping)

+ Fluorescence In Situ

Hybridization (FISH)

Karyotyping

FISH

Example: BioNano Can Replace Dual Method (Karyotyping & FISH) for Finding the 8 Lesions of AML

BioNano Irys

Systematic SV detection to simplify hematological malignancy detection

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PacBioAlone

BioNanoAlone

Hybrid (PacBio + BioNano)

Improvement By Adding BioNano

# of Scaffolds 22,433 1,039 202 99%reduction

N50/Scaffold N50 906kb 4.6Mb 31.1Mb 34.0x

increase

Irys Is the “Go To” Technology for Hybrid Scaffolding: BioNano & PacBio

Seminal publication shows that Irys resolves genome complexity that NGS alone cannot

June 2015 Nature Methods Publication, Mt. Sinai

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Illumina+10x

BioNanoAlone

Illumina + 10x + BioNano

Improvement By Adding BioNano

# of Scaffolds 5,697 1,079 170 97%reduction

N50/Scaffold N50 7.0Mb 4.6Mb 33.5Mb 4.8x

increase

Irys Is the “Go To” Technology for Hybrid Scaffolding: BioNano, Illumina & 10x

Another seminal publication shows that Irys resolves genome complexity that NGS alone cannot

May 2016 Nature Methods Publication, UCSF

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Irys Complements All Three NGS Approaches for Comprehensive Genome Assembly

or or

NGM

NGS

• Unprecedented levels of completion for human and non-human genome assemblies• Eliminates need for laborious, time-consuming and extremely costly clone methods (BAC, YAC, etc)• Essential for creating gold standards for bio-marker discovery and for building reference genomes

for non-model organisms• BioNano is the essential component for achieving these results

Technology

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The Key of Irys Is Its Proprietary Nanoscale Confinement

Biophysics tells us that by using a gradient of micro and nanostructures we can load and confine long DNA molecules into nanochannels for imaging.

• Genomic organization and architecture is related and directly observable in linear DNA.

• Molecules are suspended in biologically relevant buffers for full analysis and repeated imaging.

• Linearization requires 2D confinement in space the size of persistent length (150 bp) — ~50 nm.

Free DNA Solution DNA in a Microchannel DNA in a Nanochannel

Gaussian Coil Partially Elongated Linearized

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Irys’ Nanochannel Arrays on Silicon – Leveraging Established Semiconductor Industry Technologies

• High-throughput cartridge• Multiple samples per device

Thousands of parallel nanochannels• Imparts uniform andorderly format for

accuratemeasurements

Leverages mature semiconductor manufacturing• High-quality wafer-scalemanufacturing in state-ofthe-art semiconductor facility

The IrysChip™

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Nanochannels Enable Unprecedented Single Molecule Imaging of Truly Long Strands of DNA

Sequence motif labeling:• Nickases• PNAs• Zinc fingers• Antibodies• Etc.

Molecules are suspended and imaged in massively parallel nanochannel arrays

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Irys Workflow

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BioNano’s Nanochannel Technology Is Covered by an Extensive IP Portfolio

• BioNano has the industry leading patent estate in long-range genomic technology• 36 issued, 1 allowed and 101 pending patents worldwide

U.S. Outside U.S. Worldwide Total

Issued 7 29 36

Allowed 0 1 1

Pending 26 75 101

Total 33 105 138

Appendix

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Bionano Genomics

• Commercial stage life sciences company selling the Irys System for whole genome analysis

• Addresses the need for a better understanding of genome biology and for more actionable results from genome analyses

• Researchers and clinicians use Bionano to broaden the scope of detectable genome variation to include large structural variations and chromosomal rearrangements

• Applications in human genomics include molecular diagnostics and biomarker discovery for translational research

• Applications in non-human genomics include genome assembly for basic research in academia and industry

• Estimates of the market sizes for these applications range from $5 billion to $100+ billion

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Conventional Wisdom

Sequencing =

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Reality: Something’s Missing

=

The NGS revolution has made it possible to analyze more genomes for less cost than ever dreamed … but Something’s Missing with NGS

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SNP Detection Alone Is Not Enough to Propel Precision Medicine

SNPs:Biology ofTherapeuticResponse

SVs:Biology of

Disease

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Low Diagnosis Rate for Sequencing-Based Dx

