A N N U A L R E P O R T
1
2 0 2 1
YEAR IN REVIEW
2020
$69m
$105m
FISCAL YEAR 2021
TOTAL REVENUE
2020
$30m
$71m
PRODUCT REVENUE
2020
55%
69%
PRODUCT GROSS MARGIN
Patented and generic drugs
manufactured with Codexis enzymes
Codexis-discovered
drug candidates in clinical trials
33
Sustainable manufacturing products &
processes being developed
5
New enzymes
developed for life
science tools
13
Products in life
science tools
innovation pipeline
therapy programs
7 Projects in oral enzyme
6Projects in
gene therapy
programs
2
3
20 2 0 2 1
YEAR IN REVIEW
2020
$69m
$105m
FISCAL YEAR 2021
TOTAL REVENUE
2020
$30m
$71m
PRODUCT REVENUE
2020
55%
69%
PRODUCT GROSS MARGIN
Patented and generic drugs
manufactured with Codexis enzymes
Codexis-discovered
drug candidates in clinical trials
33
Sustainable manufacturing products &
processes being developed
5
New enzymes
developed for life
science tools
13
Products in life
science tools
innovation pipeline
therapy programs
7 Projects in oral enzyme
6Projects in
gene therapy
programs
2
3
20 Sustainable Manufacturing
Sustainable Manufacturing remains the core foundation of the company. Our
high-performance enzymes enable our customers to reduce the cost and
increase the sustainability of product manufacturing through higher yields,
less energy usage and lower waste generation. This segment continues to
represent the majority of our revenues.
Our pipeline of enzyme catalysts enabling small molecule pharmaceutical
processes continues to expand and remains a core driver of long-term growth
for the company. In 2021, we executed on our largest annual product sale to
Pfizer for one of our proprietary enzymes to be used in the manufacture of
their COVID-19 antiviral therapeutic. This project is expected to not only drive
significant growth for the company this year and beyond, but also provides
tangible evidence of the critical impact our products can have on the health of
people and the planet by enabling rapid and efficient manufacturing processes.
Continuing our well-established work with Merck’s Januvia® (sitagliptin), we
announced new multi-year agreements to extend our long-standing sitagliptin
business into its generic chapter. These agreements include an extension of
our enzyme supply contract with Merck through at least the end of 2026, as
well as an innovative tri-party relationship with Almelo Private Ltd. and RC2
Pharma Connect LLC for the enzymatic production of low cost sitagliptin for
the generic market.
In the food and beverage space, we expanded the research collaboration
and entered into an exclusive supply agreement with Kalsec, Inc. for a novel
enzyme to produce a clean-label beverage ingredient, their newest natural hop
acid. The new enzyme was engineered for improved functionality, stability, and
efficiency, delivering consistent hop characteristics and taste that offer unique
advantages for beverage products.
We also extended our partnership with Tate & Lyle to enhance the production
of two new sweeteners. New enzyme variants, which replace existing Codexis
enzymes on our two sweetener product collaborations with Tate & Lyle (DOLCIA
PRIMA® Allulose and TASTEVA® M Stevia Sweetener), will enable additional
improvements in process productivity and economics, further reducing the
already highly competitive cost of goods on the two products.
We continue to invest in broadening the reach of our technology and products
to wide-ranging
increasingly targeting new customer
segments and expanding our capacity and capability to both improve and
economically produce enzymes in multiple organisms – a key requirement for
success in industrial biotechnology.
industrial markets,
codexis.com/pharma-mfg
codexis.com/food-and-nutrition
codexis.com/industrial-applications
4
Pharma Manufacturing
Biocatalysis as the go-to
process technology
• Proprietary enzyme production of a key
intermediate for Pfizer’s COVID anti-viral
• Extended enzyme agreement with Merck for
sitagliptin production
• Tri-party collaboration with Almelo and RC2
for enzymatic production of sitagliptin for the
generic market
• Other products utilizing proprietary Codexis
enzymes for their manufacture commercialized
in 2021
Food, Beverage & Nutrition
Sustainable, clean label, high purity products
• New enzyme for Kalsec’s natural hop acid
production
• New enzyme variants for DOLCIA PRIMA®
Allulose and TASTEVA® M Stevia Sweetener
production
Industrial Applications
Innovate and execute in new verticals
• Active expansion into new market segments
• Increased investment in application team
5
Sustainable Manufacturing
Sustainable Manufacturing remains the core foundation of the company. Our
high-performance enzymes enable our customers to reduce the cost and
increase the sustainability of product manufacturing through higher yields,
less energy usage and lower waste generation. This segment continues to
represent the majority of our revenues.
Our pipeline of enzyme catalysts enabling small molecule pharmaceutical
processes continues to expand and remains a core driver of long-term growth
for the company. In 2021, we executed on our largest annual product sale to
Pfizer for one of our proprietary enzymes to be used in the manufacture of
their COVID-19 antiviral therapeutic. This project is expected to not only drive
significant growth for the company this year and beyond, but also provides
tangible evidence of the critical impact our products can have on the health of
people and the planet by enabling rapid and efficient manufacturing processes.
Continuing our well-established work with Merck’s Januvia® (sitagliptin), we
announced new multi-year agreements to extend our long-standing sitagliptin
business into its generic chapter. These agreements include an extension of
our enzyme supply contract with Merck through at least the end of 2026, as
well as an innovative tri-party relationship with Almelo Private Ltd. and RC2
Pharma Connect LLC for the enzymatic production of low cost sitagliptin for
the generic market.
In the food and beverage space, we expanded the research collaboration
and entered into an exclusive supply agreement with Kalsec, Inc. for a novel
enzyme to produce a clean-label beverage ingredient, their newest natural hop
acid. The new enzyme was engineered for improved functionality, stability, and
efficiency, delivering consistent hop characteristics and taste that offer unique
advantages for beverage products.
We also extended our partnership with Tate & Lyle to enhance the production
of two new sweeteners. New enzyme variants, which replace existing Codexis
enzymes on our two sweetener product collaborations with Tate & Lyle (DOLCIA
PRIMA® Allulose and TASTEVA® M Stevia Sweetener), will enable additional
improvements in process productivity and economics, further reducing the
already highly competitive cost of goods on the two products.
We continue to invest in broadening the reach of our technology and products
to wide-ranging
increasingly targeting new customer
segments and expanding our capacity and capability to both improve and
economically produce enzymes in multiple organisms – a key requirement for
success in industrial biotechnology.
industrial markets,
codexis.com/pharma-mfg
codexis.com/food-and-nutrition
codexis.com/industrial-applications
4
Pharma Manufacturing
Biocatalysis as the go-to
process technology
• Proprietary enzyme production of a key
intermediate for Pfizer’s COVID anti-viral
• Extended enzyme agreement with Merck for
sitagliptin production
• Tri-party collaboration with Almelo and RC2
for enzymatic production of sitagliptin for the
generic market
• Other products utilizing proprietary Codexis
enzymes for their manufacture commercialized
in 2021
Food, Beverage & Nutrition
Sustainable, clean label, high purity products
• New enzyme for Kalsec’s natural hop acid
production
• New enzyme variants for DOLCIA PRIMA®
Allulose and TASTEVA® M Stevia Sweetener
production
Industrial Applications
Innovate and execute in new verticals
• Active expansion into new market segments
• Increased investment in application team
5
Life Science Tools
Engineered enzymes enable value creating performance
improvements in genomics workflows, DNA and RNA synthesis
and numerous other life science applications. To date, we have
launched three enzymes to address challenges for high-growth
market segments: Codex® HiFi Hot Start DNA polymerase for
next generation sequencing (NGS) library prep and diagnostic
molecular assays; Codex® HiCap RNA polymerase for the
manufacture of mRNA therapeutics; and, most recently, Codex®
HiTemp reverse transcriptase for one-step RT-qPCR assays.
We continue to invest significantly in Life Science Tools, both in
our own program and in partnered programs, to accelerate the
cadence of our product launches.
In late 2021, to address the market demand for viral diagnostics
such as SARS-CoV-2 nucleic acid amplification tests and in
response to the well-documented challenges faced in handling
clinical samples, we commercialized Codex® HiTemp reverse
transcriptase for use in one-step RT-qPCR assays. This enzyme
is specifically engineered for enhanced thermostability to tackle
complicated RNA structures and is optimized for improved
robustness to address obstacles such as sample degradation,
stability at room temperature, varying pH conditions, and the
presence of impurities.
Codexis and Molecular Assemblies, Inc. (MAI) are established
partners, collaborating to revolutionize DNA production using
enzymatic synthesis. Since mid-2020, we have been applying our
technology to improve the enzymes that are critical for DNA chain
extension in MAI’s industrial scale manufacturing process. MAI has
been leveraging Codexis’ highly engineered enzyme variants in its
workflows to drive process performance and economics to the
levels required for successful commercialization. In November
2021, Codexis and Casdin Capital invested a combined $10
million in the Series B funding round of MAI to accelerate its novel
enzymatic DNA synthesis technology toward commercialization.
Codexis contributed $7 million of this investment, becoming
MAI’s second largest shareholder; this investment comes on top
of previous investments by Codexis.
codexis.com/life-sciences
Sequencing & Detection
Improve NGS and diagnostic workflows
Codex® HiFi Hot Start DNA polymerase for NGS
• Amplifies DNA with enhanced fidelity and
reduced bias
Codex® HiTemp reverse transcriptase for
one-step PCR testing
• Enhanced thermostability and improved
robustness for challenging clinical samples
DNA & RNA Synthesis
Improve oligonucleotide synthesis
Codex® HiCap RNA polymerase for
mRNA synthesis
• Capping efficiency over native enzyme,
improving yield and reducing ‘cap’ usage
New enzyme for enzymatic DNA Synthesis
• Further investment to commercialize
enzymatic DNA synthesis technology
6
7
Life Science Tools
Engineered enzymes enable value creating performance
improvements in genomics workflows, DNA and RNA synthesis
and numerous other life science applications. To date, we have
launched three enzymes to address challenges for high-growth
market segments: Codex® HiFi Hot Start DNA polymerase for
next generation sequencing (NGS) library prep and diagnostic
molecular assays; Codex® HiCap RNA polymerase for the
manufacture of mRNA therapeutics; and, most recently, Codex®
HiTemp reverse transcriptase for one-step RT-qPCR assays.
We continue to invest significantly in Life Science Tools, both in
our own program and in partnered programs, to accelerate the
cadence of our product launches.
In late 2021, to address the market demand for viral diagnostics
such as SARS-CoV-2 nucleic acid amplification tests and in
response to the well-documented challenges faced in handling
clinical samples, we commercialized Codex® HiTemp reverse
transcriptase for use in one-step RT-qPCR assays. This enzyme
is specifically engineered for enhanced thermostability to tackle
complicated RNA structures and is optimized for improved
robustness to address obstacles such as sample degradation,
stability at room temperature, varying pH conditions, and the
presence of impurities.
Codexis and Molecular Assemblies, Inc. (MAI) are established
partners, collaborating to revolutionize DNA production using
enzymatic synthesis. Since mid-2020, we have been applying our
technology to improve the enzymes that are critical for DNA chain
extension in MAI’s industrial scale manufacturing process. MAI has
been leveraging Codexis’ highly engineered enzyme variants in its
workflows to drive process performance and economics to the
levels required for successful commercialization. In November
2021, Codexis and Casdin Capital invested a combined $10
million in the Series B funding round of MAI to accelerate its novel
enzymatic DNA synthesis technology toward commercialization.
Codexis contributed $7 million of this investment, becoming
MAI’s second largest shareholder; this investment comes on top
of previous investments by Codexis.
codexis.com/life-sciences
Sequencing & Detection
Improve NGS and diagnostic workflows
Codex® HiFi Hot Start DNA polymerase for NGS
• Amplifies DNA with enhanced fidelity and
reduced bias
Codex® HiTemp reverse transcriptase for
one-step PCR testing
• Enhanced thermostability and improved
robustness for challenging clinical samples
DNA & RNA Synthesis
Improve oligonucleotide synthesis
Codex® HiCap RNA polymerase for
mRNA synthesis
• Capping efficiency over native enzyme,
improving yield and reducing ‘cap’ usage
New enzyme for enzymatic DNA Synthesis
• Further investment to commercialize
enzymatic DNA synthesis technology
6
7
Biotherapeutics
We are leveraging our CodeEvolver® technology platform to improve
multiple protein properties in parallel, allowing us to rapidly build and
advance a high-value pipeline of oral enzyme therapy and gene
therapy candidates with the goal of addressing unmet patient needs.
Our current focus is on discovering safe and efficacious GI-active
enzymes and transgenes for treatment of Inborn Errors of Metabolism
(IEMs) and other metabolic diseases. Our application-focused high
throughput screens generate large data sets that we analyze with our
bioinformatics software, enabling us to generate enzymes uniquely
designed for a specific therapeutic indication.
Two of our therapeutic enzyme candidates are in Phase 1 clinical trials.
Our first Codexis-discovered candidate, CDX-6114, is being advanced
by Nestlé Health Science for potential treatment of phenylketonuria.
Our second clinical program, CDX-7108, is being assessed as potential
treatment for exocrine pancreatic insufficiency (EPI) and is also being
advanced in partnership with Nestlé Health Science. CDX-7108 is a
lipase variant specifically engineered to overcome the limitations of the
current standard of care: traditional pancreatic enzyme replacement
therapy (PERT). EPI is a debilitating condition of the GI-tract that
is caused by conditions that impair pancreatic function, such as
pancreatitis, pancreatic cancer, Crohn’s disease, celiac disease, and
cystic fibrosis. CDX-7108 was specifically engineered to be highly
stable in the acidic conditions in the stomach and resistant to proteases
in the upper intestines.
Our wholly owned enzyme therapy programs also moved forward
in 2021. Pre-clinical data on CDX-6512 for the treatment of
homocystinuria (HCU) and enzyme variants for the treatment of maple
syrup urine disease (MSUD) were presented at the 14th International
Congress of Inborn Errors of Metabolism (ICIEM) 2021. In January
2022, the FDA granted orphan drug designation and rare pediatric
disease designation for CDX-6512 for HCU. CDX-6512 is currently in
IND-enabling studies.
We expanded our strategic collaboration and license agreement with
Takeda for the research and development of an additional gene therapy
for a lysosomal storage disorder, bringing the total number of programs
under the agreement to four. To date, we have generated novel genetic
sequences that encode more efficacious enzymes for the potential
treatment of Fabry and Pompe Diseases, as well as an undisclosed
blood factor deficiency.
codexis.com/therapeutics/
8
Oral Enzyme Therapies
Optimized enzymes for safe
and efficacious treatments
GI-active therapies
• Orally delivered enzymes for treatment of
genetic metabolic and gastrointestinal
disorders
• Targeting best-in-class safety and efficacy
• Four programs progressing under a strategic
collaboration with Nestlé Health Science
• Two Codexis-discovered candidates being
studied in clinical trials
• Two wholly-owned candidates undergoing
IND-enabling studies
Gene Therapies
Enhanced transgenes and delivery
vectors for safe and efficacious
treatments
Liver-depot or tissue-expressed
therapies
• Engineered transgenes to enable best-in-class
gene therapies for lysosomal storage disorders,
hematologic diseases, and other inborn errors
of metabolism
• Optimized viral vectors for enhanced delivery
and manufacturability
• Targeting best-in-class safety and efficacy
• Four programs progressing under a strategic
collaboration with Takeda
9
Biotherapeutics
We are leveraging our CodeEvolver® technology platform to improve
multiple protein properties in parallel, allowing us to rapidly build and
advance a high-value pipeline of oral enzyme therapy and gene
therapy candidates with the goal of addressing unmet patient needs.
Our current focus is on discovering safe and efficacious GI-active
enzymes and transgenes for treatment of Inborn Errors of Metabolism
(IEMs) and other metabolic diseases. Our application-focused high
throughput screens generate large data sets that we analyze with our
bioinformatics software, enabling us to generate enzymes uniquely
designed for a specific therapeutic indication.
Two of our therapeutic enzyme candidates are in Phase 1 clinical trials.
Our first Codexis-discovered candidate, CDX-6114, is being advanced
by Nestlé Health Science for potential treatment of phenylketonuria.
Our second clinical program, CDX-7108, is being assessed as potential
treatment for exocrine pancreatic insufficiency (EPI) and is also being
advanced in partnership with Nestlé Health Science. CDX-7108 is a
lipase variant specifically engineered to overcome the limitations of the
current standard of care: traditional pancreatic enzyme replacement
therapy (PERT). EPI is a debilitating condition of the GI-tract that
is caused by conditions that impair pancreatic function, such as
pancreatitis, pancreatic cancer, Crohn’s disease, celiac disease, and
cystic fibrosis. CDX-7108 was specifically engineered to be highly
stable in the acidic conditions in the stomach and resistant to proteases
in the upper intestines.
Our wholly owned enzyme therapy programs also moved forward
in 2021. Pre-clinical data on CDX-6512 for the treatment of
homocystinuria (HCU) and enzyme variants for the treatment of maple
syrup urine disease (MSUD) were presented at the 14th International
Congress of Inborn Errors of Metabolism (ICIEM) 2021. In January
2022, the FDA granted orphan drug designation and rare pediatric
disease designation for CDX-6512 for HCU. CDX-6512 is currently in
IND-enabling studies.
We expanded our strategic collaboration and license agreement with
Takeda for the research and development of an additional gene therapy
for a lysosomal storage disorder, bringing the total number of programs
under the agreement to four. To date, we have generated novel genetic
sequences that encode more efficacious enzymes for the potential
treatment of Fabry and Pompe Diseases, as well as an undisclosed
blood factor deficiency.
codexis.com/therapeutics/
8
Oral Enzyme Therapies
Optimized enzymes for safe
and efficacious treatments
GI-active therapies
• Orally delivered enzymes for treatment of
genetic metabolic and gastrointestinal
disorders
• Targeting best-in-class safety and efficacy
• Four programs progressing under a strategic
collaboration with Nestlé Health Science
• Two Codexis-discovered candidates being
studied in clinical trials
• Two wholly-owned candidates undergoing
IND-enabling studies
Gene Therapies
Enhanced transgenes and delivery
vectors for safe and efficacious
treatments
Liver-depot or tissue-expressed
therapies
• Engineered transgenes to enable best-in-class
gene therapies for lysosomal storage disorders,
hematologic diseases, and other inborn errors
of metabolism
• Optimized viral vectors for enhanced delivery
and manufacturability
• Targeting best-in-class safety and efficacy
• Four programs progressing under a strategic
collaboration with Takeda
9
Employee Safety & Wellness
+40%
Safety First
With a more than 40% increase in our employee
headcount in 2021 and the opening of our new
facility in San Carlos, CA, providing a safe workplace
for all remains a top priority. We had zero lost time
incidents and zero reportable incidents with OSHA
in 2021. Throughout the year, we also reinstated
several in-person training sessions on preventative
programs and emergency procedures.
COVID Measures
Our COVID-19 Task Force continues to monitor
guidance from the Federal government, the State
of California, San Mateo county, and CalOSHA.
They also regularly reassess the safety measures
put in place to ensure employee safety. 96% of our
employees have been vaccinated for COVID-19.
Health & Wellness
To alleviate workplace stress and maintain physical
wellness, many employees have joined the
Company’s weekly bayside stroll program to get
active and stay healthy.
10
11
Employee Safety & Wellness
+40%
Safety First
With a more than 40% increase in our employee
headcount in 2021 and the opening of our new
facility in San Carlos, CA, providing a safe workplace
for all remains a top priority. We had zero lost time
incidents and zero reportable incidents with OSHA
in 2021. Throughout the year, we also reinstated
several in-person training sessions on preventative
programs and emergency procedures.
COVID Measures
Our COVID-19 Task Force continues to monitor
guidance from the Federal government, the State
of California, San Mateo county, and CalOSHA.
They also regularly reassess the safety measures
put in place to ensure employee safety. 96% of our
employees have been vaccinated for COVID-19.
Health & Wellness
To alleviate workplace stress and maintain physical
wellness, many employees have joined the
Company’s weekly bayside stroll program to get
active and stay healthy.
10
11
Diversity, Equity & Inclusion (DEI)
Social Responsibility
Underrepresented
Ethnic Groups*
Women In Leadership
Positions**
Women In
Technical Roles
2020
14%
2021
14%
2020
33%
2021
47%
2020
57%
2021
51%
Women On Board
Of Directors
2020
30%
2021
33%
*Hispanic/Latino, Black/African American, Native Hawaiian and other Pacific Islander, Native American, and two or more races
**People leaders with positions at director level and above
In 2021, we hosted online seminars and presented at conferences to increase awareness of
rare diseases at the global level. Locally, our employees participated in awareness run/walk
events to fundraise for Fabry disease and HCU.
Rare Disease Awareness
Mentorship Program
Many of our employees volunteered in a local high school’s mentoring program. The
mentoring program pairs students with professionals to discuss both academic and career
goals for a future in research, engineering, programming, and business development
in biotechnology.
www.carlmontbti.org/mentor-or-volunteer/.
Future Protein Engineers
To encourage students to explore the science field more extensively, we worked with several
middle and high school teachers to add enzyme engineering to their science curriculum.
With their support, the spring and fall contests of this hybrid education program sparked
innovation and creativity in 2021.
Arindam Bagga, 17
(First Place, Spring 2021 16+ Video Contest)
“I had a great time competing in the competition, and I learned a lot as a
result of it. This competition gave me the chance to delve deeper into my
biochemistry interests and present what I had learned to an audience.”
Zoe Gregory, 18
(First place, Fall 2021 16+ infographics)
“I am really glad I participated in this contest because it was a great
opportunity to not only research enzymes related to environmental
issues but also to learn more about the processes scientists undergo
to modify enzymes so that they perform different functions.”
12
13
Diversity, Equity & Inclusion (DEI)
Social Responsibility
Underrepresented
Ethnic Groups*
Women In Leadership
Positions**
Women In
Technical Roles
2020
14%
2021
14%
2020
33%
2021
47%
2020
57%
2021
51%
Women On Board
Of Directors
2020
30%
2021
33%
*Hispanic/Latino, Black/African American, Native Hawaiian and other Pacific Islander, Native American, and two or more races
**People leaders with positions at director level and above
In 2021, we hosted online seminars and presented at conferences to increase awareness of
rare diseases at the global level. Locally, our employees participated in awareness run/walk
events to fundraise for Fabry disease and HCU.
Rare Disease Awareness
Mentorship Program
Many of our employees volunteered in a local high school’s mentoring program. The
mentoring program pairs students with professionals to discuss both academic and career
goals for a future in research, engineering, programming, and business development
in biotechnology.
www.carlmontbti.org/mentor-or-volunteer/.
Future Protein Engineers
To encourage students to explore the science field more extensively, we worked with several
middle and high school teachers to add enzyme engineering to their science curriculum.
With their support, the spring and fall contests of this hybrid education program sparked
innovation and creativity in 2021.
Arindam Bagga, 17
(First Place, Spring 2021 16+ Video Contest)
“I had a great time competing in the competition, and I learned a lot as a
result of it. This competition gave me the chance to delve deeper into my
biochemistry interests and present what I had learned to an audience.”
Zoe Gregory, 18
(First place, Fall 2021 16+ infographics)
“I am really glad I participated in this contest because it was a great
opportunity to not only research enzymes related to environmental
issues but also to learn more about the processes scientists undergo
to modify enzymes so that they perform different functions.”
12
13
Letter to Shareholders
Dear fellow shareholders, partners and employees:
I am delighted to report that Codexis delivered another year
of exceptional performance. Total revenue for 2021 grew
52%, year-over-year, to $105 million, up from $69 million in
2020. Product revenue more than doubled to $71 million
in 2021, up from $30 million in 2020, and product gross
margin reached a new high of 69%. Over the past year, we
continued to diversify our customer base with 30 customers
contributing over $200,000 in revenue in 2021, twelve of
these contributed over $2 million in revenue.
Beyond the financials, I am grateful for the commitment our
employees demonstrated to our core mission and vision:
to create differentiated enzymes to improve the health of
people and the planet.
In our Biotherapeutics business, we now have a pipeline of
over a dozen programs and we are increasingly progressing
selected assets into clinical development on our own to
enhance their value for Codexis shareholders. This requires
investment on a product-by-product basis and greater
investment to grow the capacity and capabilities of the
organization. We believe strongly in the reward associated
with these investments and expect to advance several
candidates toward clinical studies over the coming few years.
We are thrilled to have entered the clinic in 2021 with
CDX- 7108 – a potential treatment for exocrine pancreatic
insufficiency, which is co-owned with Nestlé Health Science.
This is the second Codexis-designed therapeutic candidate
to enter Phase 1 clinical trials, after CDX-6114 for the
potential treatment of phenylketonuria, which is now licensed
to Nestlé Health Science. Two oral enzyme therapy programs
co-owned with Nestlé Health Science and three self-funded
programs are advancing
in research and development.
Our efforts in gene therapy have also made tremendous
progress. Our collaboration with Takeda to advance novel
gene therapies for treatment of rare diseases expanded
to four programs during 2021, and Codexis is generating
novel gene sequences to encode enzyme variants targeting
enhanced efficacy by increasing activity, stability, and cellular
uptake. Takeda is leveraging our improved transgenes with its
gene therapy capabilities to develop novel candidates for the
treatment of rare genetic disorders.
Our Sustainable Manufacturing business demonstrated step-
out growth in 2021, driven in large part by our ability to meet
the substantial needs of Pfizer with one of our proprietary
enzymes to manufacture a critical intermediate for their
new, oral COVID-19 antiviral treatment. We are pleased
with the speed at which we were able to quickly scale up our
supply chain and manufacturing partners in 2021 in order to
support such a meaningful endeavor. We achieved multi- ton
production of this enzyme within just a few months, enabling
us to meet demand for tens of millions of treatment courses
in the first half of 2022.
We have also positioned ourselves well for the upcoming
generic chapter of sitagliptin by extending our enzyme
supply agreement with Merck and establishing a multi-year
agreement with Almelo and RC2 as our first step into the
generic sitagliptin market. In addition, enzymes sales to
other innovative pharmaceutical customers grew in 2021,
with three products using our enzymes achieving important
regulatory approval milestones last year.
In adjacent markets such as food & nutrition and industrial
applications, we announced an expanded collaboration with
Kalsec, a leading producer of natural extracts, colors and
food protection for the food and beverage industry. We
continue to serve Tate & Lyle in their production of low caloric
sweeteners, DOLCIA PRIMA® Allulose and TASTEVA® M
Stevia, and demand for our enzymes for production of these
commercialized food ingredients increased meaningfully in
2021. Our ability to sustainably manufacture high-volume,
non-pharmaceutical products is a long-term value driver for
Codexis and has been increasingly recognized in the market
by a growing number of partners.
In our exciting and dynamic Life Science Tools business,
we achieved first commercial sales on two key products
- Codex® HiFi Hot Start DNA Polymerase for genomic
applications and Codex® HiCap RNA polymerase for mRNA
production. Our latest Life Science Tools enzyme, Codex®
HiTemp Reverse Transcriptase, specifically engineered with
improved sensitivity and inhibitor resistance for use in RT-
qPCR for RNA-based disease detection, launched in the
fourth quarter.
The partnership between Codexis and Molecular Assemblies,
Inc. is also making great strides, bringing the disruptive
enzymatic approach to DNA synthesis closer to reality. Given
our confidence, both in the partnership and in the market
opportunity, we increased our equity stake in Molecular
Assemblies, investing $7 million in September 2021, and
becoming their second largest shareholder in the process.
Our partner in the SynBio Innovation Accelerator, Casdin
John Nicols
President and Chief Executive Officer
Capital, invested $3 million, becoming a new shareholder in
Molecular Assemblies. It is exciting to leverage our enzyme
engineering and product supply capabilities to access
downstream value
in the fast-growing DNA synthesis
marketplace via these strategic moves.
To support this rapid business growth, and to continue
investing for future value creation, we grew our employee
base by over 40% in 2021 and added several strategic
positions to strengthen our leadership and to improve
capacity and productivity. Codexis maintained strong
momentum throughout the year, executed on several high
value opportunities in pharmaceuticals, food ingredients and
life science tools, and advanced our second drug candidate
into the clinic. 2021 was a very strong year for Codexis
across all of our target sectors, and we have a bright outlook
for 2022.
On behalf of Codexis’ leadership team, employees, and
Board of Directors, I thank you for your continued support.
14
15
Letter to Shareholders
Dear fellow shareholders, partners and employees:
I am delighted to report that Codexis delivered another year
of exceptional performance. Total revenue for 2021 grew
52%, year-over-year, to $105 million, up from $69 million in
2020. Product revenue more than doubled to $71 million
in 2021, up from $30 million in 2020, and product gross
margin reached a new high of 69%. Over the past year, we
continued to diversify our customer base with 30 customers
contributing over $200,000 in revenue in 2021, twelve of
these contributed over $2 million in revenue.
Beyond the financials, I am grateful for the commitment our
employees demonstrated to our core mission and vision:
to create differentiated enzymes to improve the health of
people and the planet.
In our Biotherapeutics business, we now have a pipeline of
over a dozen programs and we are increasingly progressing
selected assets into clinical development on our own to
enhance their value for Codexis shareholders. This requires
investment on a product-by-product basis and greater
investment to grow the capacity and capabilities of the
organization. We believe strongly in the reward associated
with these investments and expect to advance several
candidates toward clinical studies over the coming few years.
We are thrilled to have entered the clinic in 2021 with
CDX- 7108 – a potential treatment for exocrine pancreatic
insufficiency, which is co-owned with Nestlé Health Science.
This is the second Codexis-designed therapeutic candidate
to enter Phase 1 clinical trials, after CDX-6114 for the
potential treatment of phenylketonuria, which is now licensed
to Nestlé Health Science. Two oral enzyme therapy programs
co-owned with Nestlé Health Science and three self-funded
programs are advancing
in research and development.
Our efforts in gene therapy have also made tremendous
progress. Our collaboration with Takeda to advance novel
gene therapies for treatment of rare diseases expanded
to four programs during 2021, and Codexis is generating
novel gene sequences to encode enzyme variants targeting
enhanced efficacy by increasing activity, stability, and cellular
uptake. Takeda is leveraging our improved transgenes with its
gene therapy capabilities to develop novel candidates for the
treatment of rare genetic disorders.
Our Sustainable Manufacturing business demonstrated step-
out growth in 2021, driven in large part by our ability to meet
the substantial needs of Pfizer with one of our proprietary
enzymes to manufacture a critical intermediate for their
new, oral COVID-19 antiviral treatment. We are pleased
with the speed at which we were able to quickly scale up our
supply chain and manufacturing partners in 2021 in order to
support such a meaningful endeavor. We achieved multi- ton
production of this enzyme within just a few months, enabling
us to meet demand for tens of millions of treatment courses
in the first half of 2022.
We have also positioned ourselves well for the upcoming
generic chapter of sitagliptin by extending our enzyme
supply agreement with Merck and establishing a multi-year
agreement with Almelo and RC2 as our first step into the
generic sitagliptin market. In addition, enzymes sales to
other innovative pharmaceutical customers grew in 2021,
with three products using our enzymes achieving important
regulatory approval milestones last year.
In adjacent markets such as food & nutrition and industrial
applications, we announced an expanded collaboration with
Kalsec, a leading producer of natural extracts, colors and
food protection for the food and beverage industry. We
continue to serve Tate & Lyle in their production of low caloric
sweeteners, DOLCIA PRIMA® Allulose and TASTEVA® M
Stevia, and demand for our enzymes for production of these
commercialized food ingredients increased meaningfully in
2021. Our ability to sustainably manufacture high-volume,
non-pharmaceutical products is a long-term value driver for
Codexis and has been increasingly recognized in the market
by a growing number of partners.
In our exciting and dynamic Life Science Tools business,
we achieved first commercial sales on two key products
- Codex® HiFi Hot Start DNA Polymerase for genomic
applications and Codex® HiCap RNA polymerase for mRNA
production. Our latest Life Science Tools enzyme, Codex®
HiTemp Reverse Transcriptase, specifically engineered with
improved sensitivity and inhibitor resistance for use in RT-
qPCR for RNA-based disease detection, launched in the
fourth quarter.
The partnership between Codexis and Molecular Assemblies,
Inc. is also making great strides, bringing the disruptive
enzymatic approach to DNA synthesis closer to reality. Given
our confidence, both in the partnership and in the market
opportunity, we increased our equity stake in Molecular
Assemblies, investing $7 million in September 2021, and
becoming their second largest shareholder in the process.
Our partner in the SynBio Innovation Accelerator, Casdin
John Nicols
President and Chief Executive Officer
Capital, invested $3 million, becoming a new shareholder in
Molecular Assemblies. It is exciting to leverage our enzyme
engineering and product supply capabilities to access
downstream value
in the fast-growing DNA synthesis
marketplace via these strategic moves.
To support this rapid business growth, and to continue
investing for future value creation, we grew our employee
base by over 40% in 2021 and added several strategic
positions to strengthen our leadership and to improve
capacity and productivity. Codexis maintained strong
momentum throughout the year, executed on several high
value opportunities in pharmaceuticals, food ingredients and
life science tools, and advanced our second drug candidate
into the clinic. 2021 was a very strong year for Codexis
across all of our target sectors, and we have a bright outlook
for 2022.
On behalf of Codexis’ leadership team, employees, and
Board of Directors, I thank you for your continued support.
14
15
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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended: December 31, 2021
☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from to .
Commission File No.: 001-34705
Codexis, Inc.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of incorporation or organization)
200 Penobscot Drive, Redwood City, California
(Address of principal executive offices)
71-0872999
(I.R.S. Employer Identification No.)
94063
(Zip Code)
Title of Each Class:
Common Stock, par value $0.0001 per share
Registrant’s telephone number, including area code: (650) 421-8100
Securities Registered Pursuant to Section 12(b) of the Act:
Trading Symbols(s):
CDXS
Securities Registered Pursuant to Section 12(g) of the Act: None
Name of Each Exchange on which Registered:
The Nasdaq Global Select Market
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☒ No ☐
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the
Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was
required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
Yes ☒ No ☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be
submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for
such shorter period that the registrant was required to submit such files).
Yes ☒ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller
reporting company, or emerging growth company. See the definitions of “large accelerated filer, “accelerated filer” and “smaller
reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act:
Large accelerated filer
Non-accelerated filer
☒
☐
Accelerated filer
Smaller reporting company
Emerging growth company
☐ ☐
☐
☐ ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for
complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of
the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15
U.S.C.7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☒
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act).
Yes ☒ No ☐
Yes ☐ No ☒
The aggregate market value of voting and non-voting common stock held by non-affiliates of Codexis as of June 30, 2021 was approximately
$737.5 million based upon the closing price reported for such date on the Nasdaq Global Select Market.
As of February 24, 2022, there were 65,160,679 shares of the registrant’s Common Stock, par value $0.0001 per share, outstanding.
______________________________________
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the registrant’s Definitive Proxy Statement to be filed with the Commission pursuant to Regulation 14A in connection with
the registrant’s 2022 Annual Meeting of Stockholders (the "Proxy Statement"), to be filed subsequent to the date hereof, are incorporated by
reference into Part III of this Report. Such Definitive Proxy Statement will be filed with the Securities and Exchange Commission not later
than 120 days after the conclusion of the registrant’s fiscal year ended December 31, 2021. Except with respect to information specifically
incorporated by reference in this Form 10-K, the Proxy Statement is not deemed to be filed as part of this Form 10-K.
Codexis, Inc.
Annual Report on Form 10-K
For The Year Ended December 31, 2021
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures
INDEX
PART I
PART II
Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity
Securities
[Reserved]
Management's Discussion and Analysis of Financial Condition and Results of Operations
Quantitative and Qualitative Disclosures About Market Risk
Financial Statements and Supplementary Data
Changes in and Disagreements with Accountants on Accounting and Financial Disclosures
Controls and Procedures
Other Information
Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
Directors, Executive Officers and Corporate Governance
Executive Compensation
PART III
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
Certain Relationships and Related Transactions, and Director Independence
Principal Accounting Fees and Services
PART IV
Exhibits and Financial Statement Schedules
Form 10-K Summary
Signatures
Item 1
Item 1A
Item 1B
Item 2
Item 3
Item 4
Item 5
Item 6
Item 7
Item 7A
Item 8
Item 9
Item 9A
Item 9B
Item 9C
Item 10
Item 11
Item 12
Item 13
Item 14
Item 15
Item 16
4
25
56
56
56
56
57
58
59
78
79
124
124
124
125
125
125
125
125
125
126
133
134
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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
The following discussion and analysis should be read in conjunction with our audited Consolidated Financial Statements and
the related Notes that appear elsewhere in this Annual Report on Form 10-K. This Annual Report on Form 10-K contains
“forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended (“the
Exchange Act”), particularly in Part I, Item 1: “Business,” Part I, Item 1A: “Risk Factors” and Part 2, Item 7: “Management’s
Discussion and Analysis of Financial Condition and Results of Operations.” These statements are often identified by the use of
words such as “may,” “will,” “expect,” “believe,” “anticipate,” “intend,” “could,” “should,” “estimate” or “continue,” and
similar expressions or variations. All statements other than statements of historical fact could be deemed forward-looking,
including, but not limited to: any projections of financial information or performance; any statements about historical results
that may suggest trends for our business; any statements of the plans, strategies, and objectives of management for future
operations; any statements of expectation or belief regarding future events, technology developments, our products and product
candidates, product sales, revenues, expenses, liquidity, cash flow, market growth rates or enforceability of our intellectual
property rights and related litigation expenses; and any statements of assumptions underlying any of the foregoing. Such
forward-looking statements are subject to risks, uncertainties and other factors that could cause actual results and the timing of
certain events to differ materially from future results expressed or implied by such forward-looking statements. Accordingly, we
caution you not to place undue reliance on these statements. For a discussion of some of the factors that could cause actual
results to differ materially from our forward-looking statements, see the discussion on risk factors that appear in Part I,
Item 1A: “Risk Factors” of this Annual Report on Form 10-K and other risks and uncertainties detailed in this and our other
reports and filings with the Securities and Exchange Commission (“SEC”). The forward-looking statements in this Annual
Report on Form 10-K represent our views as of the date of this Annual Report on Form 10-K. We anticipate that subsequent
events and developments will cause our views to change. However, while we may elect to update these forward-looking
statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law.
You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the
date of this Annual Report on Form 10-K.
3
PART I
ITEM 1. BUSINESS
COMPANY OVERVIEW
We discover, develop and sell enzymes and other proteins that deliver value to our clients in a growing set of industries. We
view proteins as a vast, largely untapped source of value-creating products, and we are using our proven technologies, which
we have been continuously improving since our inception in 2002, to commercialize an increasing number of novel enzymes,
both as proprietary Codexis products and in partnership with our customers.
We are a pioneer in harnessing computational technologies to drive biology advancements. Since 2002, we have made
substantial investments in the development of our CodeEvolver® protein engineering technology platform, the primary source
of our competitive advantage. Our technology platform is powered by proprietary, artificial intelligence-based, computational
algorithms that rapidly mine the structural and performance attributes of our large and continuously growing library of protein
variants. These computational outputs enable increasingly reliable predictions for next generation protein variants to be
engineered, enabling time- and cost-efficient delivery of the targeted performance enhancements. In addition to its
computational prowess, our CodeEvolver® protein engineering technology platform integrates additional modular
competencies, including robotic high-throughput screening and genomic sequencing, organic chemistry and bioprocess
development which are all coordinated to rapidly innovate novel, fit-for-purpose products.
The core historical application of the technology has been in developing commercially viable biocatalytic manufacturing
processes for more sustainable production of complex chemicals. It begins by conceptually designing the most cost-effective
and practical process for a targeted product. We then develop optimized biocatalysts to enable the designed process, using our
CodeEvolver® platform. Engineered biocatalyst candidates, numbering many thousands for each project, are then rapidly
screened and validated using high throughput methods under process-relevant operating conditions. This approach results in an
optimized biocatalyst that enables cost-efficient processes that are relatively simple to run in conventional manufacturing
equipment allowing for efficient technical transfer of our processes to our manufacturing partners. This also allows for efficient
technical transfer of our processes to our manufacturing partners.
The successful embodiment of our CodeEvolver® protein engineering technology platform in commercial manufacturing
processes requires well-integrated expertise in a number of technical disciplines. In addition to those competencies directly
integrated in our CodeEvolver® protein engineering platform, such as molecular biology, enzymology, microbiology, cellular
engineering, metabolic engineering, bioinformatics, biochemistry and high throughput analytical chemistry, our process
development projects also involve integrated expertise in organic chemistry, chemical process development, chemical
engineering, bioprocess development and fermentation engineering. Our integrated, multi-disciplinary approach to product and
process development is a critical success factor for the Company.
We initially commercialized our CodeEvolver® protein engineering technology platform and products in the manufacture
of small molecule pharmaceuticals, which remains a primary business focus. Our customers, which include many large, global
pharmaceutical companies, use our technology, products and services in their process development and in manufacturing.
Additionally, we have licensed our proprietary CodeEvolver® protein engineering technology platform to global pharmaceutical
companies enabling them to use this technology, in house, to engineer enzymes for their own businesses. In May 2019, we
entered into a Platform Technology Transfer and License Agreement (the “Novartis CodeEvolver® Agreement”) with Novartis
Pharma AG (“Novartis”). The Novartis CodeEvolver® Agreement (Codexis’ third such agreement with large pharma
companies) allows Novartis to use our proprietary CodeEvolver® protein engineering platform technology in the field of human
healthcare.
As evidence of our strategy to extend our technology beyond pharmaceutical manufacturing, we have also used the
technology to develop biocatalysts and enzyme products for use in a broader set of industrial markets, including several large
verticals, such as food, feed, consumer care and fine chemicals. In addition, we are using our technology to develop enzymes
for various life science related applications, such as next generation sequencing (“NGS”), DNA and RNA synthesis and other
molecular biology research applications. In December 2019, we entered into a license agreement to provide Roche Sequencing
Solutions, Inc. ("Roche") with our first enzyme for this target market: the Company’s EvoT4™ DNA ligase. In June 2020, we
entered into a co-marketing and enzyme supply collaboration agreement with Alphazyme LLC for the production and co-
marketing of enzymes for life science applications including, initially, high-fidelity DNA polymerase, T7 RNA polymerase and
reverse transcriptase enzymes. In June 2020, we also entered into a Master Collaboration and Research Agreement with
Molecular Assemblies, Inc. ("MAI") (the “MAI Agreement”) pursuant to which we are leveraging our CodeEvolver® platform
4
technology to improve the DNA polymerase enzymes that are critical for enzymatic DNA synthesis. We anticipate completing
an enzyme engineering project with MAI in the first quarter of 2022.
We have been using the CodeEvolver® protein engineering technology platform to develop early stage, novel
biotherapeutic product candidates, both in partnership with customers and for our own proprietary Codexis drug candidates.
Our first program was for the potential treatment of phenylketonuria ("PKU") in humans. PKU is an inherited metabolic
disorder in which the enzyme that converts the essential amino acid phenylalanine into tyrosine is deficient. In October 2017,
we entered into a Global Development, Option and License Agreement (the “Nestlé License Agreement”) with Societé des
Produits Nestlé S.A., formerly known as Nestec Ltd. (“Nestlé Health Science”) to advance CDX-6114, our enzyme
biotherapeutic product candidate for the potential treatment of PKU. In February 2019, Nestlé Health Science exercised its
option to obtain an exclusive license to develop and commercialize CDX-6114. Also in October 2017, we entered into a
strategic collaboration agreement with Nestle Health Science (“Nestlé SCA”) pursuant to which we and Nestlé Health Science
are collaborating to leverage the CodeEvolver® platform technology to develop other novel enzymes for Nestlé Health
Science’s established Consumer Care and Medical Nutrition business areas.
In March 2020, we entered into a Strategic Collaboration and License Agreement (“Takeda Agreement”) with Shire Human
Genetic Therapies, Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited (“Takeda”), for the research
and development of novel gene therapies for certain disease indications, including the treatment of lysosomal storage disorders
and a blood factor deficiency.
BUSINESS SEGMENTS
We manage our business as two business segments: Performance Enzymes and Novel Biotherapeutics. See Note 15,
“Segment, Geographical and Other Revenue Information” in the Notes to the Consolidated Financial Statements set forth in
Item 8 of this Annual Report on Form 10-K.
Performance Enzymes
We initially commercialized our CodeEvolver® protein engineering technology platform and products in the manufacture
of small molecule pharmaceuticals and, to date, this continues to be our largest market served. Our customers, which include
many large global pharmaceutical companies, use our technology, products and services in their manufacturing processes and
process development. We have also used the technology to develop customized enzymes for use in other industrial markets.
These markets consist of several large industrial verticals, including food, feed, consumer care, and fine chemicals. We also use
our technology in the life sciences markets to develop enzymes for customers using NGS and PCR/qPCR for in vitro molecular
diagnostic and molecular biology research applications, as well DNA/RNA synthesis and health monitoring applications.
Novel Biotherapeutics
We are also targeting new opportunities in the pharmaceutical industry to discover, improve, and/or develop biotherapeutic
drug candidates. We believe that our CodeEvolver® protein engineering platform technology can be used to discover novel
biotherapeutic drug candidates that will target human diseases that are in need of improved therapeutic interventions. Similarly,
we believe that we can deploy our platform technology to improve specific characteristics of a customer’s pre-existing
biotherapeutic drug candidate, such as its activity, stability or immunogenicity. Our first lead program was for the potential
treatment of hyperphenylalaninemia (“HPA”) (also referred to as PKU) in humans. PKU is an inherited metabolic disorder in
which the enzyme that converts the essential amino acid phenylalanine into tyrosine is deficient. In October 2017, we
announced a global development, option and license agreement with Nestlé Health Science to advance CDX-6114, our own
novel orally administrable enzyme therapeutic candidate for the potential treatment of PKU. In July 2018, we announced that
we had dosed the first subjects in a first-in-human Phase 1a dose-escalation trial with CDX-6114, which was conducted in
Australia. The initiation of the trial triggered a $4.0 million milestone payment from Nestlé Health Science. The $1.0 million
milestone payment that was triggered by the achievement of a formulation relating to CDX-6114 was received in February
2019. In January 2019, we received notice from the U.S. Food and Drug Administration ("FDA") that it had completed its
review of our investigational new drug application ("IND") for CDX-6114 and concluded that we may proceed with the
proposed Phase 1b multiple ascending dose study in healthy volunteers in the United States. In February 2019, Nestlé Health
Science exercised its option to obtain an exclusive, worldwide, royalty-bearing, sub-licensable license for the global
development and commercialization of CDX-6114 for the management of PKU. As a result of the option exercise, we earned a
milestone and recognized $3.0 million in revenues in the first quarter of 2019. Upon exercising its option, Nestlé Health
Science assumed all responsibilities for future clinical development and commercialization of CDX-6114.
5
In October 2017, we separately entered into the Nestlé SCA with Nestlé Health Science pursuant to which we and Nestlé
Health Science are collaborating to leverage the CodeEvolver® platform technology to develop other novel enzymes for Nestlé
Health Science’s established Consumer Care and Medical Nutrition business areas. The term of the Nestlé SCA has been
extended through December 2022.
In January 2020, we and Nestlé Health Science entered into a development agreement pursuant to which we and Nestlé
Health Science are collaborating to advance CDX-7108, a lead candidate targeting a gastrointestinal disorder, discovered
through the Nestlé SCA, into preclinical and early clinical studies. During 2021, we, together with Nestlé Health Science,
continued to advance CDX-7108 towards initiation of a Phase 1 clinical trial with the first subject being dosed in November
2021.
In March 2020, we entered into the Takeda Agreement with Takeda pursuant to which we are collaborating to research and
develop protein sequences for use in gene therapy products for certain disease indications in accordance with the respective
program plans for Fabry Disease, Pompe Disease, and an undisclosed blood factor deficiency. In March 2020, we received a
one-time, non-refundable cash payment of $8.5 million. Of these programs, the Fabry disease program is the most advanced,
with multiple sequences, including CDX-6311, which were provided to Takeda. We also provided sequences to Takeda for the
Pompe program. In May 2021, Takeda elected to exercise their option to initiate an additional program for a certain undisclosed
rare genetic disorder and we received the option exercise fee during the third quarter of 2021.
RECENT DEVELOPMENT - PFIZER (PAXLOVID™)
In the first and second quarters of 2021, we began to receive purchase orders from Pfizer, Inc. (“Pfizer”) for large
quantities of our proprietary enzyme product, CDX-616, for use by Pfizer in the manufacture of a critical intermediate for its
proprietary active pharmaceutical ingredient, nirmatrelvir. Pfizer markets, sells and distributes nirmatrelvir, in combination with
the active pharmaceutical ingredient ritonavir, as its PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) product, which
received emergency use authorization by the U.S. Food and Drug Administration (“FDA”) in late 2021 for the treatment of
COVID-19 in humans.
In 2021, we recognized approximately $34.5 million in revenue from the sale of quantities of CDX-616 to Pfizer. In
addition, as of December 31, 2021, we have received additional purchase orders from Pfizer for delivery of a significant
quantity of CDX-616 in 2022. We have received and currently expect to receive additional purchase orders from Pfizer for
significant quantities of CDX-616 during the course of 2022 for delivery in 2022 and 2023. As of December 31, 2021, we have
not yet executed a long-term purchase and sale agreement with Pfizer for CDX-616; with or without a long-term purchase and
sale agreement, we currently expect that future orders for quantities of CDX-616 by Pfizer will continue to be based on the
needs of Pfizer for quantities of CDX-616 and there will be no minimum purchase obligation on the part of Pfizer.
BUSINESS UPDATE REGARDING COVID-19
We are subject to risks and uncertainties as a result of the current COVID-19 pandemic. The COVID-19 pandemic has
presented a substantial public health and economic challenge around the world and is affecting our employees, communities
and business operations, as well as the U.S. economy and other economies worldwide. The full extent to which the COVID-19
pandemic will directly or indirectly impact our business, results of operations and financial condition will depend on future
developments that are highly uncertain and may not be accurately predicted, including the duration and severity of the
pandemic, the prevalence of more contagious and or virulent variants such as the Delta and Omicron variants, and the extent
and severity of the impact on our customers, new information that may emerge concerning COVID-19, the actions taken to
contain it or treat its impact and the economic impact on local, regional, national and international markets.
In the United States, the impact of COVID-19, including governmental orders (“Orders”) governing the operation of
businesses during the pandemic, caused the temporary closure of our Redwood City, California facilities in 2020 and disrupted
our R&D operations. R&D operations for several projects were temporarily suspended from mid-March 2020 through the end
of April 2020 in accordance with these Orders. In May 2020, we re-initiated limited R&D operations and have ramped up
operations such that we are currently utilizing our normal R&D capacity while following county, state and federal COVID-19
guidance for the protection of our employees. Additionally, we resumed manufacturing at our Redwood City pilot plant in May
2020.
To date, we and our collaboration partners have been able to continue to supply our enzymes to our customers worldwide.
However, we are dependent on our manufacturing and logistics partners and consequently, disruptions in operations of our
partners and customers may affect our ability to supply enzymes to our customers. Furthermore, our ability to provide future
research and development (“R&D”) services will continue to be impacted as a result of governmental orders and any
disruptions in operations of our customers with whom we collaborate. We believe that these disruptions have had a minimal
6
impact on our revenue for the year ended December 31, 2021. The extent to which the pandemic may impact our business
operations and operating results will continue to remain highly dependent on future developments, which are uncertain and
cannot be predicted with confidence.
Our future results of operations and liquidity could be adversely impacted by delays in payments of outstanding receivable
amounts beyond normal payment terms, supply chain disruptions and uncertain demand, and the impact of any initiatives or
programs that we may undertake to address financial and operations challenges faced by our customers. The near-and-long term
impact of COVID-19 to our financial condition, liquidity, or results of operations remains uncertain. Although some of the
Orders that were enacted to control the spread of COVID-19 have begun to be scaled back and the vaccine rollout has
expanded, surges in the spread of COVID-19 due to the emergence of new more contagious or virulent variants or the
ineffectiveness of the vaccines against such strains, may result in the reimplementation of certain Orders, which could adversely
impact our business. The extent to which the COVID-19 pandemic may materially impact our financial condition, liquidity, or
results of operations in the future is uncertain.
As a result of the COVID-19 pandemic we have received purchase orders from Pfizer for large quantities of our proprietary
enzyme product, CDX-616, for use by Pfizer in the manufacture of a critical intermediate for its proprietary active
pharmaceutical ingredient, nirmatrelvir, used by Pfizer in combination with the active pharmaceutical ingredient ritonavir, as its
PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) product for the treatment of COVID-19 infections in humans. These
purchase orders have had a substantial impact on our revenue in 2021.
For additional information on the various risks posed by the COVID-19 pandemic, see “Risk Factors” set forth in Item 1A
of this Annual Report on Form 10-K.
OUR STRATEGY
Our strategy is to grow our revenues, profits, and stockholder value by leveraging our CodeEvolver® protein engineering
technology platform in the following ways:
Licensing our CodeEvolver® protein engineering technology platform. We intend to continue to pursue opportunities
•
to license our CodeEvolver® protein engineering technology platform to third parties so they can create cost-saving
biocatalyst solutions utilizing their own in-house protein engineering capability.
• Growing our pharmaceutical biocatalysts business. We intend to continue to pursue opportunities in the
pharmaceutical market to use our protein catalysis products and services to reduce the costs for manufacturing small
molecule drugs. We intend to increase the number of pharmaceutical customers and processes that utilize and benefit from
our novel, cost-saving biocatalyst solutions.
• Creating and advancing novel biotherapeutic drug candidates. We intend to continue to pursue opportunities to apply
our protein engineering capabilities to the creation and development of novel biotherapeutic drug candidates, both in
partnership with customers and as proprietary Codexis drug candidates. We have also invested in research and development
in an effort to generate additional early stage novel biotherapeutic candidates.
• Extending our biocatalysts and industrial enzymes business into new markets. We intend to continue to pursue
opportunities to use biocatalyst products and services to reduce the costs and improve sustainability for manufacturing in
markets such as food and food ingredients. We intend to increase the number of customers and industrial verticals that
utilize and benefit from our novel performance enzyme solutions.
• Developing high-performance enzymes for use in diagnostic applications. We intend to offer high-performance
enzymes to customers using NGS and PCR/qPCR for in vitro molecular diagnostic applications.
In this Annual Report, the “Company,” “we,” “us” and “our” refer to Codexis, Inc. and its subsidiaries on a consolidated
basis.
OUR MARKET OPPORTUNITIES
Pharmaceutical Market
We believe the pharmaceutical industry represents a significant market opportunity for us and is our primary business
focus. Pharmaceutical companies are in constant search for new drugs to offer to their customers, and are under significant
competitive pressure both to reduce costs and to increase the speed to market for their products. To meet these pressures,
pharmaceutical companies are discovering and developing novel protein-based drug products, as well as seeking manufacturing
processes for their new and existing drugs that reduce overall costs, simplify production and increase efficiency and product
yield, while not affecting drug safety and efficacy. Cost reduction is even more important to developers (known as innovators)
7
of patent-protected pharmaceutical products when the patents for those products expire and such innovators are forced to
compete with manufacturers of generic drugs.
The pharmaceutical product lifecycle begins with the discovery of new chemical entities and continues through preclinical
and clinical development, regulatory review and approval, commercial scale-up, product launch, and, ultimately, patent
expiration and the transition from branded to generic products. As innovators develop, produce and then market products,
manufacturing priorities and processes evolve. Historically, innovators have focused on production cost reduction in the later
stages of clinical development and have been reluctant to make process changes after a product has been launched. However, as
pressures to reduce costs have increased, innovators have pursued cost reduction measures much earlier in the pharmaceutical
product lifecycle and are increasingly looking for opportunities to improve their operating margins, including making
manufacturing process changes for marketed products after the products have been launched if these changes can result in
significant cost reductions. As a result, innovators are investing in new technologies, including our CodeEvolver® protein
engineering technology platform, to improve their manufacturing productivity and efficiency or outsourcing the manufacture of
their intermediates and active pharmaceutical ingredients ("API").
Our Solutions for the Pharmaceutical Market
Small Molecule Manufacturing Cost Reduction
Our pharmaceutical customers, which include many large global pharmaceutical companies, use our technology, products
and services in their manufacturing processes and process development. Our CodeEvolver® protein engineering technology
platform enables us to deliver solutions to our customers in this market by developing and delivering optimized biocatalysts
that perform chemical transformations at a lower cost and improve the efficiency and productivity of manufacturing processes.
