Transcript Yield10 Slides_9_10_15_public deck_NEW LOGO

Planned spin out to
commercialize crop science
innovations from Metabolix
September 2015
Planned Spin Out of Yield10
MBLX spun out of MIT in 1992
A world leader in metabolic engineering
Shares traded on the NASDAQ as MBLX
Innovation Engine
MBLX Commercial Focus
 Specialty Biopolymers
 Strong synergy between core
bioscience and fermentation
 PHA recovery – Biopolymers
 Proprietary PHA compositions
Biomedical spin out
 Proprietary PHA applications
 Medical devices
 FDA approved PHA polymer
 Future optionality
 TephaFlexTM sutures (B. Braun)
 Fermentation based chemicals
 PhasixTM hernia repair mesh (Bard)
 FASTTM recovery process
 Acrylic and
 GBL/butanediol
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Confidential
 GalaFlexTM (Galatea)
Global Portfolio
More Than 450 Patents
Where Nature Performs TM
 >700,000 patients treated
 Equity and licensing revenue to
Metabolix
Why Yield10?
Breakthrough
Science
Outstanding
Team
Transformative Traits
Strong IP
Yield10
Bioscience
“Where Nature
Performs”
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Confidential
Where Nature Performs TM
Global
Opportunity
Yield10 Investment Considerations
is… Aligned with compelling megatrends
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Global population growth from 7 billion to 9 billion by 2050 driving need for
>70% increase in food production over the same period
Growing pressure on water and land resources, issues with intensive agriculture
developing… Breakthrough technology for improved crop yield
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Novel yield trait technologies for both C3 and C4 photosynthetic crops
Foundation IP in place (owned/in-licensed)
Development/Scientific staff (16 FTEs) and research facilities in place
creates… Large addressable market opportunity
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Crop R&D $4 billion
GMO Seed $40 billion
Global food $4 trillion
enables… Numerous opportunities for value capture
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Confidential
Commercialize seed lines for select crops
Licensing and/or funded development projects with strategic partners
Where Nature Performs TM
Yield10 The Opportunity
A New Crop Science Paradigm to Enhance Global Food Security
9 October 2009
GA/EF/3242
Food Production Must Double by 2050 to Meet Demand from
World’s Growing Population, Innovative Strategies Needed to
Combat Hunger, Experts Tell Second Committee
is… Aligned with compelling megatrends
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Global population growth from 7 billion to 9 billion by 2050
Reduction in available land due to infrastructure growth
Increased pressure on scarce water and other resources
Changing global weather patterns
Environmental issues with intensive agriculture
Need for… >70% increase in food production over the same period
Key question… Can the current rates of crop yield increase get us there?
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Confidential
Where Nature Performs TM
Realizing a New Vision for Agriculture:
A roadmap for stakeholders
http://www3.weforum.org/docs/WEF_IP_NVA_Roadmap_Report.pdf
Yield10 Solution
Enhanced Global Food Security and Sustainability Through Advanced Bioscience
Enhanced Carbon Capture
Targeted Carbon Deposition
Robust
Plants
CO 2
with
Fix more carbon
per acre/unit
input
Targeted
Carbon
Deposition
Enhanced Carbon Capture
Photosynthesis (Source)
Enhanced Carbon Metabolism
Step Changes in Food Crop Yield
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Confidential
Where Nature Performs TM
Biomass Yield
Seed Yield
Starch or oil
Nutrition
Industrial
Products
Carbon fixed in
products (Sink)
Yield10 Solution: Step Changes in Crop Yield
DRAFT
Enhanced Seed Yield: simplified carbon flow chart
Enhanced Carbon Capture
CO2
CO2
Seed
Sugar
Biomass
CO2
Central Carbon
Metabolism
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Confidential
Where Nature Performs TM
Yield10 The Science
A New Crop Science Paradigm to Enhance Global Food Security
 Metabolic
modelling
 Systems biology
Metabolic Pathway Engineering
Microbial genes to
enhance crop
carbon pathways
 Bioinformatics
Crop genomics “Big Data”
advanced transcriptome network analysis
Key global
regulatory genes
Complex genomics data
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Confidential
Functional modules
targeting pathways of interest
Where Nature Performs TM
• Crop yield is complex and challenging
• Yield10 leverages microbial diversity to
eliminate bottlenecks in plant carbon
metabolism integrated with advanced
“big data” transcriptome network
analysis to control complex global
regulatory networks to achieve step
changes in crop yield
• Different solutions may be required for
different crops and involve modulating
multiple genes e.g. soybean will be
different from sugarcane
Yield10 Target: Increase Yield in C3 Crops
A New Crop Science Paradigm to Enhance Global Food Security
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Over 90% of global food production is based on crops having the C3 photosynthetic system (canola, soybean, rice,
wheat, potato etc)
Chloroplast
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The concentration of [CO2] available to the rubisco enzyme is the bottleneck
Loss of fixed CO2 by photorespiration
Increased flow of CO2 through the leaf surface pores results in increased water loss
Yield can be increased under artificial conditions, high CO2 and high water
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Objective: Double seed yield in C3 crops (Proof of concept in Camelina)
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Scientific approaches
1. Increase photosynthetic carbon capture (C3003 gene trait)
2. Direct more carbon to the seed (C3004 gene trait)
3. Increase the efficiency of converting fixed carbon into seed using high efficiency metabolic pathways
from microbes (C3005 pathway trait; C3006 pathway trait)
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Confidential
Where Nature Performs TM
Yield10 Target: Increase Yield in C4 Plants
A New Crop Science Paradigm to Enhance Global Food Security
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Major C4 crops are corn, sugarcane, sorghum etc.
