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Natera

ntra · NASDAQ Healthcare
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Employees 501-1000
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FY2021 Annual Report · Natera
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2021 ANNUAL REPORT

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 

OR 

☐ 

TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 

For the transition period from                       to                       

Commission file number: 001-37478 

NATERA, INC. 
(Exact Name of Registrant as Specified in its Charter) 

Delaware 
State or Other Jurisdiction of Incorporation or Organization

01-0894487 
(I.R.S. Employer Identification No.)

13011 McCallen Pass 
Building A Suite 100 
Austin, TX 
(Address of Principal Executive Offices) 

78753 
(Zip Code) 

(650) 249-9090 
Registrant’s Telephone Number, Including Area Code 

Securities registered pursuant to Section 12(b) of the Act: 

Title of each class

Trading Symbol  

Common Stock, par value $0.0001 per share 

NTRA 

Name of each exchange on which registered
The Nasdaq Stock Market LLC 
(NASDAQ Global Select Market)

Securities registered pursuant to Section 12(g) of the Act:  None 

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 Securities 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 an emerging 
growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “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 Exchange Act).    Yes  ☐    No  ☒ 

The aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant was approximately $9.33 billion based on the last 
reported sale price of $113.53 per share as reported on the Nasdaq Global Select Market on June 30, 2021, the last trading day of the most recently completed second 
fiscal quarter. 

As of February 18, 2022, the number of outstanding shares of the registrant’s common stock, par value $0.0001 per share, was 95,470,898. 

Information required in response to Part III of this annual report on Form 10-K is hereby incorporated by reference to portions of the Registrant’s proxy 
statement for its Annual Meeting of Stockholders to be held in 2022. The proxy statement will be filed by the registrant with the Securities and Exchange Commission 
within 120 days after the end of the registrant’s fiscal year ended December 31, 2021. 

DOCUMENTS INCORPORATED BY REFERENCE 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
Natera, Inc. 

FORM 10-K FOR THE YEAR ENDED DECEMBER 31, 2021 

TABLE OF CONTENTS 

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

PART I 

Item 1. 
Business . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 1A.  Risk Factors  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 1B.  Unresolved Staff Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Properties  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 2. 
Legal Proceedings  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 3. 
Item 4.  Mine Safety Disclosures  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

PART II 

Item 5.  Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases 

of Equity Securities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Selected Financial Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 6. 
Item 7.  Management’s Discussion and Analysis of Financial Condition and Results of Operations . . . . .
Item 7A.  Quantitative and Qualitative Disclosures About Market Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Financial Statements and Supplementary Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 8. 
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure . . . . .
Item 9. 
Item 9A.  Controls and Procedures  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 9B.  Other Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

PART III 

Item 10.  Directors, Executive Officers and Corporate Governance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 11.  Executive Compensation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 12.  Security Ownership of Certain Beneficial Owners and Management and Related Stockholder 

Matters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 13.  Certain Relationships and Related Transactions, and Director Independence . . . . . . . . . . . . . . . . .
Item 14.  Principal Accounting Fees and Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

PART IV 

Item 15.  Exhibits and Financial Statement Schedules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Item 16.  Form 10-K Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Signatures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS 

This report contains forward-looking statements. The forward-looking statements are contained principally in the 
sections  titled  “Risk  Factors”  and  “Management’s  Discussion  and  Analysis  of  Financial  Condition  and  Results  of 
Operations,” but are also contained elsewhere in this report. Forward-looking statements include information concerning 
our  future  results  of  operations  and  financial  position,  strategy  and  plans,  and  our  expectations  for  future  operations. 
Forward-looking statements include all statements that are not historical facts and, in some cases, can be identified by 
terms such as "believe," "may," "will," "estimate," "continue," "anticipate," "design," "intend," "expect," "could," "plan," 
"potential," "predict," "seek," "should," "would" or the negative version of these words and similar expressions.  

Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause 
our  actual  results,  performance  or  achievements  to  be  materially  different  from  any  future  results,  performance  or 
achievements expressed or implied by the forward-looking statements, including those described in "Risk Factors" and 
elsewhere  in  this  report.  Given  these  uncertainties,  you  should  not  place  undue  reliance  on  these  forward-looking 
statements. Also, forward-looking statements represent our beliefs and assumptions only as of the date of this report. In 
light  of  the  significant  uncertainties  in  these  forward-looking  statements,  you  should  not  regard  these  statements  as  a 
representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time 
frame, or at all. You should read this report completely and with the understanding that our actual future results may be 
materially different from what we expect.  

These forward-looking statements include, but are not limited to, statements concerning the following: 

• 

• 
• 

• 

• 

• 

• 
• 
• 
• 

• 
• 

• 
• 

• 

• 

• 

our expectation that, for the foreseeable future, a significant portion of our revenues will be derived from 
sales of Panorama, our non-invasive prenatal test, and Horizon, our carrier screening test; 
our ability to increase demand for Panorama and Horizon; 
our  expectation  that  Panorama  will  be  adopted  for  broader  use  in  average-risk  pregnancies  and  for  the 
screening of microdeletions and that third-party payer reimbursement will be available for these applications, 
including our expectations that the results from our single nucleotide polymorphism-based Microdeletion 
and Aneuploidy RegisTry, or SMART, Study may support broader use and reimbursement for the use of 
Panorama in average risk pregnancies and for microdeletions; 
the extent and duration of the impact of the COVID-19 pandemic on our business, results of operations, stock 
price, or overall financial condition; 
our  expectations  of  the reliability,  accuracy,  and performance of  our  tests,  as  well  as  expectations of  the 
benefits of our tests to patients, providers, and payers; 
our  ability  to  successfully  develop  additional  revenue  opportunities  and  expand  our  product  offerings  to 
include new tests; 
our efforts to successfully develop and commercialize our oncology and organ health products; 
the effect of improvements in our cost of goods sold; 
our estimates of the total addressable markets for our current and potential product offerings; 
our ability and expectations regarding obtaining, maintaining and expanding third-party payer coverage of, 
and reimbursement for, our tests; 
the effect of changes in the way we account for our revenue; 
the  scope  of  protection  we  establish  and  maintain  for,  and  developments  or  disputes  concerning,  our 
intellectual property or other proprietary rights; 
our ability to successfully compete in the markets we serve; 
our reliance on collaborators such as medical institutions, contract laboratories, laboratory partners, and other 
third parties; 
our  ability  to  operate  our  laboratory  facility  and  meet  expected  demand,  and  to  successfully  scale  our 
operations; 
our reliance on a limited number of suppliers, including sole source suppliers, which may impact our ability 
to maintain a continued supply of laboratory instruments and materials and to run our tests; 
our expectations of the rate of adoption of Panorama, Horizon and of any of our other current or future tests 
by laboratories, clinics, clinicians, payers, and patients; 

3 

 
 
 
 
 
• 

• 
• 
• 

our  ability  to  complete  clinical  studies  and  publish  compelling  clinical  data  in  peer-reviewed  medical 
publications regarding Panorama and any of our future tests, and the effect of such data or publications on 
professional society or practice guidelines or coverage and reimbursement determinations from third-party 
payers,  including  our  SMART  and  CIRCULATE-Japan  studies  and  our  ongoing  and  planned  trials  in 
oncology and transplant rejection; 
our reliance on our partners to market and offer our tests in the United States and in international markets; 
our expectations regarding acquisitions, dispositions and other strategic transactions; 
our expectations regarding the conversion of our outstanding 2.25% convertible senior notes due 2027 in the 
aggregate  principal  amount  of  $287.5  million  and  our  ability  to  make  debt  service  payments  under  the 
Convertible Notes if such Convertible Notes are not converted; 
our ability to fund our working capital requirements; 
the factors that may impact our financial results; 
anticipated trends and challenges in our business and the markets in which we operate; 

• 
• 
• 
•  whether we will elect to exercise the option we have to acquire certain assets of a third party and, if exercised, 

• 

whether that acquisition will be consummated and meet our expectations; and 
our ability to comply with federal, state, and foreign regulatory requirements, programs and policies and to 
successfully operate our business in response to changes in such requirements, programs and policies. 

Any forward-looking statement made by us in this report speaks only as of the date on which it is made. Except 
as  required  by  law,  we  disclaim  any  obligation  to  update  these  forward-looking  statements  publicly,  or  to  update  the 
reasons  actual  results  could  differ  materially  from  those  anticipated  in  these  forward-looking  statements,  even  if  new 
information becomes available in the future. 

SUMMARY OF RISK FACTORS 

The below is a summary of principal risks to our business and risks associated with ownership of our stock. This 
summary does not address all of the risks that we face. We encourage you to carefully review the full risk factors contained 
in this Annual Report on Form 10-K in their entirety for additional information regarding the material factors that make 
an  investment  in  our  securities  speculative  or  risky.  These  risks  and  uncertainties  include,  but  are  not  limited  to,  the 
following: 

• 

• 

the  COVID-19  pandemic  has  materially  impacted  and  could  continue  to  materially  impact  our  business, 
results of operations, financial condition and/or stock price; 

if  we  are  unable  to  increase  demand  for  Panorama  and  Horizon,  which  together  represent  a  significant 
majority  of  our  revenues,  obtain  favorable  coverage  and  reimbursement  determinations  from  third-party 
payers, and expand geographically, our business will be harmed; 

•  Panorama  may  not  be  adopted  for  broader  use  in  average-risk  pregnancies  or  for  the  screening  of 

microdeletions, or third-party payer reimbursement may not be available for these applications; 

• 

if we are not successful in our efforts to develop additional revenue opportunities and expand our product 
offerings to include new tests, including in oncology and organ health, our business and prospects, as well 
as our stock price, will be adversely affected; 

•  we have incurred net losses since our inception, and anticipate that we will continue to incur losses for the 

foreseeable future; 

•  we have incurred substantial indebtedness that may decrease our business flexibility, access to capital, and/or 

increase our borrowing costs, which may adversely affect our operations and financial results; 

• 

• 

our quarterly results may fluctuate from period to period, which could adversely impact the value of our 
common stock;  

competition  in  our  industry  is  intense,  and  if  we  are  unable  to  complete  successfully  with  respect  to  our 
current  or  future  products  or  services,  we  may  be  unable  to  increase  or  sustain  our  revenues  or  achieve 
profitability; 

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• 

our estimates of the total addressable markets for our current and potential product offerings may turn out to 
be inaccurate, or the markets for our tests may not grow as we expect; 

•  we may be unable to obtain, maintain or expand third-party payer coverage of, and reimbursement for, our 

tests; 

• 

• 

if we are not successful in our research and development or clinical development activities, including clinical 
trials  and  publication  of  compelling  data,  our  ability  to  commercialize  our  products,  and  therefore  our 
competitive position, will be adversely impacted; 

our  strategic  or  commercial  partnerships,  such  as  our  agreements  with  BGI  Genomics Co., Ltd.  and 
Foundation Medicine, Inc., may not be successful, and we may be unable to enter into additional partnerships 
in the future; 

•  we operate in a crowded technology area in which there has been substantial litigation and other proceedings 
regarding patent and other intellectual property rights, and we may fail to adequately protect or enforce our 
intellectual property relating to our tests, or fail to defend against infringement claims brought against us by 
other parties; 

•  we rely on a limited number of suppliers, including sole source suppliers, which may impact our ability to 

maintain a continued supply of laboratory instruments and materials and to run our tests;  

•  we have experienced rapid growth, particularly in recent years, and may be unable to successfully scale our 

operations, which could harm our business and results of operations;  

•  we may engage in acquisitions, dispositions or other strategic transactions that could disrupt our business, 

cause dilution to our stockholders or reduce our financial resources; and 

• 

third-party payers, such as commercial health insurers and government insurance programs, may decide not 
to reimburse our existing or future products, may set the amounts of any reimbursements at prices that do 
not allow us to cover our expenses or may otherwise adopt policies and procedures that restrict or harm our 
business. 

As used in this Annual Report on Form 10-K, the terms “Natera,” “Registrant,” “Company,” “we,” “us,” and 

“our” mean Natera, Inc. and its subsidiaries unless the context indicates otherwise. 

5 

 
 
 
 
Item 1.  BUSINESS 

Note: A glossary of terms used in this Form 10-K appears at the end of this Item 1. 

PART I 

Overview  

We are a diagnostics company with proprietary molecular and bioinformatics technology that we are applying to 
change the management of disease worldwide. Our cell-free DNA, or cfDNA, technology combines our novel molecular 
assays, which reliably measure many informative regions across the genome from samples as small as a single cell, with 
our  statistical  algorithms  which  incorporate  data  available  from  the  broader  scientific  community  to  identify  genetic 
variations  covering  a  wide  range  of  serious  conditions  with  high  accuracy  and  coverage.  Our  initial  focus  was  in  the 
women’s health space, in which we develop and commercialize non- or minimally- invasive tests to evaluate risk for, and 
thereby enable early detection of, a wide range of genetic conditions, such as Down syndrome. Our technology is now also 
being proven in the oncology market, in which we are commercializing, among others, a personalized blood-based DNA 
test to detect molecular residual disease and monitor disease recurrence, as well as in the organ health market, with tests 
to assess organ transplant rejection. Since 2009, we have launched a comprehensive suite of products to improve patient 
care outcomes in women’s health, oncology and organ health. We intend to continue to expand our product portfolio and 
launch new products in the future. We seek to enable even wider adoption of our technology through our global cloud-
based distribution model. In addition to our direct sales force in the United States, we have a global network of over 100 
laboratory and distribution partners, including many of the largest international laboratories.  

We launched Panorama, our non-invasive prenatal test, or NIPT, in 2013 and have since gone from being the 
fourth company to enter the NIPT market to being the market leader by volume in the United States. We launched our 
Horizon carrier screening test in 2012. Panorama and Horizon together represent the significant majority of our revenues. 
Our revenues were $625.5 million in 2021 compared to $391.0 million in 2020 and $302.3 million in 2019. Our product 
revenues,  which  are  primarily  generated  from  testing  in  women’s  health,  were  $567.1  million,  $367.2  million,  and 
$269.9 million for the years ended December 31, 2021, 2020, and 2019, respectively. Our net losses increased to $471.7 
million in 2021, from $229.7 million in 2020 and $124.8 million in 2019.  

Our Solution  

In women’s health, oncology and organ health, the use of blood-based tests offers significant advantages over 
older methods, but the significant technological challenge is that such testing often requires the measurement of very small 
amounts of relevant genetic material – fetal DNA in reproductive health, tumor DNA in oncology, and donor DNA in 
transplant rejection – circulating within a much larger blood sample. Our approach combines proprietary molecular biology 
and computational techniques to measure genomic variations in tiny amounts of DNA, as small as a single cell.  

DNA  is  a  naturally  occurring  information  storage  system  that  conveys  genetic  inheritance.  DNA  stores 
information in a linear sequence of the chemical bases adenine, cytosine, guanine and thymine, represented by the symbols 
A, C, G, and T. Billions of bases of A, C, G, and T link together inside living cells to form the genome, which can be read 
like a code or a molecular blueprint for life. While differences in the specific sequence and structure of this code drive 
biological diversity, certain variations can also cause disease. Examples of genetic diversity include CNVs and SNVs. A 
CNV is a genetic mutation in which relatively large regions of the genome have been deleted or duplicated, and an SNV 
is a mutation where a single base has changed. When single base changes are common in the population, that position on 
the chromosome, or loci, is called a single nucleotide polymorphism, or SNP. 

Our molecular biology techniques are based on measuring thousands of SNPs simultaneously using massively 
multiplexed polymerase chain reaction, or mmPCR, to multiplex, or target, many thousands of regions of the genome 
simultaneously in a single test reaction. Our method avoids losing molecules, which can happen when samples are split 

6 

 
 
 
into separate reaction tubes, so that all relevant variants can be detected. To make sense of the resulting deep and rich set 
of biological data and deliver a test result, we have developed computationally intensive algorithms that combine the data 
generated by mmPCR with the ever-expanding set of publicly available data on genetic variations. Our technologies allow 
us to achieve a high signal-to-noise ratio when detecting fragments of DNA at frequencies as low as a single copy, which 
allows us to deliver tests with a high degree of specificity and sensitivity. Furthermore, our women’s health tests assess 
the risk of a broad range of conditions, which we refer to as “clinical coverage,” including common fetal aneuploidies, 
microdeletions, triploidy, and inherited genetic conditions that could be passed on from parent to child, from a single blood 
draw. 

We  believe  our  approach  represents  a  fundamental  advance  in  molecular  biology.  In  women’s  health,  this 
approach is distinct from the approach employed with other commercially available NIPTs, which use first-generation 
“quantitative”, or counting, methods to compare the relative number of sequence reads from a chromosome of interest to 
a  reference  chromosome.  Based  on  data  published  in  the  journals  Obstetrics  &  Gynecology,  American  Journal  of 
Obstetrics & Gynecology, Prenatal Diagnosis, and others, we believe Panorama is the most accurate NIPT commercially 
available  in  the  United States.  In  oncology,  with our  Signatera  circulating  tumor DNA, or  ctDNA, test  that  is  custom 
designed for, informed by and specific to, the tumor DNA for each patient, we have demonstrated the ability to detect 
ctDNA  with  a  high  degree  of  sensitivity  and  specificity.  In  organ  health,  we  have  demonstrated  the  ability  of  our 
technology to measure the fraction of cell-free DNA that is donor-derived, or dd-cfDNA, which is DNA that is shed from 
a transplanted organ into circulation. We have expanded our test capabilities beyond kidney and into heart as well as lung, 
each demonstrating a high area under the curve, or AUC, in validation studies.  

Our technology is compatible with standard equipment used globally and a range of next generation sequencing, 
or NGS, platforms, and we have optimized our algorithms to enable laboratories around the world to run tests locally and 
access  our  algorithms  in  the  cloud  using  our  Constellation  platform.  We  sell  our  tests  directly  and  partner  with  other 
clinical  laboratories  to  distribute  our  tests  globally.  Currently,  all  of  our  products  other  than  our  Constellation  cloud 
software  product  are  laboratory  developed  tests,  or  LDTs.  We  perform  commercial  testing  in  our  CLIA-certified 
laboratories. 

Our Technology 

An illustration of the resolution that can be achieved with our mmPCR capability is provided below. The figures 
display data from our approximately 20,000 primer mmPCR assay, where each primer targets one SNP. On the left, the 
assay is applied to a large genomic DNA sample from a child. On the right, the assay is applied to a single cell from the 
same child. Each dot represents data from a particular SNP location on a chromosome. The assay measures the amount of 
each of the two possible sequences of nucleotides, or alleles, at each SNP. The plots below show the relative proportion 
of the two alleles, plotted along the vertical axis, for each of the approximately 20,000 SNPs, arranged sequentially along 
the vertical axis. The two alleles are arbitrarily labeled A and B, and each dot is colored according to the allelic contribution 
of the mother—red (A) or blue (B). Those SNPs where both copies of DNA in the child contain only the A allele are red 
and are found at the very top of the plot, and those SNPs where both copies of DNA in the child contain only the B allele 
are blue and are found at the very bottom of the plot. The SNPs where the fetus contains at least one copy of the A allele 
and one copy of the B allele are found near the center of the plot. The four vertical bars separated by dotted lines display 
data from chromosomes 13 (Patau syndrome), 18 (Edwards syndrome), 21 (Down syndrome) and X. For chromosomes 
13, 18 and X, the middle band is centered on 0.5; which indicates that for those SNPs, the child has one copy of the A 
allele  and  one  copy  of  a  B  allele  (and  therefore  a  relative  proportion  of  0.5),  and,  therefore,  has  the  right  number  of 
chromosomes—two. In this sample, an additional chromosome is present at chromosome 21, which indicates the presence 
of trisomy 21. For chromosome 21, the bands centered at 0.33 and 0.66 signal the additional nucleotides contributed by 
the mother. The band centered at 0.33 represents SNPs where the child has two copies of the B allele and one copy of the 
A allele, and the band centered at 0.66 represents SNPs where the child has two copies of the A allele and one copy of the 
B allele. The assay clearly quantifies the difference between single molecules of a particular allele at each SNP. The images 
demonstrate our ability to derive actionable information from tiny quantities of DNA, as the data from a single cell in the 
image on the right is nearly as informative as the data from a large genomic sample in the image on the left. 

7 

Our bioinformatics technology utilizes proprietary complex statistical techniques to combine the measurements 
of  our  molecular  assays  with  our  internal  databases  and  the  vast  and  growing  sources  of  publicly  available  genomic 
information to build highly detailed models of the genome of interest. As our patient volumes grow, our internal database 
of samples with genetic mutations and corresponding clinical outcomes further enhances our ability to interpret the clinical 
significance of complex genetic mutations. As the genomic data from the scientific community, such as from the Cosmic 
Database and the Cancer Genome Atlas, becomes richer, we can seamlessly integrate new clinical knowledge into our 
bioinformatics algorithm, driving further improvement in our tests.  

Women’s Health 

We provide testing to support a spectrum of women’s health needs, from family planning and prenatal testing to 

hereditary cancer screening.  

Panorama 

Panorama helps physicians assess the risk of fetal genetic abnormalities by non-invasively screening for fetal 
chromosomal  abnormalities,  including  Down  syndrome,  Edwards  syndrome,  Patau  syndrome,  Turner  syndrome  and 
triploidy,  which  often  result  in  intellectual  disability,  severe  organ  abnormalities  and  miscarriage.  Panorama  can  also 
identify fetal sex for single birth pregnancies as well as of each fetus in twin pregnancies. Panorama demonstrates the 
capabilities of our technology by employing our fundamentally unique approach of simultaneously measuring thousands 
of SNPs in a single test reaction to identify genetic variations in fetal DNA with a high degree of specificity and sensitivity, 
which we believe can give patients and their physicians a greater degree of comfort in choosing to forego unnecessary 
invasive  procedures,  limiting  the  resulting  risk  of  spontaneous  miscarriage  associated  with  invasive  procedures  and 
lowering  the  total  cost  to  the  healthcare  system  of  these  procedures.  Furthermore,  with  recent  technological  advances 
validated  in  our  SNP-based  Microdeletions  and  Aneuploidy  RegisTry  (SMART)  study  described  below,  Panorama 
leverages artificial intelligence to enable highly accurate results on samples for which a result would otherwise be difficult 
to determine. Panorama screens for common genetic conditions that affect both high-risk pregnancies, where maternal age 
is over 35 and which we estimate represent approximately 800,000 of the approximately 4.4 million pregnancies in the 
United States, and average-risk pregnancies, which we estimate represent approximately 3.6 million pregnancies in the 
United States. 

Panorama is performed on a maternal blood sample and can be performed as early as nine weeks into a pregnancy, 
which is significantly earlier than traditional methods, such as serum protein measurement whereby doctors measure the 
presence and amount of certain hormones in the blood. Panorama starts with a simple blood draw from the mother, either 
in a doctor’s office, in a laboratory or through a phlebotomist that travels to the patient, and the sample is sent to one of 
our CLIA-certified and CAP-accredited laboratories for processing. After Panorama generates its result, we provide the 

8 

 
 
 
 
doctor or the laboratory with a report showing whether there is a high risk or low risk that abnormalities are present in the 
fetus.  

The  analytic  and  clinical  validity  of  our  technology  demonstrated  in  NIPT  has  been  described  in  more  peer-
reviewed publications covering more patients than our competitors. Based on data published in Prenatal Diagnosis, Fetal 
Diagnosis and Therapy, Obstetrics & Gynecology, and the American Journal of Obstetrics and Gynecology, Panorama 
demonstrated greater than 99% overall sensitivity for aneuploidies on chromosomes 13 and 21 and triploidy and 98.2% 
sensitivity on chromosome 18, and specificity of greater than 99% for each disorder tested – which we believe makes it 
overall the most accurate NIPT commercially available in the United States. A paper published in Obstetrics & Gynecology 
reported that Panorama had a statistically significant lower false positive rate than other NIPT methods practiced by our 
U.S. competitors. Based on data published in Obstetrics & Gynecology, Prenatal Diagnosis, and American Journal of 
Obstetrics  &  Gynecology,  we  have  also  demonstrated  the  ability  to  identify  fetal  sex  more  accurately  than  competing 
NIPTs. This is partially a result of Panorama's unique ability to detect a vanishing twin, which is a known driver of fetal 
sex errors with quantitative methods used by our competitors. The American Journal of Obstetrics & Gynecology noted 
that the ability of Panorama to identify additional fetal haplotypes is expected to result in fewer false positive calls and 
prevent  incorrect  fetal  sex  calls.  A  study  reporting  on  the  use  of  Panorama  in  over  30,000  women,  published  in  the 
American Journal of Obstetrics & Gynecology, supported the use of NIPT as a first-line screening test for aneuploidy. 

Our  Panorama  microdeletions  panel  screens  for  five  of  the  most  common  genetic  diseases  caused  by 
microdeletions  –  22q11.2  deletion  syndrome  (DiGeorge  syndrome),  1p36  deletion,  Angelman  syndrome,  Cri-du-chat 
syndrome and Prader-Willi syndrome. 22q11.2 deletion syndrome can also be screened as an individual add-on without 
the other four microdeletions on the panel. Microdeletions are missing sub-chromosomal pieces of DNA, and can have 
serious health implications depending on the location of the deletion. Unlike Down syndrome, where the risk increases 
with maternal age, the risk of these five microdeletions is independent of maternal age. Based on data published in Prenatal 
Diagnosis and American Journal of Obstetrics & Gynecology, the combined prevalence of these targeted microdeletions 
is approximately one in 1,000 pregnancies, which collectively makes them more common than Down syndrome for women 
younger  than  approximately  28  years  of  age.  Diseases  caused  by  microdeletions  are  often  not  detected  via  common 
screening techniques such as ultrasound or hormone-based screening, yet the presence of a microdeletion can critically 
impact  postnatal  treatment.  For  example, when  learning  prior  to birth  that  a  newborn has 22q11.2 deletion  syndrome, 
doctors  will  know  to  monitor  the  infant  and  administer  calcium  if  needed  to  avoid  seizures  and  permanent  cognitive 
impairment, and will know to avoid administering routine vaccinations due to the immunodeficiency frequently associated 
with this condition. 

Panorama has demonstrated best-in-class performance in screening for microdeletions, achieving sensitivity of 
over 93% for all five of the microdeletions screened. In particular, the most common microdeletion – 22q11.2 deletion 
syndrome – was a focus of our SMART observational study, which evaluated the performance of SNP-based NIPT for 
22q11.2 deletion syndrome by tracking birth outcomes in the general population among over 18,000 women who presented 
clinically and elected Panorama microdeletions and aneuploidy screening as part of their routine care. The 22q11.2 deletion 
syndrome results from the SMART study, published in American Journal of Obstetrics and Gynecology in January 2022, 
demonstrated  sensitivity  of  83%,  clinical  PPV  of  approximately  53%,  and  a  false  positive  rate  of  0.05%  for  22q11.2 
deletion syndrome using our updated artificial intelligence algorithm.  

Panorama is also the only commercially available NIPT for twin pregnancies that can distinguish between each 
twin’s DNA, and therefore can determine zygosity, or whether the twins are identical or fraternal, and the fetal sex of each 
twin. Determining zygosity early in a pregnancy can help guide the management of a pregnancy, as certain monozygotic, 
or identical twin, pregnancies are at higher risk for various complications such as twin-twin transfusion syndrome, where 
there is an unequal sharing of blood, and therefore unequal growth, between the twins. Panorama screens twin pregnancies 
for  Down,  Edwards  and  Patau  syndromes  and,  for  identical  twins,  Turner  syndrome  and  22q11.2  deletion  syndrome, 
among others. In  validation  studies,  Panorama  identified  identical  twins with over  99%  sensitivity  and  specificity  and 
achieved a combined sensitivity of over 99% and specificity of over 99% for Down, Edwards and Patau syndromes in twin 
pregnancies. 

9 

Panorama’s commercial performance has been consistent with our initial validation data. Data published in the 
Journal of Clinical Medicine on over one million commercial cases of Panorama that were screened for Down, Edwards, 
Patau  and  Turner  syndromes  demonstrated  an  overall  PPV  of  90%  for  all  of  these  conditions  combined.  We  believe 
Panorama’s performance in commercial practice represents a significant improvement over first-generation NIPTs that 
rely on quantitative methods. Because Panorama does not require a reference chromosome, it is uniquely able to detect 
triploidy as well as full molar pregnancies. Panorama’s ability to differentiate between maternal and fetal DNA also allows 
Panorama  to  identify  the  presence  of  a  vanishing  twin,  as  well  as  maternal  abnormalities,  which  have  been  shown  in 
multiple studies to lead to false positives when using quantitative methods, particularly in the sex chromosomes where 
maternal abnormalities are common. 

Panorama has demonstrated substantial commercial success to date. We believe our test performance – including 
our continuous research, development and innovation to improve performance and efficiency – has allowed us to command 
a price premium compared to low-cost NIPTs while continuing to maintain growth in volume and revenue from Panorama. 

Horizon 

Horizon helps individuals and couples determine if they are carriers of genetic variations that cause certain genetic 
conditions. Depending  on  the  condition,  if one or  both parents  are  carriers,  it  could  result  in  a  child affected with  the 
condition. Many people do not know they are a carrier for an inherited genetic condition until they have an affected child. 
These conditions are often rare and usually there is no family history, and although certain condition are more common in 
certain ethnic groups, ethnicity may not be a reliable predictor of carrier status, as patients are increasingly of mixed or 
uncertain  ethnicities.  The  industry’s  approach  to  carrier  screening  has  accordingly  evolved  over  time,  from  screening 
targeting specific ethnicities with a higher incidence of screened conditions, to pan-ethnic screening for certain conditions 
based on incidence and clinical utility, and most recently to expanded screening for many conditions simultaneously.  

Horizon was created based on recommended screening guidelines from ACOG, ACMG, and the Victor Center 
for the Prevention of Jewish Genetic Diseases. Horizon screens for more than 200 inherited conditions, including Cystic 
Fibrosis, Duchenne Muscular Dystrophy, or DMD, Spinal Muscular Atrophy, Fragile X Syndrome and other conditions. 
The sample required for Horizon can be obtained simultaneously with the sample required for Panorama, which makes it 
easier for us to offer, and for patients to take, both tests. Horizon employs various methodologies to analyze the DNA from 
the individual’s blood or saliva sample to determine if the individual is a carrier for the genetic conditions being screened. 
These methodologies include next generation sequencing to detect single nucleotide variants, insertions and deletions, and 
copy number changes, and PCR fragment analysis to detect certain genetic variants.  

Other women’s health products 

While  Panorama  and  Horizon  represent  the  significant  majority  of  our  women’s  health  revenues,  we  offer  a 
portfolio of tests addressing reproductive and women’s health. Our Vistara single-gene NIPT screens for 25 single-gene 
disorders that cause severe skeletal, cardiac and neurological conditions which affect quality of life, are often associated 
with cognitive disabilities and could benefit from medical and/or surgical intervention. The conditions screened by Vistara 
have a combined incidence of approximately 1 in 600, which is higher than that of Down syndrome as well as Cystic 
Fibrosis; however, these conditions may otherwise go undetected until after birth or into childhood as traditional NIPTs 
do not screen for these conditions, prenatal ultrasound findings are not a reliable indicator, and family history is not a good 
indicator of risk for these conditions, which are commonly caused by new, and not inherited, mutations. Screening for 
these  conditions  early  in  a  pregnancy  can  facilitate  early  diagnosis,  enable  patients  to  be  referred  to  MFMs  and  other 
specialists for targeted evaluations, to guide labor and delivery management, and to allow families to mobilize resources, 
ask questions and anticipate future needs. We have received a CE Mark for Vistara from the European Commission. In 
validation studies, Vistara demonstrated a combined analytical sensitivity and analytical specificity of greater than 99%. 

Spectrum comprises our preimplantation genetic tests for couples undergoing IVF. Spectrum can improve the 
chance  of  a  successful  pregnancy  while  reducing  the  chance  of  miscarriage  or  of  having  a  child  with  a  chromosomal 
condition, by helping to identify the healthiest embryos during an IVF cycle. Spectrum PGT-A evaluates the number of 
chromosomes in embryos to detect extra or missing pieces of chromosomes prior to transfer of embryos created through 

10 

 
IVF procedures, which have a high rate of non-viable chromosomal abnormalities, known as aneuploidy. Couples that are 
at risk of having a child with an inherited genetic condition as a result of being carriers for that condition can also test for 
single gene conditions (PGT-M), which predicts which embryos are affected with specific genetic conditions; and PGT-
SR can be used to test for inherited translocations or inversions, or extra or missing chromosome pieces. This allows IVF 
physicians  to  select  and  transfer  chromosomally  normal  embryos.  In  particular,  aneuploidy  is  common  in  human 
embryos—particularly as women age—and is the primary cause of failed IVF. PGT-A has been shown to improve IVF 
outcomes  for  all  women,  regardless  of  maternal  age.  In  a  study  published  in  April  2018,  a  retrospective  analysis  of 
pregnancy  outcomes  demonstrated  that  use  of  Spectrum  during  IVF  led  to  increased  rates  of  implantation,  clinical 
pregnancy, and live births. The study findings also demonstrated that use of PGT-A can increase the use of single embryo 
transfer, which can reduce the risks of multiple pregnancies. Spectrum incorporates our proprietary technology to confirm 
parentage, determine the parental origin of the chromosomal abnormality, and further screen for uniparental disomy, in 
which two copies of a chromosome come from the same parent.  

Anora, our products of conception, or POC, test, analyzes miscarriage tissue from women who have experienced 
one or more pregnancy losses to determine whether there was an underlying chromosomal reason for the loss. Anora can 
detect  trisomy,  triploidy,  extra  or  missing  chromosome  pieces,  and  uniparental  disomy.  The  Anora  test  is  helpful  to 
obstetricians, gynecologists and IVF physicians in supporting their patients’ reproductive goals. Anora can help couples 
understand the likelihood of another miscarriage, their future reproductive options, and whether there are any steps that 
could help them avoid a miscarriage in future pregnancies.  

Empower,  our  hereditary  cancer  screening  test,  screens  for  certain  genes  associated  with  increased  risk  for 
common hereditary cancers, such as breast, ovarian, endometrial, and colorectal cancers. Information from the test can 
lead  to  earlier  detection  of  cancer,  identify  cancer  risk-reducing  strategies,  inform  surgical  and  therapeutic  decisions 
following  a  cancer  diagnosis,  and  provide  an  opportunity  to  notify  family  members  who  may  be  at  similar  risk  for 
hereditary cancer. 

Our non-invasive prenatal paternity product allows a couple to safely establish paternity without waiting for the 
child to be born. Testing can be done as early as nine weeks in gestation using a blood draw from the pregnant mother and 
alleged  father.  Our  internal  data  indicates  that  the  accuracy  of  this  test  is  greater  than  99.99%.  We  have  licensed  this 
technology to a third party to perform the test in its clinical laboratory.  

Oncology 

In oncology, we have been initially focused on detecting molecular residual disease, which we refer to as MRD, 
and recurrence monitoring in solid tumors, where we have generated data in over a dozen different cancer types and have 
published data in, among others, lung, bladder, colorectal and breast cancer, as well as multiple myeloma and other tumor 
types. Molecular residual disease is the presence of small traces of cancer in the blood, such as ctDNA or microscopic 
pieces of tumor DNA that are often undetectable with standard imaging techniques. If left untreated, residual cancer cells 
can multiply and cause recurrence. MRD testing and molecular monitoring offers the potential for physicians to change or 
escalate treatment in patients who are MRD-positive, and to de-escalate or avoid unnecessary treatment in patients who 
are MRD-negative. It also holds potential as a surrogate endpoint in clinical trials. Based on our internal estimates, we 
believe  that  the  total  addressable  market  in  the  United  States  for  recurrence  and  treatment  monitoring  for  solid  tumor 
cancers is over $15 billion. 

Signatera 

Signatera is our personalized ctDNA blood test for MRD assessment and surveillance of disease recurrence in 
patients previously diagnosed with cancer. Each patient receives a custom assay that tracks the presence of 16 tumor-
specific clonal mutations that are selected based on the unique mutational signature found in that patient’s tumor tissue, 
which is intended to maximize accuracy for detecting the presence or absence of residual disease in a blood sample, even 
at variant allele frequency, or VAF, of mutations as low as 0.01% in the blood. We believe this approach is optimal in the 
MRD setting, in which it is common for tumor DNA to be present only at low frequencies immediately after treatment. 
Unlike  static  liquid  biopsy  panels,  which  screen  for  a  generic  set  of  mutations  independent  of  an  individual’s  tumor, 

11 

 
Signatera is not intended to match patients with any particular therapy. Rather, it is intended to detect and assess how much 
cancer is left in the body, detect recurrence earlier, and help optimize treatment decisions. Signatera can detect residual 
disease earlier than clinical or radiological recurrence in patients with solid tumors who have received treatment.  

We launched Signatera in 2017 for research use only to cancer researchers and biopharmaceutical companies. 
Signatera was commercially launched in 2019 for clinical use as an LDT in our own CLIA-certified and CAP-accredited 
laboratory. We have received a final Medicare local coverage determination for the use of Signatera in patients with certain 
forms of colorectal cancer. We have also received a final Medicare local coverage determination for the use of Signatera 
in immunotherapy response monitoring for all tumor types in any patient for whom immunotherapy is indicated; this local 
coverage determination also creates a pathway for coverage of the use of Signatera in additional solid tumor types and 
indications,  where  it  is  clinically  validated  with  peer-reviewed  evidence  and  where  the  clinical  utility  is  established. 
Signatera has been granted three Breakthrough Device Designations by the FDA – for use in the post-surgical detection 
and quantification of ctDNA in patients previously diagnosed with certain types of cancer and in combination with certain 
drugs, and for use as a companion diagnostic to two cancer therapies. 

Signatera has been shown in various clinical studies to identify MRD significantly earlier than standard diagnostic 
tools, and that Signatera test status is a significant indicator of long-term patient outcomes after surgery and treatment, 
relative  to  other  clinical  and  pathological  factors.  Furthermore,  a  study  published  in  Clinical  Cancer  Research 
demonstrated the ability of Signatera to assess the rate of change in quantity over time, or velocity, of ctDNA in early-
stage colorectal cancer patients, providing additional information that may be used to predict patient survival and outcomes, 
further stratify MRD-positive patients, and inform disease management.  

In a clinical validation study conducted in collaboration with Aarhus University in Denmark, published in JAMA 
Oncology, Signatera detected relapse in patients with Stage II-III colorectal cancer an average of 8.7 months earlier than 
standard diagnostic tools. Patients who remained MRD-negative throughout the study had significantly reduced risk of 
relapse, as low as 3%. This study, along with another research collaboration with Aarhus University in locally advanced 
muscle invasive bladder cancer, published in Journal of Clinical Oncology, demonstrated the ability of Signatera to stratify 
patients by whether they are MRD positive or negative based on post-treatment presence or absence of ctDNA in the blood. 
In both the colorectal and bladder cancer studies, a positive Signatera test result after treatment was the strongest prognostic 
marker of disease recurrence and long-term patient outcomes, relative to all other risk factors. 

We  have  also  published  results  in  lung  cancer.  Our  technology  was  selected  for  use  in  Cancer  Research 
UK/University College London’s Tracking Cancer Evolution through Therapy (TRACERx) clinical trial for the multi-
year monitoring of patient-specific SNVs in plasma, to understand the evolution of cancer mutations over time, and to 
monitor patients for disease recurrence. Results from the first 100 early-stage lung cancer patients analyzed as part of the 
study were featured on the cover of the May 2017 issue of Nature and showed that an early prototype version of Signatera 
identified 43% more ctDNA-positive early-stage lung cancer cases than a generic lung cancer panel and demonstrated its 
potential to detect residual disease, measure treatment response, and identify recurrence an average of four months earlier 
than the standard of care, with a sensitivity of 93% at time of relapse.  

We  have  also  completed  multiple  studies  in  breast  cancer.  In  our  study  with  Cancer  Research  UK-funded 
researchers  at  Imperial  College  London  and  the  University  of  Leicester,  U.K. published  in  Clinical Cancer  Research, 
which included patients with all three of the key breast cancer subtypes (ER+, HER2+, and Triple Negative), Signatera 
detected molecular residual disease with a lead time of up to two years prior to clinical or radiological detection, and 
overall detected clinical relapse with a sensitivity of 89% at time of relapse. The Investigation of Serial Studies to Predict 
Your Therapeutic Response with Imaging and Molecular Analysis 2 (I-SPY 2) trial with the University of California, San 
Francisco and QuantumLeap Healthcare Collaborative, launched in 2010, was a multi-center study evaluating the safety 
and efficacy of investigational therapies combined with early treatment in women with newly diagnosed, locally advanced 
breast cancer. The results of this trial demonstrated that the change of measurable ctDNA from positive to negative during 
neoadjuvant treatment predicted therapeutic response, while failure to clear ctDNA after neoadjuvant treatment correlated 
with poor clinical outcomes. ctDNA levels were also associated with disease burden as determined by imaging. 

12 

We are currently conducting research across multiple cancer types in collaboration with various cancer centers 
and pharmaceutical companies. For example, Signatera was selected as the MRD test to be used in the Japan arm of the 
CIRCULATE-IDEA trial to evaluate ctDNA-guided treatment strategies for patients with Stage II-III colon cancer. We 
presented data on the first 1,040 patients from this study confirming prior data on the prognostic value of Signatera as an 
indicator of patient outcomes, as well as prognostic data indicating that Signatera may be predictive of treatment benefit 
and efficacy. We believe that these results may lead to the adoption of MRD testing into current medical practice as well 
as reimbursement of MRD testing in Japan. Signatera has also been selected to be used in the U.S. arm of CIRCULATE-
IDEA, also to evaluate ctDNA-guided treatment strategies for patients with Stages II and III colon cancer after resection. 
In addition, we are enrolling patients for BESPOKE CRC, a nationwide, multi-center, 1,000-patient registry study for 
patients diagnosed with Stage II-III colorectal cancer. The objective of the BESPOKE CRC study is to assess the impact 
of Signatera test results on changes in treatment decisions and clinical outcomes. 

Altera 

We have also expanded our efforts in oncology into therapy selection, which based on our internal estimates 
represents  an  approximate  $6  billion  market  opportunity.  We  have  launched  Altera,  our  tissue  based  comprehensive 
genomic profiling test that provides insight into genomic alterations and biomarkers found in a patient’s tumor, supporting 
treatment  decisions  and  therapy  selection  by  prioritizing  potentially  beneficial  therapies  based  on  the  patient’s  tumor 
biomarkers and cancer type. Altera can be ordered as a stand-alone test, as well as in conjunction with our Signatera MRD 
test to combine therapy selection with ongoing monitoring.  

Empower 

We plan to begin selling Empower, our hereditary cancer test, to oncologists through our oncology sales channel. 
Because  Empower  screens  for  genetic  mutations  in  genes  that  are  associated  with  increased  risk  of  certain  hereditary 
cancers, information from the test can help determine if a patient who has been diagnosed with such a cancer is a carrier 
of  a  mutation  associated  with  their  cancer.  This  can  inform  surgical  and  therapeutic  decisions,  as  well  as  provide  an 
opportunity to notify family members who may be at similar risk for hereditary cancer. 

Organ Health 

We began commercializing our first offering in organ health in 2020, with the launch of our Prospera Kidney test 
to assess active rejection in patients who have undergone kidney transplantation by measuring the fraction of dd-cfDNA 
in the recipient’s blood, which can spike relative to background cfDNA when the transplanted organ is injured due to 
immune rejection. In 2021 we launched our Prospera Heart and Prospera Lung tests, which use the same core technology 
to assess heart and lung transplants, respectively, as well as product enhancements to address various needs. The current 
tools  for  assessing  organ  transplant  rejection  are  either  invasive  (biopsies)  or  inaccurate  (serum  creatinine  for  kidney 
transplants), resulting in an unmet need for better diagnostic tools to monitor for allograft rejection and improve patient 
management  and  outcomes.  Many  patients  are  still  subjected  to  unnecessary  biopsies,  while  other  patients  remain 
undiagnosed in the case of subclinical rejection, which can increase the risk of graft failure. Our Prospera test is designed 
for use by physicians to help rule in or rule out active rejection when evaluating the need for diagnostic testing or the 
results  of  an  invasive  biopsy,  and  thereby  potentially  lowering  the  overall  costs  associated  with  transplant  care  and 
improving graft survival. We received a final Medicare local coverage determination for Prospera Kidney in December 
2019, covering all kidney transplant recipients, including those with multiple kidney transplants. Based on our internal 
estimates, we believe the total addressable market in the United States for tests such as ours that assess kidney, heart and 
lung transplant rejection is over $2.75 billion. 

Our  clinical  validation  study,  conducted  in  collaboration  with  the  University  of  California,  San  Francisco,  a 
recognized  leader  in  transplantation  care,  and  published  in  the  Journal  of  Clinical  Medicine,  demonstrated  strong 
performance of our mmPCR technology for detecting active rejection in patients with kidney transplants. In the blinded, 
retrospective  study,  we  leveraged  our  SNP  technology  to  measure  dd-cfDNA  levels  in  plasma  samples  from  kidney 
transplant patients, including patients experiencing active rejection. Our assay demonstrated 89% sensitivity in detecting 

13 

 
active rejection, with specificity of 73%, based on a cutoff of 1% dd-cfDNA. The assay performed particularly well in 
detecting T-cell mediated rejection (TCMR) and subclinical rejection, both of which we believe are areas of unmet need. 

In an analytical validation study published in the February 2019 issue of Transplantation, our assay demonstrated 
superior precision, up to 5 times better than the competing dd-cfDNA assay. Precision is a measure of the test’s ability to 
produce the same result when a single sample is tested repeatedly. This study also included donor-recipient pairs that were 
related, such as parents or siblings, as well as those that were not related. This is significant because an estimated 52% of 
live kidney donations are from a biological relative of the patient, but it is technically challenging to differentiate between 
DNA  patterns  of  close  relatives.  We  were  able  to  achieve  a  high  degree  of  accuracy  in  these  challenging  cases  by 
leveraging our experience with SNP-based methods in the reproductive health setting. Furthermore, we recently launched 
an update to Prospera Kidney to further improve test performance by reporting, in addition to the fraction of dd-cfDNA, 
the quantity of dd-cfDNA and total cfDNA; in a study published in the Journal of the American Society of Nephrology of 
41 kidney transplant patients, incorporating these additional two metrics improved the sensitivity of the Prospera test from 
detecting 7/9 cases of active rejection to detecting 9/9 cases.  

We are currently enrolling participants for several studies. Among others, our ProActive registry study, one of 
the  industry’s  largest  known  prospective  studies  to  date  incorporating  dd-cfDNA  testing  into  medical  management  of 
organ transplant recipients, is expected to enroll 3,000 kidney transplant patients from the time of surgery, and will measure 
changes in biopsy usage and clinical outcomes based on physician-directed use of the Prospera test to rule in or rule out 
active rejection. We have also been selected to participate in a global, prospective multicenter study in collaboration with 
Molecular Microscope Diagnostic System, in which 1,000 patients will be evaluated on the basis of clinical information, 
cfDNA  measures,  biopsies,  molecular  microscope,  evaluations,  and  donor-specific  antibodies  to  assess  the  potential 
benefits of integrated data analysis in managing kidney transplantation. We are also enrolling participants in a study to 
determine the utility of Prospera in multiple organ transplant patients by evaluating 400 kidney-liver, kidney-pancreas and 
kidney-heart patients. 

Constellation 

Our Constellation software forms the core of our cloud-based distribution model. Through this model, we have 
been able to expand access to our molecular and bioinformatics capabilities worldwide, enabling laboratories, under a 
license from us, to run the molecular workflows themselves and then access our computation-intensive bioinformatics 
algorithms through Constellation, which runs in the cloud, to analyze the results. We currently have licensing contracts 
with various laboratories in the United States and internationally who are using our Constellation platform commercially 
in NIPT and in prenatal paternity testing, and we plan to expand this distribution model to other products in the future. We 
also leverage Constellation to perform our internal commercial laboratory activities and research and development of our 
products. 

We  have  received  CE  Marks  from  the  European  Commission  for  our  Constellation  software  and  for  the  key 
reagents that our laboratory licensees use to run their NIPT test prior to accessing our Constellation software. These CE 
Marks enable us to offer Constellation in the European Union and other countries that accept a CE Mark. We are pursuing 
other regulatory approvals, as needed, to allow the international roll out of Constellation in regions that do not accept a 
CE Mark. 

Commercial Capabilities 

We have established a broad distribution channel, comprising our direct sales efforts and, for our women’s health 
and Signatera products, a worldwide network of over 100 laboratory and distribution partners. Our own direct sales force 
and managed care teams anchor our commercial engagement with physicians, laboratory partners, and payers, and sell 
directly  to  MFMs,  OB/GYNs,  physicians  or  physician  practices,  IVF  centers,  transplant  centers,  or  integrated  health 
systems.  

Where possible, we aim to maximize sales opportunities by educating the physician practices on the benefits of 
combining complementary tests from our portfolio of products. For example, in women’s health, Panorama NIPT, our 

14 

 
Panorama microdeletions panel, Vistara single-gene NIPT, and Horizon together can provide valuable information for 
pregnant women who have not had a carrier screen at the time they are ready to have an NIPT performed; these tests can 
all be run using one blood draw from the mother and can be ordered on one requisition form and with one shipment of the 
patient’s  samples  by  the  physician.  Also,  because  of  the  importance  and  demand  for  screening  for  22q11.2  deletion 
syndrome, we have made that feature available as part of our basic Panorama panel, or as part of a broader microdeletions 
panel. In the year ended December 31, 2021, approximately three-quarters of customers who ordered the basic Panorama 
panel  directly  from  us  also  ordered  screening  for  22q11.2  deletion  syndrome  or  the  full  microdeletions  panel,  and 
approximately one-third of customers who ordered Panorama directly from us also ordered Horizon carrier screening.  

In  addition  to  our  sales  force,  we  market  to  physicians  through  clinical  journals,  educational  webinars, 
conferences, tradeshows and e-mail marketing campaigns. While we currently do not sell directly to patients, we do engage 
in brand awareness campaigns directed at patients to highlight our products. Our marketing and medical science liaison 
teams work extensively with key opinion leaders in the reproductive health, oncology and organ health fields.  

Our  partners’  capabilities  augment  our  direct  sales  capabilities,  and  where  we  have  identified  laboratory  or 
distribution partners who share our focus on premium quality and service, we also contract with them to distribute our 
tests. In NIPT, we have partnered with leading academic and commercial laboratories and hospital systems in the United 
States  to  capitalize  on  their  relationships  with  MFMs  and  OB/GYNs,  large  distribution  capabilities,  and  commercial 
infrastructure. These distribution partners also frequently have in-network contracts with key third-party payers. As of 
December 31, 2021, we had in-network contracts with insurance providers that accounted for over 230 million covered 
lives in the United States. We continue our efforts to increase the number of our in-network contracts with payers. Our 
target  market  for  NIPT  is  a  much  smaller  subset  of  these  covered  lives,  because  it  excludes  men,  children  and  post-
menopausal women who would not  be users  of  the  majority  of our products.  Outside  of  the United  States,  where our 
products are sold in over 80 countries, we currently sell predominantly through partner laboratories.  

Enhanced User Experience  

NateraCore  is  our  suite  of  resources  designed  to  enhance  the  patient  and  provider  experience.  Through  this 
platform, we provide patient and provider educational materials, information about insurance coverage and test costs, test 
and phlebotomy, or blood draw, ordering capabilities, test results reporting, and next steps, in each case as applicable to a 
particular patient or test. These resources make available a completely remote testing option for patients, fulfilled through 
our online tools combined with a nationwide mobile phlebotomy network whereby a patient can request and schedule a 
phlebotomist visit at the patient’s home or office. This capability has proven to be especially important during the COVID-
19 pandemic, enabling continuity of care for all patients and particularly for those who may be immunocompromised or 
immune-suppressed.  

We have also created provider portals for clinicians in each of women’s health, oncology and organ health, which 
enable physicians to easily complete various tasks online such as ordering and tracking tests, managing patient consents 
and results, accessing billing and other documentation, connecting with genetic counselors and other support, and ordering 
supplies and educational materials. We also provide a service to integrate with our customers’ Electronic Medical Records, 
or EMR, systems to provide physicians a seamless experience of ordering tests and reviewing patient test results directly 
through their EMR systems. 

We  have  a  team  of  board-certified  genetic  counselors  to  support  patients  with  pre-  and  post-test  genetic 

information sessions, and physicians should they have any questions or require any support in interpreting the results.  

In addition to our mobile phlebotomy service, we have a network of over 2,000 phlebotomy centers across the 

United States.  

15 

Key Relationships  

Illumina 

We are party to a supply agreement with Illumina, Inc., or Illumina, for the supply of Illumina genetic sequencing 
instruments and reagents for NIPT, oncology and transplant diagnostic testing. For oncology, we also received rights to 
develop and sell in vitro diagnostic kits and services worldwide, in exchange for which we agreed to make certain milestone 
and royalty payments to Illumina. During the term of the supply agreement, which expires in August 2033, Illumina has 
agreed to supply us with sequencers, reagents and other consumables for use with the Illumina sequencers, and we must 
provide a forecast, on a monthly basis, detailing our needs for certain of the Illumina products. The first four calendar 
months of each forecast are binding and the fourth month can vary by only up to 25% more or less than what was forecasted 
for that month in the prior month's forecast. In addition, during each calendar quarter, we must spend a minimum amount 
on reagents under this agreement. We and Illumina have agreed on prices for the sequencers and reagents, for which we 
are entitled to certain discounts based on total spend and other factors. Illumina has the right to adjust these prices under 
certain conditions. Illumina may not increase pricing for products currently supplied to us as of October 2021, or new 
versions of such products, subject to certain exceptions, and excluding new versions of products that result in material 
improvements in performance and capability. The agreement states Illumina will provide volume-based pricing that is no 
less favorable pricing than volume-based pricing offered by Illumina to other similarly situated customers or to GRAIL, 
LLC, an Illumina affiliate. In addition, we must pay a fee to Illumina for each clinical NIPT test that we perform using 
Illumina reagents. Illumina is currently the sole supplier of our sequencers and related reagents for many of our tests, along 
with certain hardware and software. Illumina is prohibited under the supply agreement from discontinuing products that 
we  continue  to  purchase  from  Illumina,  subject  to  certain  exceptions.  We  are  not  bound  to  use  exclusively  Illumina's 
sequencing  instruments  and  reagents  for  conducting  our  sequencing,  but  if  we  use  other  sequencing  instruments  and 
reagents for more than specified percentages of our total NIPT clinical volume, we may no longer be entitled to volume-
based discounts from Illumina.  

Illumina may terminate the agreement upon the following circumstances: if we materially breach the agreement 
and fail to cure such breach within 60 days after receiving written notice of such breach, and only after complying with 
additional notice provisions; if we become the subject of certain bankruptcy or insolvency proceedings; or in connection 
with certain changes of control of Natera. Illumina also has the right to terminate: (a) certain rights under the agreement 
upon two years’ prior notice; and (b) our rights with respect to IVDs if we have not obtained a premarket approval for at 
least one IVD from the United States Food and Drug Administration by June 8, 2026, unless we are diligently pursuing 
approval of an active PMA application at such time. We may terminate the agreement: if Illumina materially breaches the 
agreement  and  fails  to  cure  such  breach  within  60  days  after  receiving  written  notice  of  such  breach,  and  only  after 
complying  with  additional  notice  provisions;  if  Illumina  becomes  the  subject  of  certain  bankruptcy  or  insolvency 
proceedings; in connection with certain supply failures by Illumina; or for convenience with a specified period of advance 
written notice. The agreement also contains use limitations, representations and warranties, indemnification, limitations of 
liability and other provisions.  

Competition  

The  markets  in  which  we  operate  are  characterized  by  innovation  and  rapid  change,  and  we  primarily  face 
competition  from  various  companies  that  develop  and  commercialize  molecular  diagnostic  tests  in  women’s  health, 
oncology, and organ transplant rejection.  

Our competitors in the NIPT space include Sequenom, Inc., or Sequenom, which was acquired by Laboratory 
Corporation of America Holdings, or LabCorp; Illumina, through its subsidiary Verinata; Myriad Genetics, Inc., which 
acquired  Counsyl,  Inc.;  Invitae  Corp.;  Quest  Diagnostics  Incorporated,  or  Quest;  Premaitha  Health  PLC;  BGI;  Bio-
Reference, a business unit of OPKO Health, Inc. and which acquired Ariosa, Inc.; NxGen; BillionToOne Inc.; PerkinElmer 
Inc.; and Mount Sinai Genomics, Inc. d/b/a Sema4. We also compete against companies providing carrier screening tests 
such  as  LabCorp;  Myriad  Genetics,  Inc.;  Sema4;  Invitae  Corp.;  BillionToOne  Inc.;  Quest;  NxGen;  GeneDx,  Inc.,  a 
subsidiary of Bio-Reference; and GenPath Diagnostics, a business unit of Bio-Reference. Each of these companies offers 
comprehensive carrier screening panels. 

16 

In the field of ctDNA-based MRD assessment and recurrence surveillance, we compete with various companies 
that  offer  or  seek  to  offer  competing  solutions,  such  as  Roche  Diagnostics,  Guardant  Health,  Inc.,  Adaptive 
Biotechnologies, Personal Genome Diagnostics, Inc., which has entered into an agreement to be acquired by Labcorp, one 
of  our  primary  competitors  in  both  NIPT  and  carrier  screening,  Exact  Sciences  Corp.,  Inivata, Inc.,  which  has  been 
acquired  by  NeoGenomics,  Inc., and  ArcherDX,  Inc.,  which  has  been  acquired  by  Invitae  Corp.,  one  of  our  primary 
competitors in both NIPT and carrier screening.  

In organ health, our competitors include CareDx, Inc. and Eurofins Viracor, Inc.  

We expect additional competition as other established and emerging companies enter these markets, including 
through business combinations, and as new tests and technologies are introduced. These competitors could have greater 
technological, financial, reputational and market access resources than us.  

We believe the principal competitive factors in our molecular diagnostic testing markets include the following: 

• 

• 

• 

• 

• 

• 

• 

• 

• 

• 

• 

test performance, as demonstrated in clinical and analytical studies and clinical trials as well as in commercial 
experience; 

comprehensiveness of coverage and ease of use, including user experience for both patients and providers; 

value of product offerings, including pricing and impact on other healthcare spending;    

scope and extent of reimbursement and payer coverage;   

effectiveness of sales and marketing efforts;   

breadth of distribution of products and partnership base;   

reputation among patients and providers for development and introduction of new, innovative products;   

operational execution, including test turn-around time and test failures;    

key opinion leader support;   

brand awareness; and   

ease of integration for laboratories, including for cloud-based distribution models. 

Specific market share data regarding our products is not publicly available, and consumers may choose to use 
competing products for a variety of reasons, including lower cost. We believe, however, that we compete favorably on the 
basis of several factors, particularly test performance, comprehensiveness of coverage of conditions or indications, our 
commercial capabilities and effectiveness of sales and marketing efforts, and user experience.    

17 

 
 
 
 
 
 
 
 
 
 
Intellectual Property  

Our success and ability to compete depend in part on securing and preserving enforceable patent, trade secret, 
trademark  and  other  intellectual  property  rights;  operating  without  having  competitors  infringe,  misappropriate  or 
otherwise  circumvent  these  rights;  operating  without  infringing  the  proprietary  rights  of  others;  and  obtaining  and 
maintaining licenses for technology development and/or product commercialization. As of December 31, 2021, we held 
over 100 issued U.S. and foreign patents, which expire between November 2026 and February 2038, and over 200 pending 
U.S. and foreign patent applications. Our patents and patent applications relate generally to molecular diagnostics, and 
more  specifically  to  biochemical  and  analytical  techniques  for  obtaining  and  analyzing  genetic  information  to  detect 
genetic abnormalities in relatively small complex samples, such as cell free fetal DNA or circulating tumor DNA. We 
intend to seek patent protection as we develop new technologies and products in this area. 