We provide value throughout the pharmaceutical product lifecycle. Our products and services allow us to provide benefits to
our pharmaceutical customers in a number of cost saving ways, including any - and sometimes all - of the following:
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reducing the use of raw materials and reagents;
eliminating multiple steps in the manufacturing process;
improving purity, productivity and yield;
using water as a primary solvent;
eliminating hazardous inputs;
enabling the use of simple equipment and reducing the need for capital expenditure;
reducing energy requirements;
reducing the generation of chemical byproducts or waste; and
reducing the need for late-stage purifications.
Early in a pharmaceutical product’s lifecycle, pharmaceutical manufacturers can use our biocatalyst products and services
to reduce manufacturing costs. If an innovator incorporates our products or processes into an approved product, we expect the
innovator to continue to use our products or processes at least over the patent life of the marketed drug.
Pharmaceutical manufacturers can also use our products and services to reduce manufacturing costs after a product is
launched. At this stage, changes in the manufacturing process originally approved by the drug regulator may require additional
regulatory review. Typically, pharmaceutical companies will only seek regulatory approval for a manufacturing change if
substantial cost savings are realizable. We believe that the cost savings associated with our products may lead our customers to
change their manufacturing processes for approved products and, if necessary, seek regulatory approval of the new processes
which incorporate our biocatalyst products. Moreover, we believe these cost savings are potentially attractive to generics
manufacturers, who compete primarily on price.
In addition, manufacturing processes that utilize our biocatalysts can frequently enable processes that are more sustainable
and environmentally friendly compared to alternative, traditional manufacturing approaches. This has led us to earn three U.S.
EPA Presidential Green Chemistry Challenge awards for improved pharmaceutical manufacturing processes since we were
founded. All three of these awards were associated with blockbuster drug products.
Licensing Our CodeEvolver® Protein Engineering Technology Platform
Licensing our CodeEvolver® protein engineering technology platform to pharmaceutical companies enables them to
rapidly develop custom-designed enzymes that are highly optimized for efficient manufacturing processes. To date, we have
entered into platform technology licensing agreements with each of GlaxoSmithKline Intellectual Property Development
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Limited, a subsidiary of GlaxoSmithKline plc ("GSK"), Merck, Sharp & Dohme ("Merck") and Novartis Pharma AG
("Novartis"), and we intend to continue to enter into license arrangements with third parties that will allow them to use our
CodeEvolver® protein engineering technology platform to discover and develop novel proteins for their internal use.
GlaxoSmithKline
We entered into our first CodeEvolver® protein engineering Platform Technology Transfer, Collaboration and License
Agreement (“GSK CodeEvolver® Agreement”) in July 2014 with GlaxoSmithKline Intellectual Property Development Limited,
a subsidiary of GSK, pursuant to which we granted GSK a non-exclusive, worldwide license to use our CodeEvolver® protein
engineering technology platform in the field of human healthcare for its internal development purposes.
Under the GSK CodeEvolver® Agreement, we licensed and transferred our certain patents, patent applications and know-
how from our CodeEvolver® protein engineering technology platform to GSK, completing the transfer in April 2016. Under this
agreement, we have the potential to receive contingent payments that range from $5.75 million to $38.5 million per project
based on GSK's successful application of the licensed technology. We are also eligible to receive royalties based on net sales, if
any, of a limited set of products developed by GSK using our CodeEvolver® protein engineering technology platform.
The term of the GSK CodeEvolver® Agreement continues, unless earlier terminated, until the expiration of all payment
obligations under the GSK CodeEvolver® Agreement. GSK can terminate the GSK CodeEvolver® Agreement by providing 90
days written notice to us.
In 2019, we received a $2.0 million milestone payment on the advancement of an enzyme developed by GSK using our
CodeEvolver® protein engineering platform technology. In 2021, we received two additional milestone payments from GSK
under the GSK CodeEvolver® Agreement.
Merck
In August 2015, we entered into a CodeEvolver® Platform Technology Transfer and License Agreement (the “Merck
CodeEvolver® Agreement”) with Merck. The Merck CodeEvolver® Agreement allows Merck to use our proprietary
CodeEvolver® protein engineering platform technology in the field of human and animal healthcare.
Under the terms of the Merck CodeEvolver® Agreement, we granted to Merck an exclusive license under certain patents,
patent applications and know-how from our CodeEvolver® protein engineering technology platform for the research,
development and manufacture of novel enzymes for use by Merck in the chemical synthesis of therapeutic products owned or
controlled by Merck ("Merck Exclusive Field") and a non-exclusive worldwide license to use the CodeEvolver® protein
engineering technology platform to research, develop and manufacture novel enzymes for use by Merck in its internal research
programs (“Merck Non-Exclusive Field”).
Under the terms of the Merck CodeEvolver® Agreement, Merck paid us upfront technology transfer and license fees and
milestone payments over the technology transfer period of 15 months from August 2015. We also have the potential to receive
product-related payments of up to $15.0 million for each API that is manufactured by Merck using one or more enzymes that
have been developed or are in development using the CodeEvolver® protein engineering technology platform during the 10-
year period that begins on the conclusion of the 15-month technology transfer period. These product-related payments, if any,
will be paid by Merck to us for each quarter that Merck manufactures API using a CodeEvolver®-developed enzyme. The
payments will be based on the total volume of API produced using the CodeEvolver®-developed enzyme.
In September 2016, we completed the full transfer of the engineering platform technology. In October 2018, we entered
into an amendment to the Merck CodeEvolver® Agreement whereby we amended certain licensing provisions and one exhibit.
In January 2019, we entered into an amendment to the Merck CodeEvolver® Agreement whereby we installed certain
CodeEvolver® protein engineering technology upgrades into Merck’s platform license installation. We maintained those
upgrades for a multi-year term that expired in January 2022.
Novartis
In May 2019, we entered into a Platform Technology Transfer and License Agreement (the “Novartis CodeEvolver®
Agreement”) with Novartis. The Novartis CodeEvolver® Agreement allows Novartis to use our proprietary CodeEvolver®
protein engineering platform technology in the field of human healthcare.
Under the terms of the Novartis CodeEvolver® Agreement, Codexis granted to Novartis a worldwide license to use certain
patents, patent applications and know-how from our CodeEvolver® protein engineering technology platform to research,
develop and manufacture novel enzymes for use by or on behalf of Novartis as biocatalysts in the chemical synthesis of small
molecule and bioconjugate active pharmaceutical ingredients (“API”). The license is exclusive for the research, development
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and manufacture of novel enzymes for use by Novartis as biocatalysts in the chemical synthesis of API owned or controlled by
Novartis (“Novartis Exclusive Field”) and non-exclusive license for the research, development and manufacture of novel
enzymes for use by Novartis in the chemical synthesis of API not owned or controlled by Novartis or any third party (“Novartis
Non-Exclusive Field”).
In July 2021, we announced the completion of the technology transfer period during which we transferred our proprietary
CodeEvolver® platform technology to Novartis (the “Technology Transfer Period”).
Pursuant to the Novartis CodeEvolver® Agreement, we received an upfront payment of $5.0 million shortly after the
effective date. We completed the second technology milestone transfer under the agreement and received a milestone payment
of $4.0 million in 2020. We have also received an aggregate of $5.0 million for the completion of the third technology transfer
milestone in 2021.
In consideration for the continued disclosure and license of improvements to the technology and materials during a multi-
year period that began on the conclusion of the Technology Transfer Period (“Improvements Term”), Novartis will pay us
annual payments over four years which amount to an additional $8.0 million in aggregate. We also have the potential to receive
quantity-dependent, usage payments for each API that is manufactured by Novartis using one or more enzymes that have been
developed or are in development using the CodeEvolver® platform technology during the period that began on the conclusion
of the Technology Transfer Period and ends on the expiration date of the last to expire licensed patent. These product-related
usage payments, if any, will be paid by Novartis to Codexis for each quarter that Novartis manufactures API using a
CodeEvolver ® -developed enzyme.
The licenses to Novartis are granted under patents, patent applications and know-how that Codexis owns or controls as of
the effective date and that cover the CodeEvolver® platform technology. Any improvements to the CodeEvolver® platform
technology during the Technology Transfer Period will also be included in the license grants from Codexis to Novartis.
See also "Recent Development - Pfizer (PAXLOVID™)" above for information on our relationship with Pfizer.
Biotherapeutic Discovery and Development Partnerships
We are also targeting new opportunities in the pharmaceutical industry to discover or improve biotherapeutic drug
candidates for our customers. We believe that our CodeEvolver® protein engineering platform technology can be used to
discover novel biotherapeutic drug candidates that will target human diseases that are in need of improved therapeutic
interventions. Similarly, we believe that we can deploy our platform technology to improve specific characteristics of a
customer’s pre-existing biotherapeutic drug candidate, such as its activity, stability or immunogenicity.
We approach biopharmaceutical companies to collaborate and utilize our platform technology for the discovery of specific
novel biotherapeutic candidates. We currently have one such biotherapeutic discovery partnership in progress under the Nestlé
SCA with Nestlé Health Science and another discovery partnership in progress under the Takeda Agreement with Takeda. We
continue to pursue other partners who could benefit by the application of our CodeEvolver® protein engineering platform
technology to improve the discovery and/or development of other biotherapeutics in partnership with us.
Biotherapeutic Product Discovery and Development
We are also using our platform technology to self-fund the development of our own early stage, novel enzyme therapeutic
product candidates. The first product candidate that resulted from this is CDX-6114, an enzyme which we have engineered to
be orally administered and is being developed by Nestlé Health Science as a potential treatment of PKU in humans. PKU is an
inborn metabolic disorder in which the enzyme that converts the essential amino acid phenylalanine into tyrosine is deficient.
As a result, phenylalanine accumulates to toxic levels in the brain, causing serious neurological problems including intellectual
disability, seizures and cognitive and behavioral problems. To avoid toxic levels of phenylalanine in their blood, individuals
with PKU must follow a strict, life-long diet that is low in phenylalanine and supplement their diet with a synthetic
phenylalanine-free formula to provide them with sufficient nutrients. Maintaining a strict, life-long diet can be challenging for
individuals with PKU. There are an estimated 50,000 people with PKU in the developed world.
Our self-funded biotherapeutic investments aim to discover therapeutic solutions for five additional rare disease conditions.
Two of those programs are targeting potential enzyme substitution treatments for patients with inborn errors of amino acid
metabolism diseases.
CDX-6512 is an orally administrable enzyme substitution therapy candidate in IND-enabling studies for potential treatment
of homocystinuria (HCU). The U.S. Food and Drug Administration (FDA) has granted the company orphan drug designation
(ODD) and rare pediatric disease (RPD) designation for CDX-6512 for the treatment of HCU, an inborn metabolic disorder
most commonly due to cystathionine beta-synthase (CBS) deficiency. CBS is an enzyme involved in the metabolism of
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homocysteine, a methionine metabolite. As a result, methionine and/or homocysteine accumulate to toxic levels, that may lead
to learning and intellectual disabilities, cardiovascular disease, osteoporosis, and stroke. To prevent blood levels of methionine
and/or homocysteine to become toxic, individuals with HCU must follow a strict, life-long diet that is low in methionine and
supplement their diet with a synthetic methionine-free formula to provide them with sufficient nutrients. Maintaining a strict,
life-long diet can be challenging for individuals with HCU. World-wide about 1 in 150,000 people has HCU due to either a
CBS or an MTHFR gene mutation. HCU is listed on the Recommended Uniform Screening Panel of disorders recommended by
the Secretary of the Department of Health and Human Services for states to screen as part of their universal newborn screening
programs.
CDX-6210 is an orally administrable enzyme substitution therapy lead for potential treatment of Maple Syrup Urine
Disease (MSUD). MSUD is an inborn metabolic disorder in which the branched-chain keto acid dehydrogenase enzyme that is
involved in the metabolism of branched-chain amino acids such as leucine, isoleucine, and valine, is deficient. As a result, these
amino acids and their ketoacid metabolites accumulate to toxic levels, that can lead to intellectual and developmental
disabilities. To prevent blood levels of these amino acids and their metabolites to become toxic, individuals with MSUD must
follow a strict, life-long diet that is low in branched-chain amino acids and supplement their diet with a synthetic branched-
chain amino acids-free formula to provide them with sufficient nutrients. Maintaining a strict, life-long diet can be challenging
for individuals with MSUD. According to the Genetic and Rare Disease Information Center (GARD), about 1 in 150,000-
185,000 people is born with MSUD. MSUD is listed on the Recommended Uniform Screening Panel of disorders
recommended by the Secretary of the Department of Health and Human Services for states to screen as part of their universal
newborn screening programs.
Our discovery program target a potential enzyme therapy for gluten management and potential treatments for patients with
lysosomal storage diseases, via a specific novel transgene, or via a new AAV technology. We expect to continue to make
additional investments with the aim of generating additional product candidates targeting these, and potentially other
therapeutic areas.
Nestlé Health Science
In October 2017, we entered into the Nestlé License Agreement with Nestlé Health Science pursuant to which we granted
to Nestlé Health Science, under certain of our patent rights and know-how: (i) an option to obtain an exclusive, worldwide,
royalty-bearing, sublicensable license to develop and commercialize certain products (each, a “Product”) based on CDX-6114
and our other therapeutic enzyme product candidates covered by specified patent applications for the treatment of HPA (also
referred to as PKU), and (ii) an exclusive right of first negotiation (the “Right of First Negotiation”) for a period of five years to
obtain an exclusive worldwide license to develop and commercialize up to two enzymes discovered by us for use in the field of
the prevention, diagnosis, treatment and management of inborn errors of amino acid metabolism. We are not under any
obligation to undertake any research and development activities relating to inborn errors of amino acid metabolism. HPA is a
medical condition characterized by elevated concentrations of the amino acid phenylalanine in the blood. PKU can result in
severe HPA.
In February 2019, Nestlé Health Science exercised its option to obtain an exclusive, worldwide, royalty-bearing, sub-
licensable license for the global development and commercialization of CDX-6114 for the management of PKU.
Upon exercising its option, Nestlé Health Science assumed all responsibilities for future clinical development and
commercialization of CDX-6114, with the exception of the completion of an extension study, CDX-6114-004, which was
substantially completed in the fourth quarter of 2019. The parties established a patent committee to discuss strategies and
coordinate activities for the patents related to CDX-6114 and product containing CDX-6114, and we will jointly own all
inventions and information that result from each party’s activities performed under the Nestlé License Agreement. The Nestlé
License Agreement also contains customary representations and warranties by the parties, intellectual property protection
provisions, certain indemnification rights in favor of each party and customary confidentiality provisions and limitations of
liability.
We are also eligible to receive payments from Nestlé Health Science under the Nestlé License Agreement that include (i)
development and approval milestones of up to $85.0 million, (ii) sales-based milestones of up to $250.0 million in the
aggregate, which aggregate amount is achievable if net sales exceed $1.0 billion in a single year, and (iii) tiered royalties, at
percentages ranging from the mid-single digits to low double-digits, of net sales of products.
In October 2017, we entered into the Nestlé SCA pursuant to which we and Nestlé Health Science are collaborating to
leverage the CodeEvolver® protein engineering technology platform to develop novel enzymes for Nestlé Health Science’s
established Consumer Care and Medical Nutrition business areas. The term of the Nestlé SCA has been extended through
December 2022.
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In January 2020, we entered into a development agreement with Nestlé Health Science pursuant to which we and Nestlé
Health Science are collaborating to advance CDX-7108 into preclinical and early clinical studies. CDX-7108 is the lead
candidate targeting exocrine pancreatic insufficiency discovered under the Nestlé SCA. During 2021, we, together with Nestlé
Health Science, continued to advance CDX-7108 towards initiation of a Phase 1 clinical trial with the first subject being dosed
in November 2021. Additionally, the parties are progressing one orally administered enzyme therapy program under the Nestlé
SCA targeting a gastrointestinal disorder.
Shire Human Genetic Therapies/Takeda Pharmaceutical
In March 2020, we entered into the Takeda Agreement with Takeda pursuant to which we are collaborating to research and
develop protein sequences for use in gene therapy products for certain diseases (each, a “Field”) in accordance with each
applicable program plan (each, a “Program Plan”). On execution of the Takeda Agreement, we received an upfront
nonrefundable cash payment of $8.5 million and we initiated activities under three Program Plans for Fabry Disease, Pompe
Disease, and an undisclosed blood factor deficiency, respectively (the “Initial Programs”). We are primarily responsible for the
research and development of protein sequences under the Program Plans (the “Protein Sequences”) and we are eligible to earn
up to $10.5 million of research and development fees and preclinical milestone payments for the Initial Programs. Takeda has
the right, but not the obligation, to develop, manufacture and commercialize gene therapy products that include nucleic acid
sequences that encode the protein sequences (“products”) at their expense. Takeda has the right to a certain number of
additional disease indications (“Reserved Target Indications”) for a limited time period during which Takeda may initiate a
Program Plan for one or more Reserved Target Indications (“Additional/Option Program,” with Initial Programs, the
“Programs”), provided, (a) if Takeda elects to initiate an Additional/Option Program while the parties are collaborating on three
other Programs at the time of such election, or (b) if Takeda elects to initiate an Additional/Option Program using the last
remaining Reserved Target Indication, then Takeda must pay us an option exercise fee to initiate such Additional/Option
Program. We will own all rights to the protein sequences and corresponding nucleic acid sequences and related intellectual
property rights and Takeda will own all rights to products and related intellectual property rights. In May 2021, Takeda elected
to exercise their option to initiate an additional program for a certain undisclosed rare genetic disorder; as a result we received
the option exercise fee during the third quarter of 2021. We are also eligible to receive up to $8.3 million of research and
development fees and preclinical milestone payments for the fourth program under the Takeda Agreement.
We granted to Takeda an exclusive, worldwide, royalty-bearing, sublicensable license to use the protein sequences and
their corresponding nucleic acid sequences to develop, manufacture and commercialize the applicable products in the
applicable Field. We also granted to Takeda a limited non-exclusive, worldwide, sublicensable license (a) to research the protein
sequences within or outside the applicable Fields and (b) to research the products outside of the applicable Fields, which such
rights exclude Takeda's right to perform any Investigational New Drug-enabling activities. The licenses to research the Protein
Sequences expire after a pre-determined period of time.
The term of the Takeda Agreement begins on the effective date of the Takeda Agreement and continues on a product-by-
product and country-by-country basis, until the expiration of Takeda’s obligation to pay royalties to the Company with respect
to that product in that country. The Takeda Agreement expires in its entirety upon the expiration of Takeda’s obligation to pay
royalties to the Company with respect to the products in all countries worldwide. Subject to the terms of the Takeda Agreement,
and after the first anniversary of the Effective Date with respect to the Initial Programs or after the first anniversary of
confirmation of the applicable Program Plan by the parties with respect to the Additional/Option Programs, Takeda may
terminate a Program upon specified prior written notice to the Company. Subject to the terms of the Takeda Agreement, Takeda
may terminate the Takeda Agreement, at will, on a product-by-product basis upon specified prior written notice to the Company
and the Takeda Agreement in its entirety upon specified prior written notice to the Company. Subject to the terms of the Takeda
Agreement, Takeda may terminate the Takeda Agreement on a product-by-product basis for safety reasons upon specified prior
written notice to the Company. Either party may terminate the Takeda Agreement for an uncured material breach by the other
party, or the other party’s insolvency or bankruptcy. Pursuant to the Takeda Agreement, we are eligible to receive other
payments that include (i) clinical development and commercialization-based milestones, per target gene, of up to $100.0 million
and (ii) tiered royalty payments based on net sales of applicable products at percentages ranging from the mid-single digits to
low single-digits.
Fine Chemicals and Industrial Enzyme Markets
Beyond the pharmaceutical industry, our CodeEvolver® protein engineering platform technology has enabled cost-savings
for our partners in the fine chemicals markets, and the food industry in particular. In November 2016, we entered into an
exclusive agreement with Tate & Lyle, a market-leading food ingredients company, to supply a proprietary enzyme for use in
Tate & Lyle’s food ingredient production. In March 2017, we entered into a multi-year research and development agreement
with Tate & Lyle for the development of a second ingredient for the food ingredient industry. We engineered a suite of enzymes
that enable Tate & Lyle’s novel bioconversion route for the manufacture of their newly-launched zero-calorie TASTEVA® M
Stevia sweetener. In July 2021, we entered into a multi-year supply agreement with Kalsec to supply an enzyme product for
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use in the production of Kalsec's newest natural hop acid.
We are seeking to expand our enzyme offerings in the fine chemical and industrial enzyme markets within and beyond the
food industry, including, for example, to the animal feed, agricultural chemicals, consumer care, flavors and fragrances markets.
Molecular Biology and In Vitro Diagnostic Enzymes
We believe that our protein engineering capability can also be deployed to commercialize novel enzymes as improvements
to enzymes consumed by customers in many industrial sectors. As our first effort in this strategy, we have developed enzymes
for customers using NGS and PCR/qPCR for in vitro molecular diagnostic applications. In December 2019, we entered into a
license agreement to provide Roche with our EvoT4™ DNA ligase high-performance molecular diagnostic enzyme. This
enzyme was developed using our proprietary CodeEvolver® protein engineering platform and is expected to be incorporated
into Roche’s NGS library preparation kits and other sequencing products. During 2021, we commercialized three additional
enzymes, our Codex® HiFi DNA Polymerase for use in next generation sequencing, our Codex® HiTemp Reverse Transcriptase
for use in molecular diagnostic applications, and our Codex® HiCap RNA Polymerase for use in RNA synthesis applications.
Biocatalyst Products and Services
Our biocatalyst products and services can deliver value to our customers in multiple potential ways:
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manufacture their products at lower cost;
manufacture their products with lower fixed capital investment;
reduce the cost of development of complex chemical synthesis processes;
enable their products to achieve higher product purity;
allow the removal of entire steps from chemical production; and
provide flexibility to apply at any point across their product’s lifecycle.
Our products include biocatalysts, chemical intermediates and Codex® biocatalyst panels and kits. We sell our products
worldwide primarily through our direct sales and business development force in the United States and Europe.
In addition to products, we also offer research and development services to our customers. These research and development
service agreements often contain service fee payments and intellectual property provisions under which we screen and/or
engineer biocatalysts for customers in connection with their process development efforts. In these collaborations, we typically
receive consideration in the form of one or more of the following: upfront payments, milestone payments, payments for
screening and engineering services, licensing fees and royalties.
Biocatalysts
We often sell biocatalysts, by the gram or kilogram, that have already been engineered, scaled up, and installed in a
customer’s commercial process. For example, we sell biocatalysts to Merck for their manufacture of Sitagliptin, the active
ingredient in Januvia®. We also sell biocatalysts which are in developmental stages. These are enzymes that are sold by the
batch or by the gram or kilogram that are in the process of being engineered or scaled up by Codexis, or are in the process of
being trialed or approved for use in the customer’s process. We may sell batches of specific biocatalysts that are in the midst of
protein engineering efforts, in order to test their performance at a larger scale or to accelerate a customer’s process
development. We may also sell batches of specific biocatalysts for use in a customer’s developmental products (for example,
for use in the manufacture of a customer’s Phase 2 drug candidate). Finally, we may sell batches of specific biocatalysts as a
customer performs trials for approval in their commercial manufacturing operations.
Chemical Intermediates
In some cases, we sell intermediate chemicals products that are produced in a process that uses our biocatalysts. These
chemical intermediates are then used by our customer for further chemical processing.
Codex® Biocatalyst Panels and Kits
We sell kits and panels of our biocatalysts. These kits and panels assemble a relevant subset of our engineered enzymes to
enable customers to perform chemistry screening on their own. These kits and panels are organized by specific types of
chemical reactions that are widely applicable in the pharmaceutical and fine chemical markets.
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Biocatalyst Screening Services
If a customer prefers, rather than purchasing our Codex® Biocatalyst Panels or Kits to use for its own screening, it may
send us its starting materials and desired chemical reaction, and we will test against our existing libraries of enzymes on a
research and development service fee basis. If we detect desired activity in a specific enzyme, we can supply the customer with
this enzyme or perform engineering services to improve the performance of the enzyme.
Protein Engineering Services
We work with our customers throughout their product development lifecycle to optimize enzymes that have been
engineered specifically to perform a desired process according to a highly selective set of specifications. We typically charge
customers for research and development services by project or project-month. These are typically larger research and
development service fees than screening services.
The protein engineering process starts by identifying genes that code for enzymes known to have the general type of
catalytic reactivity for a desired chemical reaction. Typically, we identify gene sequences from our extensive in-house
collection or from published databases and then synthesize candidate genes having those sequences. Using a variety of
biotechnology tools, we diversify these genes by introducing mutations, giving rise to changes in the enzymes for which they
encode. The methods for diversifying these genes, and types of diversity being tested, often vary over the course of a protein
engineering program. For finding initial diversity, methods typically include random mutagenesis and site-directed (included
computational structure-guided) mutagenesis. We also test mutational variations from related enzymes found in different
organisms.
Once we have identified potentially beneficial mutations, we create libraries of thousands of variants with combinations of
these mutations. With our proprietary genetic manipulation tools, we generate libraries of genes that have programmed and
random combinations of mutations for testing. The pool of genes is used to transform host cells, which entails introducing the
various genes into host cells. These cells are then grown into colonies. Cells from individual colonies are cultured in high
throughput to produce the enzyme encoded by the genetic variant in those cells. The enzymes expressed by these cells are then
screened in high throughput using test conditions relevant to the desired application. The screening results allow us to identify
and catalog individual genes that produce improved enzymes with beneficial mutations as well as enzymes having detrimental
ones. Using specifically developed test conditions and analytical methods, we can identify variant enzymes that exhibit various
improved performance characteristics, such as stability, activity and selectivity, under conditions relevant to the desired
chemical process.
In the next step in our optimization process, we use our proprietary bioinformatics software to analyze protein sequence-
activity relationships. Our software and algorithms relate the screening results to the mutations and rank the individual and
interacting protein sequence mutations with regard to their degree of benefit or detriment, relative to the process parameter(s)
tested. Using this information, we can create a select pool of mutational diversity in the next iteration to further the
accumulation of beneficial diversity and cancel out detrimental diversity in the individual genes in the resulting library. The
gene that codes for the best performing enzyme in one iteration is used as the starting gene for the next iteration of
recombination and screening. As the enzymes improve over these iterations, the screening conditions are made increasingly
more stringent. In this way, the biocatalyst is rapidly optimized until all in-process performance requirements have been
achieved and the economic objectives for the desired process have been met.
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INTELLECTUAL PROPERTY
Our success depends in large part on our ability to protect our proprietary products and technology under patent, copyright,
trademark and trade secret laws. We also rely heavily on confidential disclosure agreements for further protection of our
proprietary products and technologies. Protection of our technologies is important for us to offer our customers and partners
proprietary services and products that are not available from our competitors, and to exclude our competitors from practicing
technology that we have developed or exclusively licensed from other parties. For example, our ability to supply innovator
pharmaceutical manufacturers depends on our ability to supply proprietary enzymes or methods for making pharmaceutical
intermediates or APIs that are not available from our competitors. Likewise, in the generic pharmaceutical area, proprietary
protection, through patent, trade secret or other protection of our enzymes and methods of producing a pharmaceutical product
is important for us and our customers to maintain a lower cost production advantage over competitors.
As of December 31, 2021, we owned or controlled approximately 1,900 issued patents and pending patent applications in
the United States and in various foreign jurisdictions, many of which are directed to our enabling technologies and specific
methods and products that support our business in the pharmaceutical markets. In addition, our portfolio includes patents and
pending patent applications that support our businesses in the biotherapeutics, molecular diagnostics, food and other markets.
Our patents and pending patent applications, if issued, have terms that expire between 2022 and approximately 2042. Our
United States ("U.S.") patents and pending patent applications directed to the CodeEvolver® proprietary enabling technology
platform developed internally by us have terms that expire between 2029 and approximately 2034. It is possible that some U.S.
patents may be entitled to patent term extensions and/or patent term adjustments, which would extend the protection beyond
these expiration dates. It is also possible that some patents in other jurisdictions will be entitled to additional patent term. Our
current intellectual property rights also include patents, trademarks, copyrights, software and certain assumed contracts that we
acquired from Maxygen, Inc. (“Maxygen”) in October 2010, which are associated with directed evolution technology, known as
the MolecularBreeding™ technology platform developed by Maxygen. The intellectual property rights and assets that we
acquired from Maxygen continue to be subject to existing exclusive and non-exclusive license rights granted by Maxygen to
third parties. We continue to file new patent applications, for which terms generally extend 20 years from the non-provisional
filing date in the United States.
As of December 31, 2021, we owned 100 trademark registrations in the United States and foreign jurisdictions, as well as
many common law trademarks. These include, but are not limited to: Codexis®, Codex®, CodeEvolver®, Mosaic®, Sage®,
Microcyp®, MCYP®, ProSAR®, Unlock the Power of Proteins®, the Codexis Protein Engineering Experts® logo, Strategist™,
Continuity®™, Ameli™, Forager®™, Analogene®™, Harvester®™, Atoms®™, Riptide®™, APS™ and a Codexis design mark
(i.e., the stylized Codexis logo).
COMPETITION
We face differing forms of competition in the small molecule pharmaceuticals, biotherapeutics and fine chemicals markets,
as set forth below.
Small Molecule Pharmaceuticals
We market our biocatalyst products and services to manufacturers of small molecule pharmaceutical intermediates and
APIs. Our primary competitors in that market are companies marketing either conventional, non-enzymatic catalysts or
alternative biocatalyst products and services. We also sometimes face competition from existing in-house technologies (both
biocatalysts and conventional catalysts) within our client and potential client companies. The principal methods of competition
and competitive differentiation in this market are price, product quality and performance, including manufacturing yield, safety
and environmental benefits and speed of delivery of product. Pharmaceutical manufacturers that use biocatalytic processes can
face increased competition from manufacturers that use more conventional processes and/or manufacturers that are based in
regions (such as India and China) with lower regulatory, safety and environmental costs.
The market for the manufacture and supply of APIs and intermediates is large, with many established companies. These
companies include many of our large innovator and generic pharmaceutical customers, such as Merck, GSK, Novartis, Pfizer
Inc. ("Pfizer"), Bristol-Myers Squibb Company ("Bristol-Myers"), KYORIN Pharmaceutical Co., Ltd. ("Kyorin"), Urovant
Sciences GmbH ("Urovant"), and Teva Pharmaceutical Industries Limited ("Teva"), which have significant internal research
and development efforts directed at developing processes to manufacture APIs and intermediates. The processes used by these
companies include classical conventional organic chemistry reactions, chemo-catalytic reactions, biocatalytic reactions or
combinations thereof. Our biocatalyst based manufacturing processes must compete with these internally developed routes.
We also compete with companies developing and marketing conventional catalysts include Solvias AG, BASF, Johnson-
Matthey and Takasago International Corporation.
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The market for supplying enzymes for use in pharmaceutical manufacturing is quite fragmented. There is competition from
large industrial enzyme companies, such as Novozymes and Dupont, as well as subsidiaries of larger contract research/contract
manufacturing organizations (“CRO/CMO”), such as Royal DSM N.V. (“DSM”), Cambrex Corporation, Lonza, WuXi STA and
Almac Group Ltd. Some fermentation pathway design companies, like Ginkgo Bioworks and Zymergen, whose traditional
focus has been to design microorganisms that express small molecule chemicals, could extend into designing organisms that
express enzymes. There is also competition in the enzyme customization and optimization area from several smaller companies,
such as BRAIN AG, Arzeda, c-LEcta GmbH and Evocatal GmbH.
We believe that our principal advantage is our ability to rapidly deliver customized biocatalysts for existing and new
intermediates and APIs in the pharmaceutical manufacturing market. This capability has allowed us to create a breadth of
biocatalysts with improved performance characteristics including, for example, better activity, stability, and activity on a range
of substrates, compared to traditional chemistry-based manufacturing processes and naturally occurring (and thus not
optimized) biocatalysts. We believe that our CodeEvolver® protein engineering platform technology provides substantially
superior results, in shorter time frames, than companies offering competing biocatalyst development services.
Biotherapeutics
There are other companies that participate in the biotherapeutics market generally and the PKU market specifically. Many
of these companies are large, successful and well-capitalized. BioMarin Pharmaceutical Inc. (“BioMarin”) and Daiichi Sankyo
Company market Kuvan® in the United States, Europe and Japan for the treatment of a certain type of PKU. In addition,
BioMarin had gained FDA approval in May 2018 and began the commercial sales of Palynziq®, an injectable enzyme
substitution therapy to address different options for care in the treatment of PKU. Subsequently in May 2019, BioMarin
obtained marketing authorization for Palynziq® from the European Commission. Several companies, including Synlogic,
Homology Medicines and Rubius have reported clinical efforts to develop biotherapeutic candidates for PKU. Beyond targeting
PKU, Takeda, Genzyme / Sanofi S.A., BioMarin, and other companies market or are actively developing enzyme therapeutics.
There are numerous companies that are developing other forms of therapeutics, such as small molecules, gene therapy, as well
as therapies based on gene editing, which could compete with biotherapeutics.
Fine Chemicals
We face similar forms of competition in this market as in the small molecule pharmaceutical markets, with the exception
that the risk of losing opportunities to larger competitors in fine chemicals is greater given the larger scale of opportunities
available in the fine chemicals market compared to the pharmaceutical market. Our significant competitors in the fine
chemicals markets include companies that have been in these marketplaces for many years, such as DuPont Industrial
Biosciences ("DuPont Genencor"), DSM, Novozymes and A.B. Enzymes. These companies have greater resources in these
markets than we do and have long-term supply arrangements already in place with customers. Our ability to compete in these
markets may be limited by our relatively late entrance. We also face competition in both the fine chemicals and small molecule
pharmaceutical markets from emerging companies, like Zymergen and Gingko Bioworks, who offer engineered microbe
metabolic pathway approaches to these markets.
Core Technology
We are a leader in the field of protein engineering to create novel biocatalysts. Both our pharmaceuticals and fine
chemicals businesses rely on our core technology. We are aware that other companies, organizations and persons have
developed technologies that appear to have some similarities to our patented proprietary technologies. For example, we are
aware that other companies, including Zymergen, Gingko Bioworks, Amyris, Absci and Amicus Therapeutics have alternative
methods for obtaining and generating genetic diversity or use mutagenesis techniques to produce genetic diversity. In addition,
academic institutions such as the California Institute of Technology, the Max Planck Institute and the Austrian Centre of
Industrial Biotechnology are also working in this field. This field is highly competitive with companies and academic and
research institutions actively seeking to develop technologies that could be competitive with our technologies.
Technological developments by others may result in our products and technologies, as well as products manufactured by
our customers using our biocatalysts, becoming obsolete. We monitor publications and patents that relate to directed molecular
evolution to be aware of developments in the field and evaluate appropriate courses of action in relation to these developments.
Many of our competitors have substantially greater manufacturing, financial, research and development, personnel and
marketing resources than we do. As a result, our competitors may be able to develop competing and/or superior technologies
and processes, and compete more aggressively and sustain that competition over a longer period of time than we could. Our
technologies and products may be rendered obsolete or uneconomical by technological advances or entirely different
approaches developed by one or more of our competitors.
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OPERATIONS
Our corporate headquarters are located in Redwood City, California and provide general administrative support to our
business and are the center of our research, development and business operations. We have limited internal manufacturing
capacity at our headquarters in Redwood City. We expect to rely on third-party manufacturers for commercial production of our
biocatalysts for the foreseeable future. Our in-house manufacturing is dedicated to producing both Codex® biocatalyst panels
and kits and enzymes for use by our customers in pilot scale production. We also supply initial commercial quantities of
biocatalysts for use by our collaborators to produce pharmaceutical intermediates and manufacture biocatalysts that we sell. In
the first quarter of 2021, we entered into an arrangement to lease a facility in San Carlos, California to serve as an additional
office and research and development laboratory space which we occupied beginning December 2021. Please see Note 15,
“Segment, Geographical and Other Revenue Information” in the Notes to the Consolidated Financial Statements set forth in
Item 8 of this Annual Report on Form 10-K for a description of our revenues and long-lived assets both within and outside of
the United States, and with respect to the San Carlos facility, please see Note 13, “Commitments and Contingencies” in the
Notes to our Consolidated Financial Statements set forth in Item 8 of this Annual Report on Form 10-K.
Our research and development operations include efforts directed towards engineering biocatalysts, bioprocess
development, cellular engineering, biocatalyst screening, metabolites, strain improvement, fermentation development and
process engineering. We conduct enzyme evolution, enzyme production development, microbial bioprocess development,
cellular engineering, microbial evolution and process engineering evaluations and design primarily at our headquarters in
Redwood City, California. Manufacturing of our enzymes is conducted primarily in four locations, at our in-house facility in
Redwood City, California and at third-party contract manufacturing organizations, Lactosan GmbH & Co. KG (“Lactosan”) in
Kapfenberg, Austria, ACS Dobfar S.p.A. ("ACSD") (formerly know as DPhar S.p.A.) in Anagni, Italy, and Alphazyme LLC
("Alphazyme") in Florida, United States. Generally, we perform smaller scale manufacturing in-house and outsource the larger
scale manufacturing and a large percentage of our production of novel enzymes to contract manufacturing organizations.
GOVERNMENT REGULATION
In the United States, the FDA extensively regulates, among other things, the research, development, testing, manufacture,
quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval,
advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of drug and biologic products under
the Federal Food, Drug and Cosmetic Act, its implementing regulations and other laws, including, in the case of biologics, the
Public Health Service Act. Our biotherapeutic product candidates are subject to regulation by the FDA as biologics. Biologics
require the submission of a biologics license application (“BLA”) and licensure, which constitutes approval, by the FDA before
being marketed in the United States. We, along with third-party contractors and our collaborators, will be required to navigate
the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in
which we wish to conduct studies or seek approval or licensure of our product candidates. The process of obtaining regulatory
approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations require the
expenditure of substantial time and financial resources.
The process required by the FDA before a biologic product may be marketed in the United States generally involves the
following:
completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s good laboratory
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practice (“GLP”) regulations;
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submission to the FDA of an IND, which must become effective before clinical trials in the United States may begin;
approval by an institutional review board (“IRB”), or ethics committee at each clinical site before the trial is
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commenced;
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performance of adequate and well-controlled human clinical trials to establish the safety, purity, and potency of the
product candidate for each proposed indication, conducted in accordance with the FDA’s good clinical practice (“GCP”)
regulations;
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•
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preparation and submission to the FDA of a BLA after completion of all pivotal clinical trials:
satisfactory completion of an FDA Advisory Committee review, if applicable;
a determination by the FDA within 60 days of its receipt of a BLA to file the application for review;
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satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is
produced to assess compliance with current good manufacturing practice (“cGMP”) regulations and to assure that the
facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency, and
of selected clinical investigation sites to assess compliance with Good Clinical Practices, or GCPs; and
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FDA review and approval of the BLA prior to any commercial marketing, sale or distribution of the product.
Preclinical and Clinical Trials
Once a product candidate is identified for development, it enters the preclinical testing stage. Preclinical studies include
laboratory evaluations of drug chemistry, formulation and stability, as well as studies to evaluate toxicity in animals, which
must be conducted in accordance with GLP requirements. The results of preclinical studies, together with manufacturing
information and analytical data, are submitted to the FDA as part of an IND. An IND is a request for authorization from the
FDA to administer an investigational new drug to humans. The central focus of an IND submission is on the general
investigational plan and the protocol(s) for clinical studies. The IND automatically becomes effective 30 days after receipt by
the FDA, unless the FDA, within the 30-day time period, raises concerns or questions about the conduct of the clinical trial,
including concerns that human research subjects will be exposed to unreasonable health risks, and imposes a clinical hold. In
such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.
A separate submission to an existing IND must also be made for each successive clinical trial conducted during product
development, and the FDA must grant permission, either explicitly or implicitly by not objecting, before each clinical trial can
begin. Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually
to the FDA and written IND safety reports must be submitted to the FDA and the investigators for serious and unexpected
suspected adverse events, findings from other studies or animal or in vitro testing that suggest a significant risk for human
subjects and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol
or investigator brochure.
Clinical trials involve the administration of the product candidate to human subjects under the supervision of qualified
investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent
for their participation in any clinical study. Clinical trials are conducted under protocols detailing, among other things, the
objectives of the clinical trial and the parameters and criteria to be used in monitoring safety and evaluating effectiveness. Each
protocol must be submitted to the FDA as part of the IND. An independent IRB for each investigator site proposing to
participate in a clinical trial must also review and approve the clinical trial and its informed consent form before it can begin at
that site, and the IRB must monitor the clinical trial until it is completed. The FDA, the IRB, or the sponsor may suspend or
discontinue a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an
unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an
independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which
provides authorization for whether or not a study may move forward at designated check points based on access to certain data
from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other
grounds, such as no demonstration of efficacy. There are also requirements governing the reporting of ongoing clinical studies
and clinical study results to public registries.
For purposes of BLA approval, clinical trials are typically conducted in three sequential phases, which may overlap or be
combined.
• Phase 1 - Phase 1 clinical trials involve initial introduction of the investigational product into healthy human subjects
or patients with the target disease or condition. These studies are typically designed to test the safety, dosage tolerance,
absorption, metabolism and distribution of the investigational product in humans, the side effects associated with
increasing doses, and, if possible, to gain early evidence of effectiveness.
• Phase 2 - Phase 2 clinical trials typically involve administration of the investigational product to a limited patient
population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosage and dosing schedule
and to identify possible adverse side effects and safety risks.
• Phase 3 - Phase 3 clinical trials typically involve administration of the investigational product to an expanded patient
population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for
safety, generally at multiple geographically dispersed clinical trial sites. These clinical trials are intended to establish the
overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval and physician
labeling.
In some cases, the FDA may condition approval of a BLA on the sponsor’s agreement to conduct additional clinical trials
to further assess the biologic’s safety and effectiveness after BLA approval. Such post-approval clinical trials are typically
referred to as Phase 4 clinical trials. Concurrent with clinical trials, companies usually complete additional animal studies and
must also develop additional information about the chemistry and physical characteristics of the biologic and finalize a process
for manufacturing the biologic in commercial quantities in accordance with cGMP requirements. The manufacturing process
must be capable of consistently producing quality batches of the product candidate and manufacturers must develop, among
other things, methods for testing the identity, strength, quality and purity of the final biological product. Additionally,
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appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product
candidate does not undergo unacceptable deterioration over its shelf life.
Although most clinical research performed in the United States in support of a BLA must be authorized in advance by the
FDA, under the IND regulations and procedures described above, there are certain circumstances under which clinical trials can
be conducted without submission of an IND. For example, a sponsor who wishes to conduct a clinical trial outside the United
States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND.
BLA Submission and FDA Review
Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the
results of preclinical studies and clinical trials, together with other detailed information, including extensive manufacturing
information and information on the composition of the biologic, are submitted to the FDA in the form of a BLA requesting
approval to market the biologic for one or more specified indications. The BLA must include all relevant data available from
preclinical and clinical studies, including negative or ambiguous results as well as positive findings, together with detailed
information relating to the product’s chemistry, manufacturing, controls, and proposed labeling, among other things. Data can
come from company-sponsored clinical studies intended to test the safety and effectiveness of a use of the product, or from a
number of alternative sources, including studies initiated by investigators. The submission of a BLA requires payment of a
substantial user fee unless a waiver is granted. Each BLA submitted to the FDA is reviewed for administrative completeness
and reviewability within 60 days of the FDA’s receipt of the application. If the BLA is found to be complete, the FDA will file
the BLA, triggering a full substantive review of the application. The FDA may refuse to file any BLA that it deems incomplete
or not properly reviewable at the time of submission.
Once a BLA has been accepted for filing under the Prescription Drug User Fee Act, the FDA has a goal of reviewing BLAs
within ten months of the 60-day filing date for BLAs designated for standard review or six months for priority review, but the
overall timeframe is often extended by FDA requests for additional information or clarification. The FDA reviews a BLA to
determine, among other things, whether the biological product is safe, pure and potent and whether the facility or facilities in
which it is manufactured meet standards designed to assure the product’s continued safety, purity and potency. The FDA may
refer the application to an advisory committee for review, evaluation and recommendation as to whether the application should
be approved. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such
recommendations.
Before approving a BLA, the FDA will inspect the facility or the facilities at which the biologic product is manufactured,
and will not license the product unless cGMP compliance is satisfactory. The FDA may also inspect the sites at which the
clinical trials were conducted to assess their compliance with GCP requirements, and will not license the biologic unless
compliance with such requirements is satisfactory. If the FDA determines that the application, manufacturing process or
manufacturing facilities are not acceptable, it will outline the deficiencies in the submission and often will request additional
testing or information. Notwithstanding the submission of any requested additional information, the FDA ultimately may decide
that the application does not satisfy the regulatory criteria for approval.
After the FDA evaluates a BLA and conducts inspections of manufacturing facilities where the investigational product
and/or its drug substance will be produced, the FDA may issue an approval letter or a Complete Response Letter (“CRL”). An
approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A
CRL will describe all of the deficiencies that the FDA has identified in the BLA, except that where the FDA determines that the
data supporting the application are inadequate to support approval, the FDA may issue the CRL without first conducting
required inspections, testing submitted product lots, and/or reviewing proposed labeling. In issuing the CRL, the FDA may
recommend actions that the applicant might take to place the BLA in condition for approval, including requests for additional
information or clarification. The FDA may delay or refuse approval of a BLA if applicable regulatory criteria are not satisfied,
require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of
a product.
If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail
limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the BLA with a
Risk Evaluation and Mitigation Strategy (“REMS”), to ensure the benefits of the product outweigh its risks. A REMS is a safety
strategy implemented to manage a known or potential serious risk associated with a product and to enable patients to have
continued access to such medicines by managing their safe use, and could include medication guides, physician communication
plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.
The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate
controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-
marketing requirements is not maintained or if problems occur after the product reaches the marketplace. The FDA may require
one or more Phase 4 post-market studies and surveillance to further assess and monitor the product’s safety and effectiveness
after commercialization, and may limit further marketing of the product based on the results of these post-marketing studies.
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Expedited Development and Review Programs
The FDA maintains several programs intended to facilitate and expedite development and review of new drugs and
biologics to address unmet medical needs in the treatment of serious or life-threatening diseases or conditions.
For example a product candidate is eligible for Fast Track designation if it is intended to treat a serious or life-threatening
disease or condition and demonstrates the potential to address unmet medical needs for such disease or condition. Fast Track
designation applies to the combination of the product candidate and the specific indication for which it is being studied. Fast
Track designation provides increased opportunities for sponsor meetings with the FDA during preclinical and clinical
development, in addition to the potential for rolling review once a marketing application is filed, meaning that the FDA may
review portions of the marketing application before the sponsor submits the complete application, if the sponsor provides a
schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and determines that the
schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.,
In addition, a product candidate may be eligible for Breakthrough Therapy designation if it is intended to treat a serious or
life-threatening disease or condition and preliminary clinical evidence indicates that the product candidate may demonstrate
substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment
effects observed early in clinical development. Breakthrough Therapy designation provides all the features of Fast Track
designation in addition to intensive guidance on an efficient development program beginning as early as Phase 1, and FDA
organizational commitment to expedited development, including involvement of senior managers and experienced review staff
in a cross-disciplinary review, where appropriate.
Any product candidate submitted to the FDA for approval, including a product candidate with Fast Track or Breakthrough
Therapy designation, may also be eligible for additional FDA programs intended to expedite the review process, including
Priority Review designation and Accelerated Approval. A BLA is eligible for Priority Review if the product candidate is
designed to treat a serious or life-threatening disease or condition, and if approved, would provide a significant improvement in
safety or effectiveness in the treatment, diagnosis or prevention of a serious disease or condition.
Additionally, product candidates studied for their safety and effectiveness in treating serious or life-threatening diseases or
conditions may receive Accelerated Approval if they can be shown to have an effect on a surrogate endpoint that is reasonably
likely to predict clinical benefit, or an effect on a clinical endpoint that can be measured earlier than an effect on irreversible
morbidity or mortality which is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical
benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative
treatments. As a condition of accelerated approval, the FDA will generally require the sponsor to perform adequate and well-
controlled post-marketing clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality or
other clinical benefit. Products receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor
fails to conduct the required post-marketing studies or if such studies fail to verify the predicted clinical benefit. In addition, the
FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely
impact the timing of the commercial launch of the product.
Fast Track designation, Breakthrough Therapy designation, Priority Review designation and Accelerated Approval do not
change the standards for approval but may expedite the development or review process. Even if a product qualifies for one or
more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide
that the time period for FDA review or approval will not be shortened.
Orphan drug designation and exclusivity
Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or
condition, defined as a disease or condition with a patient population of fewer than 200,000 individuals in the United States, or
a patient population greater than 200,000 individuals in the United States and when there is no reasonable expectation that the
cost of developing and making available the drug or biologic in the United States will be recovered from sales in the United
States for that drug or biologic. Orphan drug designation must be requested before submitting a BLA. After the FDA grants
orphan drug designation, the generic identity of the therapeutic agent and its potential orphan use are disclosed publicly by the
FDA.
If a product candidate that has orphan drug designation subsequently receives the first FDA approval for a particular active
ingredient for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means
that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same indication
for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug
exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of
sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was
designated. Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease
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or condition, or the same drug or biologic for a different disease or condition. Among the other benefits of orphan drug
designation are tax credits for certain research and a waiver of the BLA application user fee.
A designated orphan drug many not receive orphan drug exclusivity if it is approved for a use that is broader than the
indication for which it received orphan designation. In addition, orphan drug exclusive marketing rights in the United States
may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if a second
applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the
manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with
the rare disease or condition.
Post-Approval Requirements
Licensed biologics that are manufactured and distributed in the United States are subject to pervasive and continuing
regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product
distribution, advertising and promotion and reporting of adverse experiences with the product. There is also a continuing,
annual prescription drug program user fee.
Any biologics manufactured or distributed pursuant to FDA approvals remain subject to ongoing regulation by the FDA.
Manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies,
and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing
regulatory requirements, including cGMP, which impose extensive procedural and documentation requirements. Failure to
comply with statutory and regulatory requirements can subject a manufacturer to possible legal or regulatory action, such as
warning letters, suspension of manufacturing, product seizures, injunctions, civil penalties or criminal prosecution.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or
frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the
approved labeling to add new safety information, requirements for post-market studies or clinical trials to assess new safety
risks, imposition of distribution or other restrictions under a REMS. Other potential consequences include, among other things:
restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or
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product recalls;
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fines, warning letters, untitled letters, or holds on post-approval clinical trials;
refusal of the FDA to approve applications or supplements to approved applications, or suspension or revocation of
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product approvals;
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product seizure or detention, or refusal to permit the import or export of products;
• mandated modification of promotional materials and labeling and the issuance of corrective information;
the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing
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warnings or other safety information about the product; or
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injunctions or the imposition of civil or criminal penalties.
The FDA closely regulates the post-approval marketing and promotion of biologics, including standards and regulations for
direct-to-consumer advertising, off-label promotion, industry-sponsored scientific and educational activities, and promotional
activities involving the internet and social media. A company can make only those claims relating to safety and efficacy that are
approved by the FDA. Physicians may prescribe legally available biologics for uses that are not described in the product’s
labeling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medical
specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances.
The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, impose
stringent restrictions on manufacturers’ communications regarding off-label use. Failure to comply with these requirements can
result in adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties.
Biosimilars and Regulatory Exclusivity
As part of the Patient Protection and Affordable Care Act enacted in 2010, as amended by the Health Care and Education
Reconciliation Act of 2010, the Biologics Price Competition and Innovation Act (“BPCIA”) established an abbreviated pathway
for the approval of biosimilar and interchangeable biological products. The abbreviated regulatory pathway provides legal
authority for the FDA to review and approve biosimilar biologics based on their similarity to an existing brand product, referred
to as a reference product, including the possible designation of a biosimilar as interchangeable with a brand product.
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Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the
reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical
study or studies. Interchangeability requires that a product is biosimilar to the reference product and the product must
demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for
products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or
switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to
exclusive use of the reference biologic.
Under the BPCIA, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date
on which the reference product was first licensed. Moreover, the extent to which a biosimilar, once approved, will be
substituted for a reference product in a way that is similar to traditional generic substitution for non-biological drug products is
not yet clear and will depend on a number of marketplace and regulatory factors that are still developing. In addition, the period
of exclusivity provided by the BPCIA only operates against third parties seeking approval via the abbreviated pathway, but
would not prevent third parties from pursuing approval via the traditional BLA approval pathway.
In addition, a biological product can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if
granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end
of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in
accordance with an FDA-issued “Written Request” for such a study. The BPCIA is complex and continues to be interpreted and
implemented by the FDA.
Other Healthcare Laws
Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and
by authorities in the states and foreign jurisdictions in which they conduct their business and may constrain the financial
arrangements and relationships through which we and our partners research, sell, market and distribute any products for which
we obtain marketing approval. Such laws include, without limitation, state and federal anti-kickback, fraud and abuse, false
claims, data privacy and security and transparency laws regarding drug pricing and payments and other transfer of value to
physicians and other healthcare providers. If their operations are found to be in violation of any of such laws or any other
governmental regulations that apply, they may be subject to penalties, including, without limitation, administrative, civil and
criminal penalties, damages, fines, disgorgement, the curtailment or restructuring of operations, integrity oversight and
reporting obligations, exclusion from participation in federal and state healthcare programs and individual imprisonment.
Coverage and Reimbursement
Sales of any product depend, in part, on the extent to which such product will be covered by third-party payors, such as
federal, state, and foreign government healthcare programs, commercial insurance and managed healthcare organizations, and
the level of reimbursement for such product by third-party payors. Decisions regarding the extent of coverage and amount of
reimbursement to be provided are made on a plan-by-plan basis. These third-party payors are increasingly reducing
reimbursements for medical products, drugs and services. In addition, the U.S. government, state legislatures and foreign
governments have continued implementing cost-containment programs, including price controls, restrictions on coverage and
reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment
measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales
of any product. Decreases in third-party reimbursement for any product or a decision by a third-party payor not to cover a
product could reduce physician usage and patient demand for the product and also have a material adverse effect on sales.
Healthcare Reform
In March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education
Reconciliation Act, each as amended (collectively known as the “ACA”), was enacted, which substantially changed the way
healthcare is financed by both governmental and private insurers, and significantly affected the pharmaceutical industry. The
ACA contained a number of provisions, including those governing enrollment in federal healthcare programs, reimbursement
adjustments and changes to fraud and abuse laws. For example, the ACA:
increased the minimum level of Medicaid rebates payable by manufacturers of brand name drugs from 15.1% to
•
23.1% of the average manufacturer price;
•
required collection of rebates for drugs paid by Medicaid managed care organizations;
required manufacturers to participate in a coverage gap discount program, under which they must agree to offer 70
•
percent point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their
coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; and
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imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell “branded prescription
•
drugs” to specified federal government programs.
Since its enactment, there have been judicial and Congressional challenges to certain aspects of the ACA.
On June 17, 2021, the U.S Supreme Court dismissed the most recent judicial challenge to the AC brought by several states
without specifically ruling on the constitutionality of the ACA. Thus, the ACA will remain in effect in its current form.
Other legislative changes have been proposed and adopted since the Affordable Care Act was enacted, including aggregate
reductions of Medicare payments to providers of 2% per fiscal year, which was temporarily suspended from May 1, 2020
through March 31, 2022, and reduced payments to several types of Medicare providers. Moreover, there has recently been
heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has
resulted in several Congressional inquiries, proposed and enacted legislation and executive orders issued by the President
designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and
manufacturer patient programs, and reform government program reimbursement methodologies for drug products. Individual
states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical
product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and
marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other
countries and bulk purchasing.
