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OPKO Health, Inc.

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FY2015 Annual Report · OPKO Health, Inc.
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Our product candidates may have undesirable side effects and cause our approved products to be taken off the market

2 0 1 5   A N N U A L   R E P O R T  

 
UNITED STATES 
SECURITIES AND EXCHANGE COMMISSION 
WASHINGTON, DC 20549 

FORM 10-K 

(Mark One) 
(cid:58)(cid:3) ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE 

ACT OF 1934 

(cid:133)(cid:3) TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES 

EXCHANGE ACT OF 1934 

For the fiscal year ended December 31, 2015. 
OR 

For the transition period from                      to                     . 
Commission file number 001-33528 

OPKO Health, Inc. 
(Exact Name of Registrant as Specified in Its Charter) 

Delaware 
(State or Other Jurisdiction of Incorporation or Organization) 

75-2402409 
(I.R.S. Employer Identification No.)

4400 Biscayne Blvd., Miami, FL 33137 
(Address of Principal Executive Offices) (Zip Code) 

(Registrant’s Telephone Number, Including Area Code): (305) 575-4100 

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

Title of Each Class 
Common Stock, $.01 par value per share 

Name of Each Exchange on Which Registered 
New York Stock Exchange 

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  (cid:58)(cid:3)No  (cid:133) 
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act.     
Yes  (cid:133)    No  (cid:58) 
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  (cid:58)    No  (cid:133) 

Indicate by check mark whether the Registrant has submitted electronically and posted on its corporate Web site, if any, every 
Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T during the preceding 12 months 
(or for such shorter period that the registrant was required to submit and post such files).    Yes  (cid:58)    No  (cid:133) 

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and 
will  not  be  contained,  to  the  best  of  registrant’s  knowledge,  in  definitive  proxy  or  information  statements  incorporated  by 
reference in Part III of this Form 10-K or any amendment to this Form 10-K.  (cid:133) 

Indicate  by  check  mark  whether  the  registrant  is  a  large  accelerated  filer,  an  accelerated  filer,  a  non-accelerated  filer,  or  a 
smaller reporting company.  See the definitions of “large accelerated filer,” “accelerated filer” and “smaller reporting company” 
in Rule 12b-2 of the Exchange Act. 
(in Rule 12b-2 of the Exchange Act) (Check one):
Large accelerated filer  (cid:58)(cid:3)
Non-accelerated filer  (cid:133)(cid:3)(Do not check if a smaller reporting company)(cid:3)

Accelerated filer 
(cid:134)(cid:3)
Smaller reporting company (cid:133)(cid:3)

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act).    Yes  (cid:133)    No  (cid:58) 
The aggregate market value of the voting and non-voting common equity held by non-affiliates computed by reference to the 
price at which the common equity was last sold, as of the last business day of the registrant’s most recently completed second 
fiscal quarter was: $3,877,294,326. 

As of February 16, 2016, the registrant had 545,696,849 shares of Common Stock outstanding. 

Portions of the registrant’s definitive proxy statement for its 2016 Annual Meeting of Stockholders are incorporated by 

reference in Items 10, 11, 12, 13, and 14 of Part III of this Annual Report on Form 10-K. 

Documents Incorporated by Reference 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
TABLE OF CONTENTS 

Part I. 

Item 1. 

Business 

Item 1A. 

Risk Factors 

Item 1B. 

Unresolved Staff Comments 

Item 2. 

Properties 

Item 3. 

Legal Proceedings 

Item 4. 

Mine Safety Disclosures 

Part II. 

Item 5. 

Market for Registrant’s Common Equity, Related Stockholder Matters and  

Issuer Purchases of Equity Securities 

Item 6. 

Selected Financial Data 

Item 7. 

Management’s Discussion and Analysis of Financial Condition and 

Results of Operations 

Item 7A. 

Quantitative and Qualitative Disclosures about Market Risk 

Item 8. 

Financial Statements and Supplementary Data 

Item 9. 

Changes in and Disagreements with Accountants on Accounting and 

Financial Disclosure 

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, Financial Statement Schedules 

Signatures 

Certifications 

EX-21 

EX-23.1 

EX23.2 

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Page 

7 

26 

57 

57 

58 

59 

60 

62 

63 

77 

79 

130 

130 

131 

132 

132 

132 

132 

132 

133 

138 

143 

 
 
 
 
 
 
 
EX-31.1 

EX-31.2 

EX-32.1 

EX-32.2 

EX-101. INS XBRL Instance Document 

EX-101.SCH XBRL Taxonomy Extension Schema Document 

EX-101.CAL XBRL Taxonomy Extension Calculation Linkbase Document 

EX-101.DEF XBRL Taxonomy Extension Definition Linkbase Document 

EX-101.LAB XBRL Taxonomy Extension Label Linkbase Document 

EX-101.PRE XBRL Taxonomy Extension Presentation Linkbase Document

4 

 
 
CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS 

This  Annual  Report  on  Form  10-K  contains  “forward-looking  statements,”  as  that  term  is  defined  under  the 
Private  Securities  Litigation  Reform  Act  of  1995  (“PSLRA”),  Section  27A  of  the  Securities  Act  of  1933,  as 
amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements include 
statements  about  our  expectations,  beliefs  or  intentions  regarding  our  product  development  efforts,  business, 
financial condition, results of operations, strategies or prospects. You can identify forward-looking statements by the 
fact that these statements do not relate strictly to historical or current matters. Rather, forward-looking statements 
relate to anticipated or expected events, activities, trends or results as of the date they are made. Because forward-
looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and 
uncertainties that could cause our actual results to differ materially from any future results expressed or implied by 
the forward-looking statements. Many factors could cause our actual activities or results to differ materially from the 
activities and results anticipated in forward-looking statements. These factors include those described below and in 
“Item 1A-Risk Factors” of this Annual Report on Form 10-K. We do not undertake an obligation to update forward-
looking  statements.  We  intend  that  all  forward-looking  statements  be  subject  to  the  safe-harbor  provisions  of  the 
PSLRA. These forward-looking statements are only predictions and reflect our views as of the date they are made 
with respect to future events and financial performance. 

Risks and uncertainties, the occurrence of which could adversely affect our business, include the following: 

(cid:120)  we have a history of losses and may not become profitable in the near future;  

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the risks inherent in funding, developing and obtaining regulatory approvals of new, commercially-
viable and competitive products and treatments;  

our research and development activities may not result in commercially viable products; 

that earlier clinical results of effectiveness and safety may not be reproducible or indicative of future 
results;  

that we may fail to obtain regulatory approval for or successfully commercialize Rayaldee and hGH-
CTP; 

that we may not generate profits or cash flow from our laboratory operations or substantial revenue 
from our diagnostic products;  

that  currently  available  over-the-counter  and  prescription  products,  as  well  as  products  under 
development by others, may prove to be as or more effective than our products for the indications 
being studied; 

our ability to develop a pharmaceutical sales and marketing infrastructure; 

our  ability  and  our  distribution  and  marketing  partners’  ability  to  comply  with  regulatory 
requirements  regarding  the  sales,  marketing  and  manufacturing  of  our  products  and  product 
candidates and the operation of our laboratories;  

the performance of our third-party distribution partners, licensees and manufacturers over which we 
have limited control; 

our  success  is  dependent  on  the  involvement  and  continued  efforts  of  our  Chairman  and  Chief 
Executive Officer;  

integration challenges for Bio-Reference, EirGen and other acquired businesses; 

changes  in  regulation  and  policies  in  the  United  States  and  other  countries,  including  increasing 
downward pressure on health care reimbursement; 

our ability to manage our growth and our expanded operations; 

increased competition, including price competition; 

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(cid:120) 

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changing  relationships  with  payers,  including  the  various  state  and  multi-state  Blues  programs, 
suppliers and strategic partners;  

efforts by third-party payors to reduce utilization and reimbursement for clinical testing services; 

failure to timely or accurately bill for our services; 

failure  to  obtain  and  retain  new  clients  and  business  partners,  or  a  reduction  in  tests  ordered  or 
specimens submitted by existing clients; 

failure to establish, and perform to, appropriate quality standards to assure that the highest level of 
quality is observed in the performance of our testing services; 

failure to maintain the security of patient-related information; 

our ability to obtain and maintain intellectual property protection for our products;  

our ability to defend our intellectual property rights with respect to our products;  

our ability to operate our business without infringing the intellectual property rights of others;  

our ability to attract and retain key scientific and management personnel;  

our need for, and ability to obtain, additional financing; 

adverse results in material litigation matters or governmental inquiries; 

failure to obtain and maintain regulatory approval outside the U.S.; and 

legal,  economic,  political,  regulatory,  currency  exchange,  and  other  risks  associated  with 
international operations. 

6 

 
 
Unless  the  context  otherwise  requires,  all  references  in  this  Annual  Report  on  Form  10-K  to  the  “Company”, 
“OPKO”, “we”, “our”, “ours”, and “us” refer to OPKO Health, Inc., a Delaware corporation, including our wholly-
owned subsidiaries. 

PART I 

ITEM 1.  BUSINESS 

OVERVIEW 

We are a diversified healthcare company that seeks to establish industry-leading positions in large and rapidly 
growing  medical  markets.    Our  diagnostics  business  includes  Bio-Reference  Laboratories  (“Bio-Reference”),  the 
nation’s third-largest clinical laboratory with a core genetic testing business and a 420-person sales force to drive 
growth  and  leverage  new  products,  including  the  4Kscore  prostate  cancer  test  and  the  Claros  1  in-office 
immunoassay  platform. 
treatment  for  secondary 
  Our  pharmaceutical  business  features  Rayaldee,  a 
hyperparathyroidism  (“SHPT”)  in  patients  with  stage  3  or  4  chronic  kidney  disease  (“CKD”)  and  vitamin  D 
insufficiency (target March 29, 2016 PDUFA date) and VARUBI™ for chemotherapy-induced nausea and vomiting 
(launched by partner TESARO in November 2015).  Our pharmaceutical business includes OPKO Biologics, which 
features hGH-CTP, a once-weekly human growth hormone injection (in Phase 3 and partnered with Pfizer), and a 
longer acting Factor VIIa drug for hemophilia (Phase 2a). 

In  addition  to  our  pharmaceutical  and  diagnostic  development  programs,  we  own  established  pharmaceutical 
platforms  in  Ireland,  Chile,  Spain  and  Mexico  which  generate  revenue  and  which  we  expect  to  facilitate  future 
market  entry  for  our  products  currently  in  development.    We  have  a  development  and  commercial  supply 
pharmaceutical  company,  as  well  as  a  global  supply  chain  operation  and  holding  company  in  Ireland,  which  we 
expect will play an important role in the development, manufacturing, distribution and approval of a wide variety of 
drugs  with  an  emphasis  on  high  potency  products.    We  also  own  a  specialty  active  pharmaceutical  ingredients 
(“APIs”) manufacturer in Israel, which we expect will facilitate the development of our pipeline of molecules and 
compounds for our proprietary molecular diagnostic and therapeutic products. 

We  have  a  highly  experienced  management  team  that  we  believe  has  demonstrated  an  ability  to  successfully 
build and manage pharmaceutical and healthcare businesses.  Based on their experience in the industry, we believe 
that our management team has extensive development, regulatory and commercialization expertise and relationships 
that provide access to commercial opportunities. 

All product or service marks appearing in type form different from that of the surrounding text are trademarks or 
service marks owned, licensed to, promoted or distributed by OPKO, its subsidiaries or affiliates, except as noted.  
All other trademarks or services marks are those of their respective owners. 

GROWTH STRATEGY 

We expect our future growth to come from leveraging our commercial infrastructure, proprietary technology and 
development  strengths,  and  by  opportunistically  pursuing  complementary,  accretive,  or  strategic  acquisitions  and 
investments. 

We have under development a broad and diversified portfolio of diagnostic tests, vaccines, small molecules, and 
biologics  targeting  a  broad  range  of  unmet  medical  needs.    We  also  operate  the  third  largest  full  service  clinical 
laboratory in the United States.  We intend to continue to leverage our proprietary technology and our strengths in 
all  phases  of  research  and  development  to  further  develop  and  commercialize  our  portfolio  of  proprietary 
pharmaceutical and diagnostic products.  In support of our strategy, we intend to: 

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obtain  requisite  regulatory  approval  and  compile  clinical  data  for  our  most  advanced  product 
candidates; 

develop a focused commercialization capability both internationally and in the U.S.; and  

expand  into  other  medical  markets  that  provide  significant  opportunities  and  that  we  believe  are 
complementary to and synergistic with our business.  

In addition, we expect to leverage the Bio-Reference business and infrastructure to drive rapid and widespread 
uptake of our diagnostic products, including the 4Kscore test and the Claros 1 in-office immunoassay platform.  We 

7 

 
also  intend  to leverage  the  genetic  and genomic  data generated  and  accumulated  through  Bio-Reference’s  genetic 
sequencing laboratory to enhance drug discovery and clinical trial programs. 

We  have  and  expect  to  continue  to  be  opportunistic  and  to  pursue  complementary  or  strategic  acquisitions, 
licenses and investments.  Our management team has significant experience in identifying, executing and integrating 
these  transactions.    We  expect  to  use  well-timed,  carefully  selected  acquisitions,  licenses  and  investments  to 
continue to drive our growth, including: 

(cid:120)  Products  and  technologies.   We  intend  to  continue  to  pursue  product  and  technology  acquisitions 
and  licenses  that  will  complement  our  existing  businesses  and  provide  new  product  and  market 
opportunities,  enhance  our  profitability,  leverage  our  existing  assets,  and  contribute  to  our  own 
organic growth. 

(cid:120)  Commercial businesses.  We intend to continue to pursue acquisitions of commercial businesses that 
will both drive our growth and provide geographically diverse sales and distribution opportunities. 

(cid:120)  Early stage investments.  We have and may continue to make investments in early stage companies 
that we perceive to have valuable proprietary technology and significant potential to create value for 
OPKO as a shareholder. 

CORPORATE INFORMATION 

We were originally incorporated in Delaware in October 1991 under the name Cytoclonal Pharmaceutics, Inc., 
which was later changed to eXegenics, Inc. (“eXegenics”).  On March 27, 2007, we were part of a three-way merger 
with Froptix Corporation (“Froptix”) and Acuity Pharmaceuticals, Inc. (“Acuity”), both research and development 
companies.  On June 8, 2007, we changed our name to OPKO Health, Inc.  Our shares are publicly traded on the 
NYSE under the ticker “OPK” and on the Tel Aviv Stock Exchange.  Our principal executive offices are located in 
leased office space in Miami, Florida. 

We  currently  manage  our  operations  in  two  reportable  segments,  diagnostics  and  pharmaceutical.    The 
pharmaceutical segment consists of our pharmaceutical operations we acquired in Chile, Mexico, Ireland, Israel and 
Spain and our pharmaceutical research and development operations.  The diagnostics segment primarily consists of 
our  clinical  laboratory  operations  we  acquired  through  the  acquisitions of  Bio-Reference  and  OPKO  Lab  and  our 
point-of-care  operations.    There  are  no  significant  inter-segment  sales.    We  evaluate  the  performance  of  each 
segment  based  on  operating  profit  or  loss.    There  is  no  inter-segment  allocation  of  interest  expense  and  income 
taxes.  Refer to Note 16 for financial information about the segments and geographic areas. 

CURRENT PRODUCTS AND SERVICES AND RELATED MARKETS 

Diagnostics 

Bio-Reference Laboratories  

In August 2015, we completed the acquisition of Bio-Reference, the third largest full service clinical laboratory 
in the United States.  Through Bio-Reference, we now offer comprehensive laboratory testing services utilized by 
healthcare providers in the detection, diagnosis, evaluation, monitoring, and treatment of diseases, including esoteric 
testing,  molecular  diagnostics,  anatomical  pathology,  genetics,  women’s  health  and  correctional  healthcare.    We 
market and sell these services to physician offices, clinics, hospitals, employers and governmental units nationally, 
with the largest concentration of business in the larger metropolitan areas across New York, New Jersey, Maryland, 
Pennsylvania, Delaware, Washington DC, Florida, California, Texas, Illinois and Massachusetts.  Bio-Reference has 
a 420-person sales force and operates a network of more than 180 patient service centers for collection of patient 
specimens. 