We are or have recently been engaged in patent infringement lawsuits and other intellectual property disputes 
against various competitors in each of the industries in which we operate, some of which are infringement claims against 
us  and  some  of  which  are  claims  we  have  asserted  against  third  parties,  as  discussed  in  “Note 8—Commitments  and 
Contingencies—Legal Proceedings” in the Notes to Consolidated Financial Statements. We may become subject to and/or 
initiate future intellectual property litigation as our product portfolio, and the level of competition in our industry segments, 
grow. The field of molecular diagnostics is complex and rapidly evolving, and we expect that we and others in our industry 
will continue to be subject to third-party infringement claims. 

Reimbursement  

We receive reimbursement for our tests from third-party payers, which includes commercial health insurers and 
government health benefits programs (such as Medicare and Medicaid). Laboratory tests, as with most other health care 
services, are classified for reimbursement purposes under a coding system known as Current Procedure Terminology, or 
CPT, which we and our customers must use to bill and receive reimbursement for our diagnostic tests. There are CPT 
codes associated with the particular tests that we provide to the patient. Once the American Medical Association, or AMA, 
establishes a CPT code, the Centers for Medicare & Medicaid Services, or CMS, establishes payment levels and coverage 
rules  under  Medicare,  while  state  Medicaid  programs  and  commercial  health  plans  establish  rates  and  coverage  rules 
independently in accordance with applicable rules. As such, the reimbursement rates for our diagnostic tests vary by third-
party payer. 

For most of the covered tests performed for Medicare or Medicaid beneficiaries, we are required to bill Medicare 
or Medicaid directly, and to accept Medicare or Medicaid reimbursement as payment in full. Prior to 2015, CMS had 
implemented a set of CPT codes without a fee schedule for most codes specific to NIPTs; a CPT code specific to NIPT 
for aneuploidies has been effective since January 2015, and a CPT code for microdeletions has been effective since January 
2017. CMS has established a pricing benchmark of $802 for aneuploidy and microdeletions testing. In addition, a CPT 
code  for  expanded  carrier  screening  tests  went  into  effect  in  January  2019,  for  which  CMS  has  established  a  pricing 
benchmark of approximately $2,450.  

The Protecting Access to Medicare Act of 2014, or PAMA, introduced a multi-year pricing program and new 
payment methodology to calculate the rates for tests listed under the CLFS that are reimbursable by Medicare Part B.  
Under the new payment methodology, the Medicare Part B CLFS payment rate is derived from a volume-weighted median 
of private payer rates for tests. This requires an “applicable laboratory” to report to CMS the private payment rates and the 
volume of tests associated with each payment rate for a specific data reporting period.  We are required under PAMA to 
report  to  CMS  the  private  payment  rates  and  the  volume  of  tests  which  are  covered  under  Medicare  Part  B.    PAMA 
authorizes  CMS  to  impose  civil  monetary  penalties  of  up  to  $10,000  per  day  for  each  failure  to  report  or  each 
misrepresentation or omission in reporting Applicable Information. 

We currently submit for reimbursement using CPT codes based on the guidance of coding experts and outside 
legal counsel. There is a risk that these codes may be rejected or withdrawn or that third-party payers will seek refunds of 
amounts that they claim were inappropriately billed to a specific CPT code or an incorrect diagnosis code. We do not 
currently have a specific CPT code assigned for all of our tests, and there is a risk that we may not be able to obtain specific 

18 

 
codes for such tests, or if obtained, we may not be able to negotiate favorable rates for one or more of these codes. In 
particular, while we have obtained a CPT code for microdeletions and CMS has set a price for microdeletions testing, we 
have experienced low average reimbursement rates for microdeletions testing under this code, and we expect that this code 
will continue to cause our microdeletions reimbursement to remain low, at least in the near term, because third-party payers 
are declining to reimburse under the new code or reimbursing at a much lower rate than we had previously received before 
the CPT code was established. The reimbursement rates for our broader Horizon screening panel have also declined as a 
result of the new CPT code becoming effective in 2019, as carrier screening tests that had previously been reimbursed on 
a per-condition basis may be reimbursed as a combined single panel instead of as multiple individual tests.  

We  believe  that  growing  recognition  from  professional  societies  of  the  importance  of  microdeletions  testing, 
combined with the performance of our microdeletions test and additional validation data from our SMART study that we 
have recently published on the sensitivity and specificity of our tests, will help drive broader reimbursement in the future. 

Reimbursement by third-party payers may depend on a number of factors, including the payer’s determination 
that tests using our technologies are: not experimental or investigational; medically necessary; demonstrated to lead to 
improved patient outcomes; appropriate for the specific patient; cost-saving or cost-effective; supported by peer-reviewed 
medical journals; and included in clinical guidelines. In making coverage determinations, third-party payers often rely on 
practice  guidelines  issued  by  professional  societies.  NIPT  has  received  positive  coverage  determinations  for  high-risk 
pregnancies  and  in  such  instances  are  reimbursed  by  most  commercial  health  insurers,  including  United  Healthcare, 
AETNA, Anthem, Humana, CIGNA and others. The use of NIPT for average-risk pregnancies has not historically been 
well reimbursed by third-party payers; however, professional societies now generally acknowledge that NIPT is the most 
sensitive screening option for, and/or are generally supportive of, NIPT in average-risk pregnancies, in addition to high-risk 
pregnancies. There has been a significant increase in the number of commercial health insurers, representing approximately 
95% of commercially covered lives in the United States, that cover the use of Panorama in the average-risk population, as 
well as an increasing number of state Medicaid programs with a positive coverage determination for NIPT for average-
risk pregnancies. 

As of December 31, 2021, we and our laboratory distribution partners had in-network contracts with commercial 
health plans that accounted for over 230 million covered lives in the United States. Our target market for NIPT is a much 
smaller subset of these covered lives, because it does not include men, children and post-menopausal women who would 
not be users of our tests. 

Government Regulations  

Our business is subject to and impacted by extensive and frequently changing laws and regulations in the United 
States (at both the federal and state levels) and internationally. These laws and regulations include regulations particular 
to our business and laws and regulations relating to conducting business generally (e.g., export controls laws, U.S. Foreign 
Corrupt Practices Act and similar laws of other jurisdictions). We also are subject to inspections, audits and other inquiries 
by certain federal and state governmental agencies, including informal requests for documents, civil investigative demands, 
and subpoenas. Set forth below are highlights of certain key regulatory schemes applicable to our business. 

FDA  

In the United States, medical devices are subject to extensive regulation by the FDA under the Federal Food, 
Drug, and Cosmetic Act, or FDC Act, and its implementing regulations, and other federal and state statutes and regulations. 
The laws and regulations govern, among other things, medical device development, testing, labeling, storage, premarket 
clearance or approval, advertising and promotion and product sales and distribution. To be commercially distributed in the 
United States, medical devices must receive from the FDA prior to marketing, unless subject to an exemption, clearance 
of a premarket notification, or 510(k), premarket approval, or a PMA, or a de novo authorization. 

IVDs  are  a  type  of  medical  device  that  can  be  used  in  the  diagnosis  or  detection  of  diseases  or  conditions, 
including assessment of state of health, through collection, preparation and examination of specimens from the human 
body. IVDs can be used to detect the presence of certain chemicals, genetic information or other biomarkers related to 

19 

 
health or disease. IVDs include tests for disease prediction, prognosis, diagnosis, and screening (e.g., carrier screening).  
A subset of IVDs are known as analyte specific reagents, or ASRs. An ASR is a single reagent that, through specific 
binding  or  chemical  reaction  with  substances  in  a  specimen,  is  intended  for  use  in  a  diagnostic  application  for  the 
identification and quantification of an individual chemical substance in biological specimens. Most ASRs are exempt from 
the premarket review processes but must comply with some quality system regulation, or QSR, provisions and other device 
requirements. 

The FDC Act classifies medical devices into one of three categories based on the risks associated with the device 
and the level of control necessary to provide reasonable assurance of safety and effectiveness. Class I devices are deemed 
to be low risk and are subject to the fewest regulatory controls. Many Class I devices are exempt from FDA premarket 
review requirements. Class II devices, including some software products to the extent that they qualify as a device, are 
deemed  to  be  moderate  risk,  and  generally  require  clearance  through  the  premarket  notification,  or  510(k)  clearance, 
process. Class III devices are generally the highest risk devices and are subject to the highest level of regulatory control to 
provide reasonable assurance of the device's safety and effectiveness. Class III devices typically require a PMA by the 
FDA before they are marketed. A clinical trial is almost always required to support a PMA application and is sometimes 
required for 510(k) clearance. All clinical studies of investigational devices must be conducted in compliance with any 
applicable  FDA  and  Institutional  Review  Board  requirements.  Devices  that  are  exempt  from  FDA  premarket  review 
requirements must nonetheless comply with post-market general controls as described below, unless the FDA has chosen 
otherwise. 

510(k)  clearance  pathway.  To  obtain  510(k)  clearance,  a  manufacturer  must  submit  a  premarket  notification 
demonstrating to the FDA's satisfaction that the proposed device is substantially equivalent to a previously 510(k)-cleared 
device  or  to  a  device  that  was  in  commercial  distribution  before  May  28,  1976  for  which  the  FDA  has  not  called  for 
submission of a PMA application. The previously cleared device is known as a predicate. The FDA's 510(k) clearance 
pathway usually takes from three to 12 months from submission, but it can take longer, particularly for a novel type of 
product. In addition, the COVID-19 pandemic has resulted in significant workload increases within the Center for Devices 
and Radiological Health that could affect 510(k) review timelines. 

PMA  pathway.  The  PMA  pathway  requires  proof  of  the  safety  and  effectiveness  of  the  device  to  the  FDA's 
satisfaction. The PMA pathway is costly, lengthy, and uncertain. A PMA application must provide extensive preclinical 
and clinical trial data as well as information about the device and its components regarding, among other things, device 
design, manufacturing, and labeling. As part of its PMA review process, the FDA will typically inspect the manufacturer's 
facilities for compliance with QSR requirements, which impose elaborate testing, control, documentation, and other quality 
assurance procedures. The PMA review process typically takes one to three years from submission but can take longer, 
including, as noted above, due to delays resulting from the COVID-19 pandemic.  

De  novo  pathway.  If  no  predicate  device  can  be  identified,  a  device  is  automatically  classified  as  Class  III, 
requiring a PMA application. However, the FDA can reclassify, or use “de novo classification,” for a device for which 
there was no predicate device if the device is low- or moderate-risk. If the device is reclassified as Class II, the FDA will 
identify “special controls” that the manufacturer must implement, which may include labeling, performance standards or 
other requirements. Subsequent applicants can rely upon the de novo product as a predicate for a 510(k) clearance, unless 
FDA exempts subsequent devices from the need for a 510(k). The de novo route is intended to be less burdensome than 
the PMA process. In October 2021, the FDA issued final regulations codifying FDA’s expectations for de novo requests, 
which went into effect in January 2022.  In October 2021, FDA also issued updated and final guidance on the de novo 
request and classification process, for the purpose of providing clarity and transparency regarding the de novo classification 
process.  

The  de  novo  route  has  historically  been  used  for  many  IVD  products.  The  FDA  has  indicated  to  us  that  our 
software that enables our cloud-based distribution model may be appropriate for review under the de novo classification 
process. However, the FDA has not committed to this position and may take a different position in the future. 

Post-market general controls. After a device, including a device exempt from FDA premarket review, is placed 
on the market, numerous regulatory requirements apply. These include: the QSR, labeling regulations, registration and 

20 

 
listing, the Medical Device Reporting regulation (which requires that manufacturers report to the FDA if their device may 
have caused or contributed to a death or serious injury or malfunctioned in a way that would likely cause or contribute to 
a death or serious injury if it were to recur), and the Reports of Corrections and Removals regulation (which requires 
manufacturers to report to the FDA corrective actions made to products in the field, or removal of products once in the 
field if such actions were initiated to reduce a risk to health posed by the device or to remedy a violation of the FDC Act). 
Depending on the severity of the legal violation that led to correction or removal, the FDA may classify the manufacturer’s 
action as a recall. 

The FDA enforces compliance with its requirements through inspection and market surveillance. If the FDA finds 
a violation, it can institute a wide variety of actions, ranging from an untitled or public warning letter to enforcement 
actions such as fines, injunctions, and civil penalties; recall or seizure of products; operating restrictions, partial suspension 
or total shutdown of production; refusing requests for 510(k) clearance or PMA approval of new products; withdrawing 
PMAs  already  granted;  and  criminal  prosecution.  For  additional  information,  see  “Risk  Factors—Reimbursement  and 
Regulatory Risks Related to Our Business.”  

Research use only. Research use only, or RUO, products are exempt from FDA medical device requirements 
provided their manufacturers comply with specified labeling and restrictions on distribution. The products must bear the 
statement: “For Research Use Only. Not for Use in Diagnostic Procedures.” Manufacturers of RUO products cannot make 
any claims related to safety, effectiveness or diagnostic utility, and RUO products cannot be intended by the manufacturer 
for clinical diagnostic use. An RUO product promoted for diagnostic use may be viewed by the FDA as adulterated and 
misbranded under the FDC Act and is subject to FDA enforcement activities. Our LDTs use instruments and reagents 
labeled as RUO.  

Laboratory-developed tests. The FDA considers LDTs to be tests that are designed, developed, validated and 
used within a single laboratory. The FDA historically has taken the position that it has the authority to regulate such tests 
as medical devices under the FDC Act but has for the most part exercised enforcement discretion and has not required 
clearance or approval of LDTs prior to marketing.  

In  2014,  the  FDA  issued  two  draft  guidance  documents  regarding  oversight  of  LDTs.  These  draft  guidance 
documents proposed more active review of LDTs. The draft guidances were the subject of considerable controversy, and 
in 2016, the FDA announced that it would not be finalizing the 2014 draft guidance documents. Subsequently, in 2017, 
the FDA issued a discussion paper which laid out elements of a possible revised future LDT regulatory framework, but 
did not establish any regulatory requirements.  

The FDA’s efforts to regulate LDTs have prompted the drafting of legislation governing diagnostic products and 
services that has sought to substantially revamp the regulation of both LDTs and IVDs. Congress may still act to provide 
further direction to the FDA on the regulation of LDTs and substantially modify the regulation of IVDs.  

In August 2020, the Department of Health and Human Services, or HHS, announced that FDA would not require 
premarket review of LDTs absent notice-and-comment rulemaking, and rescinded FDA guidance documents and other 
informal statements concerning premarket review of LDTs. The HHS announcement did not define the term LDT. In an 
accompanying FAQ document, HHS stated that, while LDTs are not subject to premarket review, FDA may still regulate 
LDTs under the Public Health Service Act. In November 2021, HHS withdrew its LDT policy, which allowed FDA to 
resume  its  historical  approach  to  LDT  oversight.  FDA  thereafter  began  requiring  submission  of  emergency  use 
authorization, or EUA, requests, for COVID-19 LDTs. FDA has not indicated its intent to regulate other, non-COVID, 
LDTs since HHS withdrew the policy. We believe that other than the RUO version of Signatera, all of the tests we currently 
offer, including Panorama, meet the definition of LDTs, as they have been designed, developed, and validated for use in a 
single CLIA-certified laboratory. If our tests are LDTs, then, based on FDA’s historical approach, we believe they are 
currently subject to FDA enforcement discretion. 

Clinical Laboratory Improvement Amendments of 1988 and State Regulation  

21 

As a clinical laboratory, we are required to hold certain federal and state licenses, certifications and permits to 
conduct  our  business.  As  to  federal  certifications,  in  1988,  Congress  passed  the  Clinical  Laboratory  Improvement 
Amendments of 1988, or CLIA, establishing more rigorous quality standards for all commercial laboratories that perform 
testing on human specimens for the purpose of providing information for the diagnosis, prevention, or treatment of disease 
or the assessment of the health or impairment of human beings. CLIA requires such laboratories to be certified by the 
federal government and mandates compliance with various operational, personnel, facilities administration, quality and 
proficiency testing requirements intended to ensure the accuracy, reliability and timeliness of patient test results. CLIA 
certification is also a prerequisite to be eligible to bill state and federal healthcare programs, as well as many commercial 
third-party payers, for laboratory testing services. 

Our laboratories located in Austin, Texas and in San Carlos, California are CLIA certified, and must comply with 
all applicable CLIA requirements. If a clinical laboratory is found to be out of compliance with CLIA standards, CMS 
may impose sanctions, limit or revoke the laboratory’s CLIA certificate (and prohibit the owner, operator or laboratory 
director  from  owning,  operating,  or  directing  a  laboratory  for  two  years  following  license  revocation),  subject  the 
laboratory to a directed plan of correction, on-site monitoring, civil monetary penalties, civil actions for injunctive relief, 
criminal penalties, or suspension or exclusion from the Medicare and Medicaid programs. 

CLIA provides that a state may adopt laboratory licensure requirements and regulations that are more stringent 
than  those  under  federal  law,  and  requires  compliance  with  such  laws  and  regulations.  A  number  of  states  have 
implemented their own more stringent laboratory regulatory requirements. State laws may require the laboratory to obtain 
state  licensure  and/or  laboratory  personnel to  meet  certain  qualifications,  specify  certain  quality  control  procedures  or 
facility requirements, or prescribe record maintenance requirements. Moreover, several states impose the same or similar 
state requirements on out-of-state laboratory testing specimens collected or received from, or test results reported back to, 
residents within that state. Therefore, we are required to meet certain laboratory licensing requirements for those states in 
which we offer services or from which we accept specimens and that have adopted regulations beyond CLIA. For more 
information  on  state  licensing  requirements,  see  “—California  Laboratory  Licensing”,  “—New  York  Laboratory 
Licensing,” and “—Other State Laboratory Licensing Laws.” 

Our laboratories have each also been accredited by the College of American Pathologists, or CAP, which means 
that our laboratories have been certified as following CAP standards and guidelines in operating the laboratory facility and 
in performing tests that ensure the quality of our test results.  

California Laboratory Licensing  

In addition to federal certification requirements for laboratories under CLIA, we are required under California 
law to maintain a California state license for our San Carlos clinical laboratory and comply with California state laboratory 
laws and regulations. Similar to the federal CLIA regulations, the California state laboratory laws and regulations establish 
standards for the operation of a clinical laboratory and performance of test services, including the education and experience 
requirements  of  the  laboratory  director  and  personnel  (including  requirements  for  documentation  of  competency), 
equipment validations, and quality management practices. All testing personnel must maintain a California state license 
or be supervised by licensed personnel. 

Clinical  laboratories  are  subject  to  both  routine  and  complaint-initiated  on-site  inspections  by  the  state.  If  a 
clinical laboratory is found to be out of compliance with California laboratory standards, the California Department of 
Public Health, or CAPH, may suspend, restrict or revoke the California state laboratory license to operate the clinical 
laboratory  (and  exclude  persons  or  entities  from  owning,  operating,  or  directing  a  laboratory  for  two  years  following 
license revocation), assess civil money penalties, and/or impose specific corrective action plans, among other sanctions. 
Clinical laboratories must also provide notice to CAPH of any changes in the ownership, directorship, name or location of 
the laboratory. Failure to provide such notification may result in revocation of the state license and sanctions under the 
CLIA certificate. Any revocation of a CLIA certificate or exclusion from participation in Medicare or Medicaid programs 
may result in suspension of the California state laboratory license. 

New York Laboratory Licensing  

22 

Because we test specimens in our San Carlos, California laboratory originating from, and return test results to, 
New York State, our San Carlos clinical laboratory is required to obtain a New York state laboratory permit and comply 
with  New  York  state  laboratory  laws  and  regulations.  We  maintain  a  valid  permit  in  the  State  of  New  York  for  the 
molecular genetic testing services furnished by our San Carlos clinical laboratory. The New York state laboratory laws, 
regulations and rules are equal to or more stringent than the CLIA regulations and establish standards for the operation of 
a clinical laboratory and performance of test services, including education and experience requirements of a laboratory 
director  and  personnel,  physical  requirements  of  a  laboratory  facility,  equipment  validations,  and  quality  management 
practices. The laboratory director(s) must maintain a Certificate of Qualification issued by the New York State Department 
of Health, or DOH, in the permitted test categories. 

Our San Carlos clinical laboratory is subject to proficiency testing and on-site survey inspections conducted by 
the Clinical Laboratory Evaluation Program, or CLEP, under the DOH. If a laboratory is found to be out of compliance 
with New York’s CLEP standards, the DOH, may suspend, limit, revoke or annul the New York laboratory permit, censure 
the holder of the license or assess civil money penalties. Statutory or regulatory noncompliance may result in a laboratory’s 
operator,  owners  and/or  laboratory  director  being  found  guilty  of  a  misdemeanor  under  New  York  law.  Clinical 
laboratories must also provide notice to CLEP of any changes in ownership, directorship, name or location of the laboratory. 
Failure to provide such notification may result in revocation of the state license and sanctions under the CLIA certificate. 
Any revocation of a CLIA certificate or exclusion from participation in the Medicare or Medicaid programs may result in 
suspension of the New York laboratory permit. 

The DOH also must approve each LDT before the test is offered to patients located in New York. Our San Carlos 
clinical laboratory has received approval from New York’s CLEP to offer our Panorama, Horizon, Spectrum, Anora non-
invasive prenatal paternity, and Prospera tests.  

Other State Laboratory Licensing Laws 

In addition to New York and California, certain other states require licensing of out-of-state laboratories under 
certain circumstances. We have obtained licenses in the states that we believe require us to do so, and believe we are in 
compliance with applicable state laboratory licensing laws, including Maryland, Pennsylvania and Rhode Island. The State 
of Texas does not impose state licensure or registration requirements upon an independent laboratory facility or collection 
station outside of maintaining CLIA certification.  

Potential  sanctions  for  violation  of  state  statutes  and  regulations  can  include  significant  monetary  fines,  the 
rejection of license applications, the suspension or loss of various licenses, certificates and authorizations, and in some 
cases criminal penalties, which could harm our business. CLIA does not preempt state laws that have established laboratory 
quality standards that are more stringent than federal law. 

State Genetic Testing Laws  

Many states have implemented genetic testing and privacy laws imposing specific patient consent requirements 
and protecting test results. Under some state laws, we are prohibited from conducting genetic tests without appropriate 
documentation  of  patient  consent  by  the  physician  ordering  the  test.  As  discussed  in  more  detail  in  “Risk  Factors—
Reimbursement and Regulatory Risks Related to our Business—If the validity of an informed consent from a patient intake 
for  Panorama  or  our  other  tests  is  challenged,  we  could  be  precluded  from  billing  for  such  testing,  forced  to  stop 
performing such tests, or required to repay amounts previously received, which would adversely affect our business and 
financial  results,”  while  we  rely  on  physicians  to  obtain  the  required  patient  consent  to  perform  genetic  testing,  the 
regulatory burden may be deemed to be our responsibility and such consents, or our compliance with applicable laws and 
regulations, could be challenged. Requirements of these laws and penalties for violations vary widely from state to state.  

HIPAA and Other Privacy Laws  

23 

The privacy and security regulations under the Health Insurance Portability and Accountability Act of 1996, or 
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, 
establish uniform standards governing the conduct of certain electronic healthcare transactions and require certain entities, 
called covered entities, to comply with standards that include the privacy and security of protected health information, or 
PHI. HIPAA further requires business associates of covered entities—independent contractors or agents of covered entities 
that have access to protected health information in connection with providing a service to or on behalf of a covered entity—
to  enter  into  business  associate  agreements  with  the  covered  entity  and  to  safeguard  the  covered  entity’s  PHI  against 
improper use and disclosure. In  addition, certain of HIPAA’s privacy and security standards are directly applicable to 
business associates. 

As a covered entity and as a business associate of other covered entities (with whom we have therefore entered 
into business associate agreements), we have certain obligations regarding the use and disclosure of any PHI that may be 
provided to us, and we could incur significant liability if we fail to meet such obligations or if our business associates fail 
to meet such obligations. Among other things, HITECH imposes civil and criminal penalties against covered entities and 
business associates for noncompliance with privacy and security requirements, which may include fines up to $250,000 
per violation and/or imprisonment, and authorizes states’ attorneys general to file civil actions for damages or injunctions 
in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal 
civil  actions. While HIPAA  does  not  create  a private right of  action  allowing  individuals  to file  suit  in  civil  court  for 
violations of HIPAA, its standards have been used as the basis for duty of care cases in state civil suits such as those for 
negligence or recklessness in the misuse or breach of PHI. In addition, HIPAA mandates that the Secretary of HHS conduct 
periodic  compliance  audits  of  health  care  providers,  such  as  us,  and  their  business  associates  for  compliance  with  the 
HIPAA  privacy  and  security  standards.  HIPAA  also  tasks  HHS  with  establishing  a  methodology  whereby  harmed 
individuals who were the victims of breaches of unsecured PHI may receive a percentage of the civil monetary penalty 
paid by the violator. 

As noted above, we are required to comply with HIPAA standards promulgated by the U.S. Department of Health 
and Human Services, or HHS. First, we must comply with HIPAA’s standards for electronic transactions, which establish 
standards for common healthcare transactions, such as claims information, plan eligibility, payment information and the 
use of electronic signatures. We must also comply with the standards for the privacy of individually identifiable health 
information, which limit the use and disclosure of most paper and oral communications, as well as those in electronic form, 
regarding  an  individual’s  past,  present or  future physical or  mental  health or  condition,  or relating  to  the provision of 
healthcare to the individual or payment for that healthcare, if the individual can or may be identified by such information. 
Additionally, we must comply with HIPAA’s security standards, which require us to ensure the confidentiality, integrity 
and availability of all electronic protected health information that we create, receive, maintain or transmit, to protect against 
reasonably  anticipated  threats  or  hazards  to  the  security  of  such  information,  and  to  protect  such  information  from 
unauthorized use or disclosure. 

Various  states  in  the  United  States  have  implemented  similar  restrictive  requirements  regulating  the  use  and 
disclosure  of  health  information  and  other  personal  information  that  are  not  necessarily  preempted  by  HIPAA  or  that 
regulate different information than HIPAA. For example, in 2020 California enacted the California Consumer Privacy Act, 
which  creates  numerous  new  privacy  requirements,  such  as  greater  notice  and  transparency  obligations  and  consumer 
rights relating to the access to, deletion of, and sharing of personal information collected by certain businesses and their 
service providers. Also, the California Confidentiality of Medical Information Act, which protects the confidentiality of 
individually identifiable medical information obtained by health care providers and their contractors, is much broader than 
HIPAA and the data protected is also broader than HIPAA.  In addition, Massachusetts law requires that any company that 
obtains personal information of any resident of the Commonwealth of Massachusetts implement and maintain a security 
program that adequately protects such information from unauthorized use or disclosure. State privacy laws continue to 
evolve, and several new state privacy laws that may affect us are expected to take effect in 2023. For example, this includes 
updates to the California Consumer Privacy Act, the Colorado Privacy Act, and the Virginia Consumer Data Protection 
Act. 

There are also comprehensive foreign privacy and security laws and regulations that impose robust requirements 
on the processing of personal information, including health information. In particular, the EU’s General Data Protection 

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Regulation, or GDPR, became effective in 2018. The GDPR applies not only to organizations within the EU, but also 
applies to organizations outside of the EU, such as Natera, that offer goods or services to EU data subjects or that process 
personal data of EU data subjects. The regulation specifies higher potential liabilities for certain data protection violations, 
and we anticipate that it will result in a greater compliance burden for us as we conduct our business, particularly through 
our Constellation cloud-based distribution model, in the European Union. Fines for non-compliance can range from the 
greater of 2% of annual global revenues or €10 million, up to the greater of 4% of annual global revenues or €20 million. 

As  a  business  that  operates  both  internationally  and  throughout  the  United  States,  any  unauthorized  use  or 
disclosure  of  personal  information,  even  if  it  does  not  constitute  PHI,  by  us  or  our  third-party  contractors,  including 
disclosure due to data theft or unauthorized access to our or our third-party contractors’ computer networks, could subject 
us  to  costs,  fines  or  penalties  that  could  adversely  affect  our  business  and  results  of  operations,  including  the  cost  of 
providing notice, credit monitoring and identity theft prevention services to affected consumers.  

Healthcare Fraud and Abuse Laws  

Federal and state law enforcement authorities scrutinize arrangements between healthcare providers and potential 
referral  sources  to  ensure  that  the  arrangements  are  not  designed  as  a  mechanism  to  induce  patient  care  referrals  and 
opportunities.  Law  enforcement  authorities,  courts  and  Congress  have  demonstrated  a  willingness  to  look  behind  the 
formalities of a transaction to determine the underlying purpose of payments between healthcare providers and actual or 
potential  referral  sources. The  penalties  for  violations under  these  laws  can be  both  civil  and  criminal  in  nature.   The 
Federal Civil Penalties Inflation Adjustment Act Improvements Act of 2015 provides for an annual, automatic adjustment 
of civil monetary penalties authorized under the Social Security Act to account for inflation, which are published in the 
Federal Register annually. 

The  federal  Anti-Kickback  Statute  makes  it  a  felony  for  a  provider  or  supplier,  including  a  laboratory,  to 
knowingly and willfully offer, pay, solicit or receive remuneration, directly or indirectly, in order to induce business that 
is  reimbursable  under  any  federal  healthcare  program.  A  violation  of  the  federal  Anti-Kickback  Statute  may  result  in 
imprisonment for up to ten years and/or criminal or civil fines of up to $104,330 and exclusion from participation in federal 
healthcare programs. Claims submitted in violation of the federal Anti-Kickback Statute may not be paid by a federal 
health  care program,  and  any  person  collecting  any  amounts with  respect  to  any  such  prohibited  claim  is obligated  to 
refund such amounts. Although the federal Anti-Kickback Statute applies only to federal healthcare programs, a most U.S. 
states  have  passed  laws  substantially  similar  to  the  federal  Anti-Kickback  Statute  pursuant  to  which  similar  types  of 
prohibitions are made applicable to all commercial health plans or any health care services, depending on the state. Conduct 
which violates the federal Anti-Kickback Statute or similar laws may also involve liability under the Federal False Claims 
Act, which prohibits knowingly presenting or causing to be presented a false, fictitious or fraudulent claim for payment to 
the U.S. Government and can result in additional penalties and fines. 

Generally, courts have taken a broad interpretation of the scope of the federal Anti-Kickback Statute, holding that 

the statute may be violated if merely one purpose of a payment arrangement is to induce future referrals. 

The HHS Office of Inspector General, or OIG, has issued Special Fraud Alerts on arrangements for the provision 
of clinical laboratory services and relationships between, among others, laboratories and referral sources. The Fraud Alerts 
set forth a number of practices allegedly engaged in by some clinical laboratories and healthcare providers that raise issues 
under the federal fraud and abuse laws, including the federal Anti-Kickback Statute. The OIG emphasized in the Special 
Fraud  Alerts  that  when  one  purpose  of  such  arrangements  is  to  induce  referrals  of  government  program-reimbursed 
laboratory testing, both the clinical laboratory and the healthcare provider (e.g., physician) may be liable under the federal 
Anti-Kickback Statute, and may be subject to civil and/or criminal prosecution and exclusion from participation in the 
Medicare and Medicaid programs. 

Recognizing that the federal Anti-Kickback Statute is broad and may technically prohibit many innocuous or 
beneficial arrangements within the healthcare industry, HHS has issued a series of regulatory “safe harbors” for certain 
payment arrangements which are not considered improper remuneration under the federal Anti-Kickback Statute if one 
can  demonstrate  compliance  with  each  element  of  the  safe  harbor.  Although  full  compliance  with  these  safe  harbors 

25 

 
ensures  against  prosecution  under  the  federal  Anti-Kickback  Statute,  the  failure  of  a  transaction  or  arrangement  to  fit 
within a specific safe harbor does not necessarily mean that the payment is illegal or that prosecution under the federal 
Anti-Kickback Statute will be pursued. 

While we believe that we are in compliance with the federal Anti-Kickback Statute and similar state fraud and 
abuse laws that are applicable to us, there can be no assurance that our relationships with physicians, hospitals and other 
customers or vendors will not be subject to scrutiny or will survive regulatory challenge under such laws. If imposed for 
any reason, enforcement and sanctions under the federal Anti-Kickback Statute or any similar state statute could have a 
negative effect on our business. 

The federal Civil Monetary Penalty statute pertaining to health care fraud and abuse prohibits, among other things, 
the offer or payment of remuneration to a Medicare beneficiary that the offeror or payer knows or should know is likely 
to influence the beneficiary to order or receive a reimbursable item or service from a particular provider, practitioner, or 
supplier; contracting with an individual or entity that the person knows or should know is excluded from participation in 
a  federal  health  care  program;  and  knowingly  making  or  causing  to  be  made  any  false  statement,  omission,  or 
misrepresentation of a material fact in any application, bid, or contract to participate or enroll as a provider of services or 
a supplier under a federal health care program. A violation of the federal Civil Monetary Penalty statute may result in civil 
fines up to $104,330 plus treble damages and exclusion from participation in any federal health care program.  

Because we operate a laboratory facility located in California and licensed by California’s DHS, California law 
is  applicable  to  our  business  arrangements.  California’s  state  anti-kickback  statutes,  Business  and  Professions  Code 
Section 650 (which applies to all categories of payors) and Insurance Code Section 754, and its Medi-Cal anti-kickback 
statute,  Welfare  and  Institutions  Code  Section  14107.2,  are  analogous  to,  and  have  been  interpreted  by  the  California 
Attorney  General  and  California  courts  in  substantially  the  same  way  as  the  federal  government  and  the  courts  have 
interpreted, the federal Anti-Kickback Statute. A violation of Section 650 is punishable by up to one year of imprisonment, 
a fine up to $50,000, or both imprisonment and a fine. A violation of Section 14107.2 is punishable by imprisonment and 
fines  of  up  to  $10,000.  The  California  Insurance  Code  includes  similar  prohibitions  against  any  consideration  for  the 
referral or procurement of patients if a claim is submitted to a commercial insurer, CA Ins. Code § 750, which is punishable 
by criminal penalties mirroring those that apply to violations of Business and Professions Code Section 650. 

Because  our  San  Carlos  laboratory  holds  a  New  York  CLEP  permit,  we  must  comply  with  New  York  state 
laboratory statutes and regulations, which include anti-kickback provisions, Public Health Law Section 587, and Medicaid 
anti-kickback provisions, 18 NYCRR Section 515.2, related to laboratory services. The New York DOH may suspend, 
limit, revoke or annul the New York laboratory permit or otherwise discipline the permit holder for a violation. 

Because we operate a laboratory facility located in Texas, our business arrangements are subject to certain Texas 
laws. Texas’s primary anti-kickback statute, Texas Patient Solicitation Act (Tex. Occ. Code § 102.001) (which applies to 
all  categories  of  payors),  provides  for  an  exception  to  any  business  arrangement  that  complies  with  the  federal  Anti-
Kickback Statute or any regulation adopted under that law. Even if a business arrangement is compliant with the Texas 
Patient Solicitation Act, disclosure to the patient is required. A violation of Section 102.001 or 102.006 is punishable by 
civil penalties (up to $10,000 per violation). The Texas Medicaid anti-kickback laws, 1 TAC 371.1669, cross-references 
the Texas Patient Solicitation Act and include other prohibited self-referrals that are grounds for enforcement and sanctions. 
The Texas Insurance Code includes criminal penalties for similar prohibitions related to improper referral or procurement 
of patients if a claim is submitted to a commercial insurer. 

In addition to the requirements that are discussed above, there are other healthcare fraud and abuse laws that 

could have an impact on our business.  

The  federal  False  Claims Act  prohibits  a person  from knowingly  submitting  or  causing  to  be  submitted false 
claims or making a false record or statement in order to secure payment by the federal government. Conduct which violates 
another fraud and abuse law identified in this section may also result in liability under the federal False Claims Act as a 
result of the submission of claims pursuant to a prohibited payment arrangement. In addition to actions initiated by the 
government itself, the federal False Claims Act authorizes actions to be brought on behalf of the federal government by a 

26 

private  party  having  knowledge  of  the  alleged  fraud  (sometimes  referred  to  as  a  “whistleblower”)  under  a  qui  tam 
complaint. 

Because qui tam complaints are initially filed under seal in federal court, the action may be pending for some 
time before the defendant is even aware of the action. If the government is ultimately successful in obtaining redress in 
the matter or if the private party plaintiff succeeds in obtaining redress without the government’s involvement, then the 
private party plaintiff will receive a percentage of the recovery. Violation of the federal False Claims Act may result in 
fines  of  up  to  three  times  the  actual  damages  sustained  by  the  government,  plus  mandatory  civil  penalties  of  up  to 
approximately $23,607 per false claim or statement, imprisonment or both, reimbursement of the whistleblower’s attorneys’ 
fees, and possible exclusion from Medicare or Medicaid. The penalties will continue to be adjusted, increasing each year 
to reflect changes in the inflation rate, pursuant to the 2015 Bipartisan Budget Act. 

In 2018, the Eliminating Kickbacks in Recovery Act of 2018, or EKRA, was passed as part of the Substance Use-
Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (referred to as the 
SUPPORT Act). Similar to the federal Anti-Kickback Statute, EKRA creates criminal penalties for knowing or willful 
payment or offer, or solicitation or receipt, of any remuneration, whether directly or indirectly, overtly or covertly, in cash 
or in kind, in exchange for the referral or inducement of laboratory testing unless a specific exception applies. Unlike the 
federal Anti-Kickback Statute, EKRA is not limited to government health care benefit programs, so the prohibitions extend 
to services covered by commercial health plans. Additionally, most of the safe harbors available under the federal Anti-
Kickback Statute are not reiterated under EKRA, and certain EKRA safe harbors conflict with the safe harbors available 
under  the  federal  Anti-Kickback  Statute.  Therefore,  compliance  with  a  federal  Anti-Kickback  safe  harbor  does  not 
guarantee  protection under  EKRA.  As  currently drafted, EKRA  potentially  expands  the universe  of  arrangements that 
could be subject to government enforcement under federal fraud and abuse laws. Violation of EKRA carries potential 
penalties of up to $200,000 in fines and imprisonment of up to 10 years for each occurrence, and potential exclusion from 
participation in any federal health care program. Because EKRA is a relatively new law, there is very little additional 
guidance to indicate how and to what extent it will be interpreted, applied and enforced by the government. Currently, 
there is no proposed regulation interpreting or implementing EKRA, nor any public guidance released by a federal agency 
concerning  EKRA.  We  cannot  assure  you  that  our  relationships  with  physicians,  sales  representatives,  hospitals  or 
customers will not be subject to scrutiny or will survive a challenge under EKRA. If imposed for any reason, sanctions 
under EKRA could have a negative effect on our business. 

We are also subject to the Physician Self-Referral law, commonly known as the Stark Law, which prohibits, with 
certain exceptions, an ownership or financial arrangement with a physician (or physician’s immediate family member) in 
exchange for the referral of designated health services, including clinical laboratory services, or presenting or causing to 
be presented claims to Medicare and Medicaid for such services referred by the physician. The Stark law is a strict liability 
statute, which means proof of specific intent to violate the law is not required. Any person who presents or causes to be 
presented a claim to the Medicare or Medicaid programs in violation of the Stark Law may be subject to civil monetary 
penalties of up to $25,820 per claim submission, an assessment of up to three times the amount claimed, and exclusion 
from participation in any federal health care program. A person who engages in a scheme to circumvent the Stark Law’s 
referral prohibition may be fined up to $104,330 for each such arrangement or scheme. Claims submitted in violation of 
the Stark Law may not be paid by Medicare or Medicaid, and any person collecting any amounts with respect to any such 
prohibited claim is obligated to refund such amounts. Actions which violate the Stark Law may be bootstrapped to involve 
liability under the federal False Claims Act. 

Further,  in  addition  to  the  privacy  and  security  regulations  stated  above,  HIPAA  created  two  federal  crimes: 
healthcare fraud and false statements relating to healthcare matters. The healthcare fraud statute prohibits knowingly and 
willfully executing a scheme to defraud any healthcare benefit program, including private payers, or to obtain, by means 
of false or fraudulent pretenses, representations or promises, any money or property owned by or under the control of any 
health care benefit program in connection with the delivery of or payment for health care benefits, items or services. A 
violation  of  this  statute  is  a  felony  and  may  result  in  fines,  imprisonment  or  exclusion  from  government  sponsored 
programs. The false statements statute prohibits knowingly and willfully falsifying, concealing or covering up a material 
fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for 
healthcare benefits, items or services. A violation of this statute is a felony and may result in fines or imprisonment. 

27 

Finally, federal law prohibits any entity from offering or transferring to a Medicare or Medicaid beneficiary any 
remuneration that the entity knows or should know is likely to influence the beneficiary’s selection of a particular provider, 
practitioner  or  supplier  of  Medicare  or  Medicaid  payable  items  or  services,  including  waivers  of  copayments  and 
deductible amounts (or any part thereof), if any apply, and transfers of items or services for free or for other than fair 
market value. Entities found in violation may be liable for civil monetary penalties of up to $100,000 for each wrongful 
act. Although we believe that our business activities and practices, including our sales and marketing practices, are in 
material compliance with all applicable federal and state laws and regulations, relevant regulatory authorities may disagree, 
and violation of these laws or our exclusion from such programs as Medicare, Medicaid and other federal health care 
programs as a result of a violation of such laws could have a material adverse effect on our business, results of operations, 
financial condition and cash flows. 

Many states, including California, also have state “physician self-referral” prohibitions and other laws that are 
not limited to Medicare and Medicaid referrals, with which we must comply. We are subject to California’s Physician 
Ownership and Referral Act, or PORA, which generally prohibits us from billing a patient or any governmental or private 
payer for any laboratory services when the physician ordering the service, or any member of such physician’s immediate 
family, has a “financial interest” with us, unless the arrangement meets an exception (CA Business and Professions Code 
Section 650.02). The term “financial interest” is defined broadly and includes any type of ownership interest, debt, loan, 
lease, compensation, remuneration, discount, rebate, refund, etc. between the ordering physician and the entity receiving 
the referral. The exceptions to PORA track certain of the Stark Law exceptions, including an exception for personal service 
arrangements  and  for  ownership  of  publicly  traded  entities.  A  violation  of  PORA  is  punishable  by  civil  and  criminal 
penalties (civil penalties and criminal fines vary depending on the nature of the violation, but may reach up to $15,000 per 
violation). 

Other states may have self-referral restrictions with which we have to comply that differ from those imposed by 

federal and California law. 

We are also subject to applicable state client billing laws, which specify whether a person that did not perform 
the service is permitted to submit the claim for payment and if so, whether the non-performing person is permitted to mark 
up the cost of the services in excess of the price the purchasing provider paid for such services. California has an anti-
markup statute with which we must comply, which prohibits providers from charging for any laboratory test that it did not 
perform unless the provider (a) notifies the patient, client or customer of the name, address, and charges of the laboratory 
performing the test, and (b) charges no more than what the provider was charged by the clinical laboratory which performed 
the test except for any other service actually rendered to the patient by the provider (for example, specimen collection, 
processing  and  handling)  (Business  and  Professions  Code  Section  655.5).  This  provision  applies,  with  certain  limited 
exceptions, to licensed persons such as physicians and clinical laboratories regulated under the Business and Professions 
Code. A violation of this provision can lead to imprisonment and/or a fine of up to $10,000. Other states have similar anti-
markup prohibitions with which we must comply. In addition, many states also have “direct-bill” laws, which means that 
the  services  actually performed by  an  individual  or  entity  must be billed by  such  individual or  entity,  thus  preventing 
ordering physicians from purchasing services from a laboratory and rebilling for the services they order. For example, 
California has a direct bill rule specific to anatomic pathology services that prohibits any provider from billing for anatomic 
pathology services if those services were not actually rendered by that person or under his or her direct supervision with 
some exemptions (CA Business and Professions Code Section 655.7). 

While we have attempted to comply with the federal, Texas, California and New York fraud and abuse laws and 
similar laws of other states and non-U.S. jurisdictions that are applicable to our business, it is possible that some of our 
arrangements could be subject to regulatory scrutiny at some point in the future, and we cannot provide assurance that we 
will be found to be in compliance with these laws following any such regulatory review.  

Human Capital Management 

As of December 31, 2021, our global workforce comprised over 2,670 full time employees, representing growth 
of approximately 48% during 2021. We also engage consultants and temporary employees. We have not been subject to 
labor action or union activities, and our management considers its relationships with employees to be good.  

28 

Our global voluntary turnover rate for 2021 was approximately 13%. Based on self-identification data, women 
comprised approximately 59% of our global workforce in 2021, and over 60% of global new hires were women. Also 
based on self-identification data, minorities comprised approximately 48% of our U.S. workforce. 

We are committed to attracting, retaining, developing, and nurturing a diverse workforce, which we believe is 
necessary  in  order  to  deliver  upon  our  mission  of  changing  the  management  of  disease  worldwide.  Our  development, 
performance, and compensation programs are designed to attract and reward talented, diverse individuals who possess the 
skills necessary to support our business objectives, assist in the achievement of our strategic goals and ultimately create 
long term value for our stockholders. In addition to base pay, our compensation and benefits programs, which can vary by 
region,  can  include  annual  bonuses,  stock-based  compensation  awards,  a  401(k)  plan  with  employee  matching 
opportunities, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, parental 
leave, and employee assistance programs. We work to ensure pay equity by annually assessing our compensation practices 
and working with external compensation consultants to design and benchmark our programs.  

We  operate  in  an  industry  in  which  competition  for  highly  qualified  personnel  is  intense.  In  addition  to  our 
compensation programs, we are highly focused on talent acquisition, retention and development. We conduct an annual 
employee  engagement  survey,  the  results  of  which  inform  internal  company  and  management  goals  to  help  ensure 
impactful and meaningful actions in response to feedback received. Our annual employee evaluation process helps us to 
support developing employees as well as identify and cultivate high performers, and we have various initiatives underway 
to further develop leaders and managers. Our 2021 engagement survey participation rate was 87%, resulting in an 89% 
engagement score. Based on the survey results, 92% of our employees are excited about the future of Natera, and 85% 
would recommend Natera as a great place to work. 

Diversity is one of our company core values, as we believe that a broad range of perspectives and experiences is 
necessary  to  drive  innovation  and  leadership.  To  this  end,  it  is  important  to  us  to  create  an  inclusive  and  equitable 
environment that represents a broad spectrum of backgrounds and cultures. We have two employee resource groups, or 
ERGs, committed to furthering our efforts in this area. Women of Natera and our Diversity & Inclusion Group both serve 
as resources to the organization in fostering a culture of inclusion and diversity by providing a platform of networking, 
ongoing learning and exchange to support professional development and promote workplace equality and diversity. 

In response to the COVID-19 pandemic, we implemented significant changes that we determined were in the best 
interest of our employees and which comply with government orders in all the states and countries where we operate. In 
an  effort  to  keep  our  employees  safe  and  to  maintain  operations  during  the  COVID-19  pandemic,  we  implemented  a 
number of health-related measures, including implementing a general work from home policy and restricting on-site access 
to essential employees such as laboratory personnel, increasing hygiene, cleaning and sanitizing procedures at our office 
and laboratory facilities, and policies regarding matters such as masking and vaccinations in accordance with local rules 
and guidelines.  

Glossary of Terms 

ACOG – the American Congress of Obstetricians and Gynecologists. 

ACMG – the American College of Medical Genetics and Genomics. 

Allograft – the transplant of an organ or tissue from one individual to another individual of the same species who is not 
genetically identical. 

AMA – American Medical Association. 

AUC – area under the receiver operating curve; a measure of the diagnostic performance of a test, based on sensitivity and 
specificity. 

29 

cfDNA – cell-free DNA. 

CLIA – Clinical Laboratory Improvement Amendments. 

CMS – Centers for Medicare and Medicaid Services. 

CNV – copy number variation; a genetic mutation in which relatively large regions of the genome have been deleted or 
duplicated. 

CPT – Current Procedure Terminology.  

ctDNA – circulating tumor DNA; tumor DNA circulating in a blood sample. 

CS test – carrier screening test. 

dd-cfDNA – donor-derived cell-free DNA; DNA that is shed from a transplanted organ undergoing rejection. 

DNA – deoxyribonucleic acid. 

FDA – Food and Drug Administration. 

Fetal aneuploidy – an inherited genetic condition in which a fetus has a different number of chromosomes than are typical. 

IVD – in vitro diagnostic; tests that can be used in any laboratory that has the appropriate qualifications and authorizations. 

IVF – in vitro fertilization. 

LDT – laboratory developed test; tests that are designed, developed, validated and used within a single laboratory. 

MFM – maternal fetal medicine. 

Microdeletion – a deletion of a region of DNA from one copy of one chromosome. 

mmPCR – massively multiplexed polymerase chain reaction. 

NGS – next-generation sequencing; a DNA sequencing technology. 

NIPT – non-invasive prenatal test. 

No-call – the inability to update the prior risk, or the standard risk assigned based on maternal and gestational age, in order 
to provide a high-risk or low-risk test result due to insufficient information in the sample.  

PPV – positive predictive value; the likelihood that a positive result on a test indicates a true positive result in the patient. 

Sensitivity – the likelihood that an individual with a condition will be correctly found to have that condition. Sensitivity is 
calculated  as  the  ratio  between  the  number  of  individuals  that  test  positive  for  the  condition  over  the  total  number  of 
individuals in the tested cohort who actually have the condition. 

30 

SNP – single nucleotide polymorphism; a position on the chromosome at which single DNA base changes are common in 
the population. 

SNV – single nucleotide variant; a genetic mutation in which a single chemical base in DNA has changed. 

Specificity  –  the  likelihood  that  an  individual  without  a  condition  will  be  correctly  found  not  to  have  that  condition. 
Specificity is calculated as the ratio between the number of individuals that test negative for a condition over the total 
number of individuals in the tested cohort who do not have the condition. 

Triploidy – a type of fetal aneuploidy in which an individual has three copies of every chromosome instead of two. 

Corporate Information 

Our principal executive office is located 13011 McCallen Pass, Building A Suite 100, Austin, Texas. Our website 
address is www.natera.com. We do not incorporate the information on, or accessible through, our website into this Annual 
Report on Form 10-K or any other report we file with or finish to the SEC, and you should not consider any information 
on, or accessible through, our website as part of this Annual Report on Form 10-K or any other report we file with or 
furnish to the SEC.  

Our  annual  reports  on  Form  10-K,  quarterly  reports  on  Form  10-Q  and  current  reports  on  Form  8-K,  and 
amendments to those reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Securities Exchange Act of 
1934,  as  amended,  may  be  obtained  free  of  charge  at 
the  Investor  Relations  section  of  our  website, 
http://investor.natera.com, as soon as reasonably practicable after we electronically file such material with, or furnish it to, 
the Securities and Exchange Commission, or SEC. Additionally, the SEC maintains an internet site that contains reports, 
proxy and information statements and other information. The address of the SEC’s website is www.sec.gov.  

ITEM 1A. 

RISK FACTORS  

Investing  in  our  common  stock  involves  a  high  degree  of  risk.  You  should  consider  carefully  the  risks  and 
uncertainties  described  below,  together  with  all  of  the  other  information  in  this  report,  including  the  section  titled 
“Management’s  Discussion  and  Analysis  of  Financial  Condition  and  Results  of  Operations”  and  our  consolidated 
financial statements and related notes, before investing in our common stock. The risks and uncertainties described below 
are not the only ones we face. If any of the following risks actually occurs, our business, financial condition, results of 
operations and prospects could be materially and adversely affected. In that event, the price of our common stock could 
decline and you could lose part or all of your investment. 

Risks Related to Our Business and Industry 

We face risks related to health epidemics, including the ongoing COVID-19 pandemic, which has materially impacted 
and could continue to materially impact our business, results of operations, financial condition and/or stock price. 

Our  business  operations  have  been  and  continue  to  be  significantly  affected  by  the  ongoing  pandemic  of 
respiratory illness caused by a novel strain of coronavirus, SARS-CoV-2, causing the Coronavirus Disease 2019, also 
known as COVID-19, including the variants of SARS-CoV-2, which have compounded the effects of and contributed to 
the duration, unpredictability and difficulties relating to the pandemic. Global health concerns relating to the COVID-19 
pandemic continue to weigh on the macroeconomic environment, and the pandemic has significantly increased economic 
volatility and uncertainty. 

The pandemic has resulted in government authorities and businesses implementing numerous measures from time 
to time to try to contain the virus, such as travel bans and restrictions, quarantines, shelter-in-place or stay-at-home orders, 
and business shutdowns, restrictions or other limitations. These measures have adversely impacted and may further impact 
our employees and operations, and the operations of our customers, suppliers and business partners, and may negatively 

31 

 
 
 
 
 
impact spending patterns, payment cycles and insurance coverage levels. These measures have also adversely affected and 
may continue to adversely affect demand for our tests. For example, our personnel located at our offices and laboratories 
in Texas, California and elsewhere in the United States and in other countries have been subject to varying degrees of 
workplace  restrictions  during  the  pandemic,  including  the  health  and  safety  measures  described  below.  Many  of  our 
customers, including hospitals and clinics, suspended or limited non-emergency appointments and services, particularly 
earlier in the pandemic, which resulted in a significant decrease in our test volume; and many have implemented similar 
measures  recently  in  response  to  the  Omicron  variant  of  SARS-CoV-2,  which  has  also  impacted  our  test  volumes.  In 
addition, because we rely heavily on our direct sales force to sell our tests, we expect our sales cycle, particularly for new 
customers, will continue to be significantly impacted. The COVID-19 pandemic could limit the ability of our customers, 
suppliers  and  business  partners  to  perform  under  their  contracts  with  us,  including  third-party  payers’  ability  to  make 
timely payments to us during and following the pandemic. We may also experience a shortage of laboratory supplies and 
reagents or a suspension of services from other laboratories or third parties. We have also become increasingly dependent 
on growing and maintaining a network of mobile phlebotomy specialists who can provide testing capabilities, as many 
consumers are unable to visit clinics, hospitals or other testing facilities as a result of the pandemic. Travel bans, restrictions 
and border closures earlier in the pandemic impacted our ability to ship test kits to and receive samples from our customers. 
Such measures may be implemented to varying degrees from time to time for the foreseeable future, and they are likely to 
continue to adversely affect our test volumes, sales activities and overall operations for an indefinite period of time. 

In addition, it may be more difficult for us to develop new products for commercial release, as we expect it will 
continue to be more difficult to complete our research and development efforts and commence and complete clinical trials 
while the pandemic is ongoing. It is also possible that demand for products that we may pursue could be materially and 
adversely affected as a result of COVID-19, disruptions to our or our customers’ operations, and any related economic 
impact. 

The spread of COVID-19 has caused us to modify our business practices with various measures from time to time 
(including limiting employee travel, mandating that all non-essential personnel work from home, temporary closures of 
our  offices,  and  cancellation  of  physical  participation  in  sales  activities,  meetings,  events  and  conferences)  and  incur 
additional  operating  costs,  and  we  may  take  further  actions  as  may  be  required  by  government  authorities  or  that  we 
determine are in the best interests of our employees, customers and business partners. Such actions could also impact our 
ability to fully integrate businesses we may acquire in the future. There is no certainty that such actions will be sufficient 
to mitigate the risks posed by the virus or otherwise be satisfactory to government authorities. In addition, certain aspects 
of our business, such as laboratory processes, cannot be conducted remotely. If significant portions of our workforce, and 
particularly our laboratory staff, are unable to work effectively, including due to illness, quarantines, social distancing, 
government actions or other restrictions in connection with the COVID-19 pandemic, our operations will be impacted. 

The extent to which the COVID-19 pandemic impacts our business, results of operations and financial condition 
will depend on future developments, which remain highly uncertain and cannot be predicted, including, but not limited to, 
the continued duration and spread of the pandemic, its severity, the actions to contain the virus or address its impact, and 
when and to what extent normal economic and operating activities can resume. Even after the pandemic has subsided, we 
may continue to experience an adverse impact to our business as a result of its global economic impact, including increased 
costs due to inflation and any recession that has occurred or may occur in the future. Specifically, difficult macroeconomic 
conditions, such as inflation, decreases in per capita income and level of disposable income and related health insurance 
coverage, increased and prolonged unemployment or a decline in consumer confidence as a result of the pandemic, as well 
as limited or significantly reduced points of access of our products, could have a material adverse effect on the demand 
for some of our products, such as our products targeted for the IVF market. Decreased demand for our tests, particularly 
in the United States, could negatively affect our overall financial performance. A significant portion of our revenue is 
concentrated in the United States, where the impact of COVID-19 continues to be significant, and the potential decrease 
in demand for our tests could have a disproportionately negative impact on our business and financial results. 

In addition, the stock market has been unusually volatile during the COVID-19 pandemic and such volatility may 
continue,  and  financial  markets  generally  have  experienced  periods  of  significant  volatility.  Our  stock  price  has  also 
experienced volatility during this time, including occasional significant declines, and such declines may repeat or continue 
for the foreseeable future. 

32 

We do not yet know the full extent and duration of the impact of the COVID-19 pandemic on the United States 
or global economies as a whole, nor the resulting ultimate impact on our operations, and there are no comparable recent 
events  which  may  provide  guidance  in  this  respect.  However,  the  effects  have  materially  impacted  our  business  and 
operations, and we expect that they will continue to do so for the foreseeable future. 

We have derived the significant majority of our revenues from Panorama and Horizon, and if our efforts to further 
increase the use and adoption of Panorama and Horizon or to develop new products and services in the future do not 
succeed, our business will be harmed. 

Historically,  including  for  the  year  ended  December 31,  2021,  the  significant  majority  of  our  revenues  were 
derived from sales of our Panorama NIPT and our Horizon carrier screening, or HCS, test, and we expect this to continue 
to  be  the  case.  With  respect  to  Panorama  in  particular,  continued  and  additional  market  demand  for  Panorama,  and 
reimbursement for the average-risk population and for microdeletions, are key elements to our future success. The market 
demand for NIPTs and carrier screening tests continue to evolve. We cannot guarantee that physicians will recommend 
and order Panorama or Horizon, and our laboratory distribution partners and licensees may not actively or effectively 
market Panorama or Horizon. 

