New Patterns Emerge in Healthcare Investments and Exits

Healthcare Investments
and Exits
Mid-Year 2016 Report
Paul Schuber
Valuations Associate
SVB Analytics
Written by:
Jonathan Norris
Managing Director
Silicon Valley Bank

Table of Contents
Healthcare Investments and Exits, Mid-Year 2016 Report 2
Key Highlights 1H 2016 3
Healthcare Investments and Fundraising 4
Top 15 Crossover Investors 12
Healthcare Big Exit M&A and IPO 15
Glossary 26
About the Authors 27
Cover Photo: Cytotoxic T lymphocytes attacking cancer cell

Key Highlights 1H 2016: New Patterns Emerge
as Investor Confidence Drives Deals
Like investing and exits overall, healthcare experienced a bumpy start in
2016 — but also had some surprising highlights.
• Venture fundraising declines, but Series A investment is up in all sectors.
• We expect healthcare investment to reach $9B-$9.5B for full-year 2016, down
slightly from 2015.
• Crossover investment slows, but newly raised funds, corporate venture and family
offices are largely filling the gap. Crossover investors are instead focusing on
getting biopharma portfolio companies to an IPO.
• Potential distributions are on pace to reach $15B-$17B for the full-year 2016.
• Biopharma round sizes are skyrocketing, while exits focus on early-stage companies.
• Device remains healthy, as M&A big exits are on pace to meet full-year 2015.
• Diagnostics (dx) has experienced exit pullback due to regulatory and reimbursement
uncertainty. However, investment has picked up and M&A activity should increase.

Healthcare Investments and Fundraising:
Series A Activity Booms

With very healthy funding over the
last few years, we continue to see
strong investment into companies
and expect it to continue for at
least the next two years.
Based on Q1 2016 data, we think
investment into companies will
reach $9-$9.5B for the full year,
down slightly from 2015. This
reflects less crossover activity.
Fundraising in 1H 2016 is down
compared to 1H 2015, driven
primarily by the closing of three
big funds ($2.75B total) in 2015.
But we continue to see LP interest
in investing into healthcare.
Investors See Strong Future in Healthcare
U.S. Healthcare: Capital Invested and VC Dollars Raised
Capital Flow
Ratio 127% 368% 207% 189% 175% 149% 141%
HC $ Invested into Companies HC VC $ Fundraised Gap in Funding
0
1
2
3
4
5
6
7
8
9
10
11
2009 2010 2011 2012 2013 2014 2015
$Billions
Source: PricewaterhouseCoopers, Thomson Reuters and SVB proprietary data
$7.5B
$10.5B

Series A Activity Is Strong across All Sectors
Total Series A ($M) $1,107 $862 $1,843 $994
CVC Deals % / # 28% / 17 27% / 20 26% / 23 33% / 19
BIOPHARMA
Biopharma is on pace in 2016 for
100+ Series A deals (up 30% over
2015) with $2B in invested capital.
Both would be record highs, if
investment velocity continues.
• Significant pre-clinical focus,
especially in platform,
oncology, anti-infective,
neurology and orphan/rare
disease companies
Device deals already have eclipsed
2015 totals, driven by angel
activity.
• Significant investment activity
in neurology, cardiovascular
and surgical companies
Dx/tools deals and dollars in 1H
2016 have exceeded 2015 totals,
despite an M&A pullback.
• Grail raised $125M in Series A,
accounting for almost half of
dollars raised in 1H 2016
DEVICE
DX/TOOLS
Total Series A ($M) $227 $337 $92 $104
CVC Deals % / # 18% / 7 14% / 6 22% / 4 4% / 1
Total Series A ($M) $234 $252 $165 $263
CVC Deals % / # 10% / 4 12% / 4 24% / 4 21% / 5
60
75
87
58
0
40
80
120
2013 2014 2015 1H 2016
#ofDeals
38 42
18 24
0
40
80
120
#ofDeals
39 34
17 24
0
40
80
120
#ofDeals
Source: CB Insights, PitchBook, press releases and SVB proprietary data
U.S. Company Formation: Deals and Investments in Series A