Our  Bio-Reference  laboratory  testing  business  consists  of  routine  testing  and  esoteric  testing.    Routine  tests 
measure  various  health  parameters,  such  as  the  functions  of  the  heart,  kidney,  liver,  thyroid  and  other  organs, 
including such tests as blood cell counts, cholesterol levels, pregnancy, substance abuse and urinalysis.  These tests 
are primarily performed at our main processing facility in Elmwood Park, New Jersey, as well as satellite facilities 
in Florida, Texas, Maryland, Ohio, New York and Connecticut.  We typically operate 24 hours per day, 365 days per 
year and perform and report most routine test results within 24 hours. 

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 The  esoteric  tests  we  perform  require  sophisticated  equipment  and  materials,  highly  skilled  personnel  and 
professional  attention.    Esoteric  tests  are  ordered  less  frequently  than  routine  tests  but  typically  are  priced  higher 
than  routine  tests.    Esoteric  tests  include  tests  related  to  endocrinology,  genetics  and  genomics,  immunology, 
microbiology,  HIV  tests,  molecular  diagnostics,  oncology,  serology,  and  toxicology.    We  perform  cancer 
cytogenetic testing at our main processing facility  in Elmwood Park, and at our facilities in Clarksburg, MD, and 
Milford,  MA,  and  genetic  testing  at  our  GeneDx  facility  in  Gaithersburg,  MD,  as  well  as  at  our  Elmwood  Park 
facility.  We perform cytology testing in Frederik, MD, Milford, MA, Columbus, OH, Houston, TX, Melbourne, FL 
and Campbell, CA, and at our Elmwood Park facility. 

Through Bio-Reference, we operate in the following highly specialized laboratory divisions: 

(cid:120)  Bio-Reference Laboratories.  Bio-Reference constitutes our core clinical testing laboratory offering 
automated, high volume routine testing services, STAT testing, informatics, HIV, Hep C and other 
molecular tests. 

(cid:120)  GenPath  (Oncology).    National  Oncology  presence  with  expertise  in  cancer  pathology  and 
diagnostics, as well as molecular diagnostics.  Core tests include FLOW, IHC, MicroArray,  FISH, 
ISH, Morphology, full service oncology. 

(cid:120)  GenPath (Women’s Health).  Innovative technology platform for sexually transmitted infections has 
enabled  expansion  nationally  with  specimens  coming  from  48  contiguous  states,  including  Image 
Directed Paps, HPV Plus, and STI Testing. 

(cid:120)  GeneDx.    Industry  leading  national  laboratory  for  testing  rare  and  ultra-rare  genetic  diseases  with 

international reach, performing testings on specimens from more than 50 countries. 

(cid:120)  Laboratorio  Bueno  Salud.    National  testing  laboratory  dedicated  to  serving  the  Spanish-speaking 
population  in  the  United  States,  where  all  business  is  conducted  in  Spanish  including  patient  and 
physician interaction. 

We  have  one of  the  largest marketing  staffs  of  any  laboratory  in  the  country  with  sales  and  marketing groups 
dedicated to urology, oncology, women’s health, genetic testing and correctional health, as well as cross-over groups 
selling to large institutions.  All of our sales and marketing personnel operate in a dual capacity, as both marketing 
and client support representatives, which we believe provides better customer service and a strong connection with 
our customers. 

We expect the clinical laboratory testing industry will continue to experience growth in testing volumes due to 
aging of the population in the U.S., patient awareness of the value of laboratory tests, a decrease in the cost of tests, 
the  development  of  sophisticated  and  specialized  tests  for  detection  and  management  of  disease,  increased 
recognition  of  early  detection  and  prevention  as  a  means  of  reducing  healthcare  costs,  and  ongoing  research  and 
development in genetics and genomics and personalized medicine.  Our mission is to be recognized by our clients as 
the premier provider of clinical laboratory testing, information and related services. 

Bio-Reference  provides  us  a  significant  diagnostics  commercial  infrastructure  for  marketing  and  sales  that 
reaches more than 10 million patients a year.  In addition, its large team of managed care experts complement our 
efforts to ensure that payors recognize the value of our diagnostic and laboratory tests for reimbursement purposes.  
Since  the  acquisition  of  Bio-Reference,  we  have  begun  to  leverage  the  national  marketing,  sales  and  distribution 
resources of  Bio-Reference, along with  its  420-person  sales  force,  to  enhance  sales  of  and  reimbursement  for  our 
4Kscore test, a laboratory developed blood test that provides a personalized risk score for aggressive prostate cancer.  
We  plan  to  continue  to  leverage  the  Bio-Reference  commercial  infrastructure  and  capabilities,  as  well  as  its 
extensive  relationships  with  payers,  to  commercialize  OPKO’s  other  diagnostic  products  under  development, 
including the Claros 1. 

4Kscore 

We began selling the 4Kscore test in the U.S. in March 2014 and in Europe and Mexico in September 2014 and 
January 2015, respectively.  The 4Kscore test is a laboratory developed test that measures the blood plasma levels of 
four  different  prostate-derived  kallikrein  proteins:  Total  PSA,  Free  PSA,  Intact  PSA  and  Human  Kallikrein-2 
(“hK2”).    These  biomarkers  are  then  combined  with  a  patient’s  age,  DRE  status  (nodule  /  no  nodule),  and  prior 
negative biopsy status (yes / no) using a proprietary algorithm to calculate the risk (probability) of finding a Gleason 

9 

 
 
Score 7 or higher prostate cancer.  The four kallikrein panel of biomarkers utilized in the 4Kscore test is based on 
decades  of  research  conducted  by  scientists  at  Memorial  Sloan-Kettering  Cancer  Center  and  leading  European 
institutions.  Investigators at the University of Malmo, Sweden, University of Turku, Finland and Memorial Sloan 
Kettering Cancer Center, New York, have also demonstrated that an algorithm integrating these biomarkers along 
with patient data can predict prostate biopsy results to identify patients with the greatest risk of having aggressive 
prostate cancer. 

The 4Kscore test was developed by OPKO Lab and validated in 2014 in a prospective, blinded study of 1,012 
men  in  collaboration  with  26  urology  centers  across  the  U.S.    Results  showed  that  the  4Kscore  test  was  highly 
accurate for predicting the presence of high-grade cancer (Gleason score 7 or higher) prior to prostate biopsy.  The 
full data from the blinded, prospective U.S. clinical validation study were presented at the AUA Annual Meeting in 
Orlando,  FL  on  May 18,  2014  at  Plenary  Session  and  published  in  the  online  edition  of  European  Urology  in 
October 2014. 

The  clinical  data  presented  at  the  AUA  annual  meeting  included  1,012  men  scheduled  for  prostate  biopsy.  
Patients  were  enrolled  regardless  of  their  PSA,  age,  DRE  result,  or  primary  versus  repeat  biopsy  status,  and 
represent contemporary practice in the U.S.  The results demonstrated the ability of the 4Kscore test to discriminate 
between men with high-grade, aggressive prostate cancer and those men who had no findings of cancer or had low-
grade or indolent form of the disease.  The discrimination, measured by Area Under the Curve (“AUC”) analysis, 
was 0.82 and was significantly higher than previously developed tests.  Furthermore, the 4Kscore test demonstrated 
excellent risk calibration, indicating the accuracy of the result for an individual patient.  The high value of AUC and 
the  excellent  risk  calibration  make  the  4Kscore  test  result  valuable  information  for  the  shared  decision-making 
between the urologist and patient on whether or not to perform a prostate biopsy. 

A  recent  study  indicated  that  the  4Kscore  test  led  to  64.6%  fewer  biopsies.    The  study,  “The  4Kscore®  Test 
Reduces  Prostate  Biopsy  Rates  in  Community  and  Academic  Urology  Practices”,  published  in  the  January  2016 
edition of Reviews in Urology, which included 611 patients seen by 35 academic and community urologists across 
the  U.S.,  evaluated  the  influence  of  the  4Kscore  test  on  urologist-patient  decisions  about  whether  to  perform  a 
biopsy in men who had an abnormal PSA and or DRE result.  Test results for patients were stratified into low risk (< 
7.5%), intermediate risk (7.5%-19.9%) and high risk ((cid:149)20%) for developing aggressive prostate cancer.  Nearly half 
(49.3%)  of  the  men  were  categorized  as  low  risk;  25.7%  and  25.0%  fell  into  the  intermediate-risk  and  high-risk 
categories, respectively.  Notably, the 4Kscore test results influenced biopsy decisions in 88.7% of the men.  In the 
three risk groups, a biopsy was avoided in 94.0%, 52.9%, and 19.0% of men in the low, intermediate, and high-risk 
categories, respectively. 

We  have  been  granted  a  Category  I  CPT  code  by  the  AMA  for  our  4Kscore  test,  which  will  be  published  in 
August 2016 and effective January 1, 2017.  This upgrades the 4Kscore test from a Category III Administrative code 
to a Category I CPT code, a designation reserved for established diagnostic tests.  CPT codes are used by insurance 
companies  and  government  payers  to  describe  health  care  services  and  procedures,  and  having  a  Category  I  CPT 
code  is  critical  to  facilitate  reimbursement  in  government  programs  such  as  Medicare  and  Medicaid,  as  well  as 
private  insurance  programs.    We  believe  having  the  Category  I  CPT  code  will  help  facilitate  obtaining  broader 
coverage from payers for the 4Kscore test and allow greater access to the test for a broader group of patients across 
the U.S. 

The National Comprehensive Cancer Network (“NCCN”) also included the 4Kscore test as a recommended test 
in their  2015  Guidelines  for  Prostate  Cancer  Early  Detection.    The  panel  making  this  recommendation  concluded 
that the 4Kscore test is indicated for use prior to a first prostate biopsy, or after a negative biopsy, to assist patients 
and physicians in further defining the probability of high-grade cancer. 

As a result of our leveraging the Bio-Reference commercial infrastructure and managed care expertise, together 
with the NCCN Guidelines publication and receipt of a Category I CPT Code, we expect to significantly expand our 
efforts to obtain broad reimbursement for the 4Kscore test throughout 2016 and beyond. 

Point-of-Care Diagnostics 

OPKO  Diagnostics,  LLC  (“OPKO  Diagnostics”),  formerly  Claros  Diagnostics,  Inc.,  is  developing  a  novel 
diagnostic  instrument  system  to  provide  rapid,  high  performance  blood  test  results  and  enable  tests  to  be  run  in 
point-of-care settings.  The instrument, a microfluidics-based diagnostic test system consisting of a credit card-sized 
disposable  test  cassette  that  works  with  a  small  but  sophisticated  desktop  analyzer,  provides  high  performance 

10 

 
 
quantitative blood test results within minutes and permits the transition of complex immunoassays and other tests 
from the centralized reference laboratory to the physician’s office or hospital nurses station.  The technology only 
requires  a  finger  stick  drop of  blood  introduced  into  the  test  cassette  which  can  simultaneously  run multiple  tests 
(multiplex) on the single droplet of blood. 

We have already obtained a CE Mark for the Claros 1 point-of-care analyzer and a diagnostic test for prostate 
specific  antigen  (“PSA”)  performed  on  the  Claros  1.   We  intend  to  update  our  CE  Mark  with  all  product 
improvements made to the Claros 1 and Sangia Total PSA test since the initial CE mark approval and introduce the 
Claros 1 system for PSA in Europe in 2016. 

We intend to commence clinical trials and submit our application to the FDA for a pre-marketing authorization 
(“PMA”)  for  the  PSA  test  in  late  2016  or  early  2017.    We  also  intend  to  submit  our  application  to  the  FDA  for 
clearance of a testosterone diagnostic test for our point-of-care system in late 2016 or early 2017.  We expect to fully 
leverage  Bio-Reference’s  marketing,  sales  and  distribution  resources  for  the  launch  of  the  Claros  1  system  and 
associated diagnostic tests in the U.S after FDA clearance or approval. 

We are also presently working to add additional tests for our point-of-care system, including vitamin D, and we 
believe that there are many more applications for the technology, including infectious disease, cardiology, women’s 
health, and companion diagnostics. 

Pharmaceutical Business 

We presently have several pharmaceutical compounds and technologies in research and development for a broad 
range of indications and conditions.  Our product development candidates are in various stages of development and 
include the following: 

Renal Products 

Our two lead renal products are Rayaldee (CTAP101), a vitamin D prohormone to treat SHPT in patients with 
stage 3 or 4 CKD and vitamin D insufficiency, and Alpharen (Fermagate Tablets), a new and potent non-absorbed 
phosphate  binder  to  treat  hyperphosphatemia  in  Stage  5  patients  on  chronic  hemodialysis.    In  May  2015,  we 
submitted an NDA for Rayaldee to the FDA.  Our NDA was accepted by the FDA for review in July 2015 and the 
FDA set a PDUFA target date of March 29, 2016.  We announced successful top-line results from two pivotal phase 
3  trials  of  Rayaldee  in  the  third  quarter  of  2014.    These  trials  were  identical  randomized,  double-blind,  placebo-
controlled, multi-site studies intended to establish the safety and efficacy of Rayaldee as a new treatment for SHPT 
in patients with stage 3 or 4 CKD and vitamin D insufficiency. 

Vitamin  D  insufficiency  arises  in  CKD  due  to  the  abnormal  upregulation  of  CYP24,  an  enzyme  that  destroys 
vitamin D and its metabolites.  Studies in CKD patients have demonstrated that currently available over-the-counter 
and prescription vitamin D products cannot reliably raise blood vitamin D prohormone levels and effectively treat 
SHPT, a condition commonly associated with CKD in which the parathyroid glands secrete excessive amounts of 
parathyroid hormone (“PTH”).  Prolonged elevation of blood PTH causes excessive calcium and phosphorus to be 
released from bone, leading to elevated serum calcium and phosphorus levels, softening of the bones (osteomalacia) 
and  calcification  of  vascular  and  renal  tissues.    SHPT  affects  40-82%  of  patients  with  stage  3  or  4  CKD  and 
approximately 95% of patients with stage 5. 

The  completed  pivotal  trials  for  Rayaldee  successfully  met  all  primary  efficacy  and  safety  endpoints.    The 
primary efficacy endpoint was a responder analysis in which “responder” was defined as any treated subject who 
demonstrated an average 30% decrease in PTH from pre-treatment baseline during the last six weeks of the 26-week 
treatment period.  A significantly higher response rate was observed with  Rayaldee which steadily increased with 
treatment duration.  The response rate with Rayaldee was similar in CKD stages 3 and 4.  Safety and tolerability 
data  were  comparable  in  both  treatment  groups.    Patients  completing  the  two  pivotal  trials  were  treated,  at  their 
election, for an additional six months with Rayaldee during an open-label extension study. 

In  addition  to  SHPT  in  CKD  patients,  we  also  are  developing  Rayaldee  for  other  indications,  and  in  August 
2014,  announced  the  submission  of  an  IND  to  the  FDA  to  evaluate  Rayaldee  as  an  adjunctive  therapy  for  the 
prevention  of  skeletal-related  events  in  patients  with  bone  metastases  undergoing  anti-resorptive  therapy.    We 
commenced a phase 1 dose escalation study in the fourth quarter of 2014 in breast and prostate cancer patients with 
bone  metastases  who  are  receiving  anti-resorptive  therapy.    The  study  is  evaluating  safety,  markers  of  mineral 
metabolism and tumor progression. 