• Only 25 – 30% cases receive confirmed molecular diagnosis

• 70 – 75% of genetic disorders go undiagnosed

• Creates heavy public health burden and family burden

• One hypothesis is that the significant variants are structural variants outside the protein coding regions

Diagnosis26%

Potential Diagnosis

28%

No Significant

Variant42%

Novel Gene Discovery4% 95% CI: 25-30%

JAMA; Dec 2014; 312:1880-1887

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• Nearly 2/3 of the human genome is repetitive and unresolvable with NGS

• Genes and other functional elements are flanked by repetitive sequences that disguise their order and orientation

• Illumina NGS spans only ~5% of these repeats

• The inability to span repeats relegates NGS to SNP detection mostly in protein-coding regions (1.5% of the genome)

Genome Composition Hides Large Structural Variants & Limits NGS to Small Variant (SNP) Detection

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Physical Genome Mapping Was a Foundational Concept … But It Was Always Technology (Throughput & Cost) Limited … Until Now!

Genome Mapping

80’s Mid 90’s

Mid 90’s

2001 2013

Shotgun Sequencing & SBSNGS, SNPs, Genes

Goal: Physical Genome Map

aCGH

FISH

BAC

YAC

Late 90’s

70’s

RFLP

Mid 2000’s

2014 2015

1 Human Map 3d

1 Human Map 1dLaunch 10 Human Maps 1d

OpGen

“…the structural organization of human DNA holds the key to understanding function, …” Bob Moyzis in Los Alamos Science, 1992

2017

Next-Gen Mapping:

Optical Mapping +Nanotechnology

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Illumina Fails to See Most SVs Because It Cannot Span Most Repeats –Over Half of the Human Genome Is Tied Up in Them

• Over half of the human genome is composed of repeat segments where many structural variations (SVs) are located. • Structural variations (SVs) are being found to be inextricably linked with human disease.• Sequencing reads that do not span segments of repeats become indistinguishable from one another.

Cumulative Number of Base Pairs in Repeats in the HumanGenome (hg19) as a Function of Repeat Size

Repeats (LINE, SINE, LTR, satellites, simple repeats, low complexity and unclassified)Segmental duplications

Comprehensive SV detection requires long-range mapping

which spans nearly all repeats.

BioNano’s long-range information complements NGS by extending the range of what’s visible in genomics

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Unparalleled Sensitivity and Specificity for Structural Variation Detection –Including Heterozygous Events

Sensitivity PPV

Homozygous Deletions 99.63%

97.1%Heterozygous Deletions 92.26%

Sensitivity PPV

Homozygous Insertions 99.01%

97.9%Heterozygous Insertions 83.56%

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Bionano Selected By Dr. Erich Jarvis to Be an Anchor Technology in the Development of 66,000 Vertebrate Genome References

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2012 2013 2014 2015

# of

Pub

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Published In Process

Accelerated Expansion of BioNano’s Market Reach Will Be Driven By the Publications from Irys Users

Published (Cumulative) In Process

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Management

Han Cao, PhDFounder & Chief Scientific Officer

• Dupont• Princeton• U Penn• Peking Univ• USTC

• Domain Associates• Exiqon• BD• GeneOhm• Applied Proteomics• Xagenic

Erik Holmlin, PhDPresident & Chief Executive Officer

Mike WardChief Business Officer

• Credit Suisse• Wasserstein• Leerink Partners

Mark BorodkinVP SystemsDevelopment

• Brooks Life Science• Affymetrix• Siemens Healthcare• Life Technologies

Sean PaolinoVP Finance

• Life Technologies• Applied Biosystems

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Board and Scientific Advisors

Pui-Yan Kwok, M.D., Ph.D.Henry BachrachDistinguished Professor,University of California, San Francisco

Charles Lee, Ph.D.Director, The Jackson Laboratory for Genomic MedicineCo-chair of the Structural GenomicVariation Analysis group forthe 1000 Genomes Project(www.1000genomes.org)

Albert Luderer, PhDIndependent DirectorCEO – Integrated Dx

David Barker, PhDChairman; Independent DirectorFormer CSO – Illumina

Brian Halak, PhDDomain Associates

Darren Cai, PhDLegend Capital

Contact:

Erik Holmlin, CEOeholmlin@bionanogenomics.com