Programming Life: Understanding The Transformative Potential of Synthetic Biology

Equity Research
Healthcare | Life Science Tools
June 29, 2021

Industry Report
Matt Larew +1 312 364 8242

mlarew@williamblair.com
Max Smock +1 312 364 8336

Programming Life msmock@williamblair.com
Myles R. Minter, Ph.D. +1 312 364 5283

Understanding the mminter@williamblair.com
Raju Prasad, Ph.D. +1 312 364 8469

Transformative Potential of rprasad@williamblair.com
Synthetic Biology Bhavan Suri +1 312 364 5341

bsuri@williamblair.com
Please refer to important disclosures on pages 56 and 57. Analyst certification is on page 56.
William Blair or an affiliate does and seeks to do business with companies covered in its research reports. As a
result, investors should be aware that the firm may have a conflict of interest that could affect the objectivity of this
report. This report is not intended to provide personal investment advice. The opinions and recommendations here-
in do not take into account individual client circumstances, objectives, or needs and are not intended as recommen-
dations of particular securities, financial instruments, or strategies to particular clients. The recipient of this report
must make its own independent decisions regarding any securities or financial instruments mentioned herein.
William Blair
Contents
Overview............................................................................................................................. 3
What Is Synthetic Biology?................................................................................................. 4
Synthetic Biology Process.................................................................................................. 6
Synthetic Biology in Action – Spotlighting Three Pioneering Companies...................... 14
Ginkgo......................................................................................................................... 14
Zymergen.................................................................................................................... 19
Amyris......................................................................................................................... 24
Enabling Technologies...................................................................................................... 26
DNA Sequencing (Read).............................................................................................. 26
DNA Synthesis (Write)................................................................................................. 27
Gene Editing (Edit)...................................................................................................... 31
ESG Considerations........................................................................................................... 34
Market Opportunity......................................................................................................... 34
Kamil Mielczarek, CFA; Dylan Becker; and Sami Corwin, Ph.D., also contributed to this report.
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Overview
Synthetic biology involves the design and engineering of biological organisms. Part science, part
engineering, and part industrial design, we believe synthetic biology is best thought of as pro-
gramming—programming life. Synthetic biology is built on knowledge gained from the last several
decades of genomics research, which has led to its core principle, that biology is fundamentally
programmable, with cells not acting solely as stores of information, but also as processors of infor-
mation. In the same way that computers can be programmed with binary code, cells from every
living creature on Earth can be programmed with the code of life, DNA.
The most common application of synthetic biology today uses a process known as industrial fer-
mentation, which combines the programmable nature and manufacturing efficiency of cells to
make better-performing products more quickly, less expensively, and more sustainably. With this
in mind, perhaps the most straightforward way to think about synthetic biology is programming
cells to produce specific molecules. However, it is worth noting that molecule production is only a
subset of the applications for synthetic biology, and there are virtually limitless uses for changing
the “code” of organisms. For example, synthetic biology is already being used to program cells
to be used as therapeutics (i.e., gene and cell therapies), program living organisms to be used as
therapeutics (i.e., living medicines), and program living things such as plants and animals (e.g.,
GMO plants, genetically engineered salmon). Thus, more broadly defined, synthetic biology can be
thought of as programming cells to perform specific functions—molecule creation, pathway altera-
tion, micro or macro environment alteration, and beyond; in other words, programming life.
In this report, we describe in detail not only “what” synthetic biology is, but “how” synthetic biolo-
gy works. We do this by walking through the four main steps in the synthetic biology process (idea
generation, product design, cell programming, and product commercialization) and highlighting
the approaches of three leading synthetic biology companies (Ginkgo Bioworks, Zymergen, and
Amyris). We also discuss advances in each of the three main enabling technologies needed to pro-
gram cells—the ability to read DNA (with sequencing), write DNA (with DNA synthesis), and edit
DNA (most notably with CRISPR)—and highlight leading and emerging companies in each space.
Lastly, we include a detailed overview of the potential market opportunity for synthetic biology,
which can be broken into two components that correspond to the synthetic biology value chain:
1) the ecosystem of enabling technologies that drive the synthetic biology process and 2) the
manufacturing and commercialization of end products created on the synthetic biology platform.
While synthetic biology has the potential to revolutionize virtually every industry, initial efforts
to commercialize end products have largely focused on food (animal-free proteins), agriculture,
materials and energy (chemicals), consumer goods (cosmetics), and biopharma, in part because
of the impact that synthetic biology can have on these industries from an environmental, social,
and governance (ESG) standpoint. Over time, we expect the scope of synthetic biology to expand
into areas like small molecule synthesis, DNA data storage (storing digital information in DNA),
bioremediation (which involves using microbes to consume and break down environmental pol-
lutants), and bioprinting.
Because synthetic biology can be used to produce products more quickly, less expensively, and
more sustainably, we believe companies in the space will become core holdings in ESG-specific
portfolios or for investors with ESG screening criteria. In addition to addressing sustainability,
synthetic biology is poised to play a key role in solving social issues, such as food security, access
to clean water, and animal welfare. It is not an exaggeration to state that synthetic biology has the
potential to help solve some of the biggest challenges that humanity is facing, and we expect these
issues to only grow in importance in the coming years. As a result, we believe synthetic biology
companies represent core long-term holdings for any investor looking to gain ESG exposure.
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Concurrent with this report, we are adding co-coverage of Berkeley Lights with Brian Weinstein
and launching coverage of two companies in the synthetic biology ecosystem. We see Twist Biosci-
ence as a premier growth story in the life science space and are launching coverage with an Out-
perform rating. We see Zymergen as a core holding for investors looking for exposure to the trans-
formative potential of synthetic biology and are launching coverage with an Outperform rating.
What Is Synthetic Biology?

Synthetic biology involves the design and engineering of biological organisms. Part science, part
engineering, and part industrial design, synthetic biology is best thought of, in our opinion, as pro-
gramming—programming life. Synthetic biology is built on knowledge gained from the last several
decades of genomics research, which has led to its core principle that biology is fundamentally pro-
grammable, with cells not acting solely as stores of information, but also as processors of information.
In the same way that computers can be programmed with binary code, cells from every liv-
ing creature on Earth can be programmed with the code of life, DNA. Unlike the binary code
used for computers, which is made up of zeros and ones, DNA is made up of four nucleotides—
adenine (A), thymine (T), cytosine (C), and guanine (G). By changing the sequence of these four
nucleotides in a cell’s DNA, or inserting an entirely new code, cells can be programmed to perform
specific functions.
Of course, there are a couple of meaningful differences between the code used by computers and
the code of life.
• First, while computers read binary code, there are myriad human-readable “languages” to
write source code (Swift for iOS, Java for Android, and so on) and an established process for
compiling (translating) that source code to computer-readable machine code (i.e., binary).
Cells of course read DNA code rather than binary, and the simplicity and universality of DNA
code is why synthetic biology has the potential to be transformative in a number of indus-
tries—the same four letters used to build an ear of corn are also used to build a human ear.
However, there are not yet well-established programming languages (or even more aspira-
tional, fully integrated development environments) for cell programmers to write in, although
this is what synthetic biology pioneer Ginkgo Bioworks is building with its Foundry + Code-
base model.
• Second, and more importantly, the output of a computer reading code is digital, whereas the
output of a cell reading code is physical. So while computer applications can be helpful (like
Microsoft Word), informational (like FactSet), or entertaining (like YouTube), the output is
limited to transmitting information and instructions. Synthetic biology, on the other hand, can
be used to program a cell to make applications that are physical—for example, foods (like
Impossible Foods’ Impossible Burger), electronics (like Zymergen’s optical film product, Hya-
line), cosmetics (like Amyris’s Biossance clean skincare brand), and medicine (like monoclo-
nal antibodies, or mAbs).
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Exhibit 1
Biology Versus Computing
Computing Biology
Computing Role
example equivalent
Physical component
Hardware iPhone Cell
needed to function
Code Inform function 0101 written by Swift ATCG

Hard drive Store code Flash memory cards DNA
Software Translate code iOS mRNA
Application Perform function Square Proteins
Source: William Blair Equity Research
So if biology is programmable, then how does the program work? While the specifics are elegant
and complex, the basics are straightforward. Distinct regions within DNA strands called genes en-
code for the production of specific proteins that carry out nearly every task in an organism. The
two-step process by which a cell’s DNA is converted into functional proteins is referred to as the
central dogma of molecular biology. First, DNA is transcribed into single-stranded messenger RNA
(mRNA) in the nucleus of a cell during transcription. This mRNA is then transferred out of the
nucleus to the cytosol, where it is translated by cellular organelles called ribosomes, which join
amino acids together to form a functional protein. Consistent with our analogy, mRNA pioneer
Moderna refers to mRNA as the “software of life” as it converts information stored as code (DNA)
into applications (functional proteins). This process is illustrated below.
Exhibit 2
Schematic of DNA Transcription and mRNA Translation Events
Source: TBIO company presentation
In sum, synthetic biology leverages the programmable nature of cells to design and engineer bio-
logical organisms. The most common application of synthetic biology today uses a process known
as industrial fermentation (which we discuss briefly below and in more detail later in this report)
to produce commercial products at scale. Industrial fermentation combines the programmable
nature and manufacturing efficiency of cells to make better products more quickly, less expen-
sively, and more sustainably. Initial efforts have largely focused on food (animal-free proteins), ag-
riculture, materials and energy (chemicals), consumer goods (cosmetics), and biopharma, in part
because of the impact that synthetic biology can have on these industries from an ESG standpoint.
The ability to program life opens virtually limitless possibilities. For example, synthetic biology is
already being used to program cells to be used as therapeutics (i.e., gene and cell therapies), living
organisms to be used as therapeutics (i.e., living medicines), and living things such as plants and
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animals (e.g., GMO plants, genetically engineered salmon). Over time, we expect the scope of syn-
thetic biology to expand into areas like small molecule synthesis, DNA data storage (storing digital
information in DNA), bioremediation (which involves using microbes to consume and break down
environmental pollutants), and bioprinting. We discuss the market opportunity for synthetic biol-
ogy later in this report.
Synthetic Biology Process

Truly starting at the beginning, atoms are the building blocks of life, the smallest unit of matter
that retains all the chemical properties of an element, and when two or more atoms are bonded
together, they form a molecule. Biological molecules, or biomolecules, are organic molecules that
comprise living things (most familiar are the macromolecules: carbohydrates, proteins, lipids, and
nucleic acids).
Microbes (or micro-organisms) are tiny living things, indistinguishable to the naked eye; bacteria,
viruses, and fungi are among the most common. In the absence of free oxygen, microbes obtain en-
ergy by decomposing substances that contain oxygen (i.e., substrates) through the process of fer-
mentation. Different microbes can ferment different substrates and ultimately produce different
end molecules; for example, the mold Penicillium naturally produces the antibiotic penicillin, and
by growing Penicillium in controlled conditions inside a bioreactor along with a tailored growth
media, Pfizer was able to industrialize the production of penicillin. This process is called industrial
fermentation, and while it was initially developed for microbes, today it is used with a variety of
different cell types, including mammalian cells. In some cases, these molecules are the end prod-
uct (e.g., penicillin), but they are more often used as components in end products. For example,
Impossible Foods does not program a microbe to directly produce its Impossible Burger, but rather
to create a protein (molecule) that is used along with other ingredients in the final product.
With these examples in mind, perhaps the most straightforward way to think about synthetic biol-
ogy is programming cells to produce specific molecules. However, it is worth noting that molecule
production is only a subset of the applications for synthetic biology, and there are virtually limit-
less uses for changing the “code” of organisms. For example, Synlogic is programming gut bacteria
to treat disease, Joyn Bio is programming microbes for sustainable agriculture, and Allonnia is
programming microbes to consume and break down environmental pollutants. Synthetic biology
is also not limited to any one organism or cell type. Genetically engineering plants is a form of
synthetic biology, as is genetically engineering mammalian cells to be used as cell therapies or to
produce protein therapeutics (e.g., monoclonal antibodies) via industrial fermentation.
Thus, more broadly defined, synthetic biology can be thought of as programming cells to perform
specific functions, such as molecule creation, pathway alteration, micro or macro environment al-
teration, and beyond—in other words, programming life.
Now that we have provided some background, let’s turn to the actual process. There are four main
steps in the synthetic biology process:
1. Idea Generation
2. Product Design
3. Cell Programming
4. Product Commercialization
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Exhibit 3
Synthetic Biology Process
Idea Product Cell Programming

Product
Generation Design Commercialization
Design Build Test
Before discussing each of these steps in more detail, it is helpful to walk through a straightforward
example involving a synthetic biology company most people are already familiar with, Impossible
Foods. The company was founded on the idea that by making meat, dairy, and fish directly from
plants, it could end the use of animals for food (idea generation). By looking at proteins, textures,
and flavors at a molecular level, Impossible Foods discovered that heme, a protein found in all
plants and animals, is the ingredient that gives meat its signature taste. Instead of using the heme
protein that is encoded by cows, the company tested a wide variety of heme proteins and ultimate-
ly decided that leghemoglobin, a protein produced by soybeans, created the best-tasting burger
(product design). To manufacture leghemoglobin, Impossible Foods inserted the biosynthetic path-
way (i.e., the set of genes that, in sequence, encode for the enzymes that create leghemoglobin) for
the molecule into a yeast (microbe) called Pichia pastoris (cell programming). The programmed
microbe is then fermented, and the resulting heme molecules are combined with other ingredi-
ents to produce the end products: meatless burgers, sausage, and pork. Today, Impossible has a
large production facility in Oakland, California, and outsources additional production to OSI Group
(product commercialization).
I. Idea Generation
Exhibit 4
Synthetic Biology Process – Idea Generation

Product
Design Build Test
The synthetic biology process begins with an idea for a product, and generally speaking those
ideas fall into two buckets (nearly all of the successful applications of synthetic biology to date fall
into the first bucket).
1. For an existing product, the idea is often to use synthetic biology to make a replacement that
is better performing, less expensive, and/or more sustainable. Success here may mean improv-
ing the manufacturing efficiency of the cell used in an existing fermentation process and/or the
sustainability of the process. Success here could also mean making a synthetically generated mol-
ecule than can be used in a replacement product that is less expensive, more sustainable, and/or
better performing.
2. Alternatively, synthetic biology can be used to create entirely new products that cannot be cre-
ated using traditional chemistry or physics. Success here means solving intractable problems by
leveraging the inherent capabilities of biology, including the ability to respond to environmental
stimuli, produce complex molecules with ease, and self-replicate.
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In the Impossible Foods example, the idea was to make food products from plants rather than ani-
mals (more sustainable alternative to an existing product). Another example is a project completed
by Ginkgo Bioworks, where the company fine-tuned the DNA in yeast to produce a flavor ingredi-
ent more efficiently (a less expensive and more sustainable alternative to an existing product). Amy-
ris ferments genetically engineered yeast strains in sugarcane syrup to cheaply and sustainably
make squalane, which increases the spreadability of creams and lotions and is used in a number
of personal care products (less expensive and more sustainable alternative to an existing product).
Similarly, Genomatica is focusing on improving the cost-effectiveness and sustainability of biopro-
cesses for intermediate and specialty chemicals such as 1,4-butanediol, an important raw material
in plastics (a less expensive and more sustainable alternative to an existing product). Zymergen is
initially focusing on using synthetic biology to develop optical films with improved performance
for smartphones, tablets, and laptops (a better-performing alternative to an existing product).
Most ideas where the main objective is to make a product with improved performance also involve
manufacturing processes that are faster, less expensive, and more sustainable (and vice versa). For
example, Zymergen believes its synthetic biology process will eventually enable it to make better
products without the use of toxic chemicals, cut costs by roughly 90%, and produce materials in
about half the time. Alternatively, Amyris’s squalane molecule not only is less expensive and more
sustainable to produce, but also has demonstrated superior performance in skincare, haircare, and
CBD absorption. Ultimately, the ability to create better products more quickly, less expensively, and
more sustainably is a large part of why synthetic biology has the potential to be transformative in
a number of industries; we discuss this further in the “Market Opportunity” section of this report.
II. Product Design
Exhibit 5
Synthetic Biology Process – Product Design