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Our  phosphate  binder,  Alpharen  (Fermagate  Tablets),  has  been  shown  to  be  safe  and  effective  in  treating 
hyperphosphatemia  in  phase  2  and  3  trials  in  stage  5  CKD  patients  undergoing  chronic  hemodialysis.  
Hyperphosphatemia,  or  elevated  serum  phosphorus,  is  common  in  dialysis  patients  and  tightly  linked  to  the 
progression  of  SHPT.    The  kidneys  provide  the  primary  route  of  excretion  for  excess  phosphorus  absorbed  from 
ingested food.  As kidney function worsens, serum phosphorus levels increase and directly stimulate PTH secretion.  
Stage  5  CKD  patients  must  reduce  their  dietary  phosphate  intake  and  usually  require  regular  treatment  with 
phosphate  binding  agents  to  lower  serum  phosphorus  to  meet  the  recommendations  of  the  National  Kidney 
Foundation’s  Clinical  Practice  Guidelines  that  serum  phosphorus  levels  should  be  maintained  at  or  below  5.5 
mg/dL.    Hyperphosphatemia  contributes  to  soft  tissue  mineralization  and  affects  approximately  90%  of  dialysis 
patients.    Dialysis  patients  require  ongoing  phosphate  binder  treatment  to  maintain  controlled  serum  phosphorus 
levels.  We are currently preparing a single remaining Phase 3 clinical trial in the U.S., but are first studying novel 
characteristics of Alpharen which may offer additional competitive advantages. 

We believe the CKD patient population is large and growing as a result of obesity, hypertension and diabetes; 
therefore  this  patient  population  represents  a  significant  market  opportunity.    According  to  the  National  Kidney 
Foundation, CKD afflicts over 26 million people in the U.S., including more than 20 million patients with stage 3 or 
4 CKD.  In stage 5, kidney function is minimal to absent and patients require regular dialysis or a kidney transplant 
for survival.  An estimated 71-97% of CKD patients have vitamin D insufficiency which can lead to SHPT and its 
debilitating consequences.  CKD continues to be associated with poor outcomes, reflecting the inadequacies of the 
current standard of  care.   Vitamin  D  insufficiency,  hyperphosphatemia  and SHPT,  when  inadequately  treated,  are 
major contributors to poor CKD outcomes.  We intend to develop Rayaldee and Alpharen to constitute part of the 
foundation  for  a  new  and  markedly  improved  standard  of  care  for  CKD  patients  having  SHPT  and/or 
hyperphosphatemia. 

OPKO Biologics 

OPKO  Biologics  is  our  biopharmaceutical  business  focused  on  developing  and  commercializing  longer-acting 
proprietary versions of already approved therapeutic proteins.  One of our innovative platform technologies uses a 
short, naturally-occurring amino acid sequence (carboxl terminal peptide or “CTP”) that has the effect of slowing 
the removal from the body of the therapeutic protein to which it is attached.  This CTP can be readily attached to a 
wide array of existing therapeutic proteins, stabilizing the therapeutic protein in the bloodstream and extending its 
life  span  without  additional  toxicity  or  loss  of  desired  biological  activity.    We  are  using  the  CTP  technology  to 
develop new, proprietary versions of certain existing therapeutic proteins that have longer life spans than therapeutic 
proteins  without  CTP.    We  believe  that  our  products  will  have  greatly  improved  therapeutic  profiles  and  distinct 
market advantages. 

There are two existing biopharmaceuticals on the market that currently utilize CTP technology.  The first product 
is human chorionic gonadotropin (“hCG”), of which CTP is naturally a part.  Besides being present normally in high 
amounts during pregnancy, it is also given therapeutically to women or men as a fertility treatment (sold by Merck-
Serono, Merck & Co. and Ferring).  The second product is ELONVA® (FSH-CTP), which is sold by Merck & Co.  
The data from the clinical and therapeutic use of these products gave us confidence that the CTP technology is able 
to address the major problems faced by the other attempted approaches to increase protein lifespan.  Clinical and 
therapeutic  data  from  these  products  also  reassured  us  that  CTP  can  be  used  safely  and  that  it  is  effective  in 
extending the serum lifetime and activity.  We are the exclusive licensee for the utilization of CTP technology in all 
therapeutic proteins, peptides and their modified forms except for human FSH, LH, TSH and hCG. 

Our  lead  product  candidate  utilizing  CTP,  hGH-CTP,  is  a recombinant  human  growth  hormone  product  under 
development  for  the  treatment  of  growth  hormone  deficiency  (“GHD”),  which  is  a  pituitary  disorder  resulting  in 
short stature in children and other physical ailments in both children and adults. 

In  December  2014,  we  entered  into  an  exclusive  worldwide  agreement  with  Pfizer  for  the  development  and 
commercialization  of  hGH-CTP  for  the  treatment  of  GHD  in  adults  and  children,  as  well  as  for  the  treatment  of 
growth failure in children born SGA.  In connection with the transaction, we granted Pfizer an exclusive license to 
commercialize hGH-CTP worldwide, and we received non-refundable and non-creditable upfront payments of $295 
million  and  are  eligible  to  receive  up  to  an  additional  $275  million  upon  the  achievement  of  certain  regulatory 
milestones.    In  addition,  we  are  eligible  to  receive  initial  tiered  royalty  payments  associated  with  the 
commercialization of hGH-CTP for Adult GHD with percentage rates ranging from the high teens to mid-twenties.  
Upon the launch of hGH-CTP for Pediatric GHD in certain major markets, the royalties will transition to regional, 
tiered gross profit sharing for both hGH-CTP and Pfizer’s Genotropin®. 

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Pursuant to our agreement with Pfizer, we will lead the clinical development activities for the hGH-CTP program 
and  will  be  responsible  for  funding  the  development  programs  for  the  key  indications,  which  includes  Adult  and 
Pediatric GHD and Pediatric SGA.  Pfizer will be responsible for all development costs for additional indications as 
well as all post-marketing studies.  In addition, Pfizer will fund the commercialization activities for all indications 
and lead the manufacturing activities covered by the global development plan. 

GHD occurs when the production of growth hormone, secreted by the pituitary gland, is disrupted.  Since growth 
hormone  plays  a  critical  role  in  stimulating  body  growth  and  development,  and  is  involved  in  the  production  of 
muscle protein and in the breakdown of fats, a decrease in the hormone affects numerous body processes.  hGH is 
used for the long-term treatment of children and adults with inadequate secretion of endogenous growth hormone.  
The primary indications it treats in children are GHD, SGA, kidney disease, Prader-Willi Syndrome and Turner’s 
Syndrome.  In adults, the primary indications are replacement of endogenous growth hormone and the treatment of 
AIDS-induced  weight  loss.    Patients  using  hGH  receive  daily  injections  six  or  seven  times  a  week.    This  is 
particularly  burdensome  for  pediatric  patients.    We  believe  a  significant  market  opportunity  exists  for  a  longer-
lasting version of hGH that would require fewer injections. 

hGH-CTP is currently in a global Phase 3 trial in adults and a global phase 2 trial in children and has orphan 
drug designation in the U.S. and Europe for both adults and children with GHD.  We anticipate commencing our 
global phase 3 trial in children in the second half of 2016. 

In addition to hGH-CTP, we are developing a product to extend the life span of Factor VIIa (hemophilia) using 
the CTP technology.  In February 2013, the FDA granted orphan drug designation to our longer-acting version of 
clotting  Factor  VIIa,  Factor VIIa-CTP,  for the  treatment  of bleeding  episodes  in  patients  with hemophilia  A  or  B 
with  inhibitors  to  Factor  VIII  or  Factor  IX.    These  patients  are  currently  being  treated  by  commercially-available 
Factor VIIa, with estimated 2013 worldwide sales of $1.7 billion.  Currently, Factor VIIa therapy is available only as 
an  intravenous  (IV)  formulation  which,  due  to  Factor  VIIa’s  short  half-life,  requires  multiple  infusions  to  treat  a 
bleeding  episode.    In  addition,  frequent  infusions  are  onerous  when  used  as  preventative  prophylactic  therapy, 
especially for children. 

Pre-clinical  studies  of  IV  and  subcutaneous  formulations  of  our  product  in  hemophilic  animal  models 
demonstrated its duration of action and significantly increased survival.  In January 2015, we submitted an IND to 
the FDA to conduct a Phase 2a study of Factor VIIa-CTP for the treatment of bleeding episodes in hemophilia A or 
B patients with inhibitors to Factor VIII or Factor IX, which was accepted by the FDA in March 2015.  The Phase 
2a study commenced in February 2016.  Factor VIIa-CTP has been granted orphan designation in Europe as well as 
the U.S. 

We believe that the CTP technology may also be broadly applicable to other best-selling therapeutic proteins in 
the market and provide several key advantages over our competitor’s existing products: significant reduction in the 
number  of  injections  required  to  achieve  the  same  or  superior  therapeutic  effect  from  the  same  dosage;  faster 
commercialization  with  greater  chance  of  success  and  lower  costs  than  those  typically  associated  with  a  new 
therapeutic protein; and manufacturing using industry-standard biotechnology-based protein production processes. 

In addition to hGH-CTP and Factor VII-CTP, our internal product development program is currently focused on 
extending  the  circulatory  half  life  of  oxyntomodulin.    Oxyntomodulin,  a  natural  appetite  suppressor,  is  a  peptide 
hormone  secreted  by  the  intestine  following  food  intake  that  induces  satiety  when  it  reaches  the  brain.  
Oxyntomodulin  activates  both  the  glucagon-like  peptide-1  receptor  (“GLP1R”)  and  glucagon  receptor  (“GCGR”) 
and  has  been  found  to  decrease  food  intake  and  body  weight  as  well  as  lower  glucose  in  overweight  human 
volunteers. 

We believe oxyntomodulin has potential to be a safe, long term therapy for obese and diabetes type II patients, 
representing significant market opportunities.  More than 380 million are living with diabetes worldwide, of which 
approximately  90% have  type  II  diabetes.  According  to  the World  Health Organization,  there  are  more  than 500 
million severely overweight or obese people. 

The clinical utility of oxyntomodulin has been limited mostly because of its short circulating half life.  We are 
developing  a  long-acting  oxyntomodulin  comprising  oxyntomodulin  linked  at  its  N-terminus  to  a  polyethylene 
glycol (“PEG”) linear chain through a proprietary bi-functional hydrolysable linker.  Administration of the conjugate 
into  the  blood  results  in  slow  release  of  the    non-modified  natural  oxyntomodulin.    Our  preclinical  studies  have 
shown  that  a  single  weekly  injection  of  our  compound  in  development  significantly  inhibited  food  intake  and 

13 

 
 
reduced  body  weight  in  obese  and  diabetic  animal  models,  as  well  as  improving  the  lipid  profile  by  reducing 
cholesterol levels in obese and diabetic mice.  We expect to initiate a phase 1 study of oxyntomodulin in the first 
quarter of 2016. 

APIs 

FineTech  Pharmaceutical,  Ltd.  (“FineTech”),  is  our  Israeli-based  subsidiary  that  develops  and  produces  high 
value,  high  potency  specialty  APIs.    Through  its  FDA  registered  facility  in  Nesher,  Israel,  FineTech  currently 
manufactures  commercial  APIs  for  sale  or  license  to  pharmaceutical  companies  in  the  U.S.,  Canada,  Europe  and 
Israel.    We  believe  that  FineTech’s  significant  know-how  and  experience  with  analytical  chemistry  and  organic 
syntheses, together with its production capabilities, may play a valuable role in the development of our pipeline of 
proprietary molecules and compounds for diagnostic and therapeutic products, while providing revenues and profits 
from its existing API business. 

Oligonucleotide Therapeutics 

OPKO CURNA, LLC (“CURNA”), previously CURNA Inc., is engaged in the discovery of new drugs for the 
treatment of a wide variety of illnesses, including cancer, heart disease, metabolic disorders and a range of genetic 
anomalies.  CURNA’s broad platform technology utilizes a short, single strand oligonucleotide and is based on the 
up-regulation of protein production through interference with non-coding RNA’s, or natural antisense.  This strategy 
contrasts with established approaches which down-regulate protein production.  CURNA has designed a novel type 
of  therapeutic  modality,  termed  AntagoNAT,  and  has  initially  demonstrated  this  approach  for  up-regulation  of 
several  therapeutically  relevant  proteins  in  in  vitro  and  animal  models.    We  believe  that  this  short,  single  strand 
oligonucleotide  can  be  delivered  intravenously  or  subcutaneously  without  the  drug  delivery  or  cell  penetration 
complications typically associated with double stranded siRNA therapeutics.  CURNA has identified and developed 
compounds which increase the production of over 80 key proteins involved in a large number of individual diseases.  
We  have  ongoing  pre-clinical  studies  for  several  of  these  compounds,  with  an  initial  focus  on  orphan  diseases 
including Dravet Syndrome, Rett Syndrome and MPS-1. 

NK-1 Program 

We  acquired  rolapitant  and  other  neurokinin-1  (“NK-1”)  assets  from  Merck  &  Co.    In  December  2010,  we 
exclusively  out-licensed  the  development,  manufacture  and  commercialization  of  our  lead  NK-1  candidate, 
VARUBI™  (rolapitant),  to  TESARO.    VARUBI™,  a  potent  and  selective  competitive  antagonist  of  the  NK-1 
receptor,  had  successfully  completed  phase  2  clinical  testing  for  prevention  of  chemotherapy  induced  nausea  and 
vomiting, or CINV, and post-operative induced nausea and vomiting.  TESARO submitted its NDA to the FDA for 
approval of oral VARUBI™ in September 2014.  TESARO’s NDA for oral VARUBI™ was approved by the FDA in 
September 2015, and in November 2015, TESARO commenced the commercial launch of VARUBI™ in the United 
States. 

Under the terms of the license, we received a $6.0 million upfront payment from TESARO and are eligible to 
receive  milestone  payments  of  up  to  $30.0  million  upon  achievement  of  certain  regulatory  and  commercial  sale 
milestones (of which $20.0 million has been paid to date) and additional commercial milestone payments of up to 
$85.0  million  if  specified  levels  of  annual  net  sales  are  achieved.    TESARO  is  also  obligated  to  pay  us  tiered 
royalties on annual net sales achieved in the United States and Europe at percentage rates that range from the low 
double digits to the low twenties, and outside of the United States and Europe at low double-digit percentage rates.  
TESARO  assumed  responsibility  for  clinical  development  and  commercialization  of  licensed  products  at  its 
expense.  Under the agreement, we will continue to receive royalties on a county-by-country and product-by-product 
basis  until  the  later  of  the  date  that  all  of  the  patents  rights  licensed  from  us  and  covering  rolapitant  expire,  are 
invalidated or are not enforceable, and 12 years from the date of the first commercial sale of the product. 

If TESARO elects to develop and commercialize VARUBI™ in Japan through a third-party licensee, TESARO 
will share equally with us all amounts it receives in connection with such activities, subject to certain exceptions and 
deductions.  In addition, we will have an option to market the products in Latin America.  The term of the license 
will remain in force until the expiration of the royalty term unless we terminate the license earlier for TESARO’s 
material breach of the license or bankruptcy.  TESARO has a right to terminate the license during the term for any 
reason on three month’s written notice. 

14 

 
 
Asthma and COPD 

In  May  2010,  we  acquired  worldwide  rights  to  a  novel  heparin-derived  oligosaccharide  which  has  significant 
potential in treating asthma and chronic obstructive pulmonary disease (“COPD”).  Over 22 million people in the 
U.S. live with asthma, including nearly 6 million children.  Additionally, there are more than 12 million people in 
the U.S. who have COPD.  Currently available therapies often include unwanted side effects and may have limited 
efficacy.  We believe that our product may have an improved efficacy and side effect profile.  Our initial studies 
have demonstrated anti-inflammatory and anti-allergic activity when administered orally or inhaled with inhalers or 
nebulizers  in  sheep  and  mice  asthma  models.    We  have  also  successfully  completed  human  feasibility  studies  in 
asthma. 