Our ability to increase sales and establish significant levels of adoption and reimbursement for Panorama and 
Horizon is uncertain, and it may be challenging for us to achieve profitability for many reasons, including, among others: 

• 

• 

• 

• 

• 

• 

the market for our tests may not grow as we expect; in particular, NIPTs may not gain acceptance for use in 
the average-risk pregnancy population or as a screen for microdeletions, which would limit the market for 
Panorama, and we may fail to compete successfully in this market, whatever size; 

if we are unable to demonstrate that our tests are superior to competing tests, laboratories, clinics, clinicians, 
physicians, payers and patients may not adopt the use of Panorama, Horizon or our other tests on a broad 
basis, and may not be willing to pay the price premium over competing tests that we have, to date, been able 
to achieve; 

third-party  payers,  such  as  commercial  insurance  companies  and  government  insurance  programs,  may 
decide  not  to  reimburse  for  Panorama  or  Horizon,  may  not  reimburse  for  uses  of  Panorama  for  the 
average-risk  pregnancy  population  or  for  the  screening  of  microdeletions,  may  set  the  amounts  of  any 
reimbursements at prices that do not allow us to cover our expenses, or may otherwise adopt regulations, 
programs, policies or procedures that restrict or harm our business; in fact, many third-party payers currently 
have negative coverage determinations or otherwise do not reimburse for microdeletions screening and we 
expect low reimbursement rates for microdeletions screening to continue, at least in the near term; also, most 
state Medicaid programs currently either reimburse at low rates or do not reimburse for our tests; 

third-party payers have increasingly required that prior authorization be obtained prior to conducting genetic 
testing as a condition to reimbursing for it, which has reduced and/or delayed the reimbursement amounts 
we receive for Panorama, Horizon and our other tests and impacted our results of operations; 

the results of our SMART Study evaluating the performance of Panorama may fail to convince laboratories, 
clinics, clinicians, physicians or patients of the benefits of utilizing Panorama in average-risk pregnancies or 
for microdeletions and may not increase reimbursement for Panorama; 

the results of our clinical trials and any additional clinical and economic utility data that we may develop, 
present  and  publish  in  the  future,  including  the  data  from  our  SMART  Study,  or  that  comes  from  the 
commercial use of our tests, may be inconsistent with our existing data and may raise questions about the 
performance  of  our  tests,  or  may  fail  to  convince  laboratories,  clinics,  clinicians,  physicians,  payers  or 
patients of the value of our tests;  

•  we  may  experience  supply  constraints,  including  those  due  to  the  failure  of our key  suppliers  to  provide 
required  sequencers  and  reagents  in  sufficient  amounts  or  of  adequate  quality  or  disputes  with  our  key 

33 

suppliers,  including  those  with  respect  to  the  required  sequencers  and  reagents  from  our  supplier, 
Illumina, Inc., or Illumina, who is also one of our main NIPT competitors through its subsidiary, Verinata 
Health Inc., or Verinata, and with whom we have historically been involved in patent proceedings; 

•  we  may  experience  increased  cost  of  product  revenues,  and  cost  of  licensing  and  other  revenues,  as  a 

percentage of total revenues, as has been the case in previous fiscal periods; 

• 

• 

the U.S. Food and Drug Administration, or the FDA, or other U.S. or foreign regulatory or legislative bodies 
may adopt new regulations or policies, or take other actions that impose significant restrictions on our ability 
to market and sell Panorama, Horizon, or our other tests, including requiring FDA clearance or approval for 
the sale of Panorama, Horizon, or our other tests, or of the sequencers, reagents, kits and other consumable 
products that we purchase from third parties in order to perform our testing; 

our laboratory partners may choose to develop their own tests that are competitive with ours or offer tests 
provided by our competitors due to pricing or other reasons as has happened in the past, or otherwise fail to 
effectively  market  our  tests;  and  competitors  may  develop  and  commercialize  more  effective  and/or  less 
expensive tests that deliver comparable results to our tests; 

•  we may fail to adequately protect or enforce our intellectual property relating to our tests, leading to increased 
competition;  or  other  parties  may  claim  that  the  practice  of  our  technology  by  us  or  our  licensees  and 
collaborators  infringes  such  other  party’s  intellectual  property  rights,  as  certain  of  our  competitors  have 
claimed in lawsuits filed against us, as discussed further in “Note 8—Commitments and Contingencies—
Legal Proceedings” in the Notes to Consolidated Financial Statements; if we are required to pay license fees 
in order to license third-party intellectual property rights due to actual or alleged infringement based on our 
running our tests, we may experience increased costs in running our tests, and we may be unable to pass such 
costs on to our customers; 

•  we may be unable to dedicate adequate resources to the maintenance and further technological advancement 
of Panorama and Horizon that are necessary for such tests to be competitive in the marketplace because of 
the demands placed on our research and development and product teams with respect to our continuously 
expanding portfolio of products and programs, in particular our efforts and focus on developing our oncology 
and organ health products; 

• 

in  the  event  that  it  is  in  our  commercial  or  financial  interest  or  we  are  forced  to  transition  sequencing 
platforms for Panorama, we may be unable to do so in a commercially sustainable way and that could survive 
claims of infringement of intellectual property rights of Illumina and other competitors, in a timely manner 
or at all; and 

•  we may not be successful in commercializing our cloud-based distribution model. 

If the market for Panorama or Horizon, or our market share for either test, fail to grow or grow more slowly than 

expected, our business, operating results and financial condition will be harmed. 

We  have  incurred  net  losses  since  our  inception  and  we  anticipate  that  we  will  continue  to  incur  losses  for  the 
foreseeable future, which could harm our future business prospects. 

We have incurred net losses each year since our inception in 2003. To date, we have financed our operations 
primarily through private placements of preferred stock, convertible debt and other debt instruments, our initial public 
offering and our registered public equity offerings. Our net loss for the years ended December 31, 2021, 2020 and 2019 
was $471.7 million, $229.7 million, and $124.8 million, respectively. As of December 31, 2021, we had an accumulated 
deficit of $1.4 billion. Such losses may continue to increase in the future as we continue to devote a substantial portion of 
our resources to efforts to increase the adoption of, and reimbursement for, Panorama, Horizon and our other products, 
improve these products, and research and develop and commercialize new products, which increasingly are in industries 
that are relatively new to us, such as oncology and organ health. 

34 

In addition, the rate of growth in our revenues has fluctuated in the past, and may continue to do so in future 
periods. In particular, such rate of growth may be negative, flat, or may grow more slowly than we expect, including if the 
rate of growth of our test volumes slows. A significant element of our business strategy is to maintain increased in-network 
coverage with third-party payers; however, the negotiated fees under our contracts with third-party payers are typically 
lower than the list price of our tests, and in some cases the third-party payers that we contract with have negative coverage 
determinations for some of our offerings, in particular Panorama for microdeletions screening. Therefore, being in-network 
with third-party payers has had, and may continue to have, an adverse impact on our revenues and gross margins, especially 
if we are unable to increase the adoption of, and obtain favorable coverage determinations for reimbursement for, our 
products. Furthermore, a CPT code for microdeletions went into effect beginning in January 2017. We have experienced 
low average reimbursement rates for microdeletions testing under this code, and we expect that this code will continue to 
cause our microdeletions reimbursement to remain low, at least in the near term, either due to reduced reimbursement, or 
third-party payers declining to reimburse, under the microdeletions code, which has had and will likely continue to have 
an adverse effect on our revenues. In addition, a CPT code for expanded carrier screening went into effect beginning in 
January 2019, and has had, and may continue to have, an adverse effect on our reimbursement rates for our broader Horizon 
carrier screening panel, for which we previously primarily received reimbursement on a per condition basis, as those tests 
may be reimbursed as a combined single panel instead of as multiple individual tests. 

As further discussed in the risk factor entitled “—We may not be successful in commercializing our cloud-based 
distribution model,” our results of operations may be adversely affected if we do not sell a sufficient volume of tests under 
our cloud-based distribution model to offset the lower revenues per test performed under that model. Our ability to forecast 
our  future  operating  results,  including  revenues,  cash  flows  and  profitability,  is  limited  and  subject  to  a  number  of 
uncertainties. We have also encountered and will continue to encounter risks and uncertainties frequently experienced by 
growing companies in the life sciences and technology industry, such as those described in this report. If our assumptions 
regarding these risks and uncertainties are incorrect or these risks and uncertainties change, or if we do not address these 
risks successfully, our operating and financial results may differ materially from our expectations, and our business may 
suffer. 

Uncertainty  in  the  development  and  commercialization  of  our  enhanced  or  new  tests  or  services  could  materially 
adversely affect our business, financial condition and results of operations. 

Our success will depend in part on our ability to effectively introduce and increase market adoption of enhanced 
or new offerings. The focus of our research and development efforts has expanded beyond reproductive health products, 
as we are now also applying our expertise in processing and analyzing cell-free DNA in the fields of oncology and organ 
health. In recent years we have developed and launched several new products or enhanced versions of existing products, 
including our first offerings in oncology and in organ health, and we expect to continue our efforts in all of these areas. 
The  development  and  launch  of  enhanced  or  new  tests  requires  the  completion  of  certain  clinical  development  and 
commercialization activities that are complex, costly, time-intensive and uncertain, and requires us to accurately anticipate 
patients’, clinicians’, payers’ and other counterparties’ attitudes and needs as well as emerging technology and industry 
trends. This process is conducted in various stages, and each stage presents the risk that we will not achieve our goals. 

We  may  not  be  successful  in  our  current  or  future  efforts  to  develop  and  commercialize  cell-free  DNA  tests 
outside  of  the  reproductive  health  space.  Moreover,  we  have  limited  experience  forecasting  our  future  financial 
performance from our new products in these industries that are newer to us, and our actual results may fall below our 
financial guidance or other projections, or the expectations of analysts or investors, which could cause the price of our 
common stock to decline. We may experience research and development, regulatory, marketing and other difficulties that 
could  delay  or  prevent  our  introduction  of  enhanced  or  new  tests  and  result  in  increased  costs  and  the  diversion  of 
management’s  attention  and  resources  from  other  business  matters,  such  as  from  our  Panorama  and  Horizon  product 
offerings, which currently represent the significant majority of our revenues. For example, any tests that we may enhance 
or develop may not prove to be clinically effective in clinical trials or commercially, or may not ultimately meet our desired 
target product profile, be offered at acceptable cost and with the sensitivity, specificity and other test performance metrics 
necessary to address the relevant clinical need or commercial opportunity; our test performance in commercial experience 
may be inconsistent with our validation or other clinical data; we may not be successful in achieving market awareness 
and demand, whether through our own sales and marketing operations or through collaborative arrangements; healthcare 
providers may not order or use, or third-party payers may not reimburse for, any tests that we may enhance or develop; or 

35 

we may otherwise have to abandon a test or service in which we have invested substantial resources. In particular, we are 
subject  to  the  risk  that  the  biological  characteristics  of  the  genetic  mutations  we  seek  to  target,  and  upon  which  our 
technologies rely, are uncertain and difficult to predict. For example, in our efforts to detect and analyze circulating tumor 
DNA in plasma for MRD assessment and recurrence surveillance, our success depends on tumors shedding mutant DNA 
into the bloodstream in sufficient quantities such that our technology can detect such mutations. As further discussed in 
the risk factor entitled “If our products do not perform as expected, our operating results, reputation and business will 
suffer,”  we  may  also  experience  unforeseen  difficulties  when  implementing  updates  to  our  processes,  as  we  have 
occasionally experienced with Panorama, Horizon, and our other tests. 

We cannot assure you that we can successfully complete the clinical development of any new or enhanced product, 
or that we can establish or maintain the collaborative relationships that may be essential to our clinical development and 
commercialization efforts. Clinical development requires large numbers of patient specimens and, for certain products, 
require large, prospective, and controlled clinical trials. We may not be able to enroll patients or collect a sufficient number 
of appropriate specimens in a timely manner; or we may experience delays during clinical development due to slower than 
anticipated enrollment, which we experienced in the past with our SNP-based Microdeletions and Aneuploidy RegisTry, 
or SMART, Study, or due to changes in study design or other unforeseen circumstances, such as our decisions in the past 
to expand our SMART Study; or we may be unable to afford or manage the large-sized clinical trials that some of our 
planned future products may require. 

The  publication  of  clinical  data  in  peer-reviewed  journals  is  a  crucial  step  in  commercializing  and  obtaining 
reimbursement for tests such as ours, and our inability to control when, if ever, results are published may delay or limit 
our ability to derive sufficient revenues from any test that is the subject of a study. Peer-reviewed publications regarding 
our tests may be limited by many factors, including delays in the completion of, poor design of, or lack of compelling data 
from, clinical studies, as well as delays in the review, acceptance and publication process. If our tests or the technology 
underlying our current or future tests do not receive sufficient favorable exposure in peer-reviewed publications, the rate 
of clinician adoption of our tests and positive reimbursement coverage determinations for our tests could be negatively 
affected. Further, the data collected from any studies we complete in the future may not be favorable or consistent with 
our existing data or may not be statistically significant or compelling to the medical community or to third-party payers 
seeking such data for purposes of determining coverage for our tests. For example, results from our SMART Study have 
recently been published in two publications; however, we cannot assure you that such results or publications will convince 
laboratories, clinics, clinicians, physicians or patients of the benefits of utilizing Panorama in average-risk pregnancies or 
for  microdeletions.  We  also  cannot  be  certain  whether,  or  to  what  extent,  the  SMART  Study  may  impact  insurance 
coverage and reimbursement for Panorama in the average-risk population or for microdeletions. Similarly, we recently 
presented certain results of our CIRCULATE-Japan study, and we cannot assure you that such results, once published, 
will impact professional society or practice guidelines, or coverage and reimbursement determinations from third-party 
payers, as we anticipate. 

In addition, as further described in the risk factor entitled “—If the FDA were to begin actively regulating our 
tests, we could incur substantial costs and delays associated with trying to obtain premarket clearance or approval and 
incur costs associated with complying with post-market controls,” development of the data necessary to obtain regulatory 
clearance and approval of a test is time-consuming and carries with it the risk of not yielding the desired results. The 
performance  achieved  in  published  studies  may  not  be  repeated  in  later  studies  that  may  be  required  to  obtain  FDA 
premarket  clearance  or  approval  or  regulatory  approvals  in  foreign  jurisdictions.  Limited  results  from  earlier-stage 
verification studies may not predict results from studies in larger numbers of subjects drawn from more diverse populations 
over longer periods of time. Unfavorable results from ongoing preclinical and clinical studies may delay, limit or prevent 
regulatory approvals or clearances or commercialization of our product candidates, or could result in delays, modifications 
or abandonment of ongoing analytical or future clinical studies, or abandonment of a product development program, any 
of which could have a material adverse effect on our business, operating results or financial condition. 

These  and  other  factors  beyond  our  control  could  result  in  delays  or  other  difficulties  in  the  research  and 
development, approval, production, launch, ongoing commercialization or distribution of enhanced or new tests and could 
adversely affect our competitive position and results of operations. 

36 

Our quarterly results may fluctuate from period to period, which could adversely impact the value of our common stock. 

Our quarterly results of operations, including our revenues, gross margin, net loss and cash flows, may vary from 
period to period as a result of a variety of factors, many of which are outside of our control, including those listed elsewhere 
in this “Risk Factors” section, and as a result, period-to-period comparisons of our operating results may not be meaningful. 
Our quarterly results should not be relied upon as an indication of future performance. In addition, to the extent that we 
continue to spend considerably on our internal sales and marketing and research and development efforts, we expect to 
continue to incur costs in advance of achieving the anticipated benefits of such efforts. Fluctuations in quarterly results 
and key metrics may cause our results to fall below our financial guidance or other projections or goals, or the expectations 
of analysts or investors, which could adversely affect the price of our common stock. We also face competitive pricing 
and  reimbursement  pressures,  and  we  may  not  be  able  to  maintain  our  premium  pricing  in  the  future,  which  would 
adversely affect our operating results. 

Competition in our industry is intense; if we are unable to compete successfully with respect to our current or future 
products or services, we may be unable to increase or sustain our revenues or achieve profitability. 

We  compete  primarily  in  the  molecular  testing  field,  which  is  characterized  by  rapid  technological  changes, 
frequent new product introductions, reimbursement challenges, emerging competition, intellectual property disputes and 
litigation,  price  competition,  aggressive  marketing  practices,  evolving  industry  standards  and  changing  customer 
preferences. Our principal competition in women’s health comes from existing testing methods, technologies and products 
that are used by OB/GYNs, MFM specialists or IVF centers. These include other NIPTs and carrier screening tests offered 
by  our  competitors,  as  well  as  established,  traditional  first-line  prenatal  screening  methods,  such  as  serum  protein 
measurement,  where  doctors  measure  certain  hormones  in  the  blood,  and  invasive  prenatal  diagnostic  tests  like 
amniocentesis, which have been used for many years and are therefore difficult to displace or supplement. In addition, 
new testing methods may be developed which may displace or be preferred over NIPTs, such as whole genome sequencing 
or single cell analysis. We are relatively new to the fields of oncology and organ health, and face competition in these 
business areas from other companies, many of which are larger, more established and have more experience and more 
resources  than  we  do.  Some  companies  in  the  ctDNA-based  liquid  biopsy  field  are  expanding  their  research  and 
development efforts to include tracking more tumor-specific variants and/or other biomarkers in addition to ctDNA, on 
the basis that these analyses may collectively result in improved sensitivity and earlier detection than currently available 
tests, such as Signatera. We cannot assure you that research, discoveries or other advancements by other companies will 
not render our existing or potential products and services uneconomical or result in products and services that are superior 
or otherwise preferable to our current or future products and services. 

We  compete  with  numerous  companies  in  the  genetic  diagnostics  space.  Our  competitors  in  the  NIPT  space 
include Sequenom, Inc., or Sequenom, which was acquired by Laboratory Corporation of America Holdings, or LabCorp; 
Illumina,  through  its  subsidiary  Verinata;  Myriad  Genetics,  Inc.,  which  acquired  Counsyl,  Inc.;  Invitae  Corp.;  Quest 
Diagnostics Incorporated, or Quest; Premaitha Health PLC; BGI; Bio-Reference, a business unit of OPKO Health, Inc. 
and which acquired Ariosa, Inc.; NxGen; BillionToOne Inc.; PerkinElmer Inc.; and Mount Sinai Genomics, Inc. d/b/a 
Sema4. We also compete against companies providing carrier screening tests such as LabCorp; Myriad Genetics, Inc.; 
Sema4;  Invitae  Corp.;  BillionToOne  Inc.;  Quest;  NxGen;  GeneDx,  Inc.,  a  subsidiary  of  Bio-Reference;  and  GenPath 
Diagnostics, a business unit of Bio-Reference. In the field of ctDNA-based MRD assessment and recurrence surveillance, 
we face competition from various companies that offer or seek to offer competing solutions, such as Roche Diagnostics, a 
division  of  Roche;  Guardant  Health, Inc.,  Adaptive  Biotechnologies,  Personal  Genome  Diagnostics, Inc.,  which  has 
entered into an agreement to be acquired by Labcorp, one of our primary competitors in both NIPT and carrier screening; 
Exact  Sciences  Corp.;  Inivata, Inc.,  which  has  been  acquired  by  NeoGenomics,  Inc.;  C2i  Genomics, Inc.;  and 
ArcherDX, Inc., or ArcherDX, which has been acquired by Invitae Corp., one of our primary competitors in both NIPT 
and carrier screening. In the field of organ health, our primary competitors include CareDx and Eurofins Viracor, Inc. We 
expect that competition in these spaces will continue to increase. 

Some of our competitors’ products and services are sold at a lower price than ours, which could cause sales of 
our tests and services to decline or force us to reduce our prices. Our current and future competitors could have greater 
technological, financial, reputational and market access advantages than us, and we may not be able to compete effectively 
against  them.  Increased  competition  is  likely  to  result  in  pricing  pressures,  which  could  harm  our  revenues,  operating 
income or market share. We are increasingly subject to litigation with our competitors; for example, as disclosed elsewhere 
in these risk factors, we are or have recently been in active litigation with competitors in each of the women’s health, 

37 

oncology and organ health fields, which involve considerable costs to us as well as management time and attention. If we 
are unable to compete successfully, we may be unable to increase or sustain our revenues or achieve profitability. 

We may not be successful in commercializing our cloud-based distribution model. 

We utilize a cloud-based distribution model to deploy our bioinformatics technology for use by other laboratories. 
Under this model, clinical laboratories around the world, including in the U.S., license our technology to develop and run 
their own NIPT or other molecular testing assays in their own facilities as LDTs, and then access our proprietary algorithms 
through our cloud-based Constellation software to analyze the assay results. In the diagnostics industry, the market for 
cloud-based  solutions  and  services  is  not  as  mature  as  the  market  for  on-premise  enterprise  software,  and  it  remains 
uncertain whether and to what extent our cloud-based distribution model will achieve and sustain high levels of customer 
demand and market acceptance. As of February 15, 2022, fewer than 15 licensees are using Constellation commercially 
to market NIPT products and one licensee is using Constellation commercially to market its non-invasive prenatal paternity 
test in the United States and internationally. The rate of adoption of our cloud-based distribution model continues to be 
slower than we anticipated, and depends on a number of factors, including the cost, performance and perceived value 
associated with our solution, as well as our ability to address security, privacy and regulatory requirements or concerns. In 
particular,  all  of  our  licensees  under  our  cloud-based  distribution  model  are  required  to  use  Illumina  sequencers  and 
reagents to run their tests that they develop based on our technology. As further described in the risk factor entitled “—
We rely on a limited number of suppliers or, in some cases, single suppliers, for some of our laboratory instruments and 
materials and may not be able to find replacements or immediately transition to alternative suppliers,” we are aware that 
Illumina has required our licensees to pay an additional license fee in certain jurisdictions in order to secure a supply 
agreement for the sequencers and reagents necessary to run NIPT under our cloud-based distribution model. Furthermore, 
Illumina  competes  with  us  through  its  subsidiary  Verinata,  and  may  not  charge  a  similar  license  fee  for  Verinata’s 
licensed-based offering to other laboratories. As a result, our potential or current licensees may be unable to commercially 
launch their tests under our cloud-based distribution model in a financially viable manner, which has dissuaded and could 
continue to dissuade potential or current licensees from licensing from us or launching a test based on our technology. In 
addition, if a test developed by any of our licensees under our cloud-based distribution model in the United States is found 
not to be an LDT, the licensee may not be able to market its test, and we would not receive the anticipated revenues from 
that licensee. 

We also do not know whether, over the long term, this model will result in benefits or cost savings at the levels 
that we anticipate or at all. For example, to the extent that any of our laboratory customers for whom we currently perform 
our tests entirely in our laboratory transition to our cloud-based distribution model, our revenues from such customers will 
decrease because we are not able to charge as high an amount per test as when we perform the entire test ourselves. If the 
lower revenues per test performed is not offset by a sufficient increase in volume of tests sold, our overall revenues will 
be lower, and our results of operations may be adversely affected. 

Among the risks to our business and results of operations from our Constellation model are the following: 

• 

• 

• 

• 

our and our licensees’ ability to obtain required regulatory authorizations from the FDA and international 
regulatory  agencies  as  further  described  in  the  risk  factor  entitled  “Reimbursement  and  Regulatory  Risks 
Related to Our Business—Failure to obtain necessary regulatory approvals may adversely affect our ability 
to expand our operations internationally, including our ability to continue commercializing our cloud-based 
distribution model;” 

supply constraints, including with respect to the blood collection tubes that are used for many of our tests, 
such  as  Panorama,  Signatera  and  Prospera,  and  that  are  supplied  by  Streck, Inc.,  or  Streck,  as  further 
described in the risk factor entitled “—We rely on a limited number of suppliers or, in some cases, single 
suppliers, for some of our laboratory instruments and materials and may not be able to find replacements or 
immediately transition to alternative suppliers;” 

allegations or potential third-party claims that the tests, based on our technology, developed by our licensees 
violate such third parties’ intellectual property rights; 

licensing  portions  of  our  proprietary  technology  to  third  parties  that  may  not  take  the  same  security 
precautions as we do to protect this information; and 

38 

• 

an inability to achieve anticipated benefits and costs savings. 

If we or other cloud-based solution providers experience security incidents, loss of customer data or disruptions 
in delivery or other problems, the market for cloud-based solutions in the diagnostics industry, including our solutions, 
may be adversely affected. Such events could also result in potential lawsuits and liability claims, which could have a 
material adverse effect on our business. If there is a reduction in demand for cloud-based solutions caused by technological 
challenges, weakening economic conditions, security or privacy concerns, competing technologies and products or other 
challenges, we may not be successful in executing our Constellation business model, and our results of operations may be 
adversely affected. 

We rely on internal and third-party data centers and platforms to host our laboratory and cloud-based software, and 
any interruptions of service or failures may impair our laboratory operations or the delivery of our cloud-based services 
and harm our business. 

We  currently  maintain  a  data  center  at  our  laboratory  facilities  in  San  Carlos,  California.  In  addition,  our 
proprietary bioinformatics algorithms are a crucial component of our test processing, and combine information derived 
from our mmPCR assay workflows with publicly available data from the broader scientific community to analyze and 
return test results. We host the significant majority of these algorithms on a cloud-based software platform pursuant to an 
agreement with DNAnexus, Inc., or DNAnexus, and both we and our Constellation licensees access our algorithms through 
the  DNAnexus  platform.  The  DNAnexus  platform  is  hosted  on  third-party  data  center  hosting  facilities  operated  by 
Amazon Web Services, or AWS, located primarily in the United States and in the European Union. These algorithms are 
currently  used  to  run  our  Panorama  NIPT,  Horizon,  Signatera,  and  Prospera  tests  and  certain  of  our  research  and 
development activities, as well as for our Constellation licensees. In the event of any technical problems that may arise in 
connection with our on-site data center, the DNAnexus platform or the AWS servers on which the DNAnexus platform is 
hosted,  or  difficulties  in  or  termination  of  our  relationship  with  DNAnexus,  we  could  experience  interruptions  in  our 
laboratory operations or our cloud-based services, and we and our Constellation licensees may be unable to access our 
proprietary algorithms and therefore be unable to process tests or conduct any other activities that require access to such 
algorithms. These types of problems may be caused by a variety of factors, including infrastructure changes, human or 
software errors, viruses, security attacks, fraud, spikes in customer usage and denial of service issues. We do not have any 
backup platform, server or other means to host our algorithms, and may be unable to find and implement an alternative 
platform that is satisfactory for our needs on commercially reasonable terms, in a timely manner, or at all. Interruptions in 
our operations or service may reduce our revenue, cause us to issue refunds, result in the loss of customers, cause laboratory 
licensees to terminate their contracts with us, adversely affect our ability to attract new laboratory licensees, or harm our 
reputation. We could also be exposed to potential lawsuits and liability claims. 

If our products do not perform as expected, our operating results, reputation and business will suffer. 

Our success depends on the market’s confidence that we can provide reliable, high-quality testing results. There 
is  no  guarantee  that  the  accuracy  and  reproducibility  we  have  demonstrated  to  date  will  continue  as  our  test  volumes 
continue to increase and our product portfolio continues to expand. We believe that our customers are particularly sensitive 
to test limitations and errors, including inaccurate test results and the need on occasion to perform second blood draws, or 
redraws, on patients, for which Panorama experiences a higher rate than advertised for other NIPTs. As a result, if our 
tests do not perform as expected or favorably in comparison to competitive tests, our operating results, reputation, and 
business will suffer. We may also become subject to legal claims arising from such limitations, errors, or inaccuracies. 

Our tests use a number of complex and sophisticated biochemical and bioinformatics processes, many of which 
are highly sensitive to external factors. An operational, technological or other failure in one of these complex processes, 
or fluctuations in external variables, may result in sensitivity or specificity rates that are lower than we anticipate or that 
vary between test runs, a higher than anticipated number of tests that require redraws or fail to produce results, or longer 
than expected turnaround times, which we have experienced and will likely continue to experience on occasion as a result 
of issues with laboratory equipment, components or materials or otherwise. In addition, we regularly evaluate and refine 
our testing processes, and any refinements we make may not improve our tests as we expect and may result in unanticipated 
issues that may adversely affect our test performance as described above, which we have experienced in the past. Such 
operational, technical and other difficulties may impact the commercial attractiveness of our products, may increase our 

39 

costs or divert our resources, including management’s time and attention, from other projects and priorities, or may subject 
us to legal claims. Furthermore, any changes to our testing process may require us to use new or different suppliers or 
materials with whom or which we are unfamiliar, and which may not perform as we anticipate, and could cause delays, 
downtime or other operational issues. 

In addition, as further discussed in the risk factor entitled “If we are unable to successfully grow revenues for our 
current or future products or services in addition to Panorama, our business and results of operations may be adversely 
affected,” a growing number of our tests are relatively new offerings, such as Signatera and Prospera. Any failure to meet 
consumer expectations could harm our reputation. 

We rely on third-party laboratories to perform portions of our service offerings. 

Certain  of  our  tests,  or  components  of  our  tests,  are  performed  by  third-party  laboratories.  These  third-party 
laboratories are subject to contractual obligations to perform these services for us, but are not otherwise under our control. 
We therefore do not control the capacity and quality control efforts of these third-party laboratories other than through our 
ability to enforce contractual obligations on volume and quality systems, and we have no control over such laboratories’ 
compliance  with  applicable  legal  and  regulatory  requirements.  We  also  have  no  control  over  the  timeliness  of  such 
laboratories’ performance of their obligations to us, and third-party laboratories that we have contracted with have in the 
past had, and occasionally continue to have, issues with delivering results to us or resolving issues with us within the time 
frames we expected or established in our contracts with them, which sometimes results in longer than expected turnaround 
times for, or negatively impacts the performance of, these tests and services. Any natural or other disaster, acts of war or 
terrorism,  shipping  embargoes,  labor  unrest  or  political  instability  or  similar  events  at  one  or  more  of  our  third-party 
laboratories’ facilities that causes a loss of capacity would heighten the risks that we face. We may not have sufficient 
alternative backup if one or more of the third-party laboratories that we contract with are unable to satisfy their obligations 
to us with sufficient performance, quality and timeliness, including as a result of the COVID-19 pandemic. Changes to or 
termination of our agreements or inability to renew our agreements with these third-party laboratories or enter into new 
agreements with other laboratories that are able to perform such portions of our service offerings could impair, delay or 
suspend  our  efforts  to  market  and  sell  these  tests  and  services.  In  the  event  of  any  adverse  developments  with  these 
third-party laboratories or their ability to perform their obligations to us in a timely manner and in accordance with the 
standards that we and our customers expect, our ability to service our customers may be delayed, interrupted or otherwise 
adversely affected, which could result in a loss of customers and harm to our reputation. Furthermore, when these issues 
arise,  we  have  had  to  expend  time,  management  attention  and  other  resources  to  address  and  remedy  such  issues.  In 
addition, certain third-party payers, including some state Medicaid payers, that we are under contract with may take the 
position that sending out testing to third-party laboratories and billing for such tests is contrary to the terms of our provider 
agreement and may refuse to pay us for the testing. If any of these events occur, our business, financial condition and 
results of operations could suffer. Further, some state laws impose anti-markup restrictions that prevent an entity from 
realizing a profit margin on outsourced testing. If we or our subsidiaries are unable to markup outsourced testing, our 
revenues and operating margins may suffer. 

If we are unable to successfully grow revenues for our products or services in addition to Panorama and Horizon, our 
business and results of operations may be adversely affected. 

Our  ability  to  successfully  grow  revenues  for  products  or  services  in  addition  to  Panorama  and  Horizon,  is 
uncertain and is subject to many of the risks we face with respect to Panorama and Horizon. For example, the adoption 
and demand for such products or services may not grow as we expect; we may not be able to demonstrate that such products 
or services are equivalent or superior to competing products or services; third-party payers may not reimburse for our tests, 
or may set the amounts of such reimbursements at prices that do not allow us to cover our expenses; we may fail to compete 
successfully  in  the  relevant  product  markets,  or  our  laboratory  distribution  partners  may  choose  to  more  actively  or 
exclusively market tests by competitors; we may experience supply constraints; and we may fail to adequately protect our 
intellectual property relating to our products or others may claim we infringe their intellectual property rights, which has 
occurred, as disclosed elsewhere in these Risk Factors. In addition, because our revenues from Horizon now represent a 
significant proportion of our overall revenues, any adverse impact we experience with respect to Horizon could result in 
an impact to our overall revenues, or a component of such overall revenues; for example, a decline in our reimbursement 
rates for, and therefore our average selling price of, Horizon, could result in a decline in our overall blended average selling 

40 

price. If we are not able to increase adoption of and grow revenues for our products or services, our business and results 
of operations may be adversely affected. 

We began offering our Vistara single-gene mutations screening test, our Signatera MRD test for research use 
only, and our twin pregnancies screening capability for Panorama, in 2017; our Signatera CLIA test and Prospera transplant 
rejection test on limited bases in 2019, with full-scale commercial launches of both Signatera and Prospera, among other 
products, in 2020; and expansions of both Signatera and Prospera into additional indications in 2021. Our success with 
these offerings is subject to many of the risks affecting our business generally, as well as the inherent difficulties with 
launching a new offering and in new markets, including risks inherent in launching multiple new offerings simultaneously. 
Some of our offerings, such as Signatera and Prospera, while based upon our core molecular diagnostic technology, are in 
fields  that  are  relatively  new  to  us;  and  others,  such  as  Vistara,  are  subject  to  the  risks  inherent  in  commercializing  a 
product  with  a  laboratory  partner.  We  have  had  to  review  and,  in  some  cases,  revise  our  processes,  procedures  and 
agreements with our business partners to address unforeseen operational issues and other contingencies, and will likely 
continue to do so as these areas of our business grow. We cannot assure you that our recent or any new offerings will be 
successful. 

If either of our CLIA-certified laboratory facilities becomes inoperable, we will be unable to perform our tests and our 
business will be harmed. 

We currently operate laboratory facilities in Austin, Texas and in San Carlos, California, both of which process 
Panorama and Horizon tests, which together represent the significant majority of our revenues. All of our other tests are 
currently only able to be performed at one, but not both, of our facilities, and primarily our San Carlos facility. In particular, 
our efforts in oncology and organ health represent significant and increasing areas of focus for us, both operationally and 
financially; our Signatera CLIA and RUO tests, and our Prospera tests, are currently only performed at our San Carlos 
facility, and we currently otherwise have no backup or redundant facility to perform these tests. Our San Carlos facility is 
situated near active earthquake fault lines. Either of our facilities may be harmed or rendered inoperable, or samples could 
be damaged or destroyed, by natural or manmade disasters, including earthquakes, severe weather, flooding, power outages 
and contamination, including as a result of the COVID-19 pandemic, which may render it difficult or impossible for us to 
perform our tests for some period of time. The inability to perform our tests or the backlog of tests that could develop if 
either our San Carlos or Austin facility is inoperable for even a short period of time may result in the loss of customers or 
harm our reputation. 

We rely on a limited number of suppliers or, in some cases, single suppliers, for some of our laboratory instruments 
and materials and may not be able to find replacements or immediately transition to alternative suppliers. 

We  have  sourced  and  will  continue  to  source  components  of  our  technology,  including  sequencers,  reagents, 
tubes and other laboratory materials, from third parties. In particular, our sequencers, many of our reagents, including for 
Panorama, Horizon and Signatera as described below, and our blood collection tubes, are sole sourced. 

For example, our molecular diagnostics tests are currently only validated to perform on Illumina’s sequencing 
platform; in addition, Illumina is currently the sole supplier of our sequencers and related reagents for Panorama, Horizon, 
Signatera and Prospera, along with certain hardware and software, pursuant to a supply agreement that expires in August 
2033. Without sequencers and the related reagents, we would be unable to run our tests and commercialize our products. 
In addition, all of the licensees under our cloud-based distribution model do not have alternatives other than to use Illumina 
sequencers and reagents to run the tests that they develop based on our technology. In addition, Illumina and Sequenom, 
which was acquired by LabCorp, have entered into a patent pooling agreement pursuant to which both parties have pooled 
their intellectual property directed to NIPT. We understand from public filings that under the patent pooling agreement, 
Illumina has the exclusive worldwide rights to, among other things, license third-party laboratories to develop and sell 
NIPTs utilizing the pooled intellectual property and to enforce the pooled intellectual property against suspected infringers. 
Illumina has granted us certain rights to Illumina’s intellectual property related to NIPT, including the pooled intellectual 
property, for running our own tests; however, we do not have an express license to grant rights under the pooled intellectual 
property to the licensees under our cloud-based distribution model. We are aware that Illumina has required our licensees, 
in  order  to  secure  a  supply  agreement  for  the  sequencers  and  reagents  necessary  to  run  NIPT  under  our  cloud-based 
distribution model, to pay an additional fee for a license under the pooled intellectual property in jurisdictions in which 
Illumina believes certain of the pooled intellectual property is enforceable. This additional fee has dissuaded and could 
continue to dissuade potential or current licensees from licensing from us or launching a test based on our technology. In 

41 

addition, we have recently been involved in patent infringement litigation against Illumina, which we and Illumina have 
settled. In addition, Illumina directly competes with us in the NIPT market through its subsidiary, Verinata. We understand 
Illumina  supplies  the  same  or  similar  sequencers  and  consumables  to  Verinata.  Because  of  Illumina’s  ownership  of 
Verinata, we face increased risk and uncertainty regarding continuity of a successful working relationship with Illumina 
under our supply agreement, as well as in our ability to compete with Verinata in the marketplace in view of economic 
advantages enjoyed by Verinata with respect to the cost of sequencers and related consumables. Furthermore, Illumina has 
acquired GRAIL, a company focused on early detection of cancer, an area in oncology that we have recently begun to 
pursue. Our failure  to maintain  a  continued  supply  of  the sequencers  and  reagents,  along with  the  right  to  use  certain 
hardware and software, would adversely impact our business, financial condition, and results of operations. In particular, 
while we are seeking to validate our tests on additional sequencing platforms, such as under our license agreement with 
BGI Genomics Co., Ltd., or BGI Genomics, we have not, to date, validated any alternative sequencing platform on which 
our testing could be run in a commercially viable manner. These efforts will require significant resources, expenditures 
and time and attention of management, and there is no guarantee that we will be successful in implementing any such 
sequencing platforms in a commercially sustainable way. We also cannot guarantee that we will appropriately prioritize 
or select alternative sequencing platforms on which to focus our efforts, in particular given our limited product and research 
and development resources and various business initiatives, which could result in increased costs and delayed timelines or 
otherwise impact our business and results of operations. 

In addition, our Panorama test is currently only validated to be performed using Streck’s blood collection tubes, 
and we only use Streck tubes for the primary analysis of Signatera results, and for our Prospera test. Streck is the sole 
supplier of the blood collection tubes included in Panorama and our other cell-free DNA tests under a supply arrangement 
with  Streck  under  which  we  are  required  to  exclusively  use  Streck  tubes.  Similarly,  all  of  the  licensees  under  our 
cloud-based distribution model also have no current alternative but to use these blood collection tubes to run the tests that 
they develop based on our technology. 

Furthermore, our sequencers, sourced from Illumina, as well as certain other reagents we use for Panorama and 
our other tests, are intended for research use only and are labeled as RUO. As discussed further in the risk factor entitled 
“Reimbursement and Regulatory Risks Related to Our Business—Changes in the way the FDA regulates the reagents, 
other consumables, and testing equipment we use when developing, validating, and performing our tests could result in 
delay or additional expense in bringing our tests to market or performing such tests for our customers,” the FDA may 
determine that a product labeled RUO is, nonetheless, intended to be used diagnostically, and could take enforcement 
action against the manufacturer of the product. If this were to occur with respect to Illumina or any of our other suppliers 
of RUO products, we could be required to obtain one or more alternative sources of these products, and we may not be 
able  to  do  so  on  commercially  reasonable  terms  or  at  all.  In  addition,  Streck’s  blood  collection  tubes  have  not  been 
registered as a medical device in all countries in which we market our Panorama test. As discussed in the risk factor entitled 
“Reimbursement and Regulatory Risks Related to Our Business—Failure to obtain necessary regulatory approvals may 
adversely affect our ability to expand our operations internationally, including our ability to continue commercializing 
our  cloud-based  distribution  model,”  the  regulatory  authorities  in  some  of  these  countries  may  determine  that  such 
registration is required, which could impact our ability to offer Panorama in such countries. Furthermore, because our 
licensees under our cloud-based distribution model also exclusively use such sole-sourced components to run the tests they 
develop  based  on  our  technology,  and  our  laboratory  distribution  partners  must  use  certain  of  such  sole-sourced 
components in order to utilize our tests, any enforcement action against the supplier by the FDA or any other regulatory 
authority in the jurisdictions in which our licensees and laboratory distribution partners are located could have an adverse 
impact on our business. 

Because we rely on third-party manufacturers, we do not control the manufacture of these components, including 
whether  such  components  will  meet  our  quality  control  requirements,  nor  the  ability  of  our  suppliers  to  comply  with 
applicable legal and regulatory requirements. In many cases, our suppliers are not contractually required to supply these 
components to the quality or performance standards that we require. If the supply of components we receive does not meet 
our quality control or performance standards, we may not be able to use the components, or if we use them not knowing 
that they are of inadequate quality, which occasionally occurs with respect to certain reagents, our tests may not work 
properly or at all, or may provide erroneous results, and we may be subject to significant delays caused by interruption in 
production or manufacturing or to lost revenue from such interruption or from spoiled tests. In addition, any natural or 

42 

other disaster, acts of war or terrorism, shipping embargoes, labor unrest or political instability or similar events at our 
third-party manufacturers’ facilities that cause a loss of manufacturing capacity would heighten the risks that we face. 

In the event of any adverse developments with our sole suppliers, or if any of our sole suppliers modifies any of 
the  components  they  supply  to  us,  our  ability  to  supply  our  products  may  be  interrupted,  and  obtaining  substitute 
components could be difficult or require us to re-design or re-validate our products. In addition, if we obtain FDA clearance, 
approval or authorization for any of our tests as an in vitro diagnostic, or IVD, such issues with suppliers or the components 
that we source from suppliers could affect our commercialization efforts for such an IVD, as further described in the risk 
factor  entitled  “Reimbursement  and  Regulatory  Risks  Related  to  Our  Business—If  the  FDA  were  to  begin  actively 
regulating our tests, we could incur substantial costs and delays associated with trying to obtain premarket clearance or 
approval and incur costs associated with complying with post-market controls.” Our failure to maintain a continued supply 
of components, or a supply that meets our quality control requirements, or changes to or termination of our agreements or 
inability to renew our agreements with these parties or enter into new agreements with other suppliers, particularly in the 
case of sole suppliers such as Streck and Illumina, could result in the loss of access to important components of our tests 
and impact our test performance or affect our ability to perform our tests in a timely manner or at all, which could impair, 
delay or suspend our commercialization activities. In the event that we transition to a new supplier from any of our sole 
suppliers, doing so could be time-consuming and expensive, may result in interruptions in our ability to supply our products 
to  the  market,  could  affect  the  performance  of  our  tests  or  could  require  that  we  re-validate  our  affected  tests  using 
replacement equipment and supplies, which could delay the performance of our tests and result in increased costs. Any of 
these occurrences could have a material adverse effect on our business, financial condition and results of operations. 

We  rely  on  commercial  courier  delivery  services  to  transport  samples  to  our  facilities  in  a  timely  and  cost-efficient 
manner and if these delivery services are disrupted, our business will be harmed. 

Our core business depends on our ability to quickly and reliably deliver test results to our customers. We typically 
receive blood samples for analysis at our laboratory facilities within days of collection from the patient. Disruptions in 
delivery service – whether due to error by the courier service, labor disruptions, bad weather, natural disaster, terrorist acts 
or threats or for other reasons – some of which we have experienced in the past, could adversely affect specimen integrity, 
our ability to process or store samples in a timely manner and to service our customers, and ultimately our reputation and 
our business. In addition, if we are unable to continue to obtain expedited delivery services on commercially reasonable 
terms, our operating results may be adversely affected. 

Security  breaches,  loss  of  data  and  other  disruptions,  including  with  respect  to  cybersecurity,  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 and reputation. 

In the ordinary course of our business, we collect and store sensitive data, including legally-protected personal 
information, such as test results and other patient health information, credit card and other financial information, insurance 
information, and personally identifiable information. We also store sensitive intellectual property and other proprietary 
business  information,  including  that  of  our  customers,  payers  and  collaboration  partners.  We  are  highly  dependent  on 
information technology networks and systems, including a combination of on-site systems, managed data center systems 
and  cloud-based  data  center  systems,  and  the  Internet,  to  securely  process,  transmit,  and  store  a  wide  variety  of 
business-critical information, including research and development information, commercial information and business and 
financial information. We also communicate sensitive data, including patient data, telephonically, through our website, 
through facsimile, through integrations with third party electronic medical records systems, and through relationships with 
third  party  vendors  and  their  subcontractors,  both  in  the  United  States  and  internationally.  The  laws  of  some  foreign 
countries do not protect data privacy to the same extent as the laws of the United States. 

The  secure  processing,  storage,  maintenance  and  transmission  of  this  critical  information  are  vital  to  our 
operations and business strategy. Although we take measures to protect sensitive information from unauthorized access, 
use or disclosure, our information technology and infrastructure, and that of our technology and other third-party service 
providers and their subcontractors, are nevertheless inherently vulnerable, to some extent, to cyber-attacks by hackers or 
viruses  or  breaches  due  to  employee  error,  technical  error,  malfeasance  or  other  disruptions.  Any  such  breach  or 
interruption, whether of our systems or that of our third-party service providers or their subcontractors, could compromise 

43 

our data security, and the information we store could be inaccessible by us or could be accessed by unauthorized parties, 
publicly disclosed, lost or stolen. Any such interruption in access, improper access, disclosure, modification, or other loss 
of information could result in legal claims or proceedings, liability or penalties under laws and regulations that protect the 
privacy  of personal  information,  such  as  the  Health  Insurance  Portability  and  Accountability  Act of 1996, or HIPAA, 
European data privacy regulations, such as the General Data Protection Regulation, or GDPR, or state privacy regulations, 
such as the California Consumer Privacy Act. We may be required to comply with state breach notification laws, become 
subject to mandatory corrective action, or be required to verify the correctness of database contents. Unauthorized access, 
loss or dissemination could also disrupt our operations, including our ability to perform tests, provide test results, bill 
payers or patients, process claims and appeals, provide customer assistance services, conduct research and development 
activities,  develop  and  commercialize  tests,  collect,  process  and  prepare  company  financial  information,  provide 
information  about  our  tests,  and  manage  the  administrative  aspects  of  our  business,  any  of  which  could  damage  our 
reputation and adversely affect our business. In addition, these breaches and other inappropriate access can be difficult to 
detect, and any delay in identifying them may compound these adverse consequences. Any such breach could also result 
in the compromise of our trade secrets and other proprietary information, which could adversely affect our competitive 
position.  

We are also subject the risks described above as a result of our relationships with third party vendors and their 
subcontractors,  whose  systems  may  be  breached  and  may  cause  our  sensitive  data,  including  patient  data,  to  be 
compromised. We have on occasion experienced such disruptions by way of third-party vendors. For example, in 2020 we 
were notified of a data security incident that affected a third-party vendor, which affected a number of our patients whose 
protected health information was stored in such third-party vendor’s systems. The third-party vendor notified the affected 
individuals as required by HIPAA. 

Our  cloud-based  distribution  model  adds  additional  data  privacy  risk,  as  certain  personal  health  and  other 
information may be sent to and stored in the cloud by our laboratory licensees, many of which are located outside of the 
United  States.  We  contractually  prohibit  our  licensees  from  sending  personally-identifiable  information  to  our  cloud 
servers, and the vendor that hosts our software in the cloud is contractually required to comply with data privacy laws, 
such  as HIPAA  and  GDPR. However, we cannot  be  certain  that  these  third parties will  comply with  the  terms of our 
agreements, nor that they will not experience security breaches or other disruptions. 

The marketing, sale, and use of Panorama, Horizon and our other products could result in substantial damages arising 
from product liability or professional liability claims that exceed our resources. 

The marketing, sale and use of Panorama, Horizon and our other products could lead to product liability claims 
against us if someone were to allege that our test failed to perform as it was designed or as claimed in our promotional 
materials, was performed pursuant to incorrect or inadequate laboratory procedures, if we delivered incorrect or incomplete 
test results or our test failed to produce a result, or if someone were to misinterpret test results. In addition, we may be 
subject to liability for errors in, a misunderstanding of, or inappropriate reliance upon, the information we provide, or for 
failure to provide such information, in connection with our marketing and promotional activities or as part of the results 
generated by Panorama, Horizon and our other products. For example, Panorama could provide a low-risk result which a 
patient or physician may rely upon to make a conclusion about the health of the fetus, which may, in fact, have the condition 
for which we delivered a low-risk result because the Panorama result was a so-called false negative. Similarly, Panorama 
could provide a  so-called  false positive, which  is  a high-risk  result for a  fetus  that may not,  in fact,  have  the  relevant 
condition. Even though Panorama and our other tests are highly accurate, they are not 100% accurate and we may report 
false negative or false positive results, which may subject us to lawsuits claiming product or professional liability or other 
claims, as has happened in the past and may happen in the future. A product liability or professional liability claim could 
result  in  substantial  damages  and  be  costly  and  time-consuming  for  us  to  defend.  Although  we  maintain  product  and 
professional  liability  insurance,  our  insurance  may  not  fully  protect  us  from  the  financial  impact  of  defending  against 
product liability or professional liability claims or any judgments, fines or settlement costs arising out of any such claims. 
Any product liability or professional liability claim brought against us, with or without merit, could increase our insurance 
rates,  cause  our  insurance  coverage  to  be  terminated  or  prevent  us  from  securing  insurance  coverage  in  the  future. 
Additionally, any product liability or professional liability lawsuit could harm our reputation, result in a cessation of our 
services or cause our partners to terminate our agreements with them, any of which could adversely impact our results of 
operations. 

44 

If we are unable to successfully scale our operations, our business could suffer. 

Our overall test volumes grew from approximately 804,300 to 1,026,500 and further to 1,570,000 tests processed 
during the years ended December 31, 2019, 2020 and 2021, respectively, and since 2009 we have launched 16 product 
offerings, four of them in 2017 alone and both Signatera and Prospera, among other products, in 2020. In addition, we 
regularly evaluate and refine our testing process, often significantly updating our workflows. As our test volumes and 
product offerings continue to grow, we will need to continue to ramp up our testing capacity and implement increases in 
scale,  such  as increased headcount,  additional  or new  equipment,  laboratory  space  and qualified  laboratory  personnel, 
increased office and laboratory space, expanded customer service capabilities, billing and systems process improvements, 
enhanced  controls  and  procedures,  and  an  expanded  internal  quality  assurance  program  and  technology  platform.  The 
value of Panorama, Horizon and our other products depends on our ability to perform the tests on a timely basis and at an 
exceptionally  high  standard  of  quality,  and  on  maintaining  our  reputation  for  such  timeliness  and  quality.  Failure  to 
implement necessary procedures, transition to new facilities, equipment or processes or to hire the necessary personnel in 
a timely and effective manner could result in higher processing costs or an inability to meet market demand, or could 
otherwise affect our operating results, as we have experienced in the past. 

In addition, our efforts to scale our operations may be unable to keep pace with an increase in the frequency of 
our launches of new or enhanced products and services. Since 2017, we have launched eight new products, three in markets 
or industries new to us, with several significant product enhancements and expanded indications in 2021. As we continue 
to launch additional offerings and product enhancements, we will need to manage our resources among various initiatives, 
and such competing priorities could lead to delays in one or more of our business initiatives. Conversely, to the extent that 
we scale our operations, infrastructure and other resources but do not ultimately meet our anticipated timelines in our 
product development efforts, we will experience higher costs and expenses than necessary until our project timelines and 
operational resources become aligned. We may also, intentionally or unintentionally, allocate resources to new products 
or initiatives in a manner disproportionate to the amount of revenue that such initiatives generate compared to our existing 
or core offerings. We cannot assure you that our efforts to scale our commercial operations will not negatively affect the 
quality of our test process or results, or that we will be successful in managing the growing complexity of our business 
operations. 

To  execute  our  growth  plan,  we  must  attract  and  retain  highly  qualified  personnel.  Competition  for  these 
personnel is intense, especially for sales, scientific, medical, laboratory, research and development and other technical 
personnel, and especially in the San Francisco Bay Area where we have an office and laboratory facilities, and the turnover 
rate of such personnel can be high. We have from time to time experienced, and we expect to continue to experience, 
difficulty  in  hiring  and  retaining  employees  with  appropriate  qualifications.  Many  of  the  companies  with  which  we 
compete for highly qualified personnel have greater resources than we have. If we hire employees from competitors or 
other  companies,  their  former  employers  may  attempt  to  assert  that  these  employees  or  we  have  breached  their  legal 
obligations to their former employers, which occurs from time to time. In addition, job candidates and existing employees 
in  the  San  Francisco  Bay  Area  often  consider  the  value  of  the  equity  awards  they  receive  in  connection  with  their 
employment. To the extent that our current or potential employees perceive the value of our equity awards to be low, our 
ability to recruit, retain and motivate highly skilled employees may be adversely affected, which could then have an adverse 
effect on our business and future growth prospects. Furthermore, to the extent that we are unable to retain our employees 
and they leave our company to join one of our competitors, we cannot assure you that any invention, non-disclosure or 
non-compete agreements we have in place will provide meaningful protection against a departing employee’s unauthorized 
use or disclosure of our confidential information, as further discussed in “—Risks Relating to our Intellectual Property—
If we are not able to adequately protect our trade secrets and other proprietary information, the value of our technology 
and products could be significantly diminished.” 

In addition, our growth may place a significant strain on our operating and financial systems and our management, 
sales, marketing and administrative resources. As a result of our growth, our operating costs may escalate faster than we 
anticipate, we may face difficulties in obtaining additional office or laboratory space, and some of our internal systems 
may need to be enhanced or replaced. If we cannot effectively manage our expanding operations and our costs, we may 
not be able to grow successfully or we may grow at a slower pace, and our business could be adversely affected. 

45 

If our sales, distribution, development or other partnerships are not successful and we are not able to offset the resulting 
impact through our own efforts or through agreements with new partners, our commercialization activities may be 
impaired and our financial results could be adversely affected. 

Part of our business strategy is to develop relationships with laboratory and other partners to develop or sell our 
products,  both  in  the  United  States  and  internationally.  For  example,  we  have  entered  into  an  agreement  with  BGI 
Genomics pursuant to which, among others, we will commercialize Signatera in China and develop reproductive health 
tests on BGI Genomics’s sequencing platform; and an agreement with Foundation Medicine to develop and commercialize 
personalized circulating tumor DNA monitoring assays for use by biopharmaceutical and clinical customers who order 
Foundation Medicine’s companion diagnostic cancer test. Developing and commercializing products with third parties 
reduces our control over such development and commercialization efforts and subjects us to the various risks inherent in 
a joint effort with a third party, such as delays, operational issues, technical difficulties and other contingencies outside of 
our influence or control. Distributing Panorama, Signatera and our other products through partners reduces our control 
over our revenues, our market penetration and our gross margin on sales by the partner if we could have otherwise made 
that sale through our direct sales force. The financial condition of these third parties could weaken, or they could terminate 
their relationship with us and/or stop selling our products, as has happened in the past; reduce their marketing efforts in 
respect of our products; develop and commercialize or otherwise sell competing products in addition to or in lieu of our 
tests, as has also occurred; merge with or be acquired by a competitor of ours or a company that chooses to de-prioritize 
or cease the efforts to develop, sell or otherwise partner with us on our products; or otherwise breach their agreements 
with us. For example, as further described in “Note 3—Revenue Recognition—Licensing and Other Revenues—Qiagen” 
of  our  consolidated  financial  statements,  we  had  entered  into  a  license,  distribution  and  development  agreement  with 
Qiagen pursuant to which, among others, Qiagen would distribute an NIPT based on our Panorama test on a sequencer to 
be  developed  by  us  and  Qiagen;  however,  Qiagen  thereafter  discontinued  the  development  of  its  Next  Generation 
Sequencing Platform and instead partnered with Illumina to develop next-generation sequencing based tests. Furthermore, 
our laboratory partners may misappropriate our trade secrets or use our proprietary information in such a way as to expose 
us to litigation and potential liability; and our compliance risk may increase to the extent that we are responsible, or deemed 
responsible,  for  our  partners’  sales  and  marketing  activities.  Disagreements  or  disputes  with  our  partners,  including 
disagreements  over  customers,  proprietary  rights  or  our  or  their  compliance  with  contractual  obligations,  might  cause 
delays or impair the commercialization of Panorama, Signatera or our other tests, lead to additional responsibilities for us 
with  respect  to  new  tests,  or  result  in  litigation  or  arbitration,  any  of  which  would  divert  management  attention  and 
resources and be time-consuming and expensive. As is typical for companies in our industry, we are continually evaluating 
and pursuing various strategic or commercial partnerships, relationships, or collaborations, some of which may involve 
the sale and issuance of our common stock, which could result in additional dilution of the percentage ownership of our 
stockholders and could cause the price of our common stock to decline. 

If our partnerships are not successful, our ability to increase sales of our products and to successfully execute our 

strategy could be compromised. 

Our financial condition and results of operations may be adversely affected by international regulatory and business 
risks. 

As we expand our operations, including by offering our tests in other countries, we are increasingly subject to 
varied and complex foreign and international laws and regulations due to operating, offering our products, or contracting 
with  employees,  contractors  and  other  service  providers  in  various  other  countries.  Compliance  with  these  laws  and 
regulations often involves significant costs and may require changes in our business practices that may result in reduced 
revenues and adversely affect our operating results. 

We  are  subject  to  the  Foreign  Corrupt  Practices  Act  of  1977,  as  amended,  or  the  FCPA,  which  prohibits 
companies and their intermediaries from making payments in violation of law to non-U.S. government officials for the 
purpose  of  obtaining  or  retaining  business  or  securing  any  other  improper  advantage.  Our  reliance  on  independent 
laboratories to sell Panorama and other products internationally demands a high degree of vigilance in maintaining our 
policy against participation in corrupt activity, because these distributors could be deemed to be our agents and we could 
be held responsible for their actions. Other U.S. companies in the medical device and pharmaceutical field have faced 
criminal penalties under the FCPA for allowing their agents to deviate from appropriate practices in doing business with 
foreign government officials. We are also subject to similar anti-bribery laws in the jurisdictions in which we operate, 
including the United Kingdom’s Bribery Act of 2010, which also prohibits commercial bribery and makes it a crime for 

46 

companies to fail to prevent bribery. These laws are complex and far-reaching in nature. Any violations of these laws, or 
allegations of such violations, could disrupt our operations, involve significant management distraction, involve significant 
costs and expenses, including legal fees, and we could be subject to severe penalties, including criminal and civil penalties, 
disgorgement,  and  other  remedial  measures,  any  of  which  could  result  in  a  material  adverse  effect  on  our  business, 
prospects, financial condition, or results of operations. 

In  addition,  our  international  activities  are  subject  to  U.S.  economic  and  trade  sanctions,  which  restrict  or 
otherwise limit our ability to do business in certain designated countries. Other limitations, such as restrictions on the 
import into the United States or the export to other countries of tissue or genetic data necessary for us to perform our tests, 
or restrictions on importation and circulation of blood collection tubes or other equipment or supplies by countries outside 
of the United States, may limit our ability to offer our tests internationally. We may also face competition from companies 
located in the countries in which we or our partners or licensees offer our tests, and in which we may be at a competitive 
disadvantage because the country may favor a local provider or for other reasons. 

By operating internationally, we may experience longer accounts receivable payment cycles and difficulties in 
collecting accounts receivable; realize lower margins due to lower pricing in many countries; incur potentially adverse tax 
consequences, including the complexities of foreign value added tax systems, tax inefficiencies related to our corporate 
structure  and  restrictions  on  the  repatriation  of  earnings;  experience  financial  accounting  and  reporting  burdens  and 
complexities; experience difficulties in staffing and managing foreign operations, including under labor and employment 
laws and regulations that are new or unfamiliar to us; be subject to trade barriers such as tariffs, quotas, preferential bidding 
or  import  or  export  licensing  requirements;  be  exposed  to  political,  social  and  economic  instability  abroad,  including 
terrorist attacks and security concerns; be exposed to fluctuations in currency exchange rates; and experience reduced or 
varied protection for intellectual property rights and practical difficulties in enforcing intellectual property and other rights, 
including with respect to assignment of inventions to us by our consultants in foreign jurisdictions. 

Outside of the United States we enlist local and regional laboratories, contract employees and other contracted 
service  providers  to  assist  with  various  aspects  of  our  business  operations,  including  blood  draws,  engineering,  sales, 
marketing,  billing  and  customer  support.  Subject  to  regulatory  clearance  where  required,  we  also  contract  with 
international licensees to run the molecular portion of our tests in their own labs and then access our algorithm for analysis 
of  the  resulting  data  through  our  cloud-based  Constellation  platform.  Locating,  qualifying  and  engaging  additional 
distribution partners and local laboratories with local industry experience and knowledge is necessary to effectively market 
and  sell  our  tests  outside  of  the  United  States.  We  may  not  be  successful  in  finding,  attracting  and  retaining  such 
distribution partners  or  laboratories, or we may not be  able  to  enter  into  such  arrangements on favorable  terms.  Sales 
practices and other activities utilized by our distribution partners, contract employees and other service providers, some of 
which may be locally acceptable, may not comply with relevant standards required under United States laws that apply to 
our operations overseas, including through third parties, which could create additional compliance risk. Our training and 
compliance program and our other internal control policies and procedures, and our contractual terms with these third 
parties,  may  not  always  protect  us  from  acts  committed  by  our  employees,  contractors,  partners  or  agents  abroad. 
Non-compliance by us or our employees, contractors, partners or agents, whether maliciously or in error, of any applicable 
laws or regulations could result in fines or penalties, or adversely affect our ability to operate and grow our business. Even 
if  we  are  able  to  effectively  manage  our  international  operations,  if  our  distribution  partners  and  local  and  regional 
laboratory licensees are unable to effectively manage their businesses, our business and results of operations could be 
adversely affected. Furthermore, the legal landscape governing advertising, promotional and other marketing activities can 
vary widely from jurisdiction to jurisdiction, and is often more complex, less clear or less developed than in the United 
States. If our marketing activities are found to be in violation of local laws, regulations or practices, we may be subject to 
fines and other penalties, and may be required to cease marketing or commercialization activities in such jurisdiction. If 
our sales and marketing efforts are not successful outside of the United States, we may not achieve market acceptance for 
our tests outside of the United States, which would harm our business. 

