When Jim McCarter founded Divergence, Inc. in 1998, St. Louis was far from a start-up hub. The Company's successful acquisition by Monsanto is now but one indicator of a burgeoning entrepreneurial tech scene in St. Louis. Here's a tour from the science behind Divergence, to Monsanto Growth Ventures, to BioGenerator and other innovation engines of the region.
What makes a city a hub of entrepreneurship? Successes and reinvestment.
1. Divergence, Inc.
Enabling Innovation Through Entrepreneurship –
Divergence, Inc. and Start-ups in St. Louis
James McCarter, M.D., Ph.D.
Entrepreneur in Residence, Monsanto Growth Ventures & BioGenerator
Adjunct Professor of Genetics, Washington University
(Former President & CSO, Divergence, Inc.)
Washington University School of Medicine
Reunions, April 25, 2014, St. Louis MO
2. Divergence, Inc.
• Accelerated innovation is needed to meet massive global
challenges in health, food & environment.
• Entrepreneurship is uniquely positioned to drive innovation
through creation of multidisciplinary teams with singular focus.
• The capital formation landscape is rapidly changing with the
rise of angel investors, crowd sourcing & corporate venture.
• After a decade of capacity building, St. Louis’ entrepreneurial
ecosystem is nearing critical mass.
• The mission & culture of WashU must expand from leading in
knowledge creation to embrace innovation for societal impact.
• Join in enabling WashU & St. Louis entrepreneurship by
identifying clinical needs, mentoring, giving, & investing.
Key Messages for Innovation & Entrepreneurship
3. Divergence, Inc.
Colleagues
Divergence: Derek Rapp, Jeremy Williams, Michelle Insco
Monsanto: Robb Fraley, Tom Adams, John Hamer
BioGenerator: Eric Gulve, Dan Broderick
Washington University: Jeff Milbrandt, Evan Kharasch
Slides
Cortex Innovation District: Dennis Lower
St. Louis Regional Chamber: Jay DeLong
Balsa and Idea Labs: Yinzi Liu, Avik Som
Thank You
Financial Disclosures: Monsanto, Cultivation Capital, Neurolutions, Mobius Therapeutics
4. Divergence, Inc.
Divergence – an “Overnight Success”
that was a Decade in the Making
• St. Louis biotech acquired
by Monsanto in 2011
• 3 products in agriculture &
veterinary medicine
• Team of 25 scientists,
world-class SAB including a
Nobel laureate & 4 HHMI
Investigators
• Reputation for scientific-
excellence with 80 patents &
publications and leadership
in RNA interference
• Venture & angel financing
of $21M, Revenue of $22M
from contracts & 33 grants
4
5. Divergence, Inc.
Trichinella
Whipworm
Plant Parasites
C. elegans
Hookworm
Ascaris
Filarial Worms
Heartworm
Pinworm
Livestock
Strongylids
• Apply the public
knowledge created by
WashU’s world-
leading effort in
nematode genomics
(McCarter & Waterston,
Mitreva & Wilson)
Divergence Mission: Develop Safe & Effective Products for the
Control of Parasitic Nematodes in Humans, Animals, & Plants
Nematodes (roundworms) -
• Most abundant animals
• Infect 2 billion people
• Cause >$80 billion in crop
damage annually
Root-knot
Cyst
Lesion
Reniform
6. Divergence, Inc.
Soybeans damaged
by SCN
U.S. SCN distribution
Uptake of plant proteins
into the SCN intestine
(B. Gao & M. Hresko, Divergence)
Soybean Cyst Nematode (SCN) is the Most
Important Disease of U.S. Soybeans
• Over $1 billion in lost yield annually in U.S. alone
• Yield losses of 30% without above ground symptoms
• Neurotoxic pesticides out of favor with growers & regulators
• Rapid breaking of genetic resistance in the field
7. Divergence, Inc.
Divergence – Genomics led to Superior Diagnostic Products that
Can Replace Microscopy in Veterinary & Human Medicine
Plate ELISA for detection of
hookworm, toxocara &
whipworm in dogs
IDEXX whipworm test, launched in
2014, detects infection a month
ahead of microscopy
Divergence achieved proof-of-concept for human Ascaris detection in Brazil
(M. Crawford, Divergence)