Product
Design Build Test
After coming up with an idea, the next step is to design the product, which often involves identify-
ing a molecule that can be used to create the product. After Impossible Foods discovered that heme
was the ingredient that gives meat its taste, the company tested a wide variety of heme proteins to
replace the heme protein found in cows, ultimately identifying the molecule leghemoglobin (a
protein produced by soybeans) as the protein that created the best-tasting burger.
One approach to molecule identification is to screen primarily based on market opportunity rather
than performance. This is the approach used by Amyris, which focuses on widely used molecules
from plants and animals that can be less expensively and sustainably recreated. As an example,
Amyris produces squalane molecules that can serve as a direct substitute for squalane sourced
from shark liver. Going back to our Impossible Foods example, this would be akin to the company
electing to replace the heme protein found in cows with the exact same heme protein produced
through fermentation (as opposed to leghemoglobin).
Identifying the necessary molecule may seem relatively straightforward if the properties of the
desired end product are well understood, but in reality, it often involves scanning vast libraries of
potential targets. For example, Zymergen stores more than 1 million molecules in its Bioreachables
Database, and its graphical user interface called ZYNC (exhibit 6) helps its chemists and material
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scientists search for chemical substructures and properties among the collection. Since predicting
how molecules will perform is difficult, candidates must be selected from a database of potential
targets, incorporated into product formulations, and experimentally evaluated.
Exhibit 6
ZYNC Graphical User Interface
Source: ZY company filings
III. Cell Programming
Exhibit 7
Synthetic Biology Process – Cell Programming

Product
Design Build Test
Once product design has been completed, the next step is to program a cell to produce the mol-
ecule used to create the product. This part of the process is characterized by the design-build-test
cycle as many variations of genes and pathways must be tested to identify the optimal biosynthetic
pathway (i.e., the set of genes that, in sequence, program a cell to perform a specific function).
When using a cell to produce a molecule, the biosynthetic pathway refers to the set of genes that,
in sequence, encode for the enzymes that create the molecule.
For some molecules, the optimal biosynthetic pathway can be determined using public databas-
es. Going back to our Impossible Foods example, the biosynthetic pathway for the leghemoglobin
molecule used in its products was detailed in a Journal of Bacteriology article published in May
1996. To manufacture leghemoglobin, Impossible Foods programmed a yeast (microbe) called
Pichia pastoris with the molecule’s biosynthetic pathway. This example is straightforward, but
in most cases, coming up with the optimal biosynthetic pathway requires the use of proprietary
information from massive internal databases that have been built over time using DNA sequencing
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(discussed in more detail in the “Enabling Technologies” section of this report). These databases
are typically mined using artificial intelligence to determine a set of biosynthetic pathways to be
installed into host cells for evaluation.
After settling on a set of biosynthetic pathways to evaluate, it is time to move to the build portion.
This requires purchasing (or producing) synthetic DNA from a company like Twist Bioscience, or
potentially from an emerging player in the DNA synthesis space like Codex DNA or DNA Script.
Each biosynthetic pathway to be evaluated is inserted into a range of host cells using gene editing
(most notably CRISPR). We discuss synthetic DNA and gene editing technologies in more detail in
the “Enabling Technologies” section of this report.
Lastly, each programmed cell is tested. This involves fermenting the cell in growth media (i.e., nu-
trients) and analyzing the results. If the process successfully identifies a programmed cell that pro-
duces the right product in the right amounts, then it is time to move on to product commercializa-
tion. On the other hand, if the results do not meet expectations, then the process starts over and a
new set of pathways are selected for evaluation. An important final note as we move to the product
commercialization stage is that the cell programming and product commercialization phases are
often iterative, as some cells that perform well in laboratory or limited production settings may
not perform as well at scale.
IV. Product Commercialization
Exhibit 8
Synthetic Biology Process – Product Commercialization

Product
Design Build Test
The most common applications of synthetic biology today scale production via industrial fermen-
tation, a process that leverages the programmable nature and manufacturing efficiency of cells to
make better products more quickly, less expensively, and more sustainably. Given its importance
to many synthetic biology applications to date, industrial fermentation is important to understand
in more detail.
The process of industrial fermentation began with microbes: tiny, living, single-celled organisms
(yes, made of DNA and coded with ATCG) such as bacteria and fungi that cannot be seen without
a microscope. In the absence of free oxygen, microbes obtain energy by decomposing substances
that contain oxygen (i.e., substrates) through the process of fermentation. Different microbes can
ferment different substrates and ultimately produce different end products, some of which may be
useful, such as the mold Penicillium, which naturally produces the antibiotic penicillin.
Industrial fermentation was developed in the early 20th century to accelerate the production of
useful substances naturally created by microbes through fermentation. By providing microbes
(i.e., bacteria and fungi) with nutrients (i.e., media) in closed vessels called bioreactors (aka fer-
menters), engineers can create controllable conditions for growth. For example, by growing the
mold Penicillium in controlled conditions inside a bioreactor along with a tailored growth media
(including a kind of sugar and other ingredients), Pfizer was able to industrialize the production
of penicillin.
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Exhibit 9
Industrial Fermentation for Penicillin
Source: U.S. National Library of Medicine
While industrial fermentation was initially developed as an anaerobic (i.e., without oxygen) process
for microbes, today the term is used to refer to any large-scale aerobic or anaerobic process that in-
volves growing cells (including mammalian cells) along with culture media in a bioreactor to make a
product of interest. Industrial fermentation is used to manufacture foods (e.g., yogurt, cheese) and bev-
erages (e.g., beer, wine, distilled spirits), biologics (e.g., monoclonal antibodies), chemicals, and fuels.
Exhibit 10
Bioreactors
Source: InfoBloom
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Performance during fermentation is typically measured by three key metrics: yield (nutrients re-
quired to produce a given amount of product), titer (amount of product that can be manufactured
using an amount of fluid or filled bioreactor volume), and rate (productivity). Process optimization
often incorporates tweaks in the fermentation recipe (e.g., temperature, pressure, nutrients) to
maximize yield, with results typically confirmed by running bench scale fermentation runs.
Because commercializing a product typically means significantly scaling production of an end-

market product, this step of the process is often handled by the customer or a manufacturing part-
ner. In our Impossible Foods example, the company has scaled production both using a large in-
house production facility in Oakland, California, and outsourcing some production to OSI Group.
More broadly, there is an entire industry of outsourced manufacturing (e.g., Fermic and DuPont in
industrials and Lonza, Catalent, Aldevron [$9.6 billion acquisition by Danaher announced on June
17], and Thermo Fisher’s Patheon in biopharma). Exhibits 11 and 12 summarize current market
share and capabilities across the biopharma-oriented contract manufacturer (CDMO) landscape.
For more William Blair research on CDMOs, see here.
Exhibit 11
Estimated Drug Product Market Share – $20 Billion Market in 2020
Sources: Company reports, Outsourcing Pharma, Dun & Bradstreet, FactSet, and William Blair Equity Research
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Exhibit 12
CDMO Capabilities
Note: * denotes publicly traded

Bio = biologics/large molecule; SM = small molecule; C&GT = cell and gene therapy
Sources: Company reports, PharmSource, and William Blair Equity Research
As an example of what product commercialization with internal production looks like, Amyris has
been working on its scale-up capabilities since 2012, and the company’s ability to scale production
represents its core competency. In total, the company has scaled up 13 molecules from 100 micro-
liters (.0001 liters) to over 100,000 liters or more—this represents a billion-fold increase in scale.
Exhibit 13
Amyris Scale-Up
Source: Amyris company presentations
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Synthetic Biology in Action – Spotlighting Three Pioneering

Companies
To better explain how the synthetic biology process unfolds in the field, it is helpful to understand
the approaches of three leading synthetic biology companies—Ginkgo, Zymergen, and Amyris. We
discuss each company’s approach in more detail below.
Ginkgo
Product development requires specific industry knowledge that is difficult to scale across markets.
For this reason, Ginkgo takes a platform approach to idea generation. The company is focused on
building up the synthetic biology ecosystem with companies that leverage its platform to program
cells (including a diverse set of microbes, as well as mammalian cells), effectively outsourcing the
idea generation step of the process. Ginkgo’s customers come to them with a product specification
(e.g., “we want a product that does X”), and the company programs an organism to produce that
product at scale. Ginkgo maintains ownership of the intellectual property and licenses out only the
portions needed for commercialization to the customer. This “app store” business model involves
using royalties and equity positions to retain the value of cells programmed on its platform, allow-
ing Ginkgo to capture a portion of the total addressable market of the entire sector.
Exhibit 14
Ginkgo Commercial Model
Source: Ginkgo company presentations
In addition to partnerships with blue-chip customers in a number of different industries, Ginkgo

also enables earlier-stage start-ups to build on its platform from day one. The Ferment Consortium
(formed in October 2019 with a raise of $350 million) provides funding to more easily launch ven-
tures focused on specific industries. A sample of Ginkgo’s customers, including strategic ventures
and structured partnerships, is detailed below.
• Genomatica – a strategic partnership announced in September 2016 and expanded in Octo-

ber 2018 as part of a $90 million fundraising round. It develops bio-based process technolo-
gies to produce chemicals with better economics, sustainability, and performance.
• Joyn Bio – a joint venture with Bayer launched in September 2017 with a $100 million series
A. It engineers crop-colonizing microbes for the agriculture industry.
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• Cronos – a strategic partnership announced in September 2018. Its goal is to produce a range
of different cannabinoid molecules through fermentation.
• Motif FoodWorks – an operating company launched in February 2019 with a $90 million se-
ries A. It develops alternative protein ingredients for food.
• Synlogic – a strategic partnership announced in June 2019 and focused on making probiotic
therapeutics, i.e., gut bacteria engineered to treat disease.
• Moderna – a partnership announced in April 2020. Ginkgo is supporting Moderna’s process

optimization for key raw materials used in the manufacturing of its mRNA vaccines.
• Allonnia – an operating company launched from Ginkgo’s Ferment Consortium with a $40 mil-
lion series A in October 2020. The bioremediation company is focused on addressing pressing
waste pollution challenges.
• Corteva – a multiyear agreement announced in April 2021 that combines Corteva’s agricul-
tural expertise with Ginkgo's cell engineering platform and DNA Codebase to build next-gen-
eration, sustainable solutions for farmers to combat invasive pests and evolving resistance
challenges.
• Biogen – a gene therapy collaboration announced in May 2021. Biogen is paying Ginkgo up
to $120 million ($5 million up front, $115 million available through milestones) for access to
Ginkgo’s proprietary cell programming platform and capabilities, which the companies will
use to jointly develop a next-generation manufacturing platform to produce recombinant ad-
eno-associated virus (AAV)-based vectors.
Moving to product design and cell programming, we note that Ginkgo and Zymergen have both de-
veloped massive metagenomics databases (i.e., databases containing genetic material from many
different types of organisms and cells) that help the companies figure out what code is needed to
program a cell to perform a specific function (e.g., programming a microbe to produce a molecule).
These databases are both informed by the design-build-test process and help improve and ac-
celerate the process, creating a virtuous cycle that gives both companies a significant long-term
competitive advantage over any new entrants into the market.
Ginkgo’s platform is built around Codebase (which incorporates its metagenomics database, as
well as physical assets such as engineered strains and interchangeable genetic components) and
Foundry (its physical infrastructure, including state-of-the-art automated labs). See exhibit 15, on
the following page.
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Exhibit 15
Ginkgo Foundry + Codebase Platform
Inspired by the scale and refinement of semiconductor fabrication plants, data centers, and ge-
nomics centers, Ginkgo makes significant fixed-cost investments in its Foundries to drive increased
scale. These increases are primarily driven by advancements in automation (integration of soft-
ware and robotics), miniaturization (advanced liquid-handling and sample multiplexing), and pro-
cess development (novel techniques with fewer process steps). As shown in exhibit 16, Ginkgo’s
continued investments in its Foundries enabled throughput (as measured by the number of strain
tests per day) to increase by 3-4 times each year from 2015 through the start of COVID in 2020.
Exhibit 16
Ginkgo Strain Tests per Day
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Alongside the improvements in scale, continued investments in its Foundries have allowed Ginkgo
to recognize significant reductions in cost. By 2025, Ginkgo estimates that its cost per strain test
will be 100 times less expensive than “by hand” methods. Collectively, the continued increases in
scale and reductions in cost are referred to as “Knight’s Law” in honor of Ginkgo’s co-founder, Tom
Knight. Knight’s Law states that “the cost to genetically engineer a cell falls by 50% and the number
of designs tested increases by 3x+ per year in Ginkgo’s automated cell programming Foundries.”
Exhibit 17
Ginkgo Cell Engineering Costs
With Ginkgo’s app store business model, the company largely aims to cover its cost for cell engi-
neering work, preferring to capture value on the back end through royalties and equity positions.
This means that the cost savings recognized over time are passed on to Ginkgo’s customers, giving
them more shots on goal and creating more demand for Ginkgo’s platform.
In turn, more demand for Ginkgo’s platform drives more data for Codebase, which can be thought
of as a massive “parts catalog” of DNA sequences and host strains that the company can draw
from when developing a new organism. Codebase includes raw performance data generated from
Foundry experiments (more than 10 million strain tests run to date), data from public databases
for genetic sequences, and a proprietary data set of over 440 million additional genetic sequences.
Each program run on the company’s platform involves testing thousands or millions of DNA se-
quences, and the high-performance sequences (i.e., the handful of designs that meet its perfor-
mance goals for an experiment) identified through each program are a key component of Ginkgo’s
Codebase. The DNA sequences that do not meet performance goals for an experiment are also
valuable in that they help inform more effective programs in the future.
While characterizing sequences of DNA is important, it is difficult to predict the performance of