To complement our portfolio of respiratory products, we acquired Inspiro Medical Ltd., a medical device firm 
developing a new platform to deliver small molecule drugs like corticosteroids and beta agonists or larger molecules 
to  treat  respiratory  disease.    Inspiro’s  Inspiromatic  is  a  “smart”  easy-to-use  dry  powder  inhaler  with  several 
advantages over existing devices.  In a First In Man double blinded clinical study conducted in 30 asthmatic children 
comparing  Inspiromatic  to  a  market  leading  dry  powder  inhaler,  Inspiromatic  demonstrated  superior  pulmonary 
delivery of the active drug. 

Commercial Operations 

We  also  intend  to  continue  to  leverage  our  global  commercialization  expertise  to  pursue  acquisitions  of 
commercial  businesses  that  will  both  drive  our  growth  and  provide  geographically  diverse  sales  and  distribution 
opportunities.    During  2015,  we  acquired  EirGen,  a  growing,  profitable  and  cash  flow  positive  specialty 
pharmaceutical  company  based  in  Ireland.  EirGen  is  focused  on  the  development  and  commercial  supply  of  high 
potency, high barrier to entry, pharmaceutical products. Through its facility in Waterford, Ireland, EirGen currently 
manufactures  high  potency  pharmaceutical  products  and  exports  to  over  40  countries  all  over  the  world.    High 
potency drugs such as those used for cancer chemotherapy are typically unsuitable for manufacture in normal multi-
product facilities due to cross contamination risks. 

To date, EirGen and its commercial partners have filed 10 product applications with the FDA and 7 in Europe 
and 5 in Japan.  EirGen has a strong research and development portfolio of high barrier to entry drugs and we expect 
to  rapidly  expand  its  drug  portfolio.    We  believe  EirGen  will  play  an  important  role  in  the  development, 
manufacturing, distribution and approval of a wide variety of drugs in a variety of dosage forms with an emphasis 
on high potency products. 

OPKO Health Europe (previously Farmadiet Group Holding, S.L.) operates primarily in Spain and has more than 
20 years of experience in the development, manufacture, marketing, and sale of pharmaceutical, nutraceutical, and 
veterinary products in Europe. 

OPKO Mexico (previously Pharmacos Exakta S.A. de C.V.), is engaged in the manufacture, marketing, sale, and 
distribution  of  ophthalmic  and  other  pharmaceutical  products  to  private  and  public  customers  in  Mexico.    OPKO 
Mexico  manufacturers  and  sells  products  primarily  in  the  generics  market  in  Mexico,  although  it  has  recently 
increased its focus on the development of proprietary products as well. 

OPKO  Chile  (previously  Pharma  Genexx,  S.A.)  markets,  sells  and  distributes  pharmaceutical  and  natural 
products to the private, hospital, pharmacy and public institutional markets in Chile for a wide range of indications, 
including,  cardiovascular  products,  vaccines,  antibiotics,  gastro-intestinal  products,  and  hormones,  among  others.  
ALS Distribuidora Limitada (“ALS”) is engaged in the business of importation, commercialization and distribution 
of pharmaceutical products for private markets in Chile.  ALS started operations in 2009 as the exclusive product 
distributor  of  Arama  Laboratorios  y  Compañía  Limitada  (“Arama”),  a  company  with  more  than  20  years  of 
experience in the pharmaceutical products market.  In connection with the acquisition of ALS, OPKO acquired all of 
the product registrations and trademarks previously owned by Arama, as well as the Arama name. 

Strategic Investments 

We have and may continue to make investments in other early stage companies that we perceive to have valuable 

proprietary technology and significant potential to create value for OPKO as a shareholder. 

15 

 
 
RESEARCH AND DEVELOPMENT EXPENSES 

During the years ended December 31, 2015, 2014, and 2013, we incurred $99.5 million, $83.6 million, and $53.9 
million, respectively, of research and development expenses related to our various product candidates.  During the 
years  ended  December 31,  2015,  2014  and  2013,  our  research  and  development  expenses  primarily  consisted  of 
OPKO Biologics and OPKO Renal development programs including expenses related to the development of hGH-
CTP and phase 3 clinical trials for Rayaldee. 

INTELLECTUAL PROPERTY 

We  believe  that  technology  innovation  is  driving  breakthroughs  in  healthcare.    We  have  adopted  a 
comprehensive  intellectual  property  strategy  which  blends  the  efforts  to  innovate  in  a  focused  manner  with  the 
efforts  of  our  business  development  activities  to  strategically  in-license  intellectual  property  rights.    We  develop, 
protect, and defend our own intellectual property rights as dictated by the developing competitive environment.  We 
value  our  intellectual  property  assets  and  believe  we  have  benefited  from  early  and  insightful  efforts  at 
understanding diagnostics, as well as the disease and the molecular basis of potential pharmaceutical intervention. 

We  actively  seek,  when  appropriate  and  available,  protection  for  our  products  and  proprietary  information  by 
means  of  U.S.  and  foreign  patents,  trademarks,  trade  secrets,  copyrights,  and  contractual  arrangements.    Patent 
protection in the pharmaceutical and diagnostic fields, however, can involve complex legal and factual issues.  There 
can be no assurance that any steps taken to protect such proprietary information will be effective. 

We  own  or  license-in  over  a  thousand  U.S.  and  foreign  patents  and  applications  for  our  products,  product 
candidates  and  our  outlicensed  product  candidates.    These  patents  cover  pharmaceuticals,  diagnostics  and  other 
products  and  their uses,  pharmaceutical  and  diagnostic compositions  and  formulations  and product manufacturing 
processes.  Our patents are filed in various locations worldwide as is appropriate to the particular patent and its use. 

Rayaldee 

We have multiple U.S. patent families relating to Rayaldee.  These patents are also filed in multiple countries 
worldwide.    One  patent  family  claims  a  sustained  release  oral  dosage  formulation  and  a  method  of  treating  25-
hydroxy  vitamin  D  insufficiency  or  deficiency  and  will  not  expire  until  at  least  February  2027.    A  second  patent 
family claims a method of administering 25-hydroxy vitamin D3 by controlled release, a formulation for controlled 
release  of  a  vitamin  D  compound,  a  controlled  release  oral  dosage  formulation  of  a  vitamin  D  compound  and  a 
method  of  treatment,  and  will  not  expire  until  at  least  April  2028.    We  also  have  additional  patent  applications 
pending relating to the sustained release formulation and its use which will expire in 2034 and have licensed patents 
covering the capsule shell. 

Rolapitant 

The  rolapitant  line  of  patents,  licensed  to  TESARO,  includes  multiple  patent  families  that  cover  anti-nausea 
treatment  for  chemotherapy  patients.    These  U.S.  patents  are  also  filed  and granted  in many  countries  around  the 
world.    One  patent  family  covers  the  chemical  composition  of  rolapitant  and  related  compounds  and  expires  in 
December 2023 (with the patent term adjustment.) A patent term extension request was submitted to the USPTO in 
October 2015 to obtain an additional 1,716 days which will, upon approval, extend the rolapitant compound patent 
expiration date to August 2028.The second patent family covers pharmaceutical formulations, including a capsule 
formulation  with  a  related  method  of use  and  expires  in April  of 2027.    The  third patent  family  covers  particular 
aspects of the chemical composition of rolapitant as well as certain methods of treating delayed onset nausea and 
expires in April 2027.  The fourth patent family covers a powdered pharmaceutical composition of a crystalline salt 
of  rolapitant  and  expires  in  March  2028.    The  current  line  of  rolapitant  patents  are  approved  for  oral  treatment.  
Patent applications directed towards IV formulation of rolapitant are currently pending. 

hGH-CTP 

The hGH-CTP line of patents, which is currently licensed to Pfizer, Inc., includes two main patent families that 
cover modified human grown hormone treatment.  These U.S. patents are also filed in multiple countries around the 
world.    One  patent  family  covers  certain  CTP  modified  hGH  polypeptides  relating  to  growth  hormones  and  their 
method of use and expires in February of 2027 (with the exception of two US patents, namely US 8,304,386 and US 
8,097,435, which expire in Jan 2028 and April 2027, respectively, due to Patent Term Adjustment for each).  The 
second patent family covers cytokine-based polypeptides relating to human growth hormone treatment and expires 

16 

 
 
in  2027.    In  addition  to  the  CTP  patents  and  applications  licensed  to  Pfizer,  OPKO  has  multiple  patent  families 
covering similar biologicals with patents and applications pending in the U.S. and internationally. 

Because the patent positions of pharmaceutical, biotechnology, and diagnostics companies are highly uncertain 
and involve complex legal and factual questions, the patents owned and licensed by us, or any future patents, may 
not  prevent  other  companies  from  developing  similar  or  therapeutically  equivalent  products  or  ensure  that  others 
will  not  be  issued  patents  that  may  prevent  the  sale  of  our  products  or  require  licensing  and  the  payment  of 
significant  fees  or  royalties.    Furthermore,  to  the  extent  that  any  of  our  future  products  or  methods  are  not 
patentable,  that  such  products  or  methods  infringe  upon  the  patents  of  third  parties,  or  that  our  patents  or  future 
patents  fail  to  give  us  an  exclusive  position  in  the  subject  matter  claimed  by  those  patents,  we  will  be  adversely 
affected.  We may be unable to avoid infringement of third party patents and may have to obtain a license, defend an 
infringement action, or challenge the validity of the patents in court.  A license may be unavailable on terms and 
conditions acceptable to us, if at all.  Patent litigation is costly and time consuming, and we may be unable to prevail 
in any such patent litigation or devote sufficient resources to even pursue such litigation. 

LICENSES AND COLLABORATIVE RELATIONSHIPS 

Our  strategy  is  to  develop  a  portfolio  of  product  candidates  through  a  combination  of  internal  development, 
acquisition, and external partnerships.  Collaborations are key to our strategy and we continue to build relationships 
and forge partnerships in various areas where unmet medical need and commercial opportunities exist.  In December 
2014, we entered into an exclusive agreement with Pfizer for the development and commercialization of our long-
acting hGH-CTP for the treatment of GHD in adults and children, as well as for the treatment of growth failure in 
children  born  small  for  gestational  age.    Previously,  we  (or  entities  we  have  acquired)  have  completed  strategic 
licensing  transactions  with  the  University  of  Texas  Southwestern  Medical  Center  at  Dallas,  the  President  and 
Fellows of Harvard College, Academia Sinica, The Scripps Research Institute, TESARO, INEOS Healthcare, Arctic 
Partners, and Washington University, among others. 

COMPETITION 

The  pharmaceutical  and  diagnostic  testing  industries  are highly  competitive  and  require  an  ongoing,  extensive 
search  for  technological  innovation.    The  industries  are  characterized  by  rapidly  advancing  technologies,  intense 
competition  and  a  strong  emphasis  on proprietary  products.    They  also require, among  other  things,  the  ability  to 
effectively discover, develop, test and obtain regulatory approvals for products, as well as the ability to effectively 
commercialize, market and promote approved products. 

Numerous  companies,  including  major  pharmaceutical  companies,  specialty  pharmaceutical  companies  and 
specialized  biotechnology  companies,  are  engaged  in  the  development,  manufacture  and  marketing  of 
pharmaceutical products competitive with those that we intend to commercialize ourselves and through our partners.  
Competitors  to  our  diagnostics  business  include  major  diagnostic  companies,  reference  laboratories,  molecular 
diagnostic firms, universities and research institutions.  Most of these companies have substantially greater financial 
and  other  resources,  larger  research  and  development  staffs  and  more  extensive  marketing  and  manufacturing 
organizations  than  ours.    This  enables  them,  among  other  things,  to  make  greater  research  and  development 
investments and efficiently utilize their research and development costs, as well as their marketing and promotion 
costs, over a broader revenue base.  This also provides our competitors with a competitive advantage in connection 
with  the  highly  competitive  product  acquisition  and  product  in-licensing  process,  which  may  include  auctions  in 
which  the  highest  bidder  wins.    Our  competitors  may  also  have  more  experience  and  expertise  in  obtaining 
marketing  approvals  from  the  FDA  and other  regulatory authorities.    In  addition  to  product  development,  testing, 
approval, and promotion, other competitive factors in the pharmaceutical and diagnostics industry include industry 
consolidation, product quality and price, product technology, reputation, customer service, and access to technical 
information. 

In  our  clinical  laboratory  operations,  we  compete  with  three  types  of  providers  in  a  highly  fragmented  and 
competitive industry: hospital laboratories, physician-office laboratories and other independent clinical laboratories.  
Our  major  competitors  in  the  New  York  metropolitan  area  are  two  of  the  largest  national  laboratories,  Quest 
Diagnostics  and  Laboratory  Corporation  of  America.    Although  we  are  much  smaller  than  these  national 
laboratories, we believe that we compete successfully with them in our region due to our innovative testing services 
and our level of service.  We believe our responses to medical consultation are faster and more personalized than 
those of the national laboratories.  Our client service staff deals only with basic technical questions and those that 
have medical or scientific significance are referred directly to our senior scientists and medical staff. 

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We are seeking to commercialize our 4Kscore product in the U.S., Europe and Mexico in a laboratory setting and 
to  capitalize  on  near-term  commercialization  opportunities  for  our  proprietary  diagnostic  point-of-care  system  by 
transitioning  laboratory-based  tests,  including  the  4Kscore,  PSA,  testosterone  and  other  tests  to  our  point-of-care 
system.  We expect to leverage Bio-Reference’s national marketing, sales and distribution resources, along with its 
420-person  sales  force  to  support  commercialization  of  the  4Kscore  and  Claros  1  products.    Competitors  to  our 
diagnostics business are many and include major diagnostic companies, molecular diagnostic firms, universities, and 
research institutions. 

Our ability to commercialize our pharmaceutical and diagnostic test product candidates and compete effectively 

will depend, in large part, on: 

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our ability to meet all necessary regulatory requirements to advance our product candidates through 
clinical trials and the regulatory approval process in the U.S. and abroad; 

the perception by physicians and other members of the health care community of the safety, efficacy, 
and benefits of our products compared to those of competing products or therapies; 

our ability to manufacture products we may develop on a commercial scale; 

the effectiveness of our sales and marketing efforts; 

the  willingness  of  physicians  to  adopt  a  new  diagnostic  or  treatment  regimen  represented  by  our 
technology; 

our ability to secure reimbursement for our product candidates; 

the price of the products we may develop and commercialize relative to competing products; 

our ability to accurately forecast and meet demand for our product candidates if regulatory approvals 
are achieved; 

our  ability  to  develop  a  commercial  scale  infrastructure  either  on  our  own  or  with  a  collaborator, 
which  would  include  expansion  of  existing  facilities,  including  our  manufacturing  facilities, 
development  of  a  sales  and  distribution  network,  and  other  operational  and  financial  systems 
necessary to support our increased scale; 

our ability to maintain a proprietary position in our technologies; and 

our  ability  to  rapidly  expand  the  existing  information  technology  infrastructure  and  configure 
existing  operational,  manufacturing,  and  financial  systems  (on  our  own  or  with  third  party 
collaborators) necessary to support our increased scale, which would include existing or additional 
facilities and or partners. 

GOVERNMENT REGULATION 

The U.S. government regulates healthcare through various agencies, including but not limited to the following: 
(i) the FDA, which administers the Federal Food, Drug and Cosmetic Act (“FDCA”), as well as other relevant laws; 
(ii) the  Centers  for  Medicare &  Medicaid  Services  (“CMS”),  which  administers  the  Medicare  and  Medicaid 
programs; (iii) the Office of Inspector General (“OIG”), which enforces various laws aimed at curtailing fraudulent 
or  abusive  practices,  including  by  way  of  example,  the  Anti-Kickback  Statute,  the  Physician  Self-Referral  Law, 
commonly referred to as the Stark law, the Anti-Inducement Law, the Civil Money Penalty Law, and the laws that 
authorize the OIG to exclude healthcare providers and others from participating in federal healthcare programs; and 
(iv) the  Office  of  Civil  Rights,  which  administers  the  privacy  aspects  of  the  Health  Insurance  Portability  and 
Accountability Act of 1996.  All of the aforementioned are agencies within the Department of Health and Human 
Services  (“HHS”).    Healthcare  is  also  provided  or  regulated,  as  the  case  may  be,  by  the  Department  of  Defense 
through its TriCare program, the Department of Veterans Affairs, especially through the Veterans Health Care Act 
of  1992,  the  Public  Health  Service  within  HHS  under  Public  Health  Service  Act  §  340B  (42  U.S.C.  §  256b),  the 
Department  of  Justice  through  the  Federal  False  Claims  Act  and  various  criminal  statutes,  and  state  governments 
under the Medicaid and other state sponsored or funded programs and their internal laws regulating all healthcare 
activities. 