Data Privacy and Security Laws
Numerous state, federal and foreign laws, including consumer protection laws and regulations, govern the collection,
dissemination, use, access to, confidentiality, and security of personal information, including health-related information. In the
United States, numerous federal and state laws and regulations, including data breach notification laws, health information
privacy and security laws, and federal and state consumer protection laws and regulations (e.g., Section 5 of the Federal Trade
Commission Act) that govern the collection, use, disclosure, and protection of health-related and other personal information
could apply to our operations or the operations of our partners. In addition, certain state and non-U.S. laws, such as the
California Consumer Privacy Act ("CCPA"), the California Privacy Rights Act ("CPRA"), and the General data Protection
Regulation ("GDPR"), govern the privacy and security of personal information, including health-related information in certain
circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and
may not have the same effect, thus complicating compliance efforts. Failure to comply with these laws, were applicable, can
result in the imposition of significant civil and /or criminal penalties and private litigation. Privacy and security laws,
regulations, and other obligations are constantly evolving, may conflict with each other to make compliance efforts more
challenging, and can result in investigations, proceedings, or actions that lead to significant penalties and restrictions on data
processing.
CUSTOMERS
We rely on a limited number of key customers for the majority of our revenues. Customers that provided 10% or more of
our total revenues in any of the past three fiscal years consist of the following:
Customers:
Customer A
Customer B
Customer C
Customer D
Customer E
* Percentage was less than 10%
HUMAN CAPITAL RESOURCES
Percentage of Total Revenues
For the Years Ended December 31.
2020
2021
2019
33 %
11 %
*
*
*
*
26 %
19 %
11 %
*
*
28 %
*
15 %
23 %
As of December 31, 2021, we had 261 full-time employees and part-time employees worldwide. Of these employees, 159
were engaged in research and development, 37 were engaged in operations and quality control and 65 were engaged in selling,
general and administrative activities. None of our employees is represented by a labor union. Supported by our annual
employee survey, we believe our relationship with our employees to be generally good. Our scientists, bioinformatics experts
and other professionals work collaboratively as interdisciplinary teams to unlock and advance technological innovation.
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Compensation, benefits and development
Our goal is to attract, motivate and retain talent with a focus on encouraging performance, promoting accountability and
adhering to our company values. We offer competitive compensation and benefit programs including a company-matched
401(k) Plan, stock options for eligible employees, health savings and flexible spending accounts, paid time off, education and
training programs, and employee assistance programs. We believe it is important to help build community and enabling our
employees actively participate in community service projects and in company-sponsored philanthropic activities.
Diversity, inclusion and belonging
We are committed to our continued efforts to increase diversity and foster an inclusive work environment that supports the
global workforce and the communities we serve. We recruit the best people for the job regardless of gender, ethnicity or other
protected traits and it is our policy to fully comply with all laws applicable to discrimination in the workplace. Our diversity,
equity and inclusion principles are also reflected in our employee training and policies. We continue to enhance our diversity,
equity and inclusion policies which are guided by our executive leadership team.
Health and safety
We are committed to maintain a safe and healthy workplace for our employees. Our policies and practices are intended to
protect our employees and surrounding communities in which we operate.
In 2020, in response to the COVID-19 pandemic, we implemented safety protocols and new procedures to protect our
employees. These protocols include complying with social distancing and other health and safety standards as required by state
and local government agencies, taking into consideration guidelines of the Centers for Disease Control and Prevention and
other public health authorities. In addition, we modified the way we conduct many aspects of our business including the
practice of social distancing, wearing face coverings mandated by state and local regulations, and maintaining a quarantine for
employees determined to be in close contact with a COVID-19 case. For example, we implemented day-time shift hours in our
R&D and manufacturing at our Redwood City pilot plant to minimize the number of employees in close proximity to each other
and we have significantly expanded the use of virtual interaction whenever possible in our business. For a detailed discussion of
the impact of the COVID-19 pandemic on our human capital resources, see “Risk Factors" Item 1A of this Form 10-K.
We previously launched the Employee-Requested Work from Home Policy in late 2020. This policy establishes the process
and criteria to enable Redwood City employees to request permission to work from home on a regular basis.
CORPORATE & AVAILABLE INFORMATION
We were incorporated in Delaware in January 2002 as a wholly-owned subsidiary of Maxygen, Inc. We commenced
independent operations in March 2002, after licensing core enabling technology from Maxygen, Inc. Our principal corporate
offices are located at 200 Penobscot Drive, Redwood City, California 94063 and our telephone number is (650) 421-8100. Our
internet address is www.codexis.com. The information on, or that can be accessed through, our website is not incorporated by
reference into this Annual Report on Form 10-K or any other filings we make with the U.S. Securities and Exchange
Commission (the “SEC”).
We make available on or through our website certain reports and amendments to those reports that we file with, or furnish
to, the SEC in accordance with the Exchange Act. These include our Annual Reports on Form 10-K, our Quarterly Reports on
Form 10-Q and our Current Reports on Form 8-K, and amendments to those reports filed or furnished pursuant to Section 13(a)
or 15(d) of the Exchange Act. We make this information available on or through our website free of charge as soon as
reasonably practicable after we electronically file the information with, or furnish it to, the SEC. Copies of this information may
be obtained at the SEC website at www.sec.gov. The contents of these websites are not incorporated into this filing. Further, the
references to website URLs are intended to be inactive textual references only.
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ITEM 1A. RISK FACTORS
You should carefully consider the risks described below together with the other information set forth in this Annual
Report on Form 10-K, which could materially affect our business, financial condition or future results. The risks described
below are not the only risks facing our company. Risks and uncertainties not currently known to us or that we currently
deem to be immaterial also may materially adversely affect our business, financial condition and/or operating results.
RISK FACTORS SUMMARY
The following is a summary of the principal factors that cause an investment in the company to be speculative or risky:
• A significant portion of revenue growth in 2021 is as a result of the receipt of purchase orders from Pfizer for
CDX-616. Revenues in 2022 and in future years from our sales of CDX-616 to Pfizer are subject to a number
of factors which are outside of our control and may not materialize.
• We do not have a long term sale and purchase agreement with Pfizer for CDX-616 and we currently expect
that future orders for quantities of CDX-616 by Pfizer will continue to be based on the needs of Pfizer for
quantities of CDX-616.
• We have a history of net losses and we may not achieve or maintain profitability.
• We are dependent on our collaborators, and our failure to successfully manage these relationships could
prevent us from developing and commercializing many of our products.
• We are dependent on a limited number of customers, including Pfizer.
• The ongoing COVID-19 pandemic has adversely affected and may continue in the future to, directly or
indirectly, adversely affect our business, results of operations and financial condition.
• Our product supply agreements with customers have finite duration and may not be extended or renewed.
• With respect to customers purchasing our products for the manufacture of API, the termination or expiration
of such patent protection may materially and adversely affect our revenues, financial condition or results of
operations.
• We are dependent on a limited number of contract manufacturers for large scale production of substantially
all of our enzymes, including CDX-616.
•
If we are unable to develop and commercialize new products for the target markets, our business and
prospects will be harmed.
• Our biotherapeutic programs are early stage, highly regulated and expensive.
•
If either Nestlé Health Science or Takeda terminate their development programs under their respective license
agreements with us, any potential revenue from those license agreements will be significantly reduced or non-
existent.
• Our efforts to deploy our technology platform in the fine chemicals market may fail.
• We may need additional capital in the future in order to expand our business.
• We have investments in non-marketable securities, which may subject us to significant impairment charges.
• Competitors and potential competitors who have greater resources and experience than we do may develop
products and technologies that make ours obsolete.
• Ethical, legal and social concerns about genetically engineered products and processes could limit or prevent
the use of our products, processes, and technologies and limit our revenues.
•
If we engage in any acquisitions, we will incur a variety of costs and may potentially face numerous risks that
could adversely affect our business and operations.
• We use hazardous materials in our business and we must comply with environmental laws and regulations.
• Our ability to use our net operating loss carryforwards to offset future taxable income may be subject to
certain limitations.
• We or our customers may not be able to obtain regulatory approval for the use of our products in food and
food ingredients, if required.
• Our ongoing efforts to deploy our technology in the life science tools market may fail.
• The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time
consuming and inherently unpredictable, and we may be unable to obtain regulatory approval for our product
candidates.
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• Clinical trials are difficult to design and implement, expensive, time-consuming and involve an uncertain
outcome.
• Results of preclinical studies and early clinical trials of product candidates may not be predictive of results of
later studies or trials.
• Even if we obtain regulatory approval for any products that we develop alone or with collaborators, such
products will remain subject to ongoing regulatory requirements.
• Our business operations and future relationships with investigators, healthcare professionals, consultants,
third-party payors, patient organizations and customers will be subject to applicable healthcare regulatory
laws, which could expose us to penalties.
• The successful commercialization of product candidates developed by us or our partners will depend in part
on the extent to which governmental authorities and health insurers establish adequate coverage,
reimbursement levels and pricing policies.
• Compliance with European Union chemical regulations could be costly and adversely affect our business and
results of operations.
• We rely on third parties to conduct our clinical trials and perform some of our research and preclinical studies,
which if not satisfactorily carried out or fail to meet expected deadlines, may have an adverse effect on our
business and prospects.
• We contract with third parties for the manufacturing and supply of product candidates, which supply may
become limited or interrupted or may not be of satisfactory quality and quantity.
• Our efforts to prosecute and protect our intellectual property may not be successful.
• Our ability to compete may decline if we do not adequately protect our proprietary technologies or if we lose
some of our intellectual property rights.
• Third parties may claim that we are infringing their intellectual property rights or other proprietary rights,
which may subject us to costly and time-consuming litigation.
• We may be involved in lawsuits to protect or enforce our intellectual property rights, which could be
expensive, time-consuming and unsuccessful.
• We may not be able to enforce our intellectual property rights throughout the world.
•
If our biocatalysts are stolen, misappropriated or reverse engineered, others could use these biocatalysts to
produce competing products.
• We are subject to anti-takeover provisions in our certificate of incorporation and bylaws and under Delaware
law that could delay or prevent an acquisition of our company.
• Our quarterly or annual operating results may fluctuate in the future.
• We do not intend to pay cash dividends for the foreseeable future.
•
If securities or industry analysts do not publish research or reports about our business, or publish negative
reports about our business, our stock price and trading volume could decline.
• We face risks associated with our international business.
• Business interruptions resulting from disasters or other disturbances could delay us in the process of
developing our products and could disrupt our sales.
• Confidentiality agreements with employees and others may not adequately prevent disclosures of trade
secrets and other proprietary information.
• We are dependent on information technology systems, infrastructure and data, and any failure of these
systems could harm our business.
• Actual or perceived failures to comply with applicable data protection, privacy and security laws, regulations,
standards and other requirements could adversely affect our business, results of operations, and financial
condition.
• Evolving expectations around ESG matters may expose us to reputational and other risks.
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Risks Relating to Our Business and Strategy
A significant portion of our revenue growth in 2021 is as a result of the receipt of purchase orders from Pfizer for a
proprietary enzyme product ("CDX-616") used by Pfizer in the manufacture of its active pharmaceutical ingredient
nirmatrelvir for its COVID-19 antiviral therapeutic, PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets). Revenues in
2022 and in future years from our sales of CDX-616 to Pfizer are subject to a number of factors which are outside of
our control and may not materialize.
Starting the first and second quarters of 2021, we began to receive purchase orders from Pfizer, Inc. (“Pfizer”) for
large quantities of our proprietary enzyme product, CDX-616, for use by Pfizer in the manufacture of a critical
intermediate for its proprietary active pharmaceutical ingredient, nirmatrelvir. Pfizer markets, sells and distributes
nirmatrelvir, in combination with the active pharmaceutical ingredient ritonavir, as its PAXLOVID™ (nirmatrelvir tablets;
ritonavir tablets) product, which received emergency use authorization (“EUA”) by the U.S. Food and Drug Administration
(“FDA”) in late 2021 for the treatment of COVID-19 infections in humans.
In 2021, we recognized $34.5 million in revenue from the sale of quantities of CDX-616 to Pfizer. In addition, as of
December 31, 2021, we have received additional purchase orders from Pfizer for delivery of a significant quantity of CDX-
616 in 2022. We have received and currently expect to receive additional purchase orders from Pfizer for significant
quantities of CDX-616 during the course of 2022 for delivery in 2022 and 2023.
Revenues in 2022 and in future years from our sales of CDX-616 to Pfizer and other potential customers (including
sublicensees of Pfizer technology from The Medicines Patent Pool) are subject to a number of factors which are outside of
our control, including, without limitation, the following, all of which could reduce or eliminate our sales of CDX-616, and
therefore materially and adversely affect our business, results of operations and financial condition:
•
•
•
•
•
•
•
•
•
Pfizer has no future binding commitment to purchase any particular quantity or quantities of CDX-616 from
us, and we are dependent upon Pfizer continuing to place orders with us (whether on a spot basis or under a
long term agreement, when and if executed) for their requirements, if any, for CDX-616;
to our knowledge, sublicensees of Pfizer technology from The Medicines Patent Pool (MPP) have no
obligation to purchase CDX-616 from us under their sublicenses with MPP;
the EUA granted by the FDA for the use of PAXLOVID™ for the treatment of COVID-19 infections in
humans could be withdrawn at any time;
future vaccine development and usage and the development and usage of other new therapies for the
treatment or elimination of COVID-19 may eliminate or reduce demand for PAXLOVID™;
new variants of COVID-19 may emerge which PAXLOVID™ is not effective in treating;
Pfizer may not ultimately receive full marketing authorization for PAXLOVID™ from the FDA and other
international regulatory authorities;
Pfizer could reformulate or make changes in the manufacturing process for nirmatrelvir which would
eliminate or reduce demand for the use of CDX-616 in its manufacture;
sublicensees of Pfizer technology for the manufacture, sale and distribution of PAXLOVID™ from the MPP
may not utilize CDX-616 in the manufacture of nirmatrelvir;
national and regional governmental authorities (including those of the United States government) may
mandate that raw materials and intermediates used in the manufacture of PAXLOVID™ to be marketed, sold
and distributed within the borders of that country be domestically produced, which could eliminate or reduce
demand for the use of CDX-616 in such country; and
• we may be unable (because of lack of available manufacturing capacity at our contract manufacturers, supply
chain disruptions or an inability to obtain applicable regulatory approvals) to manufacture the quantities of
CDX-616 that Pfizer may desire to purchase from us.
27
We do not have a long term sale and purchase agreement with Pfizer for CDX-616. \Whether or not a long term-
purchase and sale agreement is executed, we currently expect that future orders for quantities of CDX-616 by Pfizer will
continue to be based on the needs of Pfizer for quantities of CDX-616 and there will be no minimum purchase
obligation on the part of Pfizer. If Pfizer ceases to issue or delays the issuance of orders for CDX-616, our results of
operations and financial condition will be materially and adversely affected.
As of December 31, 2021, we have not yet executed a long term sale and purchase agreement with Pfizer for CDX-
616. All of the orders for CDX-616 that we have received from Pfizer to date have been in the form of purchase orders for
individual deliveries of quantities of CDX-616 at mutually agreed upon pricing. Whether or not a long term purchase and
sale agreement is executed, we currently expect that future orders for quantities of CDX-616 by Pfizer will continue to be
based on the then current needs of Pfizer for quantities of CDX-616 and there will be no minimum purchase obligation on
the part of Pfizer. If Pfizer's demand for CDX-616 declines or is eliminated, and Pfizer ceases to issue or delays the
issuance of orders for CDX-616, our results of operations and financial condition will be materially and adversely affected.
We have a history of net losses and we may not achieve or maintain profitability.
We have incurred net losses since our inception, including losses of $21.3 million in 2021, $24.0 million in 2020 and
$11.9 million in 2019. As of December 31, 2021 and 2020, we had an accumulated deficit of $387.7 million and
$366.4 million, respectively. If we are unable to expand our business, through new or expanded collaborations,
development of new products or services, or increased sales of existing products and services, our net losses may increase
and we may never achieve profitability. In addition, some of our collaboration agreements, including our collaboration with
Nestlé Health Science and Takeda, and our performance enzyme agreements, including the agreements with GSK, Merck
and Novartis, provide for milestone payments, usage payments, and/or future royalty payments, which we will only receive
if we and our collaborators develop and commercialize products. We also may fund development of additional proprietary
performance enzymes and/or biotherapeutic products. There can be no assurance that any of these products will become
commercially viable or that we will ever achieve profitability on a quarterly or annual basis. If we fail to achieve
profitability, or if the time required to achieve profitability is longer than we anticipate, we may not be able to continue our
business. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or
annual basis.
We are dependent on our collaborators, and our failure to successfully manage these relationships could prevent us
from developing and commercializing many of our products and achieving or sustaining profitability, and could lead to
disagreements with our current or former collaborators.
Our ability to maintain and manage collaborations in our markets is fundamental to the success of our business. We
currently have license agreements, research and development agreements, supply agreements and/or distribution
agreements with various collaborators. For example, we have ongoing collaborations and agreements with GSK, Merck,
Novartis, Nestlé Health Science and Takeda that are important to our business and financial results. We may have limited
or no control over the amount or timing of resources that any collaborator is able or willing to devote to our partnered
products or collaborative efforts. Any of our collaborators may fail to perform its obligations. These collaborators may
breach or terminate their agreements with us or otherwise fail to conduct their collaborative activities successfully and in a
timely manner. Further, our collaborators may not develop products arising out of our collaborative arrangements or devote
sufficient resources to the development, manufacture, marketing or sale of these products. Moreover, disagreements with a
collaborator could develop, and any conflict with a collaborator could lead to litigation and could reduce our ability to enter
into future collaboration agreements and negatively impact our relationships with one or more existing collaborators. If any
of these events occur, especially if they occur in our collaborations with GSK, Merck, Novartis, Nestlé Health Science or
Takeda, or if we fail to maintain our agreements with our collaborators, we may not be able to commercialize our existing
and potential products or grow our business or generate sufficient revenues to support our operations, we may not receive
contemplated milestone payments and royalties under the collaboration, and we may be involved in litigation. Our
collaboration opportunities could be harmed and our financial condition and results of operations could be negatively
affected if:
• we do not achieve our research and development objectives under our collaboration agreements in a timely
manner or at all;
• we develop products and processes or enter into additional collaborations that conflict with the business
objectives of our other collaborators;
• we, our collaborators and/or our contract manufacturers do not receive the required regulatory and other
approvals necessary for the commercialization of the applicable product;
28
• we disagree with our collaborators as to rights to intellectual property that are developed during the
collaboration, or their research programs or commercialization activities;
• we are unable to manage multiple simultaneous collaborations;
•
•
•
•
our collaborators or licensees are unable or unwilling to implement or use the technology or products that we
provide or license to them;
our collaborators become competitors of ours or enter into agreements with our competitors;
our collaborators become unable or less willing to expend their resources on research and development or
commercialization efforts due to general market conditions, their financial condition or other circumstances
beyond our control; or
our collaborators experience business difficulties, which could eliminate or impair their ability to effectively
perform under our agreements.
Even after collaboration relationships expire or terminate, some elements of the collaboration may survive. For
instance, certain rights, licenses and obligations of each party with respect to intellectual property and program materials
may survive the expiration or termination of the collaboration. Disagreements or conflicts between and among the parties
could develop even though the collaboration has ended. These disagreements or conflicts could result in expensive
arbitration or litigation, which may not be resolved in our favor.
Finally, our business could be negatively affected if any of our collaborators or suppliers undergoes a change of control
or were to otherwise assign the rights or obligations under any of our agreements.
We are dependent on a limited number of customers, including Pfizer.
Our current revenues are derived from a limited number of key customers. For the years ended December 31, 2021 and
2020, customers that each individually contributed 10% or more of our total revenue accounted for 44% and 56% of our
total revenues in 2021 and 2020, respectively. In particular, in 2021 Pfizer accounted for $34.5 million, or approximately
33%, of our total revenue. We expect a limited number of customers to continue to account for a significant portion of our
revenues for the foreseeable future. This customer concentration increases the risk of quarterly fluctuations in our revenues
and operating results. The loss or reduction of business from one or a combination of our significant customers could,
materially adversely affect our revenues, financial condition and results of operations.
The ongoing COVID-19 pandemic has adversely affected and may continue in the future to, directly or indirectly,
adversely affect our business, results of operations and financial condition.
The COVID-19 pandemic has had, and continues to have, a significant impact globally, prompting governments and
businesses to take unprecedented measures in response. In the United States, the COVID-19 pandemic has and may
continue in the future to, directly or indirectly, adversely affect our business, results of operations and financial condition,
including as a result of compliance with governmental orders governing the operation of businesses during the pandemic,
the temporary closure of our Redwood City, California facilities from mid-March 2020 through the end of April 2020 and
disruption of our research and development operations.
The extent and severity of the impact on our business and clinical trials will be determined largely by the extent of
disruptions in the supply chains for our products and product candidates; disruptions in access by patients to therapies for
which our products are components of the supply chain; delays in the performance of research and development ("R&D")
service work, and delays in current and future clinical trials that we or our collaboration partners may conduct. In addition,
the impact of the COVID-19 pandemic on the operations of the FDA and other health authorities may delay potential
approvals of product candidates for which our products are components of the supply chain. To date, we and our
collaboration partners have been able to continue to supply our enzymes to our customers worldwide, however there can be
no guarantee this will continue. Furthermore, our ability to provide future R&D services will continue to be impacted as a
result of governmental orders and any disruptions in operations of our customers with whom we collaborate. We believe
that these disruptions have had a minimal impact on our revenue for the year ended December 31, 2021. The extent to
which the pandemic may impact our business operations and operating results will continue to remain highly dependent on
future developments, which are uncertain and cannot be predicted with confidence.
In the future, our business could be materially adversely affected, directly or indirectly, by the widespread outbreak of
contagious disease, including the ongoing COVID-19 pandemic. National, state and local governments in affected regions
have implemented and may continue to implement safety precautions, including quarantines, border closures, increased
border controls, travel restrictions, governmental orders and shutdowns, business closures, cancellations of public
29
gatherings and other measures. Organizations and individuals are taking additional steps to avoid or reduce infection,
including limiting travel and staying home from work. These measures are disrupting normal business operations both in
and outside of affected areas and have had significant negative impacts on businesses and financial markets worldwide.
The potential impact and duration of COVID-19 or another pandemic or public health crisis has had and could
continue to have, significant repercussions across regional, national and global economies and financial markets, and could
trigger a period of regional, national and global economic slowdown or regional, national or global recessions. The
outbreak of COVID-19 in many countries continues to adversely impact regional, national and global economic activity
and has contributed to significant volatility and negative pressure in financial markets. As a result, we may experience
difficulty accessing debt and equity capital on attractive terms, or at all, due to the severe disruption and instability in the
global financial markets. In addition, our customers may terminate or amend their agreements for the purchase of our
products or services due to bankruptcy, lack of liquidity, lack of funding, operational failures, or other reasons.
We continue to monitor our operations and applicable government recommendations, and we have made modifications
to our normal operations because of the COVID-19 pandemic, including requiring most office-based employees to work
remotely. Notwithstanding these measures, the COVID-19 pandemic could affect the health and availability of our
workforce as well as those of the third parties we rely on taking similar measures. If members of our management and
other key personnel in critical functions across our organization are unable to perform their duties or have limited
availability due to COVID-19, we may not be able to execute on our business strategy and/or our operations may be
negatively impacted. We may also experience limitations in employee resources, including because of sickness of
employees or their families or the desire of employees to avoid contact with individuals or large groups of people. In
addition, we have experienced and will continue to experience disruptions to our business operations resulting from
quarantines, self-isolations and other restrictions on the ability of our employees to perform their jobs.
While it is not possible at this time to estimate the entirety of the impact that the COVID-19 pandemic will have on
our business, operations, employees, customers, suppliers or our collaboration partners, the continued spread of COVID-19
and the prevalence of more contagious and or virulent variants such as the Delta and Omicron variants, measures taken by
governments, actions taken to protect employees and the broad impact of the pandemic on all business activities may
materially and adversely affect our business, results of operations and financial condition.
Our product supply agreements with customers have finite duration, may not be extended or renewed and generally
do not require the customer to purchase any particular quantity or quantities of our products.
Our product supply agreements with customers generally have a finite duration, may not be extended or renewed and
generally do not require the customer to purchase any particular quantity or quantities of our products. While our products
are not considered commodities and may not be easily substituted for by our customers, particularly when our products are
used in the manufacture of active pharmaceutical ingredients, our customers may nevertheless terminate or fail to renew
their product supply agreements with us or significantly curtail their purchases thereunder under certain circumstances.
Any such termination or reduction could materially adversely affect our revenues, financial condition and results of
operations. For the year ended December 31, 2021, we derived a majority of our product revenue from these product
supply agreements.
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With respect to customers purchasing our products for the manufacture of active pharmaceutical ingredients
("API") for which they have exclusivity due to patent protection, the termination or expiration of such patent protection
and any resulting generic competition may materially and adversely affect our revenues, financial condition or results
of operations.
With respect to customers purchasing our products for the manufacture of API, or lead to the manufacture of API, for
which exclusivity due to patent protection has or is about to expire, we can expect that the quantity of our products sold to
such customers for such products may decline as generic competition for the API increases. While we anticipate that we
may, in some cases, also be able to sell products to these generic competitors for the manufacture of these APIs, or lead to
the manufacture of these APIs, the overall effect on our revenues, financial condition and results of operations could be
materially adverse.
We are dependent on a limited number of contract manufacturers for large scale production of substantially all of
our enzymes, including CDX-616. We are working to qualify new contract manufacturers to produce certain of our
enzymes, including CDX-616, however those efforts may not be successful and therefore we may experience limitations
on our ability to supply our enzymes to customers.
Manufacturing of our enzymes is conducted primarily in four locations: our in-house facility in Redwood City,
California, and at three third-party contract manufacturing organizations, Lactosan GmbH & Co. KG (“Lactosan”), in
Kapfenberg, Austria, ACS Dobfar S.p.A. (“ACSD”) (formerly known as DPhar S.p.A.), in Anagni, Italy, and Alphazyme
LLC in Florida, United States. Generally, we perform smaller scale manufacturing in-house and outsource the larger scale
manufacturing to these contract manufacturers. We have limited internal capacity to manufacture enzymes. As a result, we
are dependent upon the performance and capacity of third-party manufacturers for the larger scale manufacturing of the
enzymes used in our pharmaceutical and fine chemicals business.
Accordingly, we face risks of difficulties with, and interruptions in, performance by third party manufacturers, the
occurrence of which could adversely impact the availability, launch and/or sales of our enzymes in the future. Enzyme
manufacturing capacity limitations at our third party manufacturers and manufacturing delays could negatively affect our
business, reputation, results of operations and financial condition. The failure of any contract manufacturer to supply us our
required volumes of enzyme on a timely basis, or to manufacture our enzymes in compliance with our specifications or
applicable quality requirements or in volumes sufficient to meet demand, would adversely affect our ability to sell
pharmaceutical and fine and complex chemicals products, could harm our relationships with our collaborators or customers
and could negatively affect our revenues and operating results. We may be forced to secure alternative sources of supply,
which may be unavailable on commercially acceptable terms, and could cause delays in our ability to deliver products to
our customers, increase our costs and decrease our profit margins.
We currently have supply agreements in place with Lactosan, ACSD, and Alphazyme. In the absence of a supply
agreement, a contract manufacturer will be under no obligation to manufacture our enzymes and could elect to discontinue
their manufacture at any time. If we require additional manufacturing capacity and are unable to obtain it in sufficient
quantity, we may not be able to increase our product sales, or we may be required to make substantial capital investments
to build that capacity or to contract with other manufacturers on terms that may be less favorable than the terms we
currently have with our suppliers. If we choose to build our own additional manufacturing facility, it could take two years
or longer before our facility is able to produce commercial volumes of our enzymes. Any resources we expend on acquiring
or building internal manufacturing capabilities could be at the expense of other potentially more profitable opportunities. In
addition, if we contract with other manufacturers, we may experience delays of several months in qualifying them, which
could harm our relationships with our collaborators or customers and could negatively affect our revenues or operating
results.
If we are unable to develop and commercialize new products for the pharmaceutical, fine chemicals,
biotherapeutics, diagnostics and life science tools markets, our business and prospects will be harmed.
We plan to launch new products for the pharmaceutical, fine chemicals, biotherapeutics, diagnostics and other life
science tools markets. These efforts are subject to numerous risks, including the following:
•
customers in these markets may be reluctant to adopt new manufacturing processes that use our enzymes;
• we may be unable to successfully develop the enzymes or manufacturing processes for our products in a
timely and cost-effective manner, if at all;
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• we may face difficulties in transferring the developed technologies to our customers and the contract
manufacturers that we may use for commercial scale production of intermediates and enzymes in these
markets;
•
•
the contract manufacturers that we may use may be unable to scale their manufacturing operations to meet the
demand for these products and we may be unable to secure additional manufacturing capacity;
customers may not be willing to purchase these products for these markets from us on favorable terms, if at
all;
• we may face product liability litigation, unexpected safety or efficacy concerns and product recalls or
withdrawals;
•
•
changes in laws or regulations relating to the pharmaceutical industry or the industries into which we sell our
fine chemicals products, including the food industry, could cause us to incur increased costs of compliance or
otherwise harm our business;
our customers’ products may experience adverse events or face competition from new products, which would
reduce demand for our products;
• we may face pressure from existing or new competitive products; and
• we may face pricing pressures from existing or new competitors, some of which may benefit from
government subsidies or other incentives.
Our biotherapeutic programs are early stage, highly regulated and expensive. Our ability to obtain additional
development partners or additional funding for the programs, to advance our product candidates to clinical trials and to
ultimately receive regulatory approvals is highly uncertain.
We are developing and have developed novel biotherapeutic candidates, including CDX-6114, the novel oral enzyme
product candidate for the treatment of PKU that we licensed to Nestlé Health Science. We are also developing protein
sequences for use in gene therapy products for Fabry Disease, Pompe Disease, an undisclosed blood factor deficiency and a
certain undisclosed rare genetic disorder for Takeda. The successful development of biotherapeutic candidates involves
many risks and uncertainties, requires long timelines and may lead to uncertain results. In addition, drug development is
highly regulated and requires areas of expertise and capital resources we do not currently possess. In order to market a
biologic product in the United States, we or our collaborators must undergo the following process required by the FDA:
•
•
•
•
•
•
•
•
completion of extensive preclinical laboratory tests and preclinical animal studies, all performed in
accordance with GLP requirements;
submission to the FDA of an IND, which must become effective before human clinical studies may begin in
the United States;
approval by an independent IRB representing each clinical site before the clinical study may be initiated at
the site;
performance of adequate and well-controlled human clinical studies (generally divided into three phases) in
accordance with GCP requirements to establish the safety, purity and potency (or efficacy) of the product
candidate for each proposed indication;
preparation of and submission to the FDA of a BLA after completion of all clinical studies;
potential review of the product candidate by an FDA advisory committee;
satisfactory completion of an FDA pre-approval inspection of the manufacturing facilities where the product
candidate is produced to assess compliance with cGMP requirements; and
FDA review and approval of a BLA prior to any commercial marketing or sale of the product in the United
States.
If we fail to comply with applicable FDA or other regulatory requirements at any time during the drug development
process, clinical testing, the approval process or after approval, we may become subject to administrative or judicial
penalties, including the FDA’s refusal to approve a pending application, withdrawal of an approval, warning letters, product
recalls, and additional enforcement actions.
Our efforts to advance our biotherapeutic candidates that we develop are subject to numerous risks, including the
following:
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• The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time
consuming and the results are inherently unpredictable. If we are ultimately unable to obtain regulatory
approval for biotherapeutic product candidates, our business will be harmed. To obtain regulatory approval to
market any product candidate, preclinical studies and costly and lengthy clinical trials are required, and the
results of the studies and trials are highly uncertain. A failure of one or more preclinical or clinical trials can
occur at any stage, and many companies that have believed their drug candidates performed satisfactorily in
preclinical and clinical testing have nonetheless failed to obtain marketing approval of their product
candidates.
• We may find it difficult to enroll patients in our clinical trials for product candidates. Any enrollment
difficulties could delay clinical trials and any potential product approval.
• We may experience difficulty or delay in obtaining the FDA’s acceptance of an IND for product candidates
we may seek to enter into clinical development, which would delay initiation of Phase 1 clinical testing.
Delays in the commencement or completion of clinical testing could significantly affect our product
development costs or the product development costs of our present and any future collaborators. We do not
know whether planned clinical trials will begin on time or be completed on schedule, if at all. The
commencement and completion of clinical trials can be delayed for a number of reasons. For example, a
clinical trial may be suspended or terminated by us, by the IRB of the institution in which such trial is being
conducted, or by the FDA due to a number of factors, including unforeseen safety issues, changes in
governmental regulations or lack of adequate funding to continue the clinical trial.
• We have limited experience in drug development or regulatory matters related to drug development. As a
result, we rely or will rely on third parties to conduct our preclinical and clinical studies, assist us with drug
manufacturing and formulation and perform other tasks for us. If these third parties do not successfully carry
out their responsibilities or comply with regulatory requirements, we may receive lower quality products or
services, suffer reputational harm and not be able to obtain regulatory approval for product candidates.
• Our efforts to use CodeEvolver® protein engineering technology platform to generate new lead biotherapeutic
candidates, whether under our collaborations with Nestlé Health Science, Takeda or otherwise, may not be
successful in creating candidates of value.
• We will be exposed to potential product liability risks through the testing of experimental therapeutics in
humans, which may expose us to substantial uninsured liabilities.
• Third parties may develop intellectual property that could limit our ability to develop, market and
commercialize product candidates.
• Changes in methods of treatment of disease, such as gene therapy, could cause us to stop development of our
product candidates or reduce or eliminate potential demand for CDX-6114, if approved, or any other product
candidates that we may develop in the future.
If either Nestlé Health Science or Takeda terminate their development programs under their respective license
agreements with us, any potential revenue from those license agreements will be significantly reduced or non-existent,
and our results of operations and financial condition will be materially and adversely affected.
We have invested significant time and financial resources in the development of CDX-6114 and other product
candidates for the treatment of HPA now included in the Nestlé License Agreement as well as in the development of
candidates for the treatment of Fabry disease and Pompe disease which are now included in the Takeda Agreement.
Under the Nestlé License Agreement, we are eligible to receive payments from Nestlé Health Science that include (i)
development and approval milestones of up to $85.0 million, (ii) sales-based milestones of up to $250.0 million in the
aggregate, which aggregate amount is achievable if net sales exceed $1.0 billion in a single year, and (iii) tiered royalties, at
percentages ranging from the mid-single digits to low double-digits, of net sales of product. Under the Takeda Agreement,
we are eligible to earn potential payments that include (i) reimbursement of research and development fees and preclinical
development milestone payments for the three initial programs of $10.5 million, in aggregate, and $8.3 million for the
fourth program, (ii) clinical development and commercialization-based milestone, per target gene, of up to $100.0 million,
and (iii) tiered royalty payments based on net sales of applicable products at percentages ranging from the mid-single digits
to low single-digits. While we have received milestone payments under the Nestlé License Agreement to date there is no
guarantee that we will receive further milestone payments under the Nestlé Agreement or Takeda Agreement in the future.
Under the Nestle Agreement and the Takeda Agreement, either Nestlé Health Science and Takeda, as applicable, may
each terminate the entire agreement or specified programs thereunder at will under certain circumstances as described in
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more detail under “Item 1. Business--Our Market Opportunities--Pharmaceutical Market--Our Solutions for the
Pharmaceutical Market--Biotherapeutic Product Discovery and Development” in this Annual Report on Form 10-K.
If Nestlé Health Science terminates its rights and obligations with respect to the Nestlé License Agreement and/or
Takeda terminates its rights and obligations with respect to the Takeda Agreement, then depending on the timing of such
event:
•
•
the development of our product candidates subject to the respective agreements may be terminated or
significantly delayed;
our cash expenditures could increase significantly if it is necessary for us to hire additional employees and
allocate scarce resources to the development and commercialization of product candidates;
• we would bear all of the risks and costs related to the further development and commercialization of product
candidates that were previously the subject of the respective agreements, including the reimbursement of third
parties; and
•
in order to fund further development and commercialization of new product candidates or programs, we may
need to seek out and establish alternative collaboration arrangements with third-party partners; this may not
be possible, or we may not be able to do so on terms which are acceptable to us, in which case it may be
necessary for us to limit the size or scope of one or more of our programs or increase our expenditures and
seek additional funding by other means.
Our efforts to deploy our technology platform in the fine chemicals market may fail.
We have recently begun to use our CodeEvolver® protein engineering technology platform to develop new products in
the fine chemicals markets. We do not know if we can successfully compete in this new market. This new market is well
established and consists of numerous large, well-funded entrenched market participants who have long and established
track records and customer relationships. We have currently developed products in the food sector of this market and these
products, or any other products that we may develop in the future for the fine chemicals market may not succeed in
displacing current products. If we succeed in commercializing new products for the fine chemicals market, we may not
generate significant revenues and cash flows from these activities. The failure to successfully deploy products in the fine
chemicals space may limit our growth and have a material adverse effect on our financial condition, operating results and
business prospects.
We may need additional capital in the future in order to expand our business.
Our future capital requirements may be substantial, particularly as we continue to develop our business. Although we
believe that, based on our current level of operations, our existing cash, cash equivalents and equity securities will provide
adequate funds for ongoing operations, planned capital expenditures and working capital requirements for at least the next
12 months, we may need additional capital if our current plans and assumptions change. Our need for additional capital
will depend on many factors, including the financial success of our performance enzyme business, our spending to develop
and commercialize new and existing products and the amount of collaboration funding we may receive to help cover the
cost of such expenditures, the effect of any acquisitions of other businesses, technologies or facilities that we may make or
develop in the future, our spending on new market opportunities, including opportunities in the fine chemicals markets, and
the filing, prosecution, enforcement and defense of patent claims. If our capital resources are insufficient to meet our
capital requirements, and we are unable to enter into or maintain collaborations with partners that are able or willing to
fund our development efforts or commercialize any products that we develop or enable, we will have to raise additional
funds to continue the development of our technology and products and complete the commercialization of products, if any,
resulting from our technologies. In addition, we may choose to raise additional capital due to market conditions or strategic
considerations even if we believe we have sufficient funds for our current or future operating plans. We may seek to obtain
such additional capital through equity offerings, debt financings, credit facilities and/or strategic collaborations. If future
financings involve the issuance of equity securities, our existing stockholders would suffer dilution. If we raise debt
financing or enter into credit facilities, we may be subject to restrictive covenants that limit our ability to conduct our
business. Strategic collaborations may also place restrictions on our business. We may not be able to raise sufficient
additional funds on terms that are favorable to us, if at all. If we fail to raise sufficient funds and fail to generate sufficient
revenues to achieve planned gross margins and to control operating costs, our ability to fund our operations, take advantage
of strategic opportunities, develop products or technologies, or otherwise respond to competitive pressures could be
significantly limited. If this happens, we may be forced to delay or terminate research or development programs or the
commercialization of products resulting from our technologies, curtail or cease operations or obtain funds through
collaborative and licensing arrangements that may require us to relinquish commercial rights, or grant licenses on terms
34
that are not favorable to us. If adequate funds are not available, we will not be able to successfully execute our business
plan or continue our business.
We have investments in non-marketable securities, which may subject us to significant impairment charges.
We have investments in illiquid non-marketable equity securities acquired in private transactions. At December 31,
2021, 5.7% of our consolidated assets consisted of investment securities, which are illiquid investments. Investments in
illiquid, or non-marketable, securities are inherently risky and difficult to value. We account for our non-marketable equity
securities under the measurement alternative. Under the measurement alternative, the carrying value of our non-marketable
equity investments is adjusted to fair value for observable transactions for identical or similar investments of the same
issuer or impairment. We evaluate our investment in non-marketable securities when circumstances indicate that we may
not be able to recover the carrying value. We may impair these securities and establish an allowance for a credit loss when
we determine that there has been an “other-than-temporary” decline in estimated fair value of the equity security compared
to its carrying value. The impairment analysis requires significant judgment to identify events or circumstances that would
likely have a material adverse effect on the fair value of the investment. Because over 5% of our total assets consisted of
non-marketable investment securities, any future impairment charges from the write down in value of these securities could
have a material adverse effect on our financial condition or results of operations.
Competitors and potential competitors who have greater resources and experience than we do may develop products
and technologies that make ours obsolete or may use their greater resources to gain market share at our expense.
The biocatalysis industry and each of our target markets are characterized by rapid technological change. Our future
success will depend on our ability to maintain a competitive position with respect to technological advances. In addition, as
we enter new markets, we will face new competition and will need to adapt to competitive factors that may be different
from those we face today.
We are aware that other companies, including Royal DSM, N.V. (“DSM”), BASF, Bayer and Novozymes have
alternative methods for obtaining and generating genetic diversity or use mutagenesis techniques to produce genetic
diversity. Academic institutions such as the California Institute of Technology, the Max Planck Institute and the Austrian
Centre of Industrial Biotechnology are also working in this field. Technological development by others may result in our
products and technologies, as well as products developed by our customers using our biocatalysts, becoming obsolete.
Our primary competitors in the performance enzymes for pharmaceutical products are companies marketing either
conventional, non-enzymatic processes or biocatalytic enzymes to manufacturers of pharmaceutical intermediates and
APIs, and also existing in-house technologies (both biocatalysts and conventional catalysts) within our client and potential
client companies. The principal methods of competition and competitive differentiation in this market are price, product
quality and performance, including manufacturing yield, safety and environmental benefits, and speed of delivery of
product. Pharmaceutical manufacturers that use biocatalytic processes can face increased competition from manufacturers
that use more conventional processes and/or manufacturers that are based in regions (such as India and China) with lower
regulatory, safety and environmental costs.
The market for the manufacture and supply of APIs and intermediates is large with many established companies. These
companies include many of our large innovator and generic pharmaceutical customers, such as Merck, GSK, Novartis,
Pfizer, Bristol-Myers, Kyorin, Urovant and Teva which have significant internal research and development efforts directed
at developing processes to manufacture APIs and intermediates. The processes used by these companies include classical
conventional organic chemistry reactions, chemo catalytic reactions, biocatalytic reactions or combinations thereof. Our
biocatalytic based manufacturing processes must compete with these internally developed routes. Additionally, we also
face competition from companies developing and marketing conventional catalysts such as Solvias Inc., BASF and
Takasago International Corporation.
The market for supplying enzymes for use in pharmaceutical manufacturing is quite fragmented. There is competition
from large industrial enzyme companies, such as Novozymes, and Dupont, as well as subsidiaries of larger contract
research/contract manufacturing organizations (“CRO/CMO”), such as DSM, Cambrex Corporation, Lonza, WuXi STA,
and Almac Group Ltd. Some fermentation pathway design companies, like Ginkgo Bioworks and Zymergen, whose
traditional focus has been to design microorganisms that express small molecule chemicals, could extend into designing
organisms that express enzymes. There is also competition in the enzyme customization and optimization area from several
smaller companies, such as BRAIN AG, Arzeda, c-LEcta GmbH and Evocatal GmbH.
We entered the fine chemicals market in 2013, by applying our protein engineering technology in the food market. We
face similar forms of competition in this market as in the pharmaceutical markets with the exception that the risk of losing
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opportunities to larger competitors in fine chemicals is greater given the larger scale of opportunities available in the fine
chemicals market compared to the pharmaceutical market. Our significant competitors in the fine chemicals markets
include companies that have been in these marketplaces for many years, such as DuPont Industrial Biosciences (DuPont
Genencor), DSM, Novozymes and A.B. Enzymes. These companies have greater resources in these markets than we do
and have long-term supply arrangements already in place with customers. Our ability to compete in these markets may be
limited by our relatively late entrance. We also face competition in both the fine chemicals and pharmaceutical markets
from emerging companies offering whole cell metabolic pathway approaches to these markets.
There are numerous companies that participate in the biotherapeutics market generally and the PKU market
specifically. Many of these companies are large, successful and well-capitalized. BioMarin Pharmaceutical Inc.
(“BioMarin”) and Daiichi Sankyo Company market Kuvan® in the United States, Europe and Japan for the treatment of a
certain type of PKU. In addition, BioMarin gained US FDA approval in 2018 and began commercial sales of PalynziqTM as
an injectable enzyme substitution therapy for the potential treatment of PKU. Several companies, i.e., Synlogic, Homology
Medicines, and Rubius have reported clinical efforts to develop biotherapeutic candidates for PKU. Beyond targeting PKU,
Takeda (who recently acquired Shire Plc), Genzyme / Sanofi S.A., BioMarin, and other companies market or are actively
developing new enzyme therapeutics. There are numerous companies that are developing other forms of therapeutics, such
as small molecules, gene therapies, as well as therapies based on gene editing, which could compete with biotherapeutics.
Our ability to compete successfully in any of these markets will depend on our ability to develop proprietary products
that reach the market in a timely manner and are technologically superior to and/or are less expensive than other products
on the market. Many of our competitors have substantially greater production, financial, research and development,
personnel and marketing resources than we do. They also started developing products earlier than we did, which may allow
them to establish blocking intellectual property positions or bring products to market before we can. In addition, certain of
our competitors may also benefit from local government subsidies and other incentives that are not available to us. As a
result, our competitors may be able to develop competing and/or superior technologies and processes, and compete more
aggressively and sustain that competition over a longer period of time than we could. Our technologies and products may
be rendered obsolete or uneconomical by technological advances or entirely different approaches developed by one or
more of our competitors. We cannot be certain that any products we develop in the future will compare favorably to
products offered by our competitors or that our existing or future products will compare favorably to any new products that
are developed by our competitors. As more companies develop new intellectual property in our markets, the possibility of a
competitor acquiring patent or other rights that may limit our products or potential products increases, which could lead to
litigation.
Our limited resources relative to many of our competitors may cause us to fail to anticipate or respond adequately to
new developments and other competitive pressures. This failure could reduce our competitiveness and market share,
adversely affect our results of operations and financial position, and prevent us from obtaining or maintaining profitability.
Ethical, legal and social concerns about genetically engineered products and processes could limit or prevent the
use of our products, processes, and technologies and limit our revenues.
Some of our products and processes are genetically engineered or involve the use of genetically engineered products or
genetic engineering technologies. If we and/or our collaborators are not able to overcome the ethical, legal, and social
concerns relating to genetic engineering, our products and processes may not be accepted. Any of the risks discussed below
could result in increased expenses, delays, or other impediments to our programs or the public acceptance and
commercialization of products and processes dependent on our technologies or inventions. Our ability to develop and
commercialize one or more of our technologies, products, or processes could be limited by the following factors:
•
•
•
public attitudes about the safety and environmental hazards of, and ethical concerns over, genetic research
and genetically engineered products and processes, which could influence public acceptance of our
technologies, products and processes;
public attitudes regarding, and potential changes to laws governing ownership of genetic material, which
could harm our intellectual property rights with respect to our genetic material and discourage collaborators
from supporting, developing, or commercializing our products, processes and technologies; and
governmental reaction to negative publicity concerning genetically modified organisms, which could result in
greater government regulation of genetic research and derivative products. The subject of genetically
modified organisms has received negative publicity, which has aroused public debate. This adverse publicity
could lead to greater regulation and trade restrictions on imports of genetically altered products. The
biocatalysts that we develop have significantly enhanced characteristics compared to those found in naturally
occurring enzymes or microbes. While we produce our biocatalysts only for use in a controlled industrial
36
environment, the release of such biocatalysts into uncontrolled environments could have unintended
consequences. Any adverse effect resulting from such a release could have a material adverse effect on our
business and financial condition, and we may have exposure to liability for any resulting harm.
If we engage in any acquisitions, we will incur a variety of costs and may potentially face numerous risks that could
adversely affect our business and operations.
We have made acquisitions in the past, and if appropriate opportunities become available, we expect to acquire
additional businesses, assets, technologies, or products to enhance our business in the future. For example, in October
2010, we acquired substantially all of the patents and other intellectual property rights associated with Maxygen’s directed
evolution technology.
In connection with any future acquisitions, we could:
•
•
•
•
issue additional equity securities, which would dilute our current stockholders;
incur substantial debt to fund the acquisitions;
use our cash to fund the acquisitions; or
assume significant liabilities including litigation risk.
Acquisitions involve numerous risks, including problems integrating the purchased operations, technologies or
products, unanticipated costs and other liabilities, diversion of management’s attention from our core businesses, adverse
effects on existing business relationships with current and/or prospective collaborators, customers and/or suppliers, risks
associated with entering markets in which we have no or limited prior experience and potential loss of key employees. We
do not have extensive experience in managing the integration process and we may not be able to successfully integrate any
businesses, assets, products, technologies, or personnel that we might acquire in the future without a significant
expenditure of operating, financial and management resources, if at all. The integration process could divert management’s
time from focusing on operating our business, result in a decline in employee morale and cause retention issues to arise
from changes in compensation, reporting relationships, future prospects or the direction of the business. Acquisitions may
also require us to record goodwill and non-amortizable intangible assets that will be subject to impairment testing on a
regular basis and potential periodic impairment charges, incur amortization expenses related to certain intangible assets,
and incur large and immediate write offs and restructuring and other related expenses, all of which could harm our
operating results and financial condition. In addition, we may acquire companies that have insufficient internal financial
controls, which could impair our ability to integrate the acquired company and adversely impact our financial reporting. If
we fail in our integration efforts with respect to any of our acquisitions and are unable to efficiently operate as a combined
organization, our business and financial condition may be adversely affected.
We use hazardous materials in our business and we must comply with environmental laws and regulations. Any
claims relating to improper handling, storage or disposal of these materials or noncompliance of applicable laws and
regulations could be time consuming and costly and could adversely affect our business and results of operations.
Our research and development and commercial processes involve the use of hazardous materials, including chemical,
radioactive, and biological materials. Our operations also produce hazardous waste. We cannot eliminate entirely the risk of
accidental contamination or discharge and any resultant injury from these materials. Federal, state, local and foreign laws
and regulations govern the use, manufacture, storage, handling and disposal of, and human exposure to, these materials. We
may be sued for any injury or contamination that results from our use or the use by third parties of these materials, and our
liability may exceed our total assets. Although we believe that our activities comply in all material respects with
environmental laws, there can be no assurance that violations of environmental, health and safety laws will not occur in the
future as a result of human error, accident, equipment failure or other causes. Compliance with applicable environmental
laws and regulations may be expensive, and the failure to comply with past, present, or future laws could result in the
imposition of fines, third party property damage, product liability and personal injury claims, investigation and remediation
costs, the suspension of production, or a cessation of operations, and our liability may exceed our total assets. Liability
under environmental laws can be joint and several and without regard to comparative fault. Environmental laws could
become more stringent over time imposing greater compliance costs and increasing risks and penalties associated with
violations, which could impair our research, development or production efforts and harm our business. In addition, we may
have to indemnify some of our customers or suppliers for losses related to our failure to comply with environmental laws,
which could expose us to significant liabilities.
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Our ability to use our net operating loss carryforwards to offset future taxable income may be subject to certain
limitations.
In general, under Section 382 of the Internal Revenue Code of 1986, as amended (the “Code”), a corporation that
undergoes an “ownership change” is subject to limitations on its ability to utilize its pre-change net operating loss
carryforwards (“NOLs”), to offset future taxable income. If the Internal Revenue Service challenges our analysis that our
existing NOLs are not subject to limitations arising from previous ownership changes, our ability to utilize NOLs could be
limited by Section 382 of the Code. Future changes in our stock ownership, some of which are outside of our control, could
result in an ownership change under Section 382 of the Code. Furthermore, our ability to utilize NOLs of companies that
we may acquire in the future may be subject to limitations. For these reasons, we may not be able to utilize a material
portion of the NOLs reflected in our financial statements, even if we attain profitability.
Risks Related to Government Regulation and Clinical Product Development
We or our customers may not be able to obtain regulatory approval for the use of our products in food and food
ingredients, if required, and, even if approvals are obtained, complying on an ongoing basis with the numerous
regulatory requirements applicable to these products will be time-consuming and costly.
The products that we develop for our food and food ingredient customers are, and any other products that we may
develop for the food and food ingredients market will likely be, subject to regulation by various government agencies,
including the FDA, state and local agencies and similar agencies outside the United States, as well as religious compliance
certifying organizations. Food ingredients are regulated by the FDA either as food additives or as substances generally
recognized as safe (“GRAS”). A substance can be listed or affirmed as GRAS by the FDA or self-affirmed by its
manufacturer upon determination that independent qualified experts would generally agree that the substance is GRAS for
a particular use. While we generally self-affirm GRAS status for the ingredients used in the products that we develop for
the food market, our customer(s) may be required to submit a GRAS notification to FDA to establish that ingredients in a
final commercial product may be considered GRAS. There can be no assurance that our customer(s) will not receive any
objections from the FDA with respect to any GRAS notification our customer(s) may submit. If the FDA were to disagree
with our customer’s determination that their commercial product and/or its ingredients are GRAS or otherwise compliant,
the FDA could ask such customer to voluntarily withdraw the final commercial product from the market or could initiate
legal action to halt its sale. Such actions by the FDA could have an adverse effect on our business, financial condition, and
results of our operations. Food ingredients that are not GRAS are regulated as food additives and require FDA approval
prior to commercialization or must be the subject of an existing food additive regulation. The food additive petition process
for ingredients that are not already authorized by regulation is generally expensive and time consuming, with approval, if
secured, potentially taking years.
Our ongoing efforts to deploy our technology in the life science tools markets may fail.
We have recently begun to use our CodeEvolver® protein engineering technology platform to develop new products
for customers using NGS and PCR/qPCR for in vitro molecular diagnostic applications. while we have entered into some
license agreements for products in this market, we do not know if we can successfully compete in this new market. This
new market is well established and consists of numerous large, well-funded entrenched market participants who have long
and established track records and customer relationships. In December 2019, we licensed our first proprietary enzyme for
this market, EvoT4™ DNA ligase, which is designed to improve library preparation for NGS users, to Roche. This
enzyme, and any products that we may develop in the future for this market, may not succeed in displacing current
products. If we succeed in commercializing new products for this market, we may not generate significant revenues and
cash flows from these activities. The failure to successfully deploy products on timely basis in this space may limit our
growth and have a material adverse effect on our financial condition, operating results and business prospects.
The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time consuming and
inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our product candidates, our
business will be substantially harmed.
We and any collaborators are not permitted to commercialize, market, promote or sell any product candidate in the
United States without obtaining marketing approval from the FDA. Foreign regulatory authorities impose similar
requirements. The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable, but
typically takes many years following the commencement of clinical trials and depends upon numerous factors, including
substantial discretion of the regulatory authorities. In addition, approval policies, regulations or the type and amount of
clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and
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may vary among jurisdictions. To date, neither we nor our collaborators have submitted a BLA to FDA or similar drug
approval submissions to comparable foreign regulatory authorities for any product candidate. We and any collaborators
must complete additional preclinical or nonclinical studies and clinical trials to demonstrate the safety, purity and potency
(or efficacy) of our product candidates in humans to the satisfaction of the regulatory authorities before we will be able to
obtain these approvals. Our product candidates could fail to receive regulatory approval for many reasons, including the
following:
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the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our
or our collaborators’ clinical trials;
• we or our collaborators may be unable to demonstrate to the satisfaction of the FDA or comparable foreign
regulatory authorities that a product candidate is safe and effective for its proposed indication;
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the results of clinical trials may not meet the level of statistical significance required by the FDA or
comparable foreign regulatory authorities for approval;
• we or our collaborators may be unable to demonstrate that a product candidate’s clinical and other benefits
outweigh its safety risks;
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the FDA or comparable foreign regulatory authorities may disagree with our or our collaborators’
interpretation of data from preclinical studies or clinical trials;
the data collected from clinical trials of product candidates may not be sufficient to support the submission of
a BLA to obtain regulatory approval in the United States or elsewhere;
the FDA or comparable foreign regulatory authorities may fail to approve the manufacturing processes or
facilities of third-party manufacturers with which we or our collaborators contract for clinical and commercial
supplies;
the FDA or comparable foreign regulatory authorities may fail to approve the companion diagnostics we
contemplate developing with collaborators; and
the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly
change in a manner rendering our or our collaborators’ clinical data insufficient for approval.
This lengthy approval process as well as the unpredictability of future clinical trial results may result in our failing to
obtain regulatory approval to market our product candidates, which would significantly harm our business, results of
operations and prospects. In addition, even if we were to obtain approval, regulatory authorities may approve any of our
product candidates for fewer or more limited indications than we request, may impose significant limitations in the form of
narrow indications, warnings, or a REMS. Regulatory authorities may not approve the price we or our collaborators intend
to charge for products we may develop, may grant approval contingent on the performance of costly post-marketing
clinical trials, or may approve a product candidate with a label that does not include the labeling claims necessary or
desirable for the successful commercialization of that product candidate. Any of the foregoing scenarios could materially
harm the commercial prospects for our product candidates.