biological “parts” in a given context based on the DNA sequence alone. Cell programmers must also
consider the ways that the genes interact with the host strain that “runs” the program. Codebase
has been developed with this in mind and is more than just the individual modular sequences of
DNA that the company uses to program an organism; it also contains information on organisms
that have been optimized for robust growth or that are particularly adept at producing certain
classes of products. Importantly, these strains can be deployed across the entire platform on mul-
tiple programs, which reduces the amount of work needed to optimize a program and make a
commercially viable organism.
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William Blair
As shown in exhibit 18, Foundry and Codebase are inextricably linked and create a flywheel effect.
Cost savings recognized over time by improvements in Foundry scale are passed on to custom-
ers, driving more demand for Ginkgo’s platform. This drives more data for Codebase, which can
be used to support further improvements in Foundry capabilities and accelerate certain projects,
driving Foundry cost per strain test down further and restarting the cycle.
Exhibit 18
Ginkgo Flywheel
After using its platform to determine a set of biosynthetic pathways (i.e., the set of genes that, in
sequence, program the cell to perform a specific function, like creating a molecule) to evaluate,
Ginkgo inserts the pathways into cells and then moves on to what it refers to as the “debugging”
(i.e., test) stage. Ginkgo leverages several technologies in this process. For example, in September
2019, the company partnered with Berkeley Lights to access its single cell screening platform. At
its core, the Berkeley Lights Platform is an integrated digital biology platform that allows custom-
ers to capture single-cell characteristics on tens of thousands of cells in parallel. This capability
looks at phenotypic, genotypic, and functional information for these cells, all while the cells remain
alive. Enabling this is the company’s combination of automated systems, single-use OptoSelect
chips that enable thousands of cells to be interrogated in parallel, reagent kits, and advanced ap-
plication workflow software. Currently, Berkeley Lights has at least two workflows in development
for Ginkgo: the Opto SynBio Discovery 1.0 and Opto SynBio Development 1.0. The company plans
to launch theses workflows by the end of 2021.
When a product is ready for commercialization, Ginkgo’s Foundries use the ambr250 disposable
bioreactor system (from Sartorius) to provide initial scaling while improving the strain and fer-
mentation process conditions. While Ginkgo does not focus on scaling production internally, the
company has transferred multiple products to commercial production at 50,000 L scale and has a
deployment team that supports customers in scale-up and downstream processing. For example,
Ginkgo helped its partner Cronos buy and qualify a fermentation facility and completed the full
tech transfer package for that company.
In essence, we believe Ginkgo has created a low-code platform (built on Codebase, robotics, and
automation) compared with the more manual coding effort (think: lab coats, benchtops, pipettes,
petri dishes, etc.) required to pursue synthetic biology projects historically. Much like it has in the
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software industry, we believe the advent of low-code platforms will help enable the democratiza-
tion of cell programming by reducing the need for highly trained laboratorians with advanced
degrees and allowing less technical business users to run and test iterations across the genera-
tion and programming phases of design. Putting it simply, low-code platforms aim to bridge the
language barrier between humans and machines, effectively enabling users to create applications
by visual means and through business logic rather than complex manual application coding. This
inherently unlocks a larger number of developers by democratizing creation tools, and provides
a significant advantage over time as the fast-follower model associated with more rapid and cost-
efficient development drives accelerated usage and data to the platform.
Exhibit 19
Low Code Versus Code
Sources: Creatio and William Blair Equity Research; Adapted by William Blair Equity Research
In addition, this fast-follower model and the associated data set from increased adoption con-
tributes to an innovation flywheel, as the number of customers and projects accelerates, enabling
more rapid iterations and insights provided by advanced AI and machine learning functionality.
We believe that over time, as data insights compound across the platform, this contributes to an
expanding data moat for providers like Ginkgo, making it inherently more cost effective to leverage
the platform’s shared infrastructure and leading to a higher probability of successful project out-
comes. In effect, we believe it will become increasingly more apparent for customers to leverage
the benefit of these platforms over time, as companies across nearly all industries look to acceler-
ate their commercialization timelines. We believe this broader adoption will lead to an increase in
overall wallet share that platform providers are able to capture relative to their customers’ R&D
spend as these dollars become increasingly more efficient.
Zymergen
Zymergen is leveraging its “biofacturing” platform to create better products more quickly, less
expensively, and more sustainably than traditional chemistry by engineering microbes to make
novel molecules that are key ingredients in those products. By integrating techniques in biology,
chemistry, materials science, lab automation systems, software applications, unique databases,
and machine learning algorithms, Zymergen believes its synthetic biology process will eventually
enable it to make better products without the use of toxic chemicals, cut costs by roughly 90%, and
produce materials in about half the time (approximately 5 years versus 10 years using traditional
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William Blair
chemical methods). Notably, Zymergen is able to work with a wider variety of host strains than its
competitors; the company has experience in engineering for all major classes of microbes, includ-
ing 15 gram-positive bacteria, 6 gram-negative bacteria, 4 yeasts, and 4 filamentous fungi.
In terms of market selection (i.e., idea generation), Zymergen prioritizes large industries based on
the following criteria: 1) applications where bio-based materials have an advantage (i.e., does biol-
ogy win?); 2) high-value markets where its products can be sold at attractive margins (i.e., does the
material create enormous value?); and 3) industries where it can bring new products to market ef-
ficiently, where its approach enables faster timelines, or where it can leverage partnerships to ad-
vance favorable economics (i.e., does the industry move quickly?). Zymergen also looks to develop
products that have significant adjacencies, meaning that once the product is successful in its initial
industry, it can be used to create new products within that industry or used in other industries.
Exhibit 20
Zymergen Market Selection
Source: ZY company filings; Adapted by William Blair Equity Research
Based on the above criteria, Zymergen is initially focusing on three markets: electronics, consumer
care, and agriculture. Management believes that the market opportunity in these three industries
alone is $150 billion. The company’s first product, Hyaline, is a novel optical film designed for
electronics companies to use in smartphones, tablets, and laptops that was launched in December
2020. To accelerate product launch and meet customer demand, Zymergen launched its Hyaline
product with a non-fermentation produced molecule sourced from a third party. The company is
now converting to a fermentation-produced molecule and expects the process to be completed in
2022. While Zymergen is still in the early stages of commercializing Hyaline, customers that have
signed research-and-development contracts with the company have manufactured and sold more
than $1 billion of products made by microbes developed and engineered by the company.
As highlighted by the light blue bar in exhibit 21, Zymergen’s long-term plan is to expand be-
yond these initial three markets and deploy its biofacturing platform more broadly to disrupt the
chemicals and materials industry. To enter new industry verticals, Zymergen expects to pursue
partnering arrangements with large, established players in order to de-risk the product develop-
ment process. This is consistent with the company’s practice to date. Through its partnership
with Sumitomo Chemical, Zymergen significantly reduced the timeline to scale manufacturing of
its Hyaline product.
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Exhibit 21
Zymergen Pipeline
Zymergen’s modular platform is built around its Unified Metagenomics Database (UMDB), auto-
mation (Reconfigurable Automation Carts [RAC]), and software (Automation Control Software
[ACS] and Laboratory Information Management System [LIMS]). The company’s UMDB is a digital
and physical collection of DNA with more than 200 million genes, and many of the enzymes that
are encoded by these genes have been characterized with associated functional information. Each
design-build-test process generates proprietary data for Zymergen, enhancing its UMDB and algo-
rithms and improving its ability to program microbes. Similar to Ginkgo’s Codebase, Zymergen’s
UMDB is informed by the design-build-test process and helps improve and accelerate the process,
creating a virtuous cycle that gives it a significant long-term competitive advantage over any new
entrants into the market.
Zymergen’s RAC system is state-of-the-art in-lab automation that leads to improved process qual-
ity, faster turnaround time, and lower cost. Because RAC can be reconfigured in hours, the com-
pany’s scientists and automation engineers are able to more easily collaborate on new process de-
velopment without capex overhead or long development lead times. Zymergen has also developed
ACS, which is its custom software orchestration layer for RACs. ACS increases flexibility and helps
create organizational resilience when supply chains are tested by reducing supply chain change-
over times from weeks to hours.
The final major component of Zymergen’s platform is its Laboratory Information Management
System (LIMS), a cloud-scale database that the company has been running since 2014. LIMS cap-
tures experimental designs, instrument execution and run parameters, relevant environmental
conditions, and data that is continuously being generated in Zymergen’s labs. It enables Zymergen
to perform analyses and train machine learning systems on a rich database that is expanding con-
tinuously in both depth and breadth.
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William Blair
Exhibit 22
Zymergen Platform
For product design, Zymergen searches its Bioreachables Database to identify novel (i.e., never-
used-before) molecules that can serve as the basis of new, improved products. Of the more than
1 million molecules in Zymergen’s Bioreachables Database, there are 1) approximately 10,000
molecules where Zymergen knows both the structure and biosynthetic pathway, 2) approximately
65,000 molecules where the company knows the structure (from external databases) but the bio-
synthetic pathway is not complete, 3) approximately 80,000 molecules where the company has
computed the structure but does not know the complete pathway, and 4) approximately 1 million
molecules where the pathway is complete, but where the company does not yet have the structure.
Zymergen’s chemists and material scientists are currently able to access approximately 75,000 of
these molecules, and the company has strategies in place to access many more of these molecules
over time. Importantly, many of the molecules included in this database have properties that are
difficult or impossible to obtain from synthetic chemistry.
The molecules stored in Zymergen’s Bioreachables Database are accessed through a graphical
user interface called ZYNC, which helps the company’s chemists and material scientists search
for chemical substructures and properties among the collection (see exhibit 6 above for ZYNC
screenshot). To select candidate molecules, Zymergen uses data science and machine learning to
predict material performance, as well as molecular simulations where appropriate to enhance hu-
man judgment. This software relies on data from the company’s UMDB, which is used to predict
molecules that can then be searched by ZYNC. Once the most promising candidate molecules have
been selected, they are incorporated into product formulations and experimentally evaluated. The
assays performed to evaluate the end product depend on the application, and Zymergen has facili-
ties and expertise to bring online additional assays as needed. The company also uses automation
and miniaturization, when possible, which helps it increase throughput, reduce the need for mate-
rial, and improve assay precision and accuracy.
To program a microbe to create the selected molecule, Zymergen starts by using ZYNC to generate
in silico biosynthetic pathways (i.e., the set of genes that, in sequence, program the microbe to cre-
ate the molecule). ZYNC suggests options for pathways and even provides a score for each pathway,
and when the company has missing pathway genes it searches UMDB for enzymes to catalyze the
missing chemical transformation. From there, Zymergen relies on its Automated Pathway Explorer
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William Blair
(APE), which takes the pathway information from ZYNC and searches UMDB to ultimately recom-
mend a diverse set of candidate pathways to be installed into host microbes for evaluation. The
basic biosynthetic pathway is chosen and then tested in different hosts to identify the optimal host
for the lifecycle of the product, and once the optimal host has been selected Zymergen builds up
to 1,000 variants of the programmed microbe to determine the best starting point for additional
improvement. Lastly, the company uses its expertise in enzymology to perform initial enzyme and
pathway optimization to help ensure that the selected biosynthetic pathway is capable of meet-
ing commercial targets. This can be done by creating engineered microbe libraries where each
microbe contains biosensors that cause the best-performing cells to fluoresce, making it easier to
identify the best starting points for further testing.
While the previous step results in a cell that can produce a specified molecule (and ultimately
product), its manufacturing efficiency must be improved before the product can be commercial-
ized. This step has historically represented a major challenge for synthetic biology companies, in
part because of our limited knowledge of microbe biology and metabolism. As shown in exhibit
23, even well-studied microbes like E. coli are missing functional information for large portions of
their genome, which makes it difficult to engineer. Further, strain engineering and process design
have not historically been optimized (something that advances in data science, machine learning,
and artificial intelligence should enable) in synthetic biology, and many of the product categories
that were targeted historically were low-price/low-margin replacements (i.e., biofuels) that did
not leave much room for error.
Exhibit 23
Microbial Functional Information
Zymergen uses an atheoretic (i.e., not founded on theory) approach to CRISPR screening that in-
volves systematically editing all parts of the genome in order to improve the manufacturing ef-
ficiency (i.e., yield, titer, and rate) of its programmed microbe. This allows it to identify beneficial
changes that defy human explanation and are identifiable only through machine learning. Just as
Zymergen’s platform uses software and machine learning to recommend a diverse set of candidate
pathways to be evaluated, its Strain Brain machine learning system proposes a specific library
of possible genomic edits to make to the programmed microbe. Additional software tools enable
Zymergen to design the large libraries of specified microbes, run lab operations, and perform sub-
sequent batch analyses, while automation is used to assemble DNA constructs and insert them into
specific locations in the programmed microbe’s genome. As of March 2021, Zymergen had built
and tested 360,000 microbes with specific genomic edits.
These engineered microbes are then evaluated using assays developed by another one of Zymer-
gen’s machine learning systems, Orion, as well as by other analytical techniques, cell-based assays
such as fluorescence-activated cell sorting (FACS), and technologies such as biosensors. After the
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William Blair
optimal edits have been identified, results are typically confirmed by running bench scale fermen-
tation runs. These runs are monitored by Zymergen’s active data capture process, and this data ul-
timately helps the company understand how incremental genetic changes affect the performance
of a specific fermentation process. In addition, Zymergen’s machine learning tool set, MassPipe,
analyzes the fermentation run data and highlights key issues that inform subsequent process and
genetic changes. While the company is still working to convert Hyaline to a fermentation-produced
molecule, the fact that customers that have signed research-and-development contracts with Zy-
mergen have manufactured and sold more than $1 billion of products made by microbes devel-
oped and engineered by the company illustrates that its platform can be used to effectively com-
mercialize better-performing products.
After the microbe has been optimized to produce the molecule at attractive economics at scale and
an end-to-end development process has been developed, Zymergen leverages contract manufac-
turing organizations (CMOs) to manufacture the product that contains the molecule produced by
the programmed microbe. In terms of its go-to-market strategy, Zymergen relies on its own sales-
force and marketing capabilities to sell its products, and the company plans to follow the same ap-
proach in all of its target markets—1) approach all parts of the value chain to understand the key
buying decisions and potential blockers in the value chain, 2) target the fastest-moving customers
for initial sales, 3) build volumes over time, and 4) eventually expand into larger, slower-moving
customers and identify adjacent use-cases.
Amyris
Amyris’s approach essentially combines the idea generation and product design steps of the syn-
thetic biology process by focusing on cheaply and sustainably re-creating molecules (specifically
hydrocarbons) that are already widely used in the health and wellness, clean beauty, flavor and
fragrance, and bioplastics markets. A good example of the type of molecule that Amyris goes after
in discovery is squalane, which increases the spreadability of creams and lotions and is used in a
number of personal care products. Traditionally, squalane is sourced from shark liver, and millions
of sharks are killed each year as a result. By producing squalane from sugarcane (i.e., ferment-
ing genetically engineered yeast strains in sugarcane syrup), Amyris is able to optimize its per-
formance, decrease costs, and provide a stabilizing impact on the oceanic ecosystem. Ultimately,
Amyris’s squalane is able to be used as a direct substitute for squalane sourced from shark liver.
Exhibit 24
Amyris Squalane Molecule
Source: AMRS company presentations
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William Blair
Amyris has scaled 13 molecules to date and has over 250 molecules in its pipeline that may be
developed and scaled-up. The company starts with a pool of hundreds of thousands of molecules
and then filters based on market opportunity, technology, and efficacy to determine which op-
portunities are worth pursuing. In terms of market opportunity, the most impactful molecules
are often ones that are currently made from animals or plants and come from a challenged supply
chain that is subject to variability in price and quality (see squalane above). Screening for technol-
ogy (i.e., unit cost, sustainability, and speed to market) helps Amyris ensure that it is focusing on
molecules that it can re-create less expensively and sustainably, and evaluating the efficacy of each
molecule ensures that the company selects molecules with appropriate safety profiles and best-
in-class function.
Exhibit 25
Amyris Molecule Screening Approach
Source: AMRS company presentations; Adapted by William Blair Equity Research
When it comes to actual product commercialization and production scale-up, Amyris’s track re-
cord stands out. Amyris has been working on its scale-up capabilities since 2012, and we view
the company’s ability to scale production as its core competency. By using prediction models and
analytics that allow it to quickly determine how a strain’s yield, titer, and rate at one scale will
translate to another scale, Amyris is capable of producing and screening more than 600,000 yeast
strain candidates per month. Exhibit 26 illustrates how dramatically Amyris’s scale-up capabilities
have improved since 2012.
Exhibit 26
Amyris Scale-Up Capabilities
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William Blair
For the molecule cannabigerol (CBG), Amyris’s first cannabinoid ingredient, the company start-
ed screening yeast strains on microliter plates in late summer of 2019. After evaluating roughly
500,000 strains, Amyris down-selected 500 candidates to test at a 0.5-liter to 2-liter scale in its
labs. These 500 strains were narrowed down to a single-digit set of candidates by the start of 2020,
and pilot testing was initiated in March 2020. In September 2020, a little over a year after begin-
ning to screen strains, Amyris launched its first manufacturing campaign, which involves produc-
ing a series of product batches at 100,000 L or more in a given period of time. For comparison,
Zymergen estimates that its typical process for scaling production takes roughly three years.
During the first quarter of 2021, Amyris ran its second CBG production campaign and delivered
volume that was six times greater than from its first campaign, while unit costs were cut by roughly
75%. The increased yield and reduced cost were driven by new generations of yeast strains used
in the process and continuous improvement in Amyris’s downstream processes (i.e., the chemistry
that polishes and cleans the molecules that come from fermentation).
Enabling Technologies
Synthetic biology is not a new discipline, but historically it has been hindered by limitations associ-
ated with its enabling technologies. In the last 10 years, there have been significant advancements
in three of the main technologies needed to program cells—the ability to read DNA (with sequenc-
ing), write DNA (with DNA synthesis), and edit DNA (most notably with CRISPR). This progress,
along with significant advancements in automation (i.e., integration of software and robotics) and
AI (most notably machine learning), has enabled researchers and companies to start to fulfill the
promise of synthetic biology.
DNA Sequencing (Read)