Venture and Corporate Investors Keep Active
Trends suggest the number of
deals by the most active investors
will increase 30% over 2015.
Pfizer, a corporate investor, leads
all investors with 9 new deals in
1H 2016.
The majority of the most active
VCs in 1H 2016 have raised new
funds between January 2015 and
June 2016.
Active crossover investors include
Deerfield Management (7), Fidelity
Investors (4) and Cormorant Asset
Management (4). See page 13.
Top 2015 VC+CVC Biopharma
INVESTOR DEALS TYPE
OrbiMed Advisors 16 VC
New Enterprise
Associates
9 VC
Novartis Venture
Funds
9 Corporate
ARCH Venture Partners 8 VC
Sofinnova Ventures 8 VC
Novo 7 VC
Pfizer Venture
Investments
7 Corporate
Versant Ventures 7 VC
Celgene 6 Corporate
Johnson & Johnson
Innovation
6 Corporate
SR One 6 Corporate
Top 1H 2016 VC+CVC Biopharma
INVESTOR DEALS TYPE
Pfizer Venture
Investments
9 Corporate
OrbiMed Advisors 8 VC
Frazier Healthcare 6 VC
Novo 6 VC
AbbVie Biotech
Ventures
5 Corporate
ARCH Venture Partners 5 VC
New Enterprise
Associates
5 VC
Canaan Partners 4 VC
MPM Capital 4 VC
Johnson & Johnson
Innovation
3 Corporate
Roche Venture Fund 3 Corporate
Most Active* New Investors in Biopharma 2015 versus 1H 2016
*Most active is defined as top 60 investors based on new investments.

Oncology Leads New Biopharma Investments
Oncology has almost three times the number of deals compared to any other category.
Anti-infective, ranked ninth in number of deals in our 2014 analysis, is now tied for second.
Platform, orphan/rare disease and neurology continue to receive significant investment.
Oncology
62 deals
$2,419M
Anti-Infective
22 deals
$686M
Platform
22 deals
$914M
Neurology
22 deals
$816M
Orphan/Rare
Disease
19 deals
$749M
Auto-Immune
6 deals
$232M
Metabolic
9 deals
$243M
Cardiovascular
5 deals
$109M
Gastrointestinal
6 deals
$128M
Respiratory
4 deals
$155M
Ophthalmology
5 deals
$201M
Most Active* New VC Investments in Biopharma by Indication 2015–1H 2016
*Most active is defined as top 60 investors based on new investments.

Biopharma Deal Size Increases
Median investment round size
from most active investors has
increased 40% over 2015.
The median deal size has almost
tripled since 2013.
Recent larger equity raises in
biopharma could compress M&A
multiples down the road,
especially as IPO optionality
declines.
$15.3
$23.0
$30.0
$42.8
$0
$5
$10
$15
$20
$25
$30
$35
$40
$45
2013 2014 2015 1H 2016
MedianDealSize($Millions)
Median Deal Size by Top 60 VC and Corporate Investors

Device Gains Traction in Large Late-Stage Deals
Active* Investors
INVESTOR TYPE INVESTOR TYPE
Action Potential Venture
Capital
Corporate Lightstone Ventures VC
Aisling Capital VC Longitude Capital VC
BioStar Ventures VC Medtronic Corporate
Deerfield Management Crossover New Enterprise Associates VC
Edwards Lifesciences Corporate OrbiMed Advisors VC
Endeavour Vision VC Sante Ventures VC
GE Ventures Corporate Sofinnova Partners VC
HealthQuest Capital VC SV Life Sciences Advisers VC
Johnson & Johnson
Innovation
Corporate Venrock VC
KCK Group Family Office Vertex Healthcare VC
Analysis of the top 10 1H 2016
device deals:
• The median deal size jumped to
$46M in Q2 2016 — the largest
median round size in two years.
• The increased deal sizes
underscore the funding of late-
stage pivotal trial and/or
commercialization rounds.
• Cardiovascular received the
most investments in 1H 2016;
this indication requires
significant clinical trial
investment. We also saw recent
big exit M&A activity in this
indication, with 8 of 17 device
big exits in 2015.
Active* Investors in Device 1H 2016
*Active defined as investors that are actively investing or actively looking at deals.