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The testing, manufacture, distribution, advertising, and marketing of drug and diagnostic products and medical 
devices, as well as the performance of clinical testing services, are subject to extensive regulation by federal, state, 
and local governmental authorities in the U.S., including the FDA, and by similar agencies in other countries.  Any 
drug, diagnostic, or device product that we develop must receive all relevant regulatory approvals or clearances, as 
the case may be, before it may be marketed in a particular country. 

Clinical Laboratory Operations 

Our  clinical  laboratory  operations  are  subject  to  regulations,  which  are  designed  to  ensure  the  quality  and 
reliability  of  clinical  laboratories  by  mandating  specific  standards  in  the  areas  of  personnel  qualifications, 
administration  and  participation  in  proficiency  testing,  patient  test  management,  quality  control,  quality  assurance 
and inspections.  Laboratories must undergo on-site surveys at least every two years, which may be conducted by 
the Federal CLIA program or by a private CMS approved accrediting agency.  The sanction for failure to comply 
with  CLIA  requirements  may  be  suspension,  revocation  or  limitation  of  a  laboratory’s  CLIA  certificate,  which  is 
necessary  to  conduct  business,  as  well  as  significant  fines  and/or  criminal  penalties.    We  are  also  subject  to 
regulation of laboratory operations under state clinical laboratory laws.  State clinical laboratory laws may require 
that laboratories and/or laboratory personnel meet certain qualifications, specify certain quality controls or require 
maintenance of certain records.  Certain states, such as California and Florida, each require that we obtain licenses to 
test specimens from patients residing in those states and additional states may require similar licenses in the future.  
Only Washington and New York State are exempt under CLIA, as these states have established laboratory quality 
standards at least as stringent as CLIA’s.  Potential sanctions for violation of these statutes and regulations include 
significant fines and the suspension or loss of various licenses, certificates and authorizations. 

Our clinical laboratory operations are subject to complex laws, regulations and licensure requirements relating to 
billing and payment for laboratory services, sales and marketing interactions with ordering physicians, security and 
confidentiality  of  health  information,  and  environmental  and  occupational  safety,  among  others. Changes  in 
regulations often increase the cost of testing or processing claims.  Also, these laws may be interpreted or applied by 
a prosecutorial, regulatory or judicial authority in a manner that could require us to make changes in our operations, 
including in our pricing, billing and/or marketing practices in a manner that could adversely affect operations. 

Drug Development 

The regulatory process, which includes overseeing preclinical studies and clinical trials of each pharmaceutical 
compound  to  establish  its  safety  and  efficacy  and  confirmation  by  the  FDA  that  good  laboratory,  clinical,  and 
manufacturing  practices  were  maintained  during  testing  and  manufacturing,  can  take  many  years,  requires  the 
expenditure  of  substantial  resources,  and  gives  larger  companies  with  greater  financial  resources  a  competitive 
advantage over us.  Delays or terminations of clinical trials that we undertake would likely impair our development 
of product candidates.  Delays or terminations could result from a number of factors, including stringent enrollment 
criteria, slow rate of enrollment, size of patient population, having to compete with other clinical trials for eligible 
patients, geographical considerations, and others. 

Although  accelerated  pathways  for  approval  exist  for  certain  drugs,  generally,  FDA  review  processes  can  be 
lengthy  and  unpredictable,  and  we  may  encounter  delays  or  rejections  of  our  applications  when  submitted.  
Generally, in order to gain FDA approval, we  must first  conduct preclinical studies in a laboratory and in animal 
models to obtain preliminary information on a compound and to identify any safety problems.  The results of these 
studies  are  submitted  as  part  of  an  IND  application  that  the  FDA  must  review  before  human  clinical  trials  of  an 
investigational drug can commence. 

Clinical  trials  are  normally  done  in  three  sequential  phases  and  generally  take  two  to  five  years  or  longer  to 
complete.  Phase 1 consists of testing the drug product in a small number of humans, normally healthy volunteers, to 
determine  preliminary  safety  and  tolerable  dose  range.    Phase  2  usually  involves  studies  in  a  limited  patient 
population to evaluate the effectiveness of the drug product in humans having the disease or medical condition for 
which  the  product  is  indicated,  determine  dosage  tolerance  and  optimal  dosage,  and  identify  possible  common 
adverse effects and safety risks.  Phase 3 consists of additional controlled testing at multiple clinical sites to establish 
clinical safety and effectiveness in an expanded patient population of geographically dispersed test sites to evaluate 
the  overall  benefit-risk  relationship  for  administering  the  product  and  to  provide  an  adequate  basis  for  product 
labeling.  Phase 4 clinical trials may be conducted after approval to gain additional experience from the treatment of 
patients in the intended therapeutic indication. 

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After  completion  of  clinical  trials  of  a  new  drug  product,  FDA  and  foreign  regulatory  authority  marketing 
approval  must  be  obtained.    Assuming  that  the  clinical  data  support  the  product’s  safety  and  effectiveness  for  its 
intended  use,  a  NDA  is  submitted  to  the  FDA  for  its  review.    Generally,  it  takes  one  to  three  years  to  obtain 
approval.  If questions arise during the FDA review process, approval may take a significantly longer period of time.  
The testing and approval processes require substantial time and effort and we may not receive approval on a timely 
basis,  if  at  all,  or  the  approval  that  we  receive  may  be  for  a  narrower  indication  than  we  had  originally  sought, 
potentially  undermining  the  commercial  viability  of  the  product.    Even  if  regulatory  approvals  are  obtained,  a 
marketed product is subject to continual review, and later discovery of previously unknown problems or failure to 
comply  with  the  applicable  regulatory  requirements  may  result  in  restrictions  on  the  marketing  of  a  product  or 
withdrawal of the product from the market as well as possible civil or criminal sanctions.  For marketing outside the 
U.S.,  we  also  will  be  subject  to  foreign  regulatory  requirements  governing  human  clinical  trials  and  marketing 
approval for pharmaceutical products.  The requirements governing the conduct of clinical trials, product licensing, 
pricing, and reimbursement vary widely from country to country. 

None  of  our  pharmaceutical  products  under  development  have  been  approved  for  marketing  in  the  U.S.  or 
elsewhere.  We may not be able to obtain regulatory approval for any such products under development in a timely 
manner,  if  at  all.    Failure  to  obtain  requisite  governmental  approvals  or  failure  to  obtain  approvals  of  the  scope 
requested will delay or preclude us, or our licensees or marketing partners, from marketing our products, or limit the 
commercial  use  of  our  products,  and  thereby  would  have  a  material  adverse  effect  on  our  business,  financial 
condition,  and  results  of  operations.    See  “Risk  Factors  —  The  results  of  pre-clinical  trials  and  previous  clinical 
trials  for our  products  may  not  be predictive  of future  results,  and  our  current  and planned clinical  trials  may  not 
satisfy the requirements of the FDA or other non-U.S. regulatory authorities.” 

Device Development 

Devices are subject to varying levels of premarket regulatory control, the most comprehensive of which requires 
that  a  clinical  evaluation  be  conducted  before  a  device  receives  approval  for  commercial  distribution.    The  FDA 
classifies medical devices into one of three classes: Class I devices are relatively simple and can be manufactured 
and  distributed  with  general  controls;  Class  II  devices  are  somewhat  more  complex  and  require  greater  scrutiny; 
Class III devices are new and frequently help sustain life. 

In the U.S., a company generally can obtain permission to distribute a new device in one of two ways.  The first 
applies  to  any  device  that  is  substantially  equivalent  to  a  device  first  marketed  prior  to  May  1976,  or  to  another 
device marketed after that date, but which was substantially equivalent to a pre-May 1976 device.  These devices are 
either  Class  I or  Class II  devices.   To obtain  FDA permission  to distribute  the device,  a  company  generally  must 
submit a section 510(k) submission, and receive an FDA order finding substantial equivalence to a predicate device 
(pre-May 1976 or post-May 1976 device that was substantially equivalent to a pre-May 1976 device) and permitting 
commercial  distribution  of  that  device  for  its  intended  use.    A  510(k)  submission  must  provide  information 
supporting a claim of substantial equivalence to the predicate device.  If clinical data  from human experience are 
required  to  support  the  510(k)  submission, these  data  must  be  gathered in  compliance  with  investigational  device 
exemption (“IDE”), regulations for investigations performed in the U.S.  The 510(k) process is normally used for 
products of the type that the Company proposes distributing.  The FDA review process for premarket notifications 
submitted pursuant to section 510(k) takes, on average, about 90 days, but it can take substantially longer if the FDA 
has concerns, and there is no guarantee that the FDA will “clear” the device for marketing, in which case the device 
cannot be distributed in the U.S.  There is also no guarantee that the FDA will deem the applicable device subject to 
the  510(k)  process,  as  opposed  to  the  more  time-consuming,  resource-intensive  and  problematic,  PMA  process 
described below. 

The second, more comprehensive, PMA process, which can take a year or longer, applies to a new device that is 
not substantially equivalent to a pre-1976 product or that is to be used in supporting or sustaining life or preventing 
impairment.  These devices are normally Class III devices.  For example, most implantable devices are subject to the 
approval process.  Two steps of FDA approval are generally required before a company can market a product in the 
U.S.  that  is  subject  to approval,  as opposed  to  clearance.    First,  a  company  must  comply  with  IDE  regulations  in 
connection with any human clinical investigation of the device.  These regulations permit a company to undertake a 
clinical  study  of  a  “non-significant  risk”  device  without  formal  FDA  approval.    Prior  express  FDA  approval  is 
required if the device is a significant risk device.  Second, the FDA must review the company’s PMA application, 
which contains, among other things, clinical information acquired under the IDE.  The FDA will approve the PMA 
application  if  it  finds  there  is  reasonable  assurance  that  the  device  is  safe  and effective  for  its  intended  use.    The 
PMA process takes substantially longer than the 510(k) process and it is conceivable that the FDA would not agree 

20 

 
 
with our assessment that a device that we propose to distribute should be a Class I or Class II device.  If that were to 
occur  we  would  be  required  to  undertake  the  more  complex  and  costly  PMA  process.    However,  for  either  the 
510(k) or the PMA process, the FDA could require us to run clinical trials, which would pose all of the same risks 
and uncertainties associated with the clinical trials of drugs, described above. 

Even when a clinical study has been approved by the FDA or deemed approved, the study is subject to factors 
beyond a manufacturer’s control, including, but not limited to the fact that the institutional review board at a given 
clinical  site  might  not  approve  the  study,  might  decline  to  renew  approval  which  is  required  annually,  or  might 
suspend or terminate the study before the study has been completed.  Also, the interim results of a study may not be 
satisfactory, leading the sponsor to terminate or suspend the study on its own initiative or the FDA may terminate or 
suspend the study.  There is no assurance that a clinical study at any given site will progress as anticipated; there 
may be an insufficient number of patients who qualify for the study or who agree to participate in the study or the 
investigator  at  the  site  may  have priorities  other  than  the  study.   Also, there  can  be no  assurance  that  the  clinical 
study  will  provide  sufficient  evidence  to  assure  the  FDA  that  the  product  is  safe  and  effective,  a  prerequisite  for 
FDA  approval  of  a  PMA,  or  substantially  equivalent  in  terms  of  safety  and  effectiveness  to  a  predicate  device,  a 
prerequisite for clearance under 510(k).  Even if the FDA approves or clears a device, it may limit its intended uses 
in  such  a  way  that  manufacturing  and  distributing  the  device  may  not  be  commercially  feasible.    For  marketing 
outside the U.S., we also will be subject to foreign regulatory requirements governing clinical trials and marketing 
approval for medical devices.  The requirements governing the conduct of clinical trials, device clearance/approval, 
pricing,  and  reimbursement  vary  widely  from  country  to  country.    In  addition  to  the  regulatory  clearance  and 
approval  processes  described  herein,  the  FDA  periodically  issues  draft  guidance  documents  designed  to  provide 
additional detail on or reform aspects of the 510(k) and PMA clearance and approval processes.  To the extent the 
FDA finalizes and implements these documents, the average 510(k) and PMA submission requirements and review 
times  may  change  and  devices  that  might  previously  have  been  cleared  under  the  510(k)  process  may  require 
approval  under  the  PMA  process  (and  vice-versa).    Additionally,  the  Medical  User  Fee  Amendments  of  2012 
authorized  the  FDA  to  collect  user  fees  for  the  review  of  certain  premarket  submissions  received  on  or  after 
October 1,  2012,  including  510(k)  and  PMA  applications.    These  fees  are  intended  to  improve  the  device  review 
process, but it is still too early to assess the actual impact on the industry. 

After clearance or approval to market is given, the FDA and foreign regulatory agencies, upon the occurrence of 
certain events, are authorized under various circumstances to withdraw the clearance or approval or require changes 
to a device, its manufacturing process or its labeling or additional proof that regulatory requirements have been met. 

A manufacturer of a device approved through the PMA is not permitted to make changes to the device, which 
affects its safety or effectiveness without first submitting a supplement application to its PMA and obtaining FDA 
approval  for  that  supplement.    In  some  instances,  the  FDA  may  require  clinical  trials  to  support  a  supplement 
application.    A  manufacturer  of  a  device  cleared  through  the  510(k)  process  must  submit  another  premarket 
notification if it intends to make a change or modification in the device that could significantly affect the safety or 
effectiveness of the device, such as a significant change or modification in design, material, chemical composition, 
energy  source  or  manufacturing  process.    Any  change  in  the  intended  uses  of  a  PMA  device  or  a  510(k)  device 
requires an approval supplement or cleared premarket notification.  Exported devices are subject to the regulatory 
requirements of each country to which the device is exported, as well as certain FDA export requirements. 

A company that intends to manufacture medical devices is required to register with the FDA before it begins to 
manufacture the device for commercial distribution.  As a result, we and any entity that manufactures products on 
our  behalf  will  be  subject  to  periodic  inspection  by  the  FDA  for  compliance  with  the  FDA’s  Quality  System 
Regulation requirements and other regulations.  In the European Community, we will be required to maintain certain 
International  Organization  for  Standardization  (“ISO”),  certifications  in  order  to  sell  products  and  we  or  our 
manufacturers  undergo  periodic  inspections  by  notified  bodies  to  obtain  and  maintain  these  certifications.    These 
regulations require us or our manufacturers to manufacture products and maintain documents in a prescribed manner 
with respect to design, manufacturing, testing and control activities.  Further, we are required to comply with various 
FDA and other agency requirements for labeling and promotion.  The Medical Device Reporting regulations require 
that we provide information to the FDA whenever there is evidence to reasonably suggest that a device may have 
caused or contributed to a death or serious injury or, if a malfunction were to occur, could cause or contribute to a 
death  or  serious  injury.    In  addition,  the  FDA  prohibits  us  from  promoting  a  medical  device  for  unapproved 
indications. 

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Diagnostic Products 

Certain of our diagnostic products in development are subject to regulation by the FDA and similar international 
health authorities.  We have an obligation to adhere to the FDA’s cGMP regulations.  Additionally, we are subject to 
periodic  FDA inspections, quality  control  procedures,  and  other detailed  validation procedures.    If  the  FDA  finds 
deficiencies  in  the  validation  of  our  manufacturing  and  quality  control  practices,  they  may  impose  restrictions  on 
marketing specific products until corrected. 