Operating internationally requires significant management attention and financial resources. We cannot be certain 
that  the  investment  and  additional  resources  required  to  increase  international  revenues  or  expand  our  international 
presence will produce desired levels of revenues or profitability. 

47 

If we lose the services of our founder and Executive Chairman or other members of our senior management team, we 
may not be able to execute our business strategy. 

Our success depends in large part upon the continued service of our senior management team. In particular, our 
founder  and  Executive  Chairman,  Matthew  Rabinowitz,  as  well  as  Steve  Chapman,  our  Chief  Executive  Officer,  are 
critical to our vision, strategic direction, culture, products and technology. Although Dr. Rabinowitz spends significant 
time with us and is active in our management, he is no longer our Chief Executive Officer. In addition, we do not maintain 
key-man insurance for Dr. Rabinowitz, Mr. Chapman or any other member of our senior management team. The loss of 
our founder and Executive Chairman, our Chief Executive Officer or one or more other members of our senior management 
team could have an adverse effect on our business. 

We  may  engage  in  acquisitions,  dispositions  or  other  strategic  transactions  that  could  disrupt  our  business,  cause 
dilution to our stockholders or reduce our financial resources. 

From time to time, we may enter into transactions to acquire or dispose of businesses, products or technologies 
or to engage in other strategic transactions. We may not be able to complete such transactions on favorable terms or at all. 
Any acquisitions or other strategic transactions we consummate may not strengthen our competitive position, and these 
transactions may be viewed negatively by customers or investors. We may decide to incur debt in connection with an 
acquisition or issue shares of our common stock or other equity securities to the stockholders of the acquired company, 
which would cause dilution to our existing stockholders. We could incur losses resulting from such strategic transactions, 
including undiscovered liabilities of an acquired business that are not covered by any indemnification we may obtain from 
the seller. In addition, we may not be able to successfully integrate any acquired personnel, technologies and operations 
into our existing business in an effective, timely and non-disruptive manner. Any dispositions may also cause us to lose 
revenue and may not strengthen our financial position. Strategic transactions may also divert management attention from 
day-to-day  responsibilities,  increase  our  expenses,  result  in  accounting  charges,  and  reduce  our  cash  available  for 
operations and other uses. We cannot predict the number, timing or size of future strategic transactions or the effect that 
any such transactions might have on our operating results. 

We may need to raise additional capital, and if we cannot do so when needed or on commercially acceptable terms, we 
will be required to slow or cease our investment in our product development and commercialization plans, which would 
have an adverse effect on our business. 

We have incurred net losses since our inception, and we anticipate net losses and negative operating cash flows 
for the near future. While we have introduced multiple products that are generating revenues, these revenues may not be 
sufficient to fund all of our operations, including our product development and commercialization plans. Consequently, 
we will need to generate additional revenues to achieve future profitability and may need to raise additional funds through 
public  or  private  equity  or  debt  financings,  corporate  collaborations  or  licensing  arrangements  to  continue  to  fund  or 
expand our operations. 

Our actual liquidity and capital funding requirements will depend on numerous factors, including: 

• 

• 

• 

• 

• 

our ability to achieve broader commercial success with Panorama, Horizon and our other products; 

the costs and success of our research, development, and commercialization efforts for potential new products 
and additional indications for, and enhancements to, current products; 

our ability to obtain more extensive coverage and reimbursement for our tests, including in the average-risk 
patient population and for microdeletions screening in NIPT, as well as in additional indications in oncology 
and organ health as we continue to invest in expanding our offerings in these fields; 

our ability to generate sufficient revenues from our cloud-based distribution model; 

our ability to collect on our accounts receivable; 

48 

 
• 

• 

• 

our need to finance capital expenditures and further expand our clinical laboratory operations; 

our ability to manage our operating costs; and 

the timing and results of any regulatory authorizations that we are required to obtain for our tests. 

Additional capital, if needed, may not be available on satisfactory terms or at all. Furthermore, any additional 
capital  raised  through  the  sale  of  equity  or  equity-linked  securities,  or  grant  of  equity  or  equity-linked  securities  in 
connection with any debt financing, will dilute stockholders’ ownership interests in us and may have an adverse effect on 
the price of our common stock. In addition, the terms of any financing may adversely affect stockholders’ holdings or 
rights. Debt financing, if available, may include restrictive covenants, and may impose other constraints on us and our 
operations. To the extent that we raise capital through collaborations and licensing arrangements, it may be necessary to 
relinquish some rights to our technologies or grant licenses on terms that may not be favorable to us. 

If we are not able to obtain adequate funding when needed, we may be required to delay or slow our investment 
in the development and commercialization of our products and significantly scale back our business and operations, which 
would have an adverse effect on our business. In addition, we may have to work with a partner on one or more of our tests 
or programs, which could lower the economic value of those programs to our company. 

We have incurred substantial indebtedness that may decrease our business flexibility, access to capital, and/or increase 
our borrowing costs, which may adversely affect our operations and financial results. 

In April 2020, we issued $287.5 million aggregate principal amount of 2.25% Convertible Senior Notes due 2027, 

or the Convertible Notes. Our indebtedness may: 

• 

• 

• 

• 

• 

• 

limit our ability to borrow additional funds for working capital, capital expenditures, acquisitions or other 
general business purposes; 

limit  our  ability  to  use  our  cash  flow  or  obtain  additional  financing  for  future  working  capital,  capital 
expenditures, acquisitions or other general business purposes; 

require us to use a substantial portion of our cash flow from operations to make debt service payments; 

limit our flexibility to plan for, or react to, changes in our business and industry; 

place us at a competitive disadvantage compared to our less leveraged competitors; and 

increase our vulnerability to the impact of adverse economic and industry conditions. 

Further,  the  indenture  governing  the  Convertible  Notes  does  not  restrict  our  ability  to  incur  additional 
indebtedness  and  we  and  our  subsidiaries  may  incur  substantial  additional  indebtedness  in  the  future,  subject  to  the 
restrictions contained in any future debt instruments existing at the time, some of which may be secured indebtedness. 

Ethical, legal and social concerns related to the use of genetic information could reduce demand for our tests. 

DNA testing, like that conducted using Panorama, Horizon, Signatera, and our other products, has raised ethical, 
legal and social issues regarding privacy and the appropriate uses of the resulting information. Governmental authorities 
could, for social or other purposes, limit or regulate the use of genomic information or genomic testing or prohibit testing 
for genetic predisposition to certain conditions, particularly for those that have no known cure. Patients may also refuse to 
use genetic tests even if permissible, for similar reasons; they may also refuse genetic testing due to concerns regarding 
eligibility for life or other insurance. Ethical and social concerns may also influence U.S. and foreign patent offices and 
courts with regard to patent protection for technology relevant to our business. These and other ethical, legal and social 
concerns may limit market acceptance of our tests or reduce the potential markets for services and products enabled by 
our technology platform, either of which could harm our business. 

49 

Our ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited. 

We have a significant amount of net operating loss, or NOL, carryforwards that can be used to offset potential 
future  taxable  income  and  related  income  taxes.  As  of  December 31,  2021,  we  had  federal,  state,  and  federal  NOL 
carryforwards of approximately $1.3 billion, $796.7 million and $4.0 million, respectively, which, if not utilized, begin to 
expire in 2027, 2028, and 2031, respectively. Approximately $950.2 million of these federal NOLs can be carried forward 
indefinitely. We also had federal research and development credit carryforwards of approximately $34.5 million, which 
begin to expire in 2027, and state research and development credit carryforwards of approximately $23.0 million, which 
can be carried forward indefinitely. Under Section 382 of the Internal Revenue Code of 1986, as amended, if a corporation 
undergoes an “ownership change” (generally defined as a greater than 50% change, by value, in equity ownership over 
any  three-year  period),  the  corporation’s  ability  to  use  its  pre-change  NOL  carryforwards  and  other  pre-change  tax 
attributes to offset its post-change income or taxes may be limited. We may experience ownership changes in the future 
as  a  result  of  shifts  in  our  stock  ownership,  some  of  which  may  not  be  within  our  control.  Our  ability  to  use  these 
carryforwards could be limited if we experience an “ownership change.” 

Our estimates of total addressable market opportunity and forecasts of market growth may prove to be inaccurate, and 
even if the market in which we compete achieves the forecasted growth, our business could fail to grow at similar rates. 

Total addressable market opportunity estimates and growth forecasts are subject to significant uncertainty and 
are based on assumptions and estimates that may not prove to be accurate. Our publicly announced estimates and forecasts 
relating to the size and expected growth of our market may prove to be inaccurate. Even if a market in which we compete 
meets our size estimates and forecasted growth for such market, our business could fail to grow at similar rates. 

Risks Related to Reimbursement 

If we are unable to expand, maintain or obtain third-party payer coverage and reimbursement for Panorama, Horizon 
and our other tests, or if we are required to refund any reimbursements already received, our revenues and results of 
operations would be adversely affected. 

Our  business  depends  on  our  ability  to  obtain  and  maintain  adequate  coverage  and  reimbursement  from 
third-party payers and patients. Third-party reimbursement for our testing represents a significant portion of our revenues, 
and we expect third-party payers such as insurance companies and government healthcare programs to continue to be our 
primary source of payments. In particular, we believe that the following will be necessary for us to continue to achieve 
commercial  success:  continued  expansion  of  insurance  coverage  from  the  high-risk  to  the  average-risk  pregnancy 
population, which represents roughly 80% of the United States pregnancy market, and for microdeletions screening, and 
obtaining positive coverage determinations and favorable reimbursement rates from commercial third-party payers, the 
Centers for Medicare & Medicaid, or CMS, and state reimbursement programs for our tests. Historically, we have not 
received reimbursement for a significant number of Panorama tests that we have performed for average-risk patients and 
for microdeletions; we have recently published data from our SMART Study, but we cannot be certain whether, or to what 
extent, the SMART Study may impact insurance coverage and reimbursement for Panorama in the average-risk population 
or for microdeletions. In addition, while we have received a positive local coverage determination from the Molecular 
Diagnostic  Services  Program,  which  identifies  and  establishes  Medicare  coverage  and  reimbursement  for  molecular 
diagnostic tests, to provide Medicare benefits for certain specified uses and indications of our Signatera test, we cannot 
guarantee  that  our  test  will  be  reimbursed  at  the  rate  we  expect.  Furthermore,  while  we  have  also  received  a  positive 
coverage decision for our Prospera Kidney test, we cannot guarantee that our test will continue to be reimbursed at the 
same  or  a  similar  rate  as  we  have  received  thus  far.  If  we  are  unable  to  obtain  or  maintain  coverage  or  adequate 
reimbursement from, or achieve in-network status with, third-party payers for our existing or future tests, our ability to 
generate revenues will be limited. For example, physicians may be reluctant to order our tests due to the potential of a 
substantial cost to the patient if reimbursement coverage is unavailable or insufficient. 

In making coverage determinations, third-party payers often rely on practice guidelines issued by professional 
societies.  The  practice  guidelines  issued  by  professional  societies  now  generally  acknowledge  that  NIPT  is  the  most 
sensitive screening option for, and/or are generally supportive of NIPT in, average-risk pregnancies, in addition to high-risk 
pregnancies. However, while many third-party payers now reimburse for NIPT for average-risk patients, it remains the 

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case that not all third-party payers, particularly state Medicaid payers, do so. Furthermore, many third-party payers do not 
reimburse for microdeletions screening. While we have published data on the performance of Panorama for the 22q11.2 
deletion  syndrome,  including  most  recently  from  our  SMART  Study,  we  have  and  may  continue  to  experience  low 
reimbursement  rates  for  Panorama  for  microdeletions,  and  we  may  otherwise  be  unable  to  obtain  positive  coverage 
determinations for our test. If third-party payers do not reimburse for NIPT for average-risk pregnancies or microdeletions 
in the future, our future revenues and results of operations would be adversely affected, particularly to the extent that we 
continue to perform large volumes of tests for which third-party payors do not reimburse. 

In  addition,  a  CPT  code  for  microdeletions  took  effect  in  January  2017.  We  have  experienced  low  average 
reimbursement  rates  for  microdeletions  under  this  code,  and  we  expect  that  this  code  will  continue  to  cause  our 
microdeletions reimbursement to remain low, at least in the near term, due to third-party payers declining to reimburse 
and as a result of reduced reimbursement, under the code, which has had, and we expect to continue to have, an adverse 
effect on our revenues. Also, a new CPT code for expanded carrier screening tests took effect in January 2019. The new 
code has caused and may continue to cause reimbursement rates for our broader Horizon carrier screening panel to decrease 
because those tests may be reimbursed as a combined single panel instead of as multiple individual tests. 

The reimbursement environment, particularly for molecular diagnostics, is continually changing and our efforts 
to broaden reimbursement for our tests with third-party payers may not be successful. Third parties, such as commercial 
health  insurers  and  government  payers  and  programs,  from  whom  we  have  received  reimbursement  may  withdraw 
coverage or decrease the amount of reimbursement for our tests at any time and for any reason, or may otherwise adopt 
requirements,  programs  or  policies  that  may  restrict  or  adversely  affect  our  business.  For  example,  the  California 
Department of Public Health, or CAPH, is implementing changes to its Prenatal Screening (PNS) Program, under which 
the state of California makes prenatal screening and follow-up diagnostic testing available to pregnant Californians, to 
offer cfDNA testing as a first line screen instead of the biochemical screening tests currently used. We are currently in 
discussions with the CAPH regarding our potential participation in the new PNS Program. It remains uncertain whether 
we will participate in the PNS program, and if we do participate, whether and to what extent our participation in the PNS 
Program may impact our overall financial and operating results. In addition, in some cases, our tests or their uses within 
certain populations, such as for microdeletions, are considered experimental by third-party payers and, as a result, some 
payers have decided not to cover or reimburse for such tests. Some third-party payers bundle payment for multiple tests 
or tests that screen for multiple conditions, such as our Horizon test or our Panorama test and the separate Panorama screen 
for microdeletions, into a single payment rate, thereby limiting our reimbursement in those situations. Payers may also 
dispute our billing or coding. Based on any of the foregoing, third-party payers may also decide to deny payment or recoup 
payment for testing that they contend to have been not medically necessary, against their coverage determinations, or for 
which they have otherwise overpaid, and we may be required to refund reimbursements already received. We deal with 
requests for recoupment from third-party payers from time to time in the ordinary course of our business, and it is likely 
that  we  will  continue  to  do  so  in  the  future.  See  “Note 8—Commitments  and  Contingencies—Third-Party  Payer 
Reimbursement  Audits”  in  the  Notes  to  Consolidated  Financial  Statements.  If  a  third-party  payer  denies  payment  for 
testing, reimbursement revenue for our testing could decline. If a third-party payer successfully proves that payment for 
prior testing was in breach of contract or otherwise contrary to law, they may recoup payment, which amounts could be 
significant and would impact our results of operations, and it may decrease reimbursement going forward. We may also 
decide  to  negotiate  and  settle  with  a  third-party  payer  in  order  to  resolve  an  allegation  of  overpayment.  Any  of  these 
outcomes might require us to restate our financials from a prior period, which would likely cause our stock price to decline. 
For example, in 2018 we reached a settlement with certain government payers regarding past reimbursement submissions; 
although the settlement involved no admission of fault by us and no corporate integrity agreement, we cannot guarantee 
that we will not be subject to similar claims, resulting in additional settlements or repayments, in the future. 

Furthermore,  some  of  our  contracts  with  third-party  payers  contain  so-called  most  favored  nation  provisions, 
pursuant to which we have agreed that we will not bill the third-party payer more than we bill any other third-party payer. 
We  must  therefore  monitor  our  billing  and  claims  submissions  to  ensure  that  we  remain  in  compliance  with  these 
contractual requirements with third-party payers. If we do not successfully manage these most favored nation provisions, 
we may need to forego revenues from some third-party payers or reduce the amount we bill to each third-party payor with 
a most-favored nation clause in its contract that is violated, which would adversely affect our revenues. This situation 
could also subject us to claims for recoupment, which could require the time and attention of our management, require the 
expense of engaging outside counsel or consultants, and may be a distraction from development of our business, adversely 

51 

impacting  our  operations.  Such  recoupment  demands  could  also  ultimately  result  in  an  obligation  to  repay  amounts 
previously earned. 

In addition, if a third-party payer denies coverage, it may be difficult for us to collect from the patient, and we 
may not be successful in doing so. In particular, we are often unable to collect the full amount of a patient’s responsibility 
where we are an out-of-network provider and the patient is left with a large balance, despite our good faith efforts to collect. 
As a result, we cannot always collect the full amount due for our tests when third-party payers deny coverage, cover only 
a  portion  of  the  invoiced  amount  or  the  patient  has  a  large  cost-sharing  obligation,  which  may  cause  payers  to  raise 
questions regarding our billing policies and patient collection practices. We believe that our billing policies and our patient 
collection practices are compliant with applicable laws and reimbursement policies. However, from time to time we receive 
inquiries from third-party payers regarding our billing policies and collection practices. We address these inquiries as and 
when they arise, but there is no guarantee that we will always be successful in addressing such concerns in the future, 
which may result in a third-party payer deciding to reimburse for our tests at a lower rate or not at all, seeking recoupment 
of amounts previously paid to us, or bringing legal action to seek reimbursement of previous amounts paid. Any of such 
occurrences could cause reimbursement revenue for our testing, which constitutes the large majority of our revenue, to 
decline. Additionally, if we were required to make a repayment, such repayment could be significant, which would impact 
our results of operations, and we might be required to restate our financials from a prior period, which would likely cause 
our stock price to decline. 

Our  revenues  may  be  adversely  affected  if  we  are  unable  to  successfully  obtain  reimbursement  from  the  Medicare 
program and state Medicaid programs. 

Our revenues from Medicare are currently relatively small, given the population that Medicare covers and the 
fact that our testing in women’s health, which comprises the significant majority of our business, generally is not received 
by Medicare beneficiaries. As a result, we do not expect our Medicare revenues to change materially with regard to NIPT. 
However,  Medicare  reimbursement  impacts  our  revenues  from  our  oncology  and  organ  health  products,  as  a  large 
proportion of these patients are covered by Medicare. Furthermore, Medicare reimbursement can affect both Medicaid 
reimbursement,  which  is  relevant  to  NIPT,  and  reimbursement  from  commercial  third-party  payers.  Specifically, 
fee-for-service Medicaid programs generally do not reimburse at rates that exceed Medicare’s fee-for-service rates, and 
many commercial third-party payers set their payment rates at a percentage of the amounts that Medicare pays for testing 
services. Medicare reimbursement rates are typically based on the Clinical Laboratory Fee Schedule, or CLFS, set by CMS. 
Our current Medicare Part B reimbursement for Panorama was not set pursuant to a national coverage determination by 
CMS.  Although  we  believe  that  coverage  is  available  under  Medicare  Part B  even  without  such  a  determination,  we 
currently lack the certainty afforded by a formal national coverage determination by CMS. Thus, CMS could issue an 
adverse coverage determination as to Panorama which could influence other third-party payers, including Medicaid, and 
could have an adverse effect on our revenues. 

It is estimated that nearly half of all births in the United States are to state Medicaid program recipients. Each 
state’s Medicaid program has its own coverage determinations related to our testing, and many state Medicaid programs 
do not provide their recipients with coverage for our testing. Even if our testing is covered by a state Medicaid program, 
we must be recognized as a Medicaid provider by the state in which the Medicaid recipient receiving the services resides 
in order for us to be reimbursed by a state’s Medicaid program, including under a Medicaid managed care plan. Our San 
Carlos, CA laboratory is currently recognized by 48 U.S. states as a Medicaid provider, and we are currently in the process 
of obtaining recognition of our Austin, TX laboratory as a Medicaid provider in states in which the Austin laboratory is 
not already credentialed; however, even if we are recognized as a Medicaid provider in a state, if Medicare’s CLFS rate 
for our services and tests are low, the Medicaid reimbursement amounts are sometimes as low, or lower, than the Medicare 
reimbursement rate. In addition, from time to time we receive requests from state Medicaid programs seeking information 
or documents to determine eligibility for and the amount of Medicaid reimbursement. As a result of all of these factors, 
many state Medicaid programs only reimburse our testing at a very low dollar amount, or not at all. Low or zero-dollar 
Medicaid reimbursement rates for our tests could have an adverse effect on our business and revenues. 

52 

Our  revenues  may  be  adversely  impacted  if  third-party  payers  withdraw  coverage  or  provide  lower  levels  of 
reimbursement due to changing policies, billing complexities or other factors. 

We are in-network, or under contract, with the significant majority of third-party payers from whom we receive 
reimbursement; this means that we have agreements with most third-party payers that govern test approval or payment 
terms. However, these contracts do not guarantee reimbursement for all testing we perform. For example, many third-party 
payers  with  whom  we  have  written  agreements  have  policies  that  state  they  will  not  reimburse  for  the  screening  of 
microdeletions, or don’t have a policy in place to reimburse for microdeletions screening. In addition, the terms of certain 
of our payer agreements require the ordering physician or qualified practitioner’s signature on test requisitions or require 
other controls and procedures prior to conducting a test. In particular, third-party payers have increasingly required prior 
authorization to be obtained prior to conducting a test, as a condition to reimbursing for the test. This has placed a burden 
on our billing operations as we have to dedicate or source resources to ensuring that these requirements are met and to 
conduct follow-up and address issues as they arise, and has also impacted our results of operations, including our gross 
margins, since these requirements began to take effect. To the extent we or the physicians ordering our tests do not follow 
the prior authorization requirements, we may be subject to claims for recoupment of reimbursement amounts previously 
paid to us, or may not receive some or all of the reimbursement payments to which we would otherwise be entitled. This 
has occurred in some cases and may occur more frequently in the future, which does and would have an adverse impact 
on our revenues. 

Where we are considered to be an out of network provider, which is the case with some third-party payers from 
whom we receive reimbursement, such third-party payers could withdraw coverage and decline to reimburse for our tests 
in the future according to each plan enrollee’s policy. Managing reimbursement on a case-by-case basis is time-consuming 
and contributes to an increase in the number of days it takes us to collect on accounts, which also increases our risk of 
non-payment. Negotiating reimbursement on a case-by-case basis also typically results in the receipt of reimbursement at 
a significant discount to the list price of our tests. 

Even if we are being reimbursed for our tests, third-party payers may review and adjust the rate of reimbursement, 
require patient cost-sharing, or stop paying for our tests. Government healthcare programs and other third-party payers 
continue to increase their efforts to control the cost, utilization and delivery of healthcare services by demanding price 
discounts or rebates and limiting coverage of, and amounts they will pay for, molecular diagnostic tests. These measures 
have  resulted  in  reduced  payment  rates  and  decreased  utilization  in  the  clinical  laboratory  industry.  Because  of  these 
cost-containment measures, governmental and commercial third-party payers may reduce, suspend, revoke or discontinue 
payments  or  coverage  at  any  time,  including  payors  that  currently  provide  reimbursement  for  our  tests.  Reduced 
reimbursement of our tests may harm our business, financial condition or results of operations. 

Billing for clinical laboratory testing services is complex. We perform tests in advance of payment and without 
certainty as  to  the outcome of  the  billing process.  In  cases  where we  expect  to receive  a fixed fee per  test due  to our 
reimbursement  arrangements,  we  may  nevertheless  encounter  disputes  over  pricing  and  billing.  Among  the  factors 
complicating our billing of third-party payers are disparity in coverage among various payers; disparity in, and increasingly 
difficult, information and billing requirements among payers, including with respect to prior authorization requirements 
and procedures and establishing medical necessity; and incorrect or missing billing information, which is required to be 
provided by the ordering healthcare practitioner. These billing complexities, and the associated uncertainty in obtaining 
payment  for  our  tests,  could  result  in  reduced  reimbursement  of  our  tests,  which  could  harm  our  business,  financial 
condition and results of operations. 

A CPT code specific to NIPT for aneuploidies, and a CPT code for microdeletions, are in place, and CMS has 
established a pricing benchmark for aneuploidy and microdeletions testing. However, our microdeletions reimbursement 
has  decreased  since  the  implementation  of  the  microdeletions  CPT  code  because  third-party  payers  are  declining  to 
reimburse under this code or reimbursing at a much lower rate than we had previously received. Furthermore, we cannot 
guarantee that we will be able to negotiate favorable rates for this code or receive reimbursement at all if we are unable to 
collect and publish sufficient data, including from our SMART Study, and obtain positive coverage determinations for 
Panorama for microdeletions. In addition, a CPT code for expanded carrier screening tests has been implemented, which 
has caused and may continue to cause reimbursement rates for our Horizon expanded carrier screening tests to decline. 
We do not currently have assay-specific CPT codes assigned for all of our tests, and there is a risk that we may not be able 
to obtain such codes or, if obtained, we may not be able to negotiate favorable rates for such codes. We currently submit 

53 

for reimbursement using CPT codes based on the guidance of outside coding experts and legal counsel. There is a risk that 
the codes we currently submit may be rejected or withdrawn or that third-party payers will seek refunds of amounts that 
they  claim  were  inappropriately  billed  based  on  either  the  CPT  code  used,  or  the  number  of  units  billed.  In  addition, 
third-party payers may not establish positive coverage policies for our tests or adequately reimburse for any CPT code we 
may use, or seek recoupment for testing previously performed, which have occurred in the past. 

Regulatory and Compliance Risks  

We may be subject to increased compliance risks as a result of our rapid growth, including our dependence on our 
sales, marketing and billing efforts. 

Approximately 89% and 87% of our total revenues for the years ended December 31, 2021 and 2020, respectively, 
were attributable to our U.S. direct sales. We have had to expand our training and compliance efforts in line with our 
increasing reliance on personnel in our sales, marketing and billing functions, and our expansion of these functions in line 
with the overall growth in our business. We continue to educate, train and monitor our personnel, but from time to time 
we  experience  situations  in  which  employees  fail  to  strictly  adhere  to  our  policies.  In  addition,  sales  and  marketing 
activities  in  the  healthcare  space  are  subject  to  various  rules  and  regulations,  as  described  in  the  risk  factor  entitled 
“Reimbursement and Regulatory Risks Related to Our Business—If we or our laboratory distribution partners, consultants 
or commercial partners act in a manner that violates healthcare fraud and abuse laws or otherwise engage in misconduct, 
we may be subject to civil or criminal penalties.” Moreover, our billing and marketing messaging can be complex and 
nuanced, and there may be errors or misunderstandings in our employees’ communication of such messaging. Furthermore, 
we utilize text messaging, email, phone calls and other similar methods to communicate with patients who are existing or 
potential users of our products for various business purposes. These activities subject us to laws and regulations relating 
to communications with consumers, such as the CAN-SPAM Act and the Telephone Consumer Protection Act, violations 
of which could subject us to claims by consumers, who may seek actual or statutory damages, as has happened in the past, 
which could be material in the aggregate. As we continue to scale up our sales and marketing efforts in line with the rapid 
growth in our business, in particular our increased pace of product launches as well as further geographical expansion, we 
will  continue  to  face  an  increased  need  to  remain  vigilant  in  monitoring  and  improving  our  policies,  processes  and 
procedures to maintain compliance with a growing number and variety of laws and regulations, including with respect to 
consumer  marketing.  To  the extent  that  there  is  any violation, whether actual, perceived or  alleged, of  our policies  or 
applicable laws and regulations, we may incur additional training and compliance costs; may, and from time to time do, 
receive inquiries, such as informal requests for documents, civil investigative demands, and subpoenas, from third-party 
payers or other third parties, including government entities; or may be held liable or otherwise responsible for such acts of 
non-compliance. Any of the foregoing could adversely affect our cash flow and financial condition. 

If the FDA were to begin actively regulating our tests, we could incur substantial costs and delays associated with trying 
to obtain premarket clearance or approval and incur costs associated with complying with post-market controls. 

We currently offer a number of genetic tests, and each of those tests is an LDT. The FDA considers an LDT to 
be a test that is designed, developed, validated and used within a single laboratory. The FDA has historically taken the 
position that it has the authority to regulate such tests as medical devices under the FDC Act, but it has generally exercised 
enforcement  discretion with regard  to LDTs.  This means  that  even  though  the FDA believes  it  can  impose regulatory 
requirements on LDTs, such as requirements to obtain premarket approval or clearance of LDTs, it has generally chosen 
not to enforce those requirements to date. The regulatory environment for LDTs is unstable; in 2020 HHS directed FDA 
to  stop  regulating  LDTs  but  in  2021  HHS  reversed  its  policy.  Thereafter,  the  FDA  resumed  requiring  submission  of 
emergency use authorization, or EUA, requests, for COVID-19 LDTs, but has not indicated an intent to regulate other, 
non-COVID, LDTs. Various legislation has been introduced seeking to substantially revamp the regulation of both LDTs 
and IVDs. For example, the VALID Act, introduced in June 2021, would clarify and enhance FDA’s authority to regulate 
LDTs, while the VITAL Act, introduced in May 2021, would assign oversight of LDTs exclusively to CMS. Congress 
may still act to provide further direction on the regulation of LDTs and substantially modify the regulation of IVDs. 

In the meantime, the regulation by the FDA of LDTs remains uncertain. If FDA premarket clearance, approval 
or authorization is required for any of our existing or future tests, or for any components or materials we use in tests, we 
may be forced to stop selling our tests or we may be required to modify claims for or make other changes to our tests while 

54 

we or our supplier work to obtain FDA clearance, approval or de novo authorization. Our business would be adversely 
affected  while  such  review  is  ongoing  and  if  we  or  our  supplier  are  ultimately  unable  to  obtain  premarket  clearance, 
approval or de novo authorization. For example, the regulatory premarket clearance, approval or de novo authorization 
process may involve, among other things, successfully completing analytical, pre-clinical and/or clinical studies beyond 
the  studies  we  have  already  performed  or  plan  to  perform  for  each  of  our  products  and  would  involve  submitting  a 
premarket notification, or 510(k), a de novo application, or filing a PMA application with the FDA. As further described 
in the risk factor entitled “Uncertainty in the development and commercialization of our enhanced or new tests or services 
could materially adversely affect our business, financial condition and results of operations,” completing such studies 
requires the expenditure of time, attention and financial and other resources, and may not yield the desired results, which 
may  delay,  limit  or  prevent  regulatory  clearances,  approvals  or  de  novo  authorizations.  In  addition,  we  may  require 
cooperation in our filings for FDA clearance, approval or de novo authorization from third-party manufacturers of the 
components of our tests. If we are unable to obtain such required cooperation, we may be unable to achieve the desired 
regulatory clearances, approvals or de novo authorizations, or may be delayed or be required to expend additional costs 
and other resources in doing so. For example, Illumina currently is our sole sequencer and sequencing reagent supplier. If 
we seek to achieve regulatory clearance, approval or de novo authorization for Panorama, to the extent that Panorama 
incorporates Illumina’s sequencer or sequencing reagents, we may require Illumina’s cooperation in the regulatory process. 
We may face difficulty obtaining cooperation from Illumina because Illumina is the parent company of Verinata, a direct 
competitor of ours in the NIPT field. In addition, we have been party to certain intellectual property proceedings with 
Illumina as described elsewhere in these Risk Factors. Furthermore, if FDA premarket clearance, approval or de novo 
authorization is required, our cash flows may be adversely affected until we obtain such clearance, approval or de novo 
authorization, as most third-party payers, including Medicaid, will not reimburse for use of medical devices which are 
required to, but which do not, have marketing authorization. 

In May 2019, the FDA granted Breakthrough Device designation for our Signatera test for use in the post-surgical 
detection and quantification of ctDNA in the blood of patients previously diagnosed with certain types of cancer and in 
combination with certain drugs, and in March 2021, the FDA granted two additional Breakthrough Device designations 
for our Signatera test, covering the development of Signatera through Phase III clinical trials as a companion diagnostic 
to two different cancer therapies. While receiving such designation enables us to have increased interactions with FDA, 
we cannot assure you that this designation will lead to accelerated review or approval of our regulatory submissions for 
Signatera. 

We cannot assure you that Panorama or any of our other tests for which we decide to pursue or are required to 
obtain premarket clearance, approval or de novo authorization by the FDA will be cleared, approved or authorized on a 
timely basis, if at all. In addition, if a test has been cleared, approved or authorized, certain kinds of changes that we may 
make to improve the test, or as a result of issues with suppliers of the components of the test or if a supplier modifies its 
component upon which our approval relies, may need to be cleared, approved or authorized by the FDA before we can 
implement  them,  which  could  increase  the  time  and  expense  involved  in  implementing  such  changes  commercially. 
Ongoing compliance with FDA regulations would increase the cost of conducting our business and subject us to heightened 
regulation by the FDA and penalties for failure to comply with these requirements, any of which may adversely impact 
our business and results of operations. 

Furthermore, the FDA or the Federal Trade Commission, or FTC, as well as state consumer protection agencies, 
may object to the materials and methods we use to promote the use of our current tests or other LDTs we may develop in 
the future, including with respect to the product claims in our promotional materials, and may initiate enforcement actions 
against us. Enforcement actions by the FDA may include, among others, untitled or warning letters; fines; injunctions; 
civil or criminal penalties; recall or seizure of current or future tests, products or services; operating restrictions and partial 
suspension or total shutdown of production. Enforcement actions by the FTC and state consumer protection agencies may 
include, among others, injunctions, civil penalties, and equitable monetary relief. 

Failure  to  obtain  necessary  regulatory  approvals  may  adversely  affect  our  ability  to  expand  our  operations 
internationally, including our ability to continue commercializing our cloud-based distribution model. 

An important part of our business strategy is to expand and offer our tests internationally, either by providing our 
testing services directly or through our laboratory partners, or through our licensees under our Constellation cloud-based 

55 

distribution model. As we do so, we will become increasingly subject to or impacted by the regulatory requirements of 
foreign jurisdictions, which are varied and complex. Our tests, and certain components of our tests, may be subject to the 
regulatory approval requirements in each foreign country in which they are sold by us or a laboratory partner, or by our 
licensees under our cloud-based distribution model, and our future performance would depend on us or our partners or 
licensees obtaining any necessary regulatory approvals in a timely manner. For example, while we have entered into a 
license agreement with BGI Genomics to commercialize our Signatera test in China and to develop reproductive health 
tests  in  select  markets  using  BGI  Genomics’s  sequencing  instruments  and  platform,  such  commercialization  and 
development activities are subject to obtaining and maintaining necessary regulatory approvals in the relevant jurisdictions. 
In addition, while we have obtained a CE Mark from the European Commission for our Constellation software and the 
key  reagents  for  our  licensees  to  run  their  NIPT  based  on  our  technology,  we  have  not  obtained  a  CE  Mark  for  our 
Panorama test as a whole. Therefore, while we are able to offer Constellation in the European Union and other countries 
that accept a CE Mark, we are unable to offer Panorama as an IVD directly in these jurisdictions. This, coupled with our 
use of our Panorama brand name under our Constellation model, has caused regulatory authorities to question whether we, 
our  laboratory  partners  or  our licensees  may  be  marketing,  commercializing  or  otherwise  offering  our  tests  without 
required approvals. We are occasionally required to address inquiries from regulatory authorities in various countries, such 
as those in the European Union, regarding the regulatory status of our Panorama or Constellation offerings, and expect 
that we will continue to face similar inquiries. If we do not continue to satisfactorily address any such questions in the 
future,  we  may  be  required  to  cease  offering  our  products,  either  directly  or  through  our  partners  or  licensees,  in  the 
relevant country. This may in turn result in similar concerns, and subsequent cessation of our sources of revenue, in other 
countries. 

We may also be at a competitive disadvantage in the European Union to our competitors who have obtained a 
CE  Mark for  their  end-to-end  NIPT.  In  addition,  as  further  described  in  the  risk  factor  entitled  “Risks  Related  to Our 
Business and Industry—We rely on a limited number of suppliers or, in some cases, single suppliers, for some of our 
laboratory instruments and materials and may not be able to find replacements or immediately transition to alternative 
suppliers,” blood collection tubes sourced solely from Streck are required to run our tests. These blood collection tubes 
are CE Marked by the European Commission; however, if such blood collection tubes are not registered in jurisdictions 
that do not accept a CE Mark, we may be unable to expand our business in such jurisdictions. 

We may also need to obtain regulatory clearance, approval or de novo authorization in the United States for our 
Constellation  software  in  order  for  it  to  be  used  by  third  parties  in  the  development  and  commercialization  of  their 
diagnostic  tests  based  on  our  technology.  We  have  discussed  with  the  FDA  the  regulatory  status  of  a  portion  of  our 
Constellation software, the copy number calculator, or CNC, to make calls of copy number variants, which are genetic 
mutations in which relatively large regions of the genome have been deleted or duplicated. The FDA has indicated that 
the  CNC  may  be  appropriate  for  review  under  the  de  novo  classification  process,  which  is  less  burdensome  than  the 
premarket approval, or PMA, process. The FDA has stated that it would not prevent us from marketing Constellation in 
the United States while we discuss with the FDA how it will be regulated; however, it is possible that the FDA may reverse 
itself  either  on  the  appropriate  regulatory  review  path  or  regarding  our  ability  to  continue  to  market  Constellation.  In 
addition, the 21st Century Cures Act, enacted in 2016, includes a number of provisions relating to the FDA’s regulatory 
approach to software that may have bearing on the regulatory status of our Constellation software. We cannot guarantee 
that we will be able to obtain such clearance, approval or authorization for our Constellation software, in the event that we 
are required to do so. If we are unable to do so, we would be unable to commercialize our cloud-based distribution model 
in the United States. If we are able to do so, we will be subject to ongoing FDA obligations and continued regulatory 
oversight  and  review,  including  compliance  with  requirements  such  as  the  quality  system  regulation,  or  QSR,  which 
establishes extensive requirements for quality assurance and control as well as manufacturing procedures; establishment 
registration and the listing of our devices with the FDA; adverse event and malfunction reporting; correction, removal, 
and recall actions and reporting; and labeling and promotional requirements. We may also be subject to additional FDA 
post-marketing obligations. If we are not able to maintain regulatory compliance to the extent required, we may not be 
permitted to offer our Constellation software and may be subject to enforcement action by the FDA, such as the issuance 
of warning or untitled letters, fines, injunctions and civil penalties; recall or seizure of products; operating restrictions and 
criminal prosecution. 

Regulatory  approval  can  be  a  lengthy,  expensive  and  uncertain  process.  In  addition,  regulatory  processes  are 
subject to change, and new or changed regulations can result in unanticipated delays and cost increases. For example, the 

56 

European  Commission  has  adopted  revised  in-vitro  diagnostic  regulations,  or  IVDR,  which  are  expected  to  become 
effective in 2022. Among others, the new regulations introduce risk-based classification for IVDs and will require notified 
body  involvement  for various  classes  of  devices,  including  reproductive health  tests  such  as  Panorama,  which will  be 
classified as a Class C product. As such, we will also be required to submit clinical evidence and post-market performance 
data to regulators. We or our partners or licensees may not be able to obtain regulatory approvals on a timely basis, if at 
all, which may cause us to incur additional costs or prevent us from marketing our tests in the United States or in foreign 
countries. 

Changes in laws and regulations, or in their application, may adversely affect our business, financial condition and 
results of operations. 

The  clinical  laboratory  testing  industry  is  highly  regulated,  and  failure  to  comply  with  applicable  regulatory, 
supervisory, accreditation, registration or licensing requirements may adversely affect our business, financial condition 
and results of operations. In particular, the laws and regulations governing the marketing and research of clinical diagnostic 
testing are extremely complex and in many instances there are no clear regulatory or judicial interpretations of these laws 
and regulations, increasing the risk that we may be found to be in violation of these laws. 

Furthermore, the molecular diagnostics industry as a whole is a growing industry and regulatory bodies such as 
HHS or the FDA may apply heightened scrutiny to our products or to new developments in the field. While we have taken 
steps to ensure compliance with the current regulatory regime in all material respects, given its nature and our geographical 
diversity,  there  could  be  areas  where  we  are  non-compliant.  Any  change  in  the  federal  or  state  laws  or  regulations, 
including as a result of political pressure, relating to our business may require us to implement changes to our business or 
practices, and we may not be able to do so in a timely or cost-effective manner. Should we be found to be non-compliant 
with current or future regulatory requirements, we may be subject to sanctions which could include substantial financial 
penalties  and  criminal  proceedings,  which  could  result  in  changes  to  our  operations,  adverse  publicity  and  other 
consequences, which may adversely affect our business, financial condition and results of operations by increasing our 
cost of compliance or limiting our ability to develop, market and commercialize our tests. 

While  we  have  a  compliance  plan  to  address  compliance  with  government  laws  and  regulations,  including 
applicable  fraud  and  abuse  laws  and  regulations  such  as  those  described  in  this  risk  factor,  the  evolving  commercial 
compliance environment and the need to build and maintain robust and scalable systems to comply with regulations in 
multiple  jurisdictions  with  different  compliance  and  reporting  requirements  increases  the  possibility  that  we  could 
inadvertently violate one or more of these requirements. 

If we fail to comply with federal, state and foreign laboratory licensing requirements, we could lose the ability to perform 
our tests or experience disruptions to our business. 

We  are  subject  to  CLIA,  a  federal  law  that,  in  partnership  with  the  states,  regulates  clinical  laboratories  that 
perform testing on specimens derived from humans for the purpose of providing information for the diagnosis, prevention 
or treatment of disease or impairment of, or assessment of the health of, human beings. CLIA regulations require clinical 
laboratories  to  obtain  a  certificate  and  mandate  specific  standards  in  areas  including  personnel  qualifications, 
administration, participation in proficiency testing, patient test management and quality assurance. CLIA certification is 
also required in order for us to be eligible to bill state and federal healthcare programs, as well as many private third-party 
payers, for our tests. Our laboratories located in Austin, Texas and San Carlos, California are both CLIA certified and 
accredited by the College of American Pathologists, or CAP, a third party accreditation organization with deeming, or 
delegated,  authority  from  CMS  to  determine  compliance.  To  renew  these  certifications,  we  are  subject  to  survey  and 
inspection  every  two  years.  Moreover,  CLIA  and/or  state  inspectors  may  conduct  random  inspections  of  our  clinical 
laboratory or conduct an inspection as a result of a complaint or reported incident, as has occurred. Any failure to address 
identified deficiencies, or to otherwise comply with CLIA, CAP or state requirements, can result in enforcement actions, 
including the revocation, suspension, or limitation of our CLIA and/or CAP certificate of accreditation or state laboratory 
permit, as well as a directed plan of correction, on-site monitoring, civil monetary penalties, civil actions for injunctive 
relief,  criminal  penalties,  suspension  or  exclusion  from  the  Medicare  and  Medicaid  programs  and  significant  adverse 
publicity.  Bringing  our  laboratory  back  into  compliance  with  CLIA  requirements  could  cause  us  to  incur  significant 
expenses and potentially lose revenues in order to address deficiencies and achieve compliance. 

57 

Some states require that we hold licenses or permits to test samples from patients in those states, even if our 
laboratory facilities are not located in those states, and as a result we are also required to maintain standards related to 
those states’ licensure requirements to conduct testing in our laboratories. California requires laboratories operating in or 
testing specimens from individuals located in California to hold state licensure in addition to CLIA certification.  California 
laboratory registration is required for our San Carlos, California as well as for our Austin, Texas laboratory, because our 
Texas laboratory receives specimens originating from California; the State of Texas implements CLIA requirements on 
laboratories  operating  within  Texas  but  does  not  impose  additional  state  licensure  or  registration  requirements. 
Additionally, all personnel involved in testing in our California laboratory must maintain a California state license or be 
supervised by licensed personnel. We maintain a license in good standing with the California Department of Public Health, 
or  CDPH,  for  both  our  California  and  Texas  laboratories.  In  addition,  the  New  York  State  Department  of  Health,  or 
NYSDOH, requires out-of-state laboratories that test specimens originating from New York to hold an NYSDOH permit 
and  to  comply  with  NYSDOH  laboratory  standards,  including  prior  NYSDOH  approval  of  LDTs.  We  test  specimens 
originating from New York at our San Carlos, California laboratory only, which has received approval from the NYSDOH 
to offer our Panorama, Horizon, Spectrum, Anora, Prospera and non-invasive prenatal paternity LDTs to residents of New 
York.  Although  we  do  not  currently  test  specimens  originating  from  New  York  at  our  Texas  laboratory,  our  Texas 
laboratory has also received approval from the NYSDOH to offer certain of our tests. Our laboratory director must also 
maintain a Certificate of Qualification issued by NYSDOH.  

As under CLIA, we are subject to routine on-site inspections or inspections in response to a complaint under both 
California  and  New  York  state  laboratory  laws  and  regulations.  If  we  are  found  to  be  out  of  compliance  with  either 
California or New York requirements, CDPH or NYSDOH may suspend, restrict or revoke our license or laboratory permit, 
respectively  (and,  with  respect  to  California,  may  exclude  persons  or  entities  from  owning,  operating  or  directing  a 
laboratory for two years following such license revocation), assess civil monetary penalties, or impose specific corrective 
action plans, among other sanctions. We cannot assure you that the regulators in any state from which we have obtained a 
required license or permit will find us to be in compliance with the applicable laws of their respective state at all times, 
which may result in suspension, limitation, revocation or annulment of our laboratory’s license for that state or negative 
impact to our CLIA certificate, censure, or civil monetary penalties, and would result in our inability to test samples from 
patients in that state. Any such consequences could materially and adversely affect our business by prohibiting or limiting 
our ability to offer testing. 

Changes in government healthcare policy could increase our costs and negatively impact coverage and reimbursement 
for our tests by governmental and other third-party payers. 

The U.S. government has shown significant interest in pursuing healthcare reform and reducing healthcare costs. 
Government healthcare policy has been and will likely continue to be a topic of extensive legislative and executive activity 
in the U.S. federal government and many U.S. state governments. As a result, our business could be affected by potentially 
significant  and  unanticipated  changes  in  government  healthcare  policy,  such  as  changes  in  reimbursement  levels  by 
government third-party payers, or in government-sponsored programs in which we may participate, such as the California 
PNS Program. Any such changes could substantially impact our revenues, increase costs and divert management attention 
from  our  business  strategy.  We  cannot  predict  the  impact,  if  any,  of  governmental  healthcare  policy  changes  on  our 
business, financial condition and results of operations. 

In the United States, the Patient Protection and Affordable Care Act, as amended by the Healthcare and Education 
Reconciliation Act of 2010, or collectively, the PPACA, was signed into law in March 2010 and significantly impacted 
the U.S. pharmaceutical and medical device industries, including the diagnostics sector, in a number of ways. Among other 
things, the PPACA expanded healthcare fraud and abuse laws such as the False Claims Act and the Anti-Kickback Statute, 
including but not limited to required disclosures of financial arrangements with physician customers, required reporting 
of  discovered  overpayments,  lower  thresholds  for  violations,  new  government  investigative  powers,  and  enhanced 
penalties  for  such  violations.  The  PPACA  restricts  insurers  from  charging  higher  premiums  or  denying  coverage  to 
individuals with pre-existing conditions, and requires insurers to cover certain preventative services without charging any 
copayment or coinsurance, including screening for lung, breast, colorectal and cervical cancers. However, there have been 
multiple attempts to repeal PPACA or significantly scale back its applicability, which if successful could negatively impact 
reimbursement for our testing, and could adversely affect our test volumes and, in turn, our business, financial condition, 
results  of  operations,  and  cash  flows.  For  example,  the  Tax  Cuts  and  Jobs  Act  of  2017,  or  the  Tax  Act,  repeals  the 

58 

requirement under PPACA that consumers buy insurance or pay a penalty unless they qualified for an applicable exemption. 
The repeal of this mandate means that fewer consumers may carry insurance coverage and therefore may be less likely to 
elect to receive our testing because they would be required to pay out of pocket for such tests, which could impact our test 
volumes and adversely affect our business, financial condition, results of operations, and cash flows. The PPACA also 
created a new system of health insurance “exchanges” designed to make health insurance available to individuals and 
certain groups through state- or federally-administered marketplaces in addition to existing channels for obtaining health 
insurance coverage. If Panorama or any of our other tests are not covered by plans offered in the health insurance exchanges, 
our business,  financial  condition  and  results  of operations could be  adversely  affected. Furthermore, various proposed 
legislative initiatives with respect to the PPACA in the past, including possible repeal of the PPACA, have resulted in 
considerable uncertainty and concern regarding, for example, a patient’s election to undergo genetic screening and whether 
doing so may impact health insurance eligibility. Because it is unclear whether or how the PPACA may continue to evolve, 
be modified, or otherwise change, and whether and to what extent NIPT, cancer screening or other genetic screening may 
be affected, we are uncertain how our business may be impacted. 

In  addition  to  the  PPACA,  various  healthcare  reform  proposals  have  also  emerged  from  federal  and  state 
governments.  Under  PAMA,  services  payable  by  Medicare  under  the  CLFS  are  being  calculated  based  on  negotiated 
payment rates paid by private payers for the same test. The implementation of the PAMA rates have negatively impacted 
overall  pricing  and  reimbursement  for  many  clinical  laboratory  testing  services  and  continue  to  be  the  subject  of 
controversy  in  the  industry. The  new rates  under PAMA  have not had  a  material  impact  on our  business  because our 
revenues from Medicare have been very low; however, we expect the new rates to have greater impact on us as we increase 
billing for our Signatera and Prospera testing. In addition, federal budgetary limitations and changes in healthcare policy, 
such as the creation of broad limits for our tests and requirements that beneficiaries of government health plans pay for, or 
pay for higher portions of, clinical laboratory tests or services received, could substantially diminish the utilization of our 
tests, increase costs and adversely affect our ability to generate revenues and achieve profitability. 

We cannot predict whether future healthcare initiatives will be implemented at the federal or state level or how 
any such future legislation, regulation or initiative may affect us. Current or potential future federal legislation and the 
expansion of government’s role in the U.S. healthcare industry, as well as changes to the reimbursement amounts paid by 
third-party payers for our current and future tests, may adversely affect our test volumes and adversely affect our business, 
financial condition, results of operations, and cash flows. 

If  we  or  our  laboratory  distribution  partners,  consultants  or  commercial  partners  act  in  a  manner  that  violates 
healthcare fraud and abuse laws or otherwise engage in misconduct, we may be subject to civil or criminal penalties. 

We are subject to healthcare fraud and abuse regulation and enforcement by both the U.S. federal government 

and the states in which we conduct our business, including: 

•  HIPAA,  which  created  federal  civil  and  criminal  laws  that  prohibit  executing  a  scheme  to  defraud  any 
healthcare  benefit  program  or  making  false  statements  relating  to  healthcare  matters  and  also  imposes 
significant  obligations  with  respect  to  maintenance  of  the  privacy  and  security,  and  transmission,  of 
individually identifiable health information; 

• 

• 

• 

federal and state laws and regulations governing informed consent for genetic testing and the use of genetic 
material; 

federal and state laws and regulations governing the submission of claims, as well as billing and collection 
practices, for healthcare services; 

the federal Anti-Kickback Statute, which prohibits, among other things, the knowing and willful solicitation, 
receipt,  offer  or  payment  of  remuneration,  directly  or  indirectly,  in  exchange  for  or  to  induce  either  the 
referral of an individual for, or the purchase, order or recommendation of, any good or service for which 
payment may be made under federal healthcare programs, such as Medicare; 

59 

• 

• 

• 

• 

the federal  False  Claims Act  which prohibits,  among other  things,  the  presentation of  false  or fraudulent 
claims for payment from Medicare, Medicaid, or other government-funded third-party payers; 

federal laws and regulations governing the Medicare program, providers of services covered by the Medicare 
program, and the submission of claims to the Medicare program, as well as the manuals and guidance issued 
by CMS and the local medical policies promulgated by the Medicare Administrative Contractors with respect 
to the implementation and interpretation of such laws and regulations; 

the federal Stark law, also known as the physician self-referral law, which, subject to certain exceptions, 
prohibits a physician from making a referral for certain designated health services covered by the Medicare 
program  (and  according  to  case  law  in  some  jurisdictions,  the  Medicaid  program  as  well),  including 
laboratory  and  pathology  services,  if  the  physician  or  an  immediate  family  member  has  a  financial 
relationship with the entity providing the designated health services; 

the  federal  Civil  Monetary  Penalties  statute,  which,  subject  to  certain  exceptions,  prohibits,  among  other 
things,  the  offer  or  transfer  of  remuneration  to  a  Medicare  or  state  healthcare  program  beneficiary  if  the 
person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, 
practitioner or supplier of services reimbursable by Medicare or a state healthcare program; 

•  EKRA,  which  applies  to  items  or  services  reimbursed  by  any  health  care  benefits  program,  including 
commercial  insurers,  that,  among  other  things,  prohibits  the  knowing  or  willful  payment  or  offer,  or  the 
solicitation or receipt, of any remuneration, whether directly or indirectly, overtly or covertly, in cash or in 
kind, in exchange for the referral or inducement of laboratory testing; 

• 

• 

the prohibition on reassignment by the program beneficiary of Medicare claims to any party; and 

state law equivalents to the above laws, which may apply to items or services reimbursed by any third-party 
payer, including commercial insurers, and state data privacy and security laws which may be more stringent 
than HIPAA. 

Furthermore, a development affecting our industry is the increased enforcement of the federal False Claims Act 
and, in particular, actions brought pursuant to the False Claims Act’s “whistleblower” or “qui tam” provisions. The False 
Claims  Act  imposes  liability  for,  among  other  things,  knowingly  presenting,  or  causing  to  be  presented,  a  false  or 
fraudulent claim for payment by a federal governmental payer program. The qui tam provisions of the False Claims Act 
allow a private individual to bring civil actions on behalf of the federal government for violations of the False Claims Act 
and permit such individuals to share in any amounts paid by the defendant to the government in fines or settlement. When 
an entity is determined to have violated the False Claims Act, it is subject to mandatory damages of three times the actual 
damages sustained by the government, plus mandatory civil penalties of up to approximately $23,607 for each false claim. 
In addition, various states have enacted false claim laws analogous to the federal False Claims Act, and in some cases go 
even further because many of these state laws apply where a claim is submitted to any third-party payer and not merely a 
governmental payer program. For example, in 2018 we reached a settlement with certain government payers regarding 
past reimbursement submissions. Although the settlement involved no admission of fault by us and no corporate integrity 
agreement, we cannot guarantee that we will not be subject to similar claims in the future. 

Many of these laws and regulations have not been fully interpreted by regulatory authorities or the courts, and 
their provisions are open to a variety of interpretations. In addition, there has been a recent trend of increased U.S. federal 
and state regulation, scrutiny and enforcement relating to payments made to referral sources, which are governed by these 
laws and regulations. 

We have adopted policies and procedures designed to comply with these laws, and in the ordinary course of our 
business, we conduct internal reviews of our compliance with these laws. However, the rapid growth and expansion of our 
business both within and outside of the United States may increase the potential for violating these laws or our internal 
policies and procedures, and the uncertainty around the interpretation of these laws and regulations increases the risk that 
we may be found in violation of these or other laws and regulations, or of allegations of such violations, including pursuant 

60 

to private qui tam actions brought by individual whistleblowers in the name of the government as described above. If our 
operations, including the conduct of our employees, distributors, consultants and commercial partners, are found to be in 
violation  of  any  laws  or  regulations  that  apply  to  us,  we  may  be  subject  to  penalties,  including  civil,  criminal  and 
administrative penalties, damages, fines, disgorgement of profits, exclusion from participation in government programs, 
injunctions, recall or seizure of products, total or partial suspension of production, denial or withdrawal of pre-marketing 
product approvals, contractual damages, reputational harm, diminished profits and future earnings and the curtailment or 
restructuring of our operations, any of which could materially and adversely affect our business, financial condition and 
results of operations. 

Failure to comply with privacy and security laws and regulations could result in fines, penalties and damage to our 
reputation and have a material adverse effect on our business. 

The federal HIPAA privacy and security regulations establish comprehensive federal standards with respect to 
the use and disclosure of protected health information by health plans, healthcare providers, and healthcare clearinghouses, 
in addition to setting standards to protect the confidentiality, integrity and security of protected health information. The 
regulations establish a complex regulatory framework on a variety of subjects, including patient authorization of the use 
and  disclosure  of,  administrative,  technical  and  physical  safeguards  for,  and  analysis  of  security  incidents  and  breach 
notification requirements with respect to, protected health information. HIPAA provides for significant fines and other 
penalties for wrongful use or disclosure of protected health information in violation of privacy and security regulations, 
including potential civil and criminal fines and penalties. 

The HIPAA privacy and security regulations establish minimum requirements, and do not supersede state laws 
that are more stringent. A number of states include medical information in the definition of personal information and have 
implemented requirements or standards more stringent than HIPAA. Therefore, while we have implemented policies and 
procedures related to compliance with the HIPAA regulations, we are also required to comply with various state privacy 
and security laws and regulations, and could incur penalties, compliance costs as a result of non-compliance, or damages 
under state laws pursuant to an action brought by a private party for the wrongful use or disclosure of confidential health 
information or other private personal information. In addition, other federal and state laws that protect the privacy and 
security of patient information may be subject to enforcement and interpretation by various governmental authorities and 
courts, resulting in complex compliance issues. 

The GDPR data privacy regulations comprehensively reform the prior data protection rules of the European Union, 
and are more stringent, provide for higher potential liabilities, and apply to a broader range of personal data than those in 
the United States. The GDPR is applicable to U.S.-based companies, such as ours, that do business or offer services in, or 
that  process or  hold  personal  data  of data  subjects  in,  the  European Union.  While  our current processes  and  practices 
comply with the GDPR, we have needed to expend considerable time and resources, including management attention, to 
revise our practices to ensure ongoing compliance with GDPR. Furthermore, the GDPR enables EU member states to enact 
jurisdiction-specific  requirements  in  key  areas,  which  could  require  us  to  implement  multiple  policies  unique  to  the 
jurisdictions in which we operate, which could make it more difficult and resource-intensive to continue to operate in the 
European Union. 

As we continue to expand and grow our business, our overall compliance with applicable laws and regulations 
may result in increased costs and attention of management, and failure to comply may result in significant fines, penalties 
and damage to our reputation. Additionally, the interpretation and application of health-related, privacy and data protection 
laws are often uncertain, contradictory and in flux, and it is possible that these laws may be interpreted and applied in a 
manner that is inconsistent with our practices. As a result, we could be subject to government-imposed fines or orders 
requiring  that  we  change  our  practices,  which  could  cause  us  to  incur  substantial  costs  and  may  adversely  affect  our 
business and our reputation. 

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Changes in the way the FDA regulates the reagents, other consumables, and testing equipment we use when developing, 
validating,  and  performing  our  tests  could  result  in  delay  or  additional  expense  in  bringing  our  tests  to  market  or 
performing such tests for our customers. 

Many of the sequencers, reagents, kits and other consumable products used to perform our testing, as well as the 
instruments and other capital equipment that enable the testing, are labeled as for research use only, or RUO. In addition, 
we offer a version of our Signatera test as a research use only offering. Products that are intended for research use only 
and  are  labeled  as  RUO  are  exempt  from  compliance  with  FDA  requirements,  including  the  approval,  clearance  or 
authorization and other product quality requirements for medical devices. A product labeled RUO but which is actually 
intended by the manufacturer for clinical diagnostic use may be viewed by the FDA as adulterated and misbranded under 
the FDC Act and subject to FDA enforcement action. The FDA has issued guidance stating that when determining the 
intended use of a product labeled RUO, it will consider the totality of the circumstances surrounding distribution of the 
product, including how the product is marketed and to whom. In addition, many of the reagents used to perform our testing 
are offered for sale as analyte specific reagents, or ASRs. ASRs are medical devices and must comply with QSR provisions 
and other device requirements, but most are exempt from premarket review. The FDA could disagree with a manufacturer’s 
assessment  that  the  manufacturer’s  products  are  ASRs,  or  could  conclude  that  products  labeled  as  RUO  are  actually 
intended by the manufacturer for clinical diagnostic use, and could take enforcement action against the manufacturer, such 
as us with respect to Signatera (RUO), including requiring the manufacturer to cease offering the product while it seeks 
clearance, approval or authorization. Manufacturers of RUO products that we employ in our other tests may cease selling 
their respective products, and we may be unable to obtain an acceptable substitute on commercially reasonable terms or at 
all, which could significantly and adversely affect our ability to provide timely testing results to our customers or could 
significantly increase our costs of conducting business. 