Top Dx/Tools Round Sizes Increase
Analysis of the top 10 1H 2016
dx/tools deals:
• Dx/tools deal size surged to a
median of $41M in Q2, nearly
tripling the 2015 median. Half
of these investments were
either Series A or B.
• The deals were equally split
between dx and tools.
The number of investments by the
Top 15 Crossover Investors in 1H
2016 equaled all of 2015.
Active* Investors
INVESTOR TYPE INVESTOR TYPE
ARCH Venture Partners VC OrbiMed Advisors VC
Arboretum Ventures VC Paladin Capital Group VC
Baird Capital VC Pfizer Venture Investments Corporate
Cormorant Asset
Management
Crossover Qiagen Corporate
Fidelity Investments Crossover Roche Venture Fund Corporate
Foresite Capital Management Crossover Sequoia Capital VC
Gilde Investment
Management
VC Venrock VC
Illumina Ventures Corporate Wuxi Venture Fund VC
Active* Investors in Dx/Tools 1H 2016
*Active defined as investors that are actively investing or actively looking at deals.

Top 15 Crossover Investors:
Investments Decline as
Crossovers Focus on IPOs

Investments in Biopharma Decline Rapidly
2013 2014 Q1 2015 Q2 2015 Q3 2015 Q4 2015 Q1 2016 Q2 2016 Total
PRIVATE
INVESTMENTS
15 68 27 46 68 22 16 13 275
MOST ACTIVE CROSSOVER INVESTORS 1H 2016
INVESTOR DEALS
Deerfield Management 7
Fidelity Investments 4
Cormorant Asset Management 4
Sectoral Asset Management 3
Crossover investment deals dropped almost 70% from 2H 2015. However, we still see crossover investor activity, and this
group continues to be an important part of the biopharma ecosystem.
In 1H 2016, 70% of crossover deals were in Series A and B.
Something to consider: Will crossover investors continue to support portfolio companies that need to raise another private
round?
Top 15 Crossover Investors: Adage Capital Management, Casdin Capital, Cormorant Asset Management, Deerfield Management, EcoR1 Capital, Fidelity Investments, Foresite Capital
Management, Jennison Associates, Perceptive Advisors, RA Capital Management, Redmile Group, Rock Springs Capital, Sectoral Asset Management, Wellington Management, Woodford
Investment Management

Investors Push for Biopharma IPOs
Crossover IPOs as Percentage of Exits
IPO / Total Exits (M&A + IPO) 55/61 (90%)
Our analysis shows that biopharma companies with a Top 15 Crossover Investor are much more likely to exit through an IPO.
Greater than 45% of these companies have exited since 2013, and 90% of those exits have been IPOs.
In 1H 2016, 11 of 15 VC-backed biopharma IPOs had a Top 15 Crossover as a private investor. The number of Top 15 Crossover
IPOs is on pace to match 2015, which is remarkable in a declining IPO market.
The challenge ahead: 55% of the portfolios of Top 15 Crossover Investors are still private. This suggests that their focus in 2H
2016 will be on helping companies go public instead of making new private investments.
Private Company Backlog
Still Private / Total Deals 74/135 (55%)
*Estimate based on 1H 2016 IPOs
2
8
23
22
32
58
19
8
0
10
20
30
40
50
60
70
2013 2014 2015 2016*
#ofIPOs
Top 15
Crossover
Other Investors
Top 15 Crossover Investors: Adage Capital Management, Casdin Capital, Cormorant Asset Management, Deerfield Management, EcoR1 Capital, Fidelity Investments, Foresite Capital
Management, Jennison Associates, Perceptive Advisors, RA Capital Management, Redmile Group, Rock Springs Capital, Sectoral Asset Management, Wellington Management, Woodford
Investment Management