Regulation  by  governmental  authorities  in  the  U.S.  and  other  countries may  be  a  significant  factor  in  how  we 
develop,  test,  produce  and  market  our  diagnostic  test  products.    Diagnostic  tests  like  ours  may  not  fall  squarely 
within the regulatory approval process for pharmaceutical or device products as described above, and the regulatory 
pathway is not as clear.  Although the FDA regulates in vitro diagnostic devices, some companies have successfully 
commercialized diagnostic tests for various conditions and disease states without seeking clearance or approval for 
such  tests  through  a  510(k)  or  PMA  approval  process.    These  tests  are  known  as  laboratory  developed  tests 
(“LDTs”)  and  are  designed,  manufactured,  and  used  within  a  single  laboratory  that  is  certified  under  the  Clinical 
Laboratory Improvement Amendments of 1988 (“CLIA”).  CLIA is a federal law that regulates clinical laboratories 
that  perform  testing  on  specimens  derived  from  humans  for  the  purpose  of  providing  information  for  diagnostic, 
preventative or treatment purpose.  Such LDT testing is currently under the purview of CMS and state agencies that 
provide oversight of the safe and effective use of LDTs. 

However,  the  FDA  has  consistently  asserted  that  it  has  the  regulatory  authority  to  regulate  LDTs  despite 
historically exercising enforcement discretion.  In furtherance of that position, the FDA issued two draft guidance 
documents  in  October  2014:  (1)  Framework  for  Regulatory  Oversight  of  Laboratory  Developed  Tests  (the 
“Framework Guidance”); and (2) FDA Notification and Medical Device Reporting for Laboratory Developed Tests 
(the “Notification Guidance”).  The Framework Guidance outlines the FDA’s plan to adopt over time a risk-based 
approach to regulating LDTs whereby different classifications of LDTs would be subject to different levels of FDA 
oversight  and  enforcement,  including,  for  example,  prohibitions  on  adulteration  and  misbranding,  establishment 
registration  and  device  listing,  premarket  notification,  banned  devices,  records  and  reports,  good  manufacturing 
practices,  adverse  event  reporting,  premarket  review  of  safety,  effectiveness,  and  clinical  validity,  and  quality 
system requirements.  The Notification Guidance is intended to explain how clinical laboratories should notify the 
FDA of the LDTs they develop and how to satisfy Medical Device Reporting requirements. 

If finalized, the Framework Guidance and the Notification Guidance may have a materially adverse effect on the 
time,  cost,  and  risk  associated  with  the  Company’s  development  and  commercialization  of  LDTs  for  the  U.S. 
market,  and  there  can  be  no  assurance  that  clearances  or  approvals  sought  by  the  Company  will  be  granted  and 
maintained.    However,  the  FDA’s  authority  to  regulate  LDTs  continues  to  be  challenged,  and  the  timeline  and 
process  for  finalizing  the  draft  guidance  documents  is  unknown.    We  will  continue  to  monitor  changes  to  all 
domestic and international LDT regulatory policy so as to ensure compliance with the current regulatory scheme. 

Impact of Regulation 

The FDA in the course of enforcing the FDCA may subject a company to various sanctions for violating FDA 
regulations or provisions of the FDCA, including requiring recalls, issuing Warning Letters, seeking to impose civil 
money  penalties,  seizing  devices  that  the  agency  believes  are  non-compliant,  seeking  to  enjoin  distribution  of  a 
specific type of device or other product, seeking to revoke a clearance or approval, seeking disgorgement of profits 
and seeking to criminally prosecute a company and its officers and other responsible parties. 

The  levels  of  revenues  and  profitability  of  biopharmaceutical  companies  may  be  affected  by  the  continuing 
efforts of  government  and  third party  payers  to  contain  or reduce  the  costs  of  health  care  through  various  means.  
For example, in certain foreign markets, pricing or profitability of therapeutic and other pharmaceutical products is 
subject to governmental control.  In the U.S., there have been, and we expect that there will continue to be, a number 
of federal and state proposals to implement similar governmental control.  In addition, in the U.S. and elsewhere, 
sales  of  therapeutic  and  other  pharmaceutical  products  are  dependent  in  part  on  the  availability  and  adequacy  of 
reimbursement from third party payers, such as the government or private insurance plans.  Third party payers are 
increasingly challenging established prices, and new products that are more expensive than existing treatments may 
have difficulty finding ready acceptance unless there is a clear therapeutic benefit.  On April 1, 2014, the Protecting 
Access to Medicare Act of 2014 (“PAMA”) was enacted into law.  Under PAMA, Medicare payment for clinical 
diagnostic laboratory tests will be established by calculating a weighted mean of private payer rates starting in 2017.  
Further, applicable laboratories will be required to report payment rates for covered tests starting in 2016.  Failure to 

22 

 
 
report such data may result in a civil money penalty in an amount of up to $10,000 per day.  It is anticipated that the 
market-based payment system will result in lower reimbursement rates for clinical diagnostic laboratory tests.  Even 
though  the  permitted  annual  decrease  will  be  capped  through  2022,  the  cap  does  not  apply  to  new  tests  or  new 
advanced diagnostic tests.  We cannot assure you that any of our products will be considered cost effective, or that 
reimbursement will be available or sufficient to allow us to sell them competitively and profitably. 

State and Federal Security and Privacy Regulations 

The privacy and security regulations under the Health Insurance Portability and Accountability Act of 1996, as 
amended  by  the  Health  Information  Technology  for  Economic  and  Clinical  Health  Act  of  2009  (  the  “HITECH 
Act”,  and  collectively,  “HIPAA”),  establish  comprehensive  federal  standards  with  respect  to  the  uses  and 
disclosures of protected health information, or PHI, by health plans and health care providers, in addition to setting 
standards  to  protect  the  confidentiality,  integrity  and  availability  of  electronic  PHI.    The  regulations  establish  a 
complex regulatory framework on a variety of subjects, including: 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

the  circumstances  under  which  uses  and  disclosures  of  PHI  are  permitted  or  required  without  a 
specific  authorization  by  the  patient,  including  but  not  limited  to  treatment  purposes,  to  obtain 
payments for services and health care operations activities; 

a patient’s rights to access, amend and receive an accounting of certain disclosures of PHI; 

the content of notices of privacy practices for PHI; and 

administrative,  technical  and  physical  safeguards  required  of  entities  that  use  or  receive  PHI 
electronically. 

The final “omnibus” rule implementing the HITECH Act took effect on March 26, 2013.  The rule is broad in 
scope, but certain provisions are particularly significant in light of our business operations.  For example, the final 
“omnibus” rule implementing the HITECH Act: 

(cid:120)  Makes  clear  that  situations  involving  impermissible  access,  acquisition,  use  or  disclosure  of 
protected health information are now presumed to be a breach unless the covered entity or business 
associate  is  able  to  demonstrate  that  there  is  a  low  probability  that  the  information  has  been 
compromised; 

(cid:120)  Defines  the  term  “business  associate”  to  include  subcontractors  and  agents  that  receive,  create, 

maintain or transmit protected health information on behalf of the business associate; 

(cid:120)  Establishes new parameters for covered entities and business associates on uses and disclosures of 

PHI for fundraising and marketing; and 

(cid:120)  Establishes clear restrictions on the sale of PHI without patient authorization. 

As a provider of clinical laboratory services and as we launch commercial diagnostic tests, we must continue to 
implement  policies  and  procedures  related  to  compliance  with  the  HIPAA  privacy  and  security  regulations,  as 
required by law.  The privacy and security regulations provide for significant fines and other penalties for wrongful 
use or disclosure of PHI, including potential civil and criminal fines and penalties. 

Anti-Kickback Laws, Physician Self-Referral Laws, False Claims Act, Civil Monetary Penalties 

We are also subject to various federal, state, and international laws pertaining to health care “fraud and abuse,” 
including  anti-kickback  laws  and  false  claims  laws.    The  federal  Anti-Kickback  Statute  prohibits  anyone  from 
knowingly  and  willfully  soliciting,  receiving,  offering,  or  paying  any  remuneration  with  the  intent  to  refer,  or  to 
arrange  for  the  referral  or  order  of,  services  or  items  payable  under  a  federal  health  care  program,  including  the 
purchase or prescription of a particular drug or the use of a service or device.  Recognizing that the Anti-Kickback 
Statute is broad and may technically prohibit many innocuous or beneficial arrangements, Congress authorized the 
U.S. Department of Health and Human Services Office of Inspector General, or OIG, to issue a series of regulations, 
known as “safe harbors.”  These safe harbors set forth requirements that, if met in their entirety, will assure health 
care providers and other parties that they will not be prosecuted under the Anti-Kickback Statute.  The failure of a 
transaction  or  arrangement  to  fit  precisely  within  one  or  more  safe  harbors  does  not  necessarily  mean  that  it  is 

23 

 
 
illegal, or that prosecution will be pursued.  However, conduct and business arrangements that do not fully satisfy 
each  applicable  safe  harbor  may  result  in  increased  scrutiny  by  government  enforcement  authorities,  such  as  the 
OIG. 

Violations of the Anti-Kickback Statute are punishable by the imposition of criminal fines, civil money penalties, 
treble damages, and/or exclusion from participation in federal health care programs.  Many states have also enacted 
similar anti-kickback laws.  The Anti-Kickback Statute and similar state laws and regulations are expansive.  If the 
government were to allege against or convict us of violating these laws, there could be a material adverse effect on 
our business, results of operations, financial condition, and our stock price.  Even an unsuccessful challenge could 
cause adverse publicity and be costly to respond to, which could have a materially adverse effect on our business, 
results of operations and financial condition.  We will consult counsel concerning the potential application of these 
and  other  laws  to  our  business  and  our  sales,  marketing  and  other  activities  and  will  make  good  faith  efforts  to 
comply  with  them.    However,  given  the  broad  reach  of  federal  and  state  anti-kickback  laws  and  the  increasing 
attention  given  by  law  enforcement  authorities,  we  are  unable  to  predict  whether  any  of  our  activities  will  be 
challenged or deemed to violate these laws. 

We are also subject to the physician self-referral laws, commonly referred to as the Stark law, which is a strict 
liability  statute  that  generally  prohibits  physicians  from  referring  Medicare  patients  to  providers  of  “designated 
health  services,”  including  clinical  laboratories,  with  whom  the  physician  or  the  physician’s  immediate  family 
member has an ownership interest or compensation arrangement, unless an applicable exception applies.  Moreover, 
many states have adopted or are considering adopting similar laws, some of which extend beyond the scope of the 
Stark  law  to  prohibit  the  payment  or  receipt  of  remuneration  for  the  prohibited  referral  of  patients  for  designated 
healthcare services and physician self-referrals, regardless of the source of the payment for the patient’s care.  If it is 
determined  that  certain  of  our  practices  or  operations  violate  the  Stark  law  or  similar  statutes,  we  could  become 
subject  to  civil  and  criminal  penalties,  including  exclusion  from  the  Medicare  programs  and  loss  of  government 
reimbursement.  The imposition of any such penalties could harm our business. 

Another development affecting the health care industry is the increased use of the federal civil False Claims Act 
and, in particular, actions brought pursuant to the False Claims Act’s “whistleblower” or “qui tam” provisions.  The 
False Claims Act, as amended by the Fraud Enforcement and Recovery Act of 2009 and the Patient Protection and 
Affordable  Care  Act  of  2010,  imposes  liability  on  any  person  or  entity  who,  among  other  things,  knowingly 
presents, or causes to be presented, a false or fraudulent claim for payment by a federal health care program.  We 
submit claims for services performed at our laboratories.  The qui tam provisions of the False Claims Act allow a 
private individual to bring actions on behalf of the federal government alleging that the defendant has submitted a 
false claim to the federal government, and to share in any monetary recovery.  In recent years, the number of suits 
brought by private individuals has increased dramatically.  In addition, various states have enacted false claim laws 
analogous to the False Claims Act.  Many of these state laws apply where a claim is submitted to any third-party 
payor and not merely a federal health care program.  When an entity is determined to have violated the False Claims 
Act, it may be required to pay up to three times the actual damages sustained by the government, plus civil penalties 
for  each  separate  false  claim.    There  are  many  potential  bases  for  liability  under  the  False  Claims  Act.    Liability 
arises, primarily, when an entity knowingly submits, or causes another to submit, a false claim for reimbursement to 
the  federal  government.    The  False  Claims  Act  has  been  used  to  assert  liability  on  the  basis  of  inadequate  care, 
kickbacks and other improper referrals, improper use of Medicare numbers when detailing the provider of services, 
and allegations as to misrepresentations with respect to the services rendered.  Our activities relating to the sale and 
marketing of our products may be subject to scrutiny under these laws.  We are unable to predict whether we would 
be subject to actions under the False Claims Act or a similar state law, or the impact of such actions.  However, the 
costs of defending such claims, as well as any sanctions imposed, could significantly adversely affect our financial 
performance. 

Further, 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) 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 $10,000 for each 
wrongful  act.    Although  we  believe  that  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 Medicaid and other governmental 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. 

24 

 
 
Foreign Corrupt Practices Act 

We  are  also  subject  to  the  U.S.  Foreign  Corrupt  Practices  Act  (“FCPA”),  which  prohibits  corporations  and 
individuals from paying, offering to pay, or authorizing the payment of anything of value to any foreign government 
official, government staff member, political party, or political candidate in an attempt to obtain or retain business or 
to otherwise influence a person working in an official capacity.  The FCPA also requires public companies to make 
and  keep  books  and  records  that  accurately  and  fairly  reflect  their  transactions  and  to  devise  and  maintain  an 
adequate  system  of  internal  accounting  controls.    Our  international  activities  create  the  risk  of  unauthorized 
payments or offers of payments by our employees, consultants, sales agents or distributors, even though they may 
not always be subject to our control.  We discourage these practices by our employees and agents.  However, our 
existing  safeguards  and  any  future  improvements  may  prove  to  be  less  than  effective,  and  our  employees, 
consultants, sales agents or distributors may engage in conduct for which we might be held responsible.  Any failure 
by us to adopt appropriate compliance procedures and ensure that our employees and agents comply with the FCPA 
and applicable laws and regulations in foreign jurisdictions could result in substantial penalties or restrictions on our 
ability to conduct business in certain foreign jurisdictions. 

MANUFACTURING AND QUALITY 

Other  than  our  facilities  in  Waterford,  Ireland,  Guadalajara,  Mexico,  Nesher,  Israel,  and  Banyoles,  Spain,  we 
currently  have  no  pharmaceutical  manufacturing  facilities.    We  have  entered  into  agreements  with  various  third 
parties  for  the  formulation  and  manufacture  of  our  pharmaceutical  clinical  supplies.    These  suppliers  and  their 
manufacturing  facilities  must  comply  with  FDA  regulations,  current  good  laboratory  practices  (“cGLPs”)  and 
current good manufacturing practices (“cGMPs”).  We plan to outsource the manufacturing and formulation of our 
clinical supplies. 

The FDA and similar regulatory bodies may inspect our facilities and the facilities of those who manufacture on 
our  behalf  worldwide.    If  the  FDA  or  similar  regulatory  bodies  inspecting  our  facilities  or  the  facilities  of  our 
suppliers find regulatory violations in manufacturing and quality control practices or procedures they may require us 
to  cease  partial  or  complete  manufacturing  operations  until  the  violations  are  corrected.    They  may  also  impose 
restrictions on distribution of specific products until the violations are corrected. 

Our  point-of-care  diagnostic  system  consists  of  a  disposable  test  cassette  and  an  analyzer.    We  prepare  all 
necessary test reagents and assemble and package the disposable cassettes at our facility in Woburn, Massachusetts.  
We rely on third parties for the manufacture of the analyzer. 

We are committed to providing high quality products to our customers, and we plan to meet this commitment by 
working  diligently  to  continue  implementing  updated  and  improved  quality  systems  and  concepts  throughout  our 
organization. 