DNA sequencing is used to determine the order of bases (A, T, C, and G) in a sample of DNA; it gives
researchers the ability to read a cell’s code. In the context of synthetic biology, the ability to read
DNA has allowed companies like Ginkgo and Zymergen to build up massive metagenomics data-
bases that can be used to figure out what code is needed to program a cell to perform a specific
function (e.g., programming a microbe to produce a molecule). Sequencing is also used directly
in the synthetic biology process to verify that the strands of synthetic DNA inserted into cells are
consistent with the biosynthetic pathways of interest.
The technology used to read DNA has improved dramatically since the Human Genome Project
was completed in 2003. Behind these improvements has been the introduction of next-generation
sequencing (NGS), which is massively parallel in nature and thus can be used to sequence millions
of short DNA fragments simultaneously per run. This allows for hundreds of thousands of genes
to be sequenced at one time, while the legacy method (i.e., Sanger sequencing) sequences only a
single DNA fragment at a time. An introduction to NGS from Illumina can be found here.
Since acquiring Solexa in 2007, Illumina has established itself as the clear market leader in NGS
and has largely been responsible for the improvements in sequencing cost (exhibit 27, on the fol-
lowing page) and throughput (i.e., the amount of data recorded per unit of time) recognized over
the last 15 years. In terms of the latter, Illumina’s high-throughput NovaSeq system is capable of
sequencing more than 3,000 Gb of data a day, a roughly million-fold improvement over legacy
Sanger sequencing. For reference, Illumina estimates that sequencing a person’s whole-genome
generates approximately 120 GB of data.
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William Blair
Exhibit 27
DNA Sequencing Cost Per Human Genome
$100,000,000
$10,000,000
January 2007: Illumina acquires

Solexa, a British company that had
$1,000,000 recently launched its first January 2014: Illumina
sequencer, the Genome Analyzer; launches its HiSeq X
the sequencing by synthesis (SBS) instrument, which delivered
Cost per genome
chemistry that Illumina gained on the long sought after

through the acquisition is still the milestone of the $1,000
$100,000 foundation of all its sequencing human genome.
January 2017: Illumina

launches its NovaSeq Series, a
$10,000 sequencing architecture
January 2010: Illumina expected to eventually enable a
launches its HiSeq 2000 $100 genome.
instrument, which for the
first time took the cost of
$1,000 sequencing a human
genome below $10,000.
$100
Sep-01 Mar-03 Sep-04 Mar-06 Sep-07 Mar-09 Sep-10 Mar-12 Sep-13 Mar-15 Sep-16 Mar-18 Sep-19
Source: National Human Genome Research Institute
While NGS has democratized reading DNA, it has a couple of notable shortcomings, particularly
with respect to its use in synthetic biology. Without going into too much detail, these shortcom-
ings are derived from its short read length (recall millions of short DNA fragments are sequenced
simultaneously) and use of amplification to generate enough DNA molecules for sequencing.
Single molecule (aka long-read) sequencing technologies aim to address the limitations associated
with NGS by increasing read length and eliminating the need for amplification. While these tech-
nologies are not new, they appear to be nearing an inflection point as improvements in accuracy,
throughput, and cost have started to make them more competitive with NGS.
Moving forward, we expect long-read sequencing to play an increasingly important role in synthet-
ic biology as it is better suited for sequencing through the complex and highly repetitive regions of
genomes, does not suffer from amplification bias (and therefore may be able to detect and identify
regions and even entire genes that may be missed by NGS), and provides a more comprehensive
picture of genomic structure. The continued development of long-read sequencing is important
for synthetic biology since our limited knowledge of host microbe biology and metabolism is a key
reason why historical efforts to scale production have failed. The leaders in the long-read sequenc-
ing space are Pacific Biosciences and Oxford Nanopore.
DNA Synthesis (Write)

Synthetic DNA is the fundamental building block of synthetic biology as companies must test many
variations of genes to figure out what code is needed to program a cell to perform a specific func-
tion (e.g., program a microbe to produce a molecule). Historically, the cost of producing synthetic
DNA has been one of the limiting factors to more widespread adoption of synthetic biology, per-
haps the main limiting factor.
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William Blair
Traditional methods of DNA synthesis are based on phosphoramidite chemistry, which is a two-
step process that involves linking together naturally occurring nucleotides and their phosphodies-
ter analogs to create short strands of DNA of up to 200 base pairs in length called oligonucleotides
(oligos). By stitching, or “assembling,” these oligos together, researchers can create longer strands
of DNA or a gene that is chemically identical to naturally occurring DNA.
Phosphoramidite chemistry is not new (it has been around since the mid-1980s), but production
constraints associated with the two legacy processes for DNA synthesis historically represented
a key bottleneck to more widespread adoption of synthetic biology. The first method, the 96-well
plate method of DNA synthesis, allows researchers to create 96 oligos in parallel, one in each well
of an 8x12 plate. As approximately 100 oligos are needed to produce one gene, the 96-well plate
method makes roughly one gene in total. The second method, the microarray method of DNA syn-
thesis, involves the synthesis of DNA directly in an array of discrete locations on a flat surface made
of plastic or glass. While the microarray method can make approximately 100 genes in parallel
(versus just one gene with the 96-well plate method), increased throughput comes at the cost of
increased downstream processing (i.e., barcoding, amplification) that makes the approach difficult
to scale.
Twist Bioscience’s DNA synthesis platform, which is built on phosphoramidite chemistry and
“writing” DNA on silicon chips, addresses the limitations in scale and cost associated with legacy
DNA synthesis methods. By using the oxide-based properties of silicon, which were initially dis-
covered and capitalized on by the semiconductor industry, Twist creates silicon chips that have
6,144 distinct spaces, or “clusters,” and within each cluster, there are 121 “devices,” which are
similar to the wells on a 96-well plate.
Each device is capable of constructing a short oligo of 50 to 300 base pairs in length, meaning
each of the 6,144 clusters on the silicon plate contains 121 oligos. As a result, each silicon chip is
able to produce roughly 6,144 genes, and the company has the capability to increase this to 9,600
genes as needed. In addition to providing increased throughput on each chip, Twist’s DNA synthe-
sis platform requires fewer reagents than legacy methods and leverages an automated production
process, allowing the company to provide customers with synthetic DNA at a lower price than
competitors ($0.09 per base pair for clonal, i.e., perfect, genes between 300 and 1,800 base pairs
in length).
Exhibit 28
Twist Bioscience Silicon Platform
Source: TWST company filings; Adapted by William Blair Equity Research
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William Blair
Twist has accelerated the process of synthesizing oligos using phosphoramidite chemistry, but
its approach to making larger genes is inherently limited by the fact that the efficiency of linking
together naturally occurring nucleotides begins to drop off at around 200 base pairs. This explains
why DNA synthesis via phosphoramidite chemistry is a two-step process. The oligos created in
the first step can only be so long, and therefore multiple oligos must be stitched together to create
longer strands of DNA or a gene. In other words, regardless of how many oligos Twist can make
on a single silicon chip, its turnaround time for clonal genes will always be limited by the fact that
these oligos must be stitched together, which also has negative implications for accuracy, cost, and
maximum gene length.
Codex DNA’s BioXp system was developed to address this inherent limitation of phosphoramidite
chemistry by automating the remaining steps of the DNA gene assembly process following the
creation of oligos (DNA assembly, DNA cloning, and DNA scale-up). The company relies on third
parties such as Integrated DNA Technologies (IDT) and Eurofins Scientific to supply it with oligos,
which are then incorporated into a suite of kits that run on its BioXp system.
Exhibit 29
Codex DNA BioXP System
Source: Codex DNA company presentations
Codex DNA aims to provide larger genes (7,000 base pairs versus 5,000 base pairs from Twist) in
an automated fashion with reduced turnaround times for the largest portion of the synthetic DNA
market that is currently not being served. Ultimately, the company believes the capabilities of its
platform will be able to dramatically improve the speed at which synthetic biology companies can
perform the build stage in the design-build-test cycle.
Exhibit 30
Process for Building DNA, mRNA, and Protein
DESIGN BUILD TEST
DNA synthesis mRNA formulation
Gene of DNA DNA assembly mRNA purification

interest design
DNA cloning 3' tailing Test

DNA
redesign
DNA scale-up in E. coli 5' capping
In vitro transcription
DNA reading (optional)
Process
No Optimized Yes development and
scale-up
Source: Codex DNA company presentations; Adapted by William Blair Equity Research
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William Blair
Beyond the build stage, Codex DNA’s BioXP instruments and kits collectively represent a democra-
tizing solution that ties together the entire synthetic biology ecosystem. Since it leverages Gibson
Assembly, a method of DNA assembly developed by Codex DNA’s CTO Daniel Gibson, the BioXp
platform is scalable across any synthetic biology application, such as pathway engineering, cell
engineering, gene synthesis, or genome engineering. Notably, the company also has one of two
intellectual property estates for enzymatic synthesis, which we discuss in more detail below.
Over the last 5 to 10 years, there has been growing interest in the use of enzymatic DNA synthesis
as a means to address the limitations associated with chemical DNA synthesis. Enzymatic synthe-
sis represents a more natural approach to DNA synthesis and involves the use of a polymerase to
fasten nucleotides together. The most commonly used polymerase is terminal deoxynucleotidyl
transferase (TdT) as it is the only enzyme known to build DNA in a template-independent fashion
(i.e., it does not already have a specific template that it uses to build DNA). This allows researchers
and companies to provide TdT with a new template for de novo synthesis, but also requires them
to come up with unique strategies for controlling how TdT knows which bases to add. Enzymatic
synthesis is still in the proof-of-concept stage, but it has the potential to speed up DNA writing and
create whole synthetic genes or even synthetic genomes in one step (i.e., without requiring the
assembly of shorter fragments of DNA). Faster DNA writing and longer gene lengths without as-
sembly would dramatically reduce turnaround time and cost, ultimately turbocharging the design-
build-test cycle and synthetic biology in general.
We view DNA Script as the leader in the enzymatic DNA synthesis space, and its SYNTAX enzymatic
DNA synthesis system is the first nucleic acid printer based on enzymatic technology. Currently,
SYNTAX is able to synthesize 96 oligos in parallel with 99.4% coupling efficiency. For oligos that
are 20 base pairs in length, the process takes as little as six hours, while synthesis of oligos 60 base
pairs in length takes 13 hours (both lengths require less than 15 minutes of hands-on time). In
February 2020, DNA Script showed that its enzymatic synthesis technology is capable of synthe-
sizing oligos up to 280 base pairs in length while maintaining coupling efficiency of 99.4%.
Exhibit 31
DNA Script SYNTAX Enzymatic DNA Synthesis System
Source: DNA Script website
Compared with Twist and Codex DNA, DNA Script’s strategy is unique in that the company is
initially focused on democratizing the creation of oligos for the molecular biology and genom-
ics markets (as opposed to serving the gene synthesis market). While Twist also makes oligos
for these markets, a major difference between the two companies is in their respective business
models; Twist operates as a service provider, while DNA Script is productizing DNA synthesis
with its SYNTAX instrument.
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While Codex DNA is initially focused on automating the remaining steps of the gene assembly pro-
cess after the creation of oligos (versus DNA Script’s initial focus on making oligos for the molecu-
lar biology and genomics market), both Codex DNA and DNA Script are attempting to productize
DNA synthesis rather than operate a service model like Twist. It will be interesting to see how
each company’s strategy plays out as the products move from limited releases to much broader
availability, but historically our view has been that democratizing access to technologies is best
accomplished with an automated product in the hands of end-users. With that said, we believe the
vast market and diverse set of applications for synthetic DNA will likely create room for multiple
companies (and business models) to be successful.
For the time being, we view Twist and Codex DNA as more direct competitors; however, Codex
DNA and DNA Script are both working to expand their capabilities in a way that should bring them
into more direct competition with each other and Twist over time.
As noted above, enzymatic synthesis is still in the proof-of-concept stage, and there are a number
of private companies in addition to DNA Script pursuing solutions, including: Ansa Biotechnolo-
gies, Camena Bioscience, Molecular Assemblies, and Nuclera. The companies in the enzymatic DNA
synthesis space can be classified based on their business model, with some companies electing
to operate as service provides (Ansa Biotechnologies and Camena Bioscience), while others are
working on distributed (product) models (DNA Script and Nuclera). Molecular Assemblies, on the
other hand, is looking to license out its technology to other companies, preferring to think about
its technology as “the ink in all of the printers.” It is also worth noting that if enzymatic synthesis
proves commercially scalable in the future, Twist has the ability to include this chemistry in its es-
tablished infrastructure, and as mentioned above, Codex DNA has one of two intellectual property
estates for enzymatic synthesis.
Enzymatic synthesis has significant potential, but we also expect continued innovation from com-
panies whose platforms are based on phosphoramidite chemistry, most notably Twist, Codex DNA,
GenScript, IDT, and Eurofins. Regardless of the approach, we expect further declines in the cost
of synthetic DNA, improvements in DNA length and complexity, and reduced turnaround time to
drive continued investment and interest in synthetic biology moving forward.
Gene Editing (Edit)

Gene-editing technologies have the most self-evident name of any of the technologies we discuss in
this report, and do exactly what you would expect; they edit the DNA, or code, of a cell. Within the
synthetic biology workflow, these technologies are used to insert the optimal biosynthetic path-
way (i.e., the set of genes that, in sequence, program a cell to perform a specific function) into the
selected cell. More importantly, gene-editing technologies are used to help identify the optimal
biosynthetic pathway and optimize the cell for manufacturing at commercial scale. This can be
done through CRISPR screening, which is used to determine the relationship between genes and
function in a cell, ultimately leading to the discovery of key genes or genetic sequences that elicit
a certain function.
The concept of gene editing has been around since the mid-1980s, but the discovery of the CRISPR-
Cas9 (CRISPR) gene-editing system in 2012 enabled scientists to make precise changes in DNA
for the first time. Often referred to as “genetic scissors,” CRISPR has generated enormous interest
from companies and investors because of its inherent ease of use and effectiveness compared with
legacy editing techniques. For those who want more background on CRISPR, a popular explainer
video from Nature Methods can be found here.
While most of the discussion about the potential for CRISPR has been focused on its therapeutic
potential, it is also useful in determining the function of specific genes. Through CRISPR screening,
researchers can introduce precise changes throughout the genome and then analyze the effect of
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William Blair
those changes. In the context of synthetic biology, the goal of CRISPR screening is to find the genes
or genetic sequences that elicit a certain function or improve the manufacturing efficiency of the
programmed cell. This requires hundreds of thousands of edits to be tested individually, followed
by the most promising changes being recombined in new ways and tested many more times to
identify the best combination of edits. Recall that Zymergen uses this process to improve the effi-
ciency of programmed microbes prior to commercialization. The company’s Strain Brain machine
learning system proposes a specific library of possible genomic edits to make to the microbe, and
these microbes are then built and tested.
CRISPR along with other gene-editing technologies, such as transcription activator-like effector
nucleases (TALENs) and zinc-finger nucleases (ZFNs), have been transformative for the field of
medicine, but there is still room for improvement, especially when it comes to generating libraries
of edits in a scalable manner. To address the current limitations of CRISPR screening, particularly
scalability, Inscripta has developed its Onyx platform, which consists of a benchtop instrument,
consumables, and software.
Exhibit 32
Inscripta Onyx Platform
Source: Inscripta website
In a typical CRISPR screening experiment, one edit is performed per well on a 96 well plate, which
means that each run on a plate is limited to 96 edits. With Onyx, experiments can include up to
10,000 edits in a single tube for E. coli and up to 6,000 edits for yeast. The potential of the Onyx
platform is illustrated by one early experiment where scientists made more than 16,000 changes
to genes in E. coli to optimize lysine productions. In just 10% of the time, the experiment was able
to increase the variant space (i.e., amount of genome changed) by 1,000 times from what was done
in previous experiments.
Typical CRISPR experiments are also limited by the variety of edits that can be made and the fact
that multiplexing (i.e., making multiple edits) is not possible, even at low throughput. While some
recent projects have shown that thousands of single-base edits (i.e., changes in one letter of DNA
code) can be made per experiment, larger edits and more diverse types of edits are needed to rap-
idly advance genome engineering efforts. Inscripta is planning to address this limitation of typical
CRISPR experiments by adding the ability to make larger insertions, deletions, and swaps across
the whole genome to its Onyx instrument in the future. In addition, the company is working to en-
able combinatorial editing on Onyx, which would allow for the effects of multiple edits to be tested
at once, further increasing the probability of discovering major improvements in the desired trait
and helping characterize important sequence-to-function relationships.
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Collectively, the current and future improvements in scalability, efficiency, and access made pos-
sible by Inscripta’s Onyx platform have the potential to dramatically accelerate the process of
CRISPR screening and deliver new, better-performing cells for synthetic biology.
Artificial Intelligence (Learn)