Healthcare Big Exit M&A and IPO:
Robust M&A Activity
Continues as IPOs Slow

Large Stemcentrx Deal Propels Overall
Distributions
Biopharma 64% 80% 69% 69% 85%
Device 27% 12% 21% 23% 13%
Dx/Tools 9% 8% 10% 8% 2%
Pre-Money IPO ValueBig Exit Milestones to be EarnedBig Exit Upfront Payments
Potential Distributions* from VC-backed IPOs
and Big Exit M&A 2012–1H 2016 One deal, Stemcentrx’s acquisition
by AbbVie, contributed almost half
of all 1H 2016 total potential
distributions.
Barring another multibillion-dollar
exit in 2H 2016, full-year potential
distributions are on pace to reach
$15B-$17B.
While below the record high in
2015, this signals another good
year for investors.
*Potential distributions are
calculated assuming 75% venture
ownership for upfront payments.
IPOs are based on the pre-money
valuation assuming 75% venture
ownership. M&A milestone
payments are discounted to 25%.
0
2
4
6
8
10
12
14
16
18
20
22
24
2012 2013 2014 2015 1H 2016
TotalValue($Billions)

Strong Biopharma Big Exit M&A Continues,
while IPO Market Slows
Q1 Q2 Q3 Q4 Total
2013
IPO 3 10 13 8 34
M&A 3 3 3 3 12
2014
IPO 24 12 17 13 66
M&A 3 4 6 1 14
2015
IPO 11 12 9 10 42
M&A 7 4 6 4 21
2016
IPO 7 8 15
M&A 5 4 9
Healthcare Investments and Exits, Mid-Year 2016 Report 17Source: CB Insights, PitchBook, press releases and SVB proprietary data
VC-backed Biopharma Exits by Quarter 2013–1H 2016
Full-year 2016 biopharma IPOs are
estimated to come close to the
2013 total.
Of the 15 IPOs in 1H 2016, 7
companies were trading above
their IPO price and 8 trading
below at the end of the first half of
2016.
We anticipate M&A big exits to
pick up in 2H 2016 and exceed the
2015 total.

Early-Stage Companies Dominate
Biopharma IPOs
Stage 2012 2013 2014 2015 1H 2016
Pre-Clinical /
Phase I
1 9 29 18 9
Total Biopharma
IPOs
10 34 66 41 15
% Early-Stage IPOs 10% 26% 44% 44% 60%
Biopharma IPOs were focused predominantly on early-stage companies in 1H 2016.
In 1H 2016, median IPO dollars raised was $53M, down from $75M in 2H 2015. Median pre-money valuation in 1H 2016 of
$176M is healthy, but below the 2H 2015 median of $233M.
Following a strong 2015 for neurology and anti-infective IPOs, these indications had none in 1H 2016. This may be related to
recent clinical setbacks at newly public companies.
VC-backed Biopharma IPOs by Stage 2012–1H 2016

Biopharma M&A Big Exit Multiples Surge;
Early-Stage Focus Continues
Healthcare Investments and Exits, Mid-Year 2016 Report
Pre-Clinical Phase I Phase II Phase III Commercial
19
0
2
4
6
8
10
12
14
16
18
20
2012 2013 2014 2015 1H 2016
#ofBigExits
VC-backed Biopharma Big Exit M&A by Stage 2012–1H 2016
Biopharma deals in 1H 2016 had a
strong median upfront multiple of
4.7X. Even more impressive, the
median all-in multiple reached
14X, up significantly from 2014
and 2015.
7 of 9 M&A big exits were pre-
clinical or Phase I:
• Pre-clinical deals were in
neurology, auto-immune and
orphan/rare disease.
• Phase I deals were in oncology
(2 deals), metabolic and
aesthetics/dermatology.

Early-Stage Biopharma M&A Remains Strong,
while Exit Time Decreases
Healthcare Investments and Exits, Mid-Year 2016 Report 20Source: CB Insights, PitchBook, press releases and SVB proprietary data
$325M
$500M
$413M
$600M
$600M
5.0
4.1
5.3 5.6
4.7
2012 2013 2014 2015 1H 2016
Median Total Deal Size and Time to Exit (Pre-Clinical & Phase I)
Median Total Deal Size Median Time to Exit (years)
n=5 n=3 n=8 n=11 n=7
31.8%
51.7%
74.0%
36.9%
51.2%
68.2%
48.3%
26.0%
63.1%
48.8%
2012 2013 2014 2015 1H 2016
Median Total Deal Size (Pre-Clinical & Phase I)
Upfront % Milestone %
$325M $500M $413M $600M $600M
M&A median total deal size
remains at record high, even as
IPO optionality is decreasing.
This suggests competition among
acquirers, which is leading them
to pay more at deal close to
acquire early-stage assets.
Biopharma M&A continues to show
a quick time to exit.

