Safe Harbor
Certain statements made in this presentation that are not based on historical
information are forward-looking statements which are made pursuant to the
safe harbor provisions of the Private Securities Litigation Reform Act of
1995. This presentation contains express or implied forward-looking
statements relating to, among other things, managements forecast of
financial performance, estimates of expenses and future revenues and
profitability, product development and marketing plans, and managements
plans, objectives and strategies. These statements are neither promises nor
guarantees, and are subject to a variety of risks and uncertainties, many of
which are beyond Helicos control, which could cause actual results to differ
materially from those contemplated in these forward-looking statements. In
particular, the risks and uncertainties include, among other things, our
ability to successfully complete the manufacturing process and commercialize
the HeliScope system; our ability to secure our first orders; our history of
operating losses and ability to achieve profitability; our ability to
establish manufacturing capabilities; the research and development spending
levels of academic, clinical and governmental research institutions and
pharmaceutical, biotechnology and agriculture companies who may purchase our
HeliScope system; our reliance on third-party suppliers; competition;
changing technology and customer requirements; our ability to operate in an
emerging market; market acceptance of our technology; the length of our sales
and implementation cycles; our dependence on large contracts for the sale and
implementation of our HeliScope system; failure of our technology and
products; our ability to maintain customer relationships and contracts;
ethical, legal and social concerns surrounding the use of genetic
information; our ability to retain our personnel and hire additional skilled
personnel; our ability to manage our rapid growth; our ability to obtain
capital when desired on favorable terms; and the volatility of the market
price of our common stock. Existing and prospective investors are cautioned
not to place undue reliance on these forward-looking statements, which speak
only as of the date hereof. Helicos undertakes no obligation to update or
revise the information contained in this presentation, whether as a result of
new information, future events or circumstances or otherwise. For additional
disclosure regarding these and other risks faced by Helicos, see the
disclosure contained in Helicos public filings with the Securities and Exchange
Commission. PLEASE NOTE: The names HeliScope, tSMS, true Single Molecule
Sequencing and Virtual Terminator and our logo are trademarks or service
marks of Helicos BioSciences Corporation.
Investment
Highlights Helicos A Clear Path to the $1,000 Genome Revolutionary and
Breakthrough Technology Proprietary tSMS technology directly sequences
molecules of DNA and copies of RNA Transform the Market by Enabling New
Science Potential to significantly expand the current $5 billion genetic
analysis market Provide Critical Advantages vs. Next-Generation Sequencers
High throughput, simplicity and greater sensitivity leads to exceptional
price performance Compelling Business Model Instrument revenue combined with
substantial, aftermarket consumables sales Experienced Leadership Team
Industry leaders with track record of scientific and business success
3 Transforming
Technology in Medicine tSMS has Parallels to Past Breakthroughs 19th Century
21st Century
3 Transforming
Technology in Medicine tSMS has Parallels to Past Breakthroughs 19th Century
21st Century
3 Transforming
Technology in Medicine tSMS has Parallels to Past Breakthroughs 19th Century
21st Century
True Single
Molecule SequencingTM A Fundamental Breakthrough in Genetics
5 Our Powerful
tSMS Science & Technology tSMS may enable genetic analysis on an
unprecedented scale Revolutionary proprietary technology First technology to
directly sequence single molecules of DNA and RNA Strong IP covering methods,
composition of matter Recipient of a grant from the National Human Genome
Research Institute Revolutionary Genome Sequencing Technologiesthe $1,000
Genome United States Patent Patent No.: US 7,282,337 Harris Date of Patent:
October 16, 2007 METHODS FOR INCREASING ACCURACY OF NUCLEIC ACID SEQUENCING
Inventors: Harris; Timothy D. (Toms River, NJ) Assignee: Helicos BioSciences
(Cambridge, MA) Abstract The invent ion provides methods for improving the
accuracy of a sequencing-by-synthesis reaction by sequencing at least a portion
of a template and at least a portion of template complementary sequence.