Clinical trials are difficult to design and implement, expensive, time-consuming and involve an uncertain outcome,
and the inability to successfully conduct clinical trials and obtain regulatory approval for our product candidates would
substantially harm our business.
Clinical testing is expensive and usually takes many years to complete, and its outcome is inherently uncertain. Failure
can occur at any time during the clinical trial process, and product candidates in later stages of clinical trials may fail to
show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials.
We do not know whether planned clinical trials will begin on time, need to be redesigned, recruit and enroll patients on
time or be completed on schedule, or at all. Clinical trials can be delayed, suspended or terminated for a variety of reasons,
including in connection with:
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the inability to generate sufficient preclinical, toxicology or other in vivo or in vitro data to support the
initiation of clinical trials;
applicable regulatory authorities disagreeing as to the design or implementation of the clinical trials;
obtaining regulatory authorization to commence a trial;
reaching an agreement on acceptable terms with prospective contract research organizations ("CROs"), and
clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly
among different CROs and trial sites;
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obtaining IRB approval at each site;
developing and validating the companion diagnostic to be used in a clinical trial, if applicable;
insufficient or inadequate supply or quality of product candidates or other materials necessary for use in
clinical trials, or delays in sufficiently developing, characterizing or controlling a manufacturing process
suitable for clinical trials;
recruiting and retaining enough suitable patients to participate in a trial;
having enough patients complete a trial or return for post-treatment follow-up;
adding a sufficient number of clinical trial sites;
inspections of clinical trial sites or operations by applicable regulatory authorities, or the imposition of a
clinical hold;
clinical sites deviating from trial protocol or dropping out of a trial;
the inability to demonstrate the efficacy and benefits of a product candidate;
discovering that product candidates have unforeseen safety issues, undesirable side effects or other
unexpected characteristics;
addressing patient safety concerns that arise during the course of a trial; receiving untimely or unfavorable
feedback from applicable regulatory authorities regarding the trial or requests from regulatory authorities to
modify the design of a trial;
non-compliance with applicable regulatory requirements by us or third parties or changes in such regulations
or administrative actions;
suspensions or terminations by IRBs of the institutions at which such trials are being conducted, by the Data
Safety Monitoring Board for such trial or by the FDA or other regulatory authorities due to a number of
factors, including those described above;
third parties being unable or unwilling to satisfy their contractual obligations to us; or
changes in our financial priorities, greater than anticipated costs of completing a trial or our inability to
continue funding the trial.
In addition, disruptions caused by the COVID-19 pandemic may increase the likelihood that we encounter such
difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing clinical trials. Many of the
factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the
denial of regulatory approval of our product candidates. Additionally, we or our collaborators may experience unforeseen
events during or resulting from clinical trials that could delay or prevent receipt of marketing approval for or
commercialization of product candidates. For example, clinical trials of product candidates may produce negative,
inconsistent or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or
abandon development programs. Regulators may also revise the requirements for approving the product candidates, or such
requirements may not be as we anticipate. If we or our collaborators are required to conduct additional clinical trials or
other testing of product candidates beyond those that we or our collaborators currently contemplate, if we or our
collaborators are unable to successfully complete clinical trials or other testing of such product candidates, if the results of
these trials or tests are not positive or are only modestly positive or if there are safety concerns, we may:
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incur unplanned costs;
be delayed in obtaining or fail to obtain marketing approval for product candidates;
obtain marketing approval in some countries and not in others;
obtain marketing approval for indications or patient populations that are not as broad as intended or desired;
obtain marketing approval with labeling that includes significant use or distribution restrictions or safety
warnings, including boxed warnings;
be subject to additional post-marketing testing requirements;
be subject to changes in the way the product is administered;
have regulatory authorities withdraw or suspend their approval of the product or impose restrictions on its
distribution;
be sued; or
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experience damage to our reputation.
If we or our collaborators experience delays in the commencement or completion of our clinical trials, or if we or our
collaborators terminate a clinical trial prior to completion, we may experience increased costs, have difficulty raising
capital and/or be required to slow down the development and approval process timelines. Furthermore, the product
candidates that are the subject of such trials may never receive regulatory approval, and their commercial prospects and our
ability to generate product revenues from them could be impaired or not realized at all.
Results of preclinical studies and early clinical trials of product candidates may not be predictive of results of later
studies or trials. Our product candidates may not have favorable results in later clinical trials, if any, or receive
regulatory approval.
Preclinical and clinical drug development is expensive and can take many years to complete, and its outcome is
inherently uncertain. Failure can occur at any time during the preclinical study or clinical trial process. Despite promising
preclinical or clinical results, any product candidate can unexpectedly fail at any stage of preclinical or clinical
development. The historical failure rate for product candidates in our industry is high. The results from preclinical studies
or early clinical trials of a product candidate may not be predictive of the results from later preclinical studies or clinical
trials, and interim results of a clinical trial are not necessarily indicative of final results. Product candidates in later stages
of clinical trials may fail to show the desired safety and efficacy characteristics despite having progressed through
preclinical studies and initial clinical trials.
Many companies in the biopharmaceutical and biotechnology industries have suffered significant setbacks at later
stages of development after achieving positive results in early stages of development, and we may face similar setbacks.
These setbacks have been caused by, among other things, preclinical findings made while clinical trials were underway or
safety or efficacy observations made in clinical trials, including previously unreported adverse events. Moreover, non-
clinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that believed
their product candidates performed satisfactorily in preclinical studies and clinical trials nonetheless failed to obtain
regulatory approval. Even if any product candidates progress to clinical trials, these product candidates may fail to show
the safety and efficacy in clinical development required to obtain regulatory approval, despite the observation of positive
results in animal studies. Our or our collaborators’ failure to replicate positive results from early research programs and
preclinical or greenhouse studies may prevent us from further developing and commercializing those or other product
candidates, which would limit our potential to generate revenues from them and harm our business and prospects.
For the foregoing reasons, we cannot be certain that any ongoing or future preclinical studies or clinical trials will be
successful. Any safety or efficacy concerns observed in any one of our preclinical studies or clinical trials in a targeted area
could limit the prospects for regulatory approval of product candidates in that and other areas, which could have a material
adverse effect on our business and prospects.
Even if we obtain regulatory approval for any products that we develop alone or with collaborators, such products
will remain subject to ongoing regulatory requirements, which may result in significant additional expense.
Even if products we develop alone or with collaborators receive regulatory approval, they will be subject to ongoing
regulatory requirements for manufacturing, labeling, packaging, distribution, storage, advertising, promotion, sampling,
record-keeping and submission of safety and other post-market information, among other things. Any regulatory approvals
received for such products may also be subject to limitations on the approved indicated uses for which they may be
marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing and
surveillance studies. For example, the holder of an approved BLA in the United States is obligated to monitor and report
adverse events and any failure of a product to meet the specifications in the BLA. In the United States, the holder of an
approved BLA must also submit new or supplemental applications and obtain FDA approval for certain changes to the
approved product, product labeling or manufacturing process. Similar provisions apply in the European Union. Advertising
and promotional materials must comply with FDA rules and are subject to FDA review, in addition to other potentially
applicable federal and state laws. Similarly, in the European Union any promotion of medicinal products is highly
regulated and, depending on the specific jurisdiction involved, may require prior vetting by the competent national
regulatory authority. In addition, product manufacturers and their facilities are subject to payment of user fees and
continual review and periodic inspections by the FDA and other regulatory authorities for compliance with cGMP
requirements and adherence to commitments made in the BLA or foreign marketing application.
If we, our collaborators or a regulatory agency discovers previously unknown problems with a product such as adverse
events of unanticipated severity or frequency or problems with the facility where the product is manufactured or disagrees
with the promotion, marketing or labeling of that product, a regulatory agency may impose restrictions relative to that
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product, the manufacturing facility or us or our collaborators, including requiring recall or withdrawal of the product from
the market or suspension of manufacturing.
Moreover, if any of our product candidates are approved, our product labeling, advertising, promotion and distribution
will be subject to regulatory requirements and continuing regulatory review. The FDA strictly regulates the promotional
claims that may be made about drug products. In particular, a product may not be promoted for uses that are not approved
by the FDA as reflected in the product’s approved labeling. If we or our collaborators fail to comply with applicable
regulatory requirements following approval of any potential products we may develop, authorities may:
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issue an untitled enforcement letter or a warning letter asserting a violation of the law;
seek an injunction, impose civil and criminal penalties, and impose monetary fines, restitution or
disgorgement of profits or revenues;
suspend or withdraw regulatory approval;
suspend or terminate any ongoing clinical trials or implement requirements to conduct post-marketing studies
or clinical trials;
refuse to approve a pending BLA or comparable foreign marketing application (or any supplements thereto)
submitted by us or our collaborators;
restrict the labeling, marketing, distribution, use or manufacturing of products;
seize or detain products or otherwise require the withdrawal or recall of products from the market;
refuse to approve pending applications or supplements to approved applications that we or our collaborators
submit;
refuse to permit the import or export of products; or
refuse to allow us or our collaborators to enter into government contracts.
Any government investigation of alleged violations of law could require us to expend significant time and resources in
response and could generate negative publicity. The occurrence of any event or penalty described above may inhibit our or
our collaborators’ ability to commercialize products and our ability to generate revenues.
In addition, the FDA’s policies, and policies of foreign regulatory agencies, may change, and additional regulations
may be enacted that could prevent, limit or delay regulatory approval of product candidates. We cannot predict the
likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive
action, either in the United States or abroad. If we are slow or unable to adapt to changes in existing requirements or the
adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may be subject to
enforcement action and we may not achieve or sustain profitability.
Our business operations and future relationships with investigators, healthcare professionals, consultants, third-
party payors, patient organizations and customers will be subject to applicable healthcare regulatory laws, which could
expose us to penalties.
Our business operations and future arrangements with investigators, healthcare professionals, consultants, third-party
payors, patient organizations and customers, may expose us to broadly applicable fraud and abuse and other healthcare
laws and regulations. These laws may constrain the business or financial arrangements and relationships through which we
will conduct our operations, including how we research, market, sell and distribute our product candidates, if approved.
Such laws include:
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the U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from
knowingly and willfully soliciting, offering, receiving or providing any remuneration (including any
kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or
reward, or in return for, either the referral of an individual for, or the purchase, lease, order or
recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part,
under U.S. federal and state healthcare programs such as Medicare and Medicaid. A person or entity does not
need to have actual knowledge of the statute or specific intent to violate it in order to have committed a
violation;
the U.S. federal false claims laws, including the civil False Claims Act, which, among other things, impose
criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or
entities for knowingly presenting, or causing to be presented, to the U.S. federal government, claims for
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payment or approval that are false or fraudulent, knowingly making, using or causing to be made or used, a
false record or statement material to a false or fraudulent claim, or from knowingly making a false statement
to avoid, decrease or conceal an obligation to pay money to the U.S. federal government. In addition, the
government may assert that a claim including items and services resulting from a violation of the U.S. federal
Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act;
the U.S. federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which imposes
criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to
execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying,
concealing or covering up a material fact or making any materially false statement, in connection with the
delivery of, or payment for, healthcare benefits, items or services; similar to the U.S. federal Anti-Kickback
Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it
in order to have committed a violation;
the U.S. federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices,
biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health
Insurance Program to report annually to the government information related to certain payments and other
transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and
chiropractors), certain non-physician practitioners such as physician assistants and nurse practitioners, and
teaching hospitals, as well as ownership and investment interests held by the physicians described above and
their immediate family members;
analogous U.S. state laws and regulations, including: state anti-kickback and false claims laws, which may
apply to our future business practices, including but not limited to, research, distribution, sales and marketing
arrangements and claims involving healthcare items or services reimbursed by any third-party payor,
including private insurers; state laws that require pharmaceutical companies to comply with the
pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance
promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare
providers and other potential referral sources; state laws and regulations that require drug manufacturers to
file reports relating to pricing and marketing information, which requires tracking gifts and other
remuneration and items of value provided to healthcare professionals and entities; and state laws governing
the privacy and security of health information in certain circumstances, many of which differ from each other
in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts; and
similar healthcare laws and regulations in the EU and other jurisdictions, including reporting requirements
detailing interactions with and payments to healthcare providers and laws governing the privacy and security
of certain protected information, such as the General Data Protection Regulation (“GDPR”), which imposes
obligations and restrictions on the collection and use of personal data relating to individuals located in the
European Economic Area (“EEA”) (including health data).
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Ensuring that our internal operations and future business arrangements with third parties comply with applicable
healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that
our business practices do not comply with current or future statutes, regulations, agency guidance or case law involving
applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of
the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to
significant penalties, including civil, criminal and administrative penalties, damages, fines, exclusion from government-
funded healthcare programs, such as Medicare and Medicaid or similar programs in other countries or jurisdictions,
disgorgement, individual imprisonment, contractual damages, reputational harm, diminished profits and the curtailment or
restructuring of our operations.
The successful commercialization of product candidates developed by us or our partners will depend in part on the
extent to which governmental authorities and health insurers establish adequate coverage, reimbursement levels and
pricing policies. Failure to obtain or maintain coverage and adequate reimbursement for such product candidates, if
approved, could limit our or our partners’ ability to market those products and decrease our ability to generate revenue.
The availability and adequacy of coverage and reimbursement by governmental healthcare programs such as Medicare
and Medicaid, private health insurers and other third-party payors are essential for most patients to be able to afford
prescription medications such as our product candidates, assuming FDA approval. Our ability to achieve acceptable levels
of coverage and reimbursement for products by governmental authorities, private health insurers and other organizations
will have an effect on our ability to successfully commercialize our product candidates. Assuming we obtain coverage for
our product candidates by a third-party payor, the resulting reimbursement payment rates may not be adequate or may
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require co-payments that patients find unacceptably high. We cannot be sure that coverage and reimbursement in the
United States, the EU or elsewhere will be available for our product candidates or any product that we may develop, and
any reimbursement that may become available may be decreased or eliminated in the future.
Third-party payors increasingly are challenging prices charged for pharmaceutical products and services, and many
third-party payors may refuse to provide coverage and reimbursement for particular drugs or biologics when an equivalent
generic drug, biosimilar or a less expensive therapy is available. It is possible that a third-party payor may consider our
product candidates as substitutable and only offer to reimburse patients for the less expensive product. Even if we show
improved efficacy or improved convenience of administration with our product candidates, pricing of existing third-party
therapeutics may limit the amount we will be able to charge for our product candidates. These payors may deny or revoke
the reimbursement status of a given product or establish prices for new or existing marketed products at levels that are too
low to enable us to realize an appropriate return on our investment in our product candidates. For products administered
under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because
of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself or the
treatment or procedure in which the product is used may not be available, which may impact physician utilization. If
reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize our
product candidates, and may not be able to obtain a satisfactory financial return on our product candidates.
No uniform policy for coverage and reimbursement for products exists among third-party payors in the United States.
Therefore, coverage and reimbursement for products can differ significantly from payor to payor. As a result, the coverage
determination process is often a time-consuming and costly process that will require us to provide scientific and clinical
support for the use of our product candidates to each payor separately, with no assurance that coverage and adequate
reimbursement will be applied consistently or obtained in the first instance. Furthermore, rules and regulations regarding
reimbursement change frequently, in some cases on short notice, and we believe that changes in these rules and regulations
are likely.
Outside the United States, international operations are generally subject to extensive governmental price controls and
other market regulations, and we believe the increasing emphasis on cost-containment initiatives in Europe and other
countries have and will continue to put pressure on the pricing and usage of our product candidates. In many countries, the
prices of medical products are subject to varying price control mechanisms as part of national health systems. Other
countries allow companies to fix their own prices for medical products, but monitor and control company profits.
Additional foreign price controls or other changes in pricing regulation could restrict the amount that we are able to charge
for our product candidates. Accordingly, in markets outside the United States, the reimbursement for our product
candidates may be reduced compared with the United States and may be insufficient to generate commercially-reasonable
revenue and profits.
Moreover, increasing efforts by governmental and third-party payors in the United States and abroad to cap or reduce
healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for newly approved
products and, as a result, they may not cover or provide adequate payment for our product candidates. We expect to
experience pricing pressures in connection with the sale of our product candidates due to the trend toward managed health
care, the increasing influence of health maintenance organizations and additional legislative changes. The downward
pressure on healthcare costs in general, particularly prescription drugs and biologics and surgical procedures and other
treatments, has become intense. As a result, increasingly high barriers are being erected to the entry of new products.
Compliance with European Union chemical regulations could be costly and adversely affect our business and
results of operations.
Some of our products are subject to the European Union regulatory regime known as The Registration, Evaluation and
Authorization of Chemicals (“REACH”). REACH mandates that certain chemicals manufactured in, or imported into, the
European Union be registered and evaluated for their potential effects on human health and the environment. Under
REACH, we and our contract manufacturers located in the European Union are required to register certain of our products
based on the quantity of such product imported into or manufactured in the European Union and on the product’s intended
end-use. The registration, evaluation and authorization process under REACH can be costly and time consuming. Problems
or delays in the registration, evaluation or authorization process under REACH could delay or prevent the manufacture of
some of our products in, or the importation of some of our products into, the European Union, which could adversely affect
our business and results of operations. In addition, if we or our contract manufacturers fail to comply with REACH, we
may be subject to penalties or other enforcement actions, which could have a material adverse effect on our business and
results of operations.
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Risks Related to our Dependence on Third Parties
We rely on third parties to conduct our clinical trials and perform some of our research and preclinical studies. If
these third parties do not satisfactorily carry out their contractual duties or fail to meet expected deadlines, our
development programs may be delayed or subject to increased costs, each of which may have an adverse effect on our
business and prospects.
We do not have the ability to conduct all aspects of our preclinical testing or clinical trials ourselves. As a result, we
are and expect to remain dependent on third parties to conduct clinical trials of our product candidates. Specifically, we
expect CROs, clinical investigators, and consultants to play a significant role in the conduct of these trials and the
subsequent collection and analysis of data. However, we will not be able to control all aspects of their activities.
Nevertheless, we are responsible for ensuring that each of our trials is conducted in accordance with the applicable protocol
and legal, regulatory and scientific standards, and our reliance on the CROs and other third parties does not relieve us of
our regulatory responsibilities. We and our CROs are required to comply with GCP requirements, which are regulations
and guidelines enforced by the FDA and comparable foreign regulatory authorities for all of our product candidates in
clinical development. Regulatory authorities enforce these GCP requirements through periodic inspections of trial
sponsors, clinical trial investigators and clinical trial sites. If we or any of our CROs or clinical trial sites fail to comply
with applicable GCP requirements, the data generated in our clinical trials may be deemed unreliable, and the FDA or
comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our
marketing applications. In addition, our clinical trials must be conducted with product produced under cGMP regulations.
Our failure to comply with these regulations may require us to stop and/or repeat clinical trials, which would delay the
marketing approval process.
There is no guarantee that any such CROs, clinical trial investigators or other third parties on which we rely will
devote adequate time and resources to our development activities or perform as contractually required. If any of these third
parties fail to meet expected deadlines, adhere to our clinical protocols or meet regulatory requirements, otherwise
performs in a substandard manner, or terminates its engagement with us, the timelines for our development programs may
be extended or delayed or our development activities may be suspended or terminated. If any of our clinical trial sites
terminates for any reason, we may experience the loss of follow-up information on subjects enrolled in such clinical trials
unless we are able to transfer those subjects to another qualified clinical trial site, which may be difficult or impossible. In
addition, clinical trial investigators for our clinical trials may serve as scientific advisors or consultants to us from time to
time and may receive cash or equity compensation in connection with such services. If these relationships and any related
compensation result in perceived or actual conflicts of interest, or the FDA or comparable foreign regulatory authorities
concludes that the financial relationship may have affected the interpretation of the trial, the integrity of the data generated
at the applicable clinical trial site may be questioned and the utility of the clinical trial itself may be jeopardized, which
could result in the delay or rejection of any marketing application we submit by the FDA or any comparable foreign
regulatory authority. Any such delay or rejection could prevent us from commercializing our product candidates.
We contract with third parties for the manufacturing and supply of product candidates for use in preclinical testing
and clinical trials and related services, which supply may become limited or interrupted or may not be of satisfactory
quality and quantity.
We do not have any manufacturing facilities. We produce in our laboratory relatively small quantities of products for
evaluation in our research programs. We rely, and expect to continue to rely, on third parties for the manufacture of our
product candidates for preclinical and clinical testing, as well as for commercial manufacture if any of our product
candidates are approved. We currently have limited manufacturing arrangements and expect that each of our product
candidates will only be covered by single source suppliers for the foreseeable future. This reliance increases the risk that
we will not have sufficient quantities of our product candidates or products, if approved, or such quantities at an acceptable
cost or quality, which could delay, prevent or impair our development or commercialization efforts.
Furthermore, all entities involved in the preparation of therapeutics for clinical trials or commercial sale, including our
existing contract manufacturers for our product candidates, are subject to extensive regulation. Components of a finished
therapeutic product approved for commercial sale or used in clinical trials must be manufactured in accordance with cGMP
requirements. These regulations govern manufacturing processes and procedures, including record keeping, and the
implementation and operation of quality systems to control and assure the quality of investigational products and products
approved for sale. Poor control of production processes can lead to the introduction of contaminants, or to inadvertent
changes in the properties or stability of our product candidates that may not be detectable in final product testing. We or our
contract manufacturers must supply all necessary documentation in support of a BLA on a timely basis and must adhere to
the FDA’s cGMP regulations enforced by the FDA through its facilities inspection program. Comparable foreign regulatory
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authorities may require compliance with similar requirements. The facilities and quality systems of our third-party
contractor manufacturers must pass a pre-approval inspection for compliance with the applicable regulations as a condition
of marketing approval of our product candidates. We do not control the manufacturing activities of, and are completely
dependent on, our contract manufacturers for compliance with cGMP regulations.
In the event that any of our manufacturers fails to comply with such requirements or to perform its obligations to us in
relation to quality, timing or otherwise, or if our supply of components or other materials becomes limited or interrupted
for other reasons, we may be forced to manufacture the materials ourselves, for which we currently do not have the
capabilities or resources, or enter into an agreement with another third party, which we may not be able to do on
commercially reasonable terms, if at all. In particular, any replacement of our manufacturers could require significant effort
and expertise because there may be a limited number of qualified replacements. In some cases, the technical skills or
technology required to manufacture our product candidates may be unique or proprietary to the original manufacturer and
we may have difficulty transferring such skills or technology to another third party and a feasible alternative may not exist.
In addition, certain of our product candidates and our own proprietary methods have never been produced or implemented
outside of our company, and we may therefore experience delays to our development programs if and when we attempt to
establish new third party manufacturing arrangements for these product candidates or methods. These factors would
increase our reliance on such manufacturer or require us to obtain a license from such manufacturer in order to have
another third party manufacture our product candidates. If we are required to change manufacturers for any reason, we will
be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and
with all applicable regulations and guidelines. The delays associated with the verification of a new manufacturer could
negatively affect our ability to develop product candidates in a timely manner or within budget.
Our or a third party’s failure to execute on our manufacturing requirements, do so on commercially reasonable terms
and comply with cGMP could adversely affect our business in a number of ways, including:
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an inability to initiate or continue clinical trials of our product candidates under development;
delay in submitting regulatory applications, or receiving marketing approvals, for our product candidates;
loss of the cooperation of future collaborators;
subjecting third-party manufacturing facilities or our manufacturing facilities to additional inspections by
regulatory authorities;
requirements to cease development or to recall batches of our product candidates; and
in the event of approval to market and commercialize our product candidates, an inability to meet commercial
demands for our product or any other future product candidates.
Risks Related to Intellectual Property and Information Technology
Our efforts to prosecute and protect our intellectual property may not be successful.
We will continue to file and prosecute patent applications and maintain trade secrets in an ongoing effort to protect our
intellectual property. It is possible that our current patents, or patents which we may later acquire, may be successfully
challenged or invalidated in whole or in part. It is also possible that we may not obtain issued patents from our pending
patent applications or other inventions we seek to protect. We sometimes permit certain patents or patent applications to
lapse or go abandoned under appropriate circumstances. Due to uncertainties inherent in prosecuting patent applications,
sometimes patent applications are rejected, and we subsequently abandon them. It is also possible that we may develop
proprietary products or technologies in the future that are not patentable or that the patents of others will limit or altogether
preclude our ability to conduct business. In addition, any patent issued to us or to our licensor may provide us with little or
no competitive advantage, in which case we may abandon such patent or license it to another entity, or terminate the
license agreement.
Our means of protecting our proprietary rights may not be adequate and our competitors may independently develop
technology or products that are similar to ours or that compete with ours. Patent, trademark, copyright and trade secret laws
afford only limited protection for our technology platform, services and products. The laws of many countries do not
protect our proprietary rights to as great an extent as do the laws of the United States. Despite our efforts to protect our
proprietary rights, unauthorized parties have in the past attempted, and may in the future attempt, to operate under aspects
of our intellectual property, technology, services or products or to obtain and use information that we regard as proprietary.
Third parties may also design around our proprietary rights, which may render our protected technology, services and
products less valuable, if the design around is favorably received in the marketplace. In addition, if any of our products,
services or technology is covered by third-party patents or other intellectual property rights, we could be subject to various
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legal actions. We cannot assure you that our technology platform, services and products do not infringe patents held by
others or that they will not in the future.
Litigation may be necessary to enforce our intellectual property rights, to protect our trade secrets, to determine the
validity and scope of the proprietary rights of others, or to defend against claims of infringement, invalidity,
misappropriation, or other claims.
Any such litigation could result in substantial costs and diversion of our resources. Moreover, any settlement of or
adverse judgment resulting from litigation relating to intellectual property could require us to obtain a license to continue to
make, use or sell the products or technology that is the subject of the claim, or otherwise restrict or prohibit our use of the
technology, product or services.
Our ability to compete may decline if we do not adequately protect our proprietary technologies or if we lose some
of our intellectual property rights.
Our success depends in part on our ability to obtain patents and maintain adequate protection of our intellectual
property for our technologies, services and products in the United States and other countries. We have adopted a strategy of
seeking patent protection in the United States and in foreign countries with respect to certain of the technologies used in or
relating to our services, products and processes. As such, as of December 31, 2021, we owned or controlled approximately
1,900 issued patents and pending patent applications in the United States and in various foreign jurisdictions. Our patents
and patent applications, if issued, as of December 31, 2021, have terms that expire between 2022 and approximately 2042.
We also have license rights to a number of issued patents and pending patent applications in the United States and in
various foreign jurisdictions. Our owned and licensed patents and patent applications include those directed to our enabling
technologies and to the methods and products that support our business in the biotherapeutics, molecular diagnostics, food
and other markets. We intend to continue to apply for patents relating to our technologies, methods, services and products
as we deem appropriate.
Issuance of claims in patent applications and enforceability of such claims once issued involve complex legal and
factual questions and, therefore, we cannot predict with any certainty whether any of our issued patents will survive
invalidity claims asserted by third parties. Issued patents and patents issuing from pending applications may be challenged,
invalidated, or circumvented. Moreover, the United States Leahy-Smith America Invents Act (“AIA”), enacted in
September 2011, brought significant changes to the United States patent system, which include a change to a “first to file”
system from a “first to invent” system and changes to the procedures for challenging issued patents and disputing patent
applications during the examination process, among other things. While interference proceedings are possible for patent
claims filed prior to March 16, 2013, many of our filings will be subject to the post- and pre-grant proceedings set forth in
the AIA, including citation of prior art and written statements by third parties, third party pre-issuance submissions, ex
parte reexamination, inter partes review, post-grant review, and derivation proceedings. We may need to utilize the
processes provided by the AIA for supplemental examination or patent reissuance. These proceedings could result in
substantial cost to us even if the outcome is favorable. Even if successful, any interference may result in loss of certain
claims. Any litigation or proceedings could divert our management's time and efforts. Even unsuccessful claims brought by
third parties could result in significant legal fees and other expenses, diversion of management time, and disruption in our
business. Uncertainties resulting from initiation and continuation of any patent or related litigation could harm our ability
to compete. We have not assessed the applicability of the AIA and new regulations on our patent portfolio. These changes
could increase the costs and uncertainties surrounding the prosecution of our patent applications and the enforcement or
defense of our patent rights.
Additional uncertainty may result from legal precedent handed down by the United States Federal Circuit Court and
Supreme Court as they determine legal issues concerning the scope and construction of patent claims and inconsistent
interpretation of patent laws by the lower courts. Accordingly, we cannot ensure that any of our pending patent applications
will result in issued patents, or even if issued, predict the breadth of the claims upheld in our and other companies' patents.
Given that the degree of future protection for our proprietary rights is uncertain, we cannot ensure that: (i) we were the first
to invent the inventions covered by each of our pending applications, (ii) we were the first to file patent applications for
these inventions, or (iii) the proprietary technologies we develop will be patentable. In addition, unauthorized parties may
attempt to copy or otherwise obtain and use our products or technology. Monitoring unauthorized use of our intellectual
property is difficult, and we cannot be certain that the steps we have taken will prevent unauthorized use of our technology,
particularly in certain foreign countries where the local laws may not protect our proprietary rights as fully as in the United
States. Moreover, third parties could practice our inventions in territories where we do not have patent protection. Such
third parties may then try to import products made using our inventions into the United States or other countries. If
competitors are able to use our technology, our ability to compete effectively could be harmed. In addition, others may
independently develop and obtain patents for technologies that are similar to or superior to our technologies. If that
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happens, we may need to license these technologies, and we may not be able to obtain licenses on reasonable terms, if at
all, which could cause harm to our business.
Third parties may claim that we are infringing their intellectual property rights or other proprietary rights, which
may subject us to costly and time consuming litigation and prevent us from developing or commercializing our
products.
Our commercial success also depends in part on our ability to operate without infringing patents and proprietary rights
of third parties, and without breaching any licenses or other agreements that we have entered into with regard to our
technologies, services, products and business. We cannot ensure that patents have not been issued to third parties that could
block our ability to obtain patents or to operate as we would like. There may be patents in some countries that, if valid, may
block our ability to make, use or sell our products in those countries, or import our products into those countries, if we are
unsuccessful in circumventing or acquiring rights to these patents. There also may be claims in patent applications filed in
some countries that, if granted and valid, may also block our ability to commercialize products or processes in these
countries if we are unable to circumvent or license them.
The industries in which we operate and the biotechnology industry, in particular, are characterized by frequent and
extensive litigation regarding patents and other intellectual property rights. Many biotechnology companies have employed
intellectual property litigation as a way to gain a competitive advantage. Our involvement in litigation or other intellectual
property proceedings inside and outside of the United States, to defend our intellectual property rights or as a result of
alleged infringement of the rights of others, may divert our management’s time from focusing on business operations and
could cause us to spend significant amounts of money. Any potential intellectual property litigation also could force us to
do one or more of the following:
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stop selling or using our products or technologies that use the subject intellectual property;
pay monetary damages or substantial royalties;
grant cross-licenses to third parties relating to our patents or proprietary rights;
obtain from the third party asserting its intellectual property rights a license to sell or use the relevant
technology, which license may not be available on reasonable terms, or at all; or
redesign those products or processes that use any allegedly infringing technology, or relocate the operations
relating to the allegedly infringing technology to another jurisdiction, which may result in significant cost or
delay to us, could be technically infeasible or could prevent us from selling some of our products in the
United States or other jurisdictions.
We are aware of some patents and patent applications relating to aspects of our technologies filed by, and issued to,
third parties. We cannot assure you that if this third party intellectual property is asserted against us that we would
ultimately prevail.
We may be involved in lawsuits to protect or enforce our intellectual property rights, which could be expensive,
time-consuming and unsuccessful.
Competitors may infringe our intellectual property rights or those of our licensors. To prevent infringement or
unauthorized use, we have in the past filed, and may in the future be required to file, infringement claims, which can be
expensive and time-consuming. In addition, in an infringement proceeding, a court may decide that the intellectual
property that we own or in-license is not valid, is unenforceable and/or is not infringed. In addition, in legal proceedings
against a third party to enforce a patent directed at one of our technologies, services or products, the defendant could
counterclaim that our patent is invalid and/or unenforceable in whole or in part. In patent litigation in the United States,
defendant counterclaims alleging invalidity and/or unenforceability are commonplace. Grounds for a patent validity
challenge include an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness or
non-enablement. Grounds for an unenforceability assertion could include an allegation that someone connected with
prosecution of the patent withheld relevant information from the United States Patent and Trademark Office (“USPTO”) or
made a misleading statement during prosecution. Third parties may also raise similar claims before the USPTO, even
outside the context of litigation. The outcome following legal assertions of invalidity and unenforceability is unpredictable,
and prior art could render our patents or those of our licensors invalid. If a defendant were to prevail on a legal assertion of
invalidity and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on such product.
Such a loss of patent protection would have a material adverse impact on our business.
Even if resolved in our favor, litigation or other legal proceedings relating to our intellectual property rights may cause
us to incur significant expenses, and could distract our technical and management personnel from their normal
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responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim
proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a
substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our
expenses and reduce the resources available for operations and research and development activities. We may not have
sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may
be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial
resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could
compromise our ability to compete in the marketplace. Furthermore, because of the substantial amount of discovery
required in connection with intellectual property litigation, there is a risk that some of our confidential information could
be compromised by disclosure during this type of litigation.
We may not be able to enforce our intellectual property rights throughout the world.
The laws of some foreign countries where we do business do not protect intellectual property rights to the same extent
as the laws of the United States. Many companies have encountered significant problems in protecting and defending
intellectual property rights in certain foreign jurisdictions. The legal systems of certain countries, particularly certain
developing countries, do not favor the enforcement of patents and other intellectual property, particularly those relating to
biotechnology and/or bioindustrial technologies. Accordingly, our efforts to protect our intellectual property rights in such
countries may be inadequate. This could make it difficult for us to stop the infringement of our patents or misappropriation
of our other intellectual property rights. Additionally, proceedings to enforce our patent rights in foreign jurisdictions could
result in substantial costs and divert our efforts and attention from other aspects of our business.
If our biocatalysts, or the genes that code for our biocatalysts, are stolen, misappropriated or reverse engineered,
others could use these biocatalysts or genes to produce competing products.
Third parties, including our contract manufacturers, customers and those involved in shipping our biocatalysts, often
have custody or control of our biocatalysts. If our biocatalysts, or the genes that code for our biocatalysts, were stolen,
misappropriated or reverse engineered, they could be used by other parties who may be able to reproduce these biocatalysts
for their own commercial gain. If this were to occur, it may be difficult for us to challenge this type of use, especially in
countries with limited intellectual property protection or in countries in which we do not have patents covering the
misappropriated biocatalysts.
Risks Related to Owning our Common Stock
We are subject to anti-takeover provisions in our certificate of incorporation and bylaws and under Delaware law
that could delay or prevent an acquisition of our company, even if the acquisition would be beneficial to our
stockholders.
Provisions in our amended and restated certificate of incorporation and our bylaws may delay or prevent an acquisition
of us. Among other things, our amended and restated certificate of incorporation and bylaws provide for a board of
directors which is divided into three classes, with staggered three-year terms and provide that all stockholder action must
be effected at a duly called meeting of the stockholders and not by a consent in writing, and further provide that only our
board of directors, the chairman of the board of directors, our chief executive officer or president may call a special
meeting of the stockholders. In addition, our amended and restated certificate of incorporation allows our board of
directors, without further action by our stockholders, to issue up to 5,000,000 shares of preferred stock in one or more
series and to fix the rights, preferences, privileges and restrictions thereof. These provisions may also frustrate or prevent
any attempts by our stockholders to replace or remove our current management by making it more difficult for
stockholders to replace members of our board of directors, who are responsible for appointing the members of our
management team. Furthermore, because we are incorporated in Delaware, we are governed by the provisions of
Section 203 of the Delaware General Corporation Law which prohibits, with some exceptions, stockholders owning in
excess of 15% of our outstanding voting stock from merging or combining with us. Finally, our charter documents
establish advanced notice requirements for nominations for election to our board of directors and for proposing matters that
can be acted upon at stockholder meetings. Although we believe these provisions together provide for an opportunity to
receive higher bids by requiring potential acquirers to negotiate with our board of directors, they would apply even if an
offer to acquire our company may be considered beneficial by some stockholders.
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Our quarterly or annual operating results may fluctuate in the future. As a result, we may fail to meet or exceed the
expectations of research analysts or investors, which could cause our stock price to decline.
Our financial condition and operating results have varied significantly in the past and may continue to fluctuate from
quarter to quarter and year to year in the future due to a variety of factors, many of which are beyond our control. Factors
relating to our business that may contribute to these fluctuations include the following factors, as well as other factors
described elsewhere in this report:
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our ability to achieve or maintain profitability;
our relationships with, and dependence on, collaborators in our principal markets;
our dependence on a limited number of customers, including Pfizer;
our product supply agreements with customers have finite duration, may not be extended or renewed and
generally do not require the customer to purchase any particular quantity or quantities of our products;
• with respect to customers purchasing our products for the manufacture of active pharmaceutical products
(API) for which they have exclusivity due to patent protection, the termination or expiration of such patent
protection and any resulting generic competition may materially and adversely affect our revenues, financial
condition or results of operations;
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our dependence on a limited number of products in our performance enzymes business;
our reliance on a limited number of contract manufacturers for large scale production of substantially all of
our enzyme products;
our ability to develop and successfully commercialize new products for the markets we serve;
our ability to obtain additional development partners for our novel biotherapeutic programs;
potential of Nestlé Health Science or Takeda terminating any development program under their license
agreements with us;
potential of GSK, Merck, Novartis or any other performance enzyme customer terminating their agreements
with us;
our ability to deploy our technology platform in the fine chemicals market;
the success of our customers’ products in the market and the ability of such customers to obtain regulatory
approvals for products and processes;
our or our customers’ ability to obtain regulatory approval for the sale and manufacturing of food products
using our enzymes;
our ability to deploy our technology platform in life science tools markets;
our ability to successfully achieve domestic and foreign regulatory approval for product candidates;
our ability to successfully design and execute clinical testing at a reasonable cost and on an acceptable time-
frame;
our dependence on product candidates which could unexpectedly fail at any stage of preclinical or clinical
development;
our dependence on product candidates which may lack the ability to work as intended or cause undesirable
side effects;
our dependency on third parties to conduct clinical trials, research, and preclinical studies;
our ability to successfully prosecute and protect our intellectual property;
our ability to compete if we do not adequately protect our proprietary technologies or if we lose some of our
intellectual property rights;
our ability to avoid infringing the intellectual property rights of third parties;
our involvement in lawsuits to protect or enforce our patents or other intellectual property rights;
our ability to enforce our intellectual property rights throughout the world;
our dependence on, and the need to attract and retain, key management and other personnel;
our ability to prevent the theft or misappropriation of our biocatalysts, the genes that code for our
biocatalysts, know-how or technologies;
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our ability to protect our trade secrets and other proprietary information from disclosure by employees and
others;
our ability to obtain substantial additional capital that may be necessary to expand our business;
our ability to comply with the terms of our credit facility;
our ability to timely pay debt service obligations;
our customers’ ability to pay amounts owed to us in a timely manner;
our ability to avoid charges to earnings as a result of any impairment of goodwill, intangible assets or other
long-lived assets;
changes in financial accounting standards or practices may cause adverse, unexpected financial reporting
fluctuations and affect our reported results of operations;
our ability to maintain effective internal control over financial reporting;
our dependency on information technology systems, infrastructure and data;
our ability to control and to improve product gross margins;
our ability to protect against risks associated with the international aspects of our business;
the cost of compliance with European Union chemical regulations;
potential advantages that our competitors and potential competitors may have in securing funding or
developing products;
our ability to accurately report our financial results in a timely manner;
results of regulatory tax examinations;
business interruptions due to natural disasters, disease outbreaks or other events beyond our control;
public concerns about the ethical, legal and social ramifications of genetically engineered products and
processes;
our ability to integrate our current business with any businesses that we may acquire in the future;
our ability to properly handle and dispose of hazardous materials in our business;
potential product liability claims;
changes to tax law and related regulations could materially affect our tax obligations and effective tax rate;
and
our ability to use our net operating loss carryforwards to offset future taxable income.
Due to the various factors mentioned above, and others, the results of any prior quarterly or annual periods should not
be relied upon as indications of our future operating performance.
We do not intend to pay cash dividends for the foreseeable future.
We currently intend to retain our future earnings, if any, to finance the further development and expansion of our
business and do not intend to pay cash dividends in the foreseeable future. Any future determination to pay dividends will
be at the discretion of our board of directors and will depend on our financial condition, results of operations, capital
requirements, restrictions contained in future agreements and financing instruments, business prospects and such other
factors as our board of directors deems relevant.
General Risk Factors
If securities or industry analysts do not publish research or reports about our business, or publish negative reports
about our business, our stock price and trading volume could decline.
The trading market for our common stock will be influenced by the research and reports that securities or industry
analysts publish about us or our business. We do not have any control over these analysts. If one or more of the analysts
who cover us downgrade our stock or change their opinion of our stock in a negative manner, our stock price would likely
decline. If one or more of these analysts cease coverage of our company or fail to regularly publish reports on us, we could
lose visibility in the financial markets, which could cause our stock price or trading volume to decline.
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We face risks associated with our international business.
While we have a limited number of employees located outside of the United States, we are and will continue to be
dependent upon contract manufacturers located outside of the United States. In addition, we have customers and partners
located outside of the United States. Conducting business internationally exposes us to a variety of risks, including:
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changes in or interpretations of foreign regulations that may adversely affect our ability to sell our products,
repatriate profits to the United States or operate our foreign-located facilities;
the imposition of tariffs;
the imposition of limitations on, or increase of, withholding and other taxes on remittances and other payments by
foreign subsidiaries or joint ventures;
the imposition of limitations on genetically-engineered products or processes and the production or sale of those
products or processes in foreign countries;
currency exchange rate fluctuations;
uncertainties relating to foreign laws, regulations and legal proceedings including tax, import/export, anti-
corruption and exchange control laws;
the availability of government subsidies or other incentives that benefit competitors in their local markets that are
not available to us;
increased demands on our limited resources created by our operations may constrain the capabilities of our
administrative and operational resources and restrict our ability to attract, train, manage and retain qualified
management, technicians, scientists and other personnel;
economic or political instability in foreign countries;
difficulties associated with staffing and managing foreign operations; and
the need to comply with a variety of United States and foreign laws applicable to the conduct of international
business, including import and export control laws and anti-corruption laws.
Business interruptions resulting from disasters or other disturbances could delay us in the process of developing
our products and could disrupt our sales. Our business continuity and disaster recovery plans may not adequately
protect us from a serious disaster or other disturbance.
Our headquarters and other facilities are located in the San Francisco Bay Area, which in the past has experienced both
severe earthquakes and wildfires. Earthquakes, wildfires or other natural disasters could severely disrupt our operations,
and have a material adverse effect on our business, results of operations, financial condition and prospects. We are also
vulnerable to other types of disasters and other events that could disrupt our operations, such as riot, civil disturbances,
war, terrorist acts, infections in our laboratory or production facilities or those of our customers or contract manufacturers
and other events beyond our control. If a natural disaster or other event occurred that prevented us from using all or a
significant portion of our headquarters, that damaged critical infrastructure, such as our enterprise financial systems or
manufacturing resource planning and enterprise quality systems, or that otherwise disrupted operations, it may be difficult
or, in certain cases, impossible, for us to continue our business for a substantial period of time. The disaster recovery and
business continuity plans we have in place currently are limited and are unlikely to prove adequate in the event of a serious
disaster or similar event. We may incur substantial expenses as a result of the limited nature of our disaster recovery and
business continuity plans. We do not carry insurance for earthquakes and we may not carry sufficient business interruption
insurance to compensate us for losses that may occur. Any losses or damages we incur could have a material adverse effect
on our cash flows and success as an overall business.
Confidentiality agreements with employees and others may not adequately prevent disclosures of trade secrets and
other proprietary information.
We rely in part on trade secret and confidentiality protection to protect our confidential and proprietary information
and processes. However, trade secrets and confidential information are difficult to protect. We have taken measures to
protect our trade secrets and confidential and proprietary information, but these measures may not be effective. We require
employees and consultants to execute confidentiality agreements upon the commencement of an employment or consulting
arrangement with us. These agreements generally require that all confidential information developed by the individual or
made known to the individual by us during the course of the individual’s relationship with us be kept confidential and not
disclosed to third parties. These agreements also generally provide that inventions conceived by the individual in the course
of rendering services to us shall be our exclusive property. Nevertheless, our confidential and proprietary information may
be disclosed, third parties could reverse engineer our biocatalysts and others may independently develop substantially
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equivalent confidential and proprietary information and techniques or otherwise gain access to our trade secrets. Costly and
time-consuming litigation could be necessary to enforce and determine the scope of our confidential and proprietary rights,
and failure to obtain or maintain trade secret protection could adversely affect our competitive business position.
We are dependent on information technology systems, infrastructure and data, and any failure of these systems
could harm our business. Security breaches, loss of data, and other disruptions could compromise sensitive information
related to our business or prevent us from accessing critical information and expose us to liability, which could
adversely affect our business, results of operations and financial condition.
Information technology helps us operate efficiently, interface with customers, maintain financial accuracy and
efficiency, and accurately produce our financial statements. If we do not allocate and effectively manage the resources
necessary to build and sustain the proper technology infrastructure, we could be subject to transaction errors, processing
inefficiencies, the loss of customers, business disruptions, or the loss of or damage to intellectual property through security
breach. If our data management systems do not effectively collect, store, process, and report relevant data for the operation
of our business, whether due to equipment malfunction or constraints, software deficiencies, or human error, our ability to
effectively plan, forecast, and execute our business plan and comply with applicable laws and regulations will be impaired,
perhaps materially. Any such impairment could materially and adversely affect our financial condition, results of
operations, cash flows, and the timeliness with which we report our internal and external operating results.
Our business may require us to use and store personal information of our customers, employees, and business partners.
This may include names, addresses, phone numbers, email addresses, contact preferences, tax identification numbers, and
payment account information. We require usernames and passwords in order to access our information technology systems.
We also use encryption and authentication technologies to secure the transmission and storage of data. However, these
security measures may be compromised as a result of security breaches by unauthorized persons, employee error,
malfeasance, faulty password management, or other irregularity, and result in persons obtaining unauthorized access to our
data or accounts. Third parties may attempt to fraudulently induce employees or customers into disclosing usernames,
passwords, or other sensitive information, which may in turn be used to access our information technology systems. For
example, our employees have received “phishing” emails and phone calls attempting to induce them to divulge passwords
and other sensitive information.
In addition, unauthorized persons may attempt to hack into our products or systems to obtain personal data relating to
employees and other individuals, our confidential or proprietary information or confidential information we hold on behalf
of third parties. We also rely on external vendors to supply and/or support certain aspects of our information technology
systems. The systems of these external vendors may contain defects in design or manufacture or other problems that could
unexpectedly compromise information security of our own systems, and we are dependent on these third parties to deploy
appropriate security programs to protect their systems. If we or our third-party vendors were to experience a significant
cybersecurity breach of our or their information systems or data, the costs associated with the investigation, remediation
and potential notification of the breach to counter-parties and data subjects could be material. Our remediation efforts may
not be successful. Further, if such an event were to occur and cause interruptions in our operations, it could result in a
material disruption of our development programs and our business operations, whether due to a loss, corruption or
unauthorized disclosure of our trade secrets, personal information or other proprietary or sensitive information or other
similar disruptions. Attacks upon information technology systems are also increasing in their frequency, levels of
persistence, sophistication and intensity, and are being conducted by sophisticated and organized groups and individuals
with a wide range of motives and expertise. As a result of the COVID-19 pandemic, we may also face increased
cybersecurity risks due to our reliance on internet technology and the number of our employees who are working remotely,
which may create additional opportunities for cybercriminals to exploit vulnerabilities. We have programs in place to
detect, contain, and respond to data security incidents, and we make ongoing improvements to our information-sharing
products in order to minimize vulnerabilities, in accordance with industry and regulatory standards. However, because the
techniques used to obtain unauthorized access to or sabotage systems change frequently and may be difficult to detect, we
may not be able to anticipate and prevent these intrusions or mitigate them when and if they occur.
If a security breach or other incident were to result in the unauthorized access to or unauthorized use, disclosure,
release or other processing of personal information, it may be necessary to notify individuals, governmental authorities,
supervisory bodies, the media and other parties pursuant to privacy and security laws. Any security compromise affecting
us, our service providers, vendors, strategic partners, other contractors, consultants, or our industry, whether real or
perceived, could harm our reputation, erode confidence in the effectiveness of our security measures and lead to regulatory
scrutiny. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or systems,
or inappropriate disclosure of confidential or proprietary or personal information, we could incur liability, including
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litigation exposure, penalties and fines, we could become the subject of regulatory action or investigation, our competitive
position could be harmed and the further development of our products could be delayed. If such an event were to occur and
cause interruptions in our operations, it could result in a material disruption of our business. Furthermore, federal, state and
international laws and regulations can expose us to enforcement actions and investigations by regulatory authorities, and
potentially result in regulatory penalties, fines and significant legal liability, if our information technology security efforts
fail. We may also be exposed to a risk of loss or litigation and potential liability, which could materially and adversely
affect our business, results of operations and financial condition.
Actual or perceived failures to comply with applicable data protection, privacy and security laws, regulations,
standards and other requirements could adversely affect our business, results of operations, and financial condition.
The global data protection landscape is rapidly evolving, and we are or may become subject to state, federal and
foreign laws, regulations, decisions, and directives governing the privacy, security, collection, storage, transmission, use,
processing, retention and disclosure of personal information. Any failure or perceived failure by us to comply with
applicable laws or regulations, our internal policies and procedures or our contracts governing our processing of personal
information could result in negative publicity, government investigations and enforcement actions, claims by third parties
and damage to our reputation, any of which could have a material adverse effect on our operations, financial performance
and business.
In the United States, HIPAA imposes, among other things, certain standards relating to the privacy, security,
transmission and breach reporting of individually identifiable health information. Certain states have also adopted
comparable privacy and security laws and regulations, some of which may be more stringent than HIPAA. Such laws and
regulations will be subject to interpretation by various courts and other governmental authorities, thus creating potentially
complex compliance issues for us and our future customers and strategic partners. For example, the CCPA went into effect
on January 1, 2020 , and introduces new compliance burdens on organizations doing business in California that collect
personal information about California residents. It creates individual privacy rights for California consumers and increases
the privacy and security obligations of entities handling certain personal information. The CCPA also provides for civil
penalties for violations, as well as a private right of action for data breaches that is expected to increase data breach
litigation. Further, the CPRA recently passed in California. The CPRA will impose additional data protection obligations on
covered businesses, including additional consumer rights processes, limitations on data uses, new audit requirements for
higher risk data, and opt outs for certain uses of sensitive data. It will also create a new California data protection agency
authorized to issue substantive regulations and could result in increased privacy and information security enforcement. The
majority of the provisions will go into effect on January 1, 2023, and additional compliance investment and potential
business process changes may be required. Similar laws have passed in Virginia and Colorado, and have been proposed in
other states and at the federal level, reflecting a trend toward more stringent privacy legislation in the United States. These
developments increase our compliance burden and our risk, including risks of regulatory fines, litigation and associated
reputational harm. Any liability from failure to comply with the requirements of these laws could adversely affect our
financial condition.
Furthermore, the Federal Trade Commission (“FTC”) and many state Attorneys General continue to enforce federal
and state consumer protection laws against companies for online collection, use, dissemination and security practices that
appear to be unfair or deceptive. For example, according to the FTC, failing to take appropriate steps to keep consumers’
personal information secure can constitute unfair acts or practices in or affecting commerce in violation of Section 5(a) of
the Federal Trade Commission Act. The FTC expects a company’s data security measures to be reasonable and appropriate
in light of the sensitivity and volume of consumer information it holds, the size and complexity of its business, and the cost
of available tools to improve security and reduce vulnerabilities.
In Europe, the GDPR went into effect in May 2018 and imposes strict requirements for processing the personal data of
individuals within the EEA. The GDPR imposes stringent requirements for controllers and processors of personal data and
increases our obligations, for example, by imposing higher standards when obtaining consent from individuals to process
their personal data, requiring more robust disclosures to individuals, strengthening individual data rights, shortening
timelines for data breach notifications, limiting retention periods and secondary use of information, increasing
requirements pertaining to health data as well as pseudonymized (i.e., key-coded) data, and imposing additional obligations
when we contract with third-party processors in connection with the processing of personal data. The GDPR provides that
EEA member states may make their own additional laws and regulations limiting the processing of genetic, biometric, or
health data, which could limit our ability to use and share personal data or could cause our costs to increase and harm our
business and financial condition. Failure to comply with the requirements of the GDPR can result in fines of up to the
greater of €20 million and 4% of the total worldwide annual turnover of the preceding financial year and other
administrative penalties. If we are required to comply with the new data protection rules imposed by GDPR, such
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compliance may be onerous and adversely affect our business, financial condition, and results of operations. Among other
requirements, the GDPR regulates transfers of personal data subject to the GDPR to third countries that have not been
found to provide adequate protection to such personal data, including the United States, and the efficacy and longevity of
current transfer mechanisms between the EU and the United States remains uncertain. For example, in July 2020, the Court
of Justice of the EU (“CJEU”) limited how organizations could lawfully transfer personal data from the EU/EEA to the
United States by invalidating the Privacy Shield for purposes of international transfers and imposing further restrictions on
the use of standard contractual clauses (“SCCs”). The European Commission issued revised SCCs on June 4, 2021 to
account for the decision of the CJEU and recommendations made by the European Data Protection Board. The revised
SCCs must be used for relevant new data transfers from September 27, 2021; existing standard contractual clauses
arrangements must be migrated to the revised clauses by December 27, 2022. The new SCCs apply only to the transfer of
personal data outside of the EEA and not the United Kingdom; the United Kingdom’s Information Commissioner’s Office
launched a public consultation on its draft revised data transfers mechanisms in August 2021. There is some uncertainty
around whether the revised clauses can be used for all types of data transfers, particularly whether they can be relied on for
data transfers to non-EEA entities subject to the GDPR. As supervisory authorities issue further guidance on personal data
export mechanisms, including circumstances where the SCCs cannot be used, and/or start taking enforcement action, we
could suffer additional costs, complaints and/or regulatory investigations or fines, and/or if we are otherwise unable to
transfer personal data between and among countries and regions in which we operate, it could affect the manner in which
we provide our services, the geographical location or segregation of our relevant systems and operations, and could
adversely affect our financial results.
Further, from January 1, 2021, companies have had to comply with the GDPR and also the United Kingdom GDPR
(“UK GDPR”), which, together with the amended UK Data Protection Act 2018, retains the GDPR in UK national law. The
UK GDPR mirrors the fines under the GDPR, i.e., fines up to the greater of €20 million (or up to £17.5 million for UK) or
4% of global turnover. The relationship between the United Kingdom and the European Union in relation to certain aspects
of data protection law remains unclear, and it is unclear how United Kingdom data protection laws and regulations will
develop in the medium to longer term. The European Commission has adopted an adequacy decision in favor of the United
Kingdom, enabling data transfers from EU member states to the United Kingdom without additional safeguards. However,
the UK adequacy decision will automatically expire in June 2025 unless the European Commission re-assesses and renews
or extends that decision.
Although we work to comply with applicable laws, regulations and standards, our contractual obligations and other
legal obligations, these requirements are evolving and may be modified, interpreted and applied in an inconsistent manner
from one jurisdiction to another, and may conflict with one another or other legal obligations with which we must comply.
Various federal, state and foreign legislative or regulatory bodies may enact new or additional laws and regulations
concerning privacy, data-retention and data-protection issues, including laws or regulations mandating disclosure to
domestic or international law enforcement bodies, which could adversely impact our business or our reputation with
customers. For example, some countries have adopted laws mandating that certain personal information regarding
customers in their country be maintained solely in their country. Having to maintain local data centers and redesign
product, service and business operations to limit Personal Information processing to within individual countries could
increase our operating costs significantly. Any failure, or perceived failure, by us to comply with federal, state or
international privacy, data-retention or data-protection-related laws, regulations, orders or industry self-regulatory
principles could result in proceedings or actions against us by governmental entities or others, a loss of customer
confidence, damage to our brand and reputation and a loss of customers, any of which could have an adverse effect on our
business.
Evolving expectations around corporate responsibility practices, specifically related to environmental, social and
governance (“ESG”) matters, may expose us to reputational and other risks.