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C4 plants are typically higher yielding
than C3 plants and more drought tolerant
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e.g. Corn @ 160+ bu/acre vs soybean @
43+ bu/acre
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C4 plants have a unique structural
arrangement of the mesophyll cells (where
the C4 part of the system takes place) and bundle
sheath cells
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Yield challenge is not amenable to a purely metabolic engineering approach
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Developed a “Systems Approach” – T3 Platform
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Where Nature Performs TM
Yield10 T3 Platform
A New Crop Science Paradigm to Enhance Global Food Security
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The T3 Platform uses big data analysis based on complex algorithms to correlate networks of transcriptomes
from different crop species with physiological outcomes (functional modules) predictive of yield
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Objective: Identify key genes to control complex regulatory networks
Crop genomics “Big Data”
advanced transcriptome network analysis
Key global
regulatory genes
(GTF)
Complex genomics data
~36,000 genes
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Confidential
Functional modules
targeting pathways of interest
20 gene candidates
Where Nature Performs TM
Functional Modules
1. Increase photosynthesis (light
harvesting pigments and electron
transport)
2. Increase central metabolism
(higher concentrations of carbon
intermediates)
3. Increase overall biomass yield
(switchgrass objective)
3 lead GTF genes tested
in switchgrass
Yield10 C4 Crop Example: Biomass Case Study
WT
+GTF1
+GTF2
+GTF3
C4001 Transgenic line 4
Photosynthesis
Chlorophyll
Carotenoids
144% of control
141% of control
+GTF1,3
Central Metabolism
Soluble sugars
Leaf starch
138% of control
160% of control
Total dry biomass
140% of control
WT
PAR
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Multiple transgenic lines in different germplasms were produced overexpressing the different GTF genes
identified using the T3 Platform
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Corresponding genes in major food crops have been identified
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Early data indicates seed yield improvement in Camelina with the C4001 trait gene
Evaluation of the C4001- C4003 genes is currently ongoing in sugarcane
Solution: GTFs up-regulate complex regulatory networks
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Where Nature Performs TM
Yield10 Transcriptome Targeted Metabolic Engineering
Metabolic
pathway genes
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Photosynthesis systems
Carbohydrate biosynthesis
Stress response
Nitrogen use efficiency
Amino acid metabolism
Test gene combinations using
transgenics
71 TFs up-regulated
34 TFs regulated by more than one GTF
Downstream
transcription factor genes
Test individual TFs
using transgenics
22 TFs down-regulated
Targets for gene deletion
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The impact of the GTF gene expression on the key metabolic pathway genes (target modules) in the
transgenic lines were fully consistent with the observed and measured phenotypes
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Multiple downstream transcription factors (TFs) were effected, including several previously patented by third
parties and many whose function is unknown – IP “WHITE SPACE”
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The results were linked to major crops by transcriptome/expression studies of homologs in corn and rice
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Where Nature Performs TM
Yield10 Steep Learning Curve
High Yield
Transgenic
Lines
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Global expression patterns
 Downstream transcription factors
 Metabolic pathway genes
Yield results validate the new paradigm and enable further discovery
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(e.g. if the yield of seed could be increased by >50% what else would happen?)