The sequencers and reagents supplied to us by Illumina are labeled as RUO in the United States. We are using 
these sequencers and reagents for clinical diagnostic use. If the FDA were to require clearance, approval or authorization 
for the sale of Illumina’s sequencers and if Illumina does not obtain such clearance, approval or authorization, we would 
have to find an alternative sequencing platform for Panorama. We currently have not validated an alternative sequencing 
platform  on  which  Panorama  could  be  run  in  a  commercially  viable  manner.  If  we  were  not  successful  in  selecting, 
acquiring on commercially reasonable terms and implementing an alternative platform on a timely basis, our business, 
financial condition and results of operations would be adversely affected. 

Our use of hazardous materials in the development of our tests exposes us to risks related to accidental contamination 
or injury and requires us to comply with regulations governing hazardous waste materials. 

Our research and development activities involve the controlled use of hazardous materials and chemicals. We 
cannot eliminate the risk of accidental contamination or injury to employees or third parties from the use, storage, handling 
or disposal of these materials. In the event of contamination or injury, we could be held liable for any resulting damages, 
and any liability could exceed our resources or any applicable insurance coverage we may have. In addition, we are subject 
on  an  ongoing  basis  to  federal,  state  and  local  regulations  governing  the  use,  storage,  handling  and  disposal  of  these 
materials and specified hazardous waste materials. An increase in the costs of compliance with such laws and regulations 
could harm our business and results of operations. 

If the validity of an informed consent from a patient intake for Panorama or our other tests is challenged, we could be 
precluded from billing for such testing, forced to stop performing such tests, or required to repay amounts previously 
received, which would adversely affect our business and financial results. 

All clinical data and blood samples that we receive for genetic testing are required to have been collected from 
individuals  who  have  provided  appropriate  informed  consent  for  us  to  perform  our  testing,  both  commercially  and  in 
clinical trials. We seek to ensure that the individuals from whom the data and samples are collected do not retain or have 
conferred any proprietary or commercial rights to the data or any discoveries derived from them. Our partners operate in 
a number of different countries in addition to the United States, and, to a large extent, we rely upon them to comply with 
the individual’s informed consent and with U.S. and international laws and regulations. The collection of data and samples 
in many different U.S. states and foreign countries results in complex legal questions regarding the adequacy of informed 
consent and the status of genetic material under different legal systems. The individual’s informed consent obtained could 
be challenged in the future in any particular jurisdiction, and those informed consents could be deemed invalid, unlawful 
or otherwise inadequate for our purposes. Any findings against us, or our laboratory distribution partners, could deny us 

62 

access to, or force us to stop testing samples in, a particular country or could call into question the results of our clinical 
trials. We could also be precluded from billing third-party payers for tests for which informed consents are challenged, or 
could be requested to refund amounts previously paid by third-party payers for such tests. We could become involved in 
legal challenges, which could require significant management and financial resources and adversely affect our revenues 
and results of operations. 

Risks Related to Our Intellectual Property 

Litigation  or  other  proceedings  resulting  from  either  third-party  claims  of  intellectual  property  infringement,  or 
asserting  infringement  by  third  parties  of  our  technology,  is  costly,  time-consuming,  and  could  limit  our  ability  to 
commercialize our products or services. 

Our success depends in part on our non-infringement of the patents or intellectual property rights of third parties, 
and our ability to successfully prevent third parties from infringing our intellectual property. We operate in a crowded 
technology area in which there has been substantial litigation and other proceedings regarding patent and other intellectual 
property rights in the genetic diagnostics industry. Third parties, including our competitors, have asserted and may in the 
future assert that we are infringing their intellectual property rights; in particular, we are or have recently been engaged in 
patent infringement lawsuits and other intellectual property disputes against various competitors in each of the industries 
in which we operate, as described in “Note 8—Commitments and Contingencies—Legal Proceedings” in the Notes to 
Consolidated Financial Statements. We may become subject to and/or initiate future intellectual property litigation as our 
product portfolio, and the level of competition in our industry segments, grow. 

Should we be unsuccessful defending against patent infringement claims, we may be required to pay substantial 
royalties, money damages, change our marketing practices, or be enjoined from offering certain products or services. In 
addition, we could experience delays in product introductions or sales growth while we attempt to develop non-infringing 
alternatives. Any of these or other adverse outcomes could prevent us from offering our tests or otherwise have a material 
adverse effect on our business, financial condition and our results of operations. 

We cannot predict whether, or offer any assurance that, the patent infringement claims we have initiated or may 
initiate in the future will be successful. We are and may become subject to counterclaims by patent infringement defendants. 
Our patents may be declared invalid or unenforceable, or narrowed in scope. Even if we prevail in an infringement action, 
we cannot assure you that we would be adequately compensated for the harm to our business. If we are unable to enjoin 
third-party infringement, our revenues may be adversely impacted and we may lose market share; and such third-party 
product may continue to exist in the market, but fail to meet our regulatory or safety standards, thereby causing irreparable 
harm to our reputation as a provider of quality products, which in turn could result in loss of market share and have a 
material adverse effect on our business, financial condition and our results of operations. 

In addition, our agreements with some of our customers, suppliers, and other entities with whom we do business 
require us to defend or indemnify these parties to the extent they become involved in patent infringement claims, including 
the types of claims described in this risk factor. We have agreed, and may in the future agree, to defend or indemnify third 
parties if we determine it to be in the best interests of our business relationships. If we are required or agree to defend or 
indemnify third parties in connection with any infringement claims, we could incur significant costs and expenses that 
could adversely affect our business, financial condition and results of operations. 

Any inability to effectively protect our proprietary technologies could harm our competitive position. 

Our success and ability to compete depend to a large extent on our ability to develop proprietary products and 
technologies and to maintain adequate protection of our intellectual property in the United States and other countries; this 
becomes  increasingly  important  as  we  expand  our  operations  and  enter  into  strategic  collaborations  with  partners  to 
develop and commercialize products. The laws of some foreign countries do not protect proprietary rights to the same 
extent as the laws of the United States, and we may encounter difficulties in establishing and enforcing our proprietary 
rights outside of the United States. In addition, the proprietary positions of companies developing and commercializing 
tools for molecular diagnostics, including ours, generally are uncertain and involve complex legal and factual questions. 

63 

This  uncertainty  may  materially  affect  our  ability  to  defend  or  obtain  patents  or  to  address  the  patents  and  patent 
applications owned or controlled by our collaborators and licensors. 

We will be able to protect our proprietary rights from unauthorized use by third parties only to the extent that our 
proprietary technologies are protected by valid and enforceable patents or are effectively maintained as trade secrets. We 
have worked to procure patents protecting our technologies, but our procurement efforts may not always be successful, 
and  any patents  we successfully  procure  may be  challenged  in  ways  that  lead  to  post-procurement scope  reduction or 
invalidity. For example, certain of our intellectual property is, or recently has been, the subject of challenges instituted by 
our  competitors,  as  described  in  “Note 8—Commitments  and  Contingencies—Legal  Proceedings”  in  the  Notes  to 
Consolidated  Financial  Statements.  These  challenges  may  impede  our  ability  to  protect  our  proprietary  rights  from 
unauthorized use. In addition, any finding that others have claims of inventorship or ownership rights to our patents and 
applications  could  require  us  to  obtain  certain  rights  to  practice  related  technologies,  which  may  not  be  available  on 
favorable terms. 

Certain of our intellectual property was partly supported by a U.S. government grant awarded by the National 
Institutes  of  Health,  and  the  government  accordingly  has  certain  rights  in  this  intellectual  property,  including  a 
non-exclusive, non-transferable, irrevocable worldwide license to use applicable inventions for any governmental purpose. 
Such rights also include “march-in” rights, which refer to the right of the U.S. government to require us to grant a license 
to the technology to a responsible applicant if we fail to achieve practical application of the technology or if action is 
necessary to alleviate health or safety needs, to meet requirements of federal regulations or to give preference to U.S. 
industry. 

Any  of  these  factors  could  adversely  affect  our  ability  to  obtain  commercially  relevant  or  competitively 

advantageous patent protection for our products. 

If we are not able to adequately protect our trade secrets and other proprietary information, the value of our technology 
and products could be significantly diminished. 

We rely on trade secret and proprietary know-how protection for our confidential and proprietary information 
and  have  taken  security  measures  to  protect  this  information.  These  measures,  however,  may  not  provide  adequate 
protection. For example, we have a policy of requiring our consultants, advisors and collaborators, including, for example, 
our  strategic  collaborators  with  whom  we  seek  to  develop  and  commercialize  products,  to  enter  into  confidentiality 
agreements and our employees to enter into invention, non-disclosure and non-compete agreements. However, breaches 
of our physical or electronic security systems, or breaches caused by our employees failing to abide by their confidentiality 
obligations during or upon termination of their employment with us, could compromise these protection efforts. Any action 
we  take  to  enforce  our  rights  may  be  time-consuming,  expensive,  and  possibly  unsuccessful.  Even  if  successful,  the 
resulting remedy may not adequately compensate us for the harm caused by the breach. These risks are heightened in 
countries where laws or law enforcement practices may not protect proprietary rights as fully as in the United States or 
Europe. Any unauthorized use or disclosure of, or access to, our trade secrets, know-how or other proprietary information, 
whether accidentally or through willful misconduct, could have a material adverse effect on our programs and our strategy, 
and on our ability to compete effectively. 

If our trademarks and trade names are not adequately protected, we may not be able to establish or maintain name 
recognition in our markets of interest, and our business may be adversely affected. 

Failure to maintain our trademark registrations, or to obtain new trademark registrations in the future, could limit 
our ability to protect our trademarks and impede our marketing efforts in the countries in which we operate. We may not 
be able to protect our rights to trademarks and trade names that we may need to build name recognition with potential 
partners or customers in our markets of interest. As a means to enforce our trademark rights and prevent infringement, we 
may be required to file trademark claims against third parties or initiate trademark opposition proceedings. This can be 
expensive and time-consuming, and possibly unsuccessful. Our registered or unregistered trademarks or trade names may 
be challenged, infringed, circumvented, declared generic or determined to infringe on other marks. 

64 

Our pending trademark applications in the United States and in other foreign jurisdictions where we may file may 
not be successful. Even if these applications result in registered trademarks, third parties may challenge these trademarks 
in the future. Over the long term, if we are unable to establish name recognition based on our trademarks and trade names, 
then we may not be able to compete effectively and our business may be adversely affected. 

We  may  be  subject  to  claims  that  our  employees,  consultants  or  independent  contractors  have  wrongfully  used  or 
disclosed confidential information of third parties. 

We employ individuals who were previously employed at other biotechnology or diagnostic companies. We may 
be subject to claims that we or our employees, consultants or independent contractors have inadvertently or willfully used 
or disclosed confidential information of our employees’ former employers or other third parties. We may also be subject 
to claims that our employees’ former employers or other third parties have an ownership interest in our patents. Litigation 
may  be  necessary  to  defend  against  these  claims,  and  if  we  are  unsuccessful,  we  could  be  required  to  pay  substantial 
damages  and  could  lose  rights  to  important  intellectual  property.  Even  if  we  are  successful,  litigation  could  result  in 
substantial costs to us and could divert the time and attention of our management and other employees. 

Risks Related to our Convertible Notes 

Servicing our debt will require a significant amount of cash. We may not have sufficient cash flow from our business 
to pay our outstanding debt, and we may not have the ability to raise the funds necessary to settle conversions of the 
Convertible Notes in cash or to repurchase the Convertible Notes upon a fundamental change, which could adversely 
affect our business and results of operations. 

Our ability to make scheduled payments of the principal of, to pay interest on, or to refinance our indebtedness, 
including  the  amounts  payable  under  the  Convertible  Notes,  depends  on  our  future  performance,  which  is  subject  to 
economic, financial, competitive, and other factors beyond our control. Our business may not continue to generate cash 
flow from operations in the future sufficient to service our indebtedness and make necessary capital expenditures. If we 
are  unable  to  generate  such  cash  flow,  we  may  be  required  to  adopt  one  or  more  alternatives,  such  as  selling  assets, 
restructuring debt, or obtaining additional equity capital on terms that may be onerous or highly dilutive. Our ability to 
refinance our indebtedness will depend on the capital markets and our financial condition at such time. We may not be 
able to engage in any of these activities or engage in these activities on desirable terms, which could result in a default on 
our debt obligations. 

Further,  holders  of  the  Convertible  Notes  have  the  right  to  require  us  to  repurchase  all  or  a  portion  of  their 
Convertible Notes upon the occurrence of a “fundamental change” (as defined in the indenture governing the Convertible 
Notes) before the maturity date at a repurchase price equal to 100% of the principal amount of the Convertible Notes to 
be repurchased, plus accrued and unpaid interest, if any. In addition, upon conversion of the Convertible Notes, unless we 
elect to deliver solely shares of our common stock to settle such conversion (other than paying cash in lieu of delivering 
any fractional share), we will be required to make cash payments in respect of the Convertible Notes being converted. 
However, we may not have enough available cash, or be able to obtain sufficient financing, at the time we are required to 
repurchase the Convertible Notes. 

The  conditional  conversion  feature  of  the  Convertible  Notes,  when  triggered,  may  adversely  affect  our  financial 
condition and operating results. 

The conditional conversion feature of the Convertible Notes has been triggered for certain applicable periods 
beginning with the quarter ended September 30, 2020. During periods for which the conditional conversion feature has 
been or is triggered, holders of the Convertible Notes are entitled to convert their Convertible Notes at any time during 
such periods at their option. If one or more holders elect to convert their Convertible Notes, unless we choose to satisfy 
our conversion obligation by delivering solely shares of our common stock (other than paying cash in lieu of delivering 
any fractional share), we would elect to settle a portion or all of our conversion obligation in cash, which could adversely 
affect our liquidity. No holders have elected to convert their Convertible Notes. 

65 

In addition, even if holders of Convertible Notes do not elect to convert their Convertible Notes, we could be 
required under applicable accounting rules to reclassify all or a portion of the outstanding principal of the Convertible 
Notes as a current rather than long-term liability, which would result in a material reduction of our net working capital.  

The accounting method for convertible debt securities that may be settled in cash, such as the Convertible Notes, could 
have a material effect on our reported financial results. 

The accounting method for reflecting the Convertible Notes on our balance sheet, accruing interest expense for 
the Convertible Notes, and reflecting the underlying shares of our common stock in our reported diluted earnings per share 
may adversely affect our reported earnings and financial condition. 

We expect that, under applicable accounting principles, the initial liability carrying amount of the Convertible 
Notes will be the fair value of a similar debt instrument that does not have a conversion feature, valued using our cost of 
capital for straight, unconvertible debt. We have reflected the difference between the net proceeds from the sale of the 
Convertible Notes and the initial carrying amount as a debt discount for accounting purposes, which is amortized into 
interest  expense  over  the  term  of  the  Convertible  Notes.  As  a  result  of  this  amortization,  the  interest  expense  to  be 
recognized for the Convertible Notes for accounting purposes will be greater than the cash interest payments we will pay 
on the Convertible Notes, which results in lower reported net income. The lower reported income (or higher net loss) 
resulting from this accounting treatment could depress the trading price of our common stock and the Convertible Notes. 

Under previous accounting standards, under certain circumstances we would be eligible to use the treasury stock 
method to reflect the shares underlying the Convertible Notes in our diluted earnings per share. Under this method, if the 
conversion value of the Convertible Notes exceeds their principal amount for a reporting period, then we would calculate 
our diluted earnings per share assuming that all the Convertible Notes were converted and that we issued shares of our 
common stock to settle the excess. However, if reflecting the Convertible Notes in diluted earnings per share in this manner 
would be anti-dilutive, or if the conversion value of the Convertible Notes would not exceed their principal amount for a 
reporting period, then the shares underlying the Convertible Notes would not be reflected in our diluted earnings per share. 
In August 2020, the Financial Accounting Standards Board (FASB) issued Accounting Standards Update 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). This guidance, which is effective for fiscal years beginning after December 15, 2021 (including 
interim periods within those fiscal years), eliminated the treasury stock method described above for convertible instruments 
such as the Convertible Notes and instead requires application of the “if-converted” method. Under that method, diluted 
earnings per share would generally be calculated assuming that all the Convertible Notes were converted solely into shares 
of common stock at the beginning of the reporting period, unless the result would be anti-dilutive. The application of the 
if-converted method may reduce our reported diluted earnings per share. 

Furthermore, if any of the conditions to the convertibility of the Convertible Notes is satisfied, then we may be 
required  under  applicable  accounting  standards  to  reclassify  the  liability  carrying  value  of  the  Convertible  Notes  as  a 
current,  rather  than  a  long-term,  liability.  This  reclassification  could  be  required  even  if  no  noteholders  convert  their 
Convertible Notes and could materially reduce our reported working capital. 

Conversion of the Convertible Notes will dilute the ownership interest of existing stockholders, including holders who 
had previously converted their Convertible Notes, or may otherwise depress the price of our common stock. 

The conversion of some or all of the Convertible Notes will dilute the ownership interests of stockholders to the 
extent we deliver shares of our common stock upon such conversion. The Convertible Notes are currently convertible and 
may from time to time in the future be convertible at the option of their holders prior to their scheduled terms under certain 
circumstances. Any sales in the public market of the common stock issuable upon such conversion could adversely affect 
prevailing market prices of our common stock. In addition, the existence of the Convertible Notes may encourage short 
selling by market participants because the conversion of the Convertible Notes could be used to satisfy short positions, or 
anticipated conversion of the Convertible Notes into shares of our common stock could depress the price of our common 
stock. 

66 

Risks Related to Ownership of Our Common Stock 

The market price of our common stock has been and may be volatile, which could subject us to litigation. 

The trading prices of the securities of life sciences companies, including ours, have been and may continue to be 
highly volatile; and financial markets in general, including our stock, have experienced particularly high volatility as a 
result of the ongoing COVID-19 pandemic. Accordingly, the market price of our common stock is likely to be subject to 
wide fluctuations in response to numerous factors, many of which are beyond our control, such as those in this “Risk 
Factors” section and others including: 

• 

• 

• 

• 

• 

• 

• 

• 

• 

• 

• 

• 

• 

actual or anticipated variations in our and our competitors’ results of operations, as well as how those results 
compare to analyst and investor expectations; 

announcements by us or our competitors of new products, significant acquisitions, other strategic transactions, 
including strategic and commercial partnerships and relationships, joint ventures, divestitures, collaborations 
or capital commitments; 

changes in reimbursement practices by current or potential payers; 

failure  of  analysts  to  initiate  or  maintain  coverage  of  our  company,  issuance  of  new  securities  analysts’ 
reports or changed recommendations for our stock; 

negative publicity, including misinformation, about our company, our tests, or the commercial markets in 
which we operate;  

forward-looking statements related to our financial guidance or projections, our failure to meet or exceed our 
financial guidance or projections or changes in our financial guidance or projections; 

actual or anticipated changes in regulatory oversight of our products; 

development of disputes concerning our intellectual property or other proprietary rights; 

commencement of, or our involvement in, litigation; 

announcement or expectation of additional debt or equity financing efforts; 

any major change in our management; 

general economic conditions and slow or negative growth of our markets, including as a result of changes in 
the rate of inflation (including the cost of raw materials, commodities, and supplies) and interest rates; and 

changes  in  business,  economic,  and  political  conditions,  including  war,  political  instability  and  related 
military action. 

In  addition,  if  the  market  for  life  sciences  stocks  or  the  stock  market  in  general  experiences  uneven  investor 
confidence,  as  has  been  the  case  in  recent  months,  the  market  price  of  our  common  stock  could  decline  for  reasons 
unrelated  to  our  business,  operating  results  or  financial  condition.  The  market  price  of  our  common  stock  might  also 
decline in reaction to events that affect other companies within, or outside, our industry even if these events do not directly 
affect us. Some companies, including us, that have experienced volatility in the trading price of their stock have been the 
subject of securities class action litigation, and we may in the future become subject to such litigation. For example, we 
have in the past been subject to a purported securities class action lawsuit filed against us, our directors and certain of our 
officers and stockholders related to our initial public offering. Under certain circumstances, we have contractual and other 
legal obligations to indemnify and to incur legal expenses on behalf of current and former directors and officers, and on 
behalf of our former underwriters, in connection with any future lawsuits. Any lawsuit to which we are a party, with or 

67 

without merit, may result in an unfavorable judgment. We also may decide to settle lawsuits on unfavorable terms. Any 
such  negative outcome  could  result  in payments of  substantial  damages  or fines,  damage  to our reputation or  adverse 
changes to our offerings or business practices. Defending against litigation is costly and time-consuming, and could divert 
our management’s attention and resources. Furthermore, during the course of litigation, there could be negative public 
announcements  of  the  results  of  hearings,  motions  or  other  interim  proceedings  or  developments,  which  could  have  a 
material adverse effect on the market price of our common stock. 

If we are unable to implement and maintain effective internal controls over financial reporting in the future, investors 
may lose confidence in the accuracy and completeness of our financial reports and the market price of our common 
stock could be adversely affected. 

We are required to maintain internal controls over financial reporting and to report any material weaknesses in 
such internal controls. Section 404 of the Sarbanes-Oxley Act requires that we evaluate and determine the effectiveness 
of  our  internal  controls  over  financial  reporting  and  provide  a  management  report  on  internal  controls  over  financial 
reporting. The Sarbanes-Oxley Act also requires that our management report on internal controls over financial reporting 
be attested to by our independent registered public accounting firm. 

Although we determined that our internal controls over financial reporting were effective as of December 31, 
2021, we must continue to monitor and assess our internal controls over financial reporting. If we have a material weakness 
in our internal controls over financial reporting, we may not detect errors on a timely basis and our financial statements 
may be materially misstated. If we identify material weaknesses in our internal controls over financial reporting, if we are 
unable to comply with the requirements of Section 404 in a timely manner, if we are unable to assert that our internal 
controls  over  financial  reporting  are  effective,  or,  when  required  in  the  future,  if  our  independent  registered  public 
accounting firm is unable to express an opinion as to the effectiveness of our internal controls over financial reporting, 
investors  may  lose  confidence  in  the  accuracy  and  completeness  of  our  financial  reports  and  the  market  price  of  our 
common stock could be adversely affected, and we could become subject to investigations by the stock exchange on which 
our securities are listed, the SEC, or other regulatory authorities. 

We do not intend to pay dividends on our capital stock so any returns will be limited to changes in the value of our 
common stock. 

We have never declared or paid any cash dividends on our capital stock. We currently anticipate that we will 
retain future earnings for the development, operation and expansion of our business and do not anticipate declaring or 
paying any cash dividends for the foreseeable future. In addition, our ability to pay cash dividends on our capital stock 
may be prohibited or limited by the terms of any current or future debt financing arrangement. Any return to stockholders 
will therefore be limited to the increase, if any, in the price of our common stock. 

Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity 
incentive plans or in connection with acquisitions or strategic or commercial transactions, could result in additional 
dilution of the percentage ownership of our stockholders and could cause the price of our common stock to decline. 

From time to time, we may issue additional securities or sell common stock, convertible securities, such as the 
Convertible Notes, or other equity securities in one or more transactions at prices and in a manner we determine. We also 
expect to continue to issue common stock to employees and directors pursuant to our equity incentive plans. If we sell or 
issue  common  stock,  convertible  securities,  or  other  equity  securities,  or  common  stock  is  issued  pursuant  to  equity 
incentive plans, investors in our common stock may be materially diluted. As we have done in the past, we may decide to 
issue common stock or other equity securities in connection with an acquisition or a strategic or commercial transaction, 
which could cause dilution to our existing stockholders. New investors in such transactions could gain rights, preferences 
and privileges senior to those of holders of our common stock. 

Sales of a substantial number of shares of our common stock in the public markets could cause the price of our common 
stock to decline. 

Sales of a substantial number of shares of our common stock in the public market or the perception that these 
sales might occur could depress the market price of our common stock and could impair our ability to raise capital through 
the sale of additional equity securities. We are unable to predict the effect that sales may have on the prevailing market 
price of our common stock. 

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As we have done in the past, we may issue our shares of common stock or securities convertible into our common 
stock,  such  as  our  Convertible  Notes,  from  time  to  time  in  connection  with  a  financing,  acquisition,  investments  or 
otherwise. Any such issuance could result in substantial dilution to our existing stockholders and cause the price of our 
common stock to decline. 

If  securities  or  industry  analysts  do  not  publish  research  or  publish  inaccurate  or  unfavorable  research  about  our 
business, our stock price and trading volume could decline. 

The trading market for our common stock depends in part on the research and reports that securities or industry 
analysts publish about us or our business. Currently, only a small number of securities analysts cover our stock. If more 
analysts do not commence coverage of us, or if industry analysts cease coverage of us or fail to publish reports on us 
regularly, the trading price for our common stock could be adversely affected. If one or more of the analysts who cover us 
downgrade our common stock or publish inaccurate or unfavorable research about our business, our common stock price 
would likely decline. 

Insiders have substantial control over us and will be able to influence corporate matters. 

As  of  December  31,  2021,  our  directors  and  executive  officers  and  their  affiliates  beneficially  owned,  in  the 
aggregate, approximately 10.55% of our outstanding capital stock. As a result, these stockholders are and will continue to 
be able to exercise significant influence over all matters requiring stockholder approval, including the election of directors 
and  approval  of  significant  corporate  transactions,  such  as  a  merger  or  other  sale  of  our  company  or  its  assets.  This 
concentration of ownership could limit stockholders’ ability to influence corporate matters and may have the effect of 
delaying or preventing a third party from acquiring control over us. 

Provisions in our amended and restated certificate of incorporation, amended and restated bylaws, and Delaware 
law might discourage, delay or prevent a change in control of our company or changes in our management and, therefore, 
depress the market price of our common stock. 

Our amended and restated certificate of incorporation and amended and restated bylaws contain provisions that 
could depress the market price of our common stock by acting to discourage, delay or prevent a change in control of our 
company or changes in our management that the stockholders of our company may deem advantageous. These provisions, 
among other things: 

• 

• 

• 

• 

• 

• 

• 

• 

authorize  the  issuance  of  “blank  check”  preferred  stock  that  our  board  of  directors  could  use  to 
implement a stockholder rights plan; 

prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a 
meeting of our stockholders; 

eliminate the ability of our stockholders to call special meetings of stockholders; 

establish  advance  notice  requirements  for  nominations  for  election  to  our  board  of  directors  or  for 
proposing matters that can be acted upon by stockholders at annual stockholder meetings; 

establish a classified board of directors so that not all members of our board are elected at one time; 

permit the board of directors to establish the number of directors; 

provide  that  directors  may  only  be  removed  “for  cause”  and  only  with  the  approval  of  75%  of  our 
stockholders; 

require  super-majority  voting  to  amend  some  provisions  in  our  amended  and  restated  certificate  of 
incorporation and amended and restated bylaws; and 

69 

• 

provide  that  the  board of directors  is  expressly  authorized  to  make,  alter  or repeal  our amended  and 
restated bylaws. 

In addition, Section 203 of the Delaware General Corporation Law may discourage, delay or prevent a change in 
control of our company. Section 203 imposes certain restrictions on mergers, business combinations and other transactions 
between us and holders of 15% or more of our common stock. 

In addition, if a “fundamental change” (as defined in the indenture governing the Convertible Notes) occurs prior 
to the maturity date of the Convertible Notes, holders of the Convertible Notes will have the right, at their option, to require 
us to repurchase all or a portion of their Convertible Notes. If a “make-whole fundamental change” (as defined in the 
indenture governing the Convertible Notes) occurs prior to the maturity date, we will in some cases be required to increase 
the conversion rate of the Convertible Notes for a holder that elects to convert its Convertible Notes in connection with 
such make-whole fundamental change. Furthermore, we are prohibited from engaging in certain mergers or acquisitions 
unless, among other things, the surviving entity of such transaction assumes our obligations under the Convertible Notes. 

Our amended and restated certificate of incorporation provides that the Court of Chancery of the State of Delaware is 
the exclusive forum for substantially all disputes between us and our stockholders, which could limit our stockholders’ 
ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees. 

Our  amended  and  restated  certificate  of  incorporation  provides  that  the  Court  of  Chancery  of  the  State  of 
Delaware is the exclusive forum for any derivative action or proceeding brought on our behalf, any action asserting a 
breach of fiduciary duty, any action asserting a claim against us arising pursuant to the Delaware General Corporation 
Law  or  any  action  asserting  a  claim  against  us  that  is  governed  by  the  internal  affairs  doctrine.  This  choice  of  forum 
provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us 
or our directors, officers or other employees and may discourage these types of lawsuits. Alternatively, if a court were to 
find the choice of forum provision contained in our certificate of incorporation to be inapplicable or unenforceable in an 
action, we may incur additional costs associated with resolving such action in other jurisdictions, which could harm our 
business, financial condition and results of operations. 

Changes in accounting standards and their interpretations could adversely affect our operating results. 

U.S. GAAP  is  subject  to  interpretation  by  the  Financial  Accounting  Standards  Board,  or  FASB,  the  Public 
Company  Accounting  Oversight  Board,  or  PCAOB,  the  SEC,  and  various  other  bodies  that  promulgate  and  interpret 
appropriate  accounting  principles.  These  principles  and  related  implementation  guidelines  and  interpretations  can  be 
highly complex and involve subjective judgments. A change in these principles or interpretations, including with respect 
to the accounting for the Convertible Notes, could have a significant effect on our reported financial results, and could 
affect the reporting of transactions completed before or after the announcement of a change in such principles. Additionally, 
the adoption of these standards may potentially require enhancements or changes in our systems and will require significant 
time and cost on behalf of our financial management. A discussion of these standards and other pending changes in GAAP, 
are further discussed in “Note 2—Summary of Significant Accounting Policies” in the Notes to Consolidated Financial 
Statements. 

ITEM 1B.  UNRESOLVED STAFF COMMENTS 

None. 

ITEM 2. 

PROPERTIES  

We lease office facilities under non-cancelable operating lease agreements. We currently occupy approximately 
136,000 square feet of laboratory and office space at 201 Industrial Road in San Carlos, California pursuant to a lease that 
we directly entered into with our landlord in October 2016. This lease covers two office spaces, referred to as the First 
Space and the Second Space. The First Space covers approximately 88,000 square feet at an average base rent of $340,972 
per  month  for  the  year  2020.  The  Second  Space  covers  approximately  48,000  square  feet  at  an  average  base  rent  of 
$197,605 per month. The original lease term is approximately 84 months and expires in October 2023. In January 2021, 

70 

 
 
 
 
we entered into an amendment of the lease to extend the term for 48 months to October 2027. The combined monthly rent 
for the First Space and Second Space will be $776,671 commencing in October 2023. 

We entered into a sublease agreement in June 2019 with a third party to sublease 25,879 square feet of space 
located on the third floor of the San Carlos, California building while maintaining its primary obligation as the intermediate 
lessor. The term of this lease is approximately 48 months commencing in October 2019 and expiring in September 2023. 
In February 2021, we entered into an amendment of the San Carlos sublease agreement whereas the third party will initially 
return approximately 3,474 rentable square feet with the remainder of the subleased premises, consisting of approximately 
22,405 rentable square feet, between October 2021 and December 2021.  

In Tukwila, Washington, we lease a facility initially to provide storage of our cord blood tissue units. The facility 
covers approximately 10,000 square feet, with a lease term of 62 months beginning in June 2018 and expiring in July 
2023. In the third quarter of 2019, we sold the Evercord business and the facility was subleased to a third party. We do not 
intend to exercise its option to renew the facility upon expiration.  

Our subsidiary leases laboratory and office space in Austin, Texas, comprising approximately 94,000 square feet 
pursuant to a lease expiring in November 2026. The lease term is 132 months beginning in December 2015 and expiring 
in  November  2026  with  monthly  payments  beginning  in  December  2016.  In  December  2021,  we  entered  into  an 
amendment of the Austin lease agreement which extended the lease of the current premises through March 2033. The 
amendment  also  includes  two  additional  office  spaces,  referred  to  as  the  First  Expansion  Premises  and  the  Second 
Expansion Premises. The First Expansion Premises consists of 32,500 rentable square feet and commences in February 
2022. The Second Expansion Premises consists of 65,222 rentable square feet and commences in September 2022. The 
terms of the First and Second Expansion Premises expire in March 2033.  

We entered into a lease agreement in November 2020 to lease 11,395 square feet of space located in South San 

Francisco, California over a three-year term. The premises is used for general office, laboratory and research use. 

As  part  of  the  in-process  research  and  development,  or  the  IPR&D,  asset  acquisition  in  September  2021,  we 
inherited  a  24-month  lease  for  7,107 square  feet  of  laboratory  space  in  Canada.  The  annual  lease  payment  starts  at 
$0.2 million. 

We have also historically entered into leases of individual workspaces and storage spaces at various locations on 
both a month-to-month basis without an established lease term, and more recently for certain locations, have committed 
to  terms  approximating one to five  years.  For  the  facilities  without  a  committed  lease  term,  we  have  elected  to  not 
recognize them as the right-of-use assets on the balance sheet as they are all considered short-term leases. For individual 
workspaces where the committed lease term exceeds one year, we have recorded a right-of-use asset. 

We may expand our facilities capacity as our employee base and laboratory processing needs grow. We believe 

that we will be able to obtain additional space on commercially reasonable terms. 

ITEM 3. 

LEGAL PROCEEDINGS 

From time to time, we are involved in legal proceedings. The results of such legal proceedings and claims cannot 
be predicted with certainty, and regardless of the outcome, legal proceedings could have an adverse impact on us because 
of defense and settlement costs, diversion of resources and other factors. 

For information regarding certain current legal proceedings, see “Note 8—Commitments and Contingencies—

Legal Proceedings” in the Notes to Consolidated Financial Statements, which is incorporated herein by reference. 

ITEM 4.  MINE SAFETY DISCLOSURES 

Not applicable. 

71 

 
 
 
 
 
 
 
 
 
 
 
 
PART II 

ITEM 5.  MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS 

AND ISSUER PURCHASES OF EQUITY SECURITIES 

Market Price of Our Common Stock 

Our common stock is listed on the Nasdaq Global Select Market under the symbol “NTRA”. 

Holders 

As of February 24, 2022, we had 2 holders of record of our common stock. The actual number of stockholders is 
greater than this number of record holders and includes stockholders who are beneficial owners, but whose shares are held 
in street name by brokers and other nominees.  This number of holders of record also does not include stockholders whose 
shares may be held in trust by other entities. 

Dividends 

No cash dividends have ever been paid or declared on our common stock. We currently intend to retain all future 
earnings, if any, for use in our business and do not anticipate paying any cash dividends on our common stock in the 
foreseeable  future.  Any  future  determination  to  declare  cash  dividends  will  be  made  at  the  discretion  of  our  board  of 
directors, subject to applicable laws, and will depend on our financial condition, results of operations, capital requirements, 
general business conditions and other factors our board of directors may deem relevant. 

72 

 
 
 
 
 
 
 
 
 
Performance Graph  

This  performance  graph  shall  not  be  deemed  “filed”  for  purposes  of  Section  18  of  the  Exchange  Act,  or 
incorporated by reference into any of our other filings under the Exchange Act or the Securities Act except to the extent 
we specifically incorporate it by reference into such filing. The following graph compares the cumulative total stockholder 
return on our common stock between our initial public offering on July 2, 2015 and December 31, 2021 with the cumulative 
total return of (i) the NASDAQ Biotechnology Index and (ii) the NASDAQ Composite Index over the same period. The 
chart assumes $100 was invested at the close of market on July 2, 2015, and assumes the reinvestment of any dividends. 
The stock price performance on the following graph is not necessarily indicative of future stock price performance. 

Trade Date 

Natera, Inc. 

Nasdaq 
Biotechnology 

Nasdaq 
Composite 

Base period 7/2/2015 . . . . . . . . . . . . . .    
12/31/2015 . . . . . . . . . . . . . . . . . . . . . . .    
12/31/2016 . . . . . . . . . . . . . . . . . . . . . . .    
12/31/2017 . . . . . . . . . . . . . . . . . . . . . . .    
12/31/2018 . . . . . . . . . . . . . . . . . . . . . . .    
12/31/2019 . . . . . . . . . . . . . . . . . . . . . . .    
12/31/2020 . . . . . . . . . . . . . . . . . . . . . . .    
12/31/2021 . . . . . . . . . . . . . . . . . . . . . . .    

$
$
$
$
$
$
$
$

Recent Sales of Unregistered Securities 

None. 

100
47.49
51.50
39.53
61.39
147.45
437.64
408.40

$
$
$
$
$
$
$
$

100    $ 
91.34    $ 
71.53    $ 
86.60    $ 
78.52    $ 
97.34    $ 
122.78    $ 
122.00    $ 

100
99.96
107.46
137.81
132.46
178.59
257.29
312.32

73 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Purchases of Equity Securities by the Issuer and Affiliated Parties 

None. 

ITEM 6. 

SELECTED FINANCIAL DATA  

The following table presents our selected historical consolidated financial data. The consolidated statements of 
operations data for the three fiscal years ended December 31, 2021, 2020, and 2019 and the consolidated balance sheet 
data as of December 31, 2021 and 2020 are derived from our audited consolidated financial statements included elsewhere 
in this annual report on Form 10-K.  

The consolidated statements of operations data for the fiscal years ended December 31, 2018, 2017 and 2016, 
and the balance sheet data as of December 31, 2019, 2018, 2017 and 2016 are derived from audited financial statements 
that are not included in this annual report on Form 10-K. 

The  selected  historical  consolidated  balance  sheet  and  operating  data  presented  below  should  be  read  in 
conjunction with the consolidated financial statements and the notes to such statements and “Management's Discussion 
and Analysis of Financial Condition and Results of Operations” included elsewhere in this annual report on Form 10-K. 
Historical results are not necessarily indicative of the results to be expected in the future.  

(in thousands, except per share data) 

2021 

Year ended December 31, 
2019 

2020 

2018 

2017 

Selected Statement of Operations Data: 
Total revenues . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    $
Total cost and expenses  . . . . . . . . . . . . . . . . . . . . .   
Interest expense and other (expense) income,  

net  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Income tax expense . . . . . . . . . . . . . . . . . . . . . . . . .   
Loss on debt extinguishment  . . . . . . . . . . . . . . . . .   
Net loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Net loss per share, basic . . . . . . . . . . . . . . . . . . . . .    $
Net loss per share, diluted . . . . . . . . . . . . . . . . . . . .    $

625,486    $ 391,005    $ 302,328   $  257,654    $  209,625
 344,966
418,615  

607,282   

372,282   

1,093,660   

(2,924) 

(7,520) 

(6,541)

(13,205) 

 (1,833)

(618) 
—  

(98) 
 (5,848) 

 (454)
 —
$ (471,716) $ (229,743) $ (124,827)  $  (128,154) $ (137,628)
(2.58)
(2.59)

(1.79) $ 
(1.79) $ 

(2.84)  $
(2.84)  $

(5.21)  $
(5.21)  $

2.22    $
2.22    $

(1,999)
—  

(321) 
—   

(in thousands) 

2021 

2020 

As of December 31, 
2019 

2018 

2017 

Selected Balance Sheet Data: 
Cash, cash equivalents and restricted cash  . . . . . .
Short-term investments . . . . . . . . . . . . . . . . . . . . . .
Inventory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Property and equipment, net . . . . . . . . . . . . . . . . . .
Total assets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Debt  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total stockholders' equity . . . . . . . . . . . . . . . . . . . .

$

84,614
829,896 
26,909
65,516 
1,236,487
330,446 
583,183
653,304 

$

48,855
688,606 
20,031
33,348 
932,153
252,547 
445,917
486,236 

$

61,981    $ 

379,065  
12,394 
23,283  
582,656 
123,779  
303,945 
278,711  

 51,004  $
107,461 
 13,633 
24,336 
 268,171 
123,510 
 236,009 
32,162 

13,021
106,247 
8,998
29,667 
214,613
123,177 
189,196
25,417 

74 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
    
    
    
 
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
    
    
    
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
ITEM 7.  MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS 

OF OPERATIONS  

You should read the following discussion and analysis of our financial condition and results of operations in conjunction 
with our consolidated financial statements and related notes included in Part II, Item 8 of this report. This discussion 
contains forward-looking statements that involve risks and uncertainties. Our actual results could differ materially from 
those discussed below. Factors that could cause or contribute to such differences include, but are not limited to, those 
identified below and those discussed in “Risk Factors” included elsewhere in this report. 

Overview 

We  are  a  diagnostics  company  with  proprietary  molecular  and  bioinformatics  technology  that  we  deploy  to 
change  the  management  of  disease  worldwide.  We  began  in  the  women’s  health  space,  in  which  we  develop  and 
commercialize non- or minimally- invasive tests to evaluate risk for, and thereby enable early detection of, a wide range 
of genetic conditions, such as Down syndrome. Our technology is now also being proven in the oncology market, in which 
we are commercializing, among others, a personalized blood-based DNA test to detect molecular residual disease and 
monitor disease recurrence, as well as in the organ health market, with tests to assess organ transplant rejection. We seek 
to  enable  even  wider  adoption  of  our  technology  through Constellation,  our  global  cloud-based distribution  model. In 
addition to our direct sales force in the United States, we have a global network of over 100 laboratory and distribution 
partners, including many of the largest international laboratories. 

We currently provide a comprehensive suite of products in women’s health, as well as our oncology and organ 
health products, and our Constellation cloud-based platform. We generate a majority of our revenues from the sale of 
Panorama, our non-invasive prenatal test (“NIPT”), as well as Horizon, our Carrier Screening (“HCS”) test. In addition to 
Panorama and Horizon, our product offerings in women’s health include Spectrum Preimplantation Genetics, our Anora 
miscarriage test, and Vistara single-gene NIPT, as well as our Empower hereditary cancer screening test, which we also 
plan to offer to oncologists through our oncology sales channel. We also offer our Signatera molecular residual disease 
test for oncology applications, which we commercialize as a test run in our CLIA laboratory and offer on a research use 
only (“RUO”) basis to research laboratories and pharmaceutical companies; and our Prospera organ transplant assessment 
tests. 

We process tests in our laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 
(“CLIA”) in Austin, Texas and San Carlos, California. A portion of our testing is performed by third-party laboratories. 
Our  customers  include  independent  laboratories,  national  and  regional  reference  laboratories,  medical  centers  and 
physician practices for our screening tests, and research laboratories and pharmaceutical companies. We market and sell 
our tests through our direct sales force and, for our women’s health tests, through our laboratory distribution partners. We 
bill  clinics,  laboratory  distribution  partners,  patients,  pharmaceutical  companies  and  insurance  payers  for  the  tests  we 
perform. In cases where we bill laboratory distribution partners, our partners in turn bill clinics, patients and insurers. The 
majority of our revenue comes from insurers with whom we have in-network contracts. Such insurers reimburse us for our 
tests pursuant to our in-network contracts with them, based on positive coverage determinations, which means that the 
insurer has determined that the test in general is medically necessary for this category of patient.  

In  addition  to  offering  tests  to  be  performed  at  our  laboratories,  either  directly  or  through  our  laboratory 
distribution  partners,  we  also  establish  licensing  arrangements  with  laboratories  under  Constellation,  our  cloud-based 
distribution  model,  whereby  our  laboratory  licensees  run  the  molecular  workflows  themselves  and  then  access  our 
bioinformatics algorithms through our cloud-based software. This cloud-based distribution model results in lower revenues 
and gross profit per test than cases in which we process a test ourselves; however, because we do not incur the costs of 
processing the tests, our costs per test under this model are also lower. We began entering into these licensing arrangements 
starting in the fourth quarter of 2015. 

The principal focus of our commercial operations is to offer our tests through both our direct sales force and 
laboratory distribution partners, and our Constellation licensees under our cloud-based distribution model. The number of 
tests that we accession is a key indicator that we use to assess our business. A test is accessioned when we receive the test 
at our laboratory, the relevant information about the test is entered into our computer system, and the test sample is routed 

75 

 
 
 
 
 
 
 
into  the  appropriate  workflow.  This  number  is  a  subset  of  the  number  of  tests  that  we  process,  which  includes  tests 
distributed through our Constellation licensees. The number of tests that we process is a key metric as it tracks overall 
volume growth, particularly as our laboratory partners may transition from sending samples to our laboratory to our cloud-
based distribution model, as a result of which our tests accessioned would decrease but our tests processed would remain 
unchanged.  

During  the  year  ended  December  31,  2021,  we  processed  approximately  1,570,000  tests,  comprised  of 
approximately 1,513,400 tests accessioned in our laboratories, compared to December 31, 2020, in which we processed 
approximately  1,026,500  tests,  comprised  of  approximately  974,400  tests  accessioned  in  our  laboratories,  and 
approximately 804,300 tests processed during the year ended December 31, 2019, comprised of approximately 753,800 
tests accessioned in our laboratories. This increase in volume represents continuous commercial growth of Panorama and 
HCS, both as tests performed in our laboratories as well as through our Constellation software platform. 

The percent of our revenues attributable to our U.S. direct sales force were 89%, 87% and 80% for the years 
ended December 31, 2021, 2020, 2019, respectively. The percent of our revenues attributable to U.S. laboratory partners 
for the year ended December 31, 2021 was 5%, which was down from 7% and 6%, when compared to the years ended 
December  31,  2020  and  2019.  The  percent  of  our  revenues  attributable  to  international  laboratory  partners  and  other 
international sales for the years ended December 31, 2021 was 6%, consistent with 6% and down from 14% for the years 
ended December 31, 2020 and December 31, 2019, respectively. 

For  the year  ended December  31,  2021,  total  revenues were $625.5  million,  compared  to $391.0  million  and 
$302.3 million in the years ended December 31, 2020 and 2019, respectively. Product revenues generated from our testing 
accounted for $567.1 million or 91% of total revenues for the year ended December 31, 2021, compared to $367.2 million 
or 94% of total revenues for the year ended December 31, 2020 and $269.9 million or 89% of total revenues for the year 
ended December 31, 2019. For the years ended December 31, 2021, 2020, and 2019, there were no customers exceeding 
10% of the total revenues on an individual basis. Revenues from customers outside the United States were $34.6 million, 
representing 6% of total revenues for the year ended December 31, 2021. For the years ended December 31, 2020 and 
2019, revenues from customers outside the United States were $25.3 million and $41.5 million, representing approximately 
6% and 14%, respectively, of total revenues. 

Our net losses for the years ended December 31, 2021, 2020, and 2019, were $471.7 million, $229.7 million, and 
$124.8 million, respectively. This included non-cash stock compensation expense of $115.2 million, $50.2 million, and 
$28.6 million for the years ended December 31, 2021, 2020, and 2019, respectively. As of December 31, 2021, we had an 
accumulated deficit of $1.4 billion. 

COVID-19 Impact 

The  COVID-19  pandemic  has  continued  to  present  a  global  public  health  and  economic  challenge  that  has 
affected our business operations and the U.S. and other major economies and financial markets. We have modified our 
business practices  in response  to  the  spread  of COVID-19  (including  temporary  closures of our  offices,  implementing 
remote work policies and practices, vaccination requirements, travel restrictions, and other measures as we have deemed 
necessary or appropriate from time to time), and incur additional operating costs, and we may take further actions from 
time to time as may be required by government authorities or that we determine are in the best interests of our employees, 
customers and business partners. Such actions could also impact our ability to fully integrate businesses we may acquire 
in the future. There is no certainty that such actions will be sufficient to mitigate the continuing risks posed by the virus 
or  otherwise  be  satisfactory  to  government  authorities.  If  significant  portions  of  our  workforce,  and  particularly  our 
laboratory  staff,  are  unable  to  work  effectively,  including  due  to  illness,  quarantines,  social  distancing,  recruiting  and 
retention difficulties, government actions, including the prospect of rising interest rates, inflationary pressure, and stock 
market volatility, or other restrictions in connection with the COVID-19 pandemic, our operations and financial results 
will be impacted. 

The extent to which the COVID-19 pandemic will continue to impact our business, results of operations and 
financial  condition  will  depend  on  future  developments,  which  continue  to  remain  highly  uncertain  and  cannot  be 
predicted, including, but not limited to, the continued duration and spread of the pandemic, including the contagiousness 

76 

  
 
 
 
 
 
of variants and their severity, the actions to contain the virus or address its impact, and whether, when and to what extent 
pre-pandemic economic and operating activities can resume. The COVID-19 pandemic could continue to limit the ability 
of our customers, suppliers and business partners to perform under their contracts with us, including third-party payers’ 
ability to make timely payments to us during and following the pandemic. We may also experience a shortage of laboratory 
supplies and reagents or a suspension of services from other laboratories or third parties. We also increased our dependence 
on growing and maintaining a network of mobile phlebotomy specialists who can provide testing capabilities, as many 
consumers are unable to visit clinics, hospitals or other testing facilities as a result of the COVID-19 pandemic. Even after 
the COVID-19 pandemic has subsided, we may continue to experience an adverse impact to our business because of its 
global economic impact, including as a result of inflation and any recession that has occurred or may occur in the future. 

Specifically, difficult macroeconomic conditions as a result of COVID-19, such as decreases in per capita income 
and level of disposable income, increased and prolonged unemployment, a decline in consumer confidence, as well as 
limited or significantly reduced points of access of our products, could have a material adverse effect on the demand for 
some of our products, such as our products targeted for the IVF market. Decreased demand for our tests, particularly in 
the  United  States,  could  negatively  affect  our  overall  financial  performance.  A  significant  portion  of  our  revenue  is 
concentrated  in  the  United  States,  where  the  impact  of  COVID-19  has  been  significant,  and  the  potential  decrease  in 
demand for our tests could have a disproportionately negative impact on our business and financial results. 

In  particular,  while  our  test  volumes  in  2021  have  increased  compared  to  the  previous  year,  and  the  average 
selling price of our tests collected from insurance payors in the year ended December 31, 2021 increased compared to the 
year ended December 31, 2020, we cannot predict volatility of the volumes and selling prices of our tests that may result 
from the continued impact of the COVID-19 pandemic, and either or both of these metrics may fluctuate from period to 
period. Further, we cannot predict the potential nature, magnitude and duration of the effects of the COVID-19 pandemic 
on our business. 

In response to the COVID-19 pandemic, we have implemented measures to protect the health of our employees 
and to support the functionality of our laboratories. We will continue to support and incur expenditures towards COVID-
19 prevention and employee safety. 

Since the World Health Organization ("WHO") declared the global outbreak of COVID-19 to be a pandemic in 
March 2020, we have operated in an uncertain and disruptive pandemic environment but to date we have successfully 
maintained  our  operational  effectiveness,  including  the  operation  of  financial  reporting  systems,  internal  control  over 
financial  reporting  and  disclosure  controls  and  procedures.  We  continue  to  closely  monitor  the  recent  developments 
surrounding  this  pandemic  and  resurgences  including,  among  other  developments,  local,  state,  national  and  global 
vaccination efforts and the potential impacts of variants. 

Components of the Results of Operations 

The section of this Management’s Discussion and Analysis generally discusses year-to-year comparisons between 
2021 and 2020. Discussions of year-to-year comparisons between 2020 and 2019 that are not included in this Annual 
Report on Form 10-K can be found in “Management’s Discussion and Analysis of Financial Condition and Results of 
Operations” in Item 7 of Part II of our Annual Report on Form 10-K for the fiscal year ended December 31, 2020, filed 
with the SEC on February 26, 2021. 

Revenues 

Product Revenues 

We generate revenues from the sale of our tests, primarily from the sale of our Panorama and HCS tests. Our two 
primary distribution channels are our direct sales force and our laboratory partners. In cases where we promote our tests 
through our direct sales force, we generally bill directly to a patient, clinic or insurance carrier, or a combination of the 
insurance carrier and patient, for the fees. Sales of our clinical tests are recorded as product revenues.  

77 

 
 
 
 
 
 
 
In cases where we sell our tests through our laboratory partners, the majority of our laboratory partners bill the 
patient, clinic or insurance carrier for the performance of our tests, and we are entitled to either a fixed price per test or a 
percentage of their collections.  

Our ability to increase our revenues will depend on our ability to further penetrate the domestic and international 
markets and, in particular, generate sales through our direct sales force, develop and commercialize additional tests, obtain 
reimbursement from additional third-party payers and increase our reimbursement rate for tests performed. In particular, 
our financial performance depends on reimbursement for Panorama in the average risk population and for microdeletions. 
There has been a significant increase in the number of commercial third-party payers that cover the use of Panorama in 
the average risk population, representing approximately 95% of commercial covered lives in the United States, as well as 
an increasing number of state Medicaid payers expanding coverage to average risk pregnancies. Many third-party payers 
do not currently reimburse for microdeletions screening in part because there is currently limited published data on the 
performance of microdeletions screening tests. A new current procedure terminology (“CPT”) code for microdeletions 
went  into  effect  beginning  January  1,  2017.  We  have  experienced  low  average  reimbursement  rates  thus  far  for 
microdeletions testing under this new code, and we expect that this new code will cause, at least in the near term, our 
microdeletions  reimbursement  to  remain  low,  due  to  third-party  payers  declining  to  reimburse  and  through  reduced 
reimbursement  under  the  new  code.  This  has  had,  and  we  expect  it  will  continue  to  have,  an  adverse  impact  on  our 
revenues. In addition, a new CPT code for expanded carrier screening went into effect beginning January 1, 2019, and has 
had, and may continue to have, an adverse effect on our reimbursement rates for our broader Horizon carrier screening 
panel for which we previously primarily received reimbursement on a per-condition basis, as those tests may be reimbursed 
as a combined single panel instead of as multiple individual tests. Because our revenues from Horizon continue to represent 
an increasing proportion of our overall revenues, a decline in our reimbursement rates for, and therefore our average selling 
price of, Horizon, could result in a decline in our overall revenue. 

Our financial performance has also been impacted by the increase in in-network coverage of our tests by third-
party payers, which we believe is crucial to our growth and long-term success. However, because the negotiated fees under 
our contracts with third-party payers are typically lower than the list price of our tests, as we enter into additional in-
network  contracts  with  insurance  providers,  our  average  reimbursement  per  test  may  decrease  as  compared  to  out-of-
network contracts. While we expect the reduction in average reimbursement per test from in-network pricing to reduce 
our revenues and gross margins in the near term, in-network pricing is more predictable than out-of-network pricing, and 
we intend to continue to mitigate the impact by driving more business from our most profitable accounts. 

Licensing and Other Revenues 

Revenues recognized from tests processed through our Constellation model, from our Qiagen, BGI Genomics, 
and  Foundation  Medicine  agreements  (collectively  the  “Strategic  Partnership  Agreements”),  and  from  our  Signatera 
research  use  only  and  companion  diagnostics  (“CDx”)  offering  are  reported  in  licensing  and  other  revenues.  We  also 
recognize licensing revenues through the licensing and the provisioning of services to support the use of our proprietary 
technology by licensees under our cloud-based distribution model. As of December 31, 2021, we are recognizing revenues 
on 15 licensing and service arrangements with laboratories under our Constellation model. 

Our strategy to offer our algorithm to laboratory licensees via our Constellation cloud-based software platform 
may also cause our revenues to decrease because we do not process the tests and perform the molecular biology analysis 
in our own laboratory under this model, and therefore are not able to charge as high an amount, and as a result realize 
lower revenues per test than when we perform the entire test ourselves. However, cost of licensing and other revenues for 
the Constellation software platform are relatively low, and therefore, its associated gross margin is higher. 

78 

 
 
 
 
 
 
Cost of Product Revenues  

The components of our cost of product revenues are material and service costs, impairment charges associated 
with  testing  equipment,  personnel  costs,  including  stock-based  compensation  expense,  equipment  and  infrastructure 
expenses  associated  with  testing  samples,  electronic  medical  records,  order  and  delivery  systems,  shipping  charges  to 
transport samples, costs incurred from third party test processing fees, and allocated overhead such as rent, information 
technology costs, equipment depreciation and utilities. Costs associated with Whole Exome Sequencing (“WES”) are also 
included,  as  well  as  labor  costs,  relating  to  our  Signatera  CLIA  offering.  Costs  associated  with  performing  tests  are 
recorded when the test is accessioned. We expect cost of product revenues in absolute dollars to increase as the number of 
tests we perform increases. 

As we continue to achieve scale, we have increased our focus on more efficient use of labor, automation, and 
DNA sequencing. For example, we updated the molecular and bioinformatics process for Panorama to further reduce the 
sequencing reagents, test steps and associated labor costs required to obtain a test result, while increasing the accuracy of 
the test to allow it to run with lower fetal fraction input. These improvements also reduced the frequency of the need to 
require blood redraws from the patient. 

Cost of Licensing and Other Revenues 

The components of our cost of licensing and other revenues are material costs associated with test kits sold to 
Constellation  clients,  development  and  support  services  relating  to  our  Strategic  Partnership  Agreements,  and  costs 
associated with specimens and Whole Exome Sequencing (“WES”), as well as labor costs, relating to our Signatera (RUO) 
and CDx offering. 

We  currently  have  15  revenue  generating  licensing  and  service  agreements  with  laboratories  under  our 
Constellation  distribution  model.  We  consider  our  cost  of  licensing  and  other  revenues  for  the  Constellation  software 
platform to be relatively low, and therefore we expect its associated gross margin is higher. We expect our cost of licensing 
will increase in relation to volume growth. 

Research and Development  

Research and development expenses include costs incurred to develop our technology, collect clinical samples 
and conduct clinical studies to develop and support our products. These costs consist of personnel costs, including stock-
based  compensation  expense;  prototype  materials;  laboratory  supplies;  consulting  costs;  regulatory  costs;  electronic 
medical  record  set  up  costs;  and  costs  associated  with  setting  up  and  conducting  clinical  studies  at  domestic  and 
international sites and allocated overhead, including rent, information technology, equipment depreciation and utilities. 
We expense all research and development costs in the periods in which they are incurred. We expect our research and 
development  expenses  to  increase  in  absolute  dollars  as  we  continue  to  invest  in  research  and  development  activities 
related to developing enhanced and new products.  

Selling, General and Administrative  

Selling,  general  and  administrative  expenses  include  executive,  selling  and  marketing,  legal,  finance  and 
accounting, human resources, billing and client services. These expenses consist of personnel costs, including stock-based 
compensation  expense;  direct  marketing  expenses;  audit  and  legal  expenses;  consulting  costs;  training  and  medical 
education activities; payer outreach programs and allocated overhead, including rent, information technology, equipment 
depreciation, and utilities.  

79 

 
 
 
 
 
 
 
 
Gain on Disposal of Business 

In September 2019, we sold our Evercord business that provided cord tissue processing and storage services for 
total estimated consideration of $15.4 million, including $9.7 million in cash, $1.0 million of cash deposited in a third-
party escrow account recorded in short-term other receivables, and $4.7 million of additional consideration. We recognized 
a gain of $14.4 million on the sale, which was included in loss from operations in the consolidated statements of operations 
and comprehensive loss. 

Interest Expense  

Interest  expense  is  attributable  to  borrowing  under  our  Credit  Line,  the  2017  Term  Loan,  as  well  as  the 

Convertible Note, including the amortization of debt discounts.  

Interest Income and Other (Expense) Income, Net  

Interest income and other (expense) income, net is comprised of interest earned on our cash, realized gains and 
losses on investments, foreign currency remeasurement gains and losses, changes in the fair value of our warrants, and 
finance charges related to the unused borrowing capacity of our 2017 Term Loan.  

Loss on Debt Extinguishment 

The loss on debt extinguishment of $5.8 million was a result of the repayment of the outstanding principal and 

interest under the 2017 Term Loan with Orbimed in the second quarter of 2020. Refer to note 10, Debt, for details. 