Investors, stockholders, customers, suppliers and other third parties are increasingly focusing on ESG and corporate
social responsibility endeavors and reporting. Companies that do not adapt to or comply with the evolving investor or
stakeholder expectations and standards, or which are perceived to have not responded appropriately, may suffer from
reputational damage and result in the business, financial condition and/or stock price of a company being materially and
adversely affected. Further, this increased focus on ESG issues may result in new regulations and/or third-party
requirements that could adversely impact our business, or certain shareholders reducing or eliminating their holdings of our
stock. Additionally, an allegation or perception that we have not taken sufficient action in these areas could negatively
harm our reputation.
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Not applicable.
Facilities
ITEM 1B. UNRESOLVED STAFF COMMENTS
ITEM 2. PROPERTIES
Our headquarters are located in Redwood City, California, where we lease approximately 77,300 square feet of office and
laboratory space.
Our lease (“RWC Lease”) with Metropolitan Life Insurance Company (“MetLife”) includes approximately 28,200 square
feet of space located at 200 and 220 Penobscot Drive, Redwood City, California (the “200/220 Penobscot Space”),
approximately 37,900 square feet of space located at 400 Penobscot Drive, Redwood City, California (the “400 Penobscot
Space”) (the 200/220 Penobscot Space and the 400 Penobscot Space are collectively referred to as the “Penobscot Space”), and
approximately 11,200 square feet of space located at 501 Chesapeake Drive, Redwood City, California (the “Chesapeake
Space”).
We entered into the initial lease with MetLife for our facilities in Redwood City in 2004 and the RWC lease has been
amended multiple times since then to adjust the leased space and terms of the RWC Lease. In February 2019, we entered into
an Eighth Amendment to the RWC Lease (the “Eighth Amendment”) with MetLife with respect to the Penobscot Space and the
501 Chesapeake Space to extend the term of the RWC Lease for additional periods. Pursuant to the Eighth Amendment, the
term of the lease of the Penobscot Space has been extended through May 2027. The lease term for the 501 Chesapeake Space
has been extended to May 2029. We have one (1) option to extend the term of the lease for the Penobscot Space for five (5)
years, and one (1) separate option to extend the term of the lease for the 501 Chesapeake Space for five (5) years.
In January 2021, we entered into a lease agreement with ARE-San Francisco No. 63, LLC (“ARE”) to lease a portion of a
facility comprising approximately 36,593 rentable square feet at 825 Industrial Road, San Carlos, California to serve as
additional office and research and development laboratory space (the “San Carlos Space”). In December 2021, we commenced
occupancy of the San Carlos Space. The lease term for the San Carlos Space is through the end of November 2031. We have
one (1) option to extend the term of the lease for the San Carlos Space for five (5) years.
In May 2021, we entered into a short-term office lease with The Inside Source, Inc., to sublease approximately 3,313
square feet of office space in a building located at 985 Industrial Blvd.. San Carlos, California. This lease will expire in April
2022.
We believe that the facilities that we currently lease in Redwood City and San Carlos, California are adequate for our needs
for the immediate future and that, should it be needed, additional space can be leased to accommodate any future growth.
ITEM 3. LEGAL PROCEEDINGS
We are currently not a party to any material pending litigation or other material legal proceedings.
Not applicable.
ITEM 4. MINE SAFETY DISCLOSURES
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PART II
ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND
ISSUER PURCHASES OF EQUITY SECURITIES
Market Information
Our common stock is quoted on the Nasdaq Global Select Market (“Nasdaq”), under the symbol “CDXS.”
As of February 24, 2022, there were approximately 129 stockholders of record. A substantially greater number of
stockholders may be “street name” or beneficial holders, whose shares are held of record by banks, brokers and other financial
institutions.
Dividend Policy
We have never declared or paid cash dividends on our common stock, and we currently do not plan to declare dividends on
shares of our common stock in the foreseeable future. We expect to retain our future earnings, if any, for use in the operation
and expansion of our business. In addition, unless waived, the terms of our Credit Facility prohibit us from paying any cash
dividends or making other distributions. The payment of cash dividends in the future, if any, will be at the discretion of our
board of directors and will depend upon such factors as earnings levels, capital requirements, our overall financial condition
and any other factors deemed relevant by our board of directors.
Securities Authorized for Issuance under Equity Compensation Plans
The information required by this item concerning securities authorized for issuance under equity compensation plans is
incorporated by reference from the information that will be set forth in the Definitive Proxy Statement to be filed with the
Securities and Exchange Commission in connection with the Annual Meeting of Stockholders to be held in 2022 (the “2022
Proxy Statement”) under the heading “Executive Compensation—Equity Compensation Plan Information.”
Stock Price Performance Graph
The following tabular information and graph compare our total common stock return with the total return for (i) the Nasdaq
Composite Index and (ii) the Nasdaq Biotechnology Index for the period December 31, 2016 through December 31, 2021. The
figures represented below assume an investment of $100 in our common stock at the closing price on December 31, 2016 and
in the Nasdaq Composite Index and the Nasdaq Biotechnology Index on December 31, 2016 and the reinvestment of dividends
into shares of common stock. The comparisons in the table and graph are required by the SEC and are not intended to forecast
or be indicative of possible future performance of our common stock. The tabular information and graph shall not be deemed
“soliciting material” or to be “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities under
that Section, and shall not be deemed to be incorporated by reference into any of our filings under the Securities Act or the
Exchange Act.
December 31,
$100 investment in stock or index Ticker
Codexis, Inc.
Nasdaq Composite Total Return
Nasdaq Biotechnology (Total Return)
Index
2016
2018
CDXS $ 100.00 $ 181.52 $ 363.04 $ 347.61 $ 474.57 $ 679.78
XCMP $ 100.00 $ 129.63 $ 125.95 $ 172.17 $ 249.51 $ 304.84
2017
2019
2020
2021
XNBI $ 100.00 $ 121.64 $ 110.86 $ 138.69 $ 175.33 $ 175.37
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Unregistered Sales of Equity Securities and Use of Proceeds
Unregistered Sales of Equity Securities
During the year ended December 31, 2021, we did not issue or sell any unregistered securities not previously disclosed in a
Quarterly Report on Form 10-Q or in a Current Report on Form 8-K.
Issuer Purchases of Equity Securities
None.
ITEM 6. [RESERVED]
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ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF
FINANCIAL CONDITION AND RESULTS OF OPERATIONS
The following discussion and analysis should be read in conjunction with our audited Consolidated Financial Statements
and the related Notes that appear elsewhere in this Annual Report on Form 10-K. This Annual Report on Form 10-K contains
“forward-looking statements” within the meaning of Section 21E of the Exchange Act. These statements are often identified by
the use of words such as “may,” “will,” “expect,” “believe,” “anticipate,” “intend,” “could,” “should,” “estimate,” or
“continue,” and similar expressions or variations. Such forward-looking statements are subject to risks, uncertainties and other
factors that could cause actual results and the timing of certain events to differ materially from future results expressed or
implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not
limited to, those discussed in the section titled “Risk Factors,” set forth in Part I, Item 1A of this Annual Report on Form 10-K
and elsewhere in this report. The forward-looking statements in this Annual Report on Form 10-K represent our views as of the
date of this Annual Report on Form 10-K. We anticipate that subsequent events and developments will cause our views to
change. However, while we may elect to update these forward-looking statements at some point in the future, we have no
current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-
looking statements as representing our views as of any date subsequent to the date of this Annual Report on Form 10-K.
Business Overview
We discover, develop and sell enzymes and other proteins that deliver value to our clients in a growing set of industries. We
view proteins as a vast, largely untapped source of value-creating products, and we are using our proven technologies, which
we have been continuously improving since our inception in 2002, to commercialize an increasing number of novel enzymes,
both as proprietary Codexis products and in partnership with our customers.
We are a pioneer in harnessing computational technologies to drive biology advancements. Since 2002, we have made
substantial investments in the development of our CodeEvolver® protein engineering technology platform, the primary source
of our competitive advantage. Our technology platform is powered by proprietary, artificial intelligence-based, computational
algorithms that rapidly mine the structural and performance attributes of our large and continuously growing library of protein
variants. These computational outputs enable increasingly reliable predictions for next generation protein variants to be
engineered, enabling time- and cost-efficient delivery of the targeted performance enhancements. In addition to its
computational prowess, our CodeEvolver® protein engineering technology platform integrates additional modular
competencies, including robotic high-throughput screening and genomic sequencing, organic chemistry and bioprocess
development which are all coordinated to rapidly innovate novel, fit-for-purpose products.
The core historical application of the technology has been in developing commercially viable biocatalytic manufacturing
processes for more sustainable production of complex chemicals. It begins by conceptually designing the most cost-effective
and practical process for a targeted product. We then develop optimized biocatalysts to enable the designed process, using our
CodeEvolver® platform. Engineered biocatalyst candidates, numbering many thousands for each project, are then rapidly
screened and validated using high throughput methods under process-relevant operating conditions. This approach results in an
optimized biocatalyst that enables cost-efficient processes that are relatively simple to run in conventional manufacturing
equipment. This also allows for efficient technical transfer of our processes to our manufacturing partners.
We initially commercialized our CodeEvolver® protein engineering technology platform and products in the manufacture
of small molecule pharmaceuticals, which remains a primary business focus. Our customers, which include many large, global
pharmaceutical companies, use our technology, products and services in their process development and in manufacturing.
Additionally, we have licensed our proprietary CodeEvolver® protein engineering technology platform to global pharmaceutical
companies enabling them to use this technology, in house, to engineer enzymes for their own businesses. In May 2019, we
entered into a Platform Technology Transfer and License Agreement (the “Novartis CodeEvolver® Agreement”) with Novartis.
The Novartis CodeEvolver® Agreement (Codexis’ third such agreement with large pharma companies) allows Novartis to use
our proprietary CodeEvolver® protein engineering platform technology in the field of human healthcare.
As evidence of our strategy to extend our technology beyond pharmaceutical manufacturing, we have also used the
technology to develop biocatalysts and enzyme products for use in a broader set of industrial markets, including several large
verticals, such as food, feed, consumer care and fine chemicals. In addition, we are using our technology to develop enzymes
for various life science related applications, such as next generation sequencing (“NGS”) and polymerase chain reaction
(“PCR/qPCR”) for in vitro molecular diagnostic and genomic research applications. In December 2019, we entered into a
license agreement to provide Roche Sequencing Solutions, Inc. with our first enzyme for this target market: the Company’s
EvoT4™ DNA ligase. In June 2020, we also entered into a Master Collaboration and Research Agreement with MAI (the “MAI
Agreement”) pursuant to which we are leveraging our CodeEvolver® platform technology to improve the DNA polymerase
enzymes that are critical for enzymatic DNA synthesis.
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Approximately six years ago, we began using the CodeEvolver® protein engineering technology platform to develop early
stage, novel biotherapeutic product candidates, both in partnership with customers and for our own proprietary Codexis drug
candidates. Our first program was for the potential treatment of phenylketonuria ("PKU") in humans. PKU is an inherited
metabolic disorder in which the enzyme that converts the essential amino acid phenylalanine into tyrosine is deficient. In
October 2017, we entered into a Global Development, Option and License Agreement (the “Nestlé License Agreement”) with
Societé des Produits Nestlé S.A., formerly known as Nestec Ltd. (“Nestlé Health Science") to advance CDX-6114, our enzyme
biotherapeutic product candidate for the potential treatment of PKU. In February 2019, Nestlé Health Science exercised its
option to obtain an exclusive license to develop and commercialize CDX-6114. Also in October 2017, we entered into the
Nestlé SCA pursuant to which we and Nestlé Health Science are collaborating to leverage the CodeEvolver® platform
technology to develop other novel enzymes for Nestlé Health Science’s established Consumer Care and Medical Nutrition
business areas. In March 2020, we entered into a Strategic Collaboration and License Agreement (“Takeda Agreement”) with
Shire Human Genetic Therapies, Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited (“Takeda”), for
the research and development of novel gene therapies for certain disease indications, including the treatment of lysosomal
storage disorders and a blood factor deficiency.
See Note 5, "Collaborative Arrangements" in the Notes to the Consolidated Financial Statements set forth in Item 8 of this
Annual Report on Form 10-K for further information.
Recent Development - Pfizer (PAXLOVID™)
In the first and second quarters of 2021, we began to receive purchase orders from Pfizer, Inc. (“Pfizer”) for large
quantities of our proprietary enzyme product, CDX-616, for use by Pfizer in the manufacture of a critical intermediate for its
proprietary active pharmaceutical ingredient, nirmatrelvir. Pfizer markets, sells and distributes nirmatrelvir, in combination
with the active pharmaceutical ingredient ritonavir, as its PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) product, which
received emergency use authorization by the U.S. Food and Drug Administration (“FDA”) in late 2021 for the treatment of
COVID-19 in humans.
In 2021, we recognized approximately $34.5 million in revenue from the sale of quantities of CDX-616 to Pfizer. In
addition, as of December 31, 2021, we have received additional purchase orders from Pfizer for delivery of a significant
quantity of CDX-616 in 2022. We have received and currently expect to receive additional purchase orders from Pfizer for
significant quantities of CDX-616 during the course of 2022 for delivery in 2022 and 2023. As of December 31, 2021, we have
not yet executed a long-term purchase and sale agreement with Pfizer for CDX-616; with or without a long-term purchase and
sale agreement, we currently expect that future orders for quantities of CDX-616 by Pfizer will continue to be based on the
needs of Pfizer for quantities of CDX-616 and there will be no minimum purchase obligation on the part of Pfizer.
Business Segments
We manage our business as two business segments: Performance Enzymes and Novel Biotherapeutics. See Note 15,
“Segment, Geographical and Other Revenue Information” in the Notes to the Consolidated Financial Statements set forth in
Item 8 of this Annual Report on Form 10-K.
Performance Enzymes
We initially commercialized our CodeEvolver® protein engineering technology platform and products in the manufacture
of small molecule pharmaceuticals and, to date, this continues to be our largest market served. Our customers, which include
many large global pharmaceutical companies, use our technology, products and services in their manufacturing processes and
process development. We have also used the technology to develop customized enzymes for use in other industrial markets.
These markets consist of several large industrial verticals, including food, feed, consumer care, and fine chemicals. We also use
our technology in the life sciences markets to develop enzymes for customers using NGS and PCR/qPCR for in vitro molecular
diagnostic and molecular biology research applications, as well DNA/RNA synthesis and health monitoring applications.
Novel Biotherapeutics
We are also targeting new opportunities in the pharmaceutical industry to discover, improve, and/or develop biotherapeutic
drug candidates. We believe that our CodeEvolver® protein engineering platform technology can be used to discover novel
biotherapeutic drug candidates that will target human diseases that are in need of improved therapeutic interventions. Similarly,
we believe that we can deploy our platform technology to improve specific characteristics of a customer’s pre-existing
biotherapeutic drug candidate, such as its activity, stability or immunogenicity.
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Business Update Regarding COVID-19
We are subject to risks and uncertainties as a result of the current COVID-19 pandemic. The COVID-19 pandemic has
presented a substantial public health and economic challenge around the world and is affecting our employees, communities
and business operations, as well as the U.S. economy and other economies worldwide. The full extent to which the COVID-19
pandemic will directly or indirectly impact our business, results of operations and financial condition will depend on future
developments that are highly uncertain and may not be accurately predicted, including the duration and severity of the
pandemic, the prevalence of more contagious and or virulent variants such as the Delta and Omicron variants, and the extent
and severity of the impact on our customers, new information that may emerge concerning COVID-19, the actions taken to
contain it or treat its impact and the economic impact on local, regional, national and international markets.
In the United States, the impact of COVID-19, including governmental orders (“Orders”) governing the operation of
businesses during the pandemic, caused the temporary closure of our Redwood City, California facilities and has disrupted our
R&D operations. R&D operations for several projects were temporarily suspended from mid-March 2020 through the end of
April 2020 in accordance with these Orders. In May 2020, we re-initiated limited R&D operations and have ramped up
operations such that we are currently utilizing our normal R&D capacity while following county, state and federal COVID-19
guidance for the protection of our employees. Additionally, we resumed manufacturing at our Redwood City pilot plant in May
2020.
To date, we and our collaboration partners have been able to continue to supply our enzymes to our customers worldwide,
however, there can be no guarantee this will continue. Furthermore, our ability to provide future R&D services will continue to
be impacted as a result of governmental orders and any disruptions in operations of our customers with whom we collaborate.
We believe that these disruptions have had a minimal impact on revenue for the year ended December 31, 2021. The extent to
which the pandemic may impact our business operations and operating results will continue to remain highly dependent on
future developments, which are uncertain and cannot be predicted with confidence.
As a result of the COVID-19 pandemic we have received purchase orders from Pfizer for large quantities of our proprietary
enzyme product, CDX-616, for use by Pfizer in the manufacture of a critical intermediate for its proprietary active
pharmaceutical ingredient, nirmatrelvir, used by Pfizer in combination with the active pharmaceutical ingredient ritonavir, as its
PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) product for the treatment of COVID-19 infections in humans. These
purchase orders have had substantial impact on our revenue in 2021.
For additional information on the various risks posed by the COVID-19 pandemic, please read Item 1A. Risk Factors
included in this Annual Report on Form 10-K.
Recent Investing and Financing Activities
In June 2020, we entered into a Stock Purchase Agreement with MAI pursuant to which we purchased 1,587,050 shares of
MAI's Series A preferred stock for $1.0 million. In connection with the transaction, John Nicols, our President and Chief
Executive Officer, also joined MAI’s board of directors. Concurrently with our initial equity investment, we entered into the
MAI Agreement pursuant to which we are performing services utilizing our CodeEvolver® protein engineering platform
technology to improve DNA polymerase enzymes in exchange for compensation in the form of additional shares of MAI's
Series A preferred stock. In April 2021, we purchased an additional 1,000,000 shares of MAI's Series A preferred stock for $0.6
million. In September 2021, we purchased 9,198,423 shares of MAI's Series B preferred stock for $7.0 million. As of
December 31, 2021, we have 16,705,320 shares of MAI's Series A and B preferred stock that we have earned or purchased
since executing the Stock Purchase Agreement with MAI.
In November 2020, we announced the SynBio Innovation Accelerator (“Accelerator”) collaboration with Casdin Capital,
LLC ("Casdin"). The goal of the Accelerator is to fund the early-stage companies with disruptive technology platforms or
unique product development capabilities in the field of synthetic and industrial biotechnology. The first investment by Codexis
associated with the Accelerator collaboration was made in Arzeda Corp., a privately-held computational protein design
company that focuses on computational approaches to designing novel enzyme functionality. We invested $1.0 million in
Arzeda and received a convertible subordinated note issued by Arzeda Corp. In July 2021, we converted the non-marketable
debt security with a carrying value of $1.3 million into 207,070 shares of Series B-2 preferred stock of Arzeda Corp.
In December 2020, we completed an underwritten public offering of 4,928,572 shares of our common stock, par value
$0.0001 per share, at a public offering price of $17.50 per share. The net proceeds to us were approximately $80.8 million after
deducting offering costs, underwriting discounts and commissions and other offering expenses of $5.5 million.
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In May 2021, we filed a Registration Statement on Form S-3 with the SEC, that automatically became effective upon its
filing, under which we may sell common stock, preferred stock, debt securities, warrants, purchase contracts, and units from
time to time in one or more offerings. In May 2021, we entered into an Equity Distribution Agreement ("EDA") with Piper
Sandler & Co ("PSC"), under which PSC, as our exclusive agent, at our discretion and at such times that we may determine
from time to time, may sell over a three-year period from the execution of the EDA up to a maximum of $50.0 million of shares
of our common stock. Under the terms of the EDA, PSC may sell the shares at market prices by any method that is deemed to
be an "at the market offering" as defined in Rule 415 under the Securities Act of 1933, as amended. During the year ended
December 31, 2021, no shares of our common stock were issued pursuant to the EDA.
Results of Operations Overview
Revenues were $104.8 million in 2021, a 52% increase from $69.1 million in 2020. Product revenue, which consists
primarily of sales of biocatalysts, pharmaceutical intermediates, and Codex® biocatalyst panels and kits, was $70.7 million in
2021, an increase of 134% compared with $30.2 million in 2020. The increase in product revenue was primarily due to $34.5
million in revenue from Pfizer related to the purchase of our performance enzyme products and an increase in demand for
enzymes used in the manufacture of branded pharmaceutical products.
Research and development revenues, which include license, technology access and exclusivity fees, research service fees,
milestone payments, royalties, and optimization and screening fees, totaled $34.1 million in 2021, a 12% decrease compared
with $38.8 million in 2020. The decrease in research and development revenue was primarily due to lower license fees from
Takeda under the Takeda Agreement and lower revenues from Novartis under the Novartis CodeEvolver® Agreement
recognized this year compared to the prior year, partially offset by higher license fees from other existing collaboration
agreements.
Our products’ profitability is affected by many factors including the mix of products we sell. Our profit margins are
affected by many factors including the costs of internal and third-party fixed and variable costs, including materials and
supplies, labor, facilities and other overhead costs. Profit margin data is used as a management performance measure to provide
additional information regarding our results of operations on a consolidated basis. Product gross margins increased to 69% in
2021, compared to 55% in 2020 due to improved product mix resulting from sales to Pfizer and an increase in customer
demand for branded pharmaceutical products.
Research and development expenses were $55.9 million in 2021, an increase of 26% from $44.2 million in 2020. The
increase was primarily due to an increase in costs associated with higher headcount, higher lab supplies, higher depreciation
and other outside services, partially offset by a decrease in costs associated with outside services relating to Chemistry,
Manufacturing and Controls ("CMC") and regulatory expenses.
Selling, general and administrative expenses were $49.3 million in 2021, an increase of 41% compared to $35.0 million in
2020. The increase was primarily due to an increase in costs associated with a higher headcount, increase in legal fees, higher
stock-based compensation costs, higher outside and temporary services, partially offset by lower allocable expenses.
Net loss was $21.3 million, or a net loss of $0.33 per share, in 2021 compared to a net loss of $24.0 million, or a net loss of
$0.40 per share, in 2020. The decrease in net loss was primarily related to an increase in product revenue with higher margins,
partially offset by higher operating expenses and lower research and development revenues.
Cash and cash equivalents decreased to $116.8 million as of December 31, 2021 compared to $149.1 million as of
December 31, 2020. In addition, net cash used in operations was $14.3 million in 2021, as compared to net cash used in
operations of $16.5 million in 2020. We believe that based on our current level of operations, our existing cash and cash
equivalents will provide adequate funds for ongoing operations, planned capital expenditures and working capital requirements
for at least the next 12 months.
In June 2017, we entered into a loan and security agreement with Western Alliance Bank that allowed us to borrow up to
$10.0 million under a term loan, and allow us to borrow up to $5.0 million under a revolving credit facility with 80% of certain
eligible accounts receivable as a borrowing base (the “Credit Facility”). Obligations under the Credit Facility are secured by a
lien on substantially all of our personal property other than our intellectual property. In September 2021, we entered into the
Ninth Amendment to the Credit Facility whereby we may draw on the term debt and the Revolving Line of Credit at any time
prior to December 31, 2021 and October 1, 2024, respectively. Draws on the term debt are subject to customary conditions for
funding. Our ability to take draws on the term debt expired on December 31, 2021. As of December 31, 2021, no amounts were
borrowed under the Credit Facility and we were in compliance with the covenants for the Credit Facility. See Note 13,
“Commitments and Contingencies” in the Notes to the Consolidated Financial Statements set forth in Item 8 of this Annual
Report on Form 10-K.
62
Recent Accounting Pronouncements
For information on recent accounting pronouncements, see Note 2, “Summary of Significant Accounting Policies” in the
Notes to the Consolidated Financial Statements set forth in Item 8 of this Annual Report on Form 10-K.
Results of Operations
The following table shows the amounts from our consolidated statements of operations for the periods presented (in
thousands, except percentages):
Year Ended December 31,
2020
2021
2019
Revenues:
Product revenue
Research and development revenue
Total revenues
Costs and operating expenses:
Cost of product revenue
Research and development
Selling, general and administrative
Total costs and operating expenses
Loss from operations
Interest income
Other income (expense), net
Loss before income taxes
Provision for income taxes
Net loss
Revenues
$
70,657 $
34,097
104,754
30,220 $
38,836
69,056
29,465
38,993
68,458
22,209
55,919
49,323
127,451
(22,697)
459
1,148
(21,090)
189
(21,279) $
13,742
44,185
35,049
92,976
(23,920)
405
(156)
(23,671)
339
(24,010) $
15,632
33,873
31,502
81,007
(12,549)
1,287
(656)
(11,918)
17
(11,935)
$
% of Total Revenues
2020
2019
2021
67 %
33 %
100 %
21 %
53 %
47 %
121 %
(21) %
— %
1 %
(20) %
— %
(20) %
44 %
56 %
100 %
20 %
64 %
51 %
135 %
(35) %
1 %
— %
(34) %
— %
(34) %
43 %
57 %
100 %
23 %
49 %
46 %
118 %
(18) %
2 %
(1) %
(17) %
— %
(17) %
Our revenues consist of product revenue and research and development revenue as follows:
Product revenue consist of sales of biocatalysts, pharmaceutical intermediates, and Codex® biocatalyst panels
•
and kits.
• Research and development revenue include license, technology access and exclusivity fees, research services
fees, milestone payments, royalties, optimization and screening fees.
Revenues are as follows (in thousands, except percentages):
Product revenue
Research and development revenue
Total revenues
$
Year Ended December 31,
2020
30,220 $
38,836
69,056 $
2021
70,657 $
34,097
$ 104,754 $
$
2019
29,465 $ 40,437
38,993
(4,739)
68,458 $ 35,698
Change
2021
%
134 % $
(12) %
52 % $
2020
$
%
755
3 %
(157) — %
598
1 %
Revenues typically fluctuate on a quarterly basis due to the variability in our customers' manufacturing schedules and the
timing of our customers' clinical trials. In addition, we have limited internal capacity to manufacture enzymes. As a result, we
are dependent upon the performance and capacity of third party manufacturers for the commercial scale manufacturing of the
enzymes used in our pharmaceutical and fine chemicals business.
We accept purchase orders for deliveries covering periods from one day up to 14 months from the date on which the order
is placed. However, some of our purchase orders can be revised or cancelled by the customer without penalty. Considering
63
these industry practices and our experience, we do not believe the total of customer purchase orders outstanding (backlog)
provides meaningful information that can be relied on to predict actual sales for future periods.
2021 compared to 2020
Total revenues increased by $35.7 million in 2021 to $104.8 million, as compared to 2020. The increase was driven by
growth in product revenue of $40.4 million, or 134%, but partially offset by a decrease in research and development revenue of
$4.7 million, or 12%.
Product revenues, which consist primarily of sales of biocatalysts, pharmaceutical intermediates, and Codex® biocatalyst
panels and kits, were $70.7 million in 2021, an increase of 134% compared with $30.2 million in 2020. The increase in product
revenue was primarily due to $34.5 million in revenue from Pfizer and an increase in demand for enzymes used in the
manufacture of branded pharmaceutical products.
Research and development revenue decreased by $4.7 million in 2021 to $34.1 million, or 12% compared with $38.8
million in 2020, primarily due to lower license and research and development fees from Takeda under the Takeda Agreement
and lower revenues from the Novartis CodeEvolver® Agreement recognized this year compared to the prior year, partially offset
by higher license fees from other existing collaboration agreements.
2020 compared to 2019
Total revenues increased by $0.6 million in 2020 to $69.1 million, as compared to 2019. The increase was driven by
growth in product revenue of $0.8 million, or 3%, offset by a decrease in research and development revenue of $0.2 million or
nominal percent.
Product revenues were $30.2 million in 2020, an increase of 3% compared with $29.5 million in 2019. The increase in
product revenue is primarily due to higher customer demand for enzymes used in the manufacture of branded pharmaceutical
products.
Research and development revenues decreased by $0.2 million in 2020 to $38.8 million compared with 39.0 million in
2019, primarily due to lower revenues from the Novartis CodeEvolver® Agreement, a prior year functional license fee revenue
from Nestlé Health Science, and a prior year milestone payment from GSK under the GSK CodeEvolver® Agreement, partially
offset by the recognition of license fees from Takeda under the Takeda Agreement, and recognition of functional license fees
revenue from Porton.
Cost and Operating Expenses (in thousands, except percentages):
Cost of product revenue
Research and development
Selling, general and administrative
Total costs and operating expenses
$
Year Ended December 31,
2020
13,742 $
44,185
35,049
92,976 $
2021
22,209 $
55,919
49,323
$ 127,451 $
$
2019
8,467
15,632 $
11,734
33,873
31,502
14,274
81,007 $ 34,475
Change
2021
2020
%
%
$
(1,890)
62 % $
10,312
26 %
41 %
3,547
37 % $ 11,969
(12) %
30 %
11 %
15 %
Cost of Product Revenue and Product Gross Margin
Our product revenues are derived entirely from our Performance Enzymes segment. Revenues from the Novel
Biotherapeutics segment are only from collaborative research and development activities.
The following table shows the amounts of our product revenue, cost of product revenue, product gross profit and product
gross margin from our consolidated statements of operations for the years ended (in thousands, except percentages):
Product revenue
Cost of product revenue (1)
Product gross profit
Product gross margin (%) (2)
Year Ended December 31,
Change
Year Ended December 31,
2021
$ 70,657
22,209
$ 48,448
2020
$ 30,220
13,742
$ 16,478
$
$ 40,437
8,467
$ 31,970
%
2020
134 % $ 30,220
62 %
13,742
194 % $ 16,478
2019
$ 29,465
15,632
$ 13,833
Change
$
755
%
$
3 %
(1,890) (12) %
19 %
$ 2,645
69 %
55 %
55 %
47 %
64
(1) Cost of product revenue comprises both internal and third-party fixed and variable costs, including materials and supplies, labor, facilities and other overhead costs associated
with our product revenue.
(2) Product gross margin is used as a performance measure to provide additional information regarding our results of operations on a consolidated basis.
2021 compared to 2020
Cost of product revenue increased by $8.5 million in 2021 to $22.2 million, as compared to 2020. The increase was
primarily due to a higher volume of product sales and variations in product mix. The product gross margin increased to 69% in
2021 as compared to 55% in 2020, primarily due to the sale of higher margin branded products.
2020 compared to 2019
Cost of product revenue decreased by $1.9 million in 2020 to $13.7 million, as compared to 2019. The decrease was
primarily due to lower costs compared to costs associated with prior year product revenue. The product gross margin increased
to 55% in 2020 as compared to 47% in 2019 due to improved product mix.
Research and Development Expenses
Research and development expenses consist of costs incurred for internal projects as well as collaborative research and
development activities. These costs primarily consist of (i) employee-related costs, which include salaries and other personnel-
related expenses (including stock-based compensation), (ii) various allocable expenses, which include occupancy-related costs,
supplies, depreciation of facilities and laboratory equipment, and (iii) external costs. Research and development expenses are
expensed when incurred.
2021 compared to 2020
Research and development expenses were $55.9 million in 2021 compared to $44.2 million in 2020, an increase of $11.7
million, or 26%. The increase was primarily due to $7.6 million in costs associated with higher headcount, $0.8 million in
higher stock-based compensation expenses, $2.6 million in higher lab supplies, $2.2 million in higher allocable expenses, $1.1
million increase in outside services, and $1.0 million in higher depreciation expenses, partially offset by a $3.7 million decrease
in costs associated with outside services related to CMC and regulatory expenses.
2020 compared to 2019
Research and development expenses were $44.2 million in 2020 compared to $33.9 million in 2019, an increase of $10.3
million, or 30%. The increase was primarily due to $5.0 million in costs associated with outside services relating to CMC and
regulatory expenses, $3.4 million in costs associated with higher headcount, $1.5 million in higher allocable expenses which
include occupancy-related costs and supplies, $0.4 million in higher outside services, and $0.3 million in higher depreciation
expense and were partially offset by a decrease of $0.4 million in lab supply expenses.
Selling, General and Administrative Expenses
Selling, general and administrative expenses consist of employee-related costs, which include salaries and other personnel-
related expenses (including stock-based compensation), hiring and training costs, consulting and outside services expenses
(including audit and legal counsel related costs), marketing costs, building lease costs, and depreciation and amortization
expenses.
2021 compared to 2020
Selling, general and administrative expenses were $49.3 million in 2021 compared to $35.0 million in 2020, an increase of
$14.3 million, or 41%. The increase was primarily due to an increase of $6.6 million in costs associated with higher headcount
to support our growth, $3.1 million in higher stock-based compensation costs, $5.1 million increase in legal fees, $1.1 million
in higher outside and temporary services, $1.0 million in higher facilities cost, and $0.4 million increase in allowance for credit
losses, partially offset by a decrease of $3.0 million in allocable expenses.
2020 compared to 2019
Selling, general and administrative expenses were $35.0 million in 2020 compared to $31.5 million in 2019, an increase of
$3.5 million or 11%. The increase was primarily due to increases of $1.7 million in salaries and personnel costs associated with
higher headcount, $0.6 million in stock-based compensation expense, $0.8 million in consultants costs, $0.8 million in legal and
65
accounting fees, $0.7 million in facilities costs, $0.7 million in outside and temporary services, and $0.4 million in licensed
technology, which were partially offset by decreases of $1.6 million in allocable expenses and $0.8 million in travel expenses.
Interest Income and Other Income (Expense), net (in thousands, except percentages):
Year Ended December 31,
2020
2021
2019
Interest income
Other income (expense), net
Total other income (expense), net
$
$
459 $
1,148
1,607 $
405 $
(156)
249 $
1,287 $
(656)
631 $
Interest Income
2021
$
54
1,304
1,358
Change
2020
%
13 % $
836 %
545 % $
$
(882)
500
(382)
%
(69) %
76 %
(61) %
Interest income increased by $0.1 million in 2021 compared to 2020, primarily due to earned interest income on a non-
marketable debt security, partially offset by a reduction in interest income from lower average interest rates on lower average
cash balances. Interest income decreased by $0.9 million in 2020 compared to 2019, primarily due to lower average interest
rates on declining average cash balances.
Other Income (Expense), net
Other income (expense), net, increased by $1.3 million in 2021 compared to 2020, primarily due to a $1.0 million gain
from remeasurement on the carrying value of our investment in MAI. Other expense decreased by $0.5 million in 2020
compared to 2019, primarily due to a $0.5 million write-down in the fair value of our investment in CO2 Solutions and
fluctuations in foreign currency in 2019.
Provision for Income Taxes (in thousands, except percentages):
Provision for income taxes
$
189 $
339 $
17 $
Year Ended December 31,
2020
2021
2019
Change
2021
2020
$
(150)
%
(44) %
$
322
%
1,894 %
The provision for income taxes for 2021 was primarily due to the income tax withholding imposed by foreign taxing
authorities on income earned in certain countries outside of the Unites States and remitted to the Unites States and the accrual
of interest and penalties on historic uncertain tax positions. The provision for income taxes in 2020 was primarily due to foreign
withholding taxes on certain sales to non-U.S. customers. The provision for income taxes in 2019 was primarily due to the
accrual of interest and penalties on historic uncertain tax positions.
Net Loss
Net loss for 2021 was $21.3 million, or a net loss per basic and diluted share of $0.33. This compared to a net loss of $24.0
million, or $0.40 per basic and diluted share for 2020. The decrease in net loss was primarily related to an increase in product
revenue with higher margins, partially offset by higher operating expenses and lower research and development revenues.
The net loss for 2020 was $24.0 million, or $0.40 per basic and diluted share. This compared to a net loss of $11.9 million,
or $0.21 per basic and diluted share for 2019. The increase in net loss was primarily related to an increase in costs associated
with outside services relating to CMC and regulatory expenses, higher headcount, higher consultants, higher stock
compensation expenses and higher facility expense.
66
Results of Operations by Segment (in thousands, except percentages)
Revenues by segment
Year Ended December 31, 2021
Year Ended December 31, 2020
Change
Performance
Enzymes
Novel
Biotherapeutics
Total
Performance
Enzymes
Novel
Biotherapeutics Total
Performance
Enzymes
$
%
Novel
Biotherapeutics
%
$
$
70,657 $
— $ 70,657 $
30,220 $
— $ 30,220 $ 40,437 134 % $ — — %
Total revenues
$
19,858
90,515 $
14,239 34,097
14,239 $ 104,754 $
17,886
48,106 $
1,972 11 % (6,711) (32) %
20,950 38,836
20,950 $ 69,056 $ 42,409 88 % $ (6,711) (32) %
Year Ended December 31, 2020
Year Ended December 31, 2019
Change
Performance
Enzymes
Novel
Biotherapeutics
Total
Performance
Enzymes
Novel
Biotherapeutics Total
Performance
Enzymes
$
%
Novel
Biotherapeutics
%
$
$
30,220 $
— $ 30,220 $
29,465 $
— $ 29,465 $
755
3 % $ — — %
Revenues:
Product
revenue
Research and
development
revenue
Revenues:
Product
revenue
Research and
development
revenue
Total revenues
$
17,886
48,106 $
20,950 38,836
20,950 $ 69,056 $
28,691
58,156 $
10,302 38,993 (10,805) (38) % 10,648 103 %
10,302 $ 68,458 $ (10,050) (17) % $ 10,648 103 %
2021 compared to 2020
Revenues from the Performance Enzymes segment increased by $42.4 million, or 88%, to $90.5 million in 2021, compared
to $48.1 million in 2020. The increase in product revenue of $40.4 million, or 134%, to $70.7 million in 2021, compared to
$30.2 million in 2020 was primarily due to $34.5 million in revenue from Pfizer and higher customer demand for enzymes used
in the manufacture of branded pharmaceutical products. The increase in research and development revenue of $2.0 million, or
11%, to $19.9 million in 2021, compared to $17.9 million in 2020 was primarily due to higher licenses fees from existing
collaboration arrangements, partially offset by lower revenues from Novartis under the Novartis CodeEvolver® Agreement.
Revenues from the Novel Biotherapeutics segment decreased by $6.7 million, or 32%, to $14.2 million in 2021, compared
to $21.0 million in 2020. The decrease in revenue was primarily due to lower license and research and development fees from
Takeda under the Takeda Agreement recognized this year compared to the prior year and a decrease in research and
development revenue from Nestlé Health Science compared to last year.
2020 compared to 2019
Revenues from the Performance Enzymes segment decreased by $10.1 million, or 17%, to $48.1 million in 2020,
compared to $58.2 million in 2019. The increase in product revenue of $0.8 million, or 3%, to $30.2 million in 2020, compared
to $29.5 million in 2019, was primarily due to higher customer demand for enzymes used in the manufacture of branded
pharmaceutical products. The decrease in research and development revenue of $10.8 million, or 38%, to $17.9 million in 2020,
compared to $28.7 million in 2019 was primarily due to lower revenues from Novartis under the Novartis CodeEvolver®
Agreement, a prior year milestone payment from GSK under the GSK CodeEvolver® Agreement, and lower license fees and
revenue from Merck, partially offset by the recognition of functional license fees revenue from Porton in 2020.
Revenues from the Novel Biotherapeutics segment increased by $10.6 million, or 103%, to $21.0 million in 2020,
compared to $10.3 million in 2019. The increase in revenue was primarily due to recognition of license fees from Takeda under
the Takeda Agreement, partially offset by a decrease in prior year functional license fee revenue from Nestlé Health Science.
67
Costs and operating expenses by segment
(1) Research and development expenses and selling, general and administrative expenses exclude depreciation and amortization of finance leases.
(2) Corporate costs include unallocated selling, general and administrative expenses.
Year Ended December 31, 2021
Novel
Biotherapeutics
Performance
Enzymes
Total
Year Ended December 31, 2020
Novel
Biotherapeutics
Performance
Enzymes
Total
Change
Performance
Enzymes
$
%
Novel
Biotherapeutics
%
$
$
22,209 $
— $ 22,209 $
13,742 $
— $ 13,742 $ 8,467 62% $ — —%
23,140
30,219
53,359
20,923
21,705 42,628
2,217 11% 8,514 39%
12,105
2,755
14,860
9,597
2,355 11,952
2,508 26%
400 17%
$
57,454 $
32,974
90,428 $
33,808
3,215
$ 127,451
44,262 $
24,060 68,322 $ 13,192 30% $ 8,914 37%
22,555
2,099
$ 92,976
Year Ended December 31, 2020
Novel
Biotherapeutics
Performance
Enzymes
Total
Year Ended December 31, 2019
Novel
Biotherapeutics
Performance
Enzymes
Total
Change
Performance
Enzymes
$
%
Novel
Biotherapeutics
%
$
$
13,742 $
— $ 13,742 $
15,632 $
— $ 15,632 $ (1,890) (12)% $ — —%
20,923
21,705
42,628
19,380
13,278 32,658
1,543
8% 8,427 63%
9,597
2,355
11,952
8,462
2,222 10,684
1,135 13%
133
6%
$
44,262 $
24,060
68,322 $
22,555
2,099
$ 92,976
43,474 $
15,500 58,974 $
20,255
788
2% $ 8,560 55%
1,778
$ 81,007
Cost of product
revenue
Research and
development(1)
Selling, general
and
administrative(1)
Total segment
costs and
operating
expenses
Corporate costs(2)
Unallocated
depreciation and
amortization
Total costs and
operating
expenses
Cost of product
revenue
Research and
development(1)
Selling, general
and
administrative(1)
Total segment
costs and
operating
expenses
Corporate costs(2)
Unallocated
depreciation and
amortization
Total costs and
operating
expenses
(1) Research and development expenses and selling, general and administrative expenses exclude depreciation and amortization of finance leases.
(2) Corporate costs include unallocated selling, general and administrative expenses.
For a discussion of product cost of revenue, see “Results of Operations”.
2021 compared to 2020
Research and development expense in the Performance Enzymes segment increased by $2.2 million, or 11%, to $23.1
million in 2021, compared to $20.9 million in 2020. The increase was primarily due to an increase in costs associated with
higher headcount, higher outside services expenses, and higher lab supplies, partially offset by lower allocable expenses.
68
Selling, general and administrative expense in the Performance Enzymes segment increased by $2.5 million, or 26%, to
$12.1 million in 2021, compared to $9.6 million in 2020. The increase was primarily due to an increase in costs associated with
higher headcount and allocable expenses, partially offset by lower outside services expenses.
Research and development expense in the Novel Biotherapeutics segment increased by $8.5 million, or 39%, to $30.2
million in 2021, compared to $21.7 million in 2020. The increase was primarily due to higher costs associated with higher
headcount and allocable expenses but partially offset by reduction in costs associated with outside services relating to CMC and
regulatory expenses.
Selling, general and administrative expense in the Novel Biotherapeutics segment increased by $0.4 million, or 17%, to
$2.8 million in 2021, compared to $2.4 million in 2020. The increase was primarily due to increase in costs associated with
higher headcount and higher allocable expenses, partially offset by lower outside services expenses.
2020 compared to 2019
Research and development expense in the Performance Enzymes segment increased by $1.5 million, or 8%, to $20.9
million in 2020, compared to $19.4 million in 2019. The increase was primarily due to an increase in costs associated with
higher headcount, higher stock-based compensation expense, higher repairs and maintenance expense, and were partially offset
by lower lab supply expenses and lower allocable expenses.
Selling, general and administrative expense in the Performance Enzymes segment increased by $1.1 million, or 13%, to
$9.6 million in 2020, compared to $8.5 million in 2019. The increase was primarily due to an increase in costs associated with
licensed technology, outside services, stock-based compensation expense, and higher allocable expenses which were partially
offset by lower travel expenses.
Research and development expense in the Novel Biotherapeutics segment increased by $8.4 million, or 63%, to $21.7
million in 2020, compared to $13.3 million in 2019. The increase was primarily due to an increase in costs associated with
outside services relating to CMC and regulatory expenses for CDX-7108 which we are developing pursuant to our development
agreement with Nestlé Health Science, higher headcount, higher outside services, and higher allocable expenses and were
partially offset by lower lab supply expenses and consultant expense.
Selling, general and administrative expense in the Novel Biotherapeutics segment increased by $0.1 million, or 6%, to $2.4
million in 2020, compared to $2.2 million in 2019. The increase was primarily due to an increase in costs associated with
headcount, licensed technology, consultants and stock-based compensation expense which were partially offset by lower
allocable expenses, outside services, and travel expenses.
Income (loss) from operations by segment
Year Ended December 31, 2021
Novel
Biotherapeutics Total
Performance
Enzymes
Year Ended December 31, 2020
Novel
Biotherapeutics Total
Performance
Enzymes
Change
Performance
Enzymes
$
%
Novel
Biotherapeutics
%
$
Income (loss)
from operations $
33,061 $
(18,735) $ 14,326 $
3,844 $
(3,110) $
734 $ 29,217 760% $ (15,625) (502)%
Year Ended December 31, 2020
Year Ended December 31, 2019
Change
Performance
Enzymes
Novel
Biotherapeutics
Total
Performance
Enzymes
Novel
Biotherapeutics
Total
Performance
Enzymes
$
%
Novel
Biotherapeutics
%
$
Income (loss)
from operations $
3,844 $
(3,110) $
734 $
14,682 $
(5,198) $ 9,484 $ (10,838) (74)% $ 2,088 40%
2021 compared to 2020
Income from operations in the Performance Enzymes segment increased by $29.2 million, or 760%, to $33.1 million, in
2021, compared to $3.8 million in 2020. The increase in income from operations was primarily due to higher product revenue
and research and development revenue, partially offset by higher costs and operating expenses.
Loss from operations in the Novel Biotherapeutics segment increased by $15.6 million, or 502%, to $18.7 million in 2021
compared to a loss from operations of $3.1 million in 2020. The increase in loss from operations was primarily due to lower
research and development revenue from Takeda under the Takeda Agreement and decrease in research and development
69
revenue from Nestlé Health Science, and higher research and development expenses associated with higher headcount and
allocable expenses.
2020 compared to 2019
Income from operations in the Performance Enzymes segment decreased by $10.8 million, or 74%, to $3.8 million, in
2020, compared to $14.7 million in 2019. The decrease in income from operations was primarily due to decrease in research
and development revenue and increases in research and development costs and selling, general and administrative expenses.
Loss from operations in the Novel Biotherapeutics segment decreased by $2.1 million, or 40%, to $3.1 million in 2020
compared to a loss from operations of $5.2 million in 2019. The decrease in loss from operation was primarily due to the
recognition of license fees from Takeda under the Takeda Agreement, partially offset by a decrease in prior year functional
license fee revenue from Nestlé Health Science, an increase in costs associated with outside services relating to CMC and
regulatory expenses, higher headcount, higher outside services, and higher allocable expenses.
Liquidity and Capital Resources
Liquidity is the measurement of our ability to meet working capital needs and to fund capital expenditures. We have
historically funded our operations primarily through cash generated from operations, stock option exercises and public and
private offerings of our common stock. We also have the ability to borrow up to $5.0 million under our Credit Facility. We
actively manage our cash usage and investment of liquid cash to ensure the maintenance of sufficient funds to meet our working
capital needs. Our cash and cash equivalents are held in U.S banks.
The following summarizes our cash and cash equivalents balance and working capital as of December 31, 2021, 2020 and
2019 (in thousands):
Cash and cash equivalents
Working capital
Sources of Capital
2021
December 31,
2020
2019
$
$
116,797 $
128,517 $
149,117 $
159,442 $
90,498
98,817
In addition to our existing cash and cash equivalents, we are eligible to earn milestone and other contingent payments for
the achievement of defined collaboration objectives and certain royalty payments under our collaboration agreements. Our
ability to earn these milestone and contingent payments and the timing of achieving these milestones is primarily dependent
upon the outcome of our collaborators’ research and development activities and is uncertain at this time. Under the Merck
CodeEvolver® Agreement, we are eligible to receive payments of up to $15.0 million for each commercial API that is
manufactured by Merck using one or more novel enzymes developed by Merck using the CodeEvolver® technology. In
addition, under the GSK CodeEvolver® Agreement, depending upon GSK's successful application of the licensed technology,
we have the potential to receive additional contingent payments that range from $5.75 million to $38.5 million per project.
In May 2019, we entered into a Platform Technology Transfer and License Agreement with Novartis. The Novartis
CodeEvolver® Agreement allows Novartis to use Codexis’ proprietary CodeEvolver® protein engineering platform technology
in the field of human healthcare. Pursuant to the agreement, we received an upfront payment of $5.0 million shortly after the
effective date. We completed the second technology milestone transfer under the agreement and received a milestone payment
of $4.0 million in 2020. We have also received aggregate of $5.0 million for the completion of the third technology milestone in
2021. In consideration for the continued disclosure and license of improvements to the technology and materials during a multi-
year period that began on the conclusion of the Technology Transfer Period (“Improvements Term”), Novartis will pay Codexis
an additional $8.0 million in aggregate over four years.
In October 2017, we entered into the Nestlé License Agreement with Nestlé Health Science. Pursuant to the Nestlé License
Agreement, Nestlé Health Science paid us an upfront cash payment and milestone payments after dosing the first subjects in a
first-in-human Phase 1a dose-escalation trail with CDX-6114 and achievement of a formulation relating to CDX-6114. We are
also eligible to receive payments from Nestlé Health Science under the Nestlé License Agreement that include (i) development
and approval milestones of up to $85.0 million, (ii) sales-based milestones of up to $250.0 million in the aggregate, which
aggregate amount is achievable if net sales exceed $1.0 billion in a single year, and (iii) tiered royalties, at percentages ranging
from the mid-single digits to low double-digits, of net sales of product.
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We are actively collaborating with new and existing customers in the pharmaceutical and food industries. We believe that
we can utilize our current products and services, and develop new products and services, to increase our revenues and gross
margins in future periods.
We have historically experienced negative cash flows from operations as we continue to invest in key technology
development projects and improvements to our CodeEvolver® protein engineering technology platform, and expand our
business development and collaboration with new customers. Our cash flows from operations will continue to be affected
principally by product sales and product gross margins, sales from licensing our technology to major pharmaceutical
companies, and collaborative research and development services provided to customers, as well as our headcount costs,
primarily in research and development. Our primary source of cash flows from operating activities is cash receipts from our
customers for purchases of products, collaborative research and development services, and licensing our technology to major
pharmaceutical companies. Our largest uses of cash from operating activities are for employee-related expenditures, rent
payments, inventory purchases to support our product sales and non-payroll research and development costs.
Equity Distribution Agreement
In May 2021, we entered into an Equity Distribution Agreement ("EDA") with Piper Sandler & Co ("PSC"), under which
PSC, as our exclusive agent, at our discretion and at such times that we may determine from time to time, may sell over a three-
year period from the execution of the EDA up to a maximum of $50.0 million of shares of our common stock. During the year
ended December 31, 2021, no shares of our common stock were issued pursuant to the EDA. As of December 31, 2021, $50.0
million of shares remained available for sale under the EDA. Sales of our common stock under this arrangement could be
subject to business, economic or competitive uncertainties and contingencies, many of which may be beyond our control, and
which could cause actual results from the sale of our common stock to differ materially from expectations.
Credit Facility
In June 2017, we entered into the Credit Facility with Western Alliance Bank which consists of term debt for loans that
allowed us to borrow up to $10.0 million and a revolving credit facility that allows us to borrow up to $5.0 million with a
certain eligible accounts receivable borrowing base of 80% of eligible accounts receivable. In September 2021, we entered into
the Ninth Amendment to the Credit Facility whereby we may draw on the Term Debt and the Revolving Line of Credit at any
time prior to December 31, 2021 and October 1, 2024, respectively, subject to customary conditions for funding including,
among others, that no event of default exists. Draws on the Credit Facility are secured by a lien on substantially all of our
personal property other than our intellectual property. On October 1, 2024, loans drawn under the Term Debt mature and the
Revolving Line of Credit terminate. Our right to take draws on the term debt expired on December 31, 2021 and no amounts
were drawn under the Credit Facility as of December 31, 2021. The Credit Facility requires us to maintain compliance with
certain financial covenants including attainment of certain lender-approved projections or maintenance of certain minimum
cash levels. Restrictive covenants in the Credit Facility restrict the payment of dividends or other distributions. At
December 31, 2021, we were in compliance with the covenants for the Credit Facility. For additional information about our
contractual obligations, see Note 13, “Commitments and Contingencies” in the Notes to the Consolidated Financial Statements
set forth in Item 8 of this Annual Report on Form 10-K.
We believe that, based on our current level of operations, our existing cash and cash equivalents will provide adequate
funds for ongoing operations, planned capital expenditures and working capital requirements for at least the next 12 months.
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However, we may need additional capital if our current plans and assumptions change. In addition, we may choose to seek
other sources of capital even if we believe we have generated sufficient cash flows to support our operating needs. Our need for
additional capital will depend on many factors, including the financial success of our business, the spending required to develop
and commercialize new and existing products, the effect of any acquisitions of other businesses, technologies or facilities that
we may make or develop in the future, our spending on new market opportunities, and the potential costs for the filing,
prosecution, enforcement and defense of patent claims, if necessary. If our capital resources are insufficient to meet our capital
requirements, and we are unable to enter into or maintain collaborations with partners that are able or willing to fund our
development efforts or commercialize any products that we develop or enable, we will have to raise additional funds to
continue the development of our technology and products and complete the commercialization of products, if any, resulting
from our technologies. If future financings involve the issuance of equity securities, our existing stockholders would suffer
dilution. If we raise debt financing or enter into credit facilities, we may be subject to restrictive covenants that limit our ability
to conduct our business. We may not be able to raise sufficient additional funds on terms that are favorable to us, if at all. If we
fail to raise sufficient funds and fail to generate sufficient revenues to achieve planned gross margins and to control operating
costs, our ability to fund our operations, take advantage of strategic opportunities, develop products or technologies, or
otherwise respond to competitive pressures could be significantly limited. If this happens, we may be forced to delay or
terminate research or development programs or the commercialization of products resulting from our technologies, curtail or
cease operations or obtain funds through collaborative and licensing arrangements that may require us to relinquish commercial
rights, or grant licenses on terms that are not favorable to us. If adequate funds are not available, we will not be able to
successfully execute our business plan or continue our business.
Cash Flows
The following is a summary of cash flows for the years ended December 31, 2021, 2020 and 2019 (in thousands):
Net cash used in operating activities
Net cash used in investing activities
Net cash provided by financing activities
Net increase (decrease) in cash, cash equivalents and restricted cash
Cash Flows from Operating Activities
Year Ended December 31,
2020
2019
2021
$
$
(14,267) $
(21,422)
3,767
(31,922) $
(16,464) $
(5,748)
80,808
58,596 $
(12,560)
(3,665)
53,961
37,736
Cash used in operating activities was $14.3 million in 2021, which resulted from a net loss of $21.3 million adjusted for
non-cash charges for depreciation of $3.1 million, right-of-use ("ROU") lease asset amortization expense of $2.8 million, stock-
based compensation of $11.6 million, $0.3 million allowance for credit losses, partially offset by equity securities earned from
research and development activities of $2.0 million and unrealized gain on non-marketable securities of $1.3 million.
Additionally, changes in operating assets and liabilities were $7.6 million. The net change in operating assets and liabilities
included a decrease in other long-term liabilities of $4.1 million, increase in financial assets of $9.2 million, increase in prepaid
expenses and other assets of $2.3 million, increase in inventories of $0.2 million, partially offset by increase in accrued
compensation and other accrued liabilities of $6.6 million, increase in deferred revenue of $1.3 million and increase of $0.3
million in accounts payable.
Cash used in operating activities was $16.5 million in 2020, which resulted from a net loss of $24.0 million adjusted for
non-cash charges for depreciation of $2.0 million, ROU lease asset amortization expense of $2.6 million and stock-based
compensation of $7.7 million, as well as changes in operating assets and liabilities. The net change in operating assets and
liabilities included decreases in other long-term liabilities of $2.6 million and combined increases in financial assets of $8.7
million, prepaid expenses and other assets of $1.0 million, as well as accrued compensation and other accrued liabilities of $6.2
million and deferred revenue of $2.7 million.
Cash used in operating activities was $12.6 million in 2019, which resulted from a net loss of $11.9 million adjusted for
non-cash charges for depreciation of $1.6 million, ROU lease asset amortization expense of $3.0 million and stock-based
compensation of $6.9 million, as well as changes in operating assets and liabilities. The net change in operating assets and
liabilities included decreases in deferred revenue of $6.2 million and in other long-term liabilities of $1.2 million, and combined
increases in financial assets of $5.9 million, prepaid expenses and other assets of $1.3 million, as well as accrued compensation
and other accrued liabilities of $2.2 million.