Artificial intelligence (AI) includes a range of software applications that mimic human capabilities
such as learning and solving problems. In the context of synthetic biology, machine learning (ML), a
core type of artificial intelligence technology, is key to improving the speed and efficiency at which
users can iterate through the synthetic biology process. Machine learning technology includes sev-
eral techniques to extract knowledge or patterns from data, including regression analysis, cluster
analysis, genetic algorithms, and neural networks. As described in the report, machine learning
algorithms sort through massive data sets to determine which molecule, pathway, or other vari-
able is needed to move on to the next step in the synthetic biology process. As the machine learning
models sort through more data, they are better able to predict the correct solution to the problem.
This cuts down on manual labor and the time needed to perform these tasks.
Just as the three previously described enabling technologies have advanced significantly in re-
cent years, step-function improvements in computer hardware size and processing speeds have
allowed for artificial intelligence software to cut down the time needed to sort through the large
molecules and gene data sets used in the synthetic biology process. While AI and ML tools have
already significantly improved efficiency and time needed to deliver value, we believe the benefits
that these tools provide are still in their early innings. To provide some context about the speed
of the inflection, Nvidia is the leading developer of GPU for data centers. These processors are
commonly used for training machine learning models with very large data sets, and Nvidia’s data
center revenues were $7.6 billion in the most recent 12 months, up 22 times from $339 million in
fiscal 2016.
Until the early 2000s, companies that managed data needed to buy storage hardware up front,
find a place to store the physical components, and hire IT personnel to manage the infrastructure.
Public cloud emerged in the mid-2000s, allowing companies to pay for cloud storage on a periodic
basis as a service rather than through high upfront capital expenditures. This has been particu-
larly beneficial to younger, more cash-strapped companies that were now able to defer the upfront
cash costs and instead invest the capital into revenue drivers such as R&D or sales and marketing.
In addition, the cost to store each byte of data has come down significantly as storage hardware
improved. The cost to store one GB of data has declined from roughly $1 in the early 2000s to less
than $0.02 in recent years.
This has also led to improvements in machine learning techniques. Deep learning, a more recently
feasible subset of machine learning, works by layering algorithms within a neural network and
combining large sets of decision trees. This allows the software to find relationships among data
sets that a human never could with traditional software code. The improvements in hardware and
software techniques create a virtuous cycle that will accelerate the pace of AI and ML innovation
over time. As the processing speeds of hardware continue to improve, artificial intelligence and
machines learning models will be able to sort through data sets at a faster pace, which in turn will
improve the efficiency of the models at a faster pace.
Looking out five years, we see potential for further disruption with the coming inflection of quan-
tum computers and potentially other storage mediums like DNA. While these quantum computers
have just recently achieved quantum supremacy (performing a calculation faster than a traditional
computer), it will take several years for a quantum computer to have real-world use-cases. This
could cut down the processing time from years or decades to minutes. Over time, we expect the
declining barriers to entry to help further expand the number of synthetic biology start-ups and
accelerate the time they need to deliver value.
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ESG Considerations
Synthetic biology can be used to produce better products more quickly, less expensively, and more
sustainably. As a result, we believe the industry is rather compelling from an environmental, so-
cial, and governance (ESG) standpoint. This is a view that seems to be shared by many leading
companies in the space, as the majority of investment has gone toward using synthetic biology to
create sustainable alternatives in industries that have a significant impact on the environment. In
addition to addressing sustainability, synthetic biology is poised to play a key role in solving social
issues such as food security, access to clean water, and animal welfare. It is not an exaggeration to
state that synthetic biology has the potential to help solve some of the biggest challenges that hu-
manity is facing, and we expect these issues to only grow in importance in the coming years. As a
result, we believe synthetic biology companies represent core long-term holdings for any investor
looking to gain ESG exposure.
In the “Market Opportunity” section below, we outline the value proposition for synthetic biol-
ogy in the areas that have seen the most investment and interest from leading companies in the
space—food, agriculture, materials and energy, consumer goods, biopharma, bioremediation,
and data storage. With the exception perhaps of biopharma and data storage, these industries
are linked by the fact that they have a significant impact on the environment and/or are dealing
with pressing societal issues that will not be resolved by following the status quo (bioremediation
is a bit of an exception in that it has a positive impact on the environment). This dynamic is best
illustrated by food and agriculture, as these industries are staring down one of the biggest chal-
lenges humanity will face over the next century; that is, how do we increase food production to
meet growing global demand while simultaneously reducing the impact of food production on the
environment? After reading through the “Market Opportunity” section, we believe that the value
of synthetic biology from an ESG perspective will be apparent.
Market Opportunity
As discussed throughout this report, the most common applications of synthetic biology today
leverage a process known as industrial fermentation to produce commercial products at scale.
Industrial fermentation combines the programmable nature and manufacturing efficiency of cells
to make better products more quickly, less expensively, and more sustainably. Initial efforts have
largely focused on food (animal-free proteins), agriculture, materials and energy (chemicals), con-
sumer goods (cosmetics), and biopharma, in part because of the impact that synthetic biology can
have on these industries from an ESG standpoint.
The ability to “program life” opens virtually limitless possibilities; for example, synthetic biology is
already being used to program cells to be used as therapeutics (i.e., gene and cell therapies), living
organisms to be used as therapeutics (i.e., living medicines), and living things such as plants and
animals (e.g., GMO plants, genetically engineered salmon). Over time, we expect the scope of syn-
thetic biology to expand into areas like small molecule synthesis, DNA data storage (storing digital
information in DNA), bioremediation (which involves using microbes to consume and break down
environmental pollutants), and bioprinting.
In our view, the synthetic biology market opportunity can be broken into two components that cor-
respond to the synthetic biology value chain: 1) the ecosystem of enabling technologies that drive
the synthetic biology process (idea generation, product design, cell programming, and product
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commercialization) and 2) the manufacturing and commercialization of end products created on

the synthetic biology platform. The makeup of the synthetic biology ecosystem is summarized in
exhibit 33.
Exhibit 33
Synthetic Biology Ecosystem
In thinking about the market opportunity for enabling technologies, Ginkgo estimates that ap-
proximately $40 billion will be spent in 2021 on cell programming research and development,
with 60% spent on labor and the remaining 40% on tools (i.e., DNA synthesis, reagents, and equip-
ment). As companies think about harnessing the power of synthetic biology, part of the strategic
decision-making process will be determining whether it makes sense to build an internal portfolio
of enabling technologies to power research and development, or whether it would be more effi-
cient to outsource much of this work to a company like Ginkgo.
As shown above, Ginkgo is developing a horizontal platform and ecosystem for cell engineering
across industries, ultimately allowing companies to avoid having to vertically integrate for product
development. In other words, Ginkgo is developing a platform that can be leveraged by customers
regardless of industry (i.e., a horizontal platform), as opposed to a vertical platform that caters
specifically to a niche user segment (like an industry). By leveraging Ginkgo’s platform, these com-
panies avoid having to vertically integrate product development—that is, buy, build, and optimize
an internal portfolio of enabling technologies that can be used in the synthetic biology process.
This capital-light approach has had a democratizing effect in drug development and software ap-
plication development. Consider the landscape for biological drugs, where it is commonplace for
companies to move molecules through the development cycle by leveraging contract research or-
ganizations (CROs) and CDMOs, and if needed even contract sales organizations to help with com-
mercialization. Another example is the iOS application landscape, where developers can leverage
AWS cloud computing services and Xcode (Apple’s integrated development environment) to bring
applications to market with minimal hardware requirements.
To the extent that the synthetic biology product development landscape evolves in a similar fash-
ion, much of that $40 billion in cell programming research and development could be in play for
a company like Ginkgo with its Foundry services, where it charges usage fees much like cloud-
computing companies charge usage fees for utilization of computing capacity or CROs charge for
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William Blair
services. The $16 billion expected to be spent on tools for cell programming research and devel-
opment in 2021 would be addressable by companies with enabling technologies, such as Twist,
Berkeley Lights, Codexis, and a host of other companies.
In terms of end products, the fact that synthetic biology has the potential to transform virtually
every industry makes it difficult to come up with definitive estimates for the current and poten-
tial market opportunity. Zymergen’s bottom-up, industry-by-industry, application-by-application
analysis, which is summarized in exhibit 34, suggests that the total opportunity is at least $1.2 tril-
lion across 20 separate industries it is targeting for potential products.
Exhibit 34
Zymergen Market Opportunity
A report from the McKinsey Global Institute estimates that in the next 10 to 20 years, there will be ap-
proximately $2 trillion to $4 trillion of annual direct economic impact from bioengineered products.
This market can be accessed by directly introducing products (e.g., Impossible Food’s Impossible
Burger, Amyris’s Biossance beauty line, and Zymergen’s optical film product, Hyaline) or by taking
equity positions or royalty streams in exchange for access to enabling technologies (like Ginkgo has
done with Motif FoodWorks and Joyn Bio). Assuming an average royalty rate of 5.0%-10.0% (could
be much higher for high-margin areas like therapeutics), we believe that $100 billion–$400 billion of
the $2 trillion to $4 trillion market described by Ginkgo is available through royalties.
We provide a brief overview of key synthetic biology end-markets and identify companies with
early leadership positions below.
Food (Animal-Free Proteins)
Synthetic biology represents the most promising solution to one of the biggest challenges human-
ity will face over the next century—how do we increase food production to meet growing global
demand while simultaneously reducing the impact of food production on the environment?
According to the World Economic Forum, the dominant view among experts is that humanity
needs to increase food production by 50% to 100% by 2050. Population growth is the driving force
behind the need for increased food production, but growing demand for animal-based foods from
developing countries further compounds the problem. Animal-based foods are more resource-in-
tensive than plant-based foods, taking up nearly 80% of global agricultural land but producing less
than 20% and 40% of the world’s supply of calories and proteins, respectively, according to the
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United Nations Food and Agriculture Organization (FAO). Livestock also has a significant impact on
the environment, and the FAO estimates that it is responsible for 14.5% of global greenhouse gas
emissions. As shown below, Bloomberg estimates that in 2018 more than one-third of land in the
United States was already being used for pasture (grazing by livestock, mainly cows), making it by
far the largest use of land. When factoring in the land required to produce feed, 41% of land in the
United States was dedicated to livestock.
Exhibit 35
Livestock in the United States
Source: Bloomberg; Adapted by William Blair Equity Research
Historically, the main method used to increase food production has been to increase the amount
of land under cultivation. This approach will not be sufficient to meet projected global food de-
mand in 2050, because climate change, urbanization, and soil degradation due to over-farming
are expected to shrink the availability of arable land (i.e., land suitable for farming), while water
scarcity and the lack of individuals choosing farming as an occupation represent challenges to
farming what arable land remains. Even if we could meet the growing global demand for food by
increasing the amount of land under cultivation, the approach could have dire consequences for
the environment.
A number of companies are leveraging the power of synthetic biology to replace the shortcomings
associated with the current approach to agriculture. In this section, we focus on the market oppor-
tunity for animal-free proteins (specifically meat, but dairy is also an opportunity) since livestock
is primarily responsible for the lack of scalability and sustainability associated with traditional
agriculture (as we have detailed above).
According to consulting firm Kearney, the global meat market is expected to grow from $1.2 tril-
lion in 2025 to $1.8 trillion in 2040. Kearney also expects that conventional animal-based meat
will peak in 2025, declining from 90% of the total market to 40% by 2040. This implies that the
opportunity for animal-free meat will grow from $120 billion in 2025 to roughly $1.1 trillion in 2040.
To come up with an estimate of the market opportunity for enabling technologies, we looked at
historical results from leading animal-based meat producers worldwide to determine how much is
being spent annually on research and development. In doing so, we found that three leading meat
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William Blair
producers (Tyson, Hormel Foods, and Pilgrim’s Pride) spent roughly 0.2% of their combined sales
on research and development in fiscal 2020. Applying this as a proxy for research and develop-
ment to the estimates for the global meat market detailed above ($120 billion in 2025, $1.1 trillion
in 2040), we come up with an addressable market for enabling technologies of $240 million in 2025
and $2.2 billion in 2040.
Given the urgent need for alternatives to animal-based proteins and the massive market oppor-
tunity, it is no surprise that competition in the space is piling up. Below, we highlight two leading
synthetic biology companies focused on animal-free proteins—Impossible Foods and Motif Food-
Works. We also discuss UPSIDE Foods, which is focusing on producing cell-cultured meat, to illus-
trate how its approach (and cell-cultured meat more broadly) differs from the synthetic biology
process discussed in this report. For more information about how alternative meats could affect
the traditional meat and livestock industries, see here.
Impossible Foods was founded to end the use of animals to make food by making meat, dairy, and
fish directly from plants. By looking at proteins, textures, and flavors at a molecular level, Impos-
sible Foods discovered that heme, a molecule found in all plants and animals, is the ingredient that
gives meat its taste. Instead of using the heme protein that is encoded by cows, the company tested
a wide variety of heme proteins and ultimately decided that leghemoglobin, a protein produced by
soybeans, created the best-tasting burger. To manufacture the molecule, Impossible Foods inserts
the biosynthesis pathway (i.e., the set of genes that, in sequence, encode for the enzymes that cre-
ate the molecule) for leghemoglobin into a yeast (microbe) called Pichia pastoris. The programmed
microbe is then fermented, and the resulting heme molecules are combined with other ingredients
to produce the end product—meatless burgers, sausage, and pork.
In 2018, Impossible Foods worked with sustainability firm Quantis to evaluate the environmental
benefit of choosing an Impossible Burger over conventionally produced ground beef from cattle. As
shown below, the study concluded that choosing an Impossible Burger reduces land use by 96%,
eliminates 89% of the greenhouse gases that cause global warming, and requires 87% less water.
The Impossible Burger also has a 92% efficiency advantage over beef’s contribution to aquatic
pollution through nutrient runoff (as shown by the aquatic eutrophication potential bars below).
Exhibit 36
Impossible Burger Environmental Impact
100%
80%
60%
40%
20% 11% 13%