Device Big Exit M&A Charges On
as IPOs Disappear
Q1 Q2 Q3 Q4 Total
2013
IPO 0 0 0 2 2
M&A 2 2 6 2 12
2014
IPO 1 5 1 3 10
M&A 2 9 5 2 18
2015
IPO 3 4 3 1 11
M&A 0 4 9 4 17
2016
IPO 0 0 0
M&A 5 4 9
VC-backed Device Exits by Quarter 2013–1H 2016
In 1H 2016 there were no device
IPOs, but we did see some reverse
merger activity.
At the same time, there were
9 M&A big exits — on pace to
match the 2015 total.
In each of the past five quarters,
there have been at least four M&A
device big exits.

Device Big Exit M&A Trends to Later Stage
Non-Approved CE Mark U.S. Commercial
Represents # of IPOs Represents Big Exits
0
2
4
6
8
10
12
14
16
18
2012 2013 2014 2015 1H 2016
#ofBigExits
1 2
7
1
2
8
1
2
The orthopedic indication leads
with three deals in 1H 2016.
There were no Medtronic venture-
backed acquisitions in 1H 2016
(13 big exit acquisitions in
2014-2015). However, we expect
Medtronic activity in 2H 2016.
Discussions with investors suggest
that the next flurry of early stage
acquisitions could focus on atrial
fibrillation, heart failure, stroke or
neurostimulation.
VC-backed Device Big Exit M&A by Stage 2012–1H 2016

Device Big Exit M&A Propels Higher
Median Values
Median
Upfront ($M) $95 $127 $180 $150 $120
Median
Total Deal ($M) $195 $175 $185 $219 $300
Median
Years to Exit 7.0 6.6 6.9 5.5 9.2
# of Structured Deals # of All-In Deals
0
2
4
6
8
10
12
14
16
18
20
2012 2013 2014 2015 1H 2016
#ofBigExits
In 1H 2016, 7 of 9 M&A device big
exits were structured. There have
never been more than 50%
structured deals in any year.
Looking at regulatory pathways in
1H 2016, the majority of deals (6
of 9) are 510k pathway. These
companies typically require
revenue ramp-up prior to
acquisition. This helps to explain
the longer time to exit and later-
stage focus.
VC-backed Device Big Exit M&A Deal Structure 2012–1H 2016

Dx/Tools Faces Exit Slowdown
2015*
While there have been multiple
dx/tools acquisitions of public
companies in 1H 2016, there have
been only two private M&A big
exits. Both deals were tools
companies focused on drug
discovery.
Dx/tools IPOs in 2015 performed
poorly, and there were none in 1H
2016.
Q1 Q2 Q3 Q4 Total
2013
IPO 1 0 2 1 4
M&A 1 1 1 0 3
2014
IPO 2 2 3 0 7
M&A 2 3 0 5 10
2015
IPO 1 2 1 1 5
M&A 3 0 2 1 6
2016
IPO 0 0 0
M&A 1 1 2
VC-backed Dx/Tools Exits by Quarter 2013–1H 2016

Dx/Tools Hits Big Exit M&A Slump
Median
Upfront ($M) $127 $350 $133 $184 $108
Median
Total Deal ($M) $127 $450 $239 $189 $108
Median
Years to Exit 5.6 8.2 6.0 4.5 6.1
# of Structured Deals # of All-In Deals
The two 1H 2016 deals were
commercial-stage tools
companies with no milestones. A
third tools deal was announced
in early Q3 2016. Revenue
traction is likely the main
predictor of M&A success.
In the dx space, uncertainty
existed for most of 1H 2016. This
was due to Medicare lab test
pricing and FDA regulation of
lab-developed tests. With more
clarity on the horizon, activity
should increase.
0
1
2
3
4
5
6
7
8
9
10
2012 2013 2014 2015 1H 2016
#ofBigExits
VC-backed Dx/Tools Big Exit M&A Deal Structure 2012–1H 2016