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Cash Flows from Investing Activities
Cash used in investing activities was $21.4 million in 2021 primarily due to the purchase of property and equipment of
$13.8 million and for the purchase of 1,000,000 shares of MAI's Series A preferred stock in April 2021 and 9,198,423 shares of
MAI's Series B preferred stock in September 2021 for $7.6 million.
Cash used in investing activities was $5.7 million in 2020 primarily due to the purchase of property and equipment of $3.7
million, and investments in non-marketable equity securities of $1.0 million and non-marketable debt securities of $1.0 million.
Cash used in investing activities was $3.7 million in 2019 primarily due to the purchase of property and equipment of $3.7
million and partially offset by proceeds from sale of CO2 investment securities of $0.1 million.
Cash Flows from Financing Activities
Cash provided by financing activities was $3.8 million in 2021, primarily due to $5.2 million of proceeds from exercises of
stock options, partially offset by $1.2 million for taxes paid related to net share settlement of equity awards and $0.2 million of
costs incurred in connection with the EDA.
Cash provided by financing activities was $80.8 million in 2020, primarily due to $80.8 million net proceeds from our
offering of common stock after deducting underwriting discounts and commission and related costs and proceeds from the
exercises of employee stock options which were partially offset by the payment of taxes related to the net share settlement of
equity awards
Cash provided by financing activities was $54.0 million in 2019, primarily due to net proceeds from our private offering of
common stock after deducting underwriting discounts and commission and related costs and proceeds from the exercises of
employee stock options which were partially offset by the payment of taxes related to the net share settlement of equity awards.
Off-Balance Sheet Arrangements
As of December 31, 2021, we had no off-balance sheet arrangements as defined in Item 303(a)(4) of Regulation S-K as
promulgated by the SEC.
Critical Accounting Policies and Estimates
Management’s discussion and analysis of our financial condition and results of operations are based upon our consolidated
financial statements. The consolidated financial statements have been prepared in conformity with generally accepted
accounting principles in the United States and include our accounts and the accounts of our wholly owned subsidiaries. The
preparation of our consolidated financial statements requires our management to make estimates, assumptions, and judgments
that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the date of the
financial statements, and the reported amounts of revenues and expenses during the applicable periods. Management bases its
estimates, assumptions and judgments on historical experience and on various other factors that are believed to be reasonable
under the circumstances. Different assumptions and judgments would change the estimates used in the preparation of our
consolidated financial statements, which, in turn, could change the results from those reported. Our management evaluates its
estimates, assumptions and judgments on an ongoing basis.
The critical accounting policies requiring estimates, assumptions, and judgments that we believe have the most significant
impact on our consolidated financial statements are described below.
Revenue Recognition
Our revenues are derived primarily from product revenue and collaborative research and development agreements. The
majority of our contracts with customers typically contain multiple products and services. We account for individual products
and services separately if they are distinct-that is, if a product or service is separately identifiable from other items in the
contract and if a customer can benefit from it on its own or with other resources that are readily available to the customer.
In determining the appropriate amount of revenue to be recognized as we fulfill our obligations under our product revenue
and collaborative research and development agreements, we perform the following steps: (i) identification of the promised
goods or services in the contract; (ii) determination of whether the promised goods or services are performance obligations,
including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the
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constraint on variable consideration; (iv) allocation of the transaction price to the performance obligations based on estimated
selling prices; and (v) recognition of revenue when (or as) we satisfy each performance obligation.
The majority of our collaborative contracts contain multiple revenue streams such as upfront and/or annual license fees,
research and development services, contingent milestone payments upon achievement of contractual criteria, and royalty fees
based on the licensees' product revenue or usage, among others. We determine the stand-alone selling price (“SSP”) and
allocate consideration to distinct performance obligations. Typically, we base our SSPs on our historical sales. If an SSP is not
directly observable, then we estimate the SSP taking into consideration market conditions, forecasted sales, entity-specific
factors and available information about the customer. We estimate the SSP for license rights by using a discounted cash flow
method which includes the following key assumptions: the development timelines, revenue forecasts, commercialization
expenses, discount rate, and the probability of technical and regulatory success. For licenses that have been previously sold to
other customers, we use historical information to determine SSP.
We account for a contract with a customer when there is approval and commitment from both parties, the rights of the
parties are identified, payment terms are identified, the contract has commercial substance and collectability of consideration is
probable. Non-cancellable purchase orders received from customers to deliver a specific quantity of product, when combined
with our order confirmation, in exchange for future consideration, create enforceable rights and obligations on both parties and
constitute a contract with a customer.
We measure revenue based on the consideration specified in the contract with each customer, net of any sales incentives
and taxes collected on behalf of government authorities. We recognize revenue in a manner that best depicts the transfer of
promised goods or services to the customer, when control of the product or service is transferred to a customer. We make
significant judgments when determining the appropriate timing of revenue recognition.
The following is a description of principal activities from which we generate revenue:
Product Revenue
Product revenue consist of sales of biocatalysts, pharmaceutical intermediates and Codex® biocatalyst panels and kits. A
majority of our product revenue is made pursuant to purchase orders or supply agreements and is recognized either at a point in
time when the control of the product has been transferred to the customer typically upon shipment or over time as the product is
manufactured because we have a right to payment from the customer under a binding, non-cancellable purchase order, and there
is no alternate use of the product for us as it is specifically made for the customer’s use.
Certain of our agreements provide options to customers which they can exercise at a future date, such as the option to
purchase our product during the contract duration at discounted prices and an option to extend their contract, among others. In
accounting for customer options, we determine whether an option is a material right and this requires us to exercise significant
judgment. If a contract provides the customer an option to acquire additional goods or services at a discount that exceeds the
range of discounts that we typically give for that product or service, or if the option provides the customer certain additional
goods or services for free, the option may be considered a material right. If the contract gives the customer the option to acquire
additional goods or services at their normal SSPs, we would likely determine that the option is not a material right and,
therefore, account for it as a separate performance obligation when the customer exercises the option. We primarily account for
options which provide material rights using the alternative approach available under ASC 606, as we concluded we meet the
criteria for using the alternative approach. Therefore, the transaction price is calculated as the expected consideration to be
received for all the goods and services we expect to provide. We update the transaction price for expected consideration, subject
to constraint, each reporting period if our estimate of future goods to be ordered by customers change.
Research and Development Revenues
We perform research and development activities as specified in each respective customer agreement. We identify each
performance obligation in our research and development agreements at contract inception. We allocate the consideration to each
distinct performance obligation based on the estimated SSP of each performance obligation. Performance obligations included
in our research and services agreements typically include research and development services for a specified term, periodic
reports and small samples of enzyme produced.
The majority of our research and development agreements are based on a contractual rate per dedicated project team
working on the project. The underlying product that we develop for customers does not create an asset with an alternative use to
us and the customer receives benefits as we perform the work towards completion. Thus, our performance obligations are
generally satisfied over time as the service is performed. We utilize an appropriate method of measuring progress towards the
completion of our performance obligations to determine the timing of revenue recognition. For each performance obligation
that is satisfied over time, we recognize revenue using a single measure of progress, typically based on hours incurred.
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Our contracts frequently provide customers with rights to use or access our products or technology, along with other
promises or performance obligations. Under ASC 606, we must first determine whether the license is distinct from other
promises, such as our promise to perform research and development services. If we determine that the customer cannot benefit
from the license without our services, the license will be accounted for as combined with the other performance obligations. If
we determine that a license is distinct, we would recognize an allocable portion of the transaction price when the license is
transferred to the customer, and the customer can use and benefit from it. We estimate the SSP for license rights by using
historical information if licenses have been previously sold to customers and for new licenses, we consider multiple methods, a
discounted cash flow method which includes the following key assumptions: the development timelines, revenue forecasts,
commercialization expenses, discount rate, and the probability of technical and regulatory success.
At the inception of each arrangement that includes variable consideration such as development milestone payments, we
evaluate whether the milestones are considered probable of being reached and estimate the amount to be included in the
transaction price using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the
associated milestone value is included in the transaction price. Milestone payments that are not within our control or the
licensee, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. The
transaction price is then allocated to each performance obligation on a relative stand-alone selling price basis, for which we
recognize revenue as or when the performance obligations under the contract are satisfied. At the end of each subsequent
reporting period, we re-evaluate the probability of achievement of such development milestones and any related constraint, and
if necessary, adjust our estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up
basis, which would affect license, collaboration and other revenues and earnings in the period of adjustment.
Our CodeEvolver® platform technology transfer collaboration agreements typically include license fees, upfront fees, and
variable consideration in the form of milestone payments, and sales or usage-based royalties. We have recognized revenues
from our platform technology transfer agreements over time.
We also have an agreement under which we have granted a functional license to some elements of our biocatalyst
technology. We will recognize revenues for the functional license at a point in time when the control of the license transfers to
the customer.
For license agreements that include sales or usage-based royalty payments to us for which the license is the predominant
item to which the royalty relates, we do not recognize revenue until the underlying sales of the product or usage has occurred.
At the end of each reporting period, we estimate the royalty amount. We recognize revenue at the later of (i) when the related
sale of the product occurs, or (ii) when the performance obligation to which some or all of the royalty has been allocated has
been satisfied, or partially satisfied.
Stock-Based Compensation
We use the Black-Scholes-Merton option pricing model to estimate the fair value of options granted under our equity
incentive plans. The Black-Scholes-Merton option pricing model requires the use of assumptions, including the expected term
of the award and the expected stock price volatility. The expected term is based on historical exercise behavior on similar
awards, giving consideration to the contractual terms, vesting schedules and expectations of future employee behavior. We use
historical volatility to estimate expected stock price volatility. The risk-free rate assumption is based on United States Treasury
instruments whose terms are consistent with the expected term of the stock options. The expected dividend assumption is based
on our history and expectation of dividend payouts.
Restricted Stock Units (“RSUs”), Restricted Stock Awards (“RSAs”) and performance-contingent restricted stock units
(“PSUs”) are measured based on the fair market values of the underlying stock on the dates of grant. Performance based options
(“PBOs”) are measured using Black-Scholes-Merton option pricing model. The vesting of PBOs and PSUs awarded is
conditioned upon the attainment of one or more performance objectives over a specified period and upon continued
employment through the applicable vesting date. At the end of the performance period, shares of stock subject to the PBOs and
PSUs vest based upon both the level of achievement of performance objectives within the performance period and continued
employment through the applicable vesting date.
Stock-based compensation expense is calculated based on awards ultimately expected to vest and is reduced for estimated
forfeitures at the time of grant and revised, if necessary, in subsequent periods if actual forfeitures differ from those estimates.
The estimated annual forfeiture rates for stock options, RSUs, PSUs, PBOs, and RSAs are based on historical forfeiture
experience.
The estimated fair value of stock options, RSUs and RSAs are expensed on a straight-line basis over the vesting term of the
grant and the estimated fair value of PSUs and PBOs are expensed using an accelerated method over the term of the award once
management has determined that it is probable that the performance objective will be achieved. Compensation expense is
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recorded over the requisite service period based on management's best estimate as to whether it is probable that the shares
awarded are expected to vest. Management assesses the probability of the performance milestones being met on a continuous
basis.
Lease Accounting
We determine if an arrangement is a lease at inception. Where an arrangement is a lease we determine if it is an operating
lease or a finance lease. At lease commencement, we record a lease liability and corresponding ROU asset. Lease liabilities
represent the present value of our future lease payments over the expected lease term which includes options to extend or
terminate the lease when it is reasonably certain those options will be exercised. The present value of our lease liability is
determined using our incremental collateralized borrowing rate at lease inception. ROU assets represent our right to control the
use of the leased asset during the lease and are recognized in an amount equal to the lease liability for leases with an initial term
greater than 12 months. Over the lease term we use the effective interest rate method to account for the lease liability as lease
payments are made and the ROU asset is amortized to consolidated statement of operations in a manner that results in straight-
line expense recognition.
We elected to apply the practical expedient for short-term leases and accordingly do not apply lease recognition
requirements for short-term leases. Instead, we recognize payments related to these arrangements in the consolidated statement
of operations as lease costs on a straight-line basis over the lease term.
Investment in Non-Marketable Securities
Investment in Non-Marketable Equity Securities
We measure investments in non-marketable equity securities without a readily determinable fair value using a measurement
alternative that measures these securities at the cost method minus impairment, if any, plus or minus changes resulting from
observable price changes on a non-recurring basis. Gains and losses on these securities are recognized in other income
(expense), net.
Investment in Non-Marketable Debt Securities
We measure available for sale investments in non-marketable debt at fair value. Unrealized gains and losses on these
securities are recognized in other comprehensive income until realized. Non-marketable debt securities are classified as
available-for-sale securities.
We classify non-marketable debt securities as Level 3 in the fair value hierarchy because we estimate the fair value based
on a qualitative analysis using the most recent observable transaction price and other significant unobservable inputs including
volatility, rights, and obligations of the securities we hold. Significant changes to the unobservable inputs may result in a
significantly higher or lower fair value estimate. We may value these securities based on significant recent arms-length
transactions with sophisticated non-strategic unrelated new investors.
We evaluate both equity and debt securities for impairment when circumstances indicate that we may not be able to recover
the carrying value. We may impair these securities and establish an allowance for a credit loss when we determine that there has
been an “other-than-temporary” decline in estimated fair value of the debt or equity security compared to its carrying value. We
calculate the estimated fair value of these securities using information from the investee, which may include:
•
•
•
•
•
•
Audited and unaudited financial statements;
Projected technological developments of the company;
Projected ability of the company to service its debt obligations;
If a deemed liquidation event were to occur;
Current fundraising transactions;
Current ability of the company to raise additional financing if needed;
•
company;
Changes in the economic environment which may have a material impact on the operating results of the
•
•
Contractual rights, obligations or restrictions associated with the investment; and
Other factors deemed relevant by our management to assess valuation.
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•
The valuation may be reduced if the company's potential has deteriorated significantly. If the factors that led
to a reduction in valuation are overcome, the valuation may be readjusted.
Recent Accounting Pronouncements
See Note 2, “Basis of Presentation and Summary of Significant Accounting Policies” in the Notes to the Consolidated
Financial Statements set forth in Item 8 of this Annual Report on Form 10-K for a full description of recent accounting
standards, including the respective dates of adoption and effects on our consolidated financial position, results of operations and
cash flows.
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ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
Interest Rate Sensitivity
Our unrestricted cash and cash equivalents total $116.8 million at December 31, 2021. We primarily invest these amounts
in money market funds which are held for working capital purposes. We do not enter into investments for trading or speculative
purposes. As of December 31, 2021, the effect of a hypothetical 10% decrease in market interest rates would have an
immaterial impact on a potential loss in future interest income and cash flows.
In June 2017, we entered into a Credit Facility with Western Alliance Bank consisting of term loans up to $10.0 million,
and advances under a revolving line of credit up to $5.0 million. Term loans made under the Term Debt bear interest at variable
rate through maturity at the greater of (i) 3.75% or (ii) the sum of (A) Index Rate (prime rate published in the Money Rates
section of the Western Edition of The Wall Street Journal plus (B) 0.50%. Advances made under the Revolving Line of Credit
bear interest at a variable annual rate equal to the greater of (i) 4.25% or (ii) the sum of (A) the prime rate plus (B) 1.00%.
Increases in these variable interest rates will increase our future interest expense and decrease our results of operations and cash
flows. Our right to take draws on the long term debt expired on December 31, 2021 and no amounts were drawn under the
Credit Facility as of December 31, 2021. Our exposure to interest rates risk relates to our 2017 Credit Facility with variable
interest rates, where an increase in interest rates may result in higher borrowing costs. Since we have no outstanding borrowings
under our 2017 Credit Facility as of December 31, 2021, the effect of a hypothetical 10% change in interest rates would not
have any impact on our interest expense.
Foreign Currency Risk
Our results of operations and cash flows are subject to fluctuations due to changes in foreign currency exchange rates. In
periods when the USD declines in value as compared to the foreign currencies in which we incur expenses, our foreign-
currency based expenses increase when translated into United States dollars. Although substantially all of our sales are
denominated in United States dollars, future fluctuations in the value of the USD may affect the price competitiveness of our
products outside the United States. Our most significant foreign currency exposure is due to non-functional currency
denominated monetary assets, primarily currencies denominated in other than their functional currency. These non-functional
currency denominated monetary assets are subject to re-measurement which may create fluctuations in other expense, net, a
component in our consolidated statement of operations and in the fair value of the assets in the consolidated balance sheets. As
of December 31, 2021, the effect of a hypothetical 10% unfavorable change in exchange rates on currencies denominated in
other than their functional currency would result in a potential loss in future earnings in our consolidated statement of
operations and a reduction in the fair value of the assets of approximately $46 thousand. We did not engage in hedging
transactions in 2021, 2020 and 2019.
Investment in Non-Marketable Equity Securities
We own investments in non-marketable equity securities without readily determinable fair values. We may value these
equity securities based on significant recent arms-length equity transactions with sophisticated non-strategic unrelated
investors, providing the terms of these security transactions are substantially similar to the security transactions terms between
the investors and us. The impact of the difference in transaction terms on the market value of the portfolio company may be
difficult or impossible to quantify.
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ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA
Codexis, Inc.
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Reports of Independent Registered Public Accounting Firm (BDO USA, LLP; San Jose, CA; PCAOB ID: 243)
Consolidated Balance Sheets
Consolidated Statements of Operations
Consolidated Statements of Stockholders' Equity
Consolidated Statements of Cash Flows
Notes to Consolidated Financial Statements
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84
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Report of Independent Registered Public Accounting Firm
Shareholders and Board of Directors
Codexis, Inc.
Redwood City, California
Opinion on the Consolidated Financial Statements
We have audited the accompanying consolidated balance sheets of Codexis, Inc. (the “Company”) as of December 31, 2021 and
2020, the related consolidated statements of operations, stockholders’ equity, and cash flows for each of the three years in the
period ended December 31, 2021, and the related notes (collectively referred to as the “Consolidated Financial Statements”). In
our opinion, the Consolidated Financial Statements present fairly, in all material respects, the financial position of the Company
at December 31, 2021 and 2020, and the results of its operations and its cash flows for each of the three years in the period
ended December 31, 2021, in conformity with accounting principles generally accepted in the United States of America.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States)
(“PCAOB”), the Company's internal control over financial reporting as of December 31, 2021, based on criteria established in
Internal Control – Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway
Commission (“COSO”) and our report dated February 28, 2022 expressed an unqualified opinion thereon.
Basis for Opinion
These Consolidated Financial Statements are the responsibility of the Company’s management. Our responsibility is to express
an opinion on the Company’s Consolidated Financial Statements based on our audits. We are a public accounting firm
registered with the Public Company Accounting Oversight Board (United States) (“PCAOB”) and are required to be
independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and
regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the
audit to obtain reasonable assurance about whether the Consolidated Financial Statements are free of material misstatement,
whether due to error or fraud.
Our audits included performing procedures to assess the risks of material misstatement of the Consolidated Financial
Statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included
examining, on a test basis, evidence regarding the amounts and disclosures in the Consolidated Financial Statements. Our audits
also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating
the overall presentation of the Consolidated Financial Statements. We believe that our audits provide a reasonable basis for our
opinion.
Critical Audit Matter
The critical audit matter communicated below is a matter arising from the current period audit of the Consolidated Financial
Statements that was communicated or required to be communicated to the audit committee and that: (1) relates to accounts or
disclosures that are material to the Consolidated Financial Statements and (2) involved our especially challenging, subjective,
or complex judgments. The communication of critical audit matters does not alter in any way our opinion on the Consolidated
Financial Statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing separate
opinions on the critical audit matter or on the accounts or disclosures to which it relates.
Revenue Recognition
As described in Notes 2 and 3 to the Consolidated Financial Statements, the Company recognizes revenue in a manner that best
depicts the transfer of promised goods or services to the customer, when control of the product or service is transferred to a
customer. The Company's contracts with customers include enzyme supply, licensing, and collaborative research and
development agreements. Contracts with customers may contain multiple performance obligations and may contain up-front or
annual license fees, fees for full time employee research and development services, contingent milestone payments upon
achievement of contractual criteria, and royalty fees based on the licensees' product revenue or usage. The Company makes
significant judgments in determining revenue recognition for customer contracts.
We identified management’s significant judgments and estimates related to revenue recognition for contracts with customers as
a critical audit matter. Auditing the evaluation of distinct performance obligations, determination and estimation of material
rights, determination of standalone selling prices, determination of the pattern of transfer of control for each distinct
80
performance obligation and estimation of variable consideration required significant audit effort and subjective judgments in
evaluating management's estimates.
The primary procedures we performed to address this critical audit matter included:
• Testing the design and operating effectiveness of internal controls relating to the identification of distinct performance
obligations and material rights, the determination of the timing of revenue recognition, the estimation of standalone
selling prices, and the estimation of variable consideration.
• Examining a sample of revenue contracts and other source documents to test management's identification of significant
terms for completeness, including the identification of distinct performance obligations, material rights and variable
consideration including sending confirmations to a sample of customers to confirm our understanding of the parties’
rights and obligations.
• Assessing the reasonableness of management's estimates and assumptions used in determining stand-alone selling
prices for new products and services and those products and services that are not sold separately.
• Evaluating the reasonableness of management’s judgments and estimates used to assess the stand-alone selling prices
for new functional licenses when granted to customers as part of contracts containing multiple performance
obligations.
• Evaluating the reasonableness and accuracy of management’s judgments and estimates used in accounting for
identified material rights, including transactions accounted for under the alternative approach to estimating the
standalone selling price of a material right. This includes testing management’s estimates of the expected consideration
from the customer’s exercise of options.
• Assessing the reasonableness of management’s judgments and estimates to calculate variable consideration, and the
timing of recognizing the related revenue subject to any constraints.
• Evaluating the appropriateness of management’s determination of whether identified performance obligations meet the
criteria for over-time revenue recognition, including whether certain products and services have alternative use.
/s/ BDO USA, LLP
We have served as the Company's auditor since 2013.
San Jose, California
February 28, 2022
81
Report of Independent Registered Public Accounting Firm
Shareholders and Board of Directors
Codexis, Inc.
Redwood City, California
Opinion on Internal Control over Financial Reporting
We have audited Codexis, Inc.’s (the “Company’s”) internal control over financial reporting as of December 31, 2021, based on
criteria established in Internal Control – Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of
the Treadway Commission (the “COSO criteria”). In our opinion, the Company maintained, in all material respects, effective
internal control over financial reporting as of December 31, 2021, based on the COSO criteria.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States)
(“PCAOB”), the consolidated balance sheets of the Company as of December 31, 2021 and 2020, the related consolidated
statements of operations, stockholders’ equity, and cash flows for each of the three years in the period ended December 31,
2021, and the related notes, and our report dated February 28, 2022 expressed an unqualified opinion thereon.
Basis for Opinion
The Company’s management is responsible for maintaining effective internal control over financial reporting and for its
assessment of the effectiveness of internal control over financial reporting, included in the accompanying “Item 9A,
Management’s Report on Internal Control over Financial Reporting”. Our responsibility is to express an opinion on the
Company’s internal control over financial reporting based on our audit. We are a public accounting firm registered with the
PCAOB and are required to be independent with respect to the Company in accordance with U.S. federal securities laws and
the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audit of internal control over financial reporting in accordance with the standards of the PCAOB. Those
standards require that we plan and perform the audit to obtain reasonable assurance about whether effective internal control
over financial reporting was maintained in all material respects. Our audit included obtaining an understanding of internal
control over financial reporting, assessing the risk that a material weakness exists, and testing and evaluating the design and
operating effectiveness of internal control based on the assessed risk. Our audit also included performing such other procedures
as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion.
Definition and Limitations of Internal Control over Financial Reporting
A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the
reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally
accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures
that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and
dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit
preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and
expenditures of the company are being made only in accordance with authorizations of management and directors of the
company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or
disposition of the company’s assets that could have a material effect on the financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also,
projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate
because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.
/s/ BDO USA, LLP
San Jose, California
February 28, 2022
82
Codexis, Inc.
Consolidated Balance Sheets
(In Thousands, Except Per Share Amounts)
Assets
Current assets:
Cash and cash equivalents
Restricted cash, current
Investment in non-marketable debt security
Financial assets:
Accounts receivable
Contract assets ($0 and $450 from a related party)
Unbilled receivables
Total financial assets
Less: allowances
Total financial assets, net
Inventories
Prepaid expenses and other current assets
Total current assets
Restricted cash
Investment in non-marketable equity securities ($12,713 and $1,450 with a related party)
Right-of-use assets - Operating leases, net
Right-of-use assets - Finance leases, net
Property and equipment, net
Goodwill
Other non-current assets
Total assets
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable
Accrued compensation
Other accrued liabilities
Current portion of lease obligations - Operating leases
Deferred revenue ($245 and $0 to a related party)
Total current liabilities
Deferred revenue, net of current portion
Long-term lease obligations, Operating leases
Other long-term liabilities
Total liabilities
Commitments and contingencies (Note 13)
Stockholders’ equity:
Preferred stock, $0.0001 par value per share; 5,000 shares authorized, none issued and
outstanding
Common stock, $0.0001 par value per share; 100,000 shares authorized; 65,109 and 64,283
shares issued and outstanding at December 31, 2021 and December 31, 2020, respectively
Additional paid-in capital
Accumulated deficit
Total stockholders’ equity
Total liabilities and stockholders’ equity
See accompanying notes to consolidated financial statements
83
December 31,
2021
2020
116,797 $
579
—
24,953
4,557
8,558
38,068
(416)
37,652
1,160
5,700
161,888
1,519
14,002
44,095
17
21,345
3,241
276
246,383 $
2,995 $
11,119
12,578
4,093
2,586
33,371
3,749
43,561
1,311
81,992
149,117
638
1,000
13,894
4,526
10,942
29,362
(74)
29,288
964
3,416
184,423
1,062
1,450
21,382
119
9,675
3,241
294
221,646
2,970
7,288
10,272
2,627
1,824
24,981
2,967
22,324
1,271
51,543
—
—
6
552,083
(387,698)
164,391
246,383 $
6
536,516
(366,419)
170,103
221,646
$
$
$
$
Codexis, Inc.
Consolidated Statements of Operations
(In Thousands, Except Per Share Amounts)
Revenues:
Product revenue
Research and development revenue ($1,955, $900 and $0 from a related party)
$
Total revenues
Costs and operating expenses:
Cost of product revenue
Research and development
Selling, general and administrative
Total costs and operating expenses
Loss from operations
Interest income
Other income (expense), net ($983, $0 and $0 from a related party)
Loss before income taxes
Provision for income taxes
Net loss
Net loss per share, basic and diluted
Weighted average common stock shares used in computing net loss per share, basic and
diluted
$
$
Year Ended December 31,
2020
2021
2019
70,657 $
34,097
104,754
22,209
55,919
49,323
127,451
(22,697)
459
1,148
(21,090)
189
(21,279) $
30,220 $
38,836
69,056
13,742
44,185
35,049
92,976
(23,920)
405
(156)
(23,671)
339
(24,010) $
29,465
38,993
68,458
15,632
33,873
31,502
81,007
(12,549)
1,287
(656)
(11,918)
17
(11,935)
(0.33) $
(0.40) $
(0.21)
64,568
59,360
56,525
See accompanying notes to consolidated financial statements
84
Codexis, Inc.
Consolidated Statements of Stockholders’ Equity
(In Thousands)
Common Stock
Amount
December 31, 2018
Exercise of stock options
Release of stock awards
Employee stock-based compensation
Taxes paid related to net share settlement of equity awards
Issuance of common stock, net of issuance costs of $123
Short swing profit settlement
Net loss
December 31, 2019
Exercise of stock options
Release of stock awards
Employee stock-based compensation
Non-employee stock-based compensation
Taxes paid related to net share settlement of equity awards
Issuance of common stock, net of issuance costs of $5,448
Net loss
December 31, 2020
Exercise of stock options
Release of stock awards
Employee stock-based compensation
Non-employee stock-based compensation
Taxes paid related to net share settlement of equity awards
Net loss
December 31, 2021
Shares
54,065 $
1,466
449
—
(152)
3,049
—
—
58,877
210
370
—
—
(103)
4,929
—
64,283
699
181
—
—
(54)
—
65,109 $
Additional
Paid-in
Capital
5 $ 386,775 $
7,099
—
—
—
6,943
—
(2,850)
—
49,876
1
77
—
—
—
6 447,920
1,323
—
—
—
7,622
—
106
—
(1,257)
—
—
80,802
—
—
6 536,516
5,180
—
—
—
11,346
—
—
247
—
(1,206)
—
—
6 $ 552,083 $
Total
Stockholders’
Equity
Accumulated
Deficit
(330,474) $
56,306
—
7,099
—
—
—
6,943
—
(2,850)
—
49,877
—
77
(11,935)
(11,935)
(342,409)
105,517
—
1,323
—
—
—
7,622
—
106
—
(1,257)
—
80,802
(24,010)
(24,010)
(366,419)
170,103
—
5,180
—
—
—
11,346
—
247
—
(1,206)
(21,279)
(21,279)
(387,698) $ 164,391
See accompanying notes to consolidated financial statements
85
Codexis, Inc.
Consolidated Statements of Cash Flows
(In Thousands)
Year Ended December 31,
2020
2021
2019
$
(21,279) $
(24,010) $
(11,935)
Operating activities:
Net loss
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation
Amortization expense - right-of-use assets - operating and finance leases
Stock-based compensation
Allowance for credit losses
Equity securities earned from research and development activities from a related
party
Unrealized gain on non-marketable securities (($983) from a related party)
Other non-cash items
Changes in operating assets and liabilities:
Financial assets ($0, ($450) and ($332) from a related party)
Inventories
Prepaid expenses and other assets
Accounts payable
Accrued compensation and other accrued liabilities
Other long-term liabilities
Deferred revenue ($245, $0 and $0 to a related party)
Net cash used in operating activities
Investing activities:
Purchase of property and equipment
Proceeds from sale of property and equipment
Proceeds from sale of investment securities
Investment in non-marketable securities (($7,630) and ($1,000) in a related party)
Net cash used in investing activities
Financing activities:
Proceeds from exercises of stock options
Proceeds from issuance of common stock in connection with public offering
Costs incurred in connection with equity financing
Proceeds from issuance of common stock in connection with private offering
Payments of lease obligations - Finance leases
Recovery of short swing profit
Taxes paid related to net share settlement of equity awards
Net cash provided by financing activities
Net increase (decrease) in cash, cash equivalents and restricted cash
Cash, cash equivalents and restricted cash at the beginning of the year
Cash, cash equivalents and restricted cash at the end of the year
Supplemental disclosure of cash flow information:
Interest paid
Income taxes
Supplemental non-cash investing and financing activities:
Capital expenditures incurred but not yet paid
$
$
$
$
86
3,113
2,834
11,593
342
(1,955)
(1,272)
(19)
(9,156)
(196)
(2,268)
268
6,575
(4,147)
1,300
(14,267)
(13,828)
36
—
(7,630)
(21,422)
1,950
2,604
7,728
40
(900)
—
15
(8,723)
(593)
(1,012)
101
6,175
(2,586)
2,747
(16,464)
(3,748)
—
—
(2,000)
(5,748)
5,180
—
(207)
—
—
—
(1,206)
3,767
(31,922)
150,817
118,895 $
1,323
86,250
(5,448)
—
(60)
—
(1,257)
80,808
58,596
92,221
150,817 $
1,570
2,987
6,943
—
—
—
525
(5,867)
217
(1,324)
(428)
2,205
(1,210)
(6,243)
(12,560)
(3,730)
3
62
—
(3,665)
7,099
—
(123)
50,000
(242)
77
(2,850)
53,961
37,736
54,485
92,221
14 $
102 $
52 $
312 $
49
5
2,533 $
1,750 $
140
The following table provides a reconciliation of cash, cash equivalents and restricted cash reported within the consolidated
balance sheets to the total of the same such amounts shown above (in thousands):
Cash and cash equivalents
Restricted cash, current and non-current
Total cash, cash equivalents and restricted cash at the end of the period
Year Ended December 31,
2020
149,117 $
1,700
150,817 $
2021
116,797 $
2,098
118,895 $
2019
90,498
1,723
92,221
$
$
See accompanying notes to consolidated financial statements
87
Codexis, Inc.
Notes to Consolidated Financial Statements
Note 1. Description of Business
In these notes to the Consolidated Financial Statements, the “Company,” “we,” “us,” and “our” refers to Codexis, Inc. and
its subsidiaries on a consolidated basis.
We discover, develop and sell enzymes and other proteins that deliver value to our clients in a growing set of industries to
commercialize an increasing number of novel enzymes, both as proprietary Codexis products and in partnership with our
customers.
We report our financial results based on two reportable segments: Performance Enzymes and Novel Biotherapeutics. The
segment information aligns with how the chief operating decision maker (CODM), who is our Chief Executive Officer (CEO),
reviews and manages the business.
Business Update Regarding COVID-19
We are subject to risks and uncertainties as a result of the current COVID-19 pandemic. The COVID-19 pandemic has
presented a substantial public health and economic challenge around the world and is affecting our employees, communities
and business operations, as well as the U.S. economy and other economies worldwide. The full extent to which the COVID-19
pandemic will directly or indirectly impact our business, results of operations and financial condition will depend on future
developments that are highly uncertain and may not be accurately predicted, including the duration and severity of the
pandemic, the prevalence of more contagious and or virulent variants such as the Delta and Omicron variants, and the extent
and severity of the impact on our customers, new information that may emerge concerning COVID-19, the actions taken to
contain it or treat its impact and the economic impact on local, regional, national and international markets.
In the United States, the impact of COVID-19, including Orders governing the operation of businesses during the
pandemic, caused the temporary closure of our Redwood City, California facilities and disrupted our R&D operations in 2020.
R&D operations for several projects were temporarily suspended from mid-March 2020 through the end of April 2020 in
accordance with these Orders. In May 2020, we initiated limited R&D operations and resumed manufacturing operations at our
Redwood City pilot plant and have ramped up operations such that we are currently utilizing our normal R&D capacity while
following county, state and federal COVID-19 guidance for the protection of our employees.
To date, we and our collaboration partners have been able to continue to supply our enzymes to our customers worldwide,
however, there can be no guarantee this will continue. Furthermore, our ability to provide future research and development
("R&D") services may continue to be impacted as a result of governmental orders ("Orders") and any disruptions in operations
of our customers with whom we collaborate. We believe that these disruptions have had a minimal impact on revenue for the
year ended December 31, 2021. The extent to which the pandemic may impact our business operations and operating results
will continue to remain highly dependent on future developments, which are uncertain and cannot be predicted with confidence.
Note 2. Basis of Presentation and Summary of Significant Accounting Policies
Basis of Presentation and Principles of Consolidation
The accompanying consolidated financial statements have been prepared in accordance with generally accepted accounting
principles in the United States of America ("GAAP") and the applicable rules and regulations of the Securities and Exchange
Commission ("SEC") and include the accounts of Codexis, Inc. and its wholly-owned subsidiaries.
Certain prior year amounts have been reclassified in the Consolidated Statements of Cash Flows to conform to the 2021
presentation, however these reclassifications had no effect on the reported results of operations.
The consolidated financial statements include the accounts of Codexis, Inc. and its wholly owned subsidiaries. All
intercompany balances and transactions have been eliminated in consolidation.
Use of Estimates
The preparation of our consolidated financial statements in conformity with GAAP requires us to make estimates,
judgments and assumptions that may affect the reported amounts of assets, liabilities, equity, revenues and expenses and related
disclosure of contingent assets and liabilities. We regularly assess these estimates which primarily affect revenue recognition,
88
inventories, valuation of equity investments, goodwill arising out of business acquisitions, accrued liabilities, stock awards, and
the valuation allowances associated with deferred tax assets. Actual results could differ from those estimates and such
differences may be material to the consolidated financial statements.
Segment Reporting
We report two business segments, Performance Enzymes and Novel Biotherapeutics, which are based on our operating
segments. Operating segments are defined as components of an enterprise about which separate financial information is
available that is evaluated regularly by the chief operating decision maker or decision making group (“CODM”), in deciding
how to allocate resources, and in assessing performance. Our CODM is our Chief Executive Officer. Our business segments are
primarily based on our organizational structure and our operating results as used by our CODM in assessing performance and
allocating resources for the Company. We do not allocate or evaluate assets by segment.
The Novel Biotherapeutics segment focuses on new opportunities in the pharmaceutical industry to discover or improve
novel biotherapeutic drug candidates that will target human diseases that are in need of improved therapeutic interventions.
Similarly, we believe that we can deploy our platform technology to improve specific characteristics of a customer’s pre-
existing biotherapeutic drug candidate, such as its activity, stability, or immunogenicity. The Performance Enzymes segment
consists of biocatalyst products and services with focus on pharmaceutical, food, molecular diagnostics, and other industrial
markets.
Foreign Currency Translation
The USD is the functional currency for our operations outside the United States. Accordingly, non-monetary assets and
liabilities originally acquired or assumed in other currencies are recorded in USD at the exchange rates in effect at the date they
were acquired or assumed. Monetary assets and liabilities denominated in other currencies are translated into United States
dollars at the exchange rates in effect at the balance sheet date. Translation adjustments are recorded in other expense in the
consolidated statements of operations. Gains and losses realized from non-USD transactions, including intercompany balances
not considered as permanent investments, denominated in currencies other than an entity’s functional currency are included in
other expense in the accompanying consolidated statements of operations.
Revenue Recognition
Our revenues are derived primarily from product revenue and collaborative research and development agreements. The
majority of our contracts with customers typically contain multiple products and services. We account for individual products
and services separately if they are distinct-that is, if a product or service is separately identifiable from other items in the
contract and if a customer can benefit from it on its own or with other resources that are readily available to the customer.
In determining the appropriate amount of revenue to be recognized as we fulfill our obligations under our product revenue
and collaborative research and development agreements, we perform the following steps: (i) identification of the promised
goods or services in the contract; (ii) determination of whether the promised goods or services are performance obligations,
including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the
constraint on variable consideration; (iv) allocation of the transaction price to the performance obligations based on estimated
selling prices; and (v) recognition of revenue when (or as) we satisfy each performance obligation.
The majority of our collaborative contracts contain multiple revenue streams such as upfront and/or annual license fees,
fees for research and development services, contingent milestone payments upon achievement of contractual criteria, and
royalty fees based on the licensees' product revenue or usage, among others. We determine the stand-alone selling price (“SSP”)
and allocate consideration to distinct performance obligations. Typically, we base our SSPs on our historical sales. If an SSP is
not directly observable, then we estimate the SSP taking into consideration market conditions, forecasted sales, entity-specific
factors and available information about the customer. We estimate the SSP for license rights by using historical information if
licenses have been previously sold to customers and for new licenses, we consider multiple methods, including a discounted
cash flow method which includes the following key assumptions: the development timelines, revenue forecasts,
commercialization expenses, discount rate, and the probability of technical and regulatory success.
We account for a contract with a customer when there is approval and commitment from both parties, the rights of the
parties are identified, payment terms are identified, the contract has commercial substance and collectability of consideration is
probable. Non-cancellable purchase orders received from customers to deliver a specific quantity of product, when combined
with our order confirmation, in exchange for future consideration, create enforceable rights and obligations on both parties and
constitute a contract with a customer.
89
We measure revenue based on the consideration specified in the contract with each customer, net of any sales incentives
and taxes collected on behalf of government authorities. We recognize revenue in a manner that best depicts the transfer of
promised goods or services to the customer, when control of the product or service is transferred to a customer. We make
significant judgments when determining the appropriate timing of revenue recognition.
The following is a description of principal activities from which we generate revenue:
Product Revenue
Product revenue consist of sales of biocatalysts, pharmaceutical intermediates and Codex® biocatalyst panels and kits. A
majority of our product revenue is made pursuant to purchase orders or supply agreements and is recognized either at a point in
time when the control of the product has been transferred to the customer typically upon shipment or over time as the product is
manufactured because we have a right to payment from the customer under a binding, non-cancellable purchase order, and there
is no alternate use of the product for us as it is specifically made for the customer’s use.
Certain of our agreements provide options to customers which they can exercise at a future date, such as the option to
purchase our product during the contract duration at discounted prices and an option to extend their contract, among others. In
accounting for customer options, we determine whether an option is a material right and this requires us to exercise significant
judgment. If a contract provides the customer an option to acquire additional goods or services at a discount that exceeds the
range of discounts that we typically give for that product or service for the same class of customer, or if the option provides the
customer certain additional goods or services for free, the option may be considered a material right. If the contract gives the
customer the option to acquire additional goods or services at their normal SSPs, we would likely determine that the option is
not a material right and, therefore, account for it as a separate performance obligation when the customer exercises the option.
We primarily account for options which provide material rights using the alternative approach available pursuant to the
applicable accounting guidance, as we concluded we meet the criteria for using the alternative approach. Therefore, the
transaction price is calculated as the expected consideration to be received for all the goods and services we expect to provide
under the contract. We update the transaction price for expected consideration, subject to constraint, each reporting period if our
estimates of future goods to be ordered by customers change.
Research and Development Revenues
We perform research and development activities as specified in each respective customer agreement. We identify each
performance obligation in our research and development agreements at contract inception. We allocate the consideration to each
distinct performance obligation based on the estimated SSP of each performance obligation. Performance obligations included
in our research and services agreements typically include research and development services for a specified term, periodic
reports and small samples of enzyme produced.
The majority of our research and development agreements are based on a contractual rate per dedicated project team
working on the project. The underlying product that we develop for customers does not create an asset with an alternative use to
us and the customer receives benefits as we perform the work towards completion. Thus, our performance obligations are
generally satisfied over time as the service is performed. We utilize an appropriate method of measuring progress towards the
completion of our performance obligations to determine the timing of revenue recognition. For each performance obligation
that is satisfied over time, we recognize revenue using a single measure of progress, typically based on hours incurred.
Our contracts frequently provide customers with rights to use or access our products or technology, along with other
promises or performance obligations. We must first determine whether the license is distinct from other promises, such as our
promise to manufacture a product. If we determine that the customer cannot benefit from the license without our manufacturing
capability, the license will be accounted for as combined with the other performance obligations. If we determine that a license
is distinct and has significant standalone functionality, we would recognize revenues from a functional license at a point in time
when the license is transferred to the customer, and the customer can use and benefit from it. We estimate the SSP for license
rights by using historical information if licenses have been previously sold to customers and for new licenses, we consider
multiple methods, including a discounted cash flow method which includes the following key assumptions: the development
timelines, revenue forecasts, commercialization expenses, discount rate, and the probability of technical and regulatory success.
For licenses that have been previously sold to other customers, we use historical information to determine SSP.
At the inception of each arrangement that includes variable consideration such as development milestone payments, we
evaluate whether the milestones are considered probable of being reached and estimate the amount to be included in the
transaction price using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the
associated milestone value is included in the transaction price. Milestone payments that are not within our control or the
licensee, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. The
transaction price is then allocated to each performance obligation on a relative stand-alone selling price basis, for which we
90
recognize revenue as or when the performance obligations under the contract are satisfied. At the end of each subsequent
reporting period, we re-evaluate the probability of achievement of such development milestones and any related constraint, and
if necessary, adjust our estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up
basis, which would affect license, collaboration and other revenues and earnings in the period of adjustment.
Our CodeEvolver® platform technology transfer collaboration agreements typically include license fees, upfront fees, and
variable consideration in the form of milestone payments, and sales or usage-based royalties. We have recognized revenues
from our platform technology transfer agreements over time as our customer learns to use our technology.
For license agreements that include sales or usage-based royalty payments to us, we do not recognize revenue until the
underlying sales of the product or usage has occurred. At the end of each reporting period, we estimate the royalty amount. We
recognize revenue at the later of (i) when the related sale of the product occurs, or (ii) when the performance obligation to
which some or all of the royalty has been allocated has been satisfied, or partially satisfied.
Practical Expedients, Elections, and Exemptions
We apply certain practical expedients available which permit us not to adjust the amount of consideration for the effects of
a significant financing component if, at contract inception, the expected period between the transfer of promised goods or
services and customer payment is one year or less.
We perform monthly services under our research and development agreements, and we use a practical expedient permitting
us to recognize revenue at the same time that we have the right to invoice our customer for monthly services completed to date.
We have elected to treat shipping and handling activities as fulfillment costs.
We have elected to record revenue net of sales and other similar taxes.
Contract Assets
Contract assets include amounts related to our contractual right to consideration for completed performance obligations not
yet invoiced. Contract assets are reclassified to receivables when the rights become unconditional.
Contract Liabilities
Contract liabilities are recorded as deferred revenues and include payments received in advance of performance under the
contract. Contract liabilities are realized when the development services are provided to the customer or control of the products
has been transferred to the customer. A portion of our contract liabilities relate to supply arrangements that contain material
rights that are recognized using the alternative method, under which the aggregate amount invoiced to the customer for shipped
products, including contractual fees, is higher than the amount of revenue recognized based on the transaction price allocated to
the shipped products.
Contract Costs
We recognize a non-current asset for the incremental costs of obtaining a contract with a customer if the entity expects to
recover such costs. Incremental costs are costs that would not have been incurred if the contract had not been obtained.
Examples of contract costs are commissions paid to sales personnel. We do not typically incur significant incremental costs
because the compensation of our salespeople is not based on contracts closed but on a mixture of company goals, individual
goals, and sales goals. If a commission paid is directly related to obtaining a specific contract, our policy is to capitalize and
amortize such costs on a systematic basis, consistent with the pattern of transfer of the good or service to which the asset
relates. Contract costs are reported in other non-current assets.
Cost of Product Revenue
Cost of product revenue comprises both internal and third party fixed and variable costs including materials and supplies,
labor, facilities, and other overhead costs associated with our product sales. Shipping costs are included in our cost of product
revenue. Such charges were not significant in any of the periods presented.
Fulfillment costs, such as shipping and handling, are recognized at a point in time and are included in cost of product sales.
Cost of Research and Development Services
Cost of research and development services related to services under research and development agreements approximate the
research funding over the term of the respective agreements and is included in research and development expense. Costs of
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services provided under license and platform technology transfer agreements are included in research and development
expenses and are expensed in the periods in which such costs are incurred.
Research and Development Expenses
Research and development expenses consist of costs incurred for internal projects and partner-funded collaborative
research and development activities, as well as license and platform technology transfer agreements, as mentioned above. These
costs include our direct and research-related overhead expenses, which include salaries and other personnel-related expenses
(including stock-based compensation), occupancy-related costs, supplies, and depreciation of facilities and laboratory
equipment, as well as external costs, and are expensed as incurred. Costs to acquire technologies that are utilized in research
and development and that have no alternative future use are expensed when incurred.
Advertising
Advertising costs are expensed as incurred and included in selling, general and administrative expenses in the consolidated
statements of operations. Advertising costs were $0.3 million, $0.3 million and $0.5 million in the years ended December 31,
2021, 2020 and 2019, respectively.
Stock-Based Compensation
We use the Black-Scholes-Merton option pricing model to estimate the fair value of options granted under our equity
incentive plans. The Black-Scholes-Merton option pricing model requires the use of assumptions, including the expected term
of the award and the expected stock price volatility. The expected term is based on historical exercise behavior on similar
awards, giving consideration to the contractual terms, vesting schedules and expectations of future employee behavior. We use
historical volatility to estimate expected stock price volatility. The risk-free rate assumption is based on United States Treasury
instruments whose terms are consistent with the expected term of the stock options. The expected dividend assumption is based
on our history and expectation of dividend payouts.
Restricted Stock Units (“RSUs"), Restricted Stock Awards (“RSAs”) and performance-contingent restricted stock units
(“PSUs”) are measured based on the fair market values of the underlying stock on the dates of grant. Performance based options
(“PBOs”) are measured using Black-Scholes-Merton option pricing model. The vesting of PBOs and PSUs awarded is
conditioned upon the attainment of one or more performance objectives over a specified period and upon continued
employment through the applicable vesting date. At the end of the performance period, shares of stock subject to the PBOs and
PSUs vest based upon both the level of achievement of performance objectives within the performance period and continued
employment through the applicable vesting date.
Stock-based compensation expense is calculated based on awards ultimately expected to vest and is reduced for estimated
forfeitures at the time of grant and revised, if necessary, in subsequent periods if actual forfeitures differ from those estimates.
The estimated annual forfeiture rates for stock options, RSUs, PSUs, PBOs, and RSAs are based on historical forfeiture
experience.
The estimated fair value of stock options, RSUs and RSAs are expensed on a straight-line basis over the vesting term of the
grant and the estimated fair value of PSUs and PBOs are expensed using an accelerated method over the term of the award once
management has determined that it is probable that the performance objective will be achieved. Compensation expense is
recorded over the requisite service period based on management's best estimate as to whether it is probable that the shares
awarded are expected to vest. Management assesses the probability of the performance milestones being met on a continuous
basis.
Cash and Cash Equivalents
We consider all highly liquid investments with maturity dates of three months or less at the date of purchase to be cash
equivalents. Cash and cash equivalents consist of cash on deposit with banks and money market funds. The majority of cash
and cash equivalents is maintained with major financial institutions in the United States. Deposits with these financial
institutions may exceed the amount of insurance provided on such deposits.
Restricted Cash
In 2016, we began the process of liquidating our Indian subsidiary. The local legal requirements for liquidation required us
to maintain our subsidiary's cash balance in an account managed by a legal trustee to satisfy our financial obligations. This
balance is recorded as current restricted cash on the consolidated balance sheets of $0.6 million as of December 31, 2021 and
2020.
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Pursuant to the terms of a lease agreement for our Redwood City, CA facilities, we obtained a letter of credit collateralized
by cash deposit balances of $1.1 million as of December 31, 2021 and 2020. Pursuant to the terms of our new lease agreement
for our San Carlos, CA facility, we also obtained a letter of credit collateralized by cash deposit balances of $0.5 million as
of December 31, 2021. These cash deposits balances are recorded as non-current restricted cash on the consolidated balance
sheets. For additional information, see Note 13, “Commitments and Contingencies”.
Fair Value Measurements
Fair value is defined as the price that would be received to sell an asset or paid to transfer a liability in an orderly
transaction between market participants at the measurement date. In determining fair value, we utilize valuation techniques that
maximize the use of observable inputs and minimize the use of unobservable inputs to the extent possible and we consider
counterparty credit risk in our assessment of fair value. Carrying amounts of financial instruments, including cash equivalents,
accounts receivable, accounts payable, and accrued liabilities, approximate their fair values as of the balance sheet dates
because of their short maturities.
The fair value hierarchy distinguishes between (1) market participant assumptions developed based on market data
obtained from independent sources (observable inputs) and (2) an entity’s own assumptions about market participant
assumptions developed based on the best information available in the circumstances (unobservable inputs). The fair value
hierarchy consists of three broad levels, giving the highest priority to unadjusted quoted prices in active markets for identical
assets or liabilities (Level 1) and the lowest priority to unobservable inputs (Level 3). The three levels of the fair value
hierarchy are described below:
• Level 1: Inputs that are unadjusted, quoted prices in active markets for identical assets or liabilities at the
measurement date.
• Level 2: Inputs that are either directly or indirectly observable for the asset or liability through correlation
with market data at the measurement date and for the duration of the instrument’s anticipated life.
• Level 3: Unobservable inputs that are supported by little or no market activity and that are significant to the
fair value of the assets or liabilities and which reflect management’s best estimate of what market participants would
use in pricing the asset or liability at the measurement date.
Concentrations of Credit Risk
Financial instruments that potentially subject us to significant concentrations of credit risk consist primarily of cash and
cash equivalents, accounts receivable and unbilled receivables, contract assets, non-marketable securities, and restricted cash.
Cash that is not required for immediate operating needs is invested principally in money market funds. Cash and cash
equivalents are invested through banks and other financial institutions in the United States, India, and the Netherlands. Such
deposits in those countries may be in excess of insured limits. The Company has not experienced material losses on its deposits
of cash and cash equivalents.
We perform ongoing credit evaluations of our customer's financial condition whenever deemed necessary. We maintain an
allowance for doubtful accounts based on the expected collectability of all financial assets, which takes into consideration an
analysis of historical bad debts, specific customer creditworthiness and current economic trends. As of December 31, 2021, we
had one customer that accounted for 62% of our accounts receivable balance. As of December 31, 2020, three customers
accounted for 70% of our accounts receivable balance. We believe the accounts receivable balances from our largest customers
do not represent a significant credit risk, based on cash flow forecasts, balance sheet analysis, and past collection experience.
Financial Assets and Allowances
We currently sell enzymes primarily to pharmaceutical and fine chemicals companies throughout the world by the
extension of trade credit terms based on an assessment of each customer's financial condition. Trade credit terms are generally
offered without collateral and may include an insignificant discount for prompt payment for specific customers. To manage our
credit exposure, we perform ongoing evaluations of our customers' financial conditions. In addition, accounts receivable
include amounts owed to us under our collaborative research and development agreements.
We recognize accounts receivable at invoiced amounts and we maintain a valuation allowance for credit losses using an
impairment model (known as the “current expected credit loss model” or “CECL”) based on estimates and forecasts of future
conditions requiring recognition of a lifetime of expected credit losses at inception on our financing receivables measured at
amortized costs which consisted of accounts receivable, contract assets, and unbilled receivables. We have determined that our
financing receivables share similar risk characteristics including: (i) customer origination in the pharmaceutical and fine
chemicals industry, (ii) similar historical credit loss pattern of customers (iii) no meaningful trade receivable differences in
terms, (iv) similar historical credit loss experience and (v) our belief that the composition of certain assets are comparable to
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our historical portfolio used to develop loss history. As a result, we measured the allowance for credit loss (“ACL”) on a
collective basis. Our ACL methodology considers how long the asset has been past due, the financial condition of the
customers, which includes ongoing quarterly evaluations and assessments of changes in customer credit ratings, and other
market data that we believe are relevant to the collectability of the assets. Nearly all financing receivables are due from
customers that are highly rated by major rating agencies and have a long history of no credit loss. We derive our ACL by
establishing an impairment rate attributable to assets not yet identified as impaired.
We derive our ACL by initially relying on our historical financing receivable loss rate which contemplates the full
contractual life of the assets sharing similar risk characteristics, adjusted to reflect (i) the extent to which we have determined
current conditions differ from the conditions that existed for the period over which historical loss information was evaluated
and (ii) by taking into consideration the changes in certain macroeconomic historical and forecasted information. We apply the
ACL to past due financing receivables and record charges to the ACL as a provision to credit loss expense in the Statement of
Operations. Financing receivables we identify as uncollectible are also charged against the ACL. We adjust the impairment rate
to reflect the extent to which we have determined current conditions differ from the conditions that existed for the period over
which historical loss information was evaluated. Adjustments to historical loss information may be qualitative or quantitative in
nature and reflect changes related to relevant data.
Unbilled Receivable
The timing of revenue recognition may differ from the timing of invoicing to our customers. When we satisfy (or partially
satisfy) a performance obligation, prior to being able to invoice the customer, we recognize an unbilled receivable when the
right to consideration is unconditional.
Inventories
Inventories are stated at the lower of cost or net realizable value. Cost is determined using a weighted-average approach,
assuming full absorption of direct and indirect manufacturing costs, or based on cost of purchasing from our vendors. If
inventory costs exceed expected net realizable value due to obsolescence or lack of demand, valuation adjustments are recorded
for the difference between the cost and the expected net realizable value.
Concentrations of Supply Risk
We rely on a limited number of suppliers for our products. We believe that other vendors would be able to provide similar
products; however, the qualification of such vendors may require substantial start-up time. In order to mitigate any adverse
impacts from a disruption of supply, we attempt to maintain an adequate supply of critical single-sourced materials. For certain
materials, our vendors maintain a supply for us. We outsource the large scale manufacturing of our products to contract
manufacturers with facilities in Austria and Italy.
Property and Equipment
Property, equipment and leasehold improvements are stated at cost less accumulated depreciation and amortization
calculated using the straight-line method over their estimated useful lives as follows:
Asset classification
Laboratory equipment
Computer equipment and software
Office equipment and furniture
Leasehold improvements
Estimated useful life
5 years
3 to 5 years
5 years
Lesser of useful life or lease term
Property and equipment classified as construction in process includes equipment that has been received but not yet placed
in service. Normal repairs and maintenance costs are expensed as incurred.