Critical Accounting Policies 

Our management’s discussion and analysis of our financial condition and results of operations is based on our 
financial statements, which have been prepared in accordance with generally accepted accounting principles in the United 
States. The preparation of these financial statements requires us to make estimates and assumptions that affect the reported 
amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, 
as well as the reported revenue generated, and expenses incurred during the reporting periods. Our estimates are based on 
our historical experience and on various other factors that we believe are reasonable under the circumstances, the results 
of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent 
from other sources. Actual results may differ from these estimates under different assumptions or conditions. We consider 
our critical accounting policies and estimates to be revenue recognition, leases, inventory, fair value measurements, and 
stock-based compensation. Refer to note 2, Summary of Accounting Policies, for details. 

Recent Accounting Pronouncements 

We have adopted ASU 2020-06, Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives 
and  Hedging—Contracts  in  Entity’s  Own  Equity  (Subtopic  815-40)  which  simplifies  the  accounting  for  convertible 
instruments. See Note 2, Summary of Significant Accounting Policies, for recently adopted accounting pronouncements. 

Revenue Recognition 

We recognize revenues when, or as, performance obligations in the contracts are satisfied, in the amount reflecting 

the expected consideration to be received from the goods or services transferred to the customers. 

Product Revenues 

Product  revenues  are  derived  from  contracts  with  insurance  carriers,  laboratory  partners  and  patients  in 
connection  with  sales  of  prenatal  genetic  and  other  diagnostics  tests.  The  majority  of  our  revenues  are  derived  from 
Panorama NIPT, HCS, and to a lesser extent, other genetic tests including Signatera CLIA and Prospera. We enter into 

80 

 
 
 
 
 
contracts with insurance carriers with primarily payment terms related to tests provided to the patients who have health 
insurance coverage. Insurance carriers are considered to be third-party payers on behalf of the patients, and the patients 
are considered as the customers who receive genetic test services. Tests may be billed to insurance carriers, patients, or a 
combination of insurance carriers and patients. Further, we sell tests to a number of domestic and international laboratory 
partners and identify the laboratory partners as customers provided that there is a test services agreement between us and 
them. 

Licensing and Other Revenues 

We recognize licensing revenues from our Constellation cloud-based distribution model, pursuant to which we 
grant  licenses  to  laboratories  to  access  our  proprietary  bioinformatics  algorithms  through  our  cloud-based  software  to 
analyze the results of molecular workflows that such licensees develop and perform in their laboratories. In addition, the 
royalties we receive from our arrangement with a prenatal paternity licensee are recognized Constellation revenues. 

We  also  recognize  revenues  from  our  Signatera  (RUO)  offering,  which  is  for  research  use  only  to  cancer 
researchers and biopharmaceutical companies as well as our CDx offering. We enter into agreements with pharmaceutical 
companies to utilize our Signatera tests typically to study new cancer treatments or to validate the outcomes of clinical 
trials for which the pharmaceutical companies are identified as customers. 

We also recognize revenues from our Strategic Partnership Agreements. The performance obligations are unique 
in each agreement and would typically require the license of intellectual property, development services, support services, 
and future test work. We also record revenues from the sale of IVD kits in licensing and other revenues. 

Income Taxes  

We  account  for  income  taxes  in  accordance  with  ASC  740, Income  Taxes (“ASC 740”),  which  requires 
recognition of deferred tax assets and liabilities for the expected tax consequences of our future financial and operating 
activities. Under ASC 740, we determine deferred tax assets and liabilities based on the temporary difference between the 
financial statement and tax bases of assets and liabilities using the tax rates in effect for the year in which we expect such 
differences to reverse.  If we determine that it is more likely than not that we will not generate sufficient taxable income 
to realize the value of some or all of our deferred tax assets (net of our deferred tax liabilities), we establish a valuation 
allowance offsetting the amount we do not expect to realize.  We perform this analysis each reporting period and reduce 
our measurement of deferred taxes, if the likelihood we will realize them becomes uncertain.   

We also account for uncertain tax positions in accordance with ASC 740, which requires us to adjust our financial 
statements to reflect only those tax positions that are more-likely-than-not to be sustained upon review by federal or state 
examiners.  We  may  recognize  a  tax  benefit  only  if  it  is  more  likely  than  not  the  tax  position  will  be  sustained  on 
examination by the taxing authorities, based on the technical merits of the position. The tax benefits recognized in the 
financial  statements  from  such  positions  are  then  measured  based  on  the  largest  benefit  that  has  a  greater  than  50% 
likelihood of being realized upon settlement. We maintained a full valuation allowance against our net deferred tax assets 
in 2021 and 2020 due to the uncertainty surrounding realization of these assets (for details, please refer to Note 13, Income 
Taxes).  In  addition,  our  policy  is  to  report  interest  and  penalties  related  to  unrecognized  tax  benefits  as  income  tax 
expenses.  

81 

 
 
 
 
 
 
  
Stock-Based Compensation 

We have included stock-based compensation as part of our cost of revenues and our operating expenses in our 

statements of operations as follows: 

2021 

Year ended December 31,  
2020 

2019 

   Employee      Non-Employee      Total        Employee    Non-Employee     Total       Employee    Non-Employee     Total 

(in thousands)

Cost of  

revenues  . . . . .     $

 4,811    $ 

 —    $

4,811

$

1,691

$

— $ 1,691

$

 905    $ 

Research and 

development  . .    

 24,507   

 1,361   

 25,868

10,777

647

11,424

5,354   

32

—

$

937

5,354

Selling, general 

and 
administrative  .    

 84,368   

Total . . . . . . . . . .     $ 113,686    $ 

 172   

 84,540
 1,533    $ 115,219

36,747
$ 49,215

$

309
956

37,056
$ 50,171

21,730   
$ 27,989    $ 

603
635

22,333
$ 28,624

Stock-based compensation related to stock options granted to our employees and non-employees is measured at 
the grant date based on the fair value of the award, which is determined by the Black-Scholes option-pricing model and 
the Monte Carlo simulation model. The fair value is recognized as expense over the requisite service period, which is 
generally the vesting period of the respective awards. No compensation cost is recognized on stock options for employees 
and  non-employees  who  do  not  render  the  requisite  service  and  therefore  forfeit  their  rights  to  the  stock  options.  The 
measurement of stock-based compensation is subject to periodic adjustments as the underlying equity instruments vest, 
and the resulting change in value, if any, is recognized in our statements of operations and comprehensive loss during the 
period that the related services are rendered. 

Impairment of Long-Lived Assets 

We evaluate our long-lived assets for indicators of possible impairment when events or changes in circumstances 
indicate the carrying amount of an asset may not be recoverable. We then compare the carrying amounts of the assets with 
the future net undiscounted cash flows expected to be generated by such asset. Should an impairment exist, the impairment 
loss  would  be  measured  based  on  the  excess  carrying  value  of  the  asset  over  the  asset’s  fair  value  determined  using 
discounted estimates of future cash flows. There were no asset impairment charges for the years ended December 31, 2021 
and 2020.  

For the year ended December 31, 2019, an asset impairment charge of $1.7 million was recorded in general and 
administrative expenses in the statements of operations and comprehensive loss. This charge is comprised of $1.2 million 
from the impairment of leasehold improvements, $0.1 million from the impairment of capitalized software held for internal 
use, and $0.4 million from the right-of-use asset related to the disposal of business. The right-of-use asset and the leasehold 
improvements relate to the storage facility located in Tukwila, Washington, and both assets were evaluated for impairment 
as  a  single  asset  group.  Subsequent  to  the  sale  of  Evercord,  we  recognized  an  impairment  charge  for  the  leasehold 
improvements that was previously capitalized for the storage facility and wrote down the right-of-use asset to its fair value 
as of the sale date. 

82 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
 
  
  
  
 
 
 
 
 
 
revenues . . . . . . . . . . . . .   
Total revenues . . . . . . . . . . . .   
Cost and expenses: 

Cost of product revenues .   
Cost of licensing and 

Results of Operations  

Comparison of the years ended December 31, 2021, 2020, and 2019 

(in thousands) 

Year Ended December 31, 
2020 

2021 

2019 

Changes 

2021 - 2020 

2020 - 2019 

Amount 

Percent 

  Amount 

Percent 

Revenues: 

Product revenues  . . . . . . .  $  567,149    $ 367,211
Licensing and other 

$ 269,881

$ 199,938

54.4  %   $  97,330

36.1 %

 58,337   
 625,486   

23,794
  391,005

32,447
302,328

34,543
234,481

145.2 
60.0 

 (8,653)
 88,677

(26.7)
29.3

 302,663   

  185,865

162,604

116,798

62.8 

 23,261

other revenues . . . . . . . .   

 15,755   

17,755

12,866

(2,000)

(11.3)

 4,889

Research and  

development . . . . . . . . . .   

 264,208   

  100,035

51,357

164,173

164.1 

 48,678

Selling, general and 

administrative  . . . . . . . .   

 511,034   

  303,627

206,176

207,407

68.3 

 97,451

Gain on disposal of 

business  . . . . . . . . . . . . .   
Total cost and  

 —   

—

(14,388)

—

* 

 14,388

expenses  . . . . . . . . . .     1,093,660   
 (468,174) 
 (8,305) 

Loss from operations  . . . . .   
Interest expense . . . . . . . . . . .   
Interest and other income,  

607,282
  (216,277)
(15,082)

418,615
(116,287)
(10,693)

486,378
80.1 
(251,897) 116.5 
(44.9)

6,777

 188,667
 (99,990)
 (4,389)

net  . . . . . . . . . . . . . . . . . . . .   

 5,381   

7,562

4,152

(2,181)

(28.8)

 3,410

Loss on debt  

extinguishment . . . . . . . . . .   
(5,848)
 (5,848)
Loss before income taxes . . .   
  (229,645)
      (106,817)
 1,901
(98)
Income tax expense . . . . . . . .   
Net loss  . . . . . . . . . . . . . . . . .  $  (471,716)  $ (229,743) $ (124,827) $ (241,973) 105.3  %   $ (104,916)

5,848 (100.0)
(241,453) 105.1 
(520) 530.6 

 —   
 (471,098) 
 (618) 

—
(122,828)
(1,999)

14.3

38.0

94.8

47.3

*

45.1
86.0
41.0

82.1

100.0
87.0
(95.1)
84.0 %

* Not meaningful 

Revenues 

Total revenues are comprised of product revenues, which are primarily driven by sales of our Panorama and HCS 
tests,  and  licensing  and  other  revenues,  which  primarily  includes  development  licensing  revenue,  licensing  of  our 
Constellation  software  to  our  licensees,  and  revenues  from  our  Signatera  (RUO)  and  CDx  offering.  Total  revenues 
increased by $234.5 million, or 60.0%, when compared to the year ended December 31, 2020. 

We derive our revenues from tests based on units reported to customers—tests delivered with a result. All reported 
units  are  either  accessioned  in  our  laboratories  or  processed  outside  of  our  laboratories.  As  noted  in  “Overview,”  the 
number of tests that we process is a key metric as it tracks overall volume growth. During the year ended December 31, 
2021,  total  reported  units  were  approximately  1,453,500,  comprised  of  approximately  1,400,100  tests  reported  in  our 
laboratories. Comparatively, during the year ended December 31, 2020, total reported units were approximately 962,400, 
comprised of approximately 912,500 tests reported in our laboratories. 

Product Revenues 

During the year ended December 31, 2021, product revenues increased by $199.9 million, or 54.4% compared to 

the year ended December 31, 2020, as a result of the continued revenue growth from increased test volumes. 

83 

 
 
 
 
 
 
 
 
 
 
 
 
  
     
    
     
  
 
   
 
 
 
 
 
 
 
      
 
    
    
 
 
 
    
    
 
    
    
    
 
    
    
    
 
    
 
    
 
    
 
    
 
 
 
 
Licensing and Other Revenues 

Licensing and other revenues increased by $34.5 million, or 145.2%, during the year ended December 31, 2021 
compared to the year ended December 31, 2020. The increase in revenue was primarily due to an increase in revenues 
recognized from our collaborative agreements and Signatera CDx development revenues. 

Cost of Product Revenues 

During the year ended December 31, 2021, cost of product revenues increased by $116.8 million or 62.8% when 
compared to the year ended December 31, 2020, primarily due to higher costs related to inventory consumption of $19.0 
million driven by an increase in accessioned cases, a $47.0 million increase in third-party fees, a $8.5 million increase in 
shipping  related  charges  due  to  higher  volume,  and  a  $42.3  million  increase  in  labor  and  overhead  costs  driven  by 
headcount growth and product support. 

Cost of Licensing and Other Revenues 

Cost of licensing and other revenues for the year ended December 31, 2021, when compared to the year ended 
December 31, 2020, decreased by approximately $2.0 million, or 11.3%, primarily due a decrease of $2.2 million from 
third party service fees associated with volume discounts and a $0.7 million net decrease in labor and overhead related 
costs, offset by a $0.9 million increase in costs related to inventory consumption. 

Research and Development 

Research and development expenses during the year ended December 31, 2021 increased by $164.2 million, or 
164.1%, when compared to the year ended December 31, 2020. The increase was driven by a $60.3 million increase in 
salary and related expenditures primarily due to headcount growth, which includes a $14.4 million increase in stock-based 
compensation expense, an increase of $24.4 million of consulting costs, a $23.0 million increase of costs related to clinical 
studies  to  support  our  new  product  offerings  and  research  and  development  project  pipeline,  $35.6  million  in-process 
research and development related to the asset acquired in 2021, $6.3 million of expenses related to acquisition-related 
milestones, a $8.2 million increase related to software licenses to support the Company’s technology for use in research 
and development, and a $6.4 million increase in facilities and other costs to support increases in the Company’s headcount. 

Selling, General and Administrative 

Selling, general and administrative expenses increased by $207.4 million, or 68.3%, in the year ended December 
31, 2021 compared to the year ended December 31, 2020. The increase was attributable to an increase of $140.6 million 
in salary and related expenditures primarily due to headcount growth to support new product offerings, which includes a 
$47.5  million  increase  in  stock-based  compensation  expense,  a  $21.3  million  increase  in  marketing  expenses,  a  $11.9 
million  increase  in  travel  related  costs,  a  $6.7  million  increase  from  third  party  billing  services  fees,  a  $15.2  million 
increase in legal fees related to the Company’s ongoing legal matters, and a $11.7 million increase related to computer 
hardware and software licenses, and bank fees, office supplies and other costs to support new product offerings. 

Interest Expense  

Interest expense decreased by $6.8 million, 44.9%, in the year ended December 31, 2021 compared to the same 
period in the prior year. The interest expense from the Convertible Notes issued in April 2020, was lower in the current 
period due to the adoption of ASU 2020-06 where the majority of the non-cash interest expense was eliminated. In addition, 
the 2017 Term Loan with Orbimed was extinguished in April 2020. 

Interest and Other Income  

Interest and other income decreased by $2.2 million, or 28.8%, in the year ended December 31, 2021, compared 
to the same period in the prior year, primarily due to less interest income as a result of lower yields from our investments. 

84 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Loss on Debt Extinguishment 

The loss on debt extinguishment of $5.8 million was a result of the repayment of the outstanding principal and 

interest under the 2017 Term Loan with OrbiMed in April 2020. 

Liquidity and Capital Resources  

We have incurred net losses each year since our inception. For the year ended December 31, 2021, we had a net 
loss of $471.7 million, and we expect to continue to incur losses in future periods as we continue to devote a substantial 
portion of our resources to our research and development and commercialization efforts for our existing and new products. 
As of December 31, 2021, we had an accumulated deficit of $1.4 billion. We had $84.6 million in cash and cash equivalents 
and  restricted  cash,  $829.9  million  in  marketable  securities,  $50.1  million  of  outstanding  balance  of  the  Credit  Line 
including accrued interest, and $287.5 million outstanding principal balance on the Convertible Notes. We used a portion 
of the net proceeds from the offering of the Convertible Notes to repay our obligations under our 2017 Term Loan with 
OrbiMed. 

While we have introduced multiple products that are generating revenues, these revenues have not been sufficient 
to fund our operations and business plans. Accordingly, we have funded the portion of operating costs and business plans 
that exceeds revenues through a combination of equity issuances and debt and other financings. We expect to develop and 
commercialize  future  products  and,  consequently,  we  will  need  to  generate  additional  revenues  to  achieve  future 
profitability and may need to raise additional equity or incur additional debt. If we raise additional funds by issuing equity 
securities,  our  stockholders  would  experience  dilution.  Additional  debt  financing,  if  available,  may  involve  covenants 
restricting our operations or our ability to incur additional debt. Any additional debt financing or additional equity that we 
raise may contain terms that are not favorable to us or our stockholders and requires significant debt service payments, 
which diverts resources from other activities. Additional financing may not be available at all, or in amounts or on terms 
acceptable to us. If we are unable to obtain additional financing when necessary, we may be required to delay or slow our 
investment  in  the  development  and  commercialization  of  our  products  and  significantly  scale  back  our  business  and 
operations. 

In April 2019, we completed an underwritten equity offering and sold 6,052,631 shares of common stock at a 
price of $19 per share to the public. Before offering expenses of $0.6 million, we received proceeds of $108.1 million net 
of the underwriting discount. In October 2019, we completed another underwritten equity offering and sold 6,571,428 
shares of its common stock at a price of $35 per share to the public. Before offering expenses of $0.4 million, we received 
proceeds of $216.2 million net of the underwriting discount. In September 2020, we completed an additional underwritten 
equity offering and sold 4,791,665 shares of our common stock at a price of $60 per share to the public. Before offering 
expenses  of  $0.3  million,  we  received  proceeds  of  $271.0  million  net  of  the  underwriting  discount. In  July  2021,  we 
completed an underwritten equity offering and sold 5,175,000 shares of our common stock at a price of $113 per share to 
the  public.  Before  offering  expenses  of  $0.4 million,  we  received  proceeds  of  $551.2 million  net  of  the  underwriting 
discount. As cash flows from our operations are currently negative, our contractual obligations and other commitments are 
satisfied by both the equity financing described above and our product, licensing, and other sales. For our commitments, 
refer to the “Contractual Obligations and Other Commitments” section below. 

Refer to additional disclosures associated with risks and our ability to generate and obtain adequate amounts of 

cash to meet capital requirements for both short-term and long-term obligations. 

Based on our current business plan, we believe that our existing cash and marketable securities will be sufficient 

to meet our anticipated cash requirements for at least 12 months after February 24, 2022. 

Credit Line Agreement 

In September 2015, we entered into the Credit Line with UBS providing for a $50.0 million revolving line of 
credit which can be drawn in increments at any time. The Credit Line was amended in July 2017 and bears interest at 30-
day LIBOR plus 1.10%, and it is secured by a first priority lien and security interest in our money market and marketable 

85 

 
 
 
 
securities held in our managed investment account with UBS. UBS has the right to demand full or partial payment of the 
Credit Line obligations and terminate it, in its discretion and without cause, at any time. 

2017 Term Loan 

In August 2017, we entered into the 2017 Term Loan with OrbiMed, which has a maximum borrowing capacity 
of $100.0 million. On the closing date of August 8, 2017, we borrowed $75.0 million, with the remaining $25.0 million 
available  to  borrow  at  our  option  at  any  time  through  December  31,  2019.  Subsequently,  we  entered  into  several 
amendments and extended the expiration date until December 31, 2019 to draw the unused borrowing capacity of $50.0 
million. After the amendments, the interest rate was equal to the sum of (i) 8.25% plus (ii) the higher of 1.00% or LIBOR, 
provided we draws the minimum capacity of $25.0 million. If the amount drawn is less than $25.0 million, the interest rate 
would remain at the sum of (i) 8.75% plus (ii) the higher of 1.00% or LIBOR. As a fee in consideration of extending the 
commitment to provide this option to draw until December 31, 2019, we issued an additional 25,000 shares of our common 
stock to OrbiMed. We did not exercise such option, and the right to draw the unused borrowing capacity expired. In April 
2020, we used a portion of the net proceeds from the offering of the Convertible Notes to repay our obligations under the 
2017 Term Loan with OrbiMed. 

Convertible Notes 

In April 2020, we issued $287.5 million aggregate principal amount of Convertible Notes in a private placement 

offering to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended. 

The Convertible Notes are senior, unsecured obligations of the Company and bear interest at a rate of 2.25% per 
year, payable in cash semi-annually in arrears in May and November of each year, beginning in November 2020. The 
Convertible Notes mature in May 2027, unless earlier converted, repurchased or redeemed in accordance with their terms. 
Upon conversion, the Convertible Notes are convertible into cash, shares of our common stock or a combination of cash 
and shares of our common stock, at our election. 

We received net proceeds from the Convertible Notes of $278.3 million, after deducting the initial purchasers’ 
discounts and debt issuance costs. We used approximately $79.2 million of the net proceeds from the Convertible Notes 
offering to repay our obligations under the 2017 Term Loan with OrbiMed. 

Cash Flows 

The following table summarizes our cash flows for the periods indicated: 

Cash used in operating activities 
Cash used in investing activities  . . . . . . . . . . . . . . . . . .
Cash provided by financing activities . . . . . . . . . . . . . .
Net increase (decrease) in cash, cash equivalents 

2021 

Year Ended  
December 31,  
2020 
(in thousands) 
$ (335,236) $ (182,512)  $  (63,444)
   (266,353)
(331,461) 
 340,774
500,847   

(205,193)
576,188

2019 

and restricted cash . . . . . . . . . . . . . . . . . . . . . . . . . . . .

35,759

(13,126) 

 10,977

Cash, cash equivalents and restricted cash, 

beginning of period  . . . . . . . . . . . . . . . . . . . . . . . . . . .

48,855

61,981   

 51,004

Cash, cash equivalents and restricted cash, end  

of year . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$

84,614

$

48,855    $  61,981

86 

 
 
 
 
 
 
 
 
 
 
 
 
 
     
 
 
 
 
 
 
 
Cash Used in Operating Activities 

Cash used in operating activities during the year ended December 31, 2021 was $335.2 million. The net loss of 
$471.7 million includes $182.5 million in non-cash charges resulting from $11.3 million of depreciation and amortization, 
$35.6 million expense of in-process research and development, $10.9 million of non-cash lease expense, $115.2 million 
of stock-based compensation expense, $0.6 million of inventory reserve adjustments, $7.8 million premium amortization 
and discount accretion on investment securities, $1.2 million for amortization of debt discount and issuance cost, $0.1 
million  in other non-cash benefits, offset by $0.2 million of provision for credit losses. Operating assets had cash outflows 
of $64.3 million resulting from $43.4 million in increases in accounts receivable, $7.5 million in increases in inventory, 
and $10.5 million in increases in prepaid expenses and $2.9 million in increases of other current assets. Operating liabilities 
resulted  in  cash  inflows  of $18.2  million  resulting  from  a  $19.2  million  increase  in  accounts payable,  a $10.5  million 
increase in accrued compensation, a $32.7 million increase in other accrued liabilities, offset by a $44.2 million decrease 
in deferred revenue. 

Cash used in operating activities during the year ended December 31, 2020 was $182.5 million. The net loss of 
$229.7 million includes $86.4 million in non-cash charges resulting from $8.6 million of depreciation and amortization, 
$7.8  million  non-cash  lease  expense,  $50.2  million  of  stock-based  compensation  expense,  $5.7  million  premium 
amortization  and discount  accretion  on  investment  securities,  $1.3  million provision  for  credit  losses, $7.0  million  for 
accretion  of  the  convertible  note,  $5.8  million  loss  on  debt  extinguishment,  and  $0.1  million  of  amortization  of  debt 
discount. These non-cash charges were offset by $0.2 million of inventory reserve adjustments, $0.1 million of gain on 
investments, and $0.2 million of non-cash benefits. Operating assets had cash outflows of $56.8 million resulting from 
$25.8 million increases in accounts receivable, $7.5 million increases in inventory, and $23.4 million decreases in prepaid 
assets, and $0.1 million increases in other assets. Operating liabilities generated cash inflows of $17.6 million resulting 
from a $10.3 million increase in other accrued liabilities, a $14.3 million increase in accrued compensation offset by $0.1 
million decrease in accounts payable and $6.9 million decrease in deferred revenue. 

Cash Used in Investing Activities 

Cash  used  in  investing  activities  for  the  year  ended  December  31,  2021  totaled  $205.2  million,  which  was 
comprised of purchasing new investments of $876.1 million, $41.0 million in acquisitions of property and equipment, and 
$8.6 million in cash paid for the acquisition of an asset, offset by $187.6 million proceeds from sale of investments and 
$532.9 million from proceeds of investments maturities.  

Cash  used  in  investing  activities  for  the  year  ended  December  31,  2020  totaled  $331.5  million,  which  was 
comprised  of  purchasing  new  investments  of  $685.2  million  and  $19.6  million  in  acquisitions  of  property,  plant  and 
equipment, offset by $343.3 million from proceeds of investments maturities and $30.0 million proceeds from sale of 
investments. 

87 

 
 
 
 
 
 
Cash Provided by Financing Activities 

Cash provided by financing activities for the year ended December 31, 2021 totaled $576.2 million comprised of 
$11.8 million cash proceeds from the exercise of stock options, $13.6 million in issuance of common stock under the 
employee stock purchase plan, and $550.8 million net proceeds from our equity offering completed in the third quarter of 
2021. 

Cash provided by financing activities for the year ended December 31, 2020 totaled $500.8 million comprised of 
$23.5  million  cash  proceeds  from  the  exercise  of  stock  options,  $7.1  million  in  issuance  of  common  stock  under  the 
employee stock purchase plan, $278.3 million net proceeds from the issuance of the Convertible Notes, and $270.7 million 
in  net  proceeds  from  our  equity  offering  completed  in  the  third  quarter  of  2020.  This  was  offset  by  a  $78.8  million 
repayment of the 2017 Term Loan with OrbiMed. 

Contractual Obligations and Other Commitments  

We have entered into arrangements that contractually obligate us to make payments that will affect our liquidity 
and  cash  flows  in  future  periods.  Such  arrangements  include  those  related  to  our  lease  commitments,  Credit  Line, 
Convertible Notes, commercial supply agreements and other agreements. 

Operating leases 

Our lease commitments consist of $115.7 million of payments, which will be paid over the term of the lease, 
including the additional office spaces totaling $29.7 million (the “First Expansion Premises” and the “Second Expansion 
Premises”) from the lease amendment for the laboratory and office space in Austin, Texas.  The leases for the First and 
Second Premises have not commenced under Accounting Standards Codification (ASC) Topic 842, Leases (ASC 842), as 
of December 31, 2021. As a result, these leases are not reflected within the consolidated balance sheets. We expect these 
leases to commence in 2022 and expire in March 2033. For additional information on our leases and timing of future 
payments, please refer to Note 7, Leases. 

Credit Line 

The short-term debt obligations consist of the $49.0 million principal amount drawn from the UBS Credit Line 
and applicable interest. The Credit Line was amended in July 2017 and bears interest at 30-day LIBOR plus 1.10%, and it 
is secured by a first priority lien and security interest in our money market and marketable securities held in our managed 
investment account with UBS. UBS has the right to demand full or partial payment of the Credit Line obligations and 
terminate it, in its discretion and without cause, at any time. Please refer to Note 10, Debt, for further details. 

Convertible Notes 

The long-term debt obligations consist of the $287.5 million principal amount from a private placement offering 
to qualified institutional buyers and applicable interest. The Convertible Notes are senior, unsecured obligations of the 
Company and bear interest at a rate of 2.25% per year, payable in cash semi-annually in arrears in May and November of 
each year, beginning in November 2020. The Convertible Notes mature in May 2027, unless earlier converted, repurchased 
or redeemed in accordance with their terms. Upon conversion, the Convertible Notes are convertible into cash, shares of 
our common stock or a combination of cash and shares of our common stock, at our election. Please refer to Note 10, Debt, 
for further details. 

Inventory purchase and other contractual obligations 

88 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
We enter into contracts in the normal course of business with various third parties for clinical trials, preclinical 
research  studies,  testing,  manufacturing,  and  other  services  for  operational  purposes.  The  contractual  obligations  also 
include a $35.0 million potential earnout payment from our IPR&D asset acquisition. Payments due upon cancellation 
generally consist only of payments for services provided or expenses incurred, including non-cancellable obligations of 
our  service  providers,  up  to  the  date  of  cancellation.  These  payments  have  not  been  included  separately  within  these 
contractual and other obligations disclosures. Please refer to Note 8, Commitments and Contingencies, for further details. 

The following table summarizes our unconditional purchase and contractual commitments as of December 31, 

2021: 

Operating leases(1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Short-term debt obligations(2) . . . . . . . . . . . . . . . . . . . . . . .
Long-term debt obligations(3) . . . . . . . . . . . . . . . . . . . . . . .
Interest accrued on debt(4) . . . . . . . . . . . . . . . . . . . . . . . . . .
Inventory purchase and other contractual obligations(5) . .
Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total 

$ 115,674
49,000
287,500
2,130
108,292
$ 562,596

     Less Than      
1 Year 

Payments Due by Period 
1 to 3 
Years 
(in thousands) 

3 to 5 
Years 

     More Than  

5 Years 

$

9,980
49,000
—
2,130
87,400
$ 148,510

$ 27,441  $  30,981  $ 47,272
—
287,500
—
—
$ 47,793    $  31,521  $ 334,772

 —   
 —   
 —   
20,352   

 — 
 — 
 — 
 540 

(1)  Includes executed leases which have not commenced. Please refer to Note 7, Leases for additional information. 
(2)  Represents proceeds drawn from our Credit Line. 
(3)  Represents the principal amount of our Convertible Notes due 2027. 
(4)  Represents interest accrued on our Convertible Notes and Credit Line. 
(5)  Represents  various  inventory  purchase  and  other  contractual  obligations.  Please  refer  to  contractual  commitments 

disclosures provided in Note 8, Commitments and contingencies for additional information. 

Off-Balance Sheet Arrangements  

We do not have any off-balance sheet arrangements during the periods presented. 

ITEM 7A:  QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK  

Interest Rate Risk 

We are exposed to market risks in the ordinary course of our business. These risks primarily relate to interest 
rates. Our Credit Line has an interest rate of one-month LIBOR plus 1.10%. The LIBOR rate is variable. An incremental 
change in the borrowing rate of 100 basis points would increase our annual interest expense by $0.5 million based on our 
$50.1 million gross debt outstanding on our Credit Line, including principal and accrued interest as of December 31, 2021. 
The interest rate for our Convertible Notes is fixed at 2.25% and not exposed to market risk related to interest rates. Our 
investment portfolio is exposed to market risk from changes in interest rates. This risk is mitigated as we have maintained 
a relatively short average maturity for our investment portfolio. An incremental change in the investment yield of 100 
basis points would increase our annual interest income by approximately $8.3 million annually in relation to amounts we 
would expect to earn, based on our short-term investments as of December 31, 2021. 

For the fiscal year ending December 31, 2021, compared to the fiscal year ending December 31, 2020, our total 

comprehensive loss increased by approximately $9.9 million due to the increase average yield rate. 

Foreign Currency Exchange Rate Fluctuations 

Our operations are currently conducted primarily in the United States. As we expand internationally, our results 
of operations and cash flows may become subject to fluctuations due to changes in foreign currency exchange rates. In 

89 

 
 
 
 
 
 
 
 
 
 
    
 
     
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
periods when the U.S. dollar declines in value as compared to the foreign currencies in which we incur expenses, our 
foreign  currency-based  expenses  will  increase  when  translated  into  U.S.  dollars.  In  addition,  future fluctuations  in the 
value of the U.S. dollar may affect the price at which we sell our tests outside the United States. To date, our foreign 
currency risk has been minimal and we have not historically hedged our foreign currency risk; however, we may consider 
doing so in the future. 

ITEM 8. 

FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 

NATERA, INC. 

INDEX TO CONSOLIDATED FINANCIAL STATEMENTS 

Report of Independent Registered Public Accounting Firm (PCAOB ID 42) . . . . . . . . . . . . . . . . . . . . . . . . . .
Consolidated Balance Sheets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Consolidated Statements of Operations and Comprehensive Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Consolidated Statements of Stockholders’ Equity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Consolidated Statements of Cash Flows . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Notes to Consolidated Financial Statements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

     Page No.
91
93
94
95
96
97

90 

 
 
 
 
 
 
 
 
Report of Independent Registered Public Accounting Firm 

To the Board of Directors and Stockholders of Natera, Inc. 

Opinion on the Financial Statements 

We have audited the accompanying consolidated balance sheets of Natera, Inc. (the Company) as of December 31, 2021 
and 2020, and the related consolidated statements of operations and comprehensive loss, 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 U.S. generally accepted 
accounting principles. 

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  issued  by  the  Committee  of  Sponsoring  Organizations  of  the  Treadway 
Commission (2013 framework) and our report dated February 24, 2022 expressed an unqualified opinion thereon. 

Change in Accounting Principle 

As discussed in Note 2 to the consolidated financial statements, the Company has changed its method of accounting for 
convertible instruments as of January 1, 2021 due to the adoption of Accounting Standards Update 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): Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity (“ASU 2020-
06”). 

Basis for Opinion 

These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion 
on the Company’s financial statements based on our audits. We are a public accounting firm registered with the 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 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  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 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 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 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 financial statements and (2) involved our especially challenging, subjective or complex 
judgments.  The  communication  of  the  critical  audit  matter  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 a 
separate opinion on the critical audit matter or on the account or disclosure to which it relates. 

91 

  
  
 
 
 
 
  
  
 
 
  Genetic Test Revenue  

Description of the 
Matter 

  For  the  year  ended  December  31,  2021,  the  Company’s  revenue  from  sales  of  genetic  tests  was 
$567.1  million.  As  explained  in  Note  3  of  the  consolidated  financial  statements,  revenue  from 
genetic tests is recognized upon delivery of the test results. The revenue recognized for the genetic 
tests is based on an estimate of the total consideration expected to be received for the genetic tests. 
In particular, the estimate of total consideration is affected by assumptions of reimbursement from 
patients  and  insurance  carriers,  including  estimates  for  disallowed  cases,  discounts,  refunds  and 
doubtful accounts. 

Auditing the measurement of the Company’s genetic test revenue was complex due to the required 
analysis of extensive data to determine the total consideration to be received by the Company for 
delivered tests and the amounts involved are material to the financial statements taken as a whole. 

How We 
Addressed the 
Matter in Our 
Audit 

  We  obtained  an  understanding,  evaluated  the  design,  and  tested  the  operating  effectiveness  of 
internal  controls  that  address  the  risks  of  material  misstatement  relating  to  the  measurement  of 
genetic  test  revenues.  This  included  testing  controls  related  to  management’s  review  of  the 
significant assumptions and inputs used in the determination of the estimated amount that would be 
collected  for  tests  performed  during  the  period.  We  also  tested  controls  over  the  data  used  by 
management in determining this estimate, including the completeness and accuracy of the data.  

We performed audit procedures that included, among others, assessing methodologies and testing 
the significant assumptions discussed above and the underlying data used by the Company in its 
analysis.  We  compared  the  significant  assumptions  used  by  management  to  those  used  in  prior 
periods and examined evidence regarding the changes in assumptions. 

/s/ Ernst & Young LLP 

We have served as the Company’s auditor since 2012 
Redwood City, California 
February 24, 2022 

92 

 
 
 
 
 
 
  
 
 
 
 
 
Natera, Inc. 
Consolidated Balance Sheets 
(in thousands, except par value per share amount) 

December 31,         December 31,   

2021 

2020 

Assets 
Current assets: 

Cash and cash equivalents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Restricted cash . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Short-term investments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accounts receivable, net of allowance of $2,429 in 2021 and $3,080 in 2020 . . . . . .
Inventory  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prepaid expenses and other current assets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total current assets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Property and equipment, net . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Operating lease right-of-use assets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other assets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total assets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$ 

 84,386    $
 228   
 829,896   
 122,074   
 26,909   
 29,645   
   1,093,138   
 65,516   
 59,013   
 18,820   
$   1,236,487    $

Liabilities and Stockholders’ Equity 
Current liabilities: 

Accounts payable . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accrued compensation  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other accrued liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Deferred revenue, current portion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Short-term debt financing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total current liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Long-term debt financing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Deferred revenue, long-term portion  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Operating lease liabilities, long-term portion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other long-term liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Commitments and contingencies (Note 8) 
Stockholders’ equity: 

Common stock, $0.0001 par value: 750,000 shares authorized at December 31, 

2021 and 2020, respectively; 95,140 and 86,223 shares issued and outstanding at 
December 31, 2021 and 2020, respectively. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Additional paid in capital . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accumulated deficit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accumulated other comprehensive gain (loss). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total stockholders’ equity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total liabilities and stockholders’ equity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

See accompanying notes. 

93 

48,668
187
688,606
78,565
20,031
26,606
862,663
33,348
21,399
14,743
932,153

8,096
30,371
60,407
50,125
50,054
199,053
202,493
22,805
21,246
320
445,917

$ 

 27,206    $
 40,941   
 93,353   
 7,404   
 50,052   
 218,956   
 280,394   
 21,318   
 61,036  
 1,479   
 583,183   

 10   
   2,050,417   
   (1,394,836) 
 (2,287) 
 653,304   
$   1,236,487    $

9
1,411,286
(929,318)
4,259
486,236
932,153

 
 
 
 
 
 
 
 
    
 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
Natera, Inc. 
Consolidated Statements of Operations and Comprehensive Loss 
 (in thousands, except per share data) 

Year ended December 31, 
2020 

2021 

2019 

Revenues 

Product revenues  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Licensing and other revenues  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
Total revenues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$

567,149   $   367,211     $ 269,881
 23,794    
58,337    
32,447
302,328
 391,005 
625,486    

Cost and expenses 

Cost of product revenues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cost of licensing and other revenues  . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Research and development  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Selling, general and administrative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gain from disposal of business . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total cost and expenses  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Loss from operations  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Interest expense . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Interest and other income, net  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Loss on debt extinguishment  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Loss before income taxes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Income tax expense . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Net loss  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Unrealized gain (loss) on available-for-sale securities, net of tax . . . . . . . . .
Comprehensive loss  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

 185,865    
302,663    
 17,755   
15,755
 100,035    
264,208    
 303,627    
511,034    
 —   
—  
1,093,660    
 607,282 
(468,174)      (216,277)
 (15,082)  
 7,562    
 (5,848) 
   (229,645)
 (98) 

162,604
12,866
51,357
206,176
(14,388)
418,615
(116,287)
(10,693)
4,152
—
(122,828)
(1,999)
$ (471,716)   $  (229,743) $ (124,827)
1,471
$ (478,262) $  (226,403) $ (123,356)

(8,305)    
5,381    
—  

(471,098)
(618)

 3,340   

(6,546)

Net loss per share (Note 14): 

Basic and diluted  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$

(5.21) $ 

 (2.84)  $

(1.79)

Weighted-average number of shares used in computing basic and 

diluted net loss per share: 
Basic and diluted  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

90,558

 81,011   

69,555

See accompanying notes. 

94 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
   
 
 
 
   
 
 
 
 
Natera, Inc. 
Consolidated Statements of Stockholders’ Equity 
 (in thousands) 

Balance as of December 31, 2018 . . . . . . . . .   

 62,083  

 7  

 607,236

 (552)  

 (574,529) 

 32,162

Additional
Paid-in 
      Shares      Amount     Capital 

Common Stock 

Accumulated 
Other 
Comprehensive   
Income (Loss)       

Accumulated 
Deficit 

Total 
Stockholders'
Equity 

13,041

4,323

323,409
507
—
28,624

(185)

—
—
976,955

23,524

7,114
-
50,171

—
—

82,873

270,649
—
1,411,286

11,816

13,550
—
115,219

(82,876)

550,821

30,601
—
$ 2,050,417

Issuance of common stock upon exercise 

of stock options . . . . . . . . . . . . . . . . . . . . .   

2,464

Issuance of common stock under employee 

stock purchase plan . . . . . . . . . . . . . . . . . .   

268

Sale of common stock through equity 

offering, net of issuance costs . . . . . . . . . .   
Issuance of common stock to Orbimed . . . . .   
Vesting of restricted stock . . . . . . . . . . . . . . .   
Stock-based compensation . . . . . . . . . . . . . .   
Cumulative-effect adjustment upon 

 12,624
25
541
—

adoption of ASU 2018-07 . . . . . . . . . . . . .   

—

Unrealized gain on available-for sale 

securities  . . . . . . . . . . . . . . . . . . . . . . . . . .   
Net loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Balance as of December 31, 2019 . . . . . . . . .   

—
—
 78,005

Issuance of common stock upon exercise 

of stock options . . . . . . . . . . . . . . . . . . . . .   

2,092

Issuance of common stock under employee 

stock purchase plan . . . . . . . . . . . . . . . . . .   
Vesting of restricted stock . . . . . . . . . . . . . . .   
Stock-based compensation . . . . . . . . . . . . . .   
Unrealized gain on available-for sale 

securities  . . . . . . . . . . . . . . . . . . . . . . . . . .   
ASC 326 Adoption - CECL  . . . . . . . . . . . . .   
Equity component of Convertible Notes,  

net  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   

Issuance of common stock for public 

234
1,100
-

-
—

—

offering, net . . . . . . . . . . . . . . . . . . . . . . . .   
Net loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Balance as of December 31, 2020 . . . . . . . . .   

4,792
—
 86,223

Issuance of common stock upon exercise 

of stock options . . . . . . . . . . . . . . . . . . . . .   

1,165

Issuance of common stock under employee 

stock purchase plan . . . . . . . . . . . . . . . . . .   
Vesting of restricted stock . . . . . . . . . . . . . . .   
Stock-based compensation . . . . . . . . . . . . . .   
Unrealized loss on available-for sale 

securities  . . . . . . . . . . . . . . . . . . . . . . . . . .   

Cumulative-effect adjustment upon 

adoption of ASU 2016-13 . . . . . . . . . . . . .   

Issuance of common stock for public 

186
2,117
—

—

—

offering, net . . . . . . . . . . . . . . . . . . . . . . . .   

5,175

Issuance of common stock for IPR&D 

acquisition . . . . . . . . . . . . . . . . . . . . . . . . .   
Net loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Balance as of December 31, 2021 . . . . . . . . .   

274
—
 95,140

$

—

—

1
—
—
—

—

—
—
8

—

—
—
—

—
—

—

1
—
9

—

—
—
—

—

—

1

—
—
10

95 

—  

—  

—  
—  
—  
—  

—  

 — 

 — 

 — 
 — 
 — 
 — 

13,041

4,323

323,410
507
-
28,624

 185 

-

1,471  
—  
919  

 — 
 (124,827)
 (699,171)

1,471
(124,827)
278,711

—  

—  
—  
—  

 — 

 — 
 — 
 — 

3,340  
—  

 — 
 (404)

23,524

7,114
-
50,171

3,340
(404)

—  

 — 

82,873

—  
—  
4,259  

 — 
 (229,743)
 (929,318)

270,650
(229,743)
486,236

 — 

 — 
 — 
 — 

 — 

11,816

13,550
—
115,219

(6,546)

 6,198 

(76,678)

 — 

550,822

—  

—  
—  
—  

—  

—  

—  
—  

—

(6,546)  

$

(2,287)   $  (1,394,836) $

 — 
 (471,716)

30,601
(471,716)
653,304

 
 
 
 
 
 
 
 
 
 
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Natera, Inc. 
Consolidated Statements of Cash Flows 
(in thousands) 

2021 

Year Ended December 31, 
2020 

2019 

$

(471,716)

$

 (229,743) 

$ 

(124,827)

Operating activities: 
Net loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Adjustments to reconcile net loss to net cash used in operating activities:

Depreciation and amortization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Expensed in-process research and development  . . . . . . . . . . . . . . . . . . . . . . . .
Non-cash lease expense . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Impairment of assets  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Stock-based compensation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Inventory reserve adjustments  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Premium amortization and discount accretion on investment securities . . . . . . .
Loss on investments  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Unrealized losses on investment securities . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amortization of debt discount and issuance cost . . . . . . . . . . . . . . . . . . . . . . . .
Other non-cash benefits (charges) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gain on disposal of business  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Provision for credit losses  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Loss on debt extinguishment  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accretion of Convertible Note . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Changes in operating assets and liabilities: 

Accounts receivable . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Inventory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prepaid expenses and other current assets . . . . . . . . . . . . . . . . . . . . . . . . . .
Other assets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accounts payable . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accrued compensation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other accrued liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Deferred revenue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other long term liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Net cash used in operating activities . . . . . . . . . . . . . . . . . . . . . . . . . . .

Investing activities: 
Purchases of investments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Proceeds from sale of investments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Proceeds from maturity of investments  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Net proceeds from disposal of business  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Purchases of property and equipment, net  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cash paid for acquisition of an asset  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Net cash used in investing activities  . . . . . . . . . . . . . . . . . . . . . . . . . . .

Financing activities: 
Proceeds from exercise of stock options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Proceeds from issuance of common stock under employee stock purchase plan. . . .
Proceeds from Convertible Note, net of issuance costs . . . . . . . . . . . . . . . . . . . . . .
Loan payment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Proceeds from public offering, net of issuance cost  . . . . . . . . . . . . . . . . . . . . . . . .
Net cash provided by financing activities  . . . . . . . . . . . . . . . . . . . . . . .

Net increase (decrease) in cash equivalents and restricted cash . . . . . . . . . . . . . . . .
Beginning - cash equivalents & restricted cash . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ending - cash equivalents and restricted cash . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Supplemental disclosure of cash flow information: 
Cash paid for income taxes  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cash paid for interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Non-cash investing and financing activities: 
Purchases of property and equipment in accounts payable and accruals. . . . . . . . . .

$

$
$

$

See accompanying notes 

96 

11,254
35,604
10,926
—
115,219
628
7,814
(46)
(11)
1,227
94
—
(156)
—
—

(43,353)
(7,506)
(10,545)
(2,933)
19,222
10,569
32,682
(44,209)
—
(335,236)

(876,095)
187,580
532,910
—
(41,030)
(8,558)
(205,193)

11,816
13,550
—
—
550,822
576,188

35,759
48,855
84,614

283
7,077

5,173

$

$
$

$

 8,613  
 —  
 7,834  
 —  
 50,171  
 (163) 
 5,761   
 (105) 
 —  
 149  
 (149) 
 —  
 1,354   
 5,848  
 7,048  

 (25,831)  
 (7,474)  
 (23,386)  
 (60)  
 (118)  
 14,284   
 10,340   
 (6,895)  
 10  
 (182,512)  

 (685,239) 
 30,067  
 343,315  
 —  
 (19,604)  
 —  
 (331,461)  

 23,524  
 7,114  
 278,316  
 (78,757) 
 270,650  
 500,847   

 (13,126)  
 61,981   
 48,855   

 67  
 3,296  

 2,781  

$ 

$ 
$ 

$ 

7,730
—
7,748
1,671
28,624
321
945
(16)
—
457
(51)
(14,388)
1,141
—
—

2,418
917
(13,956)
(9,099)
(6,262)
3,419
8,606
40,848
310
(63,444)

(446,626)
1,666
173,900
9,675
(4,968)
—
(266,353)

13,041
4,323
—
—
323,410
340,774

10,977
51,004
61,981

2,154
12,455

3,706

 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Natera, Inc. 
Notes to Consolidated Financial Statements 

1.    Description of Business 

Natera, Inc. (the “Company”) was formed in the state of California as Gene Security Network, LLC in November 
2003 and incorporated in the state of Delaware in January 2007. The Company is a diagnostics company with proprietary 
molecular  and  bioinformatics  technology  that  it  is  applying  to  change  the  management  of  disease  worldwide.  The 
Company’s  cell-free  DNA  (“cfDNA”)  technology  combines  its  novel  molecular  assays,  which  reliably  measure  many 
informative  regions  across  the  genome  from  samples  as  small  as  a  single  cell,  with  its  statistical  algorithms  which 
incorporate data available from the broader scientific community to identify genetic variations covering a wide range of 
serious  conditions  with  high  accuracy  and  coverage.  The  Company’s  technology  has  been  proven  clinically  and 
commercially in the women’s health space, in which it develops and commercializes non- or minimally-invasive tests to 
evaluate risk for, and thereby enable early detection of, a wide range of genetic conditions, such as Down syndrome.  The 
Company is now translating its success in women’s health and applying its core technology to the oncology market, in 
which it is commercializing a personalized blood-based DNA test to detect molecular residual disease and monitor disease 
recurrence,  as  well  as  to  the  organ  health  market,  initially  with  a  test  to  assess  kidney  transplants  for  rejection.  The 
Company operates laboratories certified under the Clinical Laboratory Improvement Amendments ("CLIA") providing a 
host of cell-free DNA-based molecular testing services. The Company determines its operating segments based on the way 
it organizes its business to make operating decisions and assess performance. The Company operates one segment, the 
development  and  commercialization  of  molecular  testing  services,  applying  its  proprietary  technology  in  the  fields  of 
women’s health, oncology and organ health. The Company has three subsidiaries. 

The  Company's  product  offerings  include  its  Panorama  Non-Invasive  Prenatal  Test  ("NIPT")  that  screens for 
chromosomal abnormalities of a fetus as well as in twin pregnancies, typically with a blood draw from the mother; Vistara, 
a single-gene mutations screening test performed to identify single-gene disorders; Horizon Carrier Screening ("HCS") to 
determine carrier status for a large number of severe genetic diseases that could be passed on to the carrier’s children; 
Spectrum Pre-implantation Genetics (“Spectrum”) to evaluate embryos to identify chromosomal anomalies or inherited 
genetic conditions to improve the chances of a healthy pregnancy during an in vitro fertilization ("IVF") cycle; Anora 
Miscarriage Test (“Anora”) to rapidly and extensively analyze fetal chromosomes to understand the cause of miscarriage; 
Non-Invasive Paternity Testing (“PAT”), which is exclusively marketed and sold by a licensee from whom the Company 
receives a royalty; Signatera, which detects circulating tumor DNA in patients previously diagnosed with cancer to assess 
molecular residual disease and monitor for recurrence; and Prospera, to assess organ transplant rejection. All testing is 
available principally in the United States. The Company also offers its Panorama test to customers outside of the United 
States,  primarily  in  Europe.  The  Company  also  offers  Constellation,  a  cloud-based  software  platform  that  enables 
laboratory customers to gain access through the cloud to the Company’s algorithms and bioinformatics in order to validate 
and launch their own tests based on the Company’s technology. Through the third quarter of 2019, the Company offered 
Evercord for the collection and storage of newborn cord blood and cord tissue units, which was sold in the third quarter of 
2019 to a third-party buyer. 

2.    Summary of Significant Accounting Policies 

Basis of Presentation 

The  accompanying  consolidated  financial  statements  have  been  prepared  in  conformity  with  U.S.  generally 

accepted accounting principles (“U.S. GAAP”). 

Liquidity Matters 

The Company has incurred net losses since its inception and anticipates net losses and negative operating cash 
flows for the near future. The Company had a net loss of $471.7 million for the year ended December 31, 2021 and an 
accumulated deficit of $1.4 billion as of December 31, 2021. As of December 31, 2021, the Company had $84.6 million 
in cash, cash equivalents, and restricted cash, $829.9 million in marketable securities, $50.1 million of outstanding balance 

97 

 
 
 
 
 
 
 
 
of  the  Credit  Line  (as  defined  in  Note  10,  Debt)  including  accrued  interest,  and  $287.5  million  outstanding  principal 
balance of its 2.25% Convertible Senior Notes (the “Convertible Notes”). In April 2020, the Company used a portion of 
the  net  proceeds  from  the  offering  of  the  Convertible  Notes  to  repay  its  obligations  under  its  2017  Term  Loan  with 
OrbiMed. 

While the Company has introduced multiple products that are generating revenues, these revenues have not been 
sufficient to fund all operations and business plans. Accordingly, the Company has funded the portion of its operating 
costs  and  business  plans  that  exceed  revenues  through  a  combination  of  equity  issuances,  debt  issuances,  and  other 
financings. 

The Company continues to invest in the development and commercialization of its existing and future products 
and,  consequently,  it  will  need  to  generate  additional  revenues  to  achieve  future  profitability  and  may  need  to  raise 
additional equity or debt financing. If the Company raises additional funds by issuing equity securities, its stockholders 
will experience dilution. Additional debt financing, if available, may involve covenants restricting its operations or its 
ability to incur additional debt. Any additional debt financing or additional equity that the Company raises may contain 
terms that are not favorable to it or its stockholders and requires significant debt service payments, which diverts resources 
from other activities. Additional financing may not be available when necessary, or in amounts or on terms acceptable to 
the Company. If the Company is unable to obtain additional financing, it may be required to delay or slow its investment 
in the development and commercialization of its products and significantly scale back its business and operations. 

On September 10, 2021, the Company entered into an agreement with a third party for an asset acquisition where 
the acquired asset was in-process research and development primarily in exchange for an equity consideration payment. 
In addition, pursuant to the agreement, certain employees of the third party became employees of the Company. The third 
party was a biotechnology company focused on oncology. The total upfront acquisition consideration amounts to $35.6 
million composed of the issuance of 276,346 shares of the Company's common stock with a fair value of $30.9 million, 
approximately  $3.9  million  of  cash  consideration,  assumed  net  liabilities  of  $0.2  million,  as  well  as  $0.6  million  of 
acquisition related legal and accounting costs directly attributable to the acquisition of the asset. The Company accounted 
for the transaction as an asset acquisition as substantially all of the estimated fair value of the gross assets acquired was 
concentrated in a single identified in-process research and development asset (“IPR&D”) thus satisfying the requirements 
of the screen test in ASU 2017-01. The estimated fair value of the acquired workforce was not significant. The Company 
concluded the acquired IPR&D has no alternative-future use and accordingly expensed approximately $35.6 million, on 
the day the transaction closed as research and development expense, which is reflected in its consolidated statement of 
operations. 

Further,  additional  consideration  aggregating  up  to  approximately  $35.0  million  may  be  paid  in  an  estimated 
269,547 of additional shares, consistent with the registration statement filed with the SEC on September 10, 2021, that are 
potentially  issuable  to  legacy  shareholders  of  this  third  party  upon  the  achievement  of  defined  milestones  relating  to 
product development, commercial launch and continued employment of certain selling shareholders, each of which will 
be  revalued  at  each  reporting  date  and  amount  of  compensation  expense  will  be  adjusted  accordingly.  The  Company 
assessed these milestones as probable as of September 30, 2021 and December 31, 2021. As achievement of all milestones 
is contingent upon the continued employment of certain selling shareholders, the Company accounted for the consideration 
related  to  all  of  the  milestones  as  compensation  expenses  and  recognized  these  expenses  ratably  over  the  estimated 
performance period of 24 months, to approximately August 2023. 

In April 2019, the Company completed an underwritten equity offering and sold 6,052,631 shares of its common 
stock at a price of $19 per share to the public. Before offering expenses of $0.6 million, the Company received proceeds 
of $108.1 million net of the underwriting discount. In October 2019, the Company completed another underwritten equity 
offering and sold 6,571,428 shares of its common stock at a price of $35 per share to the public. Before offering expenses 
of $0.4 million, the Company received proceeds of $216.2 million net of the underwriting discount. In September 2020, 
the Company completed an additional underwritten equity offering and sold 4,791,665 shares of its common stock at a 
price of $60.00 per share to the public. Before offering expenses of $0.3 million, the Company received proceeds of $271.0 
million net of the underwriting discount. In July 2021, the Company completed an underwritten equity offering and sold 
5,175,000 shares of its common stock at a price of $113 per share to the public. Before offering expenses of $0.4 million, 
the  Company  received  proceeds  of  $551.2  million  net  of  the  underwriting  discount.  Based  on  the  Company’s  current 

98 

 
 
business plan, the Company believes that its existing cash and marketable securities will be sufficient to meet its anticipated 
cash requirements for at least 12 months after February 24, 2022. 

Principles of Consolidation 

The accompanying consolidated financial statements include all the accounts of the Company and its subsidiaries. 
The  Company  established  a  subsidiary  that  operates  in  the  state  of  Texas  to  support  the  Company’s  laboratory  and 
operational  functions.  The  Company  established  a  subsidiary  that  operates  in  Canada  following  the  acquisition  of  the 
IPR&D  asset,  which  includes  a  lease  for  the  laboratory  space  located  in  Canada.  All  intercompany  balances  and 
transactions have been eliminated. 

Use of Estimates 

The preparation of financial statements in accordance with generally accepted accounting principles (GAAP) in 
the United States requires management to make estimates and assumptions about future events that affect the amounts of 
assets and liabilities reported, disclosures about contingent assets and liabilities, and reported amounts of revenues and 
expenses. Significant items subject to such estimates include the allowance for doubtful accounts calculated based on the 
historical uncollected balances applied to current outstanding accounts receivable balances, average selling price expected 
to be received  from  insurance  payors,  the operating  right-of-use  assets  and  the  associated  lease  liabilities,  the  average 
useful life for property and equipment, deferred revenues associated with unsatisfied performance obligations, accrued 
liability for potential refund requests, stock-based compensation, the fair value of options, income tax uncertainties, and 
the expected consideration to be received from contracts with customers. These estimates and assumptions are based on 
management's best estimates and judgment. Management regularly evaluates its estimates and assumptions using historical 
experience and other factors, including contractual terms and statutory limits; however, actual results could differ from 
these estimates and could have an adverse effect on the Company's financial statements. 

Revenue 

The  total  consideration  which  the  Company  expects  to  be  entitled  to  from  patients  and  insurance  carriers  in 
exchange for the Company's products is determined is a significant estimate when the Company calculates Average Selling 
Price based on the contractual pricing agreed to with each insurance carrier for each test (CPT code) performed adjusted 
for variable consideration related to historical percent of cases allowed, historical percent of patient responsibility collected, 
and historical percent of contract price collected from insurance carriers. The Company uses the expected-value approach 
of estimating variable consideration.  The Company also considers recent trends, past events not expected to recur, and 
future known changes such as anticipated contractual pricing changes or insurance coverages.  For insurance carriers with 
similar  reimbursement  characteristics,  the  Company  uses  a  portfolio  approach  to  estimate  the  effects  of  variable 
consideration. The Company also applies a constraint to the estimated variable consideration when it assesses it is probable 
that a significant reversal in the amount of cumulative revenue may occur in future periods.   

When assessing the total consideration for insurance carriers and patients, a certain percentage of revenues is 

further constrained for estimated refunds. 

Stock-based compensation 

The Company’s stock-based compensation relates to stock options, restricted stock units (“RSUs”), performance-

based awards, market-based awards, and stock purchase rights under an Employee Stock Purchase Plan (“ESPP”). 

Stock based compensation granted to the Company’s employees is measured at the grant date based on the fair 
value of the award. The fair value is recognized as expense over the requisite service period, which is generally the vesting 
period or estimated performance period of the respective awards.  

The Company uses the Black‑Scholes option‑pricing model to estimate the fair value of stock options issued to 
employees and non-employees. Stock-based compensation expense for stock-based awards are based on their grant date 
fair value. The fair value of stock option awards is recognized as compensation expense on a straight-line basis over the 

99 

  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
requisite service period in which the awards are expected to vest and forfeitures are estimated based on historical trends at 
the  time  of  grant  and  revised  as  necessary.  Stock  option  awards  that  include  a  service  condition  and  a  performance 
condition are considered expected to vest when the performance condition is probable of being met. The Black-Scholes 
model considers several variables and assumptions in estimating the fair value of stock-based awards. These variables 
include  the per  share  fair value of  the  underlying  common stock,  exercise price,  expected  term,  risk-free  interest rate, 
expected annual dividend yield and the expected stock price volatility over the expected term. For all stock options granted, 
we calculate the expected term using the simplified method for “plain vanilla” stock option awards. We determine expected 
volatility using the historical volatility of the stock price of similar publicly traded peer companies. The risk-free interest 
rate is based on the yield available on U.S. Treasury zero-coupon issues similar in duration to the expected term of the 
equity-settled award. 

The Company determines the fair value of RSUs based on the closing price of our stock price, which is listed on 

Nasdaq, at the date of the grant.  

For  stock  options  and  performance-based  awards  that  vest  upon  meeting  performance  conditions  or  market 
conditions in combination with performance conditions, the Company derives the requisite service period from the grant 
date to the date it is probable that the vesting conditions will be met. The requisite service period is considered to be a 
significant accounting estimate. For stock options with market conditions, the Company derives the requisite service period 
using the Monte Carlo simulation model. 