8%
4%
0%
Aquatic eutrophication Global warming potential Land occupation Water consumption
potential
Impossible Burger Beef Burger
Source: Impossible Foods website
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William Blair
Motif FoodWorks was launched by Ginkgo Bioworks in February 2019. Through its exclusive
partnership with Ginkgo Bioworks, Motif FoodWorks is able to leverage Ginkgo’s Foundry to dis-
cover proteins that solve for taste, nutrition, and other benefits. Motif FoodWorks provides cus-
tomers with individual ingredients, ingredient systems, and whole formulations for meat alter-
natives, dairy alternatives, and innovative plant-based products that have enhanced nutrition,
texture, and/or appearance. Compared with Impossible Foods, Motif takes a more comprehensive
approach to solving the underlying challenges in creating animal-free meat and dairy products,
namely the difficulty of replicating the look, feel, and experience of animal products, and is less
reliant on saturated fats, which negatively affect a product’s nutritional composition.
UPSIDE Foods (fka Memphis Meats) is a world leader in cell-cultured meat. While still animal-
free, cell-cultured meat is real meat. The process of making cell-cultured meat begins with iden-
tifying and selecting specific types of animal cells that are able to self-renew and grow to become
meat. UPSIDE Foods then feeds the cells with the most essential micronutrients needed for growth
and development. From there, the cells follow their natural process to form muscle and connec-
tive tissue in a “cultivator” (similar to a fermenting tank). The meat is simply harvested when
ready, and the entire process takes between four and six weeks. In 2016, UPSIDE Foods introduced
the world’s first cell-cultured beef meatball and then followed this up by introducing the world’s
first cell-cultured chicken and duck in 2017. Recently, the company announced that it has chosen
chicken as its first commercial product, and believes chicken production is likely to begin by the
end of 2021, pending regulatory review.
Other synthetic biology companies in the broader animal-free protein space include: Air Pro-
tein, Aleph Farms, AquaBounty Technologies, BlueNalu, Clara Foods, Eat Just, Meatable, Mission
Barns, Mosa Meat, Nature’s Fynd, Perfect Day, and Wild Earth.
Agriculture
In plant-based agriculture, synthetic biology is primarily being used to create more effective and
sustainable alternatives to pesticides and reduce dependence on nitrogen fertilizers. These ap-
plications have the potential to play a meaningful role in ensuring long-term food security and
reducing the impact of plant-based agriculture on the environment.
According to the FAO, 20% to 40% of global crop production is lost each year to “pests,” which is a
broad term that refers to organisms (e.g., insects, mammals, weeds, birds, and micro-organisms)
that cause damage to crops. While pesticides (i.e., chemicals used to kill, repel, or control pests)
are essential in helping prevent these losses, they have been linked to adverse health effects (most
notably cancer) and can contaminate soil and water.
Nitrogen is key for growing healthy and high-yielding plants, but plants are not capable of using
the native form of nitrogen found in the air we breathe. Many plants instead get nitrogen from the
soil, after it has gone through a process called nitrogen fixation, whereby bacteria and archaea
convert molecular nitrogen into ammonia or other organic compounds. Building on this under-
standing, synthetic nitrogen fertilizers were developed to increase agriculture productivity. Syn-
thetic nitrogen fertilizers have been a major driver of the increased yields achieved by modern
agriculture, but gains in productivity have come at the expense of the environment, as synthetic
nitrogen pollutes waterways and produces nitrous oxide (N2O), a greenhouse gas that is 300 times
more potent than carbon dioxide. According to a study in Nature by Tian et al. published in October
2020, N20 emissions caused by human activity have increased by 30% over the past four decades,
with 87% of the increase attributable to agriculture. This has led to industrially produced nitrogen
fertilizers currently being responsible for about 5% of worldwide greenhouse gas emissions.
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IHS Markit estimates that total global pesticide sales were approximately $60 billion in 2019, and
based on data from IHS Markit, we estimate that global sales of nitrogen fertilizers were roughly
$55 billion in 2019. This brings the total market opportunity to $115 billion. When including all
fertilizers (i.e., ammonia, phosphates, potash, and sulfur), Zymergen estimates that $200 billion is
spent on fertilizers and crop protectants globally each year. Of this total amount, the company be-
lieves its market opportunity across nutrient-use-efficiency enhancers and crop protection alone
is more than $45 billion.
historical results from leading pesticide and fertilizer companies worldwide to determine how
much is being spent annually on research and development. In doing so, we found that three lead-
ing producers of pesticides and fertilizer (Bayer, BASF, and Corteva) spent approximately 9.0% of
their combined agriculture sales on agriculture research and development in fiscal 2020. Applying
this to the estimated total global market opportunity of $115 billion from above, we come up with
an addressable market for enabling technologies of approximately $10.4 billion.
Below, we highlight Joyn Bio, a leading synthetic biology company trying to answer a key question
facing the plant-based agriculture industry—how can we get plants to fix their own nitrogen? It is
worth noting that Zymergen’s ZYM0301 product is also being designed to help reduce dependence
on synthetic nitrogen fertilizer.
Joyn Bio is a joint venture between Ginkgo Bioworks and Bayer that was launched in September
2017 to focus on engineered microbes for use in agricultural applications. By leveraging its exclu-
sive agriculture industry access to Ginkgo’s Codebase + Foundry platform and Bayer’s microbial
application expertise and library of more than 100,000 microbial strains, Joyn has a distinct advan-
tage when it comes to identifying the microbial strains that deliver a specific benefit to a plant (i.e.,
crop protection to replace pesticides and/or nutrition to replace synthetic nitrogen fertilizers).
As mentioned above, plants are not capable of using the native form of nitrogen found in the air we
breathe. Some plants, such as soybeans and peanuts, are able to take advantage of nitrogen fixa-
tion, where microbes in the soil convert nitrogen from the air into a form that the plants can use.
Unfortunately, cereal crops (corn, wheat, and rice) are not able to take advantage of this process
and therefore must rely on synthetic nitrogen fertilizers. Joyn plans to address this issue with its
first product, which will be an engineered microbe that helps cereal crops convert nitrogen from
the air into a usable form.
Other synthetic biology companies in the agriculture space include: Arcadia Biosciences, Calyxt,
Cibus, Corteva, Elo Life Systems, GreenLight Biosciences, Inari, Pivot Bio, Provivi, Tropic Biosci-
ences, Yield10, and Zymergen.
Materials and Energy (Chemicals)
Petrochemicals are organic chemical compounds made by refining petroleum and natural gas.
These chemicals serve as the building blocks for materials such as plastics, nylons, rubbers, and
polyesters, which are used to create thousands of products that people use daily, including cloth-
ing. Global demand for petrochemicals nearly doubled between 2000 and 2018, according to the
International Energy Agency, largely driven by the introduction of inexpensive natural gas, thanks
to fracking and other new drilling techniques.
While the introduction of new drilling techniques has made it less expensive to manufacture pet-
rochemicals, the process is still energy intensive and harmful to the environment. In 2018, the
International Energy Agency found that petrochemical feedstocks (i.e., petroleum and natural gas
converted to petrochemicals) accounted for approximately 12% of global oil demand. By 2030,
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petrochemical demand is projected to account for a third of the growth in global oil demand, and
by 2050, it is expected to account for half. From a climate perspective, the World Economic Fo-
rum estimates that emissions from the chemical industry account for more than 30% of global
greenhouse gas emissions. Petrochemicals are estimated to account for approximately 10% of to-
tal greenhouse gas emissions from the chemical industry, or roughly 3% of total global greenhouse
gas emissions.
In the first decade of the century, a number of early synthetic biology companies were founded to
replace the petrochemical industry. These synthetic biology pioneers largely focused on re-creat-
ing the fuel used to make the petrochemicals, as opposed to finding new ways of making the petro-
chemicals. While these companies succeeded in making biofuel, they struggled to compete on cost
as the price of oil dropped precipitously during the Great Recession. Amyris, which we discussed
in detail earlier in this report, was one of many companies that originally started out focused on
petrochemicals, but was one of only a few companies able to survive and pivot following the de-
cline in the price of oil.
Synthetic biology has the potential to replace the petroleum and natural gas that is used as feed-
stock to create petrochemicals, but recent efforts have largely revolved around developing less
expensive and more sustainable bio-based processes for petrochemicals and intermediates that
do not rely on the use of fuel. For example, Genomatica (discussed below) has developed a bio-
based process to produce 1,4-butanediol (a petrochemical intermediate used to make plastics) by
fermenting engineered micro-organisms in sugar.
Given the ubiquity of petrochemicals, it is difficult to estimate the market opportunity for synthetic
biology, but industry sources consistently point to a global petrochemicals market in excess of
$400 billion. To come up with an estimate of the market opportunity for enabling companies, we
looked at historical results from BASF, a global leader in the production of petrochemicals. In 2020,
BASF spent 1.2% of chemical sales on chemical research and development. Applying this to the
estimated total global market opportunity of $400 billion from above, we come up with an address-
able market for enabling technologies of approximately $4.8 billion.
We discuss Genomatica, a leading synthetic biology company in the materials and energy space, in
more detail below.
Genomatica leverages the power of biotechnology and micro-organism engineering to develop

commercial bio-based processes. The company gives licensees and engineering firms everything
they need to make widely used chemicals that can be used to create better, more sustainable ev-
eryday products, including engineered micro-organisms, Process Design Packages, and technical
services. Currently, Genomatica has commercialized processes for bio-BDO (for plastics) and for
bio-based butylene glycol (for cosmetics), and is working on polyamide intermediates (for nylon)
and long-chain chemicals (for flavors and fragrances, cleaning solutions, and diesel fuel). In 2016,
Genomatica entered an alliance with Ginkgo Bioworks to accelerate the engineering and construc-
tion of its microbes.
Other synthetic biology companies in the chemicals space include: Global Bioenergies, Lanza-
Tech, and Synthetic Genomics.
Consumer Goods (Cosmetics)
In the consumer industry, much of the focus from synthetic biology companies has gone toward cos-
metics (skincare, haircare, make-up, and fragrances). This is largely because cosmetic products often
involve inputs that are costly, are difficult to produce, and/or cannot be manufactured sustainably.
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William Blair
In terms of cosmetic products for skincare, haircare, and make-up, there are a number of com-
mon ingredients that are sourced from animals, leading to supply chain issues and animal rights
concerns—we previously highlighted this dynamic in our discussion on squalane (an ingredient
sourced from the livers of sharks). Other common ingredients are derived from petrochemicals,
which means their manufacturing process is energy intensive and harmful to the environment (as
discussed above). Note that here we are talking about using synthetic biology to come up with an
alternative to the petrochemical, whereas above we discussed the opportunity to use synthetic bi-
ology to make the manufacturing process for petrochemicals more cost-efficient and sustainable.
Fragrances are not typically sourced from animals, but the compounds used in their formulations
can often be difficult, wasteful, and/or costly to source. For example, Tom Ford’s Tobacco Oud uses
an essential oil called oud (hence the name) that comes from the wood of a wild tropical tree called
the agar. As only 2% of agar trees produce oud, Fortune Magazine estimates that the essential oil
can sell for more than $5,000 a pound. Jasmine is a good example of a fragrance that is expensive
and incredibly wasteful to produce, as it takes approximately 2,000 pounds of jasmine flowers to
produce one pound of oil.
Synthetic biology offers companies an opportunity to either re-create these ingredients or make
better-performing replacements cheaply and sustainably. According to L’Oréal, one of the largest
cosmetics companies in the world, the global cosmetics market was worth €213 billion in 2020.
Since the market declined 8.0% year-over-year in 2020 due to COVID, we believe using the size
of the global cosmetics market in 2019 (€232 billion) is more appropriate. For the sake of com-
parability, we use a U.S.-dollar-to-euro exchange rate of 1.142 (average conversion rate in 2020)
to come up with an estimate for the size of the global cosmetics market in dollars ($265 billion).
L’Oréal estimates that 10% of the total cosmetics market consists of hygiene products, which we
do not expect to be a major focus area for synthetic biology companies (at least in the near term).
After subtracting this 10% from the total $265 billion calculated above, we arrive at a total address-
able global market opportunity of approximately $240 billion.
historical results from leading cosmetics companies worldwide to determine how much is being
spent annually on research and development. In doing so, we found that three leading cosmetic
companies (L’Oréal, Estee Lauder, and Coty) spent approximately 2.7% of their combined sales on
research and development in fiscal 2020. Applying this to the estimated total global market oppor-
tunity of $240 billion from above, we come up with an addressable market for enabling technologies
of approximately $6.5 billion.
We highlight Amyris below as a leading synthetic biology company in the cosmetics space.
Amyris has scaled 13 molecules to date, including a replacement for squalane, which is tradition-
ally sourced from shark liver. By producing squalane from sugarcane (i.e., fermenting genetically
engineered yeast strains in sugarcane syrup), Amyris is able to optimize its performance, decrease
costs, and provide a stabilizing impact on the oceanic ecosystem. As shown below, Amyris has lev-
eraged squalane and its other unique molecules to create a portfolio of consumer brands (almost
entirely cosmetics) that are marketed directly to end-customers.
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William Blair
Exhibit 37
Amyris Consumer Brands
In addition to its consumer brands, Amyris partners with leading companies in target markets.
The company’s partners invest in the development of molecules and then use their extensive
marketing-and-sales capabilities to sell Amyris’s ingredients and formulations to their custom-
ers. These partnerships help Amyris validate targets, define winning formulations, and ultimately
drive scale and adoption.
Exhibit 38
Amyris partnerships
Other synthetic biology companies in the cosmetics space include: Conagen, DEINOVE, Evolva,
Evonik, Geltor, and Manus Bio.
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William Blair
Biopharma
Through bioproduction (i.e., industrial fermentation), microbes and mammalian cells are used to
create biologics (any drug that is manufactured in a living system, most notably monoclonal an-
tibodies). Biologics accounted for over 30% of the therapies approved by the FDA in 2020, but
there are a couple of meaningful shortcomings associated with the manufacturing process for
these therapies that can be addressed with synthetic biology. Specifically, when proteins such as
monoclonal antibodies are not produced in a mammalian cell line, they can cause adverse drug
reactions. Synthetic biology can address this problem by programming mammalian cells to make
the proteins of interest as opposed to having to rely on microbes or insect cell lines. In addition,
synthetic biology can be used to make novel protein therapeutics that have proved difficult to
manufacture using traditional expression systems (i.e., traditional E. coli, yeast, mammalian); this
is part of the value proposition for AbSci, which we discuss in more detail at the end of this section.
Synthetic biology can also be used for process optimization, increasing drug yields, and driving
down cost and time required for manufacturing.
Perhaps more importantly, synthetic biology is being used for drug discovery and to create next-
generation biologics, such as cell therapies (e.g., CAR-Ts), gene therapies (e.g., Luxturna from
Spark Therapeutics), and living medicines (e.g., Synlogic’s Synthetic Biotic medicines, which we
detail below). Synthetic biology plays a critical role in the discovery, design, and manufacturing of
next-generation biologics. This is yet another example of how the ability to “program cells” opens
virtually limitless possibilities, and the definition of synthetic biology is so broad that it could
easily encompass large areas of biopharma. Although outside the scope of this report, we also
highlight that the recent rise in AI drug discovery companies leverages synthetic biology at their
core. Outside of the AI algorithms, many of these companies focus on creating novel RNA-targeted
therapeutics (e.g., Deep Genomics) outside traditional drug repurposing and will likely leverage
synthetic biology manufacturing techniques to produce oligonucleotides. Among others, Strand
Therapeutics, Nutcracker, Twist Bioscience, and Creative Biolabs are developing technologies to
expedite production of GMP grade oligonucleotides “at the bench.” Advancements in this technol-
ogy may address current limitations in scalability and complex production of longer RNA-targeted
therapeutics alongside reducing costs of industrializing the supply chain.
In terms of manufacturing next-generation biologics, there is a massive opportunity for synthetic