Impairment of Long-Lived Assets
We have not identified property and equipment by segment since these assets are shared or commingled. We evaluate the
carrying values of long-lived assets, which include property and equipment and right-of-use assets, whenever events, changes in
business circumstances or our planned use of long-lived assets indicate that their carrying amounts may not be fully recoverable
or that their useful lives are no longer appropriate. If these facts and circumstances exist, we assess for recovery by comparing
the carrying values of long-lived assets with their future net undiscounted cash flows. If the comparison indicates that
impairment exists, long-lived assets are written down to their respective fair values based on discounted cash flows. Significant
94
management judgment is required in the forecast of future operating results that are used in the preparation of unexpected
undiscounted cash flows.
As of December 31, 2021 and 2020, there were no events or changes in circumstances which indicated that the carrying
amount of our asset group might not be recoverable. No impairment charges for long-lived assets were recorded during the
years ended December 31, 2021, 2020 and 2019.
Investment in Non-Marketable Securities
Investment in Non-Marketable Equity Securities
We measure investments in non-marketable equity securities without a readily determinable fair value using a measurement
alternative that measures these securities at the cost method minus impairment, if any, plus or minus changes resulting from
observable price changes on a non-recurring basis. Gains and losses on these securities are recognized in other income
(expense), net.
Investment in Non-Marketable Debt Securities
We measure available-for-sale investments in non-marketable debt at fair value. Unrealized gains and losses on these
securities are recognized in other comprehensive income until realized. Non-marketable debt securities are classified as
available-for-sale securities.
We classify non-marketable debt securities as Level 3 in the fair value hierarchy because we estimate the fair value based
on a qualitative analysis using the most recent observable transaction price and other significant unobservable inputs including
volatility, rights, and obligations of the securities we hold. Significant changes to the unobservable inputs may result in a
significantly higher or lower fair value estimate. We may value these securities based on significant recent arms-length
transactions with sophisticated non-strategic unrelated new investors.
We evaluate both equity and debt securities for impairment when circumstances indicate that we may not be able to recover
the carrying value. We may impair these securities and establish an allowance for a credit loss when we determine that there has
been an “other-than-temporary” decline in estimated fair value of the debt or equity security compared to its carrying value. We
calculate the estimated fair value of these securities using information from the investee, which may include:
•
•
•
•
•
•
Audited and unaudited financial statements;
Projected technological developments of the company;
Projected ability of the company to service its debt obligations;
If a deemed liquidation event were to occur;
Current fundraising transactions;
Current ability of the company to raise additional financing if needed;
•
company;
Changes in the economic environment which may have a material impact on the operating results of the
•
•
•
Contractual rights, obligations or restrictions associated with the investment; and
Other factors deemed relevant by our management to assess valuation.
The valuation may be reduced if the company's potential has deteriorated significantly. If the factors that led
to a reduction in valuation are overcome, the valuation may be readjusted.
Goodwill
Goodwill represents the excess of the consideration transferred over the fair value of net assets of businesses acquired and
is assigned to reporting units. We test goodwill for impairment considering amongst other things, whether there have been
sustained declines in our share price. If we conclude it is more likely than not that the fair value of a reporting unit is less than
its carrying amount, a quantitative fair value test is performed. We manage our business as two reporting units and we test
goodwill for impairment at the reporting unit level. We allocated goodwill to the two reporting units using a relative fair value
allocation methodology that primarily relied on our estimates of revenue and future earnings for each reporting unit. Using the
relative fair value allocation methodology, we have determined that approximately $2.4 million, or 76%, of the goodwill is
allocated to the Performance Enzymes segment and $0.8 million, or 24%, is assigned to the Novel Biotherapeutics segment.
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We test goodwill for impairment annually on a reporting unit basis, on the last day of the fourth fiscal quarter, and between
annual tests if events and circumstances indicate it is more likely than not that the fair value of a reporting unit is less than its
carrying amount. The annual impairment test is completed using either: a qualitative “Step 0” assessment based on reviewing
relevant events and circumstances; or a quantitative “Step 1” assessment, which determines the fair value of the reporting unit.
To the extent the carrying amount of a reporting unit is less than its estimated fair value, an impairment charge is recorded.
Using the relative fair value allocation methodology for assets and liabilities used in both of our reporting units, we compare the
allocated carrying amount of each reporting unit’s net assets and the assigned goodwill to its fair value. If the fair value of the
reporting unit exceeds its carrying amount, goodwill of the reporting unit is considered not impaired. Any excess of the
reporting unit’s carrying amount of goodwill over its fair value is recognized as an impairment. During 2021, 2020 and 2019,
we did not record impairment charges related to goodwill.
Lease Accounting
We determine if an arrangement is a lease at inception. Where an arrangement is a lease, we determine if it is an operating
lease or a finance lease. At lease commencement, we record a lease liability and ROU asset. Lease liabilities represent the
present value of our future lease payments over the expected lease term which includes options to extend or terminate the lease
when it is reasonably certain those options will be exercised. The present value of our lease liability is determined using our
incremental collateralized borrowing rate at lease inception. ROU assets represent our right to control the use of the leased asset
during the lease and are recognized in an amount equal to the lease liability for leases with an initial term greater than 12
months. Over the lease term, we use the effective interest rate method to account for the lease liability as lease payments are
made and the ROU asset is amortized to the consolidated statement of operations in a manner that results in straight-line
expense recognition. We do not apply lease recognition requirements for short-term leases. Instead, we recognize payments
related to these arrangements in the consolidated statement of operations as lease costs on a straight-line basis over the lease
term.
Income Taxes
We use the liability method of accounting for income taxes, whereby deferred tax asset or liability account balances are
calculated at the balance sheet date using current tax laws and rates in effect for the year in which the differences are expected
to affect taxable income. Valuation allowances are provided when necessary to reduce deferred tax assets to the amount that
will more likely than not be realized.
We make certain estimates and judgments in determining income tax expense for financial statement purposes. These
estimates and judgments occur in the calculation of tax credits, benefits and deductions and in the calculation of certain tax
assets and liabilities, which arise from differences in the timing of recognition of revenues and expenses for tax and financial
statement purposes. Significant changes to these estimates may result in an increase or decrease to our tax provision in a
subsequent period.
In assessing the realizability of deferred tax assets, we consider whether it is more likely than not that some portion or all
of the deferred tax assets will be realized on a jurisdiction by jurisdiction basis. The ultimate realization of deferred tax assets is
dependent upon the generation of taxable income in the future. We have recorded a valuation allowance against these deferred
tax assets in jurisdictions where ultimate realization of deferred tax assets is more likely than not to occur. As of December 31,
2021, we maintain a full valuation allowance in all jurisdictions against the net deferred tax assets as we believe that it is more
likely than not that the majority of deferred tax assets will not be realized.
We make estimates and judgments about our future taxable income that are based on assumptions that are consistent with
our plans and estimates. Should the actual amounts differ from our estimates, the amount of our valuation allowance may be
materially impacted. Any adjustment to the deferred tax asset valuation allowance would be recorded in the statements of
operations for the periods in which the adjustment is determined to be required.
We account for uncertainty in income taxes as required by the provisions of ASU 2009-06, Income Taxes (Topic 740)
Implementation Guidance on Accounting for Uncertainty in Income Taxes and Disclosure Amendments for Nonpublic Entities,
which clarifies the accounting for uncertainty in income taxes recognized in an enterprise’s financial statements. The first step
is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely
than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The
second step is to estimate and measure the tax benefit as the largest amount that is more than 50% likely of being realized upon
ultimate settlement. It is inherently difficult and subjective to estimate such amounts, as this requires us to determine the
probability of various possible outcomes. We consider many factors when evaluating and estimating our tax positions and tax
benefits, which may require periodic adjustments and may not accurately anticipate actual outcomes.
The Tax Reform Act of 1986 and similar state provisions limit the use of net operating loss (“NOL”) carryforwards in
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certain situations where equity transactions result in a change of ownership as defined by Internal Revenue Code
Section 382. In the event we should experience such a change of ownership, utilization of our federal and state NOL
carryforwards could be limited.
Accounting Pronouncements
Recently adopted accounting pronouncements
In December 2019, the FASB issued ASU 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income
Taxes which is intended to simplify various aspects related to accounting for income taxes. The standard is effective for fiscal
years, and interim periods within those years, beginning after December 15, 2020, with early adoption permitted. The standard
was adopted beginning January 1, 2021 on a retrospective basis. The adoption of ASU 2019-12 did not have an impact on our
consolidated financial statements and related disclosures.
In October 2020, the FASB issued ASU No. 2020-10, Codification Improvements. ASU 2020-10 provides amendments to a
wide variety of topics in the FASB’s Accounting Standards Codification, which applies to all reporting entities within the scope
of the affected accounting guidance. We adopted the standard on January 1, 2021 and it had no impact on our consolidated
financial statements and related disclosures.
Recently issued accounting pronouncements not yet adopted
From time to time, new accounting pronouncements are issued by the FASB or other standards setting bodies that are
adopted by us as of the specified effective date. Unless otherwise discussed, we believe that the impact of recently issued
standards that are not yet effective will not have a material impact on our consolidated financial statements upon adoption.
In May 2021, FASB issued ASU No. 2021-04, Earnings Per Share (Topic 260), Debt—Modifications and Extinguishments
(Subtopic 470-50), Compensation—Stock Compensation (Topic 718), and Derivatives and Hedging—Contracts in Entity’s Own
Equity (Subtopic 815-40), Issuer’s Accounting for Certain Modifications or Exchanges of Freestanding Equity-Classified
Written Call Options, a consensus of the Emerging Issues Task Force. The standard establishes a principles-based framework in
accounting for modifications of freestanding equity-classified written call options on the basis of the economic substance of the
underlying transaction. The standard also requires incremental financial statement disclosures. The standard affects entities that
present earnings per share in accordance with the guidance in Topic 260, Earnings Per Share. The standard is effective for fiscal
years beginning after December 15, 2021, including interim periods within those fiscal years with early adoption is permitted
by applying the standard as of the beginning of the fiscal year that includes that interim period. The standard may be adopted
prospectively for modifications or exchanges occurring on or after the effective date. We have evaluated that the adoption of
ASU 2021-04 will not have an impact on our consolidated financial statements and related disclosures.
In August 2020, FASB issued ASU No 2020-06 Debt—Debt with Conversion and Other Options (Subtopic 470-20) and
Derivatives and Hedging— Contracts in Entity’s Own Equity (Subtopic 815-40) No. 2020-06 August 2020 Accounting for
Convertible Instruments and Contracts in an Entity’s Own Equity, to reduce the complexity and to simplify the accounting for
convertible debt instruments and convertible preferred stock, and the derivatives scope exception for contracts in an entity's
own equity. In addition, the guidance on calculating diluted earnings per share has been simplified and made more internally
consistent. The standard is effective the for fiscal years beginning after December 15, 2021, and interim periods within those
fiscal years, with early adoption permitted for fiscal periods beginning after December 15, 2020. The standard may be adopted
on a modified retrospective or fully retrospective method of transition and on adoption, entities may irrevocably elect the fair
value option in accordance with Subtopic 825-10, Financial Instruments—Overall, for any financial instrument that is a
convertible security. We have evaluated that the adoption of ASU 2020-06 will not have an impact on our consolidated financial
statements and related disclosures.
In March 2020, the FASB issued ASU 2020-04, Reference Rate Reform (Topic 848): Facilitation of the Effects of
Reference Rate Reform on Financial Reporting. The standard provides optional expedients and exceptions for applying GAAP
to contracts, hedging relationships, and other transactions in which the reference LIBOR or another reference rate are expected
to be discontinued as a result of the Reference Rate Reform. The standard is effective for all entities. The standard may be
adopted as of any date from the beginning of an interim period that includes or is subsequent to March 12, 2020 through
December 31, 2022, on a prospective basis. We will evaluate transactions or contract modifications occurring as a result of
reference rate reform and determine whether to elect the optional expedients for contract modification; however, we believe that
the adoption of ASU 2020-04 will have no significant impact on our consolidated financial statements and related disclosures.
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Note 3. Revenue Recognition
Disaggregation of Revenue
The following table provides information about disaggregated revenue from contracts with customers into the nature of the
products and services, and geographic regions, and includes a reconciliation of the disaggregated revenue for reportable
segments. The geographic regions that are tracked are the Americas (United States, Canada, and Latin America), EMEA
(Europe, Middle East, and Africa), and APAC (Australia, New Zealand, Southeast Asia, and China).
Segment information for each of the fiscal years are as follows (in thousands):
Major products and service:
Product revenue
Research and development revenue
Total revenues
Primary geographical markets:
Americas
EMEA
APAC
Total revenues
Major products and service:
Product revenue
Research and development revenue
Total revenues
Primary geographical markets:
Americas
EMEA
APAC
Total revenues
Major products and service:
Product revenue
Research and development revenue
Total revenues
Primary geographical markets:
Americas
EMEA
APAC
Total revenues
Year Ended December 31, 2021
Performance Enzymes Novel Biotherapeutics
Total
$
$
$
$
70,657 $
19,858
90,515 $
16,114 $
13,315
61,086
90,515 $
— $
14,239
14,239 $
7,367 $
6,872
—
14,239 $
70,657
34,097
104,754
23,481
20,187
61,086
104,754
Year Ended December 31, 2020
Performance Enzymes Novel Biotherapeutics
Total
$
$
$
$
30,220 $
17,886
48,106 $
11,111 $
11,548
25,447
48,106 $
— $
20,950
20,950 $
13,241 $
7,709
—
20,950 $
30,220
38,836
69,056
24,352
19,257
25,447
69,056
Year Ended December 31, 2019
Performance Enzymes Novel Biotherapeutics
Total
29,465 $
28,691
58,156 $
13,039 $
26,831
18,286
58,156 $
— $
10,302
10,302 $
— $
10,302
—
10,302 $
29,465
38,993
68,458
13,039
37,133
18,286
68,458
$
$
$
$
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Contract Balances
The following table presents balances of contract assets, unbilled receivables, contract costs, and contract liabilities (in
thousands):
Contract assets
Unbilled receivables
Contract costs
Contract liabilities: deferred revenue
December 31, 2021
December 31, 2020
$
$
$
$
4,557 $
8,558 $
56 $
6,335 $
4,526
10,942
90
4,791
We recognize accounts receivable when we have an unconditional right to recognize revenue and have issued an invoice to
the customer. Our payment terms are generally between 30 and 90 days. We recognize unbilled receivables when we have an
unconditional right to recognize revenue and have not issued an invoice to our customer. Unbilled receivables are transferred to
accounts receivable on issuance of an invoice. Unbilled receivables are classified separately on the consolidated balance sheets
as assets. We maintain a valuation allowance on accounts receivables and unbilled receivables.
Contract assets represent our right to recognize revenue for custom products with no alternate use and under binding non-
cancellable contracts and are largely related to our procurement of product. We recognize contract assets when we have a
conditional right to recognize revenue. The transfer of control of certain of products occurs in advance of the invoicing process,
which generates contract assets. In addition, we recognize a contract asset related to milestones not eligible for royalty
accounting when we assess it is probable of being achieved and there will be no significant reversal of cumulative revenues.
Contract assets are classified separately on the consolidated balance sheets as an asset and transferred to accounts receivables
when our rights to payment become unconditional.
Contract liabilities, or deferred revenue, represent our obligation to transfer a product or service to the customer, and for
which we have received consideration from the customer. We recognize a contract liability when we receive advance customer
payments under development agreements for research and development services, upfront license payments, and from upfront
customer payments received under product supply agreements. Contract liabilities are classified as a liability on the
consolidated balance sheet.
Contract costs relate to incremental costs of obtaining a contract with a customer. Contract costs are amortized along with
the associated revenue over the term of the contract.
During the years ended December 31, 2021, 2020 and 2019, we had no asset impairment charges related to contract assets.
We recognized the following revenues (in thousands):
Revenue recognized in the period for:
Amounts included in contract liabilities at the beginning of the period:
Performance obligations satisfied
Changes in the period:
Changes in the estimated transaction price allocated to performance
obligations satisfied in prior periods
Performance obligations satisfied from new activities in the period -
contract revenue
Total revenues
$
$
Year Ended December 31,
2021
2020
1,858 $
57
7,645
95,251
104,754 $
774
68,225
69,056
99
Performance Obligations
The following table includes estimated revenue expected to be recognized in the future related to performance obligations
that are unsatisfied or partially unsatisfied at the end of the reporting periods. The estimated revenue does not include contracts
with original durations of one year or less, amounts of variable consideration attributable to royalties, or contract renewals that
are unexercised as of December 31, 2021.
The balances in the table below are partially based on judgments involved in estimating future orders from customers
subject to the exercise of material rights pursuant to respective contracts (in thousands):
2022
2023
2024
Product revenue
Research and development revenue
Total revenues
$
$
89 $
2,497
2,586 $
87 $
557
644 $
2025 and
Thereafter
Total
120 $
—
120 $
2,985 $
—
2,985 $
3,281
3,054
6,335
Note 4. Net Loss per Share
Basic net loss per share is computed by dividing the net loss by the weighted-average number of shares of common stock
outstanding, less restricted stock awards (“RSAs”) subject to forfeiture. Diluted net loss per share is computed by dividing net
loss by the weighted-average number of shares of common stock shares outstanding, less RSAs subject to forfeiture, plus all
additional common shares that would have been outstanding, assuming dilutive potential common stock shares had been issued
for other dilutive securities. For all periods presented, diluted and basic net loss per share are identical since potential common
stock shares are excluded from the calculation, as their effect was anti-dilutive.
Anti-Dilutive Securities
In periods of net loss, the weighted average number of shares outstanding, prior to the application of the treasury stock
method, excludes potentially dilutive securities from the computation of diluted net loss per common share because including
such shares would have an anti-dilutive effect.
The following shares were not considered in the computation of diluted net loss per share because their effect was anti-
dilutive (in thousands):
Shares issuable under the Equity Incentive Plan
2021
Year Ended December 31,
2020
2019
5,215
5,348
4,763
Note 5. Collaborative Arrangements
GSK Platform Technology Transfer, Collaboration and License Agreement
In July 2014, we entered into a CodeEvolver® protein engineering platform technology transfer collaboration and license
agreement (the “GSK CodeEvolver® Agreement”) with GSK. Pursuant to the terms of the agreement, we granted GSK a non-
exclusive license to use the CodeEvolver® protein engineering platform technology to develop novel enzymes for use in the
manufacture of GSK's pharmaceutical and health care products. We completed the transfer of the CodeEvolver® protein
engineering platform technology to GSK in April 2016 and all revenues relating to the technology transfer have been
recognized as of April 2016. Depending upon GSK's successful application of the licensed technology, we have the potential to
receive additional contingent payments that range from $5.75 million to $38.5 million per project.
In 2019, we received a $2.0 million milestone payment relating to the advancement of an enzyme developed by GSK using
our CodeEvolver® protein engineering platform technology. In 2021, we received two additional milestone payments from GSK
under the agreement. We recognized research and development revenue of $4.3 million, nil, and $2.0 million in the years ended
December 31, 2021, 2020, and 2019, respectively.
100
Merck Platform Technology Transfer and License Agreement
In August 2015, we entered into a CodeEvolver® platform technology transfer collaboration and license agreement (the
“Merck CodeEvolver® Agreement”) with Merck, Sharp & Dohme (“Merck”) which allows Merck to use the CodeEvolver®
protein engineering technology platform in the field of human and animal healthcare. In 2016, we completed the final phase in
the transfer of CodeEvolver® technology to Merck under the Merck CodeEvolver® Agreement.
We recognized research and development revenues of $0.6 million, $3.1 million, and $4.0 million in the years ended
December 31, 2021, 2020 and 2019, respectively, for various research projects under our collaborative arrangement.
We have the potential to receive payments of up to a maximum of $15.0 million for each commercial active pharmaceutical
ingredient (“API”) that is manufactured by Merck using one or more novel enzymes developed by Merck using the
CodeEvolver® protein engineering technology platform. The API payments, which are currently not recognized in revenue, are
based on the quantity of API developed and manufactured by Merck and will be recognized as usage-based royalties.
In October 2018, we entered into an amendment to the Merck CodeEvolver® Agreement which amended certain licensing
provisions and one exhibit. In January 2019, we amended the Merck CodeEvolver® Agreement to install certain CodeEvolver®
protein engineering technology upgrades into Merck’s platform license installation and maintain those upgrades for a multi-year
term expiring in January 2022. The license installation was completed in 2019 and we recognized $0.9 million as license fee
revenue accordingly under the amendment. We recognized $0.1 million, $0.1 million and $0.9 million in research and
development revenues under the terms of the amendment in 2021, 2020 and 2019 respectively.
Merck Sitagliptin Catalyst Supply Agreement
In February 2012, we entered into a five-year Sitagliptin Catalyst Supply Agreement (“Sitagliptin Supply Agreement”)
with Merck whereby Merck may obtain commercial scale enzyme for use in the manufacture of Januvia®, its product based on
the active ingredient Sitagliptin. In December 2015, Merck exercised its options under the terms of the Sitagliptin Catalyst
Supply Agreement to extend the agreement for an additional five years through February 2022. In September 2021, the
Sitagliptin Catalyst Supply Agreement was amended to extend the agreement through December 2026.
Effective as of January 2016, we and Merck amended the Sitagliptin Supply Agreement to prospectively provide for
variable pricing based on the cumulative volume of sitagliptin enzyme purchased by Merck. We have determined that the
variable pricing, which provides a discount based on the cumulative volume of Sitagliptin catalyst purchased by Merck,
provides Merck material rights and we are recognizing product revenues over time using the alternative method. Under the
alternative approach, we estimate the total expected consideration and allocate it proportionately with the expected sales.
Pursuant to the terms of the Sitagliptin Supply Agreement, Merck may purchase supply of sitagliptin enzyme from us for a
fee based on contractually stated prices. We recognized $9.8 million, $13.4 million and $15.1 million in product revenue under
this contract for the years ended December 31, 2021, 2020 and 2019, respectively. Revenues recognized by us under the
Sitagliptin Supply Agreement comprised 9%, 19%, and 22% of our total revenues for the years ended December 31, 2021, 2020
and 2019, respectively.
As of December 31, 2021, we recorded revenue of $2.8 million from sitagliptin enzyme sales that were recognized over
time based on the progress of the manufacturing process. These products will be shipped within the six months period
following the end of the quarter.
Enzyme Supply Agreement
In November 2016, we entered into a supply agreement whereby our customer may purchase quantities of one of our
proprietary enzymes for use in its commercial manufacture of a product. Pursuant to the supply agreement, we received an
upfront payment in December 2016 which was recorded as deferred revenue. Such upfront payment will be recognized over the
period of the supply agreement as the customer purchases our proprietary enzyme. We additionally have determined that the
volume discounts under the supply agreement provide the customer material rights and we are recognizing revenues using the
alternative method. As of December 31, 2021 and 2020, we had deferred revenue balances from the supply agreement of $2.6
million and $2.0 million.
Research and Development Agreement
In March 2017, we entered into a multi-year research and development services agreement with Tate & Lyle Ingredients
Americas LLC (“Tate & Lyle”) to develop enzymes for use in the manufacture of Tate & Lyle’s zero-calorie TASTEVA® M
Stevia sweetener. Under the agreement, we received an upfront payment which was recognized ratably over the maximum term
of the service period of 21 months.
101
Commercial Agreement
In April 2019, we entered into a multi-year commercial agreement with Tate & Lyle under which Tate & Lyle has received
an exclusive license to use a suite of Codexis novel performance enzymes in the manufacture of Tate & Lyle’s zero-calorie
stevia sweetener, TASTEVA® M, and other stevia products. Under the agreement, we will supply Tate & Lyle with its
requirements for these enzymes over a multiple year period and receive royalties on stevia products. In November 2020, we
amended the commercial agreement based on Tate & Lyle's intent to use a specific Codexis novel performance enzyme in its
production of TASTEVA® M Stevia Sweetener and became eligible to receive milestone payments of up to $1.1 million. In the
fourth quarter of 2020, we became eligible to receive a milestone payment of $0.4 million which we subsequently received in
February 2021.
Global Development, Option and License Agreement and Strategic Collaboration Agreement
In October 2017, we entered into the Nestlé License Agreement with Nestlé Health Science and, solely for the purpose of
the integration and the dispute resolution clauses of the Nestlé License Agreement, Nestlé Health Science S.A., to advance
CDX-6114, our enzyme biotherapeutic product candidate for the potential treatment of PKU.
We received an upfront cash payment of $14.0 million in 2017 upon the execution of the Nestlé License Agreement, a $4.0
million milestone payment received in 2018 after dosing the first subjects in a first-in-human Phase 1a dose-escalation trial with
CDX-6114, and a $1.0 million milestone payment received in 2019 upon achievement of a milestone relating to formulation of
CDX-6114. The upfront payment and the variable consideration relating to the progress payment of $4.0 million and a
milestone payment of $1.0 million were recognized over time as the development work was performed. Revenue was
recognized using a single measure of progress that depicted our performance in transferring control of the services, which was
based on the ratio of level of effort incurred to date compared to the total estimated level of effort required to complete all
performance obligations under the agreement. We recognized nil, $13 thousand and $1.9 million in research and development
revenue in 2021, 2020 and 2019, respectively.
In January 2019, we received notice from the FDA that it had completed its review of our IND for CDX-6114 and
concluded that we may proceed with the proposed Phase 1b multiple ascending dose study in healthy volunteers in the United
States. In February 2019, Nestlé Health Science exercised its option to obtain an exclusive, worldwide, royalty-bearing, sub-
licensable license for the global development and commercialization of CDX-6114 for the management of PKU and made an
option payment of $3.0 million which we recognized as research and development revenue in 2019. Upon exercising its option,
Nestlé Health Science assumed all responsibilities for future clinical development and commercialization of CDX-6114. We are
also eligible to receive payments from Nestlé Health Science under the Nestlé License Agreement that include (i) development
and approval milestones of up to $85.0 million, (ii) sales-based milestones of up to $250.0 million in the aggregate, which
aggregate amount is achievable if net sales exceed $1.0 billion in a single year, and (iii) tiered royalties, at percentages ranging
from the mid-single digits to low double-digits of net sales of product.
In October 2017, we entered into the Nestlé SCA pursuant to which we and Nestlé Health Science are collaborating to
leverage the CodeEvolver® protein engineering technology platform to develop novel enzymes for Nestlé Health Science’s
established Consumer Care and Medical Nutrition business areas. The term of the Nestlé SCA has been extended through
December 2022.
In January 2020, we entered into a development agreement with Nestlé Health Science pursuant to which we and Nestlé
Health Science are collaborating to advance a lead candidate, CDX-7108, targeting a gastrointestinal disorder discovered
through our Nestlé SCA into preclinical and early clinical studies. During 2021, we, together with Nestlé Health Science,
continued to advance CDX-7108 towards initiation of a Phase 1 clinical trial with the first subject being dosed in November
2021.
Under the Nestlé SCA and the development agreement, we recognized $6.9 million, $7.9 million and $5.4 million in
research and development revenue for the years ended December 31, 2021, 2020 and 2019, respectively.
Strategic Collaboration Agreement
In April 2018, we entered into the Porton Agreement with Porton to license key elements of our biocatalyst technology for
use in Porton’s global custom intermediate and API development and manufacturing business. Under the Porton Agreement, we
are eligible to receive annual collaboration fees and research and development revenues. We received initial collaboration
payments of $0.5 million and $0.5 million within 30 days of the effective date and on the first anniversary of the effective date
of the Porton Agreement, respectively. We also received annual collaboration payments of $1.0 million each during the first
through third anniversaries of the effective date of the Porton Agreement and are eligible to receive $1.0 million on the fourth
anniversary of the effective date of the Porton Agreement. We completed the technical transfer in the fourth quarter of 2018 and
102
recognized the related revenue in 2018. We recognized revenue related to the functional license provided to Porton at a point in
time when control of the license was transferred to the customer. We recognized research and development revenue related to
the Porton Agreement of $1.1 million, $1.1 million and nil in the years ended December 31, 2021, 2020 and 2019, respectively.
Platform Technology Transfer and License Agreement
In May 2019, we entered into a Platform Technology Transfer and License Agreement (the “Novartis CodeEvolver®
Agreement”) with Novartis. The Agreement allows Novartis to use our proprietary CodeEvolver® protein engineering platform
technology in the field of human healthcare. In July 2021, we announced the completion of the technology transfer period
during which we transferred our CodeEvolver® protein engineering platform technology to Novartis (the “Technology Transfer
Period”). As a part of this technology transfer, the Company provided to Novartis our proprietary enzymes, proprietary protein
engineering protocols and methods, and proprietary software algorithms. In addition, our teams and Novartis scientists
participated in technology training sessions and collaborative research projects at our laboratories in Redwood City, California
and at a designated Novartis laboratory in Basel, Switzerland. Novartis has now installed the CodeEvolver® protein engineering
platform technology at its designated laboratory.
Pursuant to the agreement, we received an upfront payment of $5.0 million shortly after the effective date of the Novartis
CodeEvolver® Agreement. We completed the second technology milestone transfer under the agreement in 2020 and received a
milestone payment of $4.0 million. We have also received an aggregate of $5.0 million for the completion of the third
technology milestone in 2021 In consideration for the continued disclosure and license of improvements to the technology and
materials during a multi-year period that began on the conclusion of the Technology Transfer Period (“Improvements Term”),
Novartis will pay Codexis annual payments over four years which amount to an additional $8.0 million in aggregate. The
Company also has the potential to receive quantity-dependent, usage payments for each API that is manufactured by Novartis
using one or more enzymes that have been developed or are in development using the CodeEvolver® protein engineering
platform technology during the period that began on the conclusion of the Technology Transfer Period and ends on the
expiration date of the last to expire licensed patent. Revenue for the combined initial license and technology transfer
performance obligation was recognized using a single measure of progress that depicted our performance in transferring control
of the services. Revenue allocated to improvements made during the Improvements Term are being recognized during the
Improvement Term.
We recognized $1.6 million, $6.2 million and $11.3 million in research and development revenue in the year ended
December 31, 2021, 2020 and 2019, respectively.
License Agreement
In December 2019, we entered a license agreement with Roche Sequencing Solutions, Inc. (“Roche”) to provide Roche
with our EvoT4 DNA™ ligase high-performance molecular diagnostic enzyme. The royalty bearing license grants Roche
worldwide rights to include the EvoT4 DNA™ ligase in its nucleic acid sequencing products and workflows. Under the license
agreement, we received an initial collaboration fee payment of $0.8 million within 45 days of the effective date of the
agreement, and we received an additional $0.9 million milestone payment after the completion of technology transfer in
October 2020. The agreement also contemplates milestone payments to Codexis upon the achievement of various development
and commercialization events and royalty payments from commercial sales of the enzyme. We recognized research and
development fees of $0.9 million and $0.9 million for the years ended December 31, 2021 and 2020, respectively.
Strategic Collaboration and License Agreement
In March 2020, we entered into a Strategic Collaboration and License Agreement (the “Takeda Agreement”) with Shire
Human Genetic Therapies, Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Co. Ltd. (“Takeda”) under which we are
collaborating to research and develop protein sequences for use in gene therapy products for certain diseases (each, a “Field”)
in accordance with each applicable program plan (each, a “Program Plan”).
On execution of the Takeda Agreement in March 2020, we received an upfront nonrefundable cash payment of $8.5 million
and we initiated activities under three Program Plans for Fabry Disease, Pompe Disease, and an undisclosed blood factor
deficiency respectively (the “Initial Programs”). In May 2021, Takeda elected to exercise its option to initiate an additional
program for a certain undisclosed rare genetic disorder; as a result, we received the option exercise fee during the third quarter
of 2021. Pursuant to the Takeda Agreement, we are eligible to receive other payments that include (i) reimbursement of
research and development fees and preclinical development milestones for the three initial programs of $10.5 million, in
aggregate, and $8.3 million for the fourth program, (ii) clinical development and commercialization-based milestones, per
target gene, of up to $100.0 million and (iii) tiered royalty payments based on net sales of applicable products at percentages
ranging from the mid-single digits to low single-digits.
103
Revenue recognized relating to the functional licenses provided to Takeda was recognized at a point in time when the
control of the license transferred to the customer. We recognized research and development revenue related to the Takeda
Agreement of $7.4 million and $13.2 million in the years ended December 31, 2021 and 2020, respectively. As of
December 31, 2021 and 2020, we had deferred revenue balances of $2.2 million and $1.5 million, respectively.
Master Collaboration and Research Agreement and Stock Purchase Agreement
In June 2020, we entered into a Stock Purchase Agreement with MAI in which we purchased 1,587,050 shares of MAI's
Series A preferred stock for $1.0 million. In connection with the June 2020, transaction, John Nicols, our President and Chief
Executive Officer, joined MAI’s board of directors. For additional information, see Note 14, "Related Party Transactions".
Concurrent with our initial equity investment, we entered into a Master Collaboration and Research Agreement with MAI
(the “MAI Agreement”) in June 2020, pursuant to which we are performing services utilizing our CodeEvolver® protein
engineering platform technology to improve DNA polymerase enzymes in exchange for compensation in the form of additional
shares of MAI's preferred stock. Based on these services, the Company is eligible to earn additional shares of MAI's preferred
stock. MAI will combine its advanced chemistries with our enzymes to drive the process to commercialization. We are eligible
to earn such non-monetary payments over 14 months, and any such shares would be issued thirty days in arrears after each
calendar quarter-end. We are also eligible to receive amounts for bonuses, targets and milestones on achievement of timeline
and project goals specified in the statement of work ("SOW"). Payments for bonuses, targets and milestones on achievement of
timeline and project goals are to be issued thirty days after the Company provides notification of completion. Under the MAI
Agreement, we will have the right to use and sell the engineered enzymes to third parties for any purpose other than for the
synthesis of native DNA. Under the MAI Agreement, we would make a $0.5 million payment to MAI upon our achievement of
a milestone of $5.0 million in aggregate commercial sales to third parties of the engineered enzymes or any product
incorporating or derived from the engineered enzymes for any purpose other than the synthesis of native DNA. The MAI
Agreement contemplates that we and MAI will enter into a Commercialization and Enzyme Supply Agreement (the “CESA”)
within six months following the completion of certain timelines specified in the SOW. In addition, we and MAI have agreed to
certain terms to be contained within the CESA in the event that the CESA becomes executed in the future. Those include: (a)
that MAI would receive an exclusive license to use the DNA polymerase enzymes engineering by us under the MAI Agreement
in the synthesis of native DNA and a non-exclusive license to use these enzymes for research and development on the synthesis
of non-native DNA, and (b) we would become the exclusive manufacturer of these enzymes for MAI, its affiliates and
licensees.
We received 3,491,505 and 714,171 shares of MAI's Series A and B preferred stock and recognized $2.0 million and $0.9
million from these services in the years ended December 31, 2021 and 2020, respectively. Payment for the services rendered
was received in the form of additional MAI Series A and Series B preferred stock.
Pfizer purchase orders
In the first and second quarters of 2021, we began to receive purchase orders from Pfizer, Inc. (“Pfizer”) for large
quantities of our proprietary enzyme product, CDX-616, for use by Pfizer in the manufacture of a critical intermediate for its
proprietary active pharmaceutical ingredient, nirmatrelvir. Pfizer markets, sells and distributes nirmatrelvir, in combination with
the active pharmaceutical ingredient ritonavir, as its PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) product, which
received emergency use authorization by the U.S. Food and Drug Administration (“FDA”) in late 2021 for the treatment of
COVID-19 infections in humans.
We recognized product revenue of $34.5 million from the sale of quantities of CDX-616 enzyme products to Pfizer in
2021. Revenues recognized by us from the sale to Pfizer comprised 33% of our total revenues for the year ended December 31,
2021. As of December 31, 2021, we recorded revenue and contract assets of $1.7 million from the sale of this enzyme product
that were recognized over time based on the progress of the manufacturing process.
Note 6. Investments in Non-Marketable Securities
Non-Marketable Debt Securities
We classify non-marketable debt securities, which are accounted for as available-for-sale, within Level 3 in the fair value
hierarchy because we estimate the fair value based on a qualitative analysis using the most recent observable transaction price
and other significant unobservable inputs including volatility, rights, and obligations of the securities we hold.
We determine gains or losses on the sale or extinguishment of non-marketable debt securities using a specific identification
method. Unrealized gains and losses from bifurcated embedded derivatives, which represent share-settled redemption features,
are recorded as other expense, net, in the consolidated statements of operations. Unrealized gains and losses on non-marketable
104
debt securities are recorded as a component of other comprehensive loss until realized. Realized gains or losses are recorded as
a component of other income (expense), net.
In November 2020, we purchased convertible subordinated notes issued by Arzeda Corp., an early-stage computational
protein design company, for $1.0 million. The investment was classified as available-for-sale non-marketable interest-bearing
debt securities with a carrying value of $1.0 million as of December 31, 2020. In July 2021, we converted the non-marketable
debt security with a carrying value of $1.3 million into 207,070 shares of Series B-2 preferred stock of Arzeda Corp. During the
year ended December 31, 2021, we recognized $0.3 million in interest income from interest earned on our investment in this
debt security.
There were no investments in non-marketable debt securities at December 31, 2021. As of December 31, 2020, the
adjusted cost, carrying value and fair value of the non-marketable debt security is the following (in thousands):
December 31, 2020
Non-marketable debt securities due in 1 year or less
Non-Marketable Equity Securities
Adjusted Cost and
Carrying Value
Fair Value
$
1,000 $
1,000
Our non-marketable equity securities are investments in privately held companies without readily determinable market
value and primarily relate to our investments in MAI and Arzeda Corp. These investments are accounted for under the
measurement alternative and are measured at cost minus impairment, if any, plus or minus changes resulting from observable
price changes for identical or similar security of the same issuer. Non-marketable equity securities are measured at fair value on
a non-recurring basis and classified within Level 2 in the fair value hierarchy because we estimate the fair value of these using
the observable transaction price paid by third party investors for the same or similar security of the same issuers. We adjust the
carrying value of non-marketable equity securities which have been remeasured during the period and recognize resulting gains
or losses as a component of other income (expense), net in the consolidated statements of operations.
For the year ended December 31, 2021, we recognized a $1.0 million unrealized gain in other income (expense), net, in the
consolidated statements of operations, and included as adjustment to the carrying value of our investment in MAI based on an
analysis of observed transaction price from MAI's recent round of financing during the third and fourth quarter of 2021. There
was no remeasurement event for our investment in MAI and Arzeda Corp that occurred during the remainder of 2021. We
recognized no realized gains or losses during the years ended December 31, 2021 and 2020. The carrying value of our
investment in MAI was $12.7 million and $1.5 million at December 31, 2021 and December 31, 2020, respectively. The
carrying value of our investment in Arzeda Corp. was $1.3 million at December 31, 2021.
The following table presents the carrying value of non-marketable equity securities (in thousands):
Non-marketable equity securities
Note 7. Fair Value Measurements
December 31, 2021
December 31, 2020
$
14,002 $
1,450
The following tables present the financial instruments that were measured at fair value on a recurring basis at
December 31, 2021 and 2020 by level within the fair value hierarchy (in thousands):
Money market funds
December 31, 2021
Level 1
Level 2
Level 3
Total
$
86,095 $
— $
— $
86,095
105
Money market funds
Non-marketable debt security
Total
Level 1
127,567 $
—
127,567 $
$
$
December 31, 2020
Level 2
Level 3
— $
—
— $
— $
1,000
1,000 $
Total
127,567
1,000
128,567
During the years ended December 31, 2021 and 2020, we did not recognize any significant credit losses nor other-than-
temporary impairment losses on non-marketable securities.
Note 8. Balance Sheet Details
Cash Equivalents
Cash equivalents consisted of the following (in thousands):
December 31, 2021
December 31, 2020
Adjusted Cost
Estimated Fair
Value
Adjusted Cost
Estimated Fair
Value
Money market funds (1)
127,567
(1) Money market funds are classified in cash and cash equivalents on our consolidated balance sheets. Average contractual maturities (in days) is
127,567 $
86,095 $
86,095 $
$
not applicable.
As of December 31, 2021, the total cash and cash equivalents balance of $116.8 million consisted of money market funds
of $86.1 million and cash of $30.7 million held with major financial institutions. As of December 31, 2020, the total cash and
cash equivalents balance of $149.1 million consisted of money market funds of $127.6 million and cash of $21.5 million held
with major financial institutions.
Inventories
Inventories consisted of the following (in thousands):
Raw materials
Work in process
Finished goods
Inventories
December 31,
2021
2020
$
$
49 $
65
1,046
1,160 $
77
82
805
964
Inventories are recorded net of reserves of $1.4 million and $1.5 million as of December 31, 2021 and December 31, 2020
respectively.
106
Property and Equipment, net
Property and equipment, net consisted of the following (in thousands):
Laboratory equipment (1)
Leasehold improvements
Computer equipment and software
Office equipment and furniture
Construction in progress (2)
Property and equipment
Less: accumulated depreciation and amortization
Property and equipment, net
December 31,
2021
2020
$
$
33,101 $
16,117
3,481
1,297
3,231
57,227
(35,882)
21,345 $
25,468
10,785
3,192
1,246
2,357
43,048
(33,373)
9,675
(1) Fully depreciated property and equipment with a cost of $0.6 million and $1.8 million were retired during the years ended December 31, 2021
and 2020, respectively.
(2) Construction in progress includes equipment received but not yet placed into service pending installation.
Depreciation expense included in both research and development expenses and selling, general and administrative
expenses in the consolidated statements of operations was as follows (in thousands):
Depreciation expense
Goodwill
Year Ended December 31,
2020
2021
2019
$
3,113 $
1,950 $
1,570
Goodwill had a carrying value of $3.2 million as of December 31, 2021 and 2020.
Other Accrued Liabilities
Other accrued liabilities consisted of the following (in thousands):
Accrued purchases
Accrued professional and outside service fees
Other
Total
Note 9. Stock-based Compensation
Equity Incentive Plans
December 31,
2021
2020
$
$
6,755 $
5,147
676
12,578 $
7,170
2,589
513
10,272
In 2019, our board of directors (the "Board") and stockholders approved the 2019 Incentive Award Plan (the "2019 Plan").
The 2019 Plan superseded and replaced in its entirety our 2010 Equity Incentive Plan (the “2010 Plan”) which was effective in
March 2010, and no further awards will be granted under the 2010 Plan; however, the terms and conditions of the 2010 Plan
will continue to govern any outstanding awards thereunder.
The 2019 Plan provides for the grant of stock options, including incentive stock options and non-qualified stock options,
stock appreciation rights, restricted stock awards ("RSAs"), restricted stock units ("RSUs"), performance-contingent restricted
stock units ("PSUs"), performance-based options ("PBOs"), other stock or cash-based awards and dividend equivalents to
eligible employees and consultants of the Company or any parent or subsidiary, as well as members of the Board.
107
The number of shares of our common stock available for issuance under the 2019 Plan is equal to the sum of (i) 7,897,144
shares and (ii) any shares subject to awards granted under the 2010 Plan that were outstanding as of April 22, 2019 and
thereafter terminate, expire, lapse or are forfeited; provided that no more than 14,000,000 shares may be issued upon the
exercise of incentive stock options (“ISOs”). In June 2019, 8.1 million shares authorized for issuance under the 2019 Plan were
registered under the Securities Act of 1933, as amended (the “Securities Act”).
The 2010 Plan provided for the grant of incentive stock options, non-statutory stock options, RSUs, RSAs, PSUs, PBOs,
stock appreciation rights, and stock purchase rights to our employees, non-employee directors and consultants.
As of December 31, 2021, total shares remaining available for issuance under the 2019 Plan were 5.9 million shares.
Stock Options
The option exercise price for incentive stock options must be at least 100% of the fair value of our common stock on the
date of grant and the option exercise price for non-statutory stock options is at least 85% of the fair value of our common stock
on the date of grant, as determined by the Board. If, at the time of a grant, the optionee directly or by attribution owns stock
possessing more than 10% of the total combined voting power of all of our outstanding capital stock, the exercise price for
these options must be at least 110% of the fair value of the underlying common stock. Stock options granted to employees
generally have a maximum term of ten years and vest over four years from the date of grant, of which 25% vest at the end of
one year, and 75% vest monthly over the remaining three years. We may grant options with different vesting terms from time to
time. Unless an employee's termination of service is due to disability or death, upon termination of service, any unexercised
vested options will be forfeited at the end of three months or the expiration of the option, whichever is earlier.
Restricted Stock Units ("RSUs")
We also grant employees RSUs, which generally vest over either a three year period with 33% of the shares subject to the
RSUs vesting on each yearly anniversary of the vesting commencement date or over a four-year period with 25% of the shares
subject to the RSU vesting on each yearly anniversary of the vesting commencement date, in each case contingent upon such
employee’s continued service on such vesting date. RSUs are generally subject to forfeiture if employment terminates prior to
the release of vesting restrictions. We may grant RSUs with different vesting terms from time to time.
Performance-contingent Restricted Stock Units ("PSUs") and Performance Based Options ("PBOs")
The compensation committee of the Board approved, solely in respect of non-executive employees, delegated to our Chief
Executive Officer the authority to approve grants of PSUs. The compensation committee of the Board also approved grants of
PBOs and PSUs to our executives. The PSUs and PBOs vest based upon both the successful achievement of certain corporate
operating milestones in specified timelines and continued employment through the applicable vesting date. When the
performance goals are deemed to be probable of achievement for these types of awards, recognition of stock-based
compensation expense commences. Once the number of shares eligible to vest is determined, those shares vest in two equal
installments with 50% vesting upon achievement and the remaining 50% vesting on the first anniversary of achievement, in
each case, subject to the recipient’s continued service through the applicable vesting date. If the performance goals are achieved
at the threshold level, the number of shares eligible to vest in respect of the PSUs and PBOs would be equal to half the number
of PSUs granted and one-quarter the number of shares underlying the PBOs granted. If the performance goals are achieved at
the target level, the number of shares eligible to vest in respect of the PSUs and PBOs would be equal to the number of PSUs
granted and half of the shares underlying the PBOs granted. If the performance goals are achieved at the superior level, the
number of shares eligible to vest in respect of the PSUs would be equal to two times the number of PSUs granted and equal to
the number of PBOs granted. The number of shares issuable upon achievement of the performance goals at the levels between
the threshold and target levels for the PSUs and PBOs or between the target level and superior levels for the PSUs would be
determined using linear interpolation. Achievement below the threshold level would result in no shares being eligible to vest in
respect of the PSUs and PBOs.
In 2021, we awarded PSUs ("2021 PSUs") and PBOs ("2021 PBOs"), each of which commenced vesting based upon the
achievement of various weighted performance goals, including corporate revenue, performance enzyme segment gross margin,
major new biotherapeutics publicity events, strategic performance enzyme and biotherapeutics deliverables, safety, and
technology and strategic plan development. As of December 31, 2021, we estimated that the 2021 PSUs and 2021 PBOs
performance goals would be achieved at 146% and 73% of the target level, respectively, and recognized stock-based
compensation expenses accordingly.
In 2020, we awarded PSUs ("2020 PSUs") and PBOs ("2020 PBOs"), each of which commenced vesting based upon the
achievement of various weighted performance goals, including corporate revenue, performance enzyme segment gross margin,
major new biotherapeutics publicity events, strategic performance enzyme and biotherapeutics deliverables, and strategic plan
108
development. In the first quarter of 2021, we determined that the 2020 PSUs and 2020 PBOs performance goals had been
achieved at 88% and 44% of the target level, respectively, and recognized the stock-based compensation expenses accordingly.
Accordingly, 50% of the shares underlying the 2020 PSUs and PBOs vested in the first quarter of 2021 and 50% of the shares
underlying the 2020 PSUs and PBOs will vest in the first quarter of 2022, in each case, subject to the recipient’s continued
service on each vesting date.
In 2019, we awarded PSUs ("2019 PSUs") and PBOs ("2019 PBOs"), each of which commenced vesting based upon the
achievement of various weighted performance goals, including sustained revenue and performance enzyme growth, strategic
advancement of biotherapeutics, cash balance and strategic plan development. In the first quarter of 2020, we determined that
the 2019 PSUs and 2019 PBOs performance goals had been achieved at 84% and 42% of the target level, respectively, and
recognized the stock-based compensation expenses accordingly. Accordingly, 50% of the shares underlying the 2019 PSUs and
PBOs vested in the first quarter of 2020 and 50% of the shares underlying the 2019 PSUs and PBOs vested in the first quarter
of 2021, in each case subject to the recipient’s continued service on each vesting date.
Stock-Based Compensation Expense
Stock-based compensation expense is included in the consolidated statements of operations as follows (in thousands):
Research and development
Selling, general and administrative
Total
Year Ended December 31,
2020
2019
2021
$
$
2,353 $
9,240
11,593 $
1,620 $
6,108
7,728 $
1,562
5,381
6,943
The following table presents total stock-based compensation expense by security type included in the consolidated
statements of operations (in thousands):
Stock options
RSUs and RSAs
PSUs
PBOs
Total
Grant Award Activities:
Stock Option Awards
Year Ended December 31,
2020
2019
2021
$
$
2,764 $
2,768
2,333
3,728
11,593 $
2,381 $
2,231
1,160
1,956
7,728 $
2,149
1,805
1,087
1,902
6,943
We estimated the fair value of stock options using the Black-Scholes-Merton option-pricing model based on the date of
grant. The following summarizes the weighted-average assumptions used to estimate the fair value of employee and non-
employee stock options granted:
Expected life (years)
Volatility
Risk-free interest rate
Expected dividend yield
Year Ended December 31,
2020
2019
2021
5.6
52.5 %
0.8 %
0.0 %
5.3
50.4 %
1.0 %
0.0 %
5.6
55.3 %
2.4 %
0.0 %
109
The following summarizes the weighted-average assumptions used to estimate the fair value of 9,000 and 76,000 shares of
stock options granted to non-employees for services valued at $0.1 million and $0.4 million during the years ended
December 31, 2021 and 2020 respectively:
Expected life (years)
Volatility
Risk-free interest rate
Expected dividend yield
Year Ended December 31,
2020
2021
5.6
54.1 %
0.9 %
0.0 %
5.4
51.6 %
0.4 %
0.0 %
The weighted average grant date fair value per share of non-employee stock options granted respectively in 2021 and 2020
was $11.29 and $5.04. The Company did not grant shares of stock options to non-employees during the year ended December
31, 2019.
The following tables summarizes stock option activities:
Number
of
Shares
(In Thousands)
Weighted
Average
Exercise Price Per
Share
Outstanding at December 31, 2018
Granted
Exercised
Forfeited/Expired
Outstanding at December 31, 2019
Granted
Exercised
Forfeited/Expired
Outstanding at December 31, 2020
Granted
Exercised
Forfeited/Expired
Outstanding at December 31, 2021
$
$
$
$
$
$
$
4,112
406
(1,045)
(326)
3,147
496
(210)
(48)
$
3,385 $
286 $
(664) $
(72) $
2,935 $
4.81
20.68
4.50
11.01
6.31
13.30
6.30
16.71
7.19
26.85
6.96
17.99
8.90
Outstanding at December 31, 2021
Exercisable at December 31, 2021
Vested and expected to vest at December 31, 2021
Number
of
Shares
(In Thousands)
Weighted
Average
Exercise Price
Per Share
2,935 $
2,861 $
2,338 $
8.90
8.56
5.99
Weighted
Average
Remaining
Contractual
Term
(In Years)
5.0
4.9
4.2
Aggregate
Intrinsic
Value
(In Thousands)
$
$
$
65,963
65,186
59,103
The weighted average grant date fair value per share of employee stock options granted in 2021, 2020 and 2019 were
$12.80, $6.03 and $10.77, respectively. The total intrinsic value of options exercised in 2021, 2020 and 2019 were
$14.9 million, $1.8 million and $13.6 million, respectively.
As of December 31, 2021, there was $4.4 million of unrecognized stock-based compensation, net of expected forfeitures,
related to unvested stock options, which we expect to recognize over a weighted average period of 2.4 years.
110
Restricted Stock Awards ("RSAs")
The following table summarizes RSA activities:
Non-vested balance at December 31, 2018
Granted
Vested
Forfeited/Expired
Non-vested balance at December 31, 2019
Granted
Vested
Non-vested balance at December 31, 2020
Granted
Vested
Non-vested balance at December 31, 2021
Number
of
Shares
(In Thousands)
Weighted Average
Grant Date
Fair Value
Per Share
55 $
40 $
(56) $
(4) $
35 $
96 $
(35) $
96 $
46 $
(62) $
80 $
12.83
17.18
12.83
17.18
17.18
11.44
17.18
11.44
21.91
11.31
17.53
The total fair value, as of the vesting date, of RSAs vested in fiscal 2021, 2020 and 2019 were $1.3 million, $0.4 million
and $1.0 million respectively.
As of December 31, 2021, there was $0.7 million of unrecognized stock-based compensation cost related to non-vested
RSAs, which we expect to recognize over a weighted average period of 1.1 years.
Restricted Stock Units ("RSUs")
The following table summarizes RSU activities:
Non-vested balance at December 31, 2018
Granted
Vested
Forfeited/Expired
Non-vested balance at December 31, 2019
Granted
Vested
Forfeited/Expired
Non-vested balance at December 31, 2020
Granted
Vested
Forfeited/Expired
Non-vested balance at December 31, 2021
Number
of
Shares
(In Thousands)
Weighted Average
Grant Date
Fair Value
Per Share
348 $
72 $
(210) $
(9) $
201 $
156 $
(168) $
(13) $
176 $
163 $
(70) $
(37) $
232 $
5.66
19.19
5.03
13.60
10.76
14.22
10.05
15.16
14.17
26.59
13.57
21.89
21.83
The total fair value, as of the vesting date, of RSUs vested in fiscal 2021, 2020 and 2019 were $1.8 million, $2.1 million
and $4.1 million respectively.
As of December 31, 2021, there was $2.8 million of unrecognized stock-based compensation cost related to non-vested
RSUs, which we expect to recognize over a weighted average period of 1.6 years.
111
Performance-Contingent Restricted Stock Units ("PSUs")
The following table summarizes PSU activities:
Non-vested balance at December 31, 2018
Granted
Vested
Forfeited/Expired
Non-vested balance at December 31, 2019
Granted
Vested
Forfeited/Expired
Non-vested balance at December 31, 2020
Granted
Vested
Forfeited/Expired
Non-vested balance at December 31, 2021
Number
of
Shares
(In Thousands)
Weighted Average
Grant Date
Fair Value
Per Share
240 $
95 $
(200) $
(15) $
120 $
124 $
(107) $
(6) $
131 $
82 $
(66) $
(19) $
128 $
7.48
14.98
6.58
15.58
13.88
13.59
11.28
21.80
15.34
26.16
16.14
19.38
21.24
The total fair value, as of the vesting date, of PSUs vested in the years ended December 31, 2021, 2020, and 2019 were
$1.3 million, $1.3 million, and $3.8 million, respectively.
As of December 31, 2021, there was $1.0 million of unrecognized stock-based compensation cost related to non-vested
PSUs, which we expect to recognize over a weighted average period of 0.5 years.
Performance Based Options ("PBOs")
We estimated the fair value of PBOs using the Black-Scholes-Merton option-pricing model based on the date of grant. The
following summarize the ranges of weighted-average assumptions used to estimate the fair value of employee stock options
granted:
Expected life (years)
Volatility
Risk-free interest rate
Expected dividend yield
Year Ended December 31,
2020
2021
2019
5.5
51.9 %
0.7 %
0.0 %
5.3
49.9 %
1.3 %
0.0 %
5.6
55.8 %
2.5 %
0.0 %
112
The following tables summarizes PBO activities:
Number
of
Shares
(In Thousands)
Weighted Average
Grant Date Fair
Value Per Share
Outstanding at December 31, 2018
Granted
Exercised
Forfeited/Expired
Outstanding at December 31, 2019
Granted
Forfeited/Expired
Outstanding at December 31, 2020
Granted
Exercised
Forfeited/Expired
Outstanding at December 31, 2021
Exercisable at December 31, 2021
Vested and expected to vest at December 31, 2021
1,582 $
718 $
(422) $
(618) $
1,260 $
689 $
(389) $
1,560 $
433 $
(35) $
(118) $
1,840 $
3.47
11.44
3.17
10.34
4.75
6.37
6.42
5.05
12.23
9.02
12.23
4.11
Weighted
Average
Remaining
Contractual Term
(In Years)
6.0
6.6
Aggregate
Intrinsic
Value
(In Thousands)
30,809
34,263
$
$
Number
of
Shares
(In Thousands)
1,374 $
1,784 $
Weighted
Average
Exercise Price
Per Share
9.08
12.11
The total fair value of exercised PBOs for 2021, 2020 and 2019, was $0.3 million, nil and $1.3 million, respectively.