The Monte Carlo simulation model is used to estimate the fair value of market-based condition awards. The model 
requires the input of the Company's expected stock price and peer stock price volatility, the expected term of the awards, 
and a risk-free interest rate. Determining these assumptions requires significant judgment. See further discussion on the 
valuation assumptions used under Note 9. 

Income Taxes 

Income taxes are recorded in accordance with Financial Accounting Standards Board ASC Topic 740, Income 
Taxes  ("ASC  740"),  which  provides  for  deferred  taxes  using  an  asset  and  liability  approach.  Deferred  tax  assets  and 
liabilities  are  recognized  for  the  future  tax  consequences  attributable  to  differences  between  the  financial  statement 
carrying amounts of existing assets and liabilities and their respective tax bases using enacted tax rates in effect for the 
year in which the differences are expected to affect taxable income. Tax benefits are recognized when it is more likely 
than not that a tax position will be sustained during an audit. Deferred tax assets are reduced by a valuation allowance if 
current evidence indicates that it is considered more likely than not that these benefits will not be realized. See further 
discussion in Note 13, Income Taxes. 

Allowance for doubtful accounts 

The  allowance  for  doubtful  accounts  for  trade  accounts  receivable  and  other  receivables.  is  based  on  the 
Company’s  assessment  of  the  collectability  of  customer  accounts.  The  Company  regularly  reviews  the  allowance  by 
considering factors such as historical experience, credit quality, the age of the accounts receivable balances, and current 
economic conditions that may affect a customer’s ability to pay. 

Appropriate provision has been made for lifetime expected credit losses in accordance with ASC Topic 326-20, 
Financial  Instruments—Credit  Losses  (“Topic  326”),  for  trade  receivables  and  available-for-sale  debt  securities.  The 
Company’s estimate of expected credit losses includes consideration of past events, current conditions and forecasts of 
future economic conditions. 

Inventory 

Inventory is recorded at the lower of cost or net realizable value, determined on a first-in, first-out basis. The 
Company uses judgment to analyze and determine if the composition of its inventory is obsolete, slow-moving or unsalable 
and frequently reviews such determinations. A write down of specifically identified unusable, obsolete, slow-moving or 
known unsalable inventory in the period is first recognized by using a number of factors including product expiration dates 

100 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
and  scrapped  inventory.  Any  write-down  of  inventory  to  net  realizable  value  establishes  a  new  cost  basis  and  will  be 
maintained even if certain circumstances suggest the inventory is recoverable in subsequent periods. Costs associated with 
the write-down of inventory are recorded to cost of revenue on our consolidated statements of operations. The Company 
makes assumptions about future demand, market conditions and the release of new products that may supersede older 
products. However, if actual market conditions are less favorable than anticipated, additional inventory write-downs may 
be required. 

Investments and financial instruments 

The Company classifies its investments as Level 1 or 2 within the fair value hierarchy. Fair values determined by 
Level 1 inputs utilize quoted prices (unadjusted) in active markets for identical assets that the Company has the ability to 
access. Fair values determined by Level 2 inputs utilize data points that are observable such as quoted prices, interest rates 
and yield curves. The Company holds Level 2 securities which are initially valued at the transaction price and subsequently 
valued by a third-party service provider using inputs other than quoted prices that are observable either directly or indirectly, 
such as yield curve, volatility factors, credit spreads, default rates, loss severity, current market and contractual prices for 
the underlying instruments or debt, broker and dealer quotes, as well as other relevant economic measures. The Company 
performs certain procedures to corroborate the fair value of these holdings.   

Right-of-use assets 

The incremental borrowing rate is used to determine the present value of the minimum future lease payments. 
The Company estimates the incremental borrowing rate of its leases based on corporate bonds with a similar credit rating 
as the Company and a similar bond term as the lease term as of the approximate lease commencement date. The Company 
calculates the weighted-average annual percentage yield of bonds with a similar credit rating and term to determine the 
incremental borrowing rate.  

Property and equipment 

Property and equipment, including purchased and internally developed software, are stated at cost. Depreciation 
and  amortization  is  calculated  using  the  straight-line  method  over  the  estimated  useful  lives  of  the  assets,  which  are 
generally three to five years determined by the classification of the property and equipment class in accordance with the 
Company’s fixed asset policy. Leasehold improvements are amortized using the straight-line method over the estimated 
useful lives of the assets or the remaining term of the lease, whichever is shorter. The Company periodically reviews the 
useful lives assigned to property and equipment placed in service in accordance with the Company’s fixed asset policy 
and changes the estimates of useful lives to reflect the results of such reviews. The Company amortizes its internal-use 
software over the estimated useful lives of three years. 

Other accrued liabilities 

The Company's uses estimates, judgments, and assumptions to determine liabilities primarily related to refunds 
reserve,  tax-related  liabilities,  payroll  and  related  expenses,  marketing  liabilities,  clinical  trials  and  other  operating 
expenses. Estimates consist of historical trends, analytical procedures, review of supporting documentation, inquiries with 
supply partners and vendors, and other relevant assumptions. Estimates are used in several areas including, but not limited 
to, estimates of progress to date for certain contacts with vendors, liabilities related to clinical trials, reserves associated 
with insurance and general overpayments, and the provision for income taxes. Although the Company believe its estimates, 
assumptions, and judgment are reasonable, it is based upon information presently available and are subject to change. 

Cash and Cash Equivalents 

Cash and cash equivalents consist of cash and money market deposits with financial institutions. 

101 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Restricted Cash 

Restricted cash is currently presented as a separate line item in the Company’s balance sheet. In the statements 
of cash flows, it is included together with cash and cash equivalents and considered as part of the total ending cash balance. 
The following is the reconciliation between how restricted cash is presented in the balance sheet and the statements of 
cash flows for all periods presented: 

Cash and cash equivalents in balance sheet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Restricted cash, current portion in balance sheet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total cash, cash equivalents and restricted cash in statements of cash flows . . . . . . . . . . . .

$ 

$ 

 84,386    $
 228   
 84,614    $

48,668
187
48,855

December 31,    December 31,

2021 

2020 

(in thousands)

Investments 

Investments  consist  primarily  of  debt  securities  such  as  U.S.  Treasuries,  U.S.  agency  and  municipal  bonds. 
Management  determines  the  appropriate  classification  of  securities  at  the  time  of  purchase  and  re-evaluates  such 
determination at each balance sheet date. The Company generally classifies its entire investment portfolio as available-
for-sale. The Company views its available-for-sale portfolio as available for use in current operations. Accordingly, the 
Company classifies all investments as short-term, irrespective of maturity date. Available-for-sale securities are carried at 
fair value, with unrealized gains and losses reported in accumulated other comprehensive income (loss), which is a separate 
component of stockholders’ equity. 

On December 6, 2021, the Company participated along with certain other investors in the series B financing of 
MyOme, Inc. (“MyOme”), and purchased preferred shares and warrants in exchange for approximately $4.0 million cash 
payment.  Matthew  Rabinowitz  is  the  Chairman  of  the  board  of  directors  and  Co-Founder  of  both  the  Company  and 
MyOme. The Company’s investment in MyOme is recorded at cost and will be evaluated for impairment at the end of 
each reporting period. 

Fair Value 

The Company discloses the fair value of financial instruments for financial assets and liabilities for which the 
value is practicable to estimate. Fair value is defined as the price that would be received upon the sale of an asset or paid 
to transfer a liability in an orderly transaction between market participants at the measurement date (exit price). 

Risk and Uncertainties 

The Company is subject to risks and uncertainties as a result of the COVID-19 pandemic. The extent of the impact 
of the COVID-19 pandemic on the Company's business is highly uncertain and difficult to predict, and the full extent and 
duration of the impact of the COVID 19 pandemic on our business, our operations, and the global economy as a whole is 
not yet known. While the Company’s test volumes as well as overall average selling prices increased in the year ended 
December 31, 2021 compared to the year ended December 31, 2020, the Company cannot predict the potential nature, 
magnitude and duration of the effects of the COVID-19 pandemic on the macroeconomic environment. 

Financial instruments that potentially subject the Company to credit risk consist of cash, accounts receivable and 
investments. The Company limits its exposure to credit loss by placing its cash in financial institutions with high credit 
ratings. The Company's cash may consist of deposits held with banks that may at times exceed federally insured limits. 
The Company performs evaluations of the relative credit standing of these financial institutions and limits the amount of 
credit exposure with any one institution. 

The Company performs evaluations of financial conditions for insurance carriers, patients, clinics and laboratory 
partners and generally does not require collateral to support credit sales. For the years ended December 31, 2021, 2020, 
and 2019, there were no customers exceeding 10% of total revenues on an individual basis. As of December 31, 2021 and 
2020, there were no customers with an outstanding balance exceeding 10% of net accounts receivable. 

102 

 
 
 
 
 
 
 
  
   
 
 
 
 
 
 
 
 
Credit Losses 

Trade accounts receivable and other receivables. The allowance for doubtful accounts is based on the Company’s 
assessment  of  the  collectability  of  customer  accounts.  The  Company  regularly  reviews  the  allowance  by  considering 
factors such as historical experience, credit quality, the age of the accounts receivable balances, and current economic 
conditions that may affect a customer’s ability to pay. 

The following is a roll-forward of the allowances for credit losses related to trade accounts receivable and other 

receivables for the year ended December 31, 2021: 

December 31,  
2021 
(in thousands)

Beginning balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Provision for credit losses  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Write-offs  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    

$ 

$ 

4,220
(156)
(1,635)
2,429

Available-for-sale  debt  securities. The  amended  guidance  from  ASU  2016-13  requires  the  measurement  of 
expected  credit  losses for  available-for-sale debt  securities held  at  the  reporting  date  over  the  remaining  life  based  on 
historical experience, current conditions, and reasonable and supportable forecasts. The Company evaluated its investment 
portfolio under the new available-for-sale debt securities impairment model guidance. The vast majority of the Company’s 
investment portfolio are low risk, investment grade securities. 

Revenue Recognition 

The Company adopted the new revenue recognition guidance, ASC 606, beginning January 1, 2018 on a full 

retrospective basis. ASC 606 mandates revenue recognition to be evaluated using the following five steps: 

Identification of a contract, or contracts, with a customer; 
Identification of the performance obligations in the contract; 

• 
• 
•  Determination of the transaction price; 
•  Allocation of the transaction price to the performance obligations in the contract; and 
•  Revenue recognition when, or as, the performance obligations are satisfied 

See Note 3, Revenue Recognition, for detailed discussions of product revenues, licensing and other revenues, and 

how the five steps described above are applied. 

103 

 
 
 
 
 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cost of Product Revenues 

The components of our cost of product revenues are material and service costs, impairment charges associated 
with  testing  equipment,  personnel  costs,  including  stock-based  compensation  expense,  equipment  and  infrastructure 
expenses  associated  with  testing  samples,  electronic  medical  records,  order  and  delivery  systems,  shipping  charges  to 
transport samples, costs incurred from third party test processing fees, and allocated overhead such as rent, information 
technology costs, equipment depreciation and utilities. Costs associated with Whole Exome Sequencing (“WES”) are also 
included,  as  well  as  labor  costs,  relating  to  our  Signatera  CLIA  offering.  Costs  associated  with  performing  tests  are 
recorded when the test is accessioned. We expect cost of product revenues in absolute dollars to increase as the number of 
tests we perform increases. 

 However, having rapidly achieved scale, we have increased our focus on more efficient use of labor, automation, 
and DNA sequencing. For example, we updated the molecular and bioinformatics process for Panorama to further reduce 
the sequencing reagents, test steps and associated labor costs required to obtain a test result, while increasing the accuracy 
of the test to allow it to run with lower fetal fraction input. These improvements also reduced the frequency of the need to 
require blood redraws from the patient. 

Cost of Licensing and Other Revenues  

The components of our cost of licensing and other revenues are material costs associated with test kits sold to 
Constellation  clients,  development  and  support  services  relating  to  our  Strategic  Partnership  Agreements,  and  costs 
associated with specimens and Whole Exome Sequencing (“WES”), as well as labor costs, relating to our Signatera (RUO) 
and CDx offering. 

We consider our cost of licensing and other revenues for the Constellation software platform to be relatively low, 
and therefore we expect its associated gross margin is higher. We expect our cost of licensing will increase in relation to 
volume growth. 

Research and Development  

The Company records research and development costs in the period incurred. Research and development costs 
consist  of  personnel  costs,  contract  services,  cost  of  materials  utilized  in  performing  tests,  costs  of  clinical  trials  and 
allocated facilities and related overhead expenses.  

Advertising Costs  

The Company expenses advertising costs as incurred. The Company incurred advertising costs of $2.2 million, 

$0.6 million, and $0.2 million for the years ended December 31, 2021, 2020, and 2019, respectively. 

Product Shipment Costs  

The Company expenses product shipment costs in cost of product revenues in the accompanying statements of 
operations. Shipping and handling costs for the years ended December 31, 2021, 2020, and 2019 were $22.0 million, $13.3 
million, and $13.3 million, respectively. 

Income Taxes  

Income taxes are recorded in accordance with Financial Accounting Standards Board ASC Topic 740, Income 
Taxes  ("ASC  740"),  which  provides  for  deferred  taxes  using  an  asset  and  liability  approach.  Deferred  tax  assets  and 
liabilities  are  recognized  for  the  future  tax  consequences  attributable  to  differences  between  the  financial  statement 
carrying amounts of existing assets and liabilities and their respective tax bases using enacted tax rates in effect for the 
year in which the differences are expected to affect taxable income. Tax benefits are recognized when it is more likely 
than not that a tax position will be sustained during an audit. Deferred tax assets are reduced by a valuation allowance if 
current evidence indicates that it is considered more likely than not that these benefits will not be realized. 

104 

 
 
 
 
 
 
 
 
 
 
 
 
 
Stock-Based Compensation 

Stock-based compensation related to stock options and restricted stock units (“RSUs”) granted to the Company’s 
employees is measured at the grant date based on the fair value of the award. The fair value is recognized as expense over 
the  requisite  service  period,  which  is  generally  the  vesting  period  of  the  respective  awards.  No  compensation  cost  is 
recognized when the requisite service has not been met and the awards are therefore forfeited. 

For stock options with market conditions, the Company derives the requisite service period using the Monte Carlo 
simulation model. For stock options and RSUs that vest upon meeting performance conditions or market conditions in 
combination with performance conditions, the Company derives the requisite service period from the grant date to the date 
it is probable that the vesting conditions will be met. 

The Company uses the Black‑Scholes option‑pricing model to estimate the fair value of stock options issued to 
employees  and  non-employees.  The  Monte  Carlo  simulation  model  is  used  to  estimate  the  fair  value  of  market-based 
condition awards. The model requires the input of the Company's expected stock price volatility, the expected term of the 
awards, and a risk-free interest rate. Determining these assumptions requires significant judgment. See further discussion 
on the valuation assumptions used under Note 9. 

Capitalized Software Held for Internal Use  

The  Company  capitalizes  salaries  and  related  costs  of  employees  and  consultants  who  devote  time  to  the 
development  of  internal-use  software  development  projects.  Capitalization  begins  during  the  application  development 
stage, once the preliminary project stage has been completed, which includes successful validation and approval from 
management. If a project constitutes an enhancement to previously developed software, the Company assesses whether 
the enhancement is significant and creates additional functionality to the software, thus qualifying the work incurred for 
capitalization. Once the project is available for general release, capitalization ceases and the Company estimates the useful 
life  of  the  asset  and  begins  amortization.  The  Company  periodically  assesses  whether  triggering  events  are  present  to 
review  internal-use  software  for  impairment.  Changes  in  estimates  related  to  internal-use  software  would  increase  or 
decrease operating expenses or amortization recorded during the reporting period.  

The Company amortizes its internal-use software over the estimated useful lives of three years. The net book 
value of capitalized software held for internal use was $2.3 million and $1.7 million as of December 31, 2021 and 2020, 
respectively. Amortization expense for amounts previously capitalized for the years ended December 31, 2021, 2020, and 
2019, was $1.1 million, $1.0 million, and $1.2 million, respectively. 

Accumulated Other Comprehensive Income (Loss) 

Comprehensive loss and its components encompass all changes in equity other than those with stockholders, and 

include net loss, and unrealized gains and losses on available-for-sale marketable securities. 

December 31, 

2021 

2020 

(in thousands)

Beginning balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Net unrealized gains (losses) on available-for-sale securities, net of tax . . . . . . . . . . . . .
Ending balance  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$ 

$ 

 4,259    $
 (6,546) 
 (2,287)  $

919
3,340
4,259

Property and Equipment 

Property and equipment, including purchased and internally developed software, are stated at cost. Depreciation 
is calculated using the straight-line method over the estimated useful lives of the assets, which are generally three to five 
years. Leasehold improvements are amortized using the straight-line method over the estimated useful lives of the assets 

105 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
or the remaining term of the lease, whichever is shorter. The Company periodically reviews the depreciable lives assigned 
to property and equipment placed in service and change the estimates of useful lives to reflect the results of such reviews.    

Impairment of Long-lived Assets 

The Company evaluates its long-lived assets for indicators of possible impairment when events or changes in 
circumstances indicate the carrying amount of an asset may not be recoverable. The Company then compares the carrying 
amounts  of  the  assets  with  the  future  net  undiscounted  cash  flows  expected  to  be  generated  by  such  asset.  Should  an 
impairment exist, the impairment loss would be measured based on the excess carrying value of the asset over the asset’s 
fair value determined using discounted estimates of future cash flows.  

Inventory  

Inventory  is  valued  at  the  lower  of  the  standard  cost,  which  approximates  actual  cost,  or  market.  Cost  is 
determined using the first-in, first-out (“FIFO”) method. Inventory consists entirely of supplies, which are consumed when 
providing its test reports, and therefore does not maintain any finished goods inventory. The Company enters into inventory 
purchases and commitments so that it can meet future delivery schedules based on forecasted demand for its tests. 

The Company recorded inventory obsolescence charges totaling $0.9 million, $0.2 million, and $0.3 million, in 

the years ended December 31, 2021, 2020, and 2019, respectively. 

Recent Accounting Pronouncements 

From time to time, new accounting pronouncements are issued by the Financial Accounting Standards Board (the 
“FASB”)  under  its  accounting  standard  codifications  (“ASC”)  or  other  standard  setting  bodies  and  adopted  by  the 
Company as of the specified effective date. Unless otherwise discussed below, the Company believes that the impact of 
recently issued standards that are not yet effective will not have a material impact on its financial position or results of 
operations upon adoption. 

Recently Adopted Accounting Pronouncements 

Income Taxes 

In  October  2020,  ASU  2020-10,  Codification  Improvements,  was  issued,  which  simplifies  the  existing 
codification. The guidance includes presentation disclosures for the amount of income tax expense or benefit related to 
other comprehensive income. ASU 2010-10 is effective for fiscal years beginning after December 15, 2020, including 
interim periods within those fiscal years. Early application of the amendments is permitted for public business entities for 
any annual or interim period for which financial statements have not been issued. The Company has adopted this standard 
as of January 1, 2021, which did not have a material impact on its consolidated financial statements upon the adoption. 

Debt 

In August 2020, ASU 2020-06, Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and 
Hedging—Contracts in Entity’s Own Equity (Subtopic 815-40) was issued which simplifies the accounting for convertible 
instruments. The guidance removes certain accounting models which separate conversion features from the host contract 
for  convertible  instruments.  Either  a  modified  retrospective  method  of  transition  or  a  fully  retrospective  method  of 
transition  is  permissible  for  the  adoption  of  this  standard.  ASU  2020-06  is  effective  for  fiscal  years  beginning  after 
December 15, 2021, including interim periods within those fiscal years. Early adoption is permitted no earlier than the 
fiscal year beginning after December 15, 2020. The Company has adopted this standard as of January 1, 2021 using the 
modified retrospective approach. As a result of the adoption of ASU 2020-06, the Convertible Notes due May 2027 are no 
longer  bifurcated  into  separate  liability  and  equity  components  in  the  December  31,  2021  consolidated  balance  sheet. 
Rather, the $287.5 million principal amount of the Company’s Convertible Notes is now classified only as a liability in 
the December 31, 2021 consolidated balance sheet. Upon adoption of ASU 2020-06, an adjustment was recorded to the 
Convertible  Notes  liability  component,  equity  component  (additional  paid-in-capital)  and  retained  earnings.  The 

106 

 
 
 
 
 
 
 
 
 
 
cumulative effect of the change was recognized as an adjustment to the opening balance of retained earnings at the date of 
adoption.  The  comparative  information  has  not  been  restated  and  continues  to  be  presented  according  to  accounting 
standards in effect for those periods. This adjustment was calculated based on the carrying amount of the Convertible 
Notes as if it had always been treated only as a liability. Further, an adjustment was recorded to the debt discount and 
issuance costs as if these had always been treated as a contra liability only. Interest expense related to the accretion of the 
Convertible Notes is no longer recognized. Interest expense for the Convertible Notes for the year ended December 31, 
2021  would  have  been  $9.4  million  higher  without  the  adoption  of  ASU  2020-06.  As  such,  net  loss  from  continuing 
operations attributable to the Company for the year ended December 31, 2021 was $0.10 per common share lower due to 
the effect of adoption of ASU 2020-06. 

Liabilities 

Outstanding Principal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Unamortized debt discount and issuance cost . . . . . . . . . .
Net carrying amount . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Equity 

Additional paid-in-capital . . . . . . . . . . . . . . . . . . . . . . . . . .
Accumulated deficit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

New Accounting Pronouncements Not Yet Adopted 

$

$

$

December 31,  
2020 

ASU 2020-06 
Adoption Adjustment  
(in thousands) 

January 1, 
2021 

287,500
(85,007)
202,493

$

$

 —  $ 
 76,674     
 76,674  $ 

287,500
(8,333)
279,167

(1,411,286) $
(929,318)

 82,876    $ 
 6,198 

(1,328,410)
(923,120)

In March 2020, ASU 2020-04, Reference Rate Reform (Topic 848) was issued which provides temporary optional 
guidance  to  ease  the  potential  burden  in  accounting  for  reference  rate  reform.  The  new  guidance  provides  optional 
expedients and exceptions for applying generally accepted accounting principles to transactions affected by reference rate 
reform  if  certain  criteria  are  met.  These  transactions  include  contract  modifications,  hedging  relationship,  and  sale  or 
transfer of debt securities classified as held to maturity. Early adoption of this ASU is permitted, and the Company may 
elect to apply the amendments prospectively through December 31, 2022. The Company’s financial instruments that are 
in the scope of ASU 2020-04 include but are not limited to the UBS credit line agreement. The Company is currently 
evaluating the impact of the adoption of this standard on its consolidated financial statements. 

3.    Revenue Recognition 

The  Company  recognizes  revenues  when,  or  as,  performance  obligations  in  the  contracts  are  satisfied,  in  the 

amount reflecting the expected consideration to be received from the goods or services transferred to the customers. 

Product Revenues 

Product  revenues  are  derived  from  contracts  with  insurance  carriers,  laboratory  partners  and  patients  in 
connection with sales primarily related to prenatal genetic tests. The Company enters into contracts with insurance carriers 
with  primarily  payment  terms  related  to  tests  provided  to  the  patients  who  have  health  insurance  coverage.  Insurance 
carriers are considered as third-party payers on behalf of the patients, and the patients are considered as the customers who 
receive genetic test services. Tests may be billed to insurance carriers, patients, or a combination of insurance carriers and 
patients. Further, the Company sells tests to a number of domestic and international laboratory partners and identifies the 
laboratory partners as customers provided that there is a test services agreement between the two parties. 

A performance obligation represents a promise in a contract to transfer a distinct good or service to a customer, 
which represents a unit of accounting in accordance with ASC 606. A performance obligation is considered distinct from 
other obligations in a contract when it provides a benefit to the customer either on its own or together with other resources 

107 

 
 
 
 
 
 
 
 
 
 
   
 
 
   
 
 
 
 
 
 
 
 
 
 
 
that are readily available to the customer and is separately identified in the contract. The Company considers a performance 
obligation satisfied once the Company has transferred control of a good or service to the customer, meaning the customer 
has the ability to use and obtain the benefit of the good or service. A portion of the consideration should be allocated to 
each distinct performance obligation and recognized as revenue when, or as, the performance obligation is satisfied. The 
Company evaluates its contracts with insurance carriers, laboratory partners and patients and identifies the performance 
obligations in those contracts, which are the delivery of the test results. 

The  total  consideration  which  the  Company  expects  to  be  entitled  to  from  patients  and  insurance  carriers  in 
exchange  for  the  Company's  products  is  determined  based  on  agreements  with  insurance  carriers,  effects  of  variable 
consideration, and customary business practices.  The transaction price is estimated based on the contractual pricing agreed 
to with each insurance carrier for each test (CPT code) performed adjusted for variable consideration related to historical 
percent  of  cases  allowed,  historical  percent  of  patient  responsibility  collected,  and  historical  percent  of  contract  price 
collected from insurance carriers. The Company uses the expected-value approach of estimating variable consideration.  
The Company also considers recent trends, past events not expected to recur, and future known changes such as anticipated 
contractual pricing changes or insurance coverages.  For insurance carriers with similar reimbursement characteristics, the 
Company  uses  a  portfolio  approach  to  estimate  the  effects  of  variable  consideration.    The  Company  also  applies  a 
constraint to the estimated variable consideration when it assesses it is probable that a significant reversal in the amount 
of cumulative revenue may occur in future periods.  The total consideration which the Company expects to be entitled to 
from lab partners is generally fixed, but can be variable depending on the volume of tests performed, which is estimated 
using the expected-value approach.  For insurance carriers, laboratory partners and patients, the Company allocates the 
total consideration to a single performance obligation, which is the delivery of the test results to the customers. 

When assessing the total consideration for insurance carriers and patients, a certain percentage of revenues is 

further constrained for estimated refunds. 

The Company generally bills an insurance carrier, a laboratory partner or a patient upon delivery of test results. 
The Company also bills patients directly for out-of-pocket costs involving co-pays and deductibles that they are responsible 
for. Tests billed to insurance carriers and directly to patients usually take an average of nine to twelve months to collect 
payment,  and 
takes 
laboratory  distribution  partners, 
approximately two to three months. At times, the Company may or may not get reimbursed for the full amount billed. 
Further, the Company may not get reimbursed at all for tests performed if such tests are not covered under the insurance 
carrier’s reimbursement policies or the Company is not a qualified provider to the insurance carrier, or if the tests were 
not previously authorized. 

the  average  collection  cycle 

tests  billed 

for 

to 

Product revenue is recognized in an amount that equals to the total consideration (as described above) at a point 
in time when the test results are delivered. The Company reserves certain amounts in other accrued liabilities on the balance 
sheet in anticipation of requests for refunds of payments previously made by insurance carriers, which are accounted for 
as reductions in product revenues in the statement of operations and comprehensive loss. During the years ended December 
31,  2021,  2020,  and  2019,  $5.7  million,  $5.4  million,  and  $2.4  million,  respectively,  were  released  from  amounts 
previously held in reserves in other accrued liabilities and recognized as product revenue. 

Licensing and Other Revenues 

The Company recognizes licensing revenues from its cloud-based distribution service offering, Constellation, by 
granting  licenses  to  its  licensees  to  use  certain  of  the  Company’s  proprietary  intellectual  properties  and  cloud-based 
software and IVD kits. The Company also recognizes revenues from the Signatera research use only (“RUO”) and CDx 
offering, the Qiagen LLC, BGI Genomics Co., Ltd., and Foundation Medicine, Inc. agreements. 

Constellation 

The laboratory partners with which the Company enters into a licensing arrangement represent the licensees and 
are identified as customers. The licensees do not have the right to possess the Company’s software, but rather receive 
professional services through the cloud software. These arrangements often include: (i) the delivery of the services through 
the cloud software, (ii) the necessary support and training, and (iii) the IVD kits to be consumed as tests are processed. 

108 

 
 
 
 
 
 
 
The Company does not consider the software as a service, the support and training as being distinct in the context of such 
arrangements, and therefore they are combined as a single performance obligation. The software, support and training are 
delivered simultaneously to the licensees over the term of the arrangement. 

The Company bills the majority of licensees, who process the tests in their laboratories, a fixed price for each test 
processed. Licensing revenues are recognized as the performance obligations are satisfied (i.e., upon the delivery of each 
test) and reported in licensing and other revenues in the statements of operations and comprehensive loss. 

Signatera 

The Company enters into agreements with pharmaceutical companies to utilize the Company’s Signatera tests 
typically  to  study  new  cancer  treatments  or  to  validate  the  outcomes  of  clinical  trials  for  which  the  pharmaceutical 
companies  are  identified  as  customers.  Such  arrangements  generally  involve  performing  whole  exome  sequencing 
(“WES”) services and the testing of patient samples to detect cancer mutations using its Signatera test. Each test is billable 
to  customers  and  the  personalized  cancer  profile  also  makes  each  test  distinct  within  the  context  of  the  contract  as 
customers can exercise control over the test results upon delivery. The Company allocates the contract price to each test 
using the stand-alone selling price for each service and recognizes the test processing revenue as individual test results are 
delivered to customers. 

Qiagen 

In March 2018, the Company entered into a License, Development and Distribution Agreement (the “Qiagen 
Agreement”) with Qiagen under which the Company granted Qiagen a license to develop, manufacture, distribute and 
commercialize  NGS-based  genetic  testing  assays  and  sequencing  systems  utilizing  such  assays,  which  incorporate  the 
Company’s proprietary technology. According to the terms of the Qiagen Agreement, the Company is initially entitled to 
receive an upfront license fee and prepaid royalties totaling $40.0 million, which was fully collected in 2018. All or a 
portion of the prepaid royalties are refundable in limited circumstances. In addition, the Company was entitled to potential 
milestone  payments  from  Qiagen  upon  the  successful  achievement  of  certain  volume,  regulatory  and  commercial 
milestones, and tiered royalties of $10.0 million, of which the Company received $5.0 million due December 31, 2018. 
The Qiagen Agreement has a term of 10 years and expires in March 2028, and it may be terminated earlier in certain 
circumstances. Upon termination of the Qiagen Agreement, the license granted to Qiagen will also terminate, except in 
certain limited circumstances. The Company provided to Qiagen standard indemnification protections, which is part of an 
assurance that the license meets the contract’s specifications and is not an obligation to provide goods or services.    

Effective  in March 2020,  the  Company  terminated  the Qiagen Agreement.  Subsequently,  in March  2021,  the 
Company and Qiagen signed a Termination and Settlement Agreement where the Company agreed to refund a net $10.0 
million as a result of the termination. The remaining $28.6 million of deferred revenue was recognized as licensing and 
other revenue in the first quarter of 2021. 

BGI Genomics 

In  February  2019,  the  Company  entered  into  a  License  Agreement  with  BGI  Genomics  Co.,  Ltd.  (“BGI 
Genomics”) to develop, manufacture, and commercialize NGS-based genetic testing assays for clinical and commercial 
use. The agreement has a term of ten years and expires in February 2029. According to the agreement, the Company is 
entitled to a total of $50 million, comprised of upfront technology license fees, prepaid royalties relating to future sales of 
licensed  products  and  performance  of  assay  interpretation  services,  and  milestone  payments.  During  the  three  months 
ended June 30, 2019, the Company received $35.6 million, net of withholding taxes, of these amounts. The Company 
recorded a receivable of $2.5 million upon achieving the first milestone as of June 30, 2019, which was received in January 
2021. Also, as required by the agreement with BGI Genomics, in June 2019 the Company prepaid $6.0 million to BGI 
Genomics for future sequencing services and $4.0 million for future sequencing equipment. These advance payments for 
equipment and services to be received in future periods aggregating to $10.0 million were recorded in long-term advances 
on the Balance Sheet. 

109 

 
 
 
 
  
 
Pursuant to the agreement, the Company licensed its intellectual property and will provide development services. 
Following completion of development services, the Company will provide assay interpretation services over the term of 
the agreement. The Company concluded that the license is not a distinct performance obligation as it does not have a stand-
alone value to BGI Genomics apart from the related development services. Therefore, license and related development 
services, for each of the NIPT and Oncology products, represents a single performance obligation. 

The  Company  is  responsible  for  granting  a  license  to  specified  intellectual  property  and  performing  certain 
development  activities  to  customize  its  genetic  testing  assays  for  oncology  and  NIPT  for  use  with  BGI  Genomics’ 
sequencing instruments and proprietary technology platform. Revenue associated with these performance obligations is 
recognized over time using the input method, based on costs incurred to perform the development services, since the level 
of  costs  incurred  over  time  best  reflect  the  transfer  of  development  services.  Revenue  associated  with  the  assay 
interpretation  services  will  be  recognized  upon  delivery  of  these  services.  Funds  received  in  advance  are  recorded  as 
deferred revenue and will be recognized as the related services are delivered. 

The initial transaction price was primarily comprised of license and milestone fees. The Company constrains the 
estimated variable consideration when it assesses it is probable that a significant reversal in the amount of cumulative 
revenue recognized may occur in future periods. Certain milestone and license fees were constrained and not included in 
the transaction price due to the uncertainties of research and development. The Company re-evaluates the transaction price, 
including  the  estimated  variable  consideration  included  in  the  transaction  price  and  all  constrained  amounts,  in  each 
reporting  period  and  as  uncertain  events  are  resolved  or  other  changes  in  circumstances  occur.  The  allocation  of  the 
transaction  price  was  performed  based  on  standalone  selling  prices,  which  are  based  on  estimated  amounts  that  the 
Company would charge for a performance obligation if it were sold separately. 

In accordance with ASC 340-40, any incremental costs incurred to obtain a contract with a customer are required 
to  be  capitalized  and  amortized  over  the  period  in  which  the  goods  and  services  are  transferred  to  the  customer.  The 
incremental costs incurred in connection with the BGI Genomics arrangement is not material on an accumulated basis and 
therefore will not be capitalized on the balance sheet but will be expensed as incurred. 

Foundation Medicine, Inc. 

In August 2019, the Company entered into a License and Collaboration Agreement (the “Foundation Medicine 
Agreement”) with Foundation Medicine to develop and commercialize personalized circulating tumor DNA monitoring 
assays, for use by biopharmaceutical and clinical customers who order Foundation Medicine’s FoundationOne CDx. The 
Foundation  Medicine  Agreement  has  an  initial  term  of  five  years,  expiring  in  August  2024,  with  automatic  renewals 
thereafter for successive one-year terms, unless the Foundation Medicine Agreement is earlier terminated in accordance 
with its terms. Natera and Foundation Medicine will share the revenues generated from both biopharmaceutical and clinical 
customers in accordance with the terms of the Foundation Medicine Agreement. The Foundation Medicine Agreement 
provides for approximately $13.3 million in upfront licensing fees and prepaid revenues payable to the Company, and up 
to approximately $32.0 million in minimum annual payments and payments tied to the Company’s achievement of certain 
developmental, regulatory, and commercial milestones. As of December 31, 2019, the Company received $16.3 million 
of these amounts, of which $3.0 million was for achieving certain milestones, and $13.3 million was for licensing fees and 
prepaid revenue. There was an additional milestone met in May 2021. The Company recorded the $1.0 million milestone 
amount against accounts receivable and short-term deferred revenue.  The milestone was paid in early July 2021.  No other 
payments have been received in the year ending December 31, 2021.  Additionally, the Company included an incremental 
$2.0 million in the transaction price of the contract based on the expectation of achieving a certain milestone in early 2022. 
This amount was not part of the initial transaction price. 

Pursuant to the agreement, the Company will provide development services in conjunction with granting the use 
of the Company’s intellectual property. Following completion of those development services, the Company will provide 
assay  testing  services  over  the  term  of  the  agreement.  The  Company  has  concluded  that  the  license  is  not  a  distinct 
performance obligation as it is highly interrelated and interdependent with the related development services. Therefore, 
license and related development services represent a single performance obligation. 

The  Company  is  responsible  for  providing  the  technology  license  and  certain  development  services  that  are 
required  to  customize  its  proprietary  Signatera  test  to  work  with  Foundation  Medicine’s  FoundationOne  CDx.  The 

110 

 
 
  
 
 
intellectual  property  has  been  licensed  to  Foundation  Medicine  for  the  customized  test.  In  addition,  the  Company  is 
responsible for delivering clinical study plans in order to demonstrate efficacy of the customized test. Revenues associated 
with each of the performance obligations are recognized over time using the input method, based on costs incurred to 
perform  the  development  services,  since  the  level  of  costs  incurred  over  time  best  reflect  the  transfer  of  development 
services. Revenue associated with the assay testing services will be recognized upon delivery of these services. Funds 
received in advance are recorded as deferred revenue and will be recognized as the related services are delivered. 

The initial transaction price was primarily comprised of license and milestone fees. The Company constrains the 
estimated variable consideration when it assesses it is probable that a significant reversal in the amount of cumulative 
revenue  recognized  may  occur  in  future  periods.  Certain  milestone  fees  were  constrained  and  not  included  in  the 
transaction price due to the uncertainties of research and development. The Company re-evaluates the transaction price, 
including  the  estimated  variable  consideration  included  in  the  transaction  price  and  all  constrained  amounts,  in  each 
reporting  period  and  as  uncertain  events  are  resolved  or  other  changes  in  circumstances  occur.  The  allocation  of  the 
transaction  price  was  performed  based  on  standalone  selling  prices,  which  are  based  on  estimated  amounts  that  the 
Company would charge for a performance obligation if it were sold separately. 

In accordance with ASC 340-40, any incremental costs incurred to obtain a contract with a customer are required 
to  be  capitalized  and  amortized  over  the  period  in  which  the  goods  and  services  are  transferred  to  the  customer.  The 
Company has elected to apply a practical expedient under ASC 340-40 to recognize the incremental costs of obtaining a 
contract as an expense when incurred provided that the amortization period of such costs, if capitalized, is one year or less. 
Since the incremental costs to obtain the Foundation Medicine Agreement would be amortized over a period of one year 
or less, these costs were expensed as incurred. 

Disaggregation of Revenues 

The following table shows disaggregation of revenues by payer types: 

Insurance carriers  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Laboratory partners . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total revenues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$

$

2021 

492,563
100,019
32,904
625,486

Year Ended December 31, 
2020 
(in thousands) 

$

$

 300,220    $ 
 58,196   
 32,589   
 391,005    $ 

2019 

210,919
59,876
31,533
302,328

The following table presents total revenues by geographic area based on the location of the Company’s payers: 

United States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Americas, excluding U.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Europe, Middle East, India, Africa  . . . . . . . . . . . . . . . . . . . . . . .
Asia Pacific and Other  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$

$

2021 

590,872
4,047
20,429
10,138
625,486

Year ended December 31,  
2020 
(in thousands) 

$

$

 365,660     $ 
 3,469    
 14,332    
 7,544    
 391,005    $ 

2019 

260,846
3,218
15,434
22,830
302,328

The  following  table  summarizes  the  Company’s  beginning  and  ending  balances  of  accounts  receivable  and 

deferred revenues: 

Balance at 
December 31, 
2021 

Balance at 
December 31, 
2020 

111 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assets: 

Accounts receivable . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Liabilities: 

Deferred revenue, current portion . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Deferred revenue, long-term portion  . . . . . . . . . . . . . . . . . . . . . . . . . .
Total deferred revenues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(in thousands) 

122,074   

7,404   
21,318   
28,722   

$ 

$ 

$ 

$

$

$

78,565

50,125
22,805
72,930

The following table shows the changes in the balance of deferred revenues during the period: 

Balance at December 31, 2020 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .     
Increase in deferred revenues  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Reclasses from deferred revenues to other to short-term liabilities . . . . . . . . . . . . . . . . . . . . . . .    
Revenue recognized during the period that was included in 

$ 

deferred revenues at the beginning of the period . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    

Revenue recognized from performance obligations satisfied 

within the same period  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Balance at December 31, 2021 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    

$ 

Deferred 
Revenues 
(in thousands)

72,930
7,915
(10,080)

(37,784)

(4,259)
28,722

During the year ended December 31, 2021, revenue recognized that was included in the deferred revenue balance 
at  the  beginning  of  the  period  totaled  $37.8  million  with  approximately  $8.9 million  related  to  BGI  Genomics  and 
Foundation Medicine, $28.6 million related to Qiagen and the remaining $0.3 million related to genetic testing services. 
During the year ended December 31, 2021, $4.3 million was recognized as deferred revenue and later earned as revenue 
in the same period. The current portion of deferred revenue includes $3.2 million from the BGI Genomics agreement and 
$0.5 million from the Foundation Medicine agreement. The non-current portion of deferred revenue includes $20.4 million 
from the BGI Genomics agreement and $0.9 million from the Foundation Medicine agreement. 

4.    Fair Value Measurements 

The Company's financial assets and liabilities carried at fair value are comprised of investment assets that include 

money market and investments.   

The fair value accounting guidance requires that assets and liabilities be carried at fair value and classified in one 

of the following three categories: 

Level I: Quoted prices in active markets for identical assets and liabilities that the Company has the ability to 
access. 

Level II: Observable market-based inputs or unobservable inputs that are corroborated by market data, such as 
quoted prices, interest rates, and yield curves. 

Level III: Inputs that are unobservable data points that are not corroborated by market data. 

This hierarchy requires the Company to use observable market data, when available, and to minimize the use of 

unobservable inputs when determining fair value. 

112 

 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assets and Liabilities That Are Measured at Fair Value on a Recurring Basis 

The following table represents the fair value hierarchy for the Company’s financial assets and financial liabilities 

measured at fair value on a recurring basis: 

     Level I 

    Level II 

   Level III   

Total 

    Level I 

December 31, 2021 

December 31, 2020 
    Level II     Level III   

Total 

(in thousands)

Financial Assets: 

Money market deposits. . . .   $  10,041    $
U.S. Treasury securities . . .      688,097   
Corporate bonds and  

—   $ —   $ 10,041   $ 28,990   $
  688,097  
—  

  597,744  

  —  

 —    $ 
 —   

 —   $ 28,990
  597,744
 —  

notes . . . . . . . . . . . . . . . . .    
Municipal securities . . . . . .    

52,337  
89,462  
Total financial assets . . . . . . .   $ 698,138    $ 141,799   $ —   $ 839,937   $ 626,734   $ 90,862    $ 

   12,328   
   78,534   

52,337  
89,462  

  —  
  —  

 —   
 —   

—  
—  

12,328
 —  
 —  
78,534
 —   $ 717,596

Fair Value of Long-Term Debt: 

As of December 31, 2021, the estimated fair value of the Convertible Notes, which are not presented at fair value 
on the Consolidated Balance Sheet as of December 31, 2021, was $715.7 million and was based upon observable Level 2 
inputs, including pricing information from recent trades of the Convertible Notes (see Note 10, Debt). 

5.    Financial Instruments 

The Company elected to invest a portion of its cash assets in conservative, income earning, liquid investments. 

Cash equivalents and investments, all of which are classified as available-for-sale securities, consisted of the following: 

December 31, 2021 
Gross 
Unrealized
(Loss) 

Gross 
Unrealized 
Gain 

Amortized 
Cost 

Estimated Fair
Value 

Amortized
Cost 

(in thousands)

December 31, 2020 
Gross 
Unrealized
(Loss) 

Gross 
Unrealized
Gain 

Estimated Fair
Value 

Money market 

deposits . . . . . . . .     $   10,041    $ 

 —    $ — $

10,041

$ 28,990

$ —    $ 

 —    $

28,990

U.S. Treasury 

securities (1) . . . .        689,640   

    1,081   

(2,624)

688,097

594,252

3,512   

 (20) 

597,744

Corporate bonds 

and notes (1) . . . .       

 52,729   

 —   

(392)

52,337

12,331

 2   

 (5) 

12,328

Municipal  

securities . . . . . . .      

 89,814   
Total . . . . . . . . . . . .     $  842,224    $   1,342    $ (3,629) $

 261   

(613)

89,462
839,937

77,764
$ 713,337

796   
$ 4,310    $ 

 (26) 
 (51)  $

78,534
717,596

Classified as: 

Cash 

equivalents (2) .      

Short-term 

investments . . . .      
Total . . . . . . . . . . . .      

$

$

10,041

829,896
839,937

  $

28,990

688,606
717,596

  $

(1)   Per  the  Company’s  investment  policy,  all  debt  securities  are  classified  as  short-term  investments  irrespective  of 

holding period. 

(2)  Cash equivalents includes cash sweep accounts and U.S. Treasury money market mutual funds. 

113 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
    
    
    
    
    
     
    
 
 
  
  
  
 
 
 
   
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
The Company invests in U.S. Treasuries, U.S. agency and high quality municipal bonds which mature at par 
value and are all paying their coupons on schedule. The Company has therefore concluded there is currently no other than 
temporary impairment of its investments and will continue to recognize unrealized gains and losses in other comprehensive 
income (loss). The Company sold $187.6 million and $30.1 million of investments during the years ended December 31, 
2021 and 2020, respectively. During the year ended December 31, 2021, the amount of gross realized gains and realized 
losses upon sales of investments were insignificant. The Company uses the specific investment identification method to 
calculate  realized  gains  and  losses  and  amounts  reclassified  out  of  other  comprehensive  income  to  net  income.  As  of 
December 31, 2021, the Company had 61 investments in an unrealized loss position in its portfolio. An allowance for 
credit losses was not necessary as decrease in the fair market value for a majority of the available-for-sale securities was 
as a result of a significant average yield rate decrease for similar securities as of December 31, 2021. The Company has 
assessed the unrealized loss position for available-for-sale debt securities for which an allowance for credit losses has not 
been  recorded.  The  fair  value  for  investment  securities  at  an  unrealized  loss  position  as  of  December  31,  2021  was 
$604.7 million.  The  aggregate  amount of unrealized  losses  of  these  securities  was  $3.6  million,  and  the  impact  of  the 
securities  in  a  continuous  loss  position  to  the  consolidated  statements  of  operations  and  comprehensive  loss  were  not 
material as of December 31, 2021.  

The following table summarizes the Company’s portfolio of available-for-sale securities by contractual maturity 

as of December 31, 2021: 

Less than or equal to one year . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Greater than one year but less than five years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

December 31, 2021 

Amortized 
Cost 

Fair 
Value 

(in thousands)
$   274,879    $ 275,331
  554,565
$   832,183    $ 829,896

 557,304   

114 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.     Balance Sheet Components 

Credit Losses 

The following is a roll-forward of the allowances for credit losses related to trade accounts receivable and other 

current assets for the years ended December 31, 2021, 2020 and 2019: 

December 31,    December 31,    December 31, 
2020 
(in thousands) 

2019 

2021 

Beginning balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $
Cumulative-effect adjustment upon adoption of ASU 2016-13. . . . . . . . . . . . . . .
Provision for credit losses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Write offs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ending balance  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $

4,220    $ 
—     
(156)   
(1,635)   
2,429    $ 

 2,919    $
 404   
 1,354   
 (457) 
 4,220    $

1,788
—
1,141
(10)
2,919

Property and Equipment, net 

The Company’s property and equipment consisted of the following:  

    Useful Life 

2021 

2020 

  December 31,  December 31,

Machinery and equipment  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Furniture and fixtures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Computer equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Capitalized software held for internal use . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Leasehold improvements  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Construction-in-process  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3-5 years    $ 
3 years
3 years
3 years

Life of lease     

Less: Accumulated depreciation and amortization . . . . . . . . . . . . . . . . . . . . . .
Total Property and Equipment, net  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

  $ 

(in thousands)

 33,722    $
 —   
 4,893   
 2,395   
 13,640   
 30,279   
 84,929   
 (19,413) 
 65,516    $

51,001
1,376
2,428
7,417
14,810
6,370
83,402
(50,054)
33,348

The Company’s property and equipment are primarily located in the United States. 

During the year ended December 31, 2021, the increase in net property and equipment was due to purchases of 
new equipment for the Company’s laboratories located in Texas and California to expand testing capabilities, offset by 
depreciation expense of $11.3 million recorded in the year ended December 31, 2021. During the year ended December 
31, 2021, the Company has written off $41.9 million in fully depreciated assets. The Company did not incur an impairment 
charge during the year ended December 31, 2021. 

115 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
    
 
 
    
   
 
 
 
 
    
    
 
 
    
 
    
    
 
 
 
 
Accrued Compensation 

The Company’s accrued compensation consisted of the following: 

Accrued paid time off . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accrued commissions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accrued bonuses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other accrued compensation  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total accrued compensation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

      December 31,      December 31,

2021 

2020 

(in thousands)

$ 

$ 

 2,567    $
 15,726   
 15,854   
 6,794   
 40,941    $

2,260
12,686
9,635
5,790
30,371

116 

 
 
 
 
 
 
 
 
    
    
 
 
 
  
  
  
 
 
Other Accrued Liabilities 

The Company’s other accrued liabilities consisted of the following:  

     December 31,  

      December 31,  

2021 

2020 

(in thousands)

Reserves for refunds to insurance carriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accrued charges for third-party testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Testing and laboratory materials from suppliers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Marketing and corporate affairs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Legal, audit and consulting fees . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accrued shipping charges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sales tax payable . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Accrued third-party service fees . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical trials, studies, and other development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Operating lease liabilities, current portion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fixed asset purchases  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other accrued interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other accrued expenses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total other accrued liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$

$

17,210   $ 
5,849   
3,799  
7,853   
11,758  
969   
2,230  
13,442   
11,218  
5,752   
1,853  
1,078   
10,342  
 93,353    $ 

17,366 
5,141 
2,720 
3,325 
4,189 
1,604 
1,723 
2,355 
2,353 
7,300 
1,691 
1,078
9,562 
60,407

Reserves for refunds to insurance carriers include overpayments from and amounts to be refunded to insurance 
carriers, and additional amounts that the Company estimates for potential refund requests during the period. When the 
Company  releases  these  previously  accrued  amounts,  they  are  recognized  as  product  revenues  in  the  statements  of 
operations and comprehensive loss. 

The following table summarizes the reserve balance and activities for refunds to insurance carriers for the year 

ended December 31, 2021: 

Beginning balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Additional reserves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Refunds to carriers  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Reserves released to revenue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ending balance  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$

$

 17,366    $ 
 16,340   
 (10,784) 
 (5,712) 
 17,210    $ 

9,410
19,427
(6,066)
(5,405)
17,366

     December 31,  

      December 31,  

2021 

2020 

(in thousands)

7.    Leases 

Operating Leases  

In September 2015, the Company’s subsidiary entered into a long-term lease agreement for laboratory and office 
space totaling approximately 94,000 square feet in Austin, Texas. The lease term is 132 months beginning in December 
2015  and  expiring  in  November  2026  with  monthly  payments  beginning  in  December  2016.  In  December  2021,  the 
Company  entered  into  an  amendment of  the  Austin  lease  agreement  which  extended  the  lease of  the  current  premises 
through March 2033. The amendment also includes two additional office spaces (the “First Expansion Premises” and the 
“Second Expansion Premises”). The First Expansion Premises consists of 32,500 rentable square feet and commences in 
February 2022. The Second Expansion Premises consists of 65,222 rentable square feet and commences in September 
2022. The terms of the First and Second Expansion Premises expire in March 2033. 

117 

 
 
 
 
 
 
 
 
 
 
    
     
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
    
     
 
 
 
 
 
 
 
 
 
In October 2016, the Company entered into a lease directly with its landlord for laboratory and office spaces at 
its  facilities  located  in  San  Carlos,  California.  The  Company  currently  occupies  approximately  113,000  square  feet 
comprised of two office spaces (the “First Space” and the “Second Space”). The First Space covers approximately 88,000 
square feet, and the Second Space totals approximately 25,000 square feet. The term of this lease is approximately 84 
months and expires in October 2023. This lease contains an option to renew the lease term for five years, but the fair 
market  rent  amount  upon  renewal  is  not  available  from  the  landlord.  In  January  2021,  the  Company  entered  into  an 
amendment of the lease to extend the term for 48 months to October 2027. The combined annual rent for the First Space 
and Second Space will be $9.3 million commencing in October 2023.  

The Company entered into a lease agreement commencing June 2018 for its cord blood tissue storage facility in 
Tukwila, Washington that covers approximately 10,000 square feet. The lease term is 62 months expiring in July 2023. 
The Company has the option to extend this lease for five years, and the fair market rent upon renewal is not determinable. 
However, since the Company sold its business related to cord blood and tissue storage in September 2019, the Company 
has subleased the facility and does not intend to exercise its option to renew the facility upon expiration. 

In addition, the Company entered into a sublease agreement in June 2019 with a third party to sublease 25,879 
square  feet  of  space  located  on  the  third  floor  of  the  San  Carlos,  California  building  while  maintaining  its  primary 
obligation as the intermediate lessor. The term of this lease is approximately 48 months commencing in October 2019 and 
expiring in September 2023. The annual lease payment starts at $1.9 million and will escalate annually commencing in 
October 2020. In February 2021, the Company entered into an amendment of the San Carlos sublease agreement whereas 
the third party will surrender 25,879 rentable square feet by December 31, 2021. For the year ended December 31, 2021, 
the Company recorded noncash activities of $44.4 million primarily related to additional right-of-use assets of which $29.7 
million was a result of the San Carlos lease extension which was accounted for as a modification under ASC 842. 

The Company entered into a lease agreement in November 2020 to lease 11,395 square feet of space located in 
South San Francisco, California over a 36-month term. The premises are used for general office, laboratory and research 
use. The annual lease payment starts at $0.9 million and will escalate annually commencing in December 2021. 

As part of the IPR&D asset acquisition in September 2021, the Company inherited a 24-month lease for 7,107 
square feet of laboratory space in Canada. The annual lease payment starts at $0.2 million. The annual lease payment starts 
at $0.2 million. 

The Company has also historically entered into leases of individual workspaces and storage spaces at various 
locations on both a month-to-month basis without an established lease term, and more recently for certain locations, has 
committed to terms approximating one to five years. For the facilities without a committed lease term, the Company has 
elected to not recognize them as right-of-use assets on the consolidated balance sheets as they are all considered short-
term leases. For individual workspaces where the committed lease term exceeds one year, the Company has recorded a 
right-of-use asset on the consolidated balance sheets. 

The operating lease right-of-use assets are classified as noncurrent assets in the balance sheet. The corresponding 

lease liabilities are separated into current and long-term portions as follows: 

Operating lease liabilities, current portion included in other accrued liabilities. . . . . . . . . . . . . . . . . . .    
Operating lease liabilities, long-term portion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Total operating lease liabilities  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    

$ 

$ 

5,752
61,036
66,788

The initial recognition of the operating lease liabilities was measured as the present value of the future minimum 
lease payments using a discount rate determined as of January 1, 2019. The operating right-of-use assets was calculated 
as  the  operating  lease  liabilities  discounted  at  the  present  value,  less  the  amount  of  unamortized  tenant  improvement 
allowance and deferred rent. The discount rate used was the Company’s incremental borrowing rate given that the implicit 

December 31,  
2021 
(in thousands)

118 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
rate to each lease was not readily determinable. In accordance with ASC 842, the incremental borrowing rate was estimated 
as the annual percentage yield resulting from a corporate debt financing over a loan term approximating the remaining 
term of each lease, with the effect of certain credit risk rating. As of December 31, 2021, the weighted-average remaining 
lease term was 4.77 years and the weighted-average discount rate was 6.4%. 

The  Company  continues  to  recognize  lease  expense  on  a  straight-line  basis.  The  lease  expense  includes  the 
amortization  of  the  right-of-assets  with  the  associated  interest  component  estimated  by  applying  the  effective  interest 
method.  Total  lease  expense  recognized  in  the  statements  of  operations  and  comprehensive  loss  were  $10.9  million, 
$7.8 million, and $7.8 million for the years ended December 31, 2021, 2020, and 2019, respectively. Cash paid for amounts 
in the measurement of operating lease liabilities totaled $10.3 million, $9.0 million, and $8.6 million for the years ended 
December 31, 2021, 2020, and 2019, respectively. 

The  present  value  of  the  future  minimum  lease  payments  under  all  non-cancellable  operating  leases  as  of 

December 31, 2021 is as follows: 

      Operating Leases   

(in thousands)

Year ending December 31: 

2022 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
2023 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
2024 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
2025 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
2026 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
2027 and thereafter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Total future minimum lease payments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Less:  imputed interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Operating lease liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    

$ 

$ 

9,980
11,082
12,258
12,494
12,845
27,331
85,990
(19,202)
66,788

119 

 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
8.    Commitments and Contingencies 

Legal Proceedings  

From time to time, the Company is involved in disputes, litigation, and other regulatory or administrative  actions, 
including those with respect to intellectual property, employment, testing, billing, reimbursement  and other matters. Such 
actions  may  include  allegations  of  negligence,  products/professional  liability  or  other  legal  claims,  and  could  involve 
claims  for  substantial  compensatory  and/or  punitive  damages  or  claims  for  indeterminate  amounts  of  damages.  The 
Company is aggressively defending and/or prosecuting its current litigation matters, but cannot provide any assurance as 
to the ultimate outcome or that an adverse resolution would not have a material adverse effect on its financial condition 
and results of operations. There are many uncertainties associated with any litigation and these actions or other third party 
claims against the Company, including by governmental entities, or by the Company against third parties, may cause the 
Company  to  incur  costly  litigation  and/or substantial  settlement  charges.  In  addition,  the resolution of  any  intellectual 
property litigation may require the Company to make royalty payments, which could adversely affect gross margins in 
future periods. If this were to occur, the Company's business, financial condition, results of operations, and cash flows 
could be adversely affected. 

The Company assesses legal contingencies to determine the degree of probability and range of possible loss for 
potential accrual in its financial statements. When evaluating legal contingencies, the Company may be unable to provide 
a meaningful estimate due to a number of factors, including the procedural status of the matter in question, the presence 
of complex or novel legal theories, and/or the ongoing discovery and development of information important to the matters. 
In  addition,  damage  amounts  claimed  in  litigation  or  other  matters  may  be  unsupported,  exaggerated  or  unrelated  to 
possible outcomes, and as such are not meaningful indicators of its potential liability. During the periods presented, the 
Company has not recorded any accrual for loss contingencies associated with such legal proceedings or other matters, 
determined that an unfavorable outcome is probable or reasonably possible, or determined that the amount or range of any 
possible loss is reasonably estimable. 

Intellectual Property Litigation Matters. 

The Company has been involved in two patent litigations against CareDx, Inc. (“CareDx”) in the United States 
District Court for the District of Delaware (“CareDx Patent Cases”). In the first suit, CareDx alleged, in a complaint filed 
jointly with the Board of Trustees of the Leland Stanford Junior University (“Stanford”) in March 2019 and amended in 
March 2020, that the Company infringed three patents. The complaint sought unspecified damages and injunctive relief. 
On September 28, 2021, the Court granted the Company’s motion for summary judgment, finding all three of Stanford’s 
patents invalid.  CareDx and Stanford have filed a notice of appeal to the United States Court of Appeals for the Federal 
Circuit.  In the second suit, filed by the Company in January 2020, the Company alleged infringement by CareDx of two 
of  the  Company’s  patents,  seeking  unspecified  damages  and  injunctive  relief.  The  case  is  currently  pending  and  is 
scheduled for trial in July 2023.  

The Company has filed suit against ArcherDX, Inc. (“ArcherDX”) in the United States District Court for the 
District of Delaware, alleging, in complaints filed in January, April, and August of 2020, which cases were consolidated 
in September 2020, that certain ArcherDX DNA oncology products infringe five of the Company’s patents. In June 2020, 
ArcherDX filed a motion to dismiss aspects of the Company’s case, including to invalidate several of the Company’s 
asserted patents. That motion was denied in its entirety in October 2020. In January 2021, the Company filed a second 
amended  complaint  naming  an  additional  Archer  DX  entity,  ArcherDx  LLC,  and  Invitae  Corp.  as  defendants.  The 
Company is seeking unspecified monetary damages and injunctive relief. Both parties filed motions for summary judgment 
in January 2022. A jury trial is currently set for May 16, 2022. 

The Company is the subject of a lawsuit filed against it by Ravgen, Inc. (“Ravgen”) in June 2020 in the United 
States District Court for the Western District of Texas, alleging infringement of two Ravgen patents. The complaint seeks 
monetary damages  and  injunctive  relief.  Various parties, including  Natera, have  filed challenges  to  the validity of the 
asserted patents with the Patent Office, which are pending.    