5 Our Powerful
tSMS Science & Technology tSMS may enable genetic analysis on an
unprecedented scale Revolutionary proprietary technology First technology to
directly sequence single molecules of DNA and RNA Strong IP covering methods,
composition of matter Recipient of a grant from the National Human Genome
Research Institute Revolutionary Genome Sequencing Technologiesthe $1,000
Genome United States Patent Patent No.: US 7,282,337 Harris Date of Patent:
October 16, 2007 METHODS FOR INCREASING ACCURACY OF NUCLEIC ACID SEQUENCING
Inventors: Harris; Timothy D. (Toms River, NJ) Assignee: Helicos BioSciences
(Cambridge, MA) Abstract The invent ion provides methods for improving the accuracy
of a sequencing-by-synthesis reaction by sequencing at least a portion of a
template and at least a portion of template complementary sequence.
Significant
Market Opportunity
Strategic
Factors Driving a New Generation of Genetic Analysis Experiments
Strategic
Factors Driving a New Generation of Genetic Analysis Experiments The factors
are: Increase in the number of samples per experiment
Strategic
Factors Driving a New Generation of Genetic Analysis Experiments The factors
are: Increase in the number of samples per experiment Increase in amount of
the genome known to be functionally active (ENCODE)
Strategic
Factors Driving a New Generation of Genetic Analysis Experiments The factors
are: Increase in the number of samples per experiment Increase in amount of
the genome known to be functionally active (ENCODE) A need to study variation
in Genome sequence Copy number variants Transcriptome sequence Transcript
splice variants Transcript regulation Epigenetics
Transform the Market
by Enabling New Science Significant Market Potential ~ $14B in Funding [60
grants in TRx - $576M] ~130 Provide the best applications Academic Health
Centers Private Research Institutes ~$30B ~ $2B in Funding ~ $9.5B in
assay & rgts* ~ $3.5B in tools/systems** Market Size [TAM] ~200 ~20 ~50
Number of Sites TOTAL Offer the best technology Academic Genome Centers
Reduce attrition & accelerate development Pharma & Biotech Companies
Value Proposition Total Addressable Market in Translational Research Based on
Charter, Funding, Samples, Infrastructure * 2006 Drug & Market Dev
elopment, Inc. report * * 2004 MarketResearch.com report Life Science Tools
& Technologies for Bio-Pharma R&D NIH Website 2005 NIH Extramural
Grant Awards Helicos estimates f rom various intl f unding sources
Helicos estimates f rom various genome center releases
The Experts On
$1,000 Genome Performance Enabling the New Set of Experiments Francis S.
Collins (National Human Genome Research Institute) What wouldnt we do?.....
wed probably take most of our current annual spending on DNA sequencing,
about $120 million, and devote it to sequencing 100,000 human samples for
$100 million.Leonid Kruglyak (Princeton University) A scalable technology
that can deliver a $1,000 human genome will revolutionize expression
profiling. Emma Whitelaw (Queensland Institute of Medical Research) With a
$1,000 genome, I would carry out a comprehensive analysis of the methylation
state across the genome. Yoshihide Hayashizaki (RIKEN Institute) ..... it
is possible to obtain expression information for each promoter that cannot be
achieved by current hybridization-based methods. .....[this information] is
essential for analyzing molecular networks from gene to phenotype.
Nature.com Question of the Year What would you do if it became possible
to sequence the equivalent of a full human genome for only $1,000?