SALES & MARKETING 

Our  diagnostics  business  includes  Bio-Reference’s  420-person  sales  force  in  the  U.S.  to  drive  growth  and 
leverage new products, including the 4Kscore prostate cancer test and the Claros 1 in-office immunoassay platform.  
We currently do not have pharmaceutical sales or marketing personnel in the U.S., and we have limited personnel in 
Ireland, Chile, Spain, Mexico and Israel.  In order to commercialize any pharmaceutical products that are approved 
for commercial sale, we must either build a sales and marketing infrastructure or collaborate with third parties with 
sales and marketing experience. 

EMPLOYEES 

As of December 31, 2015, we had 5,936 full-time employees worldwide.  None of our employees are represented 

by a collective bargaining agreement. 

Code of Ethics 

We  have  adopted  a  Code  of  Business  Conduct  and  Ethics.    We  require  all  employees,  including  our principal 
executive officer and principal accounting officer and other senior officers and our employee directors, to read and 
to adhere to the Code of Business Conduct and Ethics in discharging their work-related responsibilities.  Employees 
are required to report any conduct that they believe in good faith to be an actual or apparent violation of the Code of 

25 

 
 
Business  Conduct  and  Ethics.    The  Code  of  Business  Conduct  and  Ethics  is  available  on  our  website  at 
http://www.OPKO.com. 

Available Information 

We make available free of charge on or through our web site, at www.opko.com, our Annual Reports on Form 
10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and all amendments to those reports as soon 
as reasonably practicable after such material is electronically filed with the SEC.  Additionally, the public may read 
and copy any materials we file with the SEC at the SEC’s Public Reference Room at 100 F Street, NE, Room 1580, 
Washington, D.C., 20549.  Information regarding operation of the Public Reference Room is available by calling the 
SEC  at  1-800-SEC-0330.    Information  that  we  file  with  the  SEC  is  also  available  at  the  SEC’s  Web-site  at 
www.sec.gov. 

ITEM 1A.  RISK FACTORS. 

You should carefully consider the risks described below, as well as other information contained in this report, 
including the consolidated financial statements and the notes thereto and “Management’s Discussion and Analysis 
of  Financial  Condition  and  Results  of  Operations.”    The  occurrence  of  any  of  the  events  discussed  below  could 
significantly and adversely affect our business, prospects, results of operations, financial condition, and cash flows. 

RISKS RELATED TO OUR BUSINESS 

We have a history of operating losses and may not become profitable in the near future. 

We are not profitable and have incurred losses since our inception.  We do not anticipate that we will generate 
revenue from the sale of proprietary pharmaceutical products or certain of our diagnostic products for some time and 
we  have  generated  only  limited  revenue  from  our  pharmaceutical  operations  in  Chile,  Mexico,  Israel,  Spain,  and 
Ireland,  and  from  sale  of  the  4Kscore  test.    Although  we  expect  to  leverage  the  national  marketing,  sales  and 
distribution resources of Bio-Reference to enhance sales of, and reimbursement for, our 4Kscore test and our other 
diagnostic products under development, we may not be successful in our integration of Bio-Reference which would 
adversely impact our ability to generate substantial revenue from the sale of these products for some time.  We do 
not  currently  have  rights  to  any  pharmaceutical  product  candidates  that  have  been  approved  for  marketing,  other 
than  those  products  sold  by  our  Chilean,  Mexican,  Israeli,  Spanish,  and  Irish  subsidiaries.    We  continue  to  incur 
substantial research and development and general and administrative expenses related to our operations and, to date, 
we  have  devoted  most  of  our  financial  resources  to  research  and  development,  including  our  pre-clinical 
development activities and clinical trials.  We may incur losses from our operations for the foreseeable future and 
these losses could increase as we continue our research activities and conduct development of, and seek regulatory 
approvals and clearances for, our product candidates, and prepare for and begin to commercialize any approved or 
cleared products, particularly if we are unable to generate profits and cash flow from Bio-Reference and our other 
commercial  businesses.    If  we  are  unable  to  generate  profits  and  cash  flow  from  Bio-Reference  and  our  other 
commercial businesses, our product candidates fail in clinical trials or do not gain regulatory approval or clearance, 
or if our product candidates do not achieve market acceptance, we may never become profitable.  In addition, if we 
are  required  by  the  U.S.  Food  and  Drug  Administration  (“FDA”),  to  perform  studies  in  addition  to  those  we 
currently anticipate, our expenses will increase beyond current expectations and the timing of any potential product 
approval may be delayed.  Even if we achieve profitability in the future, we may not be able to sustain profitability 
in subsequent periods. 

We may require substantial additional funding, which may not be available to us on acceptable terms, or at all. 

As of December 31, 2015, we have cash and cash equivalents of $193.6 million.  We believe we have sufficient 
cash  and  cash  equivalents  on  hand  or  available  to  us  from  operations  or  through  lines  of  credit  to  meet  our 
anticipated  cash  requirements  for  operations  and  debt  service  beyond  the  next  12  months.    We  have  based  this 
estimate  on  assumptions  that  may  prove  to  be  wrong  or  subject  to  change,  and  we  may  be  required  to  use  our 
available capital resources sooner than we currently expect or curtail aspects of our operations in order to preserve 
our  capital. 
  Because  of  the  numerous  risks  and  uncertainties  associated  with  the  development  and 
commercialization  of  our  product  candidates,  the  success  of  our  relationship  with  Pfizer  and  the  success  of  our 
acquisition  of  Bio-Reference,  we  are  unable  to  estimate  the  amounts  of  increased  capital  outlays  and  operating 
expenditures  associated  with  our  current  and  anticipated  clinical  trials  and  our  expanded  commercial  operations.  
Our  future  capital  requirements  will  depend  on  a  number  of  factors,  including  our  relationship  with  Pfizer,  the 
success of the Bio-Reference acquisition and costs associated with the integration of the Bio-Reference operations, 

26 

 
 
the continued progress of our research and development of product candidates, the timing and outcome of clinical 
trials  and  regulatory  approvals,  the  costs  involved  in  preparing,  filing,  prosecuting,  maintaining,  defending,  and 
enforcing patent claims and other intellectual property rights, the status of competitive products, the availability of 
financing, and our success in developing markets for our product candidates. 

Until we can generate a sufficient amount of product and service revenue to finance our cash requirements for 
research, development and operations, we will need to finance future cash needs primarily through public or private 
equity offerings, debt financings, or strategic collaborations.  Our ability to obtain additional capital may depend on 
prevailing economic conditions and financial, business and other factors beyond our control.  Disruptions in the U.S. 
and global financial markets may adversely impact the availability and cost of credit, as well as our ability to raise 
money in the capital markets.  Economic conditions have been, and continue to be, volatile.  Continued instability in 
these  market  conditions  may  limit  our  ability  to  replace,  in  a  timely  manner,  maturing  liabilities  and  access  the 
capital necessary to fund and grow our business.  There can be no assurance that additional capital will be available 
to  us  on  acceptable  terms,  or  at  all,  which  could  adversely  impact  our  business,  results  of  operations,  liquidity, 
capital resources and financial condition.  If we are not able to secure additional funding when needed, we may have 
to delay, reduce the scope of, or eliminate one or more of our clinical trials or research and development programs.  
To the extent that we raise additional funds by issuing equity securities, our stockholders may experience additional 
significant dilution, and debt financing, if available, may involve restrictive covenants.  To the extent that we raise 
additional funds through collaboration and licensing arrangements, it may be necessary to relinquish some rights to 
our technologies or our product candidates or grant licenses on terms that may not be favorable to us.  We may seek 
to  access  the  public  or  private  capital  markets  whenever  conditions  are  favorable,  even  if  we  do  not  have  an 
immediate need for additional capital at that time. 

Our research and development activities may not result in commercially viable products. 

Many  of  our  product  candidates  are  in  the  early  stages  of  development  and  are  prone  to  the  risks  of  failure 
inherent  in drug, diagnostic, and  medical  device  product development.   These risks  further  include  the possibility 
that such products would: 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

be found to be ineffective, unreliable, or otherwise inadequate or otherwise fail to receive regulatory 
approval; 

be difficult or impossible to manufacture on a commercial scale; 

be uneconomical to market or otherwise not be effectively marketed; 

fail  to  be  successfully  commercialized  if  adequate  reimbursement  from  government  health 
administration  authorities,  private  health  insurers,  and  other  organizations  for  the  costs  of  these 
products is unavailable; 

be impossible to commercialize because they infringe on the proprietary rights of others or compete 
with products marketed by others that are superior; or 

fail to be commercialized prior to the successful marketing of similar products by competitors. 

The  results  of  pre-clinical  trials  and  previous  clinical  trials  for  our  products  may  not  be  predictive  of  future 
results, and our current and planned clinical trials may not satisfy the requirements of the FDA or other non-
U.S. regulatory authorities. 

Positive results from pre-clinical studies and early clinical trial experience should not be relied upon as evidence 
that  later-stage  or  large-scale  clinical  trials  will  succeed.    Likewise,  there  can  be  no  assurance  that  the  results  of 
studies conducted by collaborators or other third parties will be viewed favorably or are indicative of our own future 
study results.  We may be required to demonstrate with substantial evidence through well-controlled clinical trials 
that our product candidates are either (i) with respect to drugs or Class III devices, safe and effective for use in a 
diverse  population  of  their  intended  uses  or  (ii)  with  respect  to  Class  I  or  Class  II  devices,  are  substantially 
equivalent  in  terms  of  safety  and  effectiveness  to  devices  that  are  already  marketed  under  section  510(k)  of  the 
Food,  Drug  and  Cosmetic  Act.    Success  in  early  clinical  trials  does  not  mean  that  future  clinical  trials  will  be 
successful  because  product  candidates  in  later-stage  clinical  trials  may  fail  to  demonstrate  sufficient  safety  and 

27 

 
 
efficacy to the satisfaction of the FDA and other non-U.S. regulatory authorities despite having progressed through 
initial clinical trials. 

Further,  our  drug  candidates  may  not  be  approved  or  cleared  even  if  they  achieve  their  primary  endpoints  in 
phase  3  clinical  trials  or  registration  trials.    In  addition  our  diagnostic  test  candidates  may  not  be  approved  or 
cleared, as the case may be, even though clinical or other data are, in our view, adequate to support an approval or 
clearance.  The FDA or other non-regulatory authorities may disagree with our trial design and our interpretation of 
data  from  pre-clinical  studies  and  clinical  trials.    In  addition,  any  of  these  regulatory  authorities  may  change 
requirements for the approval or clearance of a product candidate even after reviewing and providing comment on a 
protocol for a pivotal clinical trial that has the potential to result in FDA and other non-U.S. regulatory authorities’ 
approval.    Any  of  these  regulatory  authorities  may  also  approve  or  clear  a  product  candidate  for  fewer  or  more 
limited  indications  or  uses  than  we  request  or  may  grant  approval  or  clearance  contingent  on  the  performance  of 
costly post-marketing clinical trials.  The FDA or other non-U.S. regulatory authorities may not approve the labeling 
claims necessary or desirable for the successful commercialization of our product candidates. 

The results of our clinical trials may show that our product candidates may cause undesirable side effects, which 
could interrupt, delay or halt clinical trials, resulting in the denial of regulatory approval by the FDA and other non-
U.S. regulatory authorities. 

In  light of widely  publicized events  concerning  the  safety risk of  certain drug products,  regulatory  authorities, 
members of Congress, the Government Accounting Office, medical professionals, and the general public have raised 
concerns  about  potential  drug  safety  issues.    These  events  have  resulted  in  the  withdrawal  of  drug  products, 
revisions  to  drug  labeling  that  further  limit  use  of  the  drug  products,  and  establishment  of  risk  management 
programs that may, for instance, restrict distribution of drug products.  The increased attention to drug safety issues 
may result in a more cautious approach by the FDA to clinical trials.  Data from clinical trials may receive greater 
scrutiny with respect to safety, which may  make the FDA or other regulatory authorities more likely to terminate 
clinical trials before completion, or require longer or additional clinical trials that may result in substantial additional 
expense and a delay or failure in obtaining approval or approval for a more limited indication than originally sought. 

The failure to obtain approval for or successfully commercialize Rayaldee would have a material adverse effect 
on our business. 

The  NDA  for  Rayaldee  is  currently  pending  before  the  FDA  with  a  PDUFA  target  date  of  March 28,  2016.  
Upon approval, we expect to begin the commercial launch of Rayaldee in the second half of 2016.  There can be no 
assurance that we will obtain regulatory approval or be able to launch Rayaldee by such dates.  Further even if we 
obtain regulatory approval of Rayaldee, there can be no assurance that we will be able to successfully commercialize 
Rayaldee.  To successfully launch and commercialize Rayaldee, we will need to establish a sales and marketing and 
clinical  support  infrastructure,  educate  the  medical  community  about  Rayaldee’s  benefits,  and  establish 
commercially  viable  pricing  and  obtain  adequate  reimbursement  from  third-party  and  government  payors.    Our 
failure  to  successfully  commercialize  Rayaldee  within  the  expected  time  frame,  or  at  all,  would  have  a  material 
adverse effect on our business. 

Our  exclusive  worldwide  agreement  with  Pfizer  Inc.  is  important  to  our  business.    If  we  do  not  successfully 
develop  hGH-  CTP  and/or  Pfizer  Inc.  does  not  successfully  commercialize  hGH-CTP,  our  business  could  be 
adversely affected. 

In December 2014, we entered into a development and commercialization agreement with Pfizer relating to our 
long-acting hGH- CTP for the treatment of growth hormone deficiency in adults and children.  Under the terms of 
the agreements with Pfizer, we received non-refundable and non-creditable upfront payments of $295 million and 
are eligible to receive up to an additional $275 million upon the achievement of certain regulatory milestones.  In 
addition, we are eligible to receive initial royalty payments associated with the commercialization of hGH-CTP for 
Adult GHD.  Upon the launch of hGH-CTP for Pediatric GHD, the royalties will transition to a regional, tiered gross 
profit sharing for both hGH-CTP and Pfizer’s Genotropin®.  We are also responsible for the development program 
and  are  obligated  to  pay  for  the  development  up  to  an  agreed  cap,  which  may  be  exceeded  under  certain 
circumstances.  If we are required to exceed the agreed cap, it could have a material adverse impact on the expected 
benefits to us from the Pfizer transaction and our overall financial condition.  In the event that the parties are able to 
obtain  regulatory  approvals  to  market  a product  covered  by  the  agreement, we will  be substantially  dependent on 
Pfizer  for  the  successful  commercialization  of  such  product.    The  success  of  the  collaboration  arrangement  with 
Pfizer  is  dependent  in  part  on,  among  other  things,  the  skills,  experience  and  efforts  of  Pfizer’s  employees 

28 

 
 
responsible  for  the  project,  Pfizer’s  commitment  to  the  arrangement,  and  the  financial  condition  of  Pfizer,  all  of 
which are beyond our control.  In the event that Pfizer, for any reason, including but not limited to early termination 
of  the  agreement,  fails  to  devote  sufficient  resources  to  successfully  develop  and  commercialize  any  product 
resulting  from  the  collaboration  arrangement,  our  ability  to  earn  milestone  payments  or  receive  royalty  or  profit 
sharing  payments  would  be  adversely  affected,  which  would  have  a  material  adverse  effect  on  our  financial 
condition and prospects. 

Our business is substantially dependent on the success of phase 3 clinical trials for hGH-CTP and our ability to 
achieve regulatory approval for the marketing of this product. 