120 

 
The Company filed suit against Progenity, Inc. (“Progenity”) in June 2020 in the United States District Court for 
the  Western  District  of  Texas  and  in  the  United  States  District  Court  for  the  Northern  District  of  Texas,  in  each  case 
alleging that Progenity’s NIPT test infringes six of the Company’s patents. The complaints sought treble damages and 
injunctive relief. In July 2020, Progenity filed suit against the Company in the United States District Court for the Southern 
District of California, seeking declaratory judgment of non-infringement of the Company’s asserted patents. Progenity 
also petitioned the Patent Trial and Appeal Board (“PTAB”) of the United States Patent and Trademark Office for inter 
partes review of all of the Company’s asserted patents. The PTAB instituted review of three of the petitions and set trial 
for  March  7,  2022,  and  denied  institution  of  the  other  three  petitions.  On  August  3,  2021,  the  parties  entered  into  a 
settlement agreement to settle the matters described above. 

In October 2020, the Company filed suit against Genosity Inc. (“Genosity”), in the United States District Court 
for the District of Delaware, alleging that various Genosity oncology products infringe one of the Company’s patents and 
seeking unspecified monetary damages and injunctive relief. In March 2021, the Company filed a motion to dismiss certain 
of Genosity’s affirmative defenses and a counterclaim. Trial is set for October 2023. 

In January 2021, the Company filed suit against Inivata, Inc. and Inivata Ltd. (collectively “Inivata”) in the United 
States District Court for the District of Delaware. The complaint, amended by the Company in May 2021, alleges that 
various Inivata oncology products infringe two of the Company’s patents and seeks unspecified monetary damages and 
injunctive relief. In June 2021, Inivata filed a motion to dismiss the Company’s amended complaint. 

The Company is the subject of lawsuits filed against it by Invitae Corp. (“Invitae”) in the United States District 
Court of the District of Delaware alleging, in complaints filed in May and November of 2021, infringement of three patents 
and seeking monetary damages and injunctive relief. Trial is set for January 2024. 

Other Litigation Matters. 

In August 2019, a suit was filed against the Company in the Circuit Court of Cook County, Illinois by a patient 

alleging claims relating to a discordant test result and seeking monetary damages. The suit was dismissed in June 2021. 

The Company is also the subject of a lawsuit filed by CareDx against the Company in April 2019 in the United 
States District Court for the District of Delaware, alleging false advertising, trademark disparagement, unfair competition, 
and unfair or deceptive trade practices based on statements describing studies that concern the Company’s technology and 
CareDx’s technology (“CareDx’s Advertising Case”). The complaint seeks unspecified damages and injunctive relief. In 
May 2019, the Company filed a motion to dismiss the entirety of CareDx’s Advertising Case for failure to state a claim, 
following which in February 2020, CareDx filed an amended complaint withdrawing its trademark disparagement claim. 
Also in February 2020, the Company filed a counterclaim against CareDx in the United States District Court for the District 
of Delaware, alleging false advertising, unfair competition and deceptive trade practices and seeking unspecified damages 
and injunctive relief. The parties cross-moved for partial summary judgment, which was denied in April 2021. The matter 
is set for trial on March 7, 2022. 

The Company is involved in litigation against Guardant, Inc. (“Guardant”). On or about May 27, 2021, Guardant 
filed suit against the Company in the United States District Court of the Northern District of California alleging false 
advertising and related claims and seeking unspecified damages and injunctive relief.  On or about May 28, 2021, the 
Company filed suit against Guardant in the Western District of Texas, alleging false advertising and related claims. The 
Company has voluntarily dismissed its Texas suit against Guardant. In the California action, the Company has answered 
Guardant’s complaint and has asserted its claims as counterclaims, seeking unspecified damages and injunctive relief. On 
August  3,  2021,  Guardant  moved  to  dismiss  the  Company’s  counterclaims,  which  motion  was  denied  in  all  material 
respects. 

In November 2021, a purported class action lawsuit was filed against the Company in the United States District 
Court for the Northern District of California, by a patient alleging various causes of action relating to the Company’s 
patient  billing  and  seeks,  among  other  relief,  class  certification,  injunctive  relief,  restitution  and/or  disgorgement, 
attorneys’ fees, and costs.  

121 

 
 
In February 2022, a purported class action lawsuit was filed against the Company in the United States District 
Court for the Northern District of California, by a patient alleging various causes of action related to the marketing of 
Panorama and seeks, among other relief, class certification, monetary damages, attorneys’ fees, and costs.  

Director and Officer Indemnifications  

As  permitted  under  Delaware  law,  and  as  set  forth  in  the  Company’s  Amended  and  Restated  Certificate  of 
Incorporation and  its  Amended  and  Restated  Bylaws,  the Company indemnifies  its  directors,  executive  officers, other 
officers, employees and other agents for certain events or occurrences that may arise while in such capacity. The maximum 
potential  amount of  future  payments  the  Company  could be required  to make  under  this  indemnification  is unlimited; 
however, the Company has insurance policies that may limit its exposure and may enable it to recover a portion of any 
future amounts paid. Assuming the applicability of coverage, the willingness of the insurer to assume coverage, and subject 
to  certain  retention,  loss  limits  and  other  policy  provisions,  the  Company  believes  any  obligations  under  this 
indemnification would not be material, other than standard retention amounts for securities related claims. However, no 
assurances  can  be  given  that  the  covering  insurers  will  not  attempt  to dispute  the validity,  applicability,  or  amount  of 
coverage without expensive litigation against these insurers, in which case the Company may incur substantial liabilities 
as a result of these indemnification obligations.   

Third-Party Payer Reimbursement Audits  

From time to time, the Company receives recoupment requests from third-party payers for alleged overpayments. 
The Company disagrees with the contentions of pending requests and/or has recorded an estimated reserve for the alleged 
overpayments.   

Contractual Commitments 

The following table sets forth the material unconditional purchase obligations and contractual commitments as 

of December 31, 2021 with a remaining term of at least one year: 

Party 

  Total Commitments

(in thousands)

Material suppliers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Application service providers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Earnouts for development with third party (1)  . . . . . . . . . . . . . . . . .
Software development provider . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Leases (2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other material suppliers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$

16,040
35,279
35,000
4,463
29,683
17,510
137,975

Expiry Date 

June 2026
March 2026
September 2023
December 2024
March 2033
Various

(1)  The earnouts for asset development with the acquired Canadian entity consists of three milestones which are achieved 
upon the satisfaction of certain contractual conditions. Upon achievement, the earnout consideration will primarily be 
paid in the Company’s common stock. 

(2)  Represents executed leases which have not commenced. Please refer to Note 7, Leases, for additional information. 

122 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.    Stock-Based Compensation 

Equity Plans 

2015 Equity Incentive Plan 

General.   The Company’s board of directors adopted its 2015 Equity Incentive Plan, or the 2015 Plan, in June 

2015. The Company’s 2015 Plan replaced all of its prior stock plans.  

Share Reserve.   The initial number of shares of the Company’s common stock available for issuance under the 
2015  Plan  was  3,451,495  shares.  The  number  of  shares  reserved  for  issuance  under  the  2015  Plan  will  be  increased 
automatically on the first business day of each fiscal year, commencing in 2016, by a number equal to the smallest of: 

• 

• 

• 

3,500,000 shares;  

4% of the shares of common stock outstanding on the last business day of the prior fiscal year; or  

the number of shares determined by the Company’s board of directors. 

Stock options vest  as  determined by  the  compensation  committee.  In general,  they will  vest  over  a four-year 
period following the date of grant. Stock options expire at the time determined by the compensation committee but in no 
event more than ten years after they are granted. These awards generally expire earlier if the participant's service terminates 
earlier.  

Restricted Shares and Stock Units.    Restricted shares and stock units may be awarded under the 2015 Plan in 
return for any lawful consideration, and participants who receive restricted shares or stock units generally are not required 
to pay cash for their awards. In general, these awards will be subject to vesting. Vesting may be based on length of service, 
the  attainment  of  performance-based  and  market-based  milestones  or  a  combination  of  both,  as  determined  by  the 
compensation committee.  

2015 Employee Stock Purchase Plan 

General.    The Company’s 2015 Employee Stock Purchase Plan, or 2015 ESPP, was adopted by its board of 
directors in June 2015 and its stockholders approved it in June 2015. The 2015 ESPP is intended to qualify under Section 
423 of the Internal Revenue Code. 

Share Reserve.    The Company has reserved 893,548 shares of its common stock for issuance under the 2015 
ESPP. As of December 31, 2021, 2,859,711 shares were available for issuance under the 2015 ESPP. The number of shares 
reserved  for  issuance  under  the  2015  ESPP  will  automatically  be  increased  on  the  first  business  day  of  each  of  the 
Company’s fiscal years, commencing in 2016, by a number equal to the least of: 

• 

• 

• 

880,000 shares; 

1% of the shares of common stock outstanding on the last business day of the prior fiscal year; or  

the number of shares determined by the Company’s board of directors. 

The number of shares reserved under the 2015 ESPP will automatically be adjusted in the event of a stock split, 

stock dividend or a reverse stock split (including an adjustment to the per-purchase period share limit). 

Purchase Price.    Employees may purchase each share of common stock under the 2015 ESPP at a price equal 
to 85% of the lower of the fair market values of the stock as of the beginning or the end of the six-month offering periods. 
An employee’s payroll deductions under the ESPP are limited to 15% of the compensation, and up to a maximum of 5,000 

123 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
shares may be purchased during any offering period. A participant shall not be granted an option under the ESPP if such 
option would permit the participant’s rights to purchase stock to accrue at a rate exceeding $25,000 fair market value of 
stock for each calendar year in which such option is outstanding at any time. 

Offering Periods.    Each offering period will last a number of months determined by the compensation committee, 
not to exceed 27 months. A new offering period will begin periodically, as determined by the compensation committee. 
Offering periods may overlap or may be consecutive. Unless otherwise determined by the compensation committee, two 
offering periods of six months' duration will begin in each year on May 1 and November 1. 

The following table summarizes the offering activity during the years ended December 31, 2021 and 2020:  

Offering Period 
November 1, 2019 - April 30, 2020 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  
May 1, 2020 - October 31, 2020  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  
November 1, 2020 - April 30, 2021 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  
May 1, 2021 - October 31, 2021  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  

Stock Options 

Number of 
Shares Purchased 

Total  
Proceeds 

(in thousands) 

97,247   
136,288   
106,435   
79,820   

$ 
$ 
$ 
$ 

3,062
4,052
6,085
7,465

The following table summarizes option and RSU activity during the year ended December 31, 2021: 

(in thousands, except for contractual life and exercise price)
Balance at December 31, 2020 . . . . . . . . . . . . . . . . . . . .
Additional shares authorized . . . . . . . . . . . . . . . . . . .
Options granted  . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Options exercised . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Options forfeited/cancelled . . . . . . . . . . . . . . . . . . . .
RSUs granted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RSUs forfeited/cancelled . . . . . . . . . . . . . . . . . . . . . .
Balance at December 31, 2021 . . . . . . . . . . . . . . . . . . . .
Exercisable at December 31, 2021 . . . . . . . . . . . . . . . . .
Vested and expected to vest at December 31, 2021 . . .

3,148
3,446
(391)
—
33
(2,208)
291
4,319

Outstanding Options 

  Weighted-  

      Weighted-      
Average 

Shares 

  Available for  Number of 

Average 
  Remaining  
Exercise    Contractual 

Grant 

Shares 

Price 

Aggregate 
Intrinsic 
Value 

$ 592,468

Life 
(in years)   
 6.04 

6,707

— $

391
(1,165)
(33)

$ 11.19    
—   
$ 104.03   
$ 10.14   
$ 15.00   

5,900
4,977
5,840

$ 17.54    
$ 10.65    
$ 17.17    

 5.40 
 4.90 
 5.37 

$ 451,505
$ 411,841
$ 449,026

The total intrinsic value of stock options exercised during the years ended December 31, 2021, 2020, and 2019 

were $97.0 million, $184.7 million, and $70.0 million, respectively. 

The weighted-average grant date fair value of options granted during the years ended December 31, 2021, 2020, 

and 2019 were $104.03, $27.70 and $8.01 per share, respectively. 

The total fair value of stock options vested during the years ended December 31, 2021, 2020, and 2019 were 

$46.0 million, $52.5 million, and $11.0 million, respectively. 

Performance-based Awards 

124 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
 
    
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The Company grants certain senior-level executives performance stock options and units which vest based on 
either market and time-based service conditions or performance and time-based service conditions, which are referred to 
herein  as  performance-based  awards.  The  Company  has  assessed  the  performance-based  award  with  the  appropriate 
valuation method and has recognized the applicable stock-based compensation expense. The following table summarizes 
the performance-based and market-based awards as of December 31, 2021: 

Period Granted 

  Options Granted 

  RSUs Granted

Q1 2019 . . . .     
Q2 2019 . . . .     
Q3 2019 . . . .    
Q1 2020 . . . .    
Q1 2020 . . . .    
Q1 2020 . . . .    
Q2 2020 . . . .    
Q3 2020 . . . .    
Q3 2020 . . . .    
Q4 2020 . . . .    
Q4 2020 . . . .    
Q1 2021 . . . .    
Q1 2021 . . . .    
Q2 2021 . . . .    
Q2 2021 . . . .    
Q2 2021 . . . .    
Q4 2021 . . . .    
Q4 2021 . . . .    

200   
 —   
 —   
150   
 —   
129   
 —   
10   
 —   
 —   
 —   
150   
 —   
163   
 29   
 —   
 —   
 —   

300
188
50
300
436
—
21
—
27
32
22
125
279
—
—
7
20
205

Options Vested
(in thousands)
200
—
—
130
—
129
—
10
—
—
—
—
—
—
—
—
—
—

RSUs Vested Milestone  

Valuation Method 

300
81
50
289
408
—
21
—
17
19
2
—
10
—
—
—
—
—

(1)
(2)
(1)
(1)
(3)
(3)
(3)
(4)
(3)
(1)
(5)
(1)
(3)
(1)
(3)
(3)
(1)
(3)

  Monte-Carlo Simulation
Fair Market Value
  Monte-Carlo Simulation
  Monte-Carlo Simulation
Fair Market Value

  Black-Scholes-Merton

Fair Market Value

  Black-Scholes-Merton

Fair Market Value
  Monte-Carlo Simulation
Fair Market Value
  Monte-Carlo Simulation
Fair Market Value
  Monte-Carlo Simulation
  Black-Scholes-Merton

Fair Market Value
  Monte-Carlo Simulation
Fair Market Value

(1)  The  awards  vest  based  on  the  achievement  of  certain  values  of  the  Company’s  common  stock  at  multiple 
thresholds within certain periods and are contingent upon the completion of requisite service through the date of 
such vesting. 

(2)  The  vesting  of  the  awards  will  be  triggered  after  the  end  of  the  achievement  milestone,  as  measured  by  the 

Company. 

(3)  The awards vest based on achievement of certain revenue targets, units, and system implementation, contingent 

upon the completion of requisite service through the date of such vesting. 

(4)  The awards have vested based on a change of coverage. 
(5)  The awards will vest based on achievement of certain revenue and recruiting targets.  

The Company has recognized $50.3 million in stock-based compensation for performance-based awards for the 
year ended December 31, 2021 compared to $17.2 million in stock-based compensation for performance-based awards for 
the year ended December 31, 2020. 

The fair value of the performance-based awards with market conditions granted estimated using a Monte Carlo 

simulation model used the following inputs for the years ended December 31, 2021 and 2020: 

Risk-free interest rate  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   0.80 % — 1.52  %  
Expected dividend yield . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  
Expected volatility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  
Expected term (years) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   7.25 — 10.0   

  — 

60 %  

December 31, 
2021 

December 31, 
2020 
  0.54 % — 1.64 %

  — 

55   

65 %

  5.25   — 7.25

125 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
 
Restricted Stock Units 

The following table summarizes restricted stock unit (“RSU”) activity for the year ended December 31, 2021: 

Balance at December 31, 2020 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  
Granted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  
Vested . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  
Canceled/Forfeited . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  

Balance at December 31, 2021 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Stock-Based Compensation Expense 

Weighted- 
Average 
Grant Date 
Fair Value 

Number of 
Shares 
(in thousands) 

 4,188    $ 
 2,208    $ 
 (2,117)  $ 
 (291)  $ 
 3,988    $ 

34.02
106.74
29.46
55.16
74.33

Stock  based  compensation  is  related  to  stock  options  and  RSUs  granted  to  the  Company’s  employees  and  is 
measured at the grant date based on the fair value of the award. The fair value is recognized as expense over the requisite 
service period, which is generally the vesting period of the respective awards on a straight-line basis. No compensation 
cost is recognized when the requisite service has not been met and the awards are therefore forfeited. 

Employee stock-based compensation expense was calculated based on awards ultimately expected to vest and 
has  been  reduced  for  estimated  forfeitures.  Forfeitures  are  estimated  at  the  time  of  grant  and  revised,  if  necessary,  in 
subsequent periods, if actual forfeitures differ from those estimates. Non-employee stock-based compensation expense 
was not adjusted for estimated forfeitures up until the occurrence of the actual forfeiture of the associated awards. 

The following table presents the effect of employee and non-employee stock-based compensation expense on 

selected statements of operations line items for the years ended December 31, 2021, 2020, and 2019. 

     Employee      Non-Employee      Total 

2021 

Year ended December 31,  

2020 

    Employee     Non-Employee     Total 
(in thousands)

    Employee     Non-Employee     Total 

2019 

Cost of  

revenues . . . . . .     $ 

 4,811    $ 

 —    $ 

4,811

$

1,691

$

— $

1,691

$

 905    $ 

32

$

937

Research and 

development . . .    

 24,507   

 1,361   

25,868

10,777

647

11,424

 5,354   

—

5,354

Selling,  

general and 
administrative . .    
Total  . . . . . . . . . .     $ 

 84,368   
 113,686    $ 

 172   
 1,533    $ 

84,540
 115,219

36,747
$ 49,215

$

309
956

37,056
$ 50,171

21,730   
$ 27,989    $ 

603
635

22,333
$ 28,624

As of December 31, 2021, approximately $233.3 million of unrecognized compensation expense, adjusted for 
estimated forfeitures, related to unvested option awards and RSUs will be recognized over a weighted-average period of 
approximately 2.8 years. 

Valuation of Stock Option Grants to Employees and Non-Employees 

The Company utilizes Black-Scholes option pricing model when estimating the fair value of stock options. For 
the  year  ended  December 31,  2021  the following valuation  assumptions  were  applied on both  the  employee  and  non-

126 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
 
 
 
employee options. In the same period of the prior year, the valuation assumptions as follows were only used for stock 
options granted to employees. 

Expected term (years) . . . . . . . . . . . . . . . . . . . . . . . . .
Expected volatility. . . . . . . . . . . . . . . . . . . . . . . . . . . .
Expected dividend rate . . . . . . . . . . . . . . . . . . . . . . . .
Risk-free interest rate  . . . . . . . . . . . . . . . . . . . . . . . . .

Year ended December 31,  
2020 

2021 
5.22 — 10.00   
5.11 — 10.00
55.33% — 63.30% 49.94% — 61.96 %     42.53%— 45.84%
0 %
0.81 % — 1.67 % 0.31 % —  1.70 %     1.60 %— 2.60 %

2019 
   5.23 — 10.00

 0  % 

0 %

As of December 31, 2021, total options outstanding include 31,553 shares of option awards that were granted to 
non-employees, of which 730 shares are unvested. Stock-based compensation expense related to stock options granted to 
non-employees is recognized as the stock option is earned and the services are rendered. The Company believes that the 
estimated fair value of the stock options is more readily measurable than the fair value of the services rendered. 

10.    Debt 

Credit Line Agreement 

In September 2015, the Company entered into a credit line with UBS (the “Credit Line”) providing for a $50.0 
million revolving line of credit which can be drawn down in increments at any time. The Credit Line was amended in July 
2017 and bears interest at 30-day LIBOR plus 1.10%, and it is secured by a first priority lien and security interest in the 
Company’s money market and marketable securities held in its managed investment account with UBS. UBS has the right 
to demand full or partial payment of the Credit Line Obligations and terminate the Credit Line, in its discretion and without 
cause, at any time.  

For the years ended December 31, 2021, 2020, and 2019, the Company recorded interest expense of $0.6 million, 
$0.8 million, and $1.7 million, respectively. Interest payments totaling $0.6 million, $0.8 million, and $1.7 million had 
been made on the Credit Line during the years ended December 31, 2021, 2020, and 2019, respectively. As of December 
31,  2021,  remaining  accrued  interest  was  $1.1  million,  and  the  total  principal  amount  outstanding  including  accrued 
interest was $49.0 million. 

Convertible Notes 

In April 2020, the Company issued $287.5 million aggregate principal amount of Convertible Notes due 2027 in 
a private placement offering to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as 
amended. The Convertible Notes are senior, unsecured obligations of the Company and bear interest at a rate of 2.25% per 
year, payable in cash semi-annually. The Convertible Notes mature in May 2027, unless earlier converted, repurchased or 
redeemed in accordance with their terms. Upon conversion, the Convertible Notes are convertible into cash, shares of the 
Company’s  common  stock  or  a  combination  of  cash  and  shares  of  the  Company’s  common  stock,  at  the  Company’s 
election. 

The Company received net proceeds from the Convertible Notes of $278.3 million, after deducting the initial 
purchasers’ discounts and debt issuance costs. The Company used approximately $79.2 million of the net proceeds from 
the Convertible Notes offering to repay its obligations under the 2017 Term Loan with OrbiMed. 

The holders of the Convertible Notes may convert all or a portion of their Convertible Notes at their option at any 
time prior to the close of business on the business day immediately preceding February 1, 2027 in multiples of $1,000 
principal amount, under any the following circumstances:   

•  During any fiscal quarter commencing after September 30, 2020 (and only during such fiscal quarter), if the 
last  reported  sale  price  of  the  Company’s  common  stock  for  at  least  20  trading  days  (whether  or  not 
consecutive) during the period of 30 consecutive trading days ending on, and including, the last trading day 

127 

 
 
 
 
 
 
 
 
   
         
          
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
of the immediately preceding fiscal quarter is greater than or equal to 130% of the conversion price on each 
applicable trading day.  

•  During the five business day period after any five consecutive trading day period in which the trading price 
per $1,000 principal amount of Convertible Notes for each trading day of that five-day consecutive trading 
period was less than 98% of the product of the last reported sale price of the Company’s common stock and 
the conversion rate on each such trading day.  
If the Company calls any or all of the Convertible Notes for redemption at any time prior to the close of 
business on the second business day prior to the redemption date.  

• 

•  Upon the occurrence of certain distributions. 
•  Upon the occurrence of specified corporate transactions.  

The Convertible Notes are convertible into shares of the Company’s common stock, par value $0.0001 per share, 
at an initial conversion rate of 25.7785 shares of common stock per $1,000 principal amount of the Convertible Notes, 
which  is  equivalent  to  an  initial  conversion  price  of  approximately  $38.79  per  share  of  common  stock,  convertible  to 
7,411,704 shares of common stock. The conversion rate and corresponding conversion price are subject to adjustment 
upon  the  occurrence  of  certain  events  but  will  not  be  adjusted  for  any  accrued  or  unpaid  interest.  The  holders  of  the 
Convertible Notes who redeem their Convertible Notes in connection with a make-whole fundamental change are, under 
certain circumstances, entitled to an increase in the conversion rate. Additionally, in the event of a fundamental change, 
the holders of the Convertible Notes may require the Company to repurchase for cash all or a portion of their Convertible 
Notes at a price equal to 100% of the principal amount, plus any accrued and unpaid interest. 

The Company may not redeem the Convertible Notes prior to May 2024, and no sinking fund is provided for the 
Convertible Notes. The Company may redeem for cash all or any portion of the Convertible Notes, at the Company’s 
option, on or after May 2024, if the last reported sale price of the Company’s common stock has been at least 130% of the 
conversion price then in effect for at least 20 trading days during any 30 consecutive trading day period ending on the 
trading day immediately preceding the date on which the Company provides notice of redemption. The redemption price 
will be equal to 100% of the principal amount of the Convertible Notes to be redeemed plus accrued and unpaid interest.  

Upon adoption of ASU 2020-06, the Company reallocated all of the debt discount to long-term debt financing. 
The debt discount is amortized to interest expense using the effective interest method, computed to be 2.72%, over the life 
of the Convertible Notes or approximately its seven-year term. The outstanding Convertible Notes balance as of December 
31, 2021 is summarized in the following table: 

Liability Component 

Outstanding Principal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  $ 
Unamortized debt discount and debt issuance cost . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Net carrying amount  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  $ 

287,500
(7,106)
280,394

The following table presents total interest expense recognized related to the Convertible Notes during the year 

ended December 31, 2021: 

December 31,  
2021 
(in thousands)

Cash interest expense 

Contractual interest expense . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  $ 

Non-cash interest expense 

Amortization of debt discount and debt issuance cost. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Total interest expense . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  $ 

December 31,  
2021 
(in thousands)

6,469

1,227
7,696

128 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.     Stockholders’ Equity 

In April 2019, the Company completed an underwritten equity offering to sell 5,263,158 shares of its common 
stock at a price to the public of $19 per share. On April 26, 2019, the Company sold an additional 789,473 shares of its 
common stock to the underwriters at the same price upon their exercise of the option to purchase those shares. Before 
offering expenses of $0.6 million, the Company received proceeds of $108.1 million net of the underwriting discount. 

In  October 2019, the Company completed an underwritten equity offering to sell 5,714,286 shares of its common 
stock at a price to the public of $35 per share. The same day, the Company sold an additional 857,142 shares of its common 
stock to the underwriters at the same price upon their exercise of the option to purchase those shares. Before offering 
expenses of $0.4 million, the Company received proceeds of $216.2 million net of the underwriting discount. 

In  September  2020,  the  Company  completed  an  underwritten  equity  offering  and  sold 4,791,665 shares  of  its 
common stock at a price of $60 per share to the public. Before offering expenses of $0.3 million, the Company received 
proceeds of $271.0 million net of the underwriting discount. 

In July 2021, the Company completed an underwritten equity offering and sold 5,175,000 shares of its common 
stock at a price of $113 per share to the public. Before offering expenses of $0.4 million, the Company received proceeds 
of $551.2 million net of the underwriting discount.  

On September 10, 2021, the Company entered into an agreement with a third party for an asset acquisition where 
the acquired asset was in-process research and development primarily in exchange for an equity consideration payment. 
The total upfront acquisition consideration amounts to $35.6 million composed of the issuance of 276,346 shares of the 
Company's common stock with a fair value of $30.9 million, approximately $3.9 million of cash consideration, assumed 
net liabilities of $0.2 million, as well as $0.6 million of acquisition related legal and accounting costs directly attributable 
to the acquisition of the asset. 

As of December 31, 2021, the Company had 50,000,000 authorized shares of its preferred stock, of which no 
shares were issued and outstanding; and 750,000,000 authorized shares of its common stock, at $0.0001 par value, and 
there were 95,140,000 shares of common stock issued and outstanding. 

129 

 
 
12.    Disposal of Business 

Sale of Evercord 

In September 2019, the Company sold the Evercord business that provides cord blood and cord tissue processing 
and storage services for total estimated consideration of $15.4 million, including $9.7 million in cash, $1.0 million of cash 
deposited  in  a  third-party  escrow  account  recorded  in  short-term  other  receivables,  and  $4.7  million  of  additional 
consideration. The additional consideration is primarily related to the accounts receivable transferred to the buyer. The 
cash held in escrow serve as security for the indemnification obligations of the Company and eligible for release 12 months 
after the closing date. The assets relating to the Evercord services transferred to the buyer had a net book value of $6.2 
million as of the sale date, and consisted of accounts receivables and equipment.  The obligations and liabilities relating 
to the Evercord services transferred to the buyer consisted of deferred revenues of $5.2 million. The sale of the Evercord 
business did not meet criteria to be reported as a discontinued operation, because it did not represent a strategic shift with 
a major effect on the Company’s operations and financial results. The Company recognized a gain of $14.4 million on the 
sale, which was included in Loss from operations in the Consolidated Statements of Operations and Comprehensive Loss. 

The following table summarizes the computation of the gain realized from the disposal of business: 

Proceeds on disposal: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    
Assets sold: 

Accounts receivable, net  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Equipment and inventory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Total assets sold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Liabilities assumed by purchaser: 

Deferred revenues  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Net assets and liabilities sold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Net gain realized on disposal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   

December 31, 
2019 
(in thousands)

$ 

15,377

5,782
419
6,201

5,212
989
14,388

$ 

$ 
$ 

In connection with the sale of the Evercord business, the Company recorded impairment expense on the retained 
assets previously used in this business of $1.7 million in selling, general, and administrative expenses in the consolidated 
statement  of  operations  and  comprehensive  loss.  This  expense  is  comprised  of  $1.2  million  from  the  impairment  of 
leasehold improvements, $0.1 million from the impairment of capitalized software held for internal use, and $0.4 million 
of  right-of-use  asset  from  the  storage  facility  lease.  In  addition,  the  Company  expects  to  incur  $0.4  million  of  exit  or 
disposal activity—$0.1 million of involuntary employee termination benefits were incurred in the third quarter of 2019, 
recorded in selling, general and administrative expense in the consolidated statements of operations and comprehensive 
loss,  and  $0.3  million  of  early  contract  termination  fee  from  biological  sample  processing  and  storage  provider  to  be 
incurred in the next fiscal year. 

130 

 
 
 
 
 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
13.    Income Taxes 

The Company's effective tax rates for the years ended December 31, 2021, 2020, and 2019 differ from the U.S. 

federal statutory rate as follows:  

U.S. federal taxes (benefit) at statutory rate  . .
State tax expense . . . . . . . . . . . . . . . . . . . . . . . .
Research and development credits . . . . . . . . . .
Stock-based compensation . . . . . . . . . . . . . . . .
Foreign tax . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other nondeductible items . . . . . . . . . . . . . . . .
Nondeductible officers' compensation . . . . . . .
Acquisition costs . . . . . . . . . . . . . . . . . . . . . . . .
Change in valuation allowance . . . . . . . . . . . . .
Provision for income taxes . . . . . . . . . . . . . . . .

2021 

2019 

December 31, 
2020 
(in thousands, except percentages) 
  $ (98,931)    (21.00)% $ (48,226)    (21.00)%    $  (25,794)    (21.00)%
(5.38)%
(1.34)%
(6.14)%
1.31  %
0.63  %
0.50 %
— %
33.05  %
1.63 %

(6.20)% (10,672)
(1.95)%
(3,964)
(9.80)% (23,791)
55
0.04  %
792
0.07  %
8,984
5.18 %
—
1.89 %
31.90  % 76,920
98

(4.65)%   
(1.73)%   
(10.36)%   
0.02  %   
0.35  %   
3.91  %   
—  %   
33.50  %   

(29,206)
(9,193)
(46,128)
167
344
24,387
8,901
150,277
618

 (6,607)
 (1,645)
 (7,544)
 1,612
 769
 609
 —
 40,599
 1,999

0.04  %    $ 

0.13 % $

$

During the year ended December 31, 2021, the Company recorded total income tax expense of $0.6 million. The 
Company provides testing to clinics and also licenses its cloud-based software to licensees that are based in a foreign 
country, which contributed to a foreign income tax expense of $0.3 million. Total income tax expense also included a state 
income tax expense of $0.3 million for the year ended December 31, 2021. 

During the year ended December 31, 2020, the Company recorded total income tax expense of $0.1 million. The 
Company provides testing to clinics and also licenses its cloud-based software to licensees that are based in a foreign 
country, which contributed to a foreign income tax expense of $0.1 million. Total income tax expense also included a state 
income  tax  benefit  of  $9,000  for  the  year  ended  December  31,  2020.  During  the  year  ended  December  31,  2019,  the 
Company recorded total income tax expense of $2.0 million, which included a foreign withholding tax expense of $1.9 
million, foreign income tax expense of $0.1 million and state income tax benefit of $0.04 million. 

131 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
     
 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
Deferred income taxes reflect the net tax effects of temporary differences between carrying amounts of assets and 
liabilities for financial reporting purposes and the amounts used for income tax purposes as well as net operating loss and 
tax credit carryforwards. The components of the net deferred income tax assets are as follows: 

December 31, 

2021 

2020 

(in thousands)

Deferred tax assets: 

Net operating loss carryforwards  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Intangibles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Research and development tax credit carryforwards . . . . . . . . . . . . . . . . . . . . . . . . . . .
Reserves and accruals  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lease Liabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Deferred revenue  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Stock-based compensation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total deferred tax assets before valuation allowance . . . . . . . . . . . . . . . . . . . . . . . . . .
Less: valuation allowance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$ 

 315,552    $
 4,443   
 38,725   
 14,098   
 16,843   
 6,363   
 15,928   
 411,952   
 (396,079)  
 15,873   

Deferred tax liabilities: 

Convertible debt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Right-of-use lease assets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Net deferred tax assets  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

 —   
 (15,873)  

$ 

 —    $

177,899
—
24,332
21,770
7,123
6,386
10,673
248,183
(222,521)
25,662

(19,143)
(6,519)
—

The Company established a full valuation allowance against its net deferred tax assets in 2021 and 2020 due to 
the  uncertainty  surrounding  realization  of  these  assets.  The  valuation  allowance  increased  to  $396.1  million  as  of 
December 31, 2021 from $222.5 million as of December 31, 2020 due to current year losses and credits claimed. 

As of December 31, 2021, the Company had federal, state, and foreign net operating loss (“NOLs”) carryforwards 
of approximately $1.3 billion, $796.7 million, and $4.0 million, respectively, which begin to expire in 2027, 2028, and 
2031, respectively, if not utilized. Approximately $950.2 million of federal net operating loss included above can be carried 
forward indefinitely. 

The Company also had federal research and development credit carryforwards of approximately $34.5 million, 
which begin to expire in 2027, and state research and development credit carryforwards of approximately $23.0 million, 
which can be carried forward indefinitely. Realization of these deferred tax assets would require $1.5 billion in taxable 
income to fully utilize. Realization is dependent on generating sufficient taxable income prior to expiration of the loss and 
credit carryforwards.  

Federal,  state  and  foreign  tax  laws  impose  substantial  restrictions  on  the  utilization  of  NOLs  and  credit 
carryforwards in the event of an "ownership change" for tax purpose, as defined in Section 382 of the Internal Revenue 
Code. Accordingly, the Company's ability to utilize these carryforwards may be limited as the result of such ownership 
change. Such a limitation could result in limitation in the use of the NOLs in future years and possibly a reduction of the 
NOLs available.  

132 

 
 
 
 
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
A reconciliation of the beginning and ending amount of gross unrecognized tax benefits is as follows:  

Balance at beginning of year  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Additions based on tax positions related to the current year . . . . . . . . . . . . . . . . .
Additions (reductions) for tax positions of prior years. . . . . . . . . . . . . . . . . . . . . .
Balance at end of year . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2021 

December 31, 
2020 
(in thousands)
 8,619 
 2,889 
 (8)
$ 17,514    $   11,500 

$ 11,500    $ 
6,017   
(3) 

2019 

$

$

7,362
1,426
(169)
8,619

During the years ended December 31, 2021, 2020, and 2019, the amount of unrecognized tax benefits increased 
$6.0 million, $2.9 million, and $1.3 million, respectively, due to additional research and development credits generated 
during  the  year.  As  of  December  31,  2021,  2020,  and  2019,  the  total  amount  of  unrecognized  tax  benefits  was  $17.5 
million,  $11.5  million,  and  $8.6  million,  respectively.  The  reversal  of  the  uncertain  tax  benefits  would  not  affect  the 
Company's effective tax rate to the extent that it continues to maintain a full valuation allowance against its deferred tax 
assets. 

The Company is subject to U.S. federal, state, and foreign income taxes. Tax regulations within each jurisdiction 
are subject to the interpretation of the related tax laws and regulations, and require significant judgment to apply. The 
Company  is  subject  to  U.S.  federal,  state  and  local  tax  examinations  by  tax  authorities  for  all  prior  tax  years  since 
incorporation.  The  Company  does  not  anticipate  significant  changes  to  its  current  uncertain  tax  positions  through 
December 31, 2022. 

The Company recognizes any interest and/or penalties related to income tax matters as a component of income 

tax expense.  As of December 31, 2021, there were no accrued interest and penalties related to uncertain tax positions. 

14.     Net Loss per Share 

Basic net loss per share is computed by dividing the net loss attributable to common stockholders by the weighted-
average  number  of  common  shares  outstanding  for  the  period,  excluding  shares  subject  to  repurchase  and  without 
consideration of potentially dilutive securities. Diluted net loss per share is computed by giving effect to all potentially 
dilutive common shares outstanding for the period. For purposes of this computation, outstanding common stock options, 
and restricted stock units are considered to be common share equivalents. Common share equivalents are excluded from 
the computation in periods in which they have an anti-dilutive effect, unless the consideration of any one of them gives a 
dilutive effect. 

The Convertible Notes are convertible as of December 31, 2021. Upon conversion, the Company has the option 
to pay cash, issue shares of common stock, or any combination thereof for the aggregate amount due upon conversion. If 
converted, the value of the Convertible Notes based on contractual settlement provisions would exceed its principal amount 
by $441.9 million as of December 31, 2021. Since the Company is in a net loss position in the periods presented, the shares 
which would be issued upon conversion of the Convertible Notes are excluded from the net loss per share calculation as 
it would have an antidilutive effect. As such, the 7.4 million shares underlying the conversion option of the Convertible 
Notes will not have an impact on the Company’s diluted earnings per share. If converted, the Company does not intend to 
settle the obligation in cash. 

133 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
     
 
 
 
 
 
 
 
 
 
 
The following table provides the basic and diluted net loss per share computations for the years ended December 

31, 2021, 2020, and 2019: 

2021 

December 31,  
2020 
(in thousands, except per share data)

2019 

Numerator: 
Net loss used to compute net loss per share, basic and diluted . . . . . . . . . . . .

$ (471,716)  $  (229,743)  $ (124,827)

Denominator: 
Weighted-average number of shares used in computing net loss per share, 

basic and diluted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

90,558     

 81,011    

69,555

Net loss per share, basic and diluted  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$

(5.21)  $ 

 (2.84)  $

(1.79)

The  following  table  shows  the  potentially  dilutive  common  stock  equivalents  that  were  excluded  from  the 
computations of diluted net loss per share as their effect would be anti-dilutive, as of December 31, 2021, 2020, and 2019: 

Options to purchase common stock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Restricted stock units  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Employee stock purchase plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Convertible Note . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Estimated earnout shares for an asset acquisition . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2021 

5,898    
3,988   
 33   
7,411   
353   
17,683    

December 31,  
2020 
(in thousands)
 6,707 
 4,188 
 37 
 7,411 
 — 
 18,343 

2019 

8,497
2,404
32
—
—
10,933

15. Subsequent Events 

None. 

ITEM 9. 

CHANGES  IN  AND  DISAGREEMENTS  WITH  ACCOUNTANTS  ON  ACCOUNTING  AND 
FINANCIAL DISCLOSURE 

None. 

ITEM 9A:  CONTROLS AND PROCEDURES 

Evaluation of Disclosure Controls and Procedures 

Our management, with the participation of our Chief Executive Officer and our Chief Financial Officer, evaluated 
the effectiveness 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 a company in the reports that it files 
or submits under the Exchange Act is recorded, processed, summarized and reported, within the time periods specified in 
the  Securities  and  Exchange  Commission’s  rules  and  forms.  Disclosure  controls  and  procedures  include,  without 
limitation, controls and procedures designed to ensure that information required to be disclosed by a company in the reports 
that it files or submits under the Exchange Act is accumulated and communicated to the company’s management, including 
its  principal  executive  and  principal  financial  officers,  as  appropriate  to  allow  timely  decisions  regarding  required 
disclosure.  

134 

 
 
 
 
 
 
 
 
 
 
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
     
    
  
 
  
 
 
 
 
 
 
 
 
 
Based on the evaluation of our disclosure controls and procedures as of December 31, 2021, management has 

concluded that, as of such date, our disclosure controls and procedures were effective at the reasonable assurance level. 

Management’s Annual Report on Internal Control over Financial Reporting 

Management is responsible for establishing and maintaining adequate internal control over financial reporting as 
defined in Rules 13a-15(f) and 15d-15(f) of the Exchange Act. Our internal control over financial reporting is 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.  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. 

Management has evaluated the effectiveness of our internal control over financial reporting as of December 31, 
2021  using  the  criteria  set  forth  in  the  2013  Internal  Control  —  Integrated  Framework issued  by  the  Committee  of 
Sponsoring Organizations of the Treadway Commission, or COSO. Based on our evaluation, management has concluded 
that we maintained effective internal control over financial reporting as of December 31, 2021 based on the COSO criteria. 

The effectiveness of our internal control over financial reporting as of December 31, 2021 has been audited by 
Ernst & Young LLP, an independent registered public accounting firm, as stated in their report which appears in Item 9A 
of this Annual Report on Form 10-K.  

Changes in Internal Control over Financial Reporting 

There were no changes in our internal control over financial reporting identified in connection with the evaluation 
required by Rule 13a-15(d) and 15d-15(d) of the Exchange Act that occurred during the year ended December 31, 2021 
that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting. 

Inherent Limitations on Effectiveness of Controls 

Our  management,  including  our  Chief  Executive  Officer  and  Chief  Financial  Officer,  do  not  expect  that  our 
disclosure controls or our internal control over financial reporting will prevent all errors and all fraud. A control system, 
no matter how well designed and operated, can provide only reasonable, not absolute, assurance that the objectives of the 
control system are met. Further, the design of a control system must reflect the fact that there are resource constraints, and 
the benefits of controls must be considered relative to their costs. Because of the inherent limitations in all control systems, 
no evaluation of controls can provide absolute assurance that all control issues and instances of fraud, if any, have been 
detected.  These  inherent  limitations  include  the  realities  that  judgments  in  decision-making  can  be  faulty,  and  that 
breakdowns can occur because of a simple error or mistake. Additionally, controls can be circumvented by the individual 
acts of some persons, by collusion of two or more people or by management override of the controls. The design of any 
system of controls is also based in part upon certain assumptions about the likelihood of future events, and there can be no 
assurance that any design will succeed in achieving its stated goals under all potential future conditions; over time, controls 
may become inadequate because of changes in conditions, or the degree of compliance with policies or procedures may 
deteriorate. Because of the inherent limitations in a cost-effective control system, misstatements due to error or fraud may 
occur and not be detected.  

135 

 
 
 
 
 
 
 
 
 
 
REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM  

To the Board of Directors and Stockholders of Natera, Inc. 

Opinion on Internal Control Over Financial Reporting 
We  have  audited  Natera,  Inc.’s  internal  control  over  financial  reporting  as  of December 31,  2021,  based  on  criteria 
established  in  Internal  Control—Integrated  Framework  issued  by  the  Committee  of  Sponsoring  Organizations  of  the 
Treadway Commission (2013 framework), (the COSO criteria). In our opinion, Natera, Inc. (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 2021 consolidated financial statements of the Company and our report dated February 24, 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 Management’s 
Annual 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 the U.S. federal securities laws and 
the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB. 

We conducted our audit 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, testing and evaluating the design and operating effectiveness of internal control based on the assessed 
risk, and 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/ Ernst & Young LLP 

Redwood City, California 
February 24, 2022 

136 

  
  
 
 
 
 
 
 
 
 
 
ITEM 9B.  OTHER INFORMATION  

None. 

PART III 

ITEM 10.  DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 

The information required by this item will be contained in our definitive proxy statement to be filed with the 
Securities and Exchange Commission in connection with our 2021 annual meeting of stockholders (the “Proxy Statement”), 
which we expect to file no later than 120 days after the end of our fiscal year ended December 31, 2021, and is incorporated 
in this report by reference.  

ITEM 11.  EXECUTIVE COMPENSATION 

The information required by this item will be contained in the Proxy Statement, which we expect to file no later 

than 120 days after the end of our fiscal year ended December 31, 2021, and is incorporated in this report by reference. 

ITEM 12.  SECURITY  OWNERSHIP  OF  CERTAIN  BENEFICIAL  OWNERS  AND  MANAGEMENT  AND 

RELATED STOCKHOLDER MATTERS 

The information required by this item will be contained in the Proxy Statement, which we expect to file no later 

than 120 days after the end of our fiscal year ended December 31, 2021, and is incorporated in this report by reference. 

ITEM 13.  CERTAIN  RELATIONSHIPS  AND  RELATED  TRANSACTIONS,  AND  DIRECTOR 

INDEPENDENCE 

The information required by this item will be contained in the Proxy Statement, which we expect to file no later 

than 120 days after the end of our fiscal year ended December 31, 2021, and is incorporated in this report by reference. 

ITEM 14.  PRINCIPAL ACCOUNTING FEES AND SERVICES 

The information required by this item will be contained in the Proxy Statement, which we expect to file no later 

than 120 days after the end of our fiscal year ended December 31, 2021, and is incorporated in this report by reference. 

137 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PART IV 

ITEM 15.  EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 

(a)  The following documents are filed as part of this Annual Report on Form 10-K: 

(1)  Financial Statements (included in Part II of this report): 

•  Report of Independent Registered Public Accounting Firm 

•  Balance Sheets 

•  Statement of Operations 

•  Statement of Stockholders’ Equity  

•  Statement of Cash Flows 

•  Notes to Financial Statements 

(2)  Financial Statement Schedules: 

All financial statement schedules are omitted because the information is inapplicable or presented 
in the notes to the financial statements. 

(b)  The following exhibits are filed with or incorporated by reference as part of this Annual Report on Form 10-

K: 

INDEX TO EXHIBITS 

Exhibit No. 

Description 

Form 

File No. 

Exhibit 

Filing Date 

Filed 
Herewith 

Incorporated by Reference 

3.1 

3.2 

4.1 

4.2 

4.3 

4.4 

Amended and Restated Certificate of 
Incorporation of Registrant. 

Amended and Restated Bylaws of 
Registrant, effective as of November 3, 
2021 

8-K 

001-37478 

3.1 

07/09/2015 

10-Q 

001-37478 

3.1 

11/05/2021 

Form of Common Stock Certificate 

S-1/A 

Amended and Restated Investors' Rights 
Agreement, dated November 20, 2014. 

S-1 

333-
204622 

333-
204622 

Description of Common Stock 

10-K 

001-37478 

4.1 

4.2 

4.3 

06/22/2015 

06/01/2015 

02/26/2021 

Indenture (including form of Note) with 
respect to the Company’s 2.25% 
Convertible Senior Notes due 2027, dated 
as of April 16, 2020, between the 
Registrant and Wilmington Trust, National 
Association, as trustee 

8-K 

001-37478 

4.1 

04/16/2020 

10.1* 

2007 Stock Plan and form of agreements 
thereunder. 

S-1 

333-
204622 

10.1 

06/01/2015 

138 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Exhibit No. 

10.2* 

Description 
2015 Equity Incentive Plan and forms of 
agreements thereunder. 

Form

File No.

Exhibit

Filing Date 

10-K 

001-37478 

10.2 

03/24/2016 

10.3* 

2015 Employee Stock Purchase Plan. 

S-1/A 

333-
204622 

10.3 

06/25/2015 

Filed 
Herewith

Incorporated by Reference 

10.4 

10.5.1** 

10.5.2** 

10.5.3** 

10.5.4** 

10.5.5*** 

10.5.6*** 

10.5.7*** 

10.6.1** 

10.6.2** 

10.6.3** 

10.6.4** 

10.7.1* 

Form of Indemnification Agreement, by 
and between Registrant and each of its 
directors and executive officers. 

Supply Agreement, dated September 18, 
2014, by and between Registrant and 
Illumina, Inc., as amended (conformed 
copy). 

Second Amendment to Supply Agreement, 
dated September 21, 2015, by and between 
Registrant and Illumina, Inc. 

Third Amendment to Supply Agreement, 
dated June 8, 2016, by and between 
Registrant and Illumina, Inc. 

Fourth Amendment to Supply Agreement, 
dated January 3, 2019, by and between 
Registrant and Illumina, Inc. 

Fifth Amendment to Supply Agreement, 
dated December 18, 2019, by and between 
Registrant and Illumina, Inc. 

Sixth Amendment to Supply 
Agreement, dated May 8, 2020, by and 
between Registrant and Illumina, Inc. 

Seventh Amendment to Supply 
Agreement, dated October 7, 2021, by and 
between the Registrant and Illumina, Inc. 

Application Service Provider Agreement, 
dated September 19, 2014, by and between 
Registrant and DNAnexus, Inc., as 
amended 

Third Amendment to Application Service 
Provider Agreement, dated January 1, 
2018, by and between Registrant and 
DNAnexus, Inc. 

Fourth Amendment to Application Service 
Provider Agreement, dated July 1, 2018, 
by and between Registrant and 
DNAnexus, Inc. 

Fifth Amendment to Application Service 
Provider Agreement, dated October 18, 
2019, by and between Registrant and 
DNAnexus, Inc. 

Amended Employment Agreement, by and 
between Registrant and Matthew 
Rabinowitz, dated June 7, 2007. 

10-K 

001-37478 

10.4 

03/16/2017 

S-1/A 

333-
204622 

10.13 

06/30/2015 

10-Q 

001-37478 

10.1 

08/11/2016 

10-Q 

001-37478 

10.2 

08/11/2016 

10-K 

001-37478 

10.8 

03/15/2019 

10-K 

001-37478 

10.5.5 

03/02/2020 

10-Q 

001-37478 

10.1 

08/07/2020 

10-Q 

001-37478 

10.1 

11/05/2021 

10-K 

001-37478 

10.11 

03/16/2017 

10-Q 

001-37478 

10.1 

11/09/2018 

10-Q 

001-37478 

10.2 

11/09/2018 

10-Q 

001-37478 

10.2 

11/08/2019 

S-1/A 

333-
204622 

10.15 

06/25/2015 

139 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Exhibit No. 

10.7.2* 

10.8* 

10.9* 

10.10* 

10.11.1 

10.11.2 

10.12* 

10.13.1 

10.13.2 

10.14.1** 

10.14.2** 

10.14.3** 

10.14.4** 

10.15** 

Description 
Amended Employment Agreement, by and 
between Registrant and Matthew 
Rabinowitz, dated May 9, 2021. 

Amended Employment Agreement, by and 
between Registrant and Jonathan Sheena, 
dated June 7, 2007. 

Amended and Restated Employment 
Agreement, by and between Registrant 
and Steve Chapman, dated January 2, 
2019. 

Amended Compensation Program for 
Non-Employee Directors. 

UBS Credit Line Agreement, dated 
September 23, 2015, as amended. 

Amendment to UBS Credit Line 
Agreement, dated July 5, 2017. 

Natera, Inc. Management Cash Incentive 
Plan. 

Lease, dated October 26, 2015, by and 
between Registrant and BMR-201 
Industrial Road LP. 

First Amendment to Lease, dated October 
6, 2016, by and between Registrant and 
BMR-201 Industrial Road LP. 

Credit Agreement, dated as of August 8, 
2017, by and between Registrant and 
OrbiMed Royalty Opportunities II, LP. 

Amendment and Waiver to Credit 
Agreement, dated as of December 28, 
2018, by and between Registrant, Natera 
International, Inc., NSTX, Inc. and 
OrbiMed Royalty Opportunities II, LP. 

Second Amendment to Credit Agreement, 
dated as of April 15, 2019, by and between 
Registrant, Natera International, Inc., 
NSTX, Inc. and OrbiMed Royalty 
Opportunities II, LP. 

Third Amendment to Credit Agreement, 
dated as of September 12, 2019, by and 
between Registrant, Natera International, 
Inc., NSTX, Inc. and OrbiMed Royalty 
Opportunities II, LP. 

Pledge and Security Agreement, dated as 
of August 8, 2017, by and between 
Registrant, Natera International, Inc., 
NSTX, Inc. and OrbiMed Royalty 
Opportunities II, LP. 

Incorporated by Reference 

Form

File No.

Exhibit

Filing Date 

Filed 
Herewith

8-K 

001-37478 

10.2 

05/10/2021 

S-1/A 

333-
204622 

10.16 

06/25/2015 

10-Q 

001-37478 

10.1 

05/10/2019 

10-Q 

001-37478 

10.2 

05/10/2019  

10-Q 

001-37478 

10.2 

11/12/2015 

10-Q 

001-37478 

10.1 

08/09/2017 

10-Q 

001-37478 

10.3 

11/12/2015 

10-K 

001-37478 

10.23 

03/23/2016 

10-Q 

001-37478 

10.1 

11/10/2016 

10-Q 

001-37478 

10.1 

11/09/2017 

10-K 

001-37478 

10.20 

03/15/2019 

10-Q 

001-37478 

10.3 

05/10/2019 

10-Q 

001-37478 

10.1 

11/08/2019 

10-Q 

001-37478 

10.2 

11/09/2017 

140 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Exhibit No. 

10.16 

10.17** 

Description 
Guarantee, dated as of August 8, 2017, by 
and between Natera International, Inc., 
NSTX, Inc. and OrbiMed Royalty 
Opportunities II, LP. 

License, Development and Distribution 
Agreement, dated as of March 9, 2018, by 
and between Registrant and QIAGEN 
LLC 

Incorporated by Reference 

Form

File No.

Exhibit

Filing Date 

Filed 
Herewith

10-Q 

001-37478 

10.3 

11/09/2017 

10-Q/A 

001-37478 

10.1 

02/06/2019 

21.1 

23.1 

24.1 

31.1 

31.2 

32.1† 

32.2† 

101.INS 

101.SCH 

101.CAL 

101.DEF 

101.LAB 

101.PRE 

104 

List of Subsidiaries of the Registrant. 

10-K 

001-37478 

21.1 

03/16/2017 

Consent of Independent Registered Public 
Accounting Firm. 

Power of Attorney (see signature page of 
this Annual Report on Form 10-K). 

Certification of Principal Executive 
Officer required by Rule 13a-14(a) or Rule 
15d-14(a) of the Securities Exchange Act 
of 1934, as adopted pursuant to Section 
302 of the Sarbanes-Oxley Act of 2002. 

Certification of Principal Financial Officer 
pursuant to Rule 13a-14(a) or Rule 15d-
14(a) of the Securities Exchange Act of 
1934, as adopted pursuant to Section 302 
of the Sarbanes-Oxley Act of 2002. 

Certification of Chief Executive Officer 
pursuant to 18 U.S.C. Section 1350, as 
adopted pursuant to Section 906 of the 
Sarbanes-Oxley Act of 2002. 

Certification of Chief Financial Officer 
pursuant to 18 U.S.C. Section 1350, as 
adopted pursuant to Section 906 of the 
Sarbanes-Oxley Act of 2002. 

XBRL Instance Document - the instance 
document does not appear in the 
Interactive Data File because its XBRL 
tags are embedded within the Inline XBRL 
document. 

XBRL Taxonomy Extension Schema 
Document. 

XBRL Taxonomy Extension Calculation 
Linkbase Document. 

XBRL Taxonomy Extension Definition 
Linkbase Document. 

XBRL Taxonomy Extension Label 
Linkbase Document. 

XBRL Taxonomy Extension Presentation 
Linkbase Document. 

Cover Page Interactive Data File 
(formatted as Inline XBRL and contained 
in Exhibit 101) 

141 

X 

X 

X 

X 

X 

X 

X 

X 

X 

X 

X 

X 

X 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* 

Indicates a management contract or compensatory plan. 

**   Portions of this exhibit (indicated by asterisks) have been omitted pursuant to an order granting confidential treatment. 

Omitted portions have been submitted separately to the Securities and Exchange Commission (SEC). 

*** Portions of this exhibit (indicated by asterisks) have been omitted pursuant to a request for confidential treatment. 

†  The certifications attached as Exhibits 32.1 and 32.2 that accompany this Annual Report on Form 10-K are not deemed 
filed with the SEC and are not to be incorporated by reference into any filing of Natera, Inc. under the Securities Act 
of 1933, as amended, or the Securities Exchange Act of 1934, as amended, whether made before or after the date of 
this Annual Report on Form 10-K, regardless of any general incorporation language contained in any filing. 

ITEM 16.  FORM 10-K SUMMARY 

None. 

142 

 
 
 
 
 
 
 
Consent of Independent Registered Public Accounting Firm 

We consent to the incorporation by reference in the following Registration Statements: 

(1)  Registration Statements (Form S-8 Nos. 333-205441, 333-210374, 333-216747, 333-223751, 333-230324, 333-
236873, and 333-253785) pertaining to the 2015 Equity Incentive Plan, 2007 Stock Plan and 2015 Employee 
Stock Purchase Plan of Natera, Inc., and 

(2)  Registration Statements (Forms S-3 No. 333-214577, 333-230902, 333-234220, 333-248690, 333-258047, and 

333-259429) of Natera, Inc., 

of  our  reports  dated  February  24,  2022,  with  respect  to  the  consolidated  financial  statements  of  Natera,  Inc.  and  the 
effectiveness of the internal control over financial reporting of Natera, Inc. included in this Annual Report (Form 10-K) 
of Natera, Inc. for the year ended December 31, 2021.  

/s/ Ernst & Young LLP  

Redwood City, California  
February 24, 2022 

143 

 
 
 
 
 
 
 
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this Annual 
Report on Form 10-K to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Austin, State 
of Texas, on this 24th day of February, 2022.  

SIGNATURES  

Natera, Inc. 

/ s /    Michael Brophy 
Michael Brophy 
Chief Financial Officer 

144 

 
 
 
 
 
 
 
 
 
POWER OF ATTORNEY  

KNOW  ALL  PERSONS  BY  THESE  PRESENTS,  that  each  person  whose  signature  appears  below  hereby 
constitutes and appoints Steve Chapman and Michael Brophy as his or her true and lawful attorney-in-fact and agent with 
full power of substitution, for him or her in any and all capacities, to sign 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 attorney-in-fact and agent full power and authority to do and 
perform each and every act and thing requisite and necessary to be done in connection therewith, as fully for all intents 
and purposes as he might or could do in person, hereby ratifying and confirming all that said attorney-in-fact and agent, 
or his substitute, may lawfully do or cause to be done by virtue hereof.  

Pursuant  to  the  requirements  of  the  Securities  Exchange  Act  of  1934,  as  amended,  this  Annual  Report  on  

Form 10-K has been signed by the following persons in the capacities and on the dates indicated.  

Signature 

/ s /    Steve Chapman 
Steve Chapman 

/ s /    Michael Brophy 
Michael Brophy 

/ s /    Matthew Rabinowitz 
Matthew Rabinowitz 

/ s /    Jonathan Sheena 
Jonathan Sheena 

/ s /    Roy Baynes 
Roy Baynes 

/ s /    Monica Bertagnolli 
Monica Bertagnolli 

/ s /    Roelof F. Botha 
Roelof F. Botha 

/ s /    Rowan Chapman 
Rowan Chapman 

/ s /    Todd Cozzens 
Todd Cozzens 

/ s /    James I. Healy 
James I. Healy 

/ s /    Gail Marcus 
Gail Marcus 

/ s /    Herm Rosenman 
Herm Rosenman 

Title

Chief Executive Officer, President and 
Director 
(Principal Executive Officer) 

Chief Financial Officer 
(Principal Financial Officer and Principal 
Accounting Officer) 

Date

February 24, 2022 

February 24, 2022 

Executive Chairman 

February 24, 2022 

Founder and Director 

February 24, 2022 

February 24, 2022 

February 24, 2022 

February 24, 2022 

February 24, 2022 

February 24, 2022 

February 24, 2022 

February 24, 2022 

February 24, 2022 

Director 

Director 

Director 

Director 

Director 

Director 

Director 

Director 

145 

 
 
 
 
  
  
 
 
 
 
 
  
  
 
  
  
 
  
  
 
  
  
 
 
 
 
 
 
  
  
 
  
  
 
 
 
  
  
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Natera, Inc.
Natera, Inc.

13011 McCallen Pass
13011 McCallen Pass

Building A Suite 100
Building A Suite 100

Austin, TX 78753
Austin, TX 78753

(650)(cid:3)249(cid:3)9090(cid:3)
www.natera.com(cid:3)