As of December 31, 2021, there was $1.3 million of unrecognized stock-based compensation cost related to non-vested
PBOs, which we expect to recognize over a weighted average period of 1.0 years.
Note 10. Capital Stock
Equity Distribution Agreement
We filed a Registration Statement on Form S-3 with the SEC, under which we may sell common stock, preferred stock,
debt securities, warrants, purchase contracts, and units from time to time in one or more offerings. The registration statement
became effective on May 7, 2021. In May 2021, we entered into an Equity Distribution Agreement ("EDA") with Piper Sandler
& Co ("PSC"), under which PSC, as our exclusive agent, at our discretion and at such times that we may determine from time
to time, may sell over a three-year period from the execution of the EDA up to a maximum of $50.0 million of shares of our
common stock. Under the terms of the EDA, PSC may sell the shares at market prices by any method that is deemed to be an“at
the market offering” as defined in Rule 415 under the Securities Act of 1933, as amended.
We are not required to sell any shares at any time during the term of the EDA. The EDA will terminate upon the earlier of:
(i) the issuance and sale of all shares through PSC on the terms and conditions of the EDA, or (ii) the termination of the EDA in
accordance with its terms. Either party may terminate the EDA at any time upon written notification to the other party in
accordance with the EDA, and upon such notification, the offering will terminate. Under no circumstances shall any shares be
sold pursuant to the EDA after the date which is three years after the registration statement is first declared effective by the
SEC. We agreed to pay PSC a commission of 3% of the gross sales price of any shares sold pursuant to the EDA. With the
exception of certain expenses, we will pay PSC up to 8% of the gross sales price of the shares sold pursuant to the EDA for a
combined amount of commission and reimbursement of PSC's expenses and fees.
During the year ended December 31, 2021, no shares of our common stock were issued pursuant to the EDA. As of
December 31, 2021, $50.0 million of shares remained available for sale under the EDA.
113
Public Offerings
In December 2020, we completed an underwritten public offering in which we issued and sold 4.9 million shares of our
common stock, par value $0.0001 per share, at a public offering price of $17.50 per share. We received gross proceeds of $86.3
million, net of underwriting discounts and commissions of $5.2 million and direct offering expenses of $0.3 million for net
proceeds of $80.8 million.
Private Placement
In June 2019, we entered into a Securities Purchase Agreement with an affiliate of Casdin Capital, LLC ("Casdin")
pursuant to which we issued and sold to Casdin 3,048,780 shares of our common stock at a purchase price of $16.40 per share.
After deducting issuance costs of $0.1 million from the Private Offering, our net proceeds were $49.9 million. The Private
Offering was exempt from registration pursuant to the exemption for transactions by an issuer not involving any public offering
under Section 4(a)(2) the Securities Act, and Regulation D under the Securities Act.
Note 11. 401(k) Plan
In January 2005, we implemented a 401(k) Plan covering certain employees. Currently, all of our United States based
employees over the age of 18 are eligible to participate in the 401(k) Plan. Under the 401(k) Plan, eligible employees may elect
to reduce their current compensation up to a certain annual limit and contribute these amounts to the 401(k) Plan. We may make
matching or other contributions to the 401(k) Plan on behalf of eligible employees. We recorded employer matching
contributions expense of $1.1 million, $0.8 million, and $0.7 million in the years ended December 31, 2021, 2020, and 2019,
respectively.
Note 12. Income Taxes
Our loss before provision for (benefit from) income taxes were as follows (in thousands):
United States
Foreign
Loss before provision for income taxes
Year Ended December 31,
2020
(23,452) $
(219)
(23,671) $
2021
(21,037) $
(53)
(21,090) $
$
$
2019
(11,751)
(167)
(11,918)
The tax provision for the years ended December 31, 2021, 2020 and 2019 consists primarily of taxes attributable to foreign
operations. The components of the provision for income taxes are as follows (in thousands):
Current provision:
State
Foreign
Total current provision
Deferred benefit:
Foreign
Total deferred benefit
Provision for income taxes
Year Ended December 31,
2020
2019
2021
$
$
$
$
— $
198
198 $
(9)
(9) $
189 $
5 $
342
347 $
(8)
(8) $
339 $
5
18
23
(6)
(6)
17
114
Reconciliation of the provision for income taxes calculated at the statutory rate to our provision for income taxes is as
follows (in thousands):
Tax benefit at federal statutory rate
State taxes
Research and development credits
Foreign operations taxed at different rates
Stock-based compensation
Other nondeductible items
Executive compensation
Change in valuation allowance
Provision for income taxes
Year Ended December 31,
2020
2019
2021
$
$
(4,429) $
(2,235)
(1,132)
80
(2,698)
711
257
9,635
189 $
(4,971) $
(708)
(811)
245
140
61
24
6,359
339 $
(2,503)
(1,120)
(693)
1
(3,599)
498
872
6,561
17
Deferred income taxes reflect the net tax effects of (a) temporary differences between the carrying amounts of assets and
liabilities for financial reporting purposes and the amounts used for income tax purposes, and (b) operating losses and tax credit
carryforwards.
Significant components of our deferred tax assets and liabilities are as follows (in thousands):
Deferred tax assets:
Net operating losses
Credits
Deferred revenues
Stock-based compensation
Reserves and accruals
Depreciation
Intangible assets
Capital losses
Unrealized gain/loss
Lease liability
Other assets
Total deferred tax assets:
Valuation allowance
Deferred tax liabilities:
Right-of-use assets
Other
Total deferred tax liabilities:
Net deferred tax liabilities
December 31,
2021
2020
$
$
78,525 $
11,895
1,490
3,946
2,928
514
1,356
26
418
11,206
122
112,426
(101,762)
(10,373)
(314)
(10,687)
(23) $
72,530
9,914
1,080
2,576
1,914
1,115
1,714
25
400
5,626
100
96,994
(92,126)
(4,848)
(52)
(4,900)
(32)
ASC 740 requires that the tax benefit of NOLs, temporary differences and credit carryforwards be recorded as an asset to
the extent that management assesses that realization is “more likely than not.” Realization of the future tax benefits is
dependent on our ability to generate sufficient taxable income within the carryforward period. Because of our history of
operating losses, management believes that recognition of the deferred tax assets arising from the above-mentioned future tax
115
benefits is currently not more likely than not to be realized and, accordingly, has provided a valuation allowance against our
deferred tax assets. Accordingly, the net deferred tax assets in all our jurisdictions have been fully reserved by a valuation
allowance. The net valuation allowance increased by $9.6 million during the year ended December 31, 2021, increased by
$6.4 million during the year ended December 31, 2020, and increased by $6.5 million during the year ended December 31,
2019. At such time as it is determined that it is more likely than not that the deferred tax assets are realizable, the valuation
allowance will be reduced.
The following table sets forth our federal, state and foreign NOL carryforwards and federal research and development tax
credits as of December 31, 2021 (in thousands):
Net operating losses, federal
Net operating losses, federal
Net operating losses, state
Tax credits, federal
Tax credits, state
Net operating losses, foreign
December 31, 2021
Amount
Expiration
Years
2022-2037
224,475
108,314 Do not expire
2028-2041
138,770
2023-2041
12,917
14,126 Do not expire
—
Various
$
$
$
$
$
$
Current U.S. federal and California tax laws include substantial restrictions on the utilization of NOLs and tax credit
carryforwards in the event of an ownership change of a corporation. Accordingly, the Company's ability to utilize NOLs and tax
credit carryforwards may be limited as a result of such ownership changes. We performed an analysis in 2020 and determined
that there was not a limitation that would result in the expiration of carryforwards before they are utilized.
Income tax expense or benefit from continuing operations is generally determined without regard to other categories of
earnings, such as discontinued operations and other comprehensive income. An exception is provided in ASC 740 when there is
aggregate income from categories other than continuing operations and a loss from continuing operations in the current year. In
this case, the tax benefit allocated to continuing operations is the amount by which the loss from continuing operations reduces
the tax expenses recorded with respect to the other categories of earnings, even when a valuation allowance has been
established against the deferred tax assets. In instances where a valuation allowance is established against current year losses,
income from other sources is considered when determining whether sufficient future taxable income exists to realize the
deferred tax assets.
In 2014, we determined that the undistributed earnings of our India subsidiary will be repatriated to the United States, and
accordingly, we have provided a deferred tax liability totaling $23 thousand and $32 thousand as of December 31, 2021 and
2020 respectively, for local taxes that would be incurred upon repatriation.
We apply the provisions of ASC 740 to account for uncertain income taxes. A reconciliation of the beginning and ending
amount of unrecognized tax benefits is as follows (in thousands):
Balance at beginning of year
Additions based on tax positions related to current year
Additions to tax position of prior years
Reductions to tax position of prior years
Balance at end of year
2021
December 31,
2020
2019
$
$
12,683 $
2,206
372
—
15,261 $
11,330 $
1,357
—
(4)
12,683 $
9,980
1,362
—
(12)
11,330
We recognize interest and penalties as a component of our income tax expense. Total interest and penalties recognized in
the consolidated statements of operations were $61 thousand, $39 thousand and $32 thousand in 2021, 2020 and 2019,
respectively. Total penalties and interest recognized in the balance sheet was $0.5 million, $0.4 million and $0.4 million as of
December 31, 2021, 2020 and 2019, respectively. The total unrecognized tax benefits that, if recognized currently, would
impact our company’s effective tax rate were $0.3 million as of December 31, 2021, 2020 and 2019. We do not expect any
116
material changes to our uncertain tax positions within the next 12 months. We are not subject to examination by United States
federal or state tax authorities for years prior to 2002 and foreign tax authorities for years prior to 2014.
Note 13. Commitments and Contingencies
Operating Leases
Our headquarters are located in Redwood City, California, where we occupy approximately 77,300 square feet of office
and laboratory space in multiple buildings within the same business park of Metropolitan Life Insurance Company ("MetLife").
Our lease agreement with MetLife ("RWC Lease") includes approximately 28,200 square feet of space located at 200 and 220
Penobscot Drive, Redwood City, California (the “200/220 Penobscot Space”) and approximately 37,900 square feet of space
located at 400 Penobscot Drive, Redwood City, California (the “400 Penobscot Space”) (the 200/220 Penobscot Space and the
400 Penobscot Space are collectively referred to as the “Penobscot Space”), and approximately 11,200 square feet of space
located at 501 Chesapeake Drive, Redwood City, California (the “501 Chesapeake Space”).
Until the end of January 2020, we also leased approximately 29,900 square feet of space located at 101 Saginaw Drive,
Redwood City, California (the “Saginaw Space”). During January 2020, we subleased approximately 26,500 square feet of the
Saginaw Space to Minerva Surgical, Inc. The lease and sublease for the Saginaw Space both expired at the end of January 2020.
During the period from February 1, 2020 through April 30, 2020, we subleased approximately 3,400 square feet at 101 Saginaw
Drive from Minerva Surgical, Inc. The sublease expired at the end of April 2020.
We entered into the initial lease with MetLife for our facilities in Redwood City in 2004 and the RWC Lease has been
amended multiple times since then to adjust the leased space and terms of the Lease. In February 2019, we entered into an
Eighth Amendment to the Lease (the “Eighth Amendment”) with MetLife with respect to the Penobscot Space and the 501
Chesapeake Space to extend the term of the Lease for additional periods. Pursuant to the Eighth Amendment, the term of the
lease of the Penobscot Space has been extended through May 2027. The lease term for the 501 Chesapeake Space has been
extended to May 2029. We have one (1) option to extend the term of the lease for the Penobscot Space for five (5) years, and
one (1) separate option to extend the term of the lease for the 501 Chesapeake Space for five (5) years.
Pursuant to the terms of the RWC Lease, we exercised our right to deliver a letter of credit in lieu of a security deposit. The
letter of credit is collateralized by deposit balances held by the bank in the amount of $1.1 million as of December 31, 2021 and
2020, and are recorded as non-current restricted cash on the consolidated balance sheets.
We entered into a short-term office lease in San Carlos, California during the second quarter of 2021 and this lease will
expire in April 2022. Our remaining future commitment pursuant to this lease is $40 thousand as of December 31, 2021.
In January 2021, we entered into a lease agreement with ARE-San Francisco No. 63, LLC (“ARE”) to lease a portion of a
facility comprising approximately 36,593 rentable square feet in San Carlos, California to serve as additional office and
research and development laboratory space (the “San Carlos Space”). The budget provided a net tenant improvement allowance
of $6.3 million and an additional allowance of up to $2.7 million. ARE will have an enforceable right to payment by us in the
form of equal monthly additional rent payments at a certain interest rate through the lease term for the additional allowance.
The terms include an initial annualized base rent of $2.5 million, subject to scheduled 3% annual rent increases, an annualized
additional allowance payment of $0.4 million, plus certain operating expenses. The lease has a 10-year term from the lease
commencement date with one option to extend the term for an additional period of 5 years. We have provided ARE with a $0.5
million security deposit in the form of a letter of credit. We have the right to sublease the facility, subject to landlord consent.
We commenced occupancy of the San Carlos Space in December 2021 and recognized the right of use asset and the
corresponding operating lease liability.
We are required to restore certain areas of the Redwood City and San Carlos facilities that we are renting to their original
form. We are expensing the asset retirement obligation over the terms of the respective leases. We review the estimated
obligation each reporting period and make adjustments if our estimates change. We recorded asset retirement obligations of
$0.4 million and $0.2 million as of December 31, 2021 and 2020, respectively, which are included in other liabilities on the
consolidated balance sheets. Accretion expense related to our asset retirement obligations was nominal in 2021 and 2020.
Lease and other information
117
Lease costs, amounts included in measurement of lease obligations and other information related to non-cancellable
operating leases and finance leases for the years ended December 31, 2021, 2020 and 2019 were as follows (in thousands):
Amortization of right-of-use assets
Interest on lease obligations
Finance lease costs
Operating lease cost
Short-term lease costs (1)
Sublease income
Total lease cost (2)
2021
Year Ended December 31,
2020
2019
$
$
106 $
—
106
4,396
70
—
4,572 $
152 $
1
153
3,879
47
(55)
4,024 $
(1) Short-term lease costs on leases with terms of over one month and less than one year.
(2) The Company had no variable lease costs.
Amounts included in measurement of lease obligations:
2021
Year Ended December 31,
2020
2019
Cash paid:
Operating cash flows from operating leases
Operating cash flow from finance leases
Financing cash flows from finance leases
Non-cash activity:
Operating Lease - Right-of-use assets obtained in exchange
for lease liabilities
Finance Lease - Right-of-use assets obtained in
exchange for lease liabilities
$
$
$
$
$
4,197 $
— $
— $
25,445 $
— $
2,816
1
60
—
—
$
$
$
$
$
217
10
227
4,556
—
(957)
3,826
3,279
10
242
26,617
493
Other information:
Weighted-average remaining lease term (in years)
Weighted-average discount rate
Operating Lease
Finance Lease
7.9 years
5.6 %
—
—
As of December 31, 2021, our maturity analysis of annual undiscounted cash flows of the non-cancellable operating leases
are as follows (in thousands):
Years ending December 31,
2022
2023
2024
2025
2026
Thereafter
Total minimum lease payments
Less: imputed interest
Lease obligations
Other Commitments
Operating Leases
6,500
7,571
7,785
8,007
8,235
20,718
58,816
11,162
47,654
$
$
We enter into supply and service arrangements in the normal course of business. Supply arrangements are primarily for
fixed-price manufacture and supply. Service agreements are primarily for the development of manufacturing processes and
certain studies. Commitments under service agreements are subject to cancellation at our discretion which may require payment
of certain cancellation fees. The timing of completion of service arrangements is subject to variability in estimates of the time
required to complete the work.
118
The following table provides quantitative data regarding our other commitments. Future minimum payments reflect
amounts that we expect to pay including potential obligations under services agreements subject to risk of cancellation by us (in
thousands):
Other Commitment Agreement Type
Manufacture and supply agreement with expected future payment date of
December 2022
Development and manufacturing services agreements
Facility maintenance agreement
Total other commitments
Credit Facility
Agreement Date
April 2016
September 2019
September 2021
Future
Minimum
Payment
$
$
101
2,469
1,475
4,045
In June 30, 2017, we entered into a credit facility (the "Credit Facility") with Western Alliance Bank consisting of term
loans (“Term Debt”) up to $10.0 million, and advances ("Advances") under a revolving line of credit ("Revolving Line of
Credit") up to $5.0 million with an accounts receivable borrowing base of 80% of eligible accounts receivable. In September
2021, we entered into the Ninth Amendment to the Credit Facility whereby we may draw on the Term Debt and the Revolving
Line of Credit at any time prior to December 31, 2021 and October 1, 2024, respectively. The right to take draws on the Term
Debt expired on December 31, 2021 and no amounts were drawn under the Credit Facility as of December 31, 2021. On
October 1, 2024, loans drawn under the Revolving Line of Credit terminate. Advances made under the Revolving Line of
Credit bear interest at a variable annual rate equal to the equal to the greater of (i) 4.25% or (ii) the sum of (A) the prime rate
plus (B) 1.00%.
Our obligations under the Credit Facility are secured by a lien on substantially all of our personal property other than our
intellectual property. The Credit Facility includes a number of customary covenants and restrictive financial covenants
including meeting minimum product revenue levels and maintaining certain minimum cash levels with the lender. The Credit
Facility's financial covenants restrict the ability of the Company to transfer collateral, incur additional indebtedness, engage in
mergers or acquisitions, pay dividends or make other distributions, make investments, create liens, sell assets, or sell certain
assets held at foreign subsidiaries. A failure to comply with these covenants could permit the lender to exercise remedies against
us and the collateral securing the Credit Facility, including foreclosure of our properties securing the Credit Facility and our
cash. At December 31, 2021, we were in compliance with the covenants for the Credit Facility.
Legal Proceedings
We are not currently a party to any material pending litigation or other material legal proceedings.
Indemnifications
We are required to recognize a liability for the fair value of any obligations we assume upon the issuance of a guarantee.
We have certain agreements with licensors, licensees and collaborators that contain indemnification provisions. In such
provisions, we typically agree to indemnify the licensor, licensee and collaborator against certain types of third party claims.
The maximum amount of the indemnifications is not limited. We accrue for known indemnification issues when a loss is
probable and can be reasonably estimated. There were no accruals for expenses related to indemnification issues for any periods
presented.
Note 14. Related Party Transactions
Molecular Assemblies, Inc.
In June 2020, we entered into a Stock Purchase Agreement with MAI pursuant to which we purchased 1,587,050 shares of
MAI's Series A preferred stock for $1.0 million. In connection with the transaction, John Nicols, our President and Chief
Executive Officer, also joined MAI’s board of directors. Concurrently with our initial equity investment, we entered into the
MAI Agreement with MAI, pursuant to which we are performing services utilizing our CodeEvolver® protein engineering
platform technology to improve DNA polymerase enzymes in exchange for compensation in the form of additional shares of
MAI's Series A preferred stock. In April 2021, we purchased an additional 1,000,000 shares of MAI's Series A preferred stock
for $0.6 million. In September 2021, we purchased 9,198,423 shares of MAI's Series B preferred stock for $7.0 million. In the
fourth quarter of 2021, we became eligible to receive the primary milestone payment of $1.0 million which we received in the
form of additional of 1,587,049 Series B preferred stock during December 2021.
119
We recognized $2.0 million and $0.9 million in research and development revenue from transactions with MAI in the years
ended December 31, 2021 and 2020, respectively. We received 3,491,505 and 714,171 shares of MAI's Series A and B preferred
stock from research and development services we provided to MAI for the years ended December 31, 2021 and 2020,
respectively. As of December 31, 2021, we have 16,705,320 shares of MAI's Series A and B preferred stock that we have
earned or purchased since executing the Stock Purchase Agreement with MAI.
The carrying value of our investment in MAI Series A and B preferred stock was $12.7 million and $1.5 million at
December 31, 2021 and 2020, respectively. We had $0.2 million and nil in deferred revenue as of December 31, 2021 and 2020,
respectively, and nil and $0.5 million in contract assets due from MAI for services rendered as of December 31, 2021 and 2020,
respectively. Payment for the services rendered was received in the form of additional Series A and Series B preferred stock.
For additional information, see Note 5, "Collaborative Arrangements".
AstraZeneca PLC
Pam P. Cheng, who served as a member of our board of directors until June 2020, joined AstraZeneca PLC as Executive
Vice President, Operations and Information Technology in June 2015. We sold biocatalyst products to AstraZeneca PLC and its
controlled purchasing agents and contract manufacturers. We recognized $0.1 million of revenue in 2020, through the date of
Ms. Cheng's departure from our board of directors. As of December 31, 2020, we had no receivables from AstraZeneca PLC
and its controlled purchasing agents and contract manufacturers that was generated during the related party period.
Note 15. Segment, Geographical and Other Revenue Information
Segment Information
We manage our business as two business segments: Performance Enzymes and Novel Biotherapeutics. Our chief operating
decision maker ("CODM") is our Chief Executive Officer. Our business segments are primarily based on our organizational
structure and our operating results as used by our CODM in assessing performance and allocating resources for the Company.
We report corporate-related expenses such as legal, accounting, information technology, and other costs that are not
otherwise included in our reportable business segments as "Corporate costs." All items not included in income (loss) from
operations are excluded from the business segments.
We manage our assets on a total company basis, not by business segment, as the majority of our operating assets are shared
or commingled. Our CODM does not review asset information by business segment in assessing performance or allocating
resources, and accordingly, we do not report asset information by business segment.
Factors considered in determining the two reportable segments of the Company include the nature of business activities,
the management structure directly accountable to our CODM for operating and administrative activities, availability of discrete
financial information and information presented to the Board of Directors. Our CODM regularly reviews our segments and the
approach provided by management for performance evaluation and resource allocation.
Operating expenses that directly support the segment activity are allocated based on segment headcount, revenue
contribution or activity of the business units within the segments, based on the corporate activity type provided to the segment.
The expense allocation excludes certain corporate costs that are separately managed from the segments. This provides the
CODM with more meaningful segment profitability reporting to support operating decisions and allocate resources.
120
The following table provides financial information by our reportable business segments along with a reconciliation to
consolidated loss before income taxes (in thousands):
Year Ended December 31, 2021
Novel
Biotherapeutics
Performance
Enzymes
Total
Year Ended December 31, 2020
Novel
Biotherapeutics
Performance
Enzymes
Total
Revenues:
Product revenue
Research and development
revenue
Total revenues
Costs and operating expenses:
Cost of product revenue
Research and development (1)
Selling, general and
administrative(1)
$
70,657 $
— $
70,657 $
30,220 $
— $
30,220
19,858
90,515
22,209
23,140
12,105
14,239
14,239
34,097
104,754
—
30,219
22,209
53,359
17,886
48,106
13,742
20,923
20,950
20,950
—
21,705
38,836
69,056
13,742
42,628
2,755
14,860
9,597
2,355
11,952
Total segment costs and operating
expenses
Income (loss) from operations
$
57,454
33,061 $
32,974
(18,735)
44,262
3,844 $
24,060
(3,110)
Corporate costs (2)
Depreciation and amortization
Loss before income taxes
(1) Research and development expenses and selling, general and administrative expenses exclude depreciation and amortization of finance leases.
(2) Corporate costs include unallocated selling, general and administrative expense, interest income, and other income (expense), net.
$
$
90,428
14,326 $
(32,201)
(3,215)
(21,090)
68,322
734
(22,306)
(2,099)
(23,671)
Year Ended December 31, 2020
Novel
Biotherapeutics
Performance
Enzymes
Total
Year Ended December 31, 2019
Novel
Biotherapeutics
Performance
Enzymes
Total
Revenues:
Product revenue
Research and development
revenue
Total revenues
Costs and operating expenses:
Cost of product revenue
Research and development (1)
Selling, general and
administrative(1)
Total segment costs and operating
expenses
Income (loss) from operations
Corporate costs (2)
Depreciation and amortization
Loss before income taxes
$
30,220 $
— $
30,220 $
29,465 $
— $
29,465
17,886
48,106
13,742
20,923
20,950
20,950
—
21,705
38,836
69,056
13,742
42,628
28,691
58,156
15,632
19,380
10,302
10,302
—
13,278
38,993
68,458
15,632
32,658
9,597
2,355
11,952
8,462
2,222
10,684
44,262
3,844 $
24,060
(3,110)
68,322
734 $
43,474
14,682 $
$
15,500
(5,198)
(22,306)
(2,099)
(23,671)
$
$
58,974
9,484
(19,624)
(1,778)
(11,918)
(1) For the years ended December 31, 2020 and 2019, research and development expenses and selling, general and administrative expenses exclude
depreciation and amortization of finance leases.
(2) Corporate costs include unallocated selling, general and administrative expense, interest income, and other income (expense), net.
121
The following table provides stock-based compensation expense included in income (loss) from operations (in thousands):
Performance Enzymes
Novel Biotherapeutics
Corporate cost
Total
Significant Customers
Year Ended December 31,
2020
2019
2021
$
$
4,514 $
1,100
5,979
11,593 $
2,970 $
768
3,990
7,728 $
2,303
695
3,945
6,943
Customers that each accounted for 10% or more of our total revenues were as follows:
Customer A
Customer B
Customer C
Customer D
Customer E
* Percentage was less than 10%
Percentage of Total Revenues
For the Year Ended December 31,
2020
2019
2021
33 %
11 %
*
*
*
*
26 %
19 %
11 %
*
*
28 %
*
15 %
23 %
Customers that each accounted for 10% or more of accounts receivable balances as of the periods presented as follows:
Customer A
Customer B
Customer D
Customer E
* Percentage was less than 10%
Geographical Information
As of December 31,
2021
2020
62 %
*
*
*
*
32 %
13 %
25 %
Geographic revenues are identified by the location of the customer and consist of the following (in thousands):
Revenues
Americas
EMEA
APAC
Total revenues
2021
Year Ended December 31,
2020
2019
$
$
23,481 $
20,187
61,086
104,754 $
24,352 $
19,257
25,447
69,056 $
13,039
37,133
18,286
68,458
Identifiable long-lived assets by location were as follows (in thousands):
United States
December 31,
2021
2020
$
65,457 $
31,176
Identifiable goodwill was as follows (in thousands):`
December 31, 2021
December 31, 2020
Performance
Enzymes
Novel
Biotherapeutics
Total
Performance
Enzymes
Novel
Biotherapeutics
Total
Goodwill
$
2,463 $
778 $
3,241 $
2,463 $
778 $
3,241
122
Note 16. Allowance for Credit Losses
The following summarizes the receivables allowance for credit losses (in thousands):
2021
December 31,
2020
2019
Balance at beginning of period
Provision for credit losses
Balance at end of period
$
$
74 $
342
416 $
34 $
40
74 $
34
—
34
The following tables below summarizes accounts receivable by aging category (in thousands):
December 31, 2021
Accounts receivable
$
536 $
569 $
1,151 $
2,256 $
22,697 $
24,953
31-60 Days
61-90 Days
91 Days and over
Total over 31
Days
Current
Total balance
Accounts receivable
$
489 $
7 $
— $
496 $
13,398 $
13,894
31-60 Days
61-90 Days
91 Days and over
Total over 31
Days
Current
Total balance
December 31, 2020
123
ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL
DISCLOSURES
None.
Evaluation of Disclosure Controls and Procedures
ITEM 9A. CONTROLS AND PROCEDURES
Our management, under the supervision of our Chief Executive Officer and Chief Financial Officer and with the participation
of our disclosure committee, evaluated the effectiveness of the design and operation of our disclosure controls and procedures
as of December 31, 2021. The term “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the
Exchange Act, means controls and other procedures of a company that are designed to ensure that information required to be
disclosed by us in the reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported
within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include, without limitation,
controls and procedures designed to ensure that information required to be disclosed by us in the reports that we file or submit
under the Exchange Act is accumulated and communicated to our management, including our Chief Executive Officer and
Chief Financial Officer, as appropriate, to allow timely decisions regarding required disclosure. Based on this evaluation, our
Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective as of
December 31, 2021 at the reasonable assurance level.
Management’s Report on Internal Control over Financial Reporting
Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as such term
is defined in Exchange Act Rules 13a-15(f) and 15d-15(f). Internal control over financial reporting is a process designed to
provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for
external reporting purposes in accordance with United States generally accepted accounting principles.
Under the supervision and with the participation of our management, including our Chief Executive Officer and Chief Financial
Officer, we conducted an evaluation of the effectiveness of our internal control over financial reporting as of December 31,
2021 based on the guidelines established in Internal Control-Integrated Framework (2013) issued by the Committee of
Sponsoring Organizations of the Treadway Commission ("COSO"). Based on the results of our evaluation, our management
concluded that our internal control over financial reporting was effective as of December 31, 2021. We reviewed the results of
management’s assessment with our Audit Committee.
Our internal control over financial reporting as of December 31, 2021 has been audited by BDO USA, LLP, an independent
registered public accounting firm, as stated in their report which is included in Item 8 of this Annual Report.
Inherent Limitations on Effectiveness of Controls
In designing and evaluating the disclosure controls and procedures, management recognizes that any controls and procedures,
even if determined effective and no matter how well designed and operated, can provide only reasonable assurance of achieving
the desired control objectives to prevent or detect misstatements. In addition, the design of disclosure controls and procedures
must reflect the fact that there are resource constraints and that management is required to apply judgment in evaluating the
benefits of possible controls and procedures relative to their costs. Also, projections of any evaluation of effectiveness to future
periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of
compliance with the policies or procedures may deteriorate.
Changes in Internal Control over Financial Reporting
There were no changes in our internal control over financial reporting (as defined in Rule 13a-15(f) of the Exchange Act)
identified in connection with the evaluation required by paragraph (d) of Rule 13a-15 or 15d-15 of the Exchange Act, which
occurred during the fourth fiscal quarter of the year ended December 31, 2021, which has materially affected, or is reasonably
likely to materially affect, our internal control over financial reporting.
Not applicable.
ITEM 9B. OTHER INFORMATION
124
ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS
Not applicable.
PART III
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE
The information required by this item concerning our directors, executive officers, compliance with Section 16 of the Exchange
Act, our code of ethics and our Nominating and Corporate Governance Committee, and our Audit Committee is incorporated by
reference from the information that will be set forth in the sections under the headings “Election of Directors,” “Other
Matters—Section 16(a) Beneficial Ownership Reporting Compliance” and “Corporate Governance Matters” in the 2022 Proxy
Statement.
ITEM 11. EXECUTIVE COMPENSATION
The information required by this item concerning executive compensation is incorporated by reference from the information
that will be set forth in the 2022 Proxy Statement under the headings “Executive Compensation,” and “Corporate Governance
Matters.”
ITEM 12. SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED
STOCKHOLDER MATTERS
The information required by this item concerning securities authorized for issuance under equity compensation plans and
security ownership of certain beneficial owners and management is incorporated by reference from the information that will be
set forth in the 2022 Proxy Statement under the headings “Executive Compensation—Equity Compensation Plan Information”
and “Information Concerning Voting and Solicitation—Security Ownership of Certain Beneficial Owners and Management.”
ITEM 13. CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS,
AND DIRECTOR INDEPENDENCE
The information required by this item concerning transactions with related persons and director independence is incorporated
by reference from the information that will be set forth in the 2022 Proxy Statement under the headings “Certain Relationships
and Related Transactions” and “Corporate Governance Matters.”
ITEM 14. PRINCIPAL ACCOUNTING FEES AND SERVICES
The information required by this item is incorporated by reference from the information that will be set forth in the 2022 Proxy
Statement under the heading “Ratification of Independent Registered Public Accounting Firm—Principal Accounting Fees and
Services.”
125
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES
PART IV
1.
2.
Financial Statements: See “Index to Consolidated Financial Statements” in Part II, Item 8 of this Annual Report on Form
10-K
Exhibits: The exhibits listed in the accompanying index to exhibits are filed or incorporated by reference as part of this
Annual Report on Form 10-K.
126
Exhibit
No.
3.1
3.2
3.3
4.1
4.2
4.3
10.1A*
10.1B*
10.1C*
10.1D*
10.1E
10.1F
10.1G
10.1H
EXHIBIT INDEX
Description
Amended and Restated Certificate of Incorporation of Codexis, Inc. filed with the Secretary of the
State of the State of Delaware on April 27, 2010 and effective as of April 27, 2010 (incorporated by
reference to Exhibit 3.1 to the Company’s Quarterly Report on Form 10-Q for the quarter ended
March 31, 2010, filed on May 28, 2010).
Certificate of Designations of Series A Junior Participating Preferred Stock of Codexis, Inc., filed
with the Secretary of State of the State of Delaware on September 4, 2012 (incorporated by reference
to Exhibit 3.1 to the Company’s Current Report on Form 8-K, filed on September 4, 2012).
Amended and Restated Bylaws of Codexis, Inc. effective as of April 27, 2010 (incorporated by
reference to Exhibit 3.2 to the Company’s Quarterly Report on Form 10-Q for the quarter ended
March 31, 2010, filed on May 28, 2010).
Reference is made to Exhibits 3.1 through 3.3.
Form of the Company’s Common Stock Certificate (incorporated by reference to Exhibit 4.1 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2012, filed on August 9,
2012).
Description of Codexis' Securities Registered Pursuant to Section 12 of the Securities Exchange Act
of 1934
Lease Agreement by and between the Company and Metropolitan Life Insurance Company dated as
of February 1, 2004.
Amendment to Lease Agreement by and between the Company and Metropolitan Life Insurance
Company dated as of June 1, 2004.
Amendment to Lease Agreement by and between the Company and Metropolitan Life Insurance
Company dated as of March 9, 2007.
Amendment to Lease Agreement by and between the Company and Metropolitan Life Insurance
Company dated as of March 31, 2008.
Fourth Amendment to Lease Agreement by and between the Company and Metropolitan Life
Insurance Company dated as of September 17, 2010 (incorporated by reference to Exhibit 10.1 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2010, filed on
November 4, 2010).
Fifth Amendment to Lease Agreement by and between the Company and Metropolitan Life Insurance
Company dated as of March 16, 2011 (incorporated by reference to Exhibit 10.1 to the Company’s
Quarterly Report on Form 10-Q for the quarter ended March 31, 2011, filed on May 6, 2011).
Sixth Amendment to Lease by and between the Company and Metropolitan Life Insurance Company
dated as of September 27, 2012 (incorporated by reference to Exhibit 10.6 to the Company’s
Quarterly Report on Form 10-Q for the quarter ended September 30, 2012, filed on November 7,
2012).
Seventh Amendment to Lease by and between the Company and Metropolitan Life Insurance
Company dated as of October 11, 2016 (incorporated by reference to Exhibit 10.3 to the Company’s
Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, filed on November 8,
2016).
127
Exhibit
No.
10.1I***
Description
Eighth Amendment to Lease, dated as of February 8, 2019, by and between the Company and
Metropolitan Life Insurance Company (incorporated by reference to Exhibit 10.3 to the Company’s
Quarterly Report on Form 10-Q for the quarter ended March 31, 2019, filed on May 8, 2019).
10.2+*
Codexis, Inc. 2010 Equity Incentive Award Plan and Form of Stock Option Agreement.
10.3A+
10.3B+
10.3C+
10.3D+
10.3E+
10.3F+
10.4*
10.5+
10.6
10.7A†
10.7B
10.8+
10.9A+
Codexis, Inc. 2019 Incentive Award Plan (incorporated by reference to Exhibit 99.1 to the Company's
Registration Statement on Form S-8 (File No. 333-232262) filed with the SEC on June 21, 2019).
Form of Restricted Stock Unit Award Grant Notice and Restricted Stock Unit Award Agreement
under 2019 Incentive Award Plan (incorporated by reference to Exhibit 99.2 to the Company's
Registration Statement on Form S-8 (File No. 333-232262) filed with the SEC on June 21, 2019).
Form of Stock Option Grant Notice and Stock Option Agreement under 2019 Incentive Award Plan
(incorporated by reference to Exhibit 99.3 to the Company's Registration Statement on Form S-8 (File
No. 333-232262) filed with the SEC on June 21, 2019).
Form of Stock Option Grant Notice and Stock Option Agreement under 2019 Incentive Award Plan
(incorporated by reference to Exhibit 99.4 to the Company's Registration Statement on Form S-8 (File
No. 333-232262) filed with the SEC on June 21, 2019).
Form of Performance Stock Unit Award Grant Notice and Performance Stock Unit Award Agreement
under 2019 Incentive Award Plan (incorporated by reference to Exhibit 99.5 to the Company's
Registration Statement on Form S-8 (File No. 333-232262) filed with the SEC on June 21, 2019).
Form of Restricted Stock Award Grant Notice and Restricted Stock Award Agreement under 2019
Incentive Award Plan (incorporated by reference to Exhibit 99.6 to the Company's Registration
Statement on Form S-8 (File No. 333-232262) filed with the SEC on June 21, 2019).
Form of Indemnification Agreement between the Company and each of its directors, officers and
certain employees.
Form of Amended and Restated Change in Control Severance Agreement between the Company and
certain of its officers (incorporated by reference to Exhibit 10.2 to the Company’s Quarterly Report
on Form 10-Q for the quarter ended September 30, 2019, filed on November 6, 2019).
Asset Purchase Agreement, dated October 28, 2010, by and among the Company, Codexis Mayflower
Holdings, LLC and Maxygen, Inc. (incorporated by reference to Exhibit 2.1 to the Company’s
Current Report on Form 8-K, filed on October 28, 2010).
Manufacture and Supply Agreement, dated May 16, 2011, by and between the Company and
Lactosan GmbH & Co. KG (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly
Report on Form 10-Q for the quarter ended June 30, 2011, filed on August 3, 2011).
Amendment No. 1 to the Manufacture and Supply Agreement by and between the Company and
Lactosan GmbH & Co. KG dated as of March 9, 2012 (incorporated by reference to Exhibit 10.1 to
the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2012, filed on May
10, 2012).
Employment Agreement by and between the Company and Ross Taylor effective as of August 4,
2019 (incorporated by reference to Exhibit 10.3 to the Company’s Quarterly Report on Form 10-Q for
the quarter ended September 30, 2019, filed on November 6, 2019).
Employment Agreement by and between the Company and John Nicols effective as of May 28, 2012
(incorporated by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q for the
quarter ended June 30, 2012, filed on August 9, 2012).
128
Exhibit
No.
10.9B+
10.9C+
10.9D+
10.9E+
10.10A†
10.10B†
10.10C
10.10D
10.10E
10.10F
10.11A†
10.11B†
Description
John Nicols Stock Option Grant Notice and Stock Option Agreement dated June 13, 2012 between
John J. Nicols and the Company (incorporated by reference to Exhibit 10.3 to the Company’s
Quarterly Report on Form 10-Q for the quarter ended June 30, 2012, filed on August 9, 2012).
Amendment to Employment Agreement between the Company and John Nicols, dated April 21, 2016
(incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q for the
quarter ended June 30, 2016, filed on August 9, 2016).
Amendment to Employment Agreement between the Company and John Nicols, dated November 16,
2017 (incorporated by reference to Exhibit 10.8E to the Company’s Annual Report on Form 10-K for
the year ended December 31, 2017, filed on March 15, 2018).
Amendment to Employment Agreement between the Company and John Nicols, effective as of June
28, 2019, (incorporated by reference to Exhibit 10.4 to the Company’s Quarterly Report on Form 10-
Q for the quarter ended September 30, 2019, filed on November 6, 2019).
Sitagliptin Catalyst Supply Agreement by and between Merck Sharp and Dohme Corp. and the
Company dated as of February 1, 2012 (incorporated by reference to Exhibit 10.25 to the Company’s
Annual Report on Form 10-K for the year ended December 31, 2012, filed on April 2, 2013).
Amendment to Sitagliptin Catalyst Supply Agreement between Merck Sharp and Dohme Corp. and
the Company dated as of October 1, 2013 (incorporated by reference to Exhibit 10.2 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013, filed on
November 12, 2013).
Amendment No. 2 to Sitagliptin Catalyst Supply Agreement between Merck Sharp and Dohme Corp.
and the Company dated as of February 25, 2015 (incorporated by reference to Exhibit 10.1 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2015, filed on May 7,
2015).
Amendment No. 3 to Sitagliptin Catalysts Supply Agreement between Merck Sharp and Dohme
Corp. and the Company dated as of December 17, 2015 (incorporated by reference to Exhibit 10.11D
to the Company’s Annual Report on Form 10-K for the year ended December 31, 2015, filed on
March 8, 2016).
Amendment No. 4 to Sitagliptin Catalysts Supply Agreement, effective as of January 1, 2016, by and
between the Company and Merck Sharp and Dohme Corp. (incorporated by reference to Exhibit 10.1
to the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, filed on
November 8, 2016).
Amendment No. 5 to Sitagliptin Catalysts Supply Agreement, effective as of July 1, 2021, by and
between the Company and Merck Sharp and Dohme Corp. (incorporated by reference to Exhibit 10.1
to the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021, filed on
November 5, 2021).
Global Development, Option and License Agreement by and among the Company, Societé des
Produits Nestlé S.A., formerly known as Nestec Ltd. (“Nestlé Health Science”), effective as of
October 12, 2017 (incorporated by reference to Exhibit 10.10 to the Company’s Annual Report on
Form 10-K for the year ended December 31, 2017, filed on March 15, 2018).
Amendment No. 1 to Global Development, Option and License Agreement by and among the
Company, Nestec Ltd. and Nestlé Amendment No. 1 to Global Development, Option and License
Agreement by and among the Company, Nestec Ltd. and Nestlé Health Science S.A., effective as of
July 26, 2018.(incorporated by reference to Exhibit 10.12B to the Company’s Annual Report on Form
10-K for the year ended December 31, 2018, filed on March 3, 2019).
10.11C†
Letter Agreement to Global Development, Option and License Agreement by and among the
Company, Nestec Ltd. and Nestlé Health Science S.A., effective as of December 12, 2018.
(incorporated by reference to Exhibit 10.12C to the Company’s Annual Report on Form 10-K for the
year ended December 31, 2018, filed on March 3, 2019).
129
Exhibit
No.
10.12A†
10.12B†
Description
Platform Technology Transfer, Collaboration and License Agreement by and between the Company
and GlaxoSmithKline Intellectual Property Limited, effective as of July 10, 2014 (incorporated by
reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q for the quarter ended
September 31, 2014, filed on November 6, 2014).
Letter Agreement, effective as of February 21, 2020, by and between Codexis, Inc. and
GlaxoSmithKline Intellectual Property Development Limited (incorporated by reference to Exhibit
10.2 to the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, filed
on May 8, 2020).
10.13A***
Platform Technology Transfer and License Agreement by and between the Company and Merck
Sharp & Dohme Corp., dated as of August 3, 2015.
10.13B†
Amendment No. 1 to Platform Technology Transfer and License Agreement by and between the
Company and Merck Sharp & Dohme Corp., dated as of October 10, 2018, incorporated by reference
to Exhibit 10.14A to the Company’s Annual Report on Form 10-K for the year ended December 31,
2018, filed on March 3, 2019).
10.13C***
Amendment No. 2 to Platform Technology Transfer and License Agreement by and between Merck
and the Company dated as of January 1, 2019 (incorporated by reference to Exhibit 10.1 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2019, filed on May 8,
2019).
10.14***
10.15***
10.16A†
10.16B†
10.16C†
10.16D†
10.16E†
10.16F
Platform Technology Transfer and License Agreement, dated May 2, 2019, by and between the
Company and Novartis Pharma AG (incorporated by reference to Exhibit 10.4 to the Company’s
Quarterly Report on Form 10-Q for the quarter ended June 30, 2019, filed on August 6, 2019).
Strategic Collaboration and License Agreement by and between Shire Human Genetic Therapies,
Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited and the Company,
dated March 23, 2020 (incorporated by reference to Exhibit 10.1 to the Company's Quarterly Report
on Form 10-Q for the quarter ended March 31, 2020, filed on May 8, 2020).
Loan and Security Agreement effective as of June 30, 2017 by and between the Company and
Western Alliance Bank (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report
on Form 10-Q for the quarter ended June 30, 2017, filed on August 9, 2017).
First Amendment to Loan and Security Agreement effective as of September 28, 2017 by and
between the Company and Western Alliance Bank (incorporated by reference to Exhibit 10.1 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2017, filed on
November 9, 2017).
Second Amendment to Loan and Security Agreement effective as of November 7, 2017 by and
between the Company and Western Alliance Bank (incorporated by reference to Exhibit 10.15B to the
Company’s Annual Report on Form 10-K for the year ended December 31, 2017, filed on March 15,
2018).
Third Amendment to Loan and Security Agreement by and between the Company and Western
Alliance Bank dated as of June 29, 2018 (incorporated by reference to Exhibit 10.1 to the Company’s
Quarterly Report on Form 10-Q for the quarter ended June 30, 2018, filed on August 9, 2018).
Fourth Amendment to Loan and Security Agreement effective as of September 28, 2018 by and
between the Company and Western Alliance Bank (incorporated by reference to Exhibit 10.1 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2018, filed on
November 9, 2018).
Fifth Amendment to Loan and Security Agreement effective as of January 23, 2019 by and between
the Company and Western Alliance Bank (incorporated by reference to Exhibit 10.2 to the Company’s
Quarterly Report on Form 10-Q for the quarter ended March 31, 2019, filed on May 8, 2019).
130
Exhibit
No.
10.16G
10.16H
10.16I
10.16J
10.17
23.1
24.1
31.1
31.2
32.1**
101
101.SCH
101.CAL
101.DEF
101.LAB
101.PRE
104
Description
Sixth Amendment to Loan and Security Agreement by and between the Company and Western
Alliance Bank dated as of July 11, 2019 (incorporated by reference to Exhibit 10.1A to the
Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019, filed on
November 6, 2019).
Seventh Amendment to Loan and Security Agreement by and between the Company and Western
Alliance Bank dated as of September 30, 2019 (incorporated by reference to Exhibit 10.1B to the
Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019, filed on
November 6, 2019).
Eighth Amendment to Loan and Security Agreement by and between the Company and Western
Alliance Bank dated as of September 30, 2020 (incorporated by reference to Exhibit 10.1 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, filed on
November 6, 2020.)
Ninth Amendment to Loan and Security Agreement by and between the Company and Western
Alliance Bank dated as of September 30, 2021 (incorporated by reference to Exhibit 10.2 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021, filed on
November 5, 2021).
Lease Agreement by and between the Company and ARE-SAN FRANCISCO NO. 63, LLC dated as
of January 29, 2021 (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on
Form 10-Q for the quarter ended March 31, 2021, filed on May 7, 2021).
Consent of BDO USA, LLP, independent registered public accounting firm.
Power of Attorney (see signature page to this Annual Report on Form 10-K).
Certification of Principal Executive Officer Required Under Rule 13a-14(a) and 15d-14(a) of the
Securities Exchange Act of 1934, as amended.
Certification of Principal Financial Officer Required Under Rule 13a-14(a) and 15d-14(a) of the
Securities Exchange Act of 1934, as amended.
Certification of Principal Executive Officer and Principal Financial Officer Required Under Rule 13a-
14(b) of the Securities Exchange Act of 1934, as amended, and 18 U.S.C. §1350.
The following materials from Registrant’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2021 formatted in Inline Extensible Business Reporting Language (iXBRL) includes:
(i) Consolidated Balance Sheets at December 31, 2021 and December 31, 2020, (ii) Consolidated
Statements of Operations for the years ended December 31, 2021, December 31, 2020 and December
31, 2019, (iii) Consolidated Statements of Cash Flows for the years ended December 31, 2021,
December 31, 2020 and December 31, 2019, (vi) Consolidated Statements of Stockholders’ Equity
for the years ended December 31, 2021, December 31, 2020 and December 31, 2019 and (vii) Notes
to Consolidated Financial Statements.
Inline XBRL Taxonomy Extension Schema Document
Inline XBRL Taxonomy Extension Calculation Linkbase Document
Inline XBRL Taxonomy Extension Definition Linkbase Document
Inline XBRL Taxonomy Extension Label Linkbase Document
Inline XBRL Taxonomy Extension Presentation Linkbase Document
The cover page from the Company’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2021, formatted in Inline XBRL and contained in Exhibit 101.
131
+
†
*
Indicates a management contract or compensatory plan or arrangement.
Confidential treatment has been granted for certain information contained in this exhibit. Such information has been
omitted and filed separately with the Securities and Exchange Commission.
Filed as exhibits to the registrant’s Registration Statement on Form S-1 (File No. 333-164044), effective April 21,
2010, and incorporated herein by reference.
**
Pursuant to Item 601(b)(32) of Regulation S-K this exhibit is furnished rather than filed with this report.
***
Portions of the exhibit, marked by brackets, have been omitted because the omitted information is (i) not material and
(ii) would be competitively harmful if publicly disclosed.
132
Not applicable.
ITEM 16. FORM 10-K SUMMARY
133
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the Registrant has duly caused this
report to be signed on its behalf by the undersigned, thereunto duly authorized.
SIGNATURES
Date:
February 28, 2022
By:
/s/ John J. Nicols
CODEXIS, INC.
President and Chief Executive Officer
(Principal Executive Officer)
134
POWER OF ATTORNEY
Each person whose individual signature appears below hereby authorizes and appoints John J. Nicols, Ross Taylor and Richard
A. Sabalot, and each of them, with full power of substitution and resubstitution and full power to act without the other, as his or
her true and lawful attorney-in-fact and agent to act in his or her name, place and stead and to execute in the name and on
behalf of each person, individually and in each capacity stated below, and to file any and all amendments to this annual report
on Form 10-K and to file the same, with all exhibits thereto, and other documents in connection therewith, with the Securities
and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do
and perform each and every act and thing, ratifying and confirming all that said attorneys-in-fact and agents or any of them or
their or his substitute or substitutes may lawfully do or cause to be done by virtue thereof.
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following
persons on behalf of the Registrant and in the capacities and on the dates indicated.
SIGNATURE
TITLE
DATE
/s/ John J. Nicols
John J. Nicols
/s/ Ross Taylor
Ross Taylor
/s/ Byron L. Dorgan
Byron L. Dorgan
/s/ Jennifer Aaker
Jennifer Aaker
/s/ Stephen Dilly
Stephen Dilly
/s/ Esther Martinborough
Esther Martinborough
/s/ Alison Moore
Alison Moore
/s/ David V. Smith
David V. Smith
/s/ Dennis P. Wolf
Dennis P. Wolf
/s/ Patrick Y. Yang
Patrick Y. Yang
President, Chief Executive Officer and
Director (Principal Executive Officer) Date:
February 28, 2022
Senior Vice President and Chief
Financial Officer (Principal Financial
and Accounting Officer)
Date:
February 28, 2022
Chairman of the Board of Directors
Date:
February 28, 2022
Date:
February 28, 2022
Date:
February 28, 2022
Date:
February 28, 2022
Date:
February 28, 2022
Date:
February 28, 2022
Date:
February 28, 2022
Date:
February 28, 2022
Director
Director
Director
Director
Director
Director
Director
135
Consent of Independent Registered Public Accounting Firm
Codexis, Inc.
Redwood City, California
We hereby consent to the incorporation by reference in the Registration Statements on Form S-8 (Nos.
333-167752, 333-172166, 333-179903, 333-187711, 333-194524, 333-202596, 333-210022, 333-216587,
333-223693, 333-224885, 333-230037, and 333-232262) and Form S-3ASR (Nos. 333-228693 and
333-255926) of Codexis, Inc. of our reports dated February 28, 2022, relating to the consolidated financial
statements, and the effectiveness of Codexis, Inc.’s internal control over financial reporting, which appear in
this Form 10-K.
/s/ BDO USA, LLP
San Jose, California
February 28, 2022
I, John J. Nicols, certify that:
CERTIFICATION
Exhibit 31.1
1.
2.
3.
4.
I have reviewed this Annual Report on Form 10-K of Codexis, Inc.;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a
material fact necessary to make the statements made, in light of the circumstances under which such statements
were made, not misleading with respect to the period covered by this report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly
present in all material respects the financial condition, results of operations and cash flows of the registrant as of,
and for, the periods presented in this report;
The registrant's other certifying officer(s) and I are responsible for establishing and maintaining disclosure
controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over
financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
(a)
(b)
(c)
(d)
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to
be designed under our supervision, to ensure that material information relating to the registrant, including
its consolidated subsidiaries, is made known to us by others within those entities, particularly during the
period in which this report is being prepared;
Designed such internal control over financial reporting, or caused such internal control over financial
reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability
of financial reporting and the preparation of financial statements for external purposes in accordance with
generally accepted accounting principles;
Evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in this
report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of
the period covered by this report based on such evaluation; and
Disclosed in this report any change in the registrant's internal control over financial reporting that
occurred during the registrant's most recent fiscal quarter (the registrant's fourth fiscal quarter in the case
of an annual report) that has materially affected, or is reasonably likely to materially affect, the
registrant's internal control over financial reporting; and
5.
The registrant's other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal
control over financial reporting, to the registrant's auditors and the audit committee of the registrant's board of
directors (or persons performing the equivalent functions):
(a)
(b)
All significant deficiencies and material weaknesses in the design or operation of internal control over
financial reporting which are reasonably likely to adversely affect the registrant's ability to record,
process, summarize and report financial information; and
Any fraud, whether or not material, that involves management or other employees who have a significant
role in the registrant's internal control over financial reporting.
Date: February 28, 2022
/s/John J. Nicols
John J. Nicols
President and Chief Executive Officer
I, Ross Taylor, certify that:
CERTIFICATION
Exhibit 31.2
1.
2.
3.
4.
I have reviewed this Annual Report on Form 10-K of Codexis, Inc.;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a
material fact necessary to make the statements made, in light of the circumstances under which such statements
were made, not misleading with respect to the period covered by this report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly
present in all material respects the financial condition, results of operations and cash flows of the registrant as of,
and for, the periods presented in this report;
The registrant's other certifying officer(s) and I are responsible for establishing and maintaining disclosure
controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over
financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
(a)
(b)
(c)
(d)
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to
be designed under our supervision, to ensure that material information relating to the registrant, including
its consolidated subsidiaries, is made known to us by others within those entities, particularly during the
period in which this report is being prepared;
Designed such internal control over financial reporting, or caused such internal control over financial
reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability
of financial reporting and the preparation of financial statements for external purposes in accordance with
generally accepted accounting principles;
Evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in this
report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of
the period covered by this report based on such evaluation; and
Disclosed in this report any change in the registrant's internal control over financial reporting that
occurred during the registrant's most recent fiscal quarter (the registrant's fourth fiscal quarter in the case
of an annual report) that has materially affected, or is reasonably likely to materially affect, the
registrant's internal control over financial reporting; and
5.
The registrant's other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal
control over financial reporting, to the registrant's auditors and the audit committee of the registrant's board of
directors (or persons performing the equivalent functions):
(a)
(b)
All significant deficiencies and material weaknesses in the design or operation of internal control over
financial reporting which are reasonably likely to adversely affect the registrant's ability to record,
process, summarize and report financial information; and
Any fraud, whether or not material, that involves management or other employees who have a significant
role in the registrant's internal control over financial reporting.
Date: February 28, 2022
/s/Ross Taylor
Ross Taylor
Senior Vice President and Chief Financial Officer
CERTIFICATION PURSUANT TO
18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32.1
In connection with the Annual Report of Codexis, Inc. (the “Company”) on Form 10-K for the fiscal year ended
December 31, 2021, as filed with the Securities and Exchange Commission (the “Report”), John J. Nicols, President and Chief
Executive Officer of the Company and Ross Taylor, Senior Vice President and Chief Financial Officer of the Company,
respectively, do each hereby certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-
Oxley Act of 2002, that:
•
•
The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934;
and
The information in the Report fairly presents, in all material respects, the financial condition and results of
operations of the Company.
Date: February 28, 2022
/s/John J. Nicols
John J. Nicols
President and Chief Executive Officer
/s/Ross Taylor
Ross Taylor
Senior Vice President and Chief Financial Officer
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Corporate Headquarters
200 Penobscot Drive, Redwood City, CA 94063, USA
+1 (650) 421-8100 | www.codexis.com
2022 Codexis, Inc. All rights reserved.
16