Glossary
Big Exit
Big Exits are defined as private, venture-backedmerger and acquisition
transactions in which the upfront payment is $75 million or more for
biopharma deals and $50 million or more for device and dx/tools deals.
Initial Public Offering
IPO is defined as a venture-backed company raising IPO proceeds more
than $25 million.
Deal Descriptions
Structured Deal
This is a pay-for-performance system that pays some of the consideration
upfront, but sets milestones in development that must be achieved before
the full value of the transaction will be realized.
All-in Deal
All consideration for the deal is paid when the deal closes.
Big Exit Upfront Payments
The upfront payment refers to payments in a structured deal that are
made at the close of the deal; it does not include milestones.
Big Exit Milestones to be Earned
The milestones to be earned refer to payments in a structured deal that
are made after the pre-determinedgoals are met.
Total Deal Value
The total deal value of a structured deal includes both the upfront
payment and the milestones to be earned.
Regulatory Definitions
Non-approved
Non-approvedrefers to a device company that has no regulatory approval
for its product.
CE Mark
CE Mark refers to a device company that has a CE Mark-only product. CE
Mark is a European Union designation that is less difficult to obtain than
FDA approval, and the approval process typically has a faster timeline.
U.S. Commercial
Commercial refers to a device company that has an FDA-approved
product, and typically is in commercial stage.
Series A
Series A companies are defined as U.S. companies raising their first
round greater than $2 million in equity or backed by institutional or
corporate venture capital.
Indication Definition
Neurology
CNS, pain, and psychologycomprise neurology.

About the Authors
27
Jonathan Norris
JonathanNorrisisa managingdirectorfor SVB'sLifeScienceandHealthcarepractice.Norrisoversees
businessdevelopmenteffortsfor bankingandlendingopportunitiesaswellasspearheadingstrategic
relationshipswithmany healthcareventurecapitalfirms.He alsohelpsSVBCapitalthroughsourcingand
advisingon limitedpartnershipallocations.
Inaddition,he speaksatmajorinvestorandindustryconferencesandauthorswidelycitedanalyses
ofhealthcareventurecapitaltrends.Norrishas morethansixteenyearsofbankingexperience
workingwithhealthcarecompaniesandventurecapitalfirms.Norrisearneda bachelor'sdegreein
businessadministrationfromtheUniversityofCalifornia,Riversideanda jurisdoctoratefrom
SantaClaraUniversity.
Managing Director
Silicon ValleyBank
jnorris@svb.com
Paul Schuber
PaulSchuberisanassociatewithSVBAnalyticsleadingvaluationengagementsandspecializinginthelife
sciences.PriortoSVBAnalytics,Schuberfacilitatedclinicaltrialson behalfof pharmaceuticalsponsors
andpre-clinicaltrialstoadvancemedicalschoolresearch,whichincludedwritingandimplementingIRB
andIACUCprotocols.Schuber’shealthcareexperiencealsoconsistsof workingasanemergencymedical
technicianandan electrocardiogramtechnician.Hehasa backgroundintechnologyaswell,workingin
many roles,includingchieftechnologyofficerofan e-commercecompany.
Schuberearneda master’sdegreeinthe businessofbiosciencefromKeckGraduateInstituteof Applied
LifeScienceswhilealsostudyingatClaremontMcKennaCollegeatthe RobertDaySchoolofEconomics
andFinance.
ValuationsAssociate
SVB Analytics
pschuber@svb.com

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services, SVB helps address the unique needs of innovators.
28
This material, including without limitation to the statistical information herein, is providedfor informationalpurposesonly. The materialis based in part on
information from third-party sourcesthat we believeto be reliable,but which have not been independentlyverifiedby us and for this reason we do not represent
that the information is accurate or complete.The information should not be viewed as tax, investment,legal or other advice nor is it to be reliedon in making an
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should be construedas a solicitation,offer or recommendation to acquire or dispose of any investmentor to engage in any other transaction.
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