Transcriptome data from these lines enables additional improvements
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Transcriptome,
metabolome
analysis
Example 1: 3 Transcription factors in switchgrass potentially involved in pant stress have been experimentally validated
Example 2: Gene targets for increasing the flux of the additional fixed carbon to the oilseed have been identified,
experimental validation is ongoing
Food crops can then be modified using transgenes or precision genome engineering
Further refinement of the T3 Platform to inform traditional breeding programs
Additional metabolic engineering projects with more complex microbial pathways are already at an
advanced stage (C3005 and C3006 pathway traits)
Confidential
Where Nature Performs TM
Yield10 Value Capture Model
Objective: Participate in Incremental Value Created by Yield10 Technologies
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Yield10 approach
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Develop seed lines for soybean and canola
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Demonstrate targeted yield increase
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Multi-site field trials in major US soybean and Canadian
canola growing areas
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Stack proprietary YIELD10 traits with off-patent or
generic herbicide traits
Develop partnerships/licensing for corn, cane, wheat,
potato, rice and cotton
• Target 15-20% share of value added through seed
sales, licensing and/or other business models
• Estimated R&D cost to achieve proof points ~ ? mm
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Where Nature Performs TM
Conceptual example of value
creation in soybean…
Approximately 84 million acres
planted in the US for 2014
Average price approximately $10.00
per bushel
10 bushel/acre increase in yield
creates approximately $8.4 billion
of value
Yield10 Timeline and Value Drivers
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Over $50 mm in cumulative investment to date
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Includes technology developed from ~$30 mm of cost shared grants
Significant value has been created from these programs including lead traits and IP
~$25 mm Prior investment
to establish crop capability
$5 mm ARPAe
targets seed yield
$9.99 mm DOE grant
Includes increasing
photosynthesis & yield
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Confidential
$2.50 mm DOE BETO award announced,
genome editing, seed yield
Metabolix Oilseeds
confirms C3003 results
Exclusive License
for C3003 trait
Switchgrass T3 platform
established, patent filed
Participation in second
$5 mm ARPAe award
targeting seed yield
ARPAe Collaboration
demonstrates and patents
C3003 trait
Where Nature Performs TM
MBLX files patent on
discovery from second
ARPAe program
License rights for IP from
third $8 mm ARPAe
program
Yield10 Technology Milestones
Yield10 Seed Line Development Major Ramp-up and Transition Underway in 2015
Crop/Trait
Current Activity
Milestone (Greenhouse)
Camelina/C3003
Single copy T3 lines
in greenhouse
Q3/4, 2015
Camelina/C3004
POC of third party data
POC - Q1, 2016
Camelina/C3005
POC of third party data
4-8 gene pathway
POC - Q2/3, 1016
Camelina/C3006
Large number of genes
POC achieved, Q3, 2015
Camelina/C4001
T1 lines,
Progress to T3
T3, Q1, 2016
Camelina/C3003+C3004
Program underway
T3, Q2, 2016
C3003/Canola
First transgenic lines in hand
uses double haploid line, in-house
POC, Q 2/3, 2016
C3003/Soybean
Program underway, collaboration
POC, 2017
C3003/Rice
Transformation initiated in-house
T2 lines Q3/4, 2016
C4001/Sugarcane
Collaboration
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Confidential
Where Nature Performs TM
Yield10 Commercialization Program
Yield10 Seed Line Development Major Ramp-up and Transition Underway in 2015
Proof of
Concept
Early
Development
Advanced
Development
Pre Launch
Camelina C3003
Commercial
2020
Canola C3003
2021
Soybean C3003
2022
Anticipate numerous
opportunities for value
capture along the path
to commercialization
2021 ?
Rice C3003
2021
Canola C3003/C3004
Partnership/licensing discussions initiated for Corn / Cane and planned for Wheat / Rice / Potato / Cotton
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Confidential
Where Nature Performs TM
Yield10 Investment Considerations
is… Aligned with compelling megatrends
•
•
Global population growth from 7 billion to 9 billion by 2050 driving need for
>70% increase in food production over the same period
Growing pressure on water and land resources, issues with intensive agriculture
developing… Breakthrough technology for improved crop yield
•
•
•
Novel yield trait technologies for both C3 and C4 photosynthetic crops
Foundation IP in place (owned/in-licensed)
Development/Scientific staff (16 FTEs) and research facilities in place
creates… Large addressable market opportunity
•
Crop R&D $4 billion
GMO Seed $40 billion
Global food $4 trillion
enables… Numerous opportunities for value capture
•
•
19
Confidential
Commercialize seed lines for select crops
Licensing and/or funded development projects with strategic partners
Where Nature Performs TM
Planned spin out to
commercialize crop science
innovations from Metabolix
Aug 2015
Yield10 Metabolic Engineering Platform
Microbial genes account for the total global GMO acreage
Gene construct,
transformation
• GMO accounts for 49% of major crop acreage (corn, soybean, cotton and canola)
• Herbicide tolerant (Roundup, Liberty Link etc.), insect resistance (Bt etc)
http://isaaa.org/resources/publications/pocketk/16/default.asp
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Leverages the diversity of microbial carbon fixation systems
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Further optimize through native gene modifications
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High throughput testing/development in Camelina sativa
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4 yield traits developed and prioritized
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Transgenic line selection
~3 cycles
T1 >T2 > T3
a) Yield performance
b) Regulatory complexity
Lead yield trait, single gene “C3003”
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Proven in Camelina
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Progressing into canola and soy
Initial
Screening
~36 weeks
Greenhouse
“breeding”
seed bulk up
Homozygous
seed
Co-production of PHB a novel carbon sink
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Provides unique insights into carbon flow
Future commercial option for environmental and feed/nutrition applications
Confidential
Where Nature Performs TM
Field results
~12-14 weeks