8. Divergence, Inc.Lee and Jez, Structure 21:1778-87, 2013.
• PEAMT: Divergence discovered a unique and essential enzymatic
pathway for nematode phosphocholine biosynthesis
• Partnered with Dr. Joe Jez at Danforth & WashU to characterize
enzyme structure and function
2005 - The Pivot: Genomics led to “Divergent” Molecular Targets
But Not Yet Pharmaceutical & Agrochemical Products
9. Divergence, Inc.
2005 - The Pivot: Divergence Leveraged its Strengths in
Informatics to Create a New Computational Chemistry Platform
The Harvest Chemical Discovery Platform
• Broad R&D platform for rapid and cost-effective
agrochemical discovery
• Developed in collaboration with UK-based
Cresset Biomolecular Discovery
• Able to search chemical structure space based
on electron distributions rather than 2D
structures
• Resulted in discovery of a molecular series with
novel mode of action, high potency, and safety
far superior to commercial nematicide standards
Jeremy Williams, PhD
Vice President,
Discovery Research
Matt Dimmic, PhD
Senior Director,
Computational
Discovery Research
10. Divergence, Inc.
2009 - Jason Bond – Southern Illinois Univ.,
Carmi IL, SCN Seed Treatment
Cysts Per Root at 5 weeks
0
10
20
30
40
DA-I DA-II oxamyl NT
1 mg/seed
2009 - Greg Tylka – Iowa State,
Nevada IA, SCN Seed Treatment
Hg Reproductive Factor
0
5
10
15
20
25
DA-I DA-II oxamyl NT
1 mg/seed
Divergence Nematicide – SCN Reproduction
Reduced at All Three Sites in Illinois and Iowa
SCN
Performance at 1 mg/seed comparable
to the carbamate oxamyl.
(B. Shortt, Divergence)
12. Divergence, Inc.
Be ready for everything to take longer than you expect.
Just because others aren’t doing it doesn’t mean it’s not
worth doing. Position yourself for exposure to smart
experienced people. Build a multidisciplinary and versatile
team. The best situation is being valued for products and
platform. Communicate fully with your team for
a shared vision. Create incentives for your team
including ownership. Things change when you accept
investors’ money. Make every decision with an eye
toward the liquidity event. Do not obsess about
valuation. Find non-dilutive sources of funding. Leading a
start-up company is an intensely personal experience.
(Start-ups are risky but not starting is risky too.)
Paraphrasing a Dozen Start-up Lessons
from Divergence CEO Derek Rapp
14. SOYBEAN CYST NEMATODE
MONSANTO RESEARCH, SUMMER 2011
New Generation of Nematicide Could Provide
Novel Formulations with Excellent Control
• Through the acquisition of
Divergence, Monsanto has added
a new nematicide to its pipeline
• Efficacy of new nematicide equal
to competitive standards against
multiple nematode species
• A variety of crops showing good
results including corn, soy and
cotton
• Regulatory submissions on track
EXPLORATORY
NEMATICIDE CHEMISTRY
UNTREATED
CONTROL
Phase 3
Advanced Product
Development
15. Our Vision: Sustainable Agriculture
A Strong Vision That Guides All We Do
• Producing More
– We are committed to increasing yields to meet
the growing demand for food, fiber & fuel
• Conserving More
– We are committed to reducing the amount
of land, water and energy needed to
grow our crops
• Improving Lives
– We are committed to improving lives around
the world
Monsanto’s Goal: Double Yields with 1/3
Less Inputs by 2030 versus the year 2000
16. Headquarters: St. Louis, MO
Total employees: ~22,000
Global locations: >500
Net Sales (FY13) $14.9 billion
United States
Latin America North
Brazil
Argentina
EU 27
India
Australia
Corn Soybeans Cotton
Vegetables Roundup®
Primary Markets
Monsanto Company is a leading global provider of technology-based tools
and agricultural products that improve farm productivity and food quality.
Monsanto is 100% Focused on Agriculture
“We succeed when farmers succeed.”
-Hugh Grant, Monsanto CEO
17. Genetically Modified Crops
Produce Food That is as Safe and Nutritious as Conventional
USED FOR GMO CROPS SINCE 1996
ACRES OF
FARMLAND3.95 Billion
SUPPORT THAT GMO CROPS ARE JUST AS SAFE AS
THOSE DEVELOPED THROUGH TRADITIONAL BREEDING
ACADEMIC
STUDIES1000+
THAT GMO CROPS HAVE BEEN RESEARCHED AND DEVELOPED
YEARS30
ON AVERAGE TO DEVELOP AND TEST GM SEEDS
BEFORE THEY’RE GROWN COMMERCIALLY IN THE U.S.
YEARS13
WHERE GM CROPS HAVE BEEN APPROVED FOR
CULTIVATION OR IMPORT
COUNTRIES63
www.gmoanswers.com
18. Agriculture is at the Center of Global Changes
1990 20121980 2050TODAY
4.4B
7.1B
9.6B+
1ACRE
perpersonin
1961
lessthan
1/3ACREperpersonin
2050 DIETARYPERCENTAGEOFMEAT
9%
in 1965
14%
in 2030
CHANGING
CHANGINGRISING
DECLINING
Challenges
Source: The World Bank, Food and Agriculture Organization of the United Nations (FAO-STAT), Monsanto Internal Calculations
20. Growth Ventures Creates Transformative Business
and Technology Opportunities for Monsanto
Venture Capital - Gaining Earlier Access to External Innovation
• Sourcing from venture capital & entrepreneurial networks provides strategic
insights to areas of disruptive innovation
• Entrepreneurs bring ideas from other industries and syndication leverages
new capital to solve challenges in agriculture
SFO STL BOS
Innovation is concentrated in entrepreneurial ecosystems with leading
research centers, VCs, angel investors, incubators, accelerators, etc.