biology companies to address the significant shortfall in supply of adeno-associated viruses, or
AAVs (as detailed by our colleagues here). Gene therapies commonly use AAVs to carry a thera-
peutic gene to target cells, and the viral vector is arguably the most critical part of gene therapy
as it has to efficiently deliver the gene of interest without causing an adverse reaction. Currently, a
greater than tenfold and potentially closer to 100-fold increase in manufacturing efficiency is likely
required to meet the demand curve for clinical products. This urgent need for improved manufac-
turing efficiency was illustrated by a recent deal between Biogen and Ginkgo, whereby Ginkgo will
use its platform to find ways of improving the manufacturability of the AAV vectors that Biogen is
developing for its gene therapies.
A key consideration for manufacturing GMP-grade material for therapeutic administration in hu-
mans using synthetic biology approaches will be correct folding and post-translational modifica-
tions of peptides. These issues remain outstanding for difficult-to-produce therapeutics outside
those produced by recombinant E. coli production. We believe that co-transfection of synthetic
biology cell systems with not only the target protein DNA/mRNA but also chaperones and other
enzymes required for correct processing of mature peptides for human use will be a challenge to
overcome as manufacturing of complex materials advances in the synthetic biology space. We also
highlight that there is outstanding debate in the AAV manufacturing space about whether to use
insect-based Sf9 cell lines, which increases efficiency but also produces insect protein contamina-
tion, or mammalian cell lines that have minimal contamination but are severalfold less efficient
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William Blair
in AAV production. It is likely that synthetic biology approaches using E. coli and other microbial
strains as a production scaffold will also need to account for any microbial product contamination
in a finished drug product for human use. This is an evolving space, and we remain optimistic that
these challenges can be overcome with fine-tuning the genetic payloads in these microbial scaf-
folds if encountered.
While it is difficult to come up with a market opportunity for synthetic biology companies in the
biopharma space, we note that roughly $500 million was invested in the CDMO/supplier gene
therapy manufacturing infrastructure in 2019 and early 2020. There have been a number of sig-
nificant transactions in the space as well, with Thermo Fisher acquiring Brammer in March 2019
for $1.7 billion, Catalent acquiring Paragon in April 2019 for $1.2 billion, and Danaher acquiring
Aldevron in June 2021 for $9.6 billion ($8.8 billion net of tax benefit). In early 2020, Discovery
Labs announced its plan to spend $1.1 billion on a 1.6 million-square-foot campus for end-to-end
gene/cell therapy manufacturing. Based on existing demand and the continued investments in this
space, we believe the market opportunity for synthetic biology companies in the biopharma space is
between $5 billion and $10 billion on the manufacturing side alone.
Below, we highlight a number of leading synthetic biology companies in the biopharma space.
AbSci’s SoluPro E. coli expression system and Protein Printing platform enable the creation of
novel next-generation protein therapeutics that have historically proved difficult to manufacture.
For each project, the company starts with a known drug sequence or with a target for de novo
discovery, builds an expression library of more than 10 million unique strains of E. coli, and then
screens them in proprietary high-throughput assays. This approach has the potential to reduce
biopharma discovery and development timelines from years to weeks, and results in a GMP-ready
manufacturing E. coli cell line that produces drug candidates with optimal target potency and af-
finity as well as high-titer expression. In addition to helping with drug discovery, AbSci believes
SoluPro could benefit biomanufacturers producing monoclonal antibodies, antibody fragments,
and next-generation biologics.
Synlogic’s proprietary Synthetic Biotic platform enables the creation of programmable living bac-
terial therapeutics. The company uses a modified strain of the probiotic E. coli Nissle as a chassis
to engineer a cell that can recycle excess metabolites in rare metabolic disorders (phenylketonuria
[PKU] and enteric hyperoxaluria) or promote immune activation for oncology indications. PKU pa-
tients have a mutation defect in the gene encoding phenylalanine hydroxylase (PAH), responsible
for metabolism of phenylalanine (Phe). Buildup of Phe is toxic, and patients are normally managed
on dietary restriction and treatment with BioMarin’s Kuvan or Palynziq if genetically eligible (50%
of patients). Synlogic’s lead asset, SYNB1618, is a non-colonizing strain genetically engineered to
express Phe transporters, allowing Phe in the gastrointestinal tract to enter the cell where it is me-
tabolized by both Phe ammonia lyase (PAL) and L-amino acid deaminase (LAAD) that are encoded
by synthetically introduced genes.
In this manner, Synlogic aims to dose patients with a synthetic biotic that restores Phe metabo-
lism in the gut and hopefully, in turn, the blood, to address remaining unmet needs for PKU pa-
tients. SYNB1618 is being evaluated in the ongoing SynPheny-1 Phase II trial in PKU patients
who do not benefit from BioMarin’s approved therapies; top-line data, including Phe lowering
endpoints, are expected in the second half of 2021. Although a deeper dive into the programs is
outside the scope of this report, preliminary target engagement has been demonstrated in both
Phase I trials of PKU and enteric hyperoxaluria (SYNB8802), but dose selection will be critical for
efficacy here, in our view, given that synthetic biotics do not colonize the GI tract and the company
discontinued a first-generation candidate, SYNB1020 in hyperammonemia, for lack of target en-
gagement. If proof-of-concept can be established from the ongoing clinical trials, it is likely that
Synlogic’s Synthetic Biotic platform will have utility in a vast array of lucrative orphan metabolic
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William Blair
disorders that have significant unmet need, and the implementation of synthetic biology is clearly
differentiated from peers in the current landscape (largely enzyme-replacement therapies and/
or gene therapy/editors).
Strand Therapeutics is developing synthetic mRNA constructs that incorporate genes coding for
self-replication derived from RNA viruses with genetically programmed logic circuits to control
the location, timing, and intensity of expression of therapeutic proteins. The aim here is to extend
the duration of protein expression from the mRNA that usually only have an intracellular half-life
of less than 10 hours depending on the rate of translation, among other parameters. The ability
to control timing and cell-specificity of expression could enable mRNA therapeutics to supplant
certain DNA-based gene therapies, but with greater safety, specificity, and efficiency, as well as
incorporating multiple signaling components.
Seminal work on the company’s proprietary RNA-delivered circuits has been published describing
generation of modified RNA circuits and replicons whose expression can be switched “on” or “off”
using small molecule administration (Wagner TE et al., 2018. Nat Chem Biol.). In addition, repli-
cons capable of producing two different “outputs” or reporters, in response to TMP/Dox supple-
mentation, were also successfully created. These circuits were capable of upregulating protein/
reporter expression by 5- to 9-fold in the presence of TMP/Dox and then switched off when the
small molecule stimulating agent was washed out of cell culture. These have important implica-
tions for chronic inducible therapy at the RNA level given that expression can potentially be regu-
lated in vivo by administration of safe small molecules provided the original synthetic RNA circuit
(replicon) can be delivered to the target tissue successfully.
This controlled RNA expression platform utilizing non-viral drug delivery methods theoretically
has broad applicability across a host of indications requiring chronic treatment. Strand is initially
targeting solid tumors with early preclinical proof-of-concept studies published (Li, et al. Nat Can-
cer. 2020). Researchers engineered self-replicating RNAs (replicons) that encode a cytokine fusion
protein of IL-12 and the matrix-binding protein lumican, theorized to avoid documented systemic
toxicity by virtue of enhanced retention of the cytokine in the tumor micro-environment via the
lumican domain. The mRNA payloads are delivered via lipid nanoparticles designed to promote
intracellular delivery as well as actively promoting an antitumor cell immunogenic response. A
single injection of LNP-replicons was capable of eradicating large established tumors in several
syngeneic tumor models and induced systemic antitumor immunity, leading to elimination of dis-
tal untreated tumors. We note that LNPs are nonviral and should permit clinical redosing if re-
quired, which is a major hurdle when using AAVs. We believe advances in nonviral tissue-specific
delivery will benefit Strand’s synthetic mRNA platform and permit expansion into other indica-
tions outside oncology and the liver.
Strand expects to initiate human clinical trials in 2022, heading into a basket open-label solid tu-
mor trial in combination with PD-1 blockers, pending completion of ongoing IND-enabling studies
for the lead IO candidate. In January 2021, Strand announced a partnership with BeiGene granting
exclusive licenses to develop and commercialize up to two immuno-oncology programs in Asia
(excluding Japan), Australia, and New Zealand. The total deal carries value of up to $277 million for
Strand. Manufacturing of the synthetic LNP-encapsulated replicons occurs in house primarily, but
the company is readily engaging CDMOs to scale up GMP material for clinical trials.
Senti Bio uses an OR and NOT logic gating strategy as a mechanism for enabling safer CAR natural
killer (NK) cell therapies for the treatment of acute myeloid leukemia (AML). The company has
built a large toolkit to engineer cells to sense inputs and transform them into appropriate outputs,
and the company is applying OR or NOT logic gating to NK cell-based therapies to distinguish
healthy cells from cancer cells. Senti’s allogeneic NK cell candidate SENTI-202 leverages a logic-
gating strategy to kill AML blasts and leukemic stem cells, while avoiding off-target destruction
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William Blair
of healthy hematopoietic stem cells (HSCs). Here the company has identified a safety antigen, re-
ferred to as safety antigen 1 (SA1), which is expressed by HSCs but not on AML leukemic stem cells.
SENTI-202 is a multi-receptor product: two of which can engage complementary AML target an-
tigens (FLT3 or CD33), with a third inhibitory CAR that can detect the presence of SA1 on healthy
HSCs to shut off product. Together, the design of SENTI-202 allows for destruction of FLT3+ or
CD33+ targets, but the inhibitory receptor acts as a NOT gate, preventing killing when SA1 is also
present (exhibit 39). Through this strategy, the company hopes to protect 10%-20% of stem cells
in the bone marrow, which could allow for regeneration of the immune system.
Exhibit 39
Logic-Gated Receptors for Clearance of Leukemic Blasts and Stem Cells While Sparing Healthy HSCs
Source: Senti Bio Emerging Cell Therapeutics Keystone Symposia; Adapted by William Blair Equity Research
Kole Roybal, Ph.D., assistant professor of microbiology and immunology at UCSF, has been engi-
neering cell therapies for solid tumors by tuning cell activity for on-target killing using logic gat-
ing. T cells are modified to express an engineered synthetic Notch (synNotch) receptor circuit.
Here, an extracellular recognition domain recognizes a target cell antigen, but unlike CARs, binding
does not trigger T-cell activation automatically. Instead, binding of the synNotch receptor drives
the expression of user-specified target genes, such as expression of a CAR recognizing a second
target antigen (Roybal et al. Cell. 2016). One of Dr. Roybal’s engineered CAR-T cell products for the
treatment of mesothelioma contained a synNotch receptor recognizing ALPPL2, a tumor-specific
surface antigen expressed by various solid tumors, to drive the expression of a CAR recognizing
MCAM acting as a type of AND logic gate for cytotoxicity.
ALPPL2 is a tumor-specific ligand for certain cancers, but heterogeneity of this antigen within
tumor cells can be an issue for its use as a sole targeting receptor. Ligation of the ALPPL2 receptor
primes, or licenses, the cell to begin expressing a MCAM-specific CAR and the subsequent kill-
ing of mesothelioma cells. In comparison to MCAM CAR-T cells, synNotch ALPPL2-MCAM CAR-T
cells show less exhaustion and greater efficacy, due to the tonic MCAM CAR signaling and antigen-
independent proliferation associated with sustained expression of this CAR construct. As proof of
concept, synNotch ALPPL2-MCAM CAR-T showed highly sensitive antigen-dependent cell toxicity
in response to MCAM+ tumor cells transfected to express a range of ALPPL2 on their surface.
ArsenalBio seeks to build on synNotch combinatorial antigen sensing by improving the receptor
design and engineering integrated circuit to address parameters of T-cell functionality to over-
come some solid tumor therapy challenges. The smaller next-gen circuits, PrimeR/CAR, introduce
a similar priming receptor with CAR-responsive element as synNotch, but with more efficient in-
sertion into T cells using CRISPR/Cas9. The company is working to identify target loci for integra-
tion outside of TRAC that can also benefit the T-cell function or the ease of manufacturing. The
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William Blair
company has employed a combination of in vitro screening assays and computational predictions
to find prime-dependent loci, which can induce the highest levels of CAR expression and give the
highest-functioning cell circuit. In addition, Arsenal is working to identify and knock down specific
gene targets within the transcriptome of activated or exhausted T cells (e.g., FAS ligand) to improve
T-cell survival and prevent exhaustion—key product attributes for solid tumor functionality.
Rogelio Hernandez-Lopez, a postdoc at UCSF, has also developed an alternative application of a

synNotch circuit to allow for discrimination between low and high antigen density on target cells.
In this application, both the synNotch receptor and the CAR that the synNotch receptor transcrip-
tionally activates recognize the same antigen with different affinities. A low-affinity synNotch re-
ceptor allows for recognition only when the target ligand is present on cells at a high density, then
allowing for the expression of the high-affinity CAR, only if there is a lot of antigen present to drive
the CAR expression through the low-affinity synNotch receptor. Incubation of the HER2-specific
synNotch T cell with tumor cells displaying different antigen densities of HER2 showed little to
no cell lysis in low-HER2 expressing cells, but a rejuvenation of killing activity when incubated
with cells of high HER2 expression. The HER2-synNotch T cell showed slower lysis kinetics upon
incubation with high HER2 density tumor cells, in comparison to traditional HER2-CAR-T cells
with constitutional CAR expression, because the CAR had to first be transcriptionally activated and
expressed in response to the initial Notch receptor binding event.
In our view, an underappreciated aspect of AAV gene therapy development from the investor per-
spective is in promoter/transgene selection and design. Promoters are cis-acting regulatory ele-
ments located upstream of the transgene that enable and control transcription. Similar to capsids,
several promoters have shown specific signatures and contain clusters of binding sites for tran-
scription factors that either stimulate or repress initiation. Furthermore, promoter next-genera-
tion development can be grouped into constitutive, tissue-specific, inducible, and synthetic.
Thus far, some of the most common promoters used include spleen focus-forming virus (SFFV),
human polypeptide chain elongation factor (EF1-alpha), the phosphoglycerate kinase (PGK), ubiq-
uitin C (UbiC), cytomegalovirus (CMV), or chicken beta-actin promoters (CBA) (Domenger and
Grimm. Hum Mol Genetics 2019). Regarding the latter two, CMV and CBA were used in Glybera and
Zolgensma, respectively. These first-gen promoters can be more prone to inactivation than tissue-
specific promoters and may also contribute to an immune reaction with inadvertent expression in
antigen-presenting cells. Studies have used enhancers or other cis-regulatory elements upstream
of a tissue-specific promoter to achieve finer regulation and maintain transgene expression; size
limitations of the AAV capsid are always a limiting factor.
Decibel Therapeutics’ gene therapy platform for targeting hearing disorders uses wild-type cap-
sids and a dual vector approach. The company’s lead gene therapy candidate, DB-OTO, is targeting
otoferlin for congenital OTOF deficiency. DB-OTO has a proprietary regulatory element (Myo15)
that provides cell-specific expression and enables improved activity versus a ubiquitous promoter
(exhibit 40). The company has a co-development partnership with Regeneron with 100% com-
mercial rights and anticipates filing an IND in fourth quarter 2021.
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William Blair
Exhibit 40
Durable Efficacy in Rodents vs. Ubiquitous Promoter (Competition)
Source: Decibel Therapeutics company reports. Adapted by William Blair Equity Research.
In August 2019, AskBio acquired Synpromics, a developer of synthetic promoter technology to