The $1,000
Genome and Personalized Medicine NHGRIs vision is to...... cut the cost of
whole-genome sequencing to $1,000 or less, which would enable the sequencing
of individual genomes as part of medical care. The ability to sequence each
persons genome cost-effectively could give rise to more individualized
strategies for diagnosing, treating, and preventing disease. Francis
Collins, NHGRI Director, in defense of his FY2006 Budget Request
The HeliScopeTM
System An Innovative and Differentiated Solution
Worlds First
Single Molecule Genetic Analyzer The HeliScopeTM Product Strategy Build an
instrument with the performance headroom for the $1,000 genome Imaging
capacity
@
1 Gbase per hour Customers access headroom through
improvements in tSMS chemistry Initial tSMS performance @ 25MB & 90MB/hr
tSMS is
performed on the HeliScope in a flow cell
tSMS is performed
on the HeliScope in a flow cell 25 Channels per Flow
tSMS is
performed on the HeliScope in a flow cell 25 Channels per Flow Cell ~56M
unique DNA strands per channel at a density of 1 strand per µm2 Imaging of
the tSMS chemistry is performed within a channel through a step and repeat
sub-imaging routine Flow Cell Channel
Demonstrating
HeliScope performance headroom Paving the way to the $1,000 genome 26 8 4
Signal to Noise Ratio 1000 900 800 700 600 500 400 300 200 100 0 -100 -200
-300 -400 -500 -600 -700 -800 -900 -1000 xxx 1400 1300 1200 1100 1000 900 800
700 600 500 400 300 200 100 0 -100 -200 -300 -400 -500 -600 -700 -800 -900
-1000 -1100 -1200 -1300 -1400
Demonstrating
HeliScope performance headroom Paving the way to the $1,000 genome
Demonstrating
HeliScope performance headroom Paving the way to the $1,000 genome
Demonstrating
HeliScope performance headroom Paving the way to the $1,000 genome
HeliScope Imaging Performance ~3.1e4 strands per image 85 millisecond image
time 1794 images per channel 25 channels per flow cell 2 flow cells per run
@
2.8B strands
@
2.1 hours per cycle
@
1.3B bases per hour
Demonstrating
1st generation tSMS performance Paving the way to the $1,000 genome Length of
Read 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 10 5 20 25 30 35 40 45
Demonstrating
1st generation tSMS performance Paving the way to the $1,000 genome
0 0.5 1 1.5 2
2.5 3 24 26 28 30 32 34 36 38 40 42 44 Length [Two Pass Aligned] Total Error
(%) Demonstrating 1st generation tSMS performance Paving the way to the
$1,000 genome Accuracy
Usable strands
LOR and accuracy Demonstrating 1st generation tSMS performance Paving the
way to the $1,000 genome - 50,000 100,000 150,000 200,000 250,000 300,000
350,000 Usable Strands 1 Flow Cell One 25 1 Flow Cell Two 25
tSMS assay
performance drives new science High-throughput chemogenomics using tSMS 89
gene signature 2 compounds 1. DMSO 2. Tretinoin DMSO Tretinoin 89 genes 2787
samples Upon statistical analysis..... 3 primary clusters classified -- 2
major clusters correspond to the two treatments (1327 DMSO + 1373 Tret) --
97% accuracy + 96.5% call rates -- 3rd cluster corresponds to the outliers
Within each primary cluster, -- secondary clusters corresponded to RNA
sources The experimental parameters were classified as tertiary clusters -- instrument-to-instrument
variability -- tSMS effect
Candidate
Oncology Genes P53 PTEN APC VHL 29 Exons: Ave length = 550 bp Total Base
Pairs: 17,061 Per base error rate: 1.4% Average 50X Coverage From germ-line
DNA sample 121407 Onco29 M+R, total Error Rate 1.39% tSMS assay performance
drives new science High-throughput medical resequencing using tSMS
Candidate
Oncology Genes P53 PTEN APC VHL 29 Exons: Ave length = 550 bp Total Base
Pairs: 17,061 Per base error rate: 1.4% Average 50X Coverage From germ-line
DNA sample 121407 Onco29 M+R, total Error Rate 1.39% tSMS assay performance
drives new science High-throughput medical resequencing using tSMS 0 20 40 60