21. Venture Capital - Gaining Earlier Access to External Innovation
• Investment builds a portfolio of early-stage assets with opportunities for
partnering, licensing, talent, and M&A
• Monsanto Growth Ventures VC team has sourced investments and
additional deals (licenses, etc.) from hundreds of leads
Growth Ventures Creates Transformative Business
and Technology Opportunities for Monsanto
22. Doubling Yields with 1/3 Less Inputs by 2030 vs. 2000 –
Farming in the Future Will Be Increasingly Information-Driven
23. General Farm Planning
Weed Control Program
Row Spacing
Variety/Hybrid
Selection
Refuge Options
Plant Population
Seed Treatment
Soil Insecticides
Pre-Plant Irrigation
Fertility Program
pH Management
Burn-Down Program
Tillage Level
Primary Tillage Program
Seed Depth
Planting Speed
Through the Field
Other Planting Operation
Decisions
Plant Population
Starter Fertilizer
Herbicide Application
Soil Insecticides
Fungicide Application –
In-Furrow
Variety/Hybrid
Selection In-Field
Keep Stand or Re-Plant
Post-Emergent Herbicide
Application
Foliar Insect Control
Fertility Program
Foliar Disease Control
Irrigation Application
In-Season
Equipment
Timing
Storage
Post-Harvest
Assessment
PLANTING IN-SEASONPRE-PLANTING HARVESTPLANNING
Grower Decisions Over the Year –
Farming in the Future Will Be Increasingly Information-Driven
24. San Francisco Bay Area Dominants U.S. Venture Capital
Investments Followed by Boston
SFO
STL
BOS
Innovation is concentrated in entrepreneurial ecosystems with leading
research centers, VCs, angel investors, incubators, accelerators, etc.
PWC Moneytree Venture Capital Report, 2013.
25.
26. St. Louis now has
>$2B in
Venture Capital
Under Management
27. the non-profit Venture Arm of BioSTL has…
• Created & funded 46 start-ups
• Invested $7.6 million, leveraged 20:1 with
over $156 million in additional investment
& revenue
• Funded WashU start-ups Cardialen,
Neurolutions & PixelEXX
• BioGenerator Accelerator Lab; 18,000
square feet of office & lab space, free for
start-ups
• Entrepreneur in Residence Program;
16 experienced EIRs mentoring over 100
companies
28. • Launched in 2012, Arch Grants is a non-profit creating a game-changing
entrepreneurial culture and infrastructure to create jobs & attract talent to St. Louis
• Arch Grants funded companies are winners of an international start-up competition
that has attracted 1,600 applications from 40 states and 20 countries
• 35 starts-up have been awarded $50K each in non-dilutive financing to launch in
St. Louis
• With $1.9M in grant funding, companies have generated $15M in revenue and
follow-on capital, 34 remain viable and St. Louis-based
29. Biotech Has Been Joined By a Thriving IT Start-up Scene That
Boosted St. Louis Capital Raised in 2013 to $380 Million
30.
31. Transform a 200-acre midtown industrial neighborhood into a
vibrant, 24-7, live-work-play-learn innovation community
32. Transform a 200-acre midtown industrial neighborhood into a
vibrant, 24-7, live-work-play-learn innovation community
• $2 billion development
• 3.7 million square feet
• 13,000 permanent jobs
• 5 Innovation Centers
• Green space & transit
33.
34. • Launched in 2010
• Consulting for Bioscience Companies
• 200 Student Participants
• 73 Consulting Projects for 37 clients
• 28 WashU OTM Technologies
• e.g. Business plans for start-ups
• Launched in 2013
• Biomedical Engineering Innovations
• 100 Student Participants
• 14 Teams with inventions based on
clinician-identified challenges
• e.g. Cursor control for locked-in patients
Student Groups Are Creating a Culture of
Entrepreneurship at Washington University
35. Divergence, Inc.
• Accelerated innovation is needed to meet massive global
challenges in health, food & environment.
• Entrepreneurship is uniquely positioned to drive innovation
through creation of multidisciplinary teams with singular focus.
• The capital formation landscape is rapidly changing with the
rise of angel investors, crowd sourcing & corporate venture.
• After a decade of capacity building, St. Louis’ entrepreneurial
ecosystem is nearing critical mass.
• The mission & culture of WashU must expand from leading in
knowledge creation to embrace innovation for societal impact.
• Join in enabling WashU & St. Louis entrepreneurship by
identifying clinical needs, mentoring, giving, & investing.
Key Messages for Innovation & Entrepreneurship
NEEDS: Successful exits
for repeat investments &
serial entrepreneurs.
NEEDS: Leadership for an
entrepreneurial culture
including alumni.
36. • Innovation requires a scientifically literate public & talented young scientists from
diverse backgrounds
• YSP was launched in 1991 to promote science literacy and attract high school
students from disadvantaged backgrounds into scientific careers through hands-on
research and contact with active scientists
• Each year more than 100 graduate student volunteers reach 1000 students in local
public schools
• More than 250 high school juniors have completed research internships at WashU
– the majority major in science in college and 1/3rd complete a graduate degree
• YSP is supported by the Endowment for Science Literacy at WashU
And One Last Message … The Importance of
Science Literacy
37. Thank you to Monsanto for support of St. Louis innovation & science education.