enable precise cell and tissue selectivity with inducible capability. According to the company, the
Synpromics promoter offers variable protein expression and integration into scAAV, is selective
to single/dual/multiple cell types, and is designed to be regulated, be inducible, or have a safety
switch. The field of discovering synthetic promoter elements and their activity involves screen-
ing of cis-regulatory elements that are active in various arrangements and in different cellular
contexts (Aysha et al. Mol Biotechnol. 2018). At ASGCT 2020, Synpromics presented on novel CNS
promoters and identified a selective midbrain dopaminergic promoter that was subsequently de-
livered intravenously to a dopamine transporter knockout mouse model.
Encoded Therapeutics presented a poster at ASGCT 2019 that highlighted its approach to engi-
neering GABAergic interneuron selective regulatory elements. Using deep sequencing, bioinfor-
matics, and machine learning, the company identified cell-type selective regulatory elements and
applied them in human iPSC-derived GABAergic neurons in vitro and in vivo. When compared
with constitutive regulatory elements (such as CBA), the engineered GABA-selective regulatory el-
ements showed a high degree of selectivity that was maintained across various AAV capsids, brain
regions, and species (including NHPs).
At ASGCT 2020, one of the most intriguing next-generation technologies we saw presented was on
enhancers for cell type-specific gene expression from the Allen Institute for Brain Science. The pre-
sentation described a multistep process to generate AAV vectors to drive subclass-specific reporter
expression across species after systemic intravenous delivery. In the first step, using a library of
single nucleus ATAC-seq libraries and quality-filtered nuclei for clustering and mapping to human
snRNA-seq data, the authors mapped cells to three major subclasses of brain cells: excitatory, in-
hibitory, and non-neuronal (which they subdivided into 11 subclasses, Mich et al. bioRxiv. 2020).
They then identified the putative regulatory elements within each subclass and cloned them into an
AAV2/PhP.eB vector. After delivery via retro-orbital injection, wide tropism for brain neurons using
the promoter hSyn1 was shown, as well as the ability to drive reporter expression in specific brain
regions and neuron subclasses using the enhancers (i.e., telencephalic interneurons with hDLXI56i).
Parvalbumin-expressing (PVALB) neuro enhancer AAVs were identified due to PVALB interneu-
ron importance in cortical microcircuit regulation that is associated with several diseases, such as
epilepsy, schizophrenia, and Alzheimer’s disease. In addition, LAMP5 inhibitory subclass-specific
enhancer AAVs were identified. Expression of PVALB-specific vectors in NHPs showed substantial
expression for neocortical cells; furthermore, they were able to show human brain subclass target-
ing in ex vivo tissue slices with hDLXI56i.
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William Blair
Another approach, called enhancer-driven gene expression (EDGE), is based on identifying cis-
regulatory elements active in particular brain regions and combining them with a heterologous
minimal promoter (Blankvoort et al. Current Biology. 2018). The results of their studies demon-
strate putative enhancers that are unique to cortical subregions that outnumber the number of
genes that have the same type of specificity. This further suggests that enhancers to target cell type
may be a sound strategy for next-generation AAV capsids, particularly in targeting the brain (Nair
et al. iScience. 2020).
The Greenberg lab at Harvard has developed PESCA (Paralleled Enhancer Single Cell Assay), a
method that combines ATAC and single-cell RNA sequencing to identify cell-type specific enhanc-
ers (Hrvatin et al. bioRxiv. 2019). In a recent study, it identified enhancer elements that drove gene
expression in a rare SST+ population of GABAergic interneurons in the mouse CNS.
Overall next-generation enhancer element work has shown efficacy in different brain regions/cell
types in vivo, but we are hopeful for additional applications in other organs (and potentially humans)
in the future. Another major consideration to CNS-based diseases is the presence of the blood–brain
barrier, combined with the desire to have more gene expression of a specific transgene and a smaller
total dose.
Other synthetic biology companies in the biopharma space include: 64x Bio, Twist Bioscience,
Codexis, and Mammoth Biosciences.
Bioremediation
Bioremediation involves stimulating the growth of certain microbes to consume and break down
environmental pollutants. Since the late 1980s, bioremediation has been used with increasing
frequency to clean up contaminated soil and water, as well as for other environmental problems,
such as oil spills. Compared with other cleanup methods, bioremediation has the potential to be
less expensive (typically does not require as much equipment, labor, or energy) and create fewer,
if any, waste byproducts (since microbes change the harmful chemicals into small amounts of
water and gases). However, limitations in scale have impeded bioremediation from becoming
more widespread.
In addition to the uses discussed above, bioremediation represents a promising solution to two
growing environmental problems—food waste and plastic pollution. The FAO previously estimat-
ed that about one-third of the world’s food is lost or wasted every year. In the United States, ReFED,
a national nonprofit working to end food loss and waste, calculated that 54 million tons of the total
229 million tons of food produced in 2019 were wasted—that is, ended up in a landfill, incinera-
tor, down the drain, or left in the field. Food that ends up in a landfill to rot produces methane, a
greenhouse gas that is 21 times more harmful than carbon dioxide.
According to a Science article published in September 2020 by The Pew Charitable Trusts and Sys-
temIQ, a London-based sustainability consultancy, there were approximately 335 million metric
tons of plastic produced globally in 2016 (versus roughly 2 million metric tons in 1950). Of this
total, the study estimates that 49 million metric tons were burned openly in 2016, which releases
greenhouse gas emissions and a number of pollutants that negatively affect human health. Another
11 million metric tons of plastic leaked into the ocean in 2016, while only 15% of plastics were
actually recycled. If the status quo continues, the study estimates that 133 million metric tons of
plastics will be burned openly and 29 million metric tons of plastic will leak into the ocean by
2040. To put the severity of the issue in more context, a report published in 2016 by the Ellen Ma-
cArthur Foundation, in partnership with the World Economic Forum, predicted that plastics in the
oceans will outweigh fish by 2050.
50 Matt Larew +1 312 364 8242

William Blair
By creating more efficient and cost-effective microbes, synthetic biology has the potential to dra-
matically improve the quality of our soil and water, clean up oil spills, and provide a solution to
the food waste and plastics problems. Programmed microbes could also be used to upcycle waste
into products with value through the process of e-waste mining. As shown below, bioremediation
company Allonnia estimates that the market opportunity in bioremediation is nearly $1 trillion.
Exhibit 41
Bioremediation Market Opportunity
Allonnia was launched from Ginkgo Bioworks’ Ferment Consortium in October 2020 with $40
million in series A funding to develop and commercialize new waste remediation and management
solutions. Initially, the company is focusing on per- and poly-fluorinated compounds (e.g., PFAS,
PFOA, and PFOS), also known as “forever chemicals” because they do not degrade and can con-
taminate soil and ground water for decades. There is a significant need for treating these chemicals
as existing processes require high energy consumption and chemical use and do not remove the
chemicals from the environment entirely. As shown above, the market size for this initial applica-
tion is estimated to be approximately $8 billion.
Other synthetic biology companies in the bioremediation space include: Puraffinity.
Data Storage
Improving hardware, increased access to the internet, the proliferation of IoT devices, and the
modernization of company technology stacks have led to an explosion in rate of data generation
over the last five years. In a 2017 study, IBM estimated that 90% of all the data that exists was
created in the prior two years. According to International Data Corporation (IDC), data generated
globally more than doubled from 30 zettabytes (i.e., 30 trillion gigabytes) in 2017 to 64 zettabytes
in 2020. IDC’s Worldwide Global DataSphere Forecast projects data generated globally to grow at
a 23% compound annual rate from 2020 through 2025, reaching 180 zettabytes of data generated
in 2025. For comparison, there were only 3 zettabytes of data generated in 2010.
As the amount of data created by humans and machines continues to rise at an exponential rate,
the need for an alternative data storage system has become even more important. The supply of
data storage is not keeping pace with the amount of data being created, and existing storage tech-
nologies face a number of considerable challenges that make them unlikely to be viable over the
long term. Specifically, existing storage technologies incur storage maintenance and replacement
costs, have density limitations that result in capital expenditure and operational cost challenges,
and are associated with energy and sustainability concerns. In regard to energy and sustainability
Matt Larew +1 312 364 8242 51

William Blair
concerns, the DNA Data Storage Alliance (discussed below) recently noted that data center elec-
tricity usage could grow to 3%-13% of total global electricity consumption by 2030 if energy-
efficiency improvements do not continue.
To address the limitations associated with today’s data storage technologies, there has been in-
creasing interest in using DNA-based data storage. While the cost of synthesizing DNA is currently
not where it needs to be for DNA-based data storage to replace legacy data storage technologies,
DNA has a number of unique properties that make it an ideal medium for storing data, including:
incredible durability and stability (it can remain intact for thousands of years at room temperature
in a dry atmosphere), low post-creation data retention costs, immutability (DNA code is univer-
sal and will be readable in thousands of years, which eliminates the need to migrate data to new
generations of media/devices), high information density (it can store a lot of data in a little bit of
space), and better energy efficiency and sustainability relative to existing storage technologies.
As shown below, the process of storing data in DNA involves encoding the original data (mapping it
from 1s and 0s to sequences of DNA bases, i.e., A, T, C, and G), synthesizing (writing) the data, and
then storing the data. To read the data, the DNA is then sequenced (read) and decoded (re-mapped
from DNA bases back to 1s and 0s).
Exhibit 42
Digital Data to DNA Pipeline
Source: DNA Data Storage Alliance; Adapted by William Blair Equity Research
In mid-2020, Twist joined forces with other industry leaders to form the DNA Data Storage Alli-
ance. This alliance was formed to generate an industry roadmap, develop use-cases, and educate
for broader awareness and adoption; basically, it was formed to “grease the wheels of future com-
mercialization.” At present, there are 30 industry leaders in the DNA Data Storage Alliance, and
other notable companies include Microsoft, Illumina, and Western Digital. In June 2021, the alli-
ance released a white paper on DNA data storage and the opportunities that lie ahead (found here).
52 Matt Larew +1 312 364 8242

William Blair
Exhibit 43
DNA Data Storage Alliance
Source: TWST company presentations
Twist estimates that the market opportunity for data storage is $35 billion, 60% of which ($21 bil-
lion) relates to storing cold data (i.e., data that is not read often). Since this data will hardly ever
be read, the cost to sequence (i.e., read) the data is less important, which means if companies can
produce a cost-efficient alternative to storing the data it should be competitive with existing stor-
age systems. As a result, Twist believes this portion of the market represents the initial address-
able market for data storage, with the remaining 40% of the market becoming addressable as the
cost of sequencing decreases over time. In terms of timeline for commercialization, Twist expects
to have a prototype silicon chip for commercial production in hand in calendar 2022.
Other synthetic biology companies in the DNA data storage space include: Catalog Technologies,
ETH Zurich, Helixworks, Iradia, Kern Systems, North Shore Bio, and Roswell.
Matt Larew +1 312 364 8242 53

William Blair
The prices of the common stock of other public companies mentioned in this report follow:
Amyris, Inc. $16.50

Apple Inc. $133.11
AquaBounty Technologies Inc. $5.91
Arcadia Biosciences, Inc. $3.00
Avid Bioservices, Inc. $25.10
BASF SE €66.12
Baxter International Inc. $82.19
Bayer AG Sponsored ADR $15.50
Berkeley Lights Inc. (Outperform) $48.10
Biogen Inc. (Outperform) $347.93
Calyxt, Inc. $4.05
Catalent Inc. (Outperform) $109.16
Codex DNA $17.76
Codexis, Inc. $22.54
Corteva Inc. $44.16
Coty Inc. $9.44
Cronos Group Inc. C$10.91
Danaher Corporation (Outperform) $266.56
Decibel Therapeutics, Inc. $8.24
DuPont de Nemours, Inc. $76.54
Estee Lauder Companies Inc. $315.95
Eurofins Scientific Societe Europeenne €96.15
Evolva Holdings SA CHF0.18
Evonik Industries AG €28.08
Evotec SE €37.74
Fujifilm Holdings Corp. ¥8,139.00
Global Bioenergies SA €6.66
Hormel Foods Corporation $47.76
Illumina, Inc. $474.66
Johnson Matthey Plc. £30.82
Jubilant Ingrevia Ltd. RS549.45
Lonza Group AG (Outperform) CHF661.00
L’Oréal SA €385.4
Microsoft Corporation $265.02
Moderna, Inc. $219.94
NVIDIA Corporation $761.24
Pacific Biosciences of California, Inc. $33.81
Pilgrim’s Pride Corporation $23.13
Piramal Enterprises Ltd. RS2,422.65
Pfizer Inc. $38.98
Porton Pharma Solutions Ltd. Y87.10
Recipharm AB KR232.40
Samsung Biologics Co., Ltd. W849,000.00
Showa Denko K.K. ¥3,335.00
Siegfried Holding AG CHF865.50
Sumitomo Chemical Co., Ltd. ¥598.00
Synlogic Inc. $4.20
Thermo Fisher Scientific Inc. $492.87
Twist Bioscience Corp. (Outperform) $122.56
Tyson Foods, Inc. $74.50
Western Digital Corporation $70.75
54 Matt Larew +1 312 364 8242

William Blair
WuXi AppTec Co., Ltd. HK$182.30

WuXi Biologics Inc. HK$142.30
Yield10 Bioscience, Inc. $10.02
Zymergen Inc. (Outperform) $41.15
Matt Larew +1 312 364 8242 55

William Blair
IMPORTANT DISCLOSURES
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Matt Larew, Raju Prasad and Myles R. Minter attests that 1) all of the views expressed in this research report accurately reflect his/her
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The compensation of the research analyst is based on a variety of factors, including performance of his or her stock recommendations;
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profitability; and competitive factors.
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William Blair
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57 | Matt Larew +1 312 364 8242

Equity Research Directory
John F. O’Toole, Partner Manager and Director of Research +1 312 364 8612
Kyle Harris, CFA, Partner Operations Manager +1 312 364 8230
CONSUMER GLOBAL INDUSTRIAL INFRASTRUCTURE

Sharon Zackfia, CFA, Partner +1 312 364 5386 Nick Heymann +1 212 237 2740
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Financial Services Distributors, Property & Casualty Insurance Bhavan Suri, Partner +1 312 364 5341
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Biotechnology Arjun Bhatia, CPA +1 312 364 5696
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Biotechnology Software
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Co-Group Head–Healthcare Technology and Services Stephen Sheldon, CFA, CPA +1 312 364 5167
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Programming Life: Understanding The Transformative Potential of Synthetic Biology

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Programming Life: Understanding The Transformative Potential of Synthetic Biology

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Equity Research

Healthcare | Life Science Tools

June 29, 2021

Matt Larew +1 312 364 8242

Max Smock +1 312 364 8336

Myles R. Minter, Ph.D. +1 312 364 5283

Raju Prasad, Ph.D. +1 312 364 8469

Synthetic Biology Bhavan Suri +1 312 364 5341

What Is Synthetic Biology?................................................................................................. 4

Synthetic Biology Process.................................................................................................. 6

Synthetic Biology in Action – Spotlighting Three Pioneering Companies...................... 14

DNA Sequencing (Read).............................................................................................. 26

DNA Synthesis (Write)................................................................................................. 27

Gene Editing (Edit)...................................................................................................... 31

2 Matt Larew +1 312 364 8242

Matt Larew +1 312 364 8242 3

What Is Synthetic Biology?

4 Matt Larew +1 312 364 8242

Code Inform function 0101 written by Swift ATCG

Source: TBIO company presentation

Matt Larew +1 312 364 8242 5

Synthetic Biology Process

6 Matt Larew +1 312 364 8242

Idea Product Cell Programming

Source: William Blair Equity Research

Idea Product Cell Programming

Source: William Blair Equity Research

Matt Larew +1 312 364 8242 7

II. Product Design

Idea Product Cell Programming

Source: William Blair Equity Research

8 Matt Larew +1 312 364 8242

Source: ZY company filings

III. Cell Programming

Idea Product Cell Programming

Source: William Blair Equity Research

Matt Larew +1 312 364 8242 9

IV. Product Commercialization

Idea Product Cell Programming

Source: William Blair Equity Research

10 Matt Larew +1 312 364 8242

Source: U.S. National Library of Medicine

Matt Larew +1 312 364 8242 11

Because commercializing a product typically means significantly scaling production of an end-

12 Matt Larew +1 312 364 8242

Note: * denotes publicly traded

Source: Amyris company presentations

Matt Larew +1 312 364 8242 13

Synthetic Biology in Action – Spotlighting Three Pioneering

Source: Ginkgo company presentations

In addition to partnerships with blue-chip customers in a number of different industries, Ginkgo

• Genomatica – a strategic partnership announced in September 2016 and expanded in Octo-

14 Matt Larew +1 312 364 8242

• Moderna – a partnership announced in April 2020. Ginkgo is supporting Moderna’s process

Matt Larew +1 312 364 8242 15

Source: Ginkgo company presentations

Source: Ginkgo company presentations

16 Matt Larew +1 312 364 8242

Source: Ginkgo company presentations

While characterizing sequences of DNA is important, it is difficult to predict the performance of

Source: Ginkgo company presentations

18 Matt Larew +1 312 364 8242

Matt Larew +1 312 364 8242 19