80 100 120 140 160 0 800 1600 2400 3200 4000 4800 5600 6400 7200 8000 8800
9600 10400 11200 12000 12800 13600 14400 15200 Base Pair 17,061 Total
Coverage Coverage (# of times base was sequenced)
Candidate
Oncology Genes P53 PTEN APC VHL 29 Exons: Ave length = 550 bp Total Base
Pairs: 17,061 Per base error rate: 1.4% Average 50X Coverage From germ-line
DNA sample 121407 Onco29 M+R, total Error Rate 1.39% tSMS assay performance
drives new science High-throughput medical resequencing using tSMS + Strand -
Strand 0 1000 2000 3000 4000 5000 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Coverage Coverage (# of sequences from each exon) exon
Candidate
Oncology Genes P53 PTEN APC VHL 29 Exons: Ave length = 550 bp Total Base
Pairs: 17,061 Per base error rate: 1.4% Average 50X Coverage From germ-line
DNA sample 121407 Onco29 M+R, total Error Rate 1.39% tSMS assay performance
drives new science High-throughput medical resequencing using tSMS + Strand -
Strand 0 1000 2000 3000 4000 5000 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Coverage Coverage (# of sequences from each exon) exon
Candidate
Oncology Genes P53 PTEN APC VHL 29 Exons: Ave length = 550 bp Total Base
Pairs: 17,061 Per base error rate: 1.4% Average 50X Coverage From germ-line
DNA sample 121407 Onco29 M+R, total Error Rate 1.39% tSMS assay performance
drives new science High-throughput medical resequencing using tSMS + Strand -
Strand 0 1000 2000 3000 4000 5000 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Coverage Coverage (# of sequences from each exon) exon
Candidate
Oncology Genes P53 PTEN APC VHL 29 Exons: Ave length = 550 bp Total Base Pairs:
17,061 Per base error rate: 1.4% Average 50X Coverage From germ-line DNA
sample 121407 Onco29 M+R, total Error Rate 1.39% tSMS assay performance
drives new science High-throughput medical resequencing using tSMS
TCCCAGAATGCCAGAGGCTGCTCCCCCCGTGGCCCCTGCACCAGCAGCTCCT
TCCCAGAATGCCAGAGGCTGCTCCCCGCGTGGCCCCTGCACCAGCAGCTCCT
CCAGAATGCCAGAGGCTGCTCCCCCCGTGGCCCCTG CCAGAATGCCAGAGGCTGCTGCCCGCGTGGCCCCTG
CCAGAATGCCAGAGGCTGCTCCCCGCGTGGCCCCTG CCAGAATGCCAGAGGCTGCTCCCCCCGTG
CCAGAATGCCAGAGGCTGCTCCCCCCGTG CCAGAATGCCAGAGGCTGCTCCCCC-GTG P53 SNP Id:
rs1042522 Reference Sequence HAP MAP Sample Reference Read One Read Two
Reference Read One Read Two Sensitivity (Identification of known alleles)
System
Configuration A real production-level genetic analyzer HeliScope Sequencer
(>1GB/hr) Laser Illumination CCD Camera Microfluidics High-speed
stage Instrument-control computer System UPS HeliScope Analysis Engine
Multi-blade tower 28 terabytes data storage Near real-time data
processing No MB/hr penalty to acquire alignable data Scalable to
$1,000 genome performance 60 tbytes Flow Cell Flow Cell (X 2) 2.8B strands
50 channels (50 samples) 56M strands
Commercial
Status Prospects and Collaborators Our sales team is getting a great
response from our target market of early adopters Genome Centers Academic
Health Centers Pharma Companies New collaboration that enables new science
with tSMS A microRNA collaboration with Victor Ambros quantitation of known
miRNAs and discovery of new miRNAs joint submission of data to the 2008
Marco Island meeting
We are on
track to ship our first production unit We have 9 HeliScopes on the
manufacturing floor in various stages of assembly and test Commercial Status
System Development Status
We are on
track to ship our first production unit We have 9 HeliScopes on the
manufacturing floor in various stages of assembly and test Commercial Status
System Development Status
We are on
track to ship our first production unit We have 9 HeliScopes on the
manufacturing floor in various stages of assembly and test Commercial Status
System Development Status Our first 2 HeliScopes are in their final stage of
production readiness testing, which we call verification and validation
(V&V)
We are on
track to ship our first production unit We have 9 HeliScopes on the
manufacturing floor in various stages of assembly and test Commercial Status
System Development Status Our 1st generation tSMS reagents and flow cells
have been manufactured and are being tested
We are on
track to ship our first production unit We have 9 HeliScopes on the
manufacturing floor in various stages of assembly and test Commercial Status
System Development Status Our 1st generation tSMS reagents and flow cells
have been manufactured and are being tested
Compelling
Business Model Attractive Financial Characteristics
The HeliScope
System Attractive Economic Profile HeliScope Instrument Instrument Sales =
Expanding Base of Recurring Revenue Significant upfront instrument sales
Rapid growth in reagent/disposables Increased utilization Expanding installed
base High gross profit margins Proprietary Reagents/ Disposables + Flow Cell
tSMS Reagents
The HeliScope
System Attractive Economic Profile HeliScope Instrument Instrument Sales =
Expanding Base of Recurring Revenue Significant upfront instrument sales
Rapid growth in reagent/disposables Increased utilization Expanding installed
base High gross profit margins Proprietary Reagents/ Disposables + Flow Cell
tSMS Reagents
The HeliScope
System Attractive Economic Profile HeliScope Instrument Instrument Sales =
Expanding Base of Recurring Revenue Significant upfront instrument sales
Rapid growth in reagent/disposables Increased utilization Expanding installed
base High gross profit margins Proprietary Reagents/ Disposables + Flow Cell
tSMS Reagents
109 to 1010 107
to 108 105 to 108 102 Theoretical Imaging Maximum Yes No No N/A Real Time
Image Processing No Yes Yes N/A Representational Bias due to Amplification X
Throughput (MB / Hour) X X capillary Sanger (ABI) X X Single Molecule
Sequencing X X Simplicity of Sample Prep Workflow single strand cluster bead
Data Unit bridge-PCR (illumina) emulsion-PCR (ABI SOLiD) Competitive
Advantage Capturing Momentum at Introduction A unique blend of price
performance and simple workflows delivers production-level value
Competitive
Advantage Capturing Momentum at Introduction At 25MB per hour, the HeliScope
will generate ~7.5 Gbases per run in ~14 days for $18,000 For whole human
genome sequencing at 10X coverage (30Gb) Requires 4 runs 8 weeks and
$72,000 The sample prep time is ~1 day and is de minimis in cost For
candidate region sequencing Run up to 50 samples (50 channels) at 150MB of
sequence for $360/sample 25 full length genes (60Kb) at 100X coverage 100
full length genes (60Kb) at 25X coverage 6,000 exons (250b) at 100X coverage
24,000 exons (250b) at 25X coverage
Competitive
Advantage Capturing Momentum at Introduction At 25MB per hour, the HeliScope
will generate ~7.5 Gbases per run in ~14 days for $18,000 For whole human
genome sequencing at 10X coverage (30Gb) Requires 4 runs 8 weeks and
$72,000 The sample prep time is ~1 day and is de minimis in cost For
candidate region sequencing Run up to 50 samples (50 channels) at 150MB of
sequence for $360/sample 25 full length genes (60Kb) at 100X coverage 100
full length genes (60Kb) at 25X coverage 6,000 exons (250b) at 100X coverage
24,000 exons (250b) at 25X coverage
Competitive
Advantage Capturing Momentum at Introduction At 25MB per hour, the HeliScope
will generate ~7.5 Gbases per run in ~14 days for $18,000 For whole human
genome sequencing at 10X coverage (30Gb) Requires 4 runs 8 weeks and
$72,000 The sample prep time is ~1 day and is de minimis in cost For
candidate region sequencing Run up to 50 samples (50 channels) at 150MB of
sequence for $360/sample 25 full length genes (60Kb) at 100X coverage 100
full length genes (60Kb) at 25X coverage 6,000 exons (250b) at 100X coverage
24,000 exons (250b) at 25X coverage
Competitive
Advantage Capturing Momentum at Introduction At 25MB per hour, the HeliScope
will generate ~7.5 Gbases per run in ~14 days for $18,000 For whole human
genome sequencing at 10X coverage (30Gb) Requires 4 runs 8 weeks and
$72,000 The sample prep time is ~1 day and is de minimis in cost For
candidate region sequencing Run up to 50 samples (50 channels) at 150MB of
sequence for $360/sample 25 full length genes (60Kb) at 100X coverage 100
full length genes (60Kb) at 25X coverage 6,000 exons (250b) at 100X coverage
24,000 exons (250b) at 25X coverage
Experienced
Leadership Team Industry Pioneers with Strong Track Record
Management Team
Experienced Executives with Proven Track Record 13 Vice President and Chief
Corporate Counsel for Affymetrix for 7 years Mark Solakian VP and General
Counsel 18 Executive Director at Pfizer Global R&D; industry leader in
pharmacogenomics Patrice Milos, PhD VP & CSO 27 Extensive experience as a
manufacturing executive, most recently at JNJ (Closure Med) Bill Cotter VP,
Operations 18 Led Affymetrix systems business for 6 years Chip Leveille VP,
Sales & Marketing 27 Led development of Applied Biosystems genetic
analysis systems for 23 years Bill Efcavitch, PhD SVP, Product R&D 20 10
years CFO experience, most recently Arqule Louise Mawhinney, CPA SVP &
CFO 29 12 years executive experience; led Applied Biosystems sequencing
business for 10 years Steve Lombardi President & COO 21 Founded two
public diagnostic companies (Cytyc, Exact Sciences) Stan Lapidus Chairman
& CEO Years in Industry Industry Experience Name Title
Board of
Directors Seasoned Industry Leaders Former President & CEO Fisher
Biosciences Co-founder and former president, The Institute for Genomic
Research Former CFO, Thermo Electron Apax Partners The Carlyle Group Ronald
Lowy Claire Fraser, PhD University of Maryland Theo Melas-Kyriazi Levitronix
(CFO) Steven St. Peter, MD MPM Capital Founder and CEO of Glycomed;
Co-founder of Perkin Elmer/Cetus JV Brian Atwood Versant Ventures Co-founder
of Highland Capital Partners Robert Higgins Highland Capital Co-founder, EVP
& CBO of Celera Genomics Peter Barrett, PhD Atlas Venture Founder &
CEO of PerSeptive Biosystems Initiated Celera Genomics while CBO at ABI
Noubar Afeyan, PhD Flagship Ventures Lead Independent Director Stan Lapidus Chairman
& CEO
Scientific
Advisory Board Unrivaled Expertise John Quackenbush, PhD DFCI & Harvard
SPH Milan Mrksich, PhD University of Chicago Victor Velculescu, MD, PhD Johns
Hopkins University Floyd Romesberg, PhD Scripps Institute Jeff Trent, PhD
TGEN Donald Crothers, PhD Yale University Gene Myers, PhD Howard Hughes
Medical Institute David Liu, PhD Harvard University George Church, PhD
Harvard Medical School Steven Chu, PhD Berkeley National Laboratory Leroy
Hood, PhD Institute for Systems Biology Steve Quake, PhD, Chair Stanford
University
44 Financial
Review
45 Financial
Results 10,176 3,615 General and Administrative $ (26,386) $ (9,964) Net Loss
1,250 663 Interest Income (net) 28,101 10,857 Total Operating Expenses $ 17,925 $ 7,242 Research and Development $ 465 $ 230 $ 230 Grant Revenue Year
to Date Quarter ($000s) as of September 30, 2007 Guidance for 2007*: cash
burn approx. $40 million; Cash at 12/31/07 approx. $40 million *NOT UPDATED
since 11/1/07
46 Balance
Sheet Data $ 54,858 $ 54,858 Cash $ 52,842 $ 52,842 Stockholders Equity $ 59,074 Total Assets as of September 30, 2007 (in $,000s) *Does NOT include
the $20M debt facility with GE Capital on 12/31/07 *
47 Investment
Highlights Helicos A Clear Path to the $1,000 Genome Revolutionary and
Breakthrough Technology Transform the Market by Enabling New Science Provide
Critical Advantages vs. Next-Generation Sequencers Compelling Business Model
Experienced Leadership Team