There  is  no  assurance  that  phase  3  trials  for  hGH-CTP  will  continue  to  be  successful  or  support  marketing 
approval, or that we will be able to obtain marketing approval for the product, or any other product candidate we are 
developing.  Before they can be marketed, our products in development must be approved by the FDA or similar 
foreign governmental agencies.  The process for obtaining FDA approval is both time-consuming and costly, with 
no certainty of a successful outcome.  Before obtaining regulatory approval for the sale of any drug candidate, we 
must conduct extensive preclinical tests and clinical trials to demonstrate the safety and efficacy in humans of our 
product  candidates.    Although  hGH-CTP  has  exhibited  no  serious  adverse  events  associated  with  the  drug 
administration  in  the  clinical  trials  conducted  to  date,  further  testing  or  patient  use  may  undermine  those 
determinations or unexpected side effects may arise.  A failure of any preclinical study or clinical trial can occur at 
any  stage  of  testing.    The  results  of  preclinical  and  initial  clinical  testing  of  these  products  may  not  necessarily 
indicate the results that will be obtained from later or more extensive testing.  It also is possible to suffer significant 
setbacks in advanced clinical trials, even after obtaining promising results in earlier trials.  If phase 3 clinical trials 
for hGH-CTP are not successful or we are unable to achieve regulatory approval for this product, our business will 
be  significantly  adversely  impacted,  which  could  have  a  materially  adverse  effect  on  our  business,  financial 
condition and results of operations. 

Our  business  is  substantially  dependent  on  our  ability  to  develop,  launch  and  generate  revenue  from  our 
diagnostic products. 

Our  business  is  dependent  on  our  ability  to  successfully  commercialize  the  4Kscore  test  and  other  diagnostic 
products,  including  the  Claros  1. 
  We  are  committing  significant  resources  to  the  development  and 
commercialization of these products, and there is no guarantee that we will be able to successfully commercialize 
these tests.  We have limited experience in developing, manufacturing, selling, marketing or distributing diagnostic 
tests.  Although we expect to leverage the national marketing, sales and distribution resources of Bio-Reference to 
enhance sale of, and reimbursement for, the 4Kscore test and other diagnostic products including the Claros 1, we 
may not be successful in our integration with Bio-Reference or be able to successfully commercialize our diagnostic 
products  utilizing  the  Bio-Reference  infrastructure.    If  we  are  not  able  to  successfully  develop,  market  or  sell 
diagnostic tests we develop for any reason, including the failure to obtain any required regulatory approvals, obtain 
reimbursement for, or successfully integrate Bio-Reference, we will not generate any meaningful revenue from the 
sale of such tests.  Even if we are able to develop effective diagnostic tests for sale in the marketplace, a number of 
factors  could  impact  our  ability  to  sell  such  tests  or  generate  any  significant  revenue  from  the  sale  of  such  tests, 
including without limitation: 

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(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

our  ability  to  establish  and maintain  adequate  infrastructure  to  support the  commercial  launch  and 
sale  of  our  diagnostic  tests,  including  establishing  adequate  laboratory  space,  information 
technology infrastructure, sample collection and tracking systems, electronic ordering and reporting 
systems and other infrastructure and hiring adequate laboratory and other personnel; 

the  success  of  the  validation  studies  for  our  diagnostic  tests  under  development  and  our  ability  to 
publish study results in peer-reviewed journals; 

the availability of alternative and competing tests or products and technological innovations or other 
advances in medicine that cause our technologies to be less competitive; 

the accuracy rates of such tests, including rates of false-negatives and/or false-positives; 

concerns regarding the safety or effectiveness or clinical utility of our diagnostic tests; 

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(cid:120) 

(cid:120) 

(cid:120) 

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changes  in  the  regulatory  environment  affecting  health  care  and  health  care  providers,  including 
changes in laws regulating laboratory testing and/or device manufacturers; 

the  extent  and  success  of  our  sales  and  marketing  efforts  and  ability  to  drive  adoption  of  our 
diagnostic tests; 

coverage and reimbursement levels by government payors and private insurers; 

pricing pressures and changes in third-party payor reimbursement policies; and 

intellectual property rights held by others or others infringing our intellectual property rights. 

Our  business  is  substantially  dependent  on  our  ability  to  generate  profits  and  cash  flow  from  our  laboratory 
operations. 

We have made a significant investment in our laboratory operations through the acquisitions of OPKO Lab and 
Bio-Reference.    We  compete  in  the  clinical  laboratory  market  primarily  on  the  basis  of  the  quality  of  testing, 
reporting  and  information  systems,  reputation  in  the  medical  community,  the  pricing  of  services  and  ability  to 
employ qualified personnel.  Our failure to successfully compete on any of these factors could result in the loss of 
clients and a reduction in our revenues and profits.  To offset efforts by payors to reduce the cost and utilization of 
clinical  laboratory  services,  we  will  need  to  obtain  and  retain  new  clients  and  business  partners  and  grow  the 
laboratory operations.    A reduction  in  tests ordered or specimens  submitted by  existing  clients,  without  offsetting 
growth  in  our  client  base,  could  impact  our  ability  to  successfully  grow  our  business  and  could  have  a  material 
adverse impact on our ability to generate profits and cash flow from the laboratory operations. 

Discontinuation  or  recalls  of  existing  testing  products,  failure  to  develop,  or  acquire,  licenses  for  new  or 
improved testing technologies; or our clients using new technologies to perform their own tests could adversely 
affect our business. 

From time to time, manufacturers discontinue or recall reagents, test kits or instruments used by us to perform 

laboratory testing.  Such discontinuations or recalls could adversely affect our costs, testing volume and revenue. 

The clinical laboratory industry is subject to changing technology and new product introductions.  Our success in 
maintaining a leadership position in genomic and other advanced testing technologies will depend, in part, on our 
ability to develop, acquire or license new and improved technologies on favorable terms and to obtain appropriate 
coverage  and  reimbursement  for  these  technologies.    We  may  not  be  able  to  negotiate  acceptable  licensing 
arrangements and it cannot be certain that such arrangements will yield commercially successful diagnostic tests.  If 
we  are  unable  to  license  these  testing  methods  at  competitive  rates,  our  research  and  development  costs  may 
increase as a result.  In addition, if we are unable to license new or improved technologies to expand our esoteric 
testing  operations,  our  testing  methods  may  become  outdated  when  compared  with  our  competition  and  testing 
volume and revenue may be materially and adversely affected. 

Currently,  most  clinical  laboratory  testing  is  categorized  as  “high”  or  “moderate”  complexity,  and  thereby  is 
subject to extensive and costly regulation under CLIA.  The cost of compliance with CLIA makes it impractical for 
most physicians to operate clinical laboratories in their offices, and other laws limit the ability of physicians to have 
ownership in a laboratory and to refer tests to such a laboratory.  Manufacturers of laboratory equipment and test 
kits could seek to increase their sales by marketing point-of-care laboratory equipment to physicians and by selling 
test kits approved for home or physician office use to both physicians and patients.  Diagnostic tests approved for 
home  use  are  automatically  deemed  to  be  “waived”  tests  under  CLIA  and  may  be  performed  in  physician  office 
laboratories  as  well  as  by  patients  in  their  homes  with  minimal  regulatory  oversight.    Other  tests  meeting  certain 
FDA criteria also may be classified as “waived” for CLIA purposes.  The FDA has regulatory responsibility over 
instruments, test kits, reagents and other devices used by clinical laboratories and has taken responsibility from the 
Centers  for  Disease  Control  for  classifying  the  complexity  of  tests  for  CLIA  purposes.    Increased  approval  of 
“waived” test kits could lead to increased testing by physicians in their offices or by patients at home, which could 
affect our market for laboratory testing services and negatively impact our revenues.  If our competitors develop and 
market products that are more effective, safer or less expensive than our current diagnostic products and our future 
product candidates, our net revenues, profitability and commercial opportunities will be negatively impacted. 

30 

 
 
If our competitors develop and market products or services that are more effective, safer or less expensive than 
our  current  and  future  products  or  services,  our  revenues,  profitability  and  commercial  opportunities  will  be 
negatively impacted. 

The pharmaceutical, diagnostic, and laboratory testing industries are highly competitive and require an ongoing, 
extensive search for technological innovation.  The industries are characterized by rapidly advancing technologies, 
intense  competition  and  a  strong  emphasis  on  proprietary  products.    They  also  require,  among  other  things,  the 
ability  to  effectively  discover,  develop,  test and obtain regulatory  approvals  for  products,  as well  as  the  ability  to 
effectively commercialize, market and promote approved products. 

Numerous  companies,  including  major  pharmaceutical  companies,  specialty  pharmaceutical  companies  and 
specialized  biotechnology  companies,  are  engaged  in  the  development,  manufacture  and  marketing  of 
pharmaceutical products competitive with those that we intend to commercialize ourselves and through our partners.  
Competitors  to  our  diagnostics  business  include  major  diagnostic  companies,  reference  laboratories,  molecular 
diagnostic firms, universities and research institutions.  Most of these companies have substantially greater financial 
and  other  resources,  larger  research  and  development  staffs  and  more  extensive  marketing  and  manufacturing 
organizations  than  ours.    This  enables  them,  among  other  things,  to  make  greater  research  and  development 
investments and efficiently utilize their research and development costs, as well as their marketing and promotion 
costs, over a broader revenue base.  This also provides our competitors with a competitive advantage in connection 
with  the  highly  competitive  product  acquisition  and  product  in-licensing  process,  which  may  include  auctions  in 
which  the  highest  bidder  wins.    Our  competitors  may  also  have  more  experience  and  expertise  in  obtaining 
marketing  approvals  from  the  FDA  and other  regulatory authorities.    In  addition  to  product  development,  testing, 
approval, and promotion, other competitive factors in the pharmaceutical and diagnostics industry include industry 
consolidation, product quality and price, product technology, reputation, customer service, and access to technical 
information. 

In  our  clinical  laboratory  operations,  we  compete  with  three  types  of  providers  in  a  highly  fragmented  and 
competitive industry: hospital laboratories, physician-office laboratories and other independent clinical laboratories.  
Our  major  competitors  in  the  New  York  metropolitan  area  are  two  of  the  largest  national  laboratories,  Quest 
Diagnostics and Laboratory Corporation of America.  We are much smaller than these national laboratories. 

The clinical laboratory business is intensely competitive both in terms of price and service.  Pricing of laboratory 
testing services is often one of the most significant factors used by health care providers and third-party payors in 
selecting  a  laboratory.    As  a  result  of  the  clinical  laboratory  industry  undergoing  significant  consolidation,  larger 
clinical laboratory providers are able to increase cost efficiencies afforded by large-scale automated  testing.  This 
consolidation results in greater price competition.  We may be unable to increase cost efficiencies sufficiently, if at 
all,  and  as  a  result,  our  net  earnings  and  cash  flows  could  be  negatively  impacted  by  such  price  competition.  
Additionally,  we  may  also  face  changes  in  fee  schedules,  competitive  bidding  for  laboratory  services  or  other 
actions or pressures reducing payment schedules as a result of increased or additional competition. 

If our competitors market products that are more effective, safer, easier to use or less expensive than our current 
products and future product candidates, or that reach the market sooner than our future product candidates, if any, 
we  may  not  achieve  commercial  success.    In  addition,  the  biopharmaceutical,  diagnostic,  medical  device,  and 
laboratory  industries  are  characterized  by  rapid  technological  change.    Because  our  research  approach  integrates 
many technologies, it may be difficult for us to stay abreast of the rapid changes in each technology.  If we fail to 
stay at the forefront of technological change, we may be unable to compete effectively.  Technological advances or 
products  developed  by  our  competitors  may  render  our  technologies  or  product  candidates  obsolete  or  less 
competitive. 

Our product development activities could be delayed or stopped. 

We do not know whether our current or planned pre-clinical and clinical studies will be completed on schedule, 
or at all.  Furthermore, we cannot guarantee that our planned pre-clinical and clinical studies will begin on time or at 
all.  The commencement of our planned clinical trials could be substantially delayed or prevented by several factors, 
including: 

(cid:120) 

a  limited  number  of,  and  competition  for,  suitable  patients  with  the  particular  types  of  disease 
required for enrollment in our clinical trials or that otherwise meet the protocol’s inclusion criteria 
and do not meet any of the exclusion criteria; 

31 

 
 
(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

a  limited  number  of,  and  competition  for,  suitable  serum  or  other  samples  from  patients  with 
particular types of disease required for our validation studies; 

a limited number of, and competition for, suitable sites to conduct our clinical trials; 

delay  or  failure  to  obtain  FDA  or  other  non-U.S.  regulatory  authorities’  approval  or  agreement  to 
commence a clinical trial; 

delay or failure to obtain sufficient supplies of the product candidate for our clinical trials; 

requirements to provide the drugs, diagnostic tests, or medical devices required in our clinical trial 
protocols or clinical trials at no cost or cost, which may require significant expenditures that we are 
unable or unwilling to make; 

delay  or  failure  to  reach  agreement  on  acceptable  clinical  trial  agreement  terms  or  clinical  trial 
protocols with prospective sites or investigators; and 

delay or failure to obtain institutional review board (“IRB”) approval to conduct or renew a clinical 
trial at a prospective site. 

The  completion  of  our  clinical  trials  could  also  be  substantially  delayed  or  prevented  by  several  factors, 

including: 

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(cid:120) 

(cid:120) 

(cid:120) 

slower than expected rates of patient recruitment and enrollment; 

failure of patients to complete the clinical trial; 

unforeseen safety issues; 

lack of efficacy evidenced during clinical trials; 

termination of our clinical trials by one or more clinical trial sites; 

inability or unwillingness of patients or medical investigators to follow our clinical trial protocols; 
and 

inability to monitor patients adequately during or after treatment. 

Our clinical trials may be suspended or terminated at any time by the FDA, other regulatory authorities, the IRB 
for  any  given site,  or  us.    Additionally,  changes  in  regulatory  requirements  and  guidance  may  occur  and we  may 
need to amend clinical trial protocols to reflect these changes with appropriate regulatory authorities.  Amendments 
may  require  us  to  resubmit  our  clinical  trial  protocols  to  IRBs  for  re-examination,  which  may  impact  the  costs, 
timing, or successful completion of a clinical trial.  Any failure or significant delay in commencing or completing 
clinical trials for our product candidates could materially harm our results of operations and financial condition, as 
well as the commercial prospects for our product candidates. 

We currently have limited marketing staff and no pharmaceutical sales or distribution capabilities in the U.S.  If 
we are unable to develop our sales, marketing and distribution capability on our own or through collaborations 
with marketing partners, we will not be successful in commercializing our pharmaceutical product candidates in 
the U.S. 

We  currently  have  no  pharmaceutical  marketing,  sales  or  distribution  capabilities  in  the  U.S.    We  intend  to 
establish  our  sales  and  marketing  organization  with  technical  expertise  and  supporting  distribution  capabilities  to 
commercialize our pharmaceutical product candidates, which will be expensive and time-consuming.  Any failure or 
delay  in  the  development  of  any  of  our  internal  sales,  marketing,  and  distribution  capabilities  would  adversely 
impact  the  commercialization  of  our  pharmaceutical  products.    With  respect  to  our  existing  and  future  product 
candidates, we may choose to collaborate with third parties that have direct sales forces and established distribution 
systems,  either  to  augment  our  own  sales  force  and  distribution  systems  or  in  lieu  of  our  own  sales  force  and 
distribution  systems.    To  the  extent  that  we  enter  into  co-promotion  or  other  licensing  arrangements,  our  product 
revenue and profit is likely to be lower than if we directly marketed or sold our products.  In addition, any revenue 

32 

 
 
we receive will depend in whole or in part upon the efforts of such third parties, which may not be successful and 
are generally not within our control.  If we are unable to enter into such arrangements on acceptable terms or at all, 
we  may  not  be  able  to  successfully  commercialize  our  existing  and  future  product  candidates.    If  we  are  not 
successful  in  commercializing  our  existing  and  future  pharmaceutical  product  candidates,  either  on  our  own  or 
through  collaborations  with  one  or  more  third  parties,  our  future  product  revenue  will  suffer  and  we  may  incur 
significant additional losses. 

Our product candidates may have undesirable side effects and cause our approved products to be taken off the 
market. 

If a product candidate receives marketing approval and we or others later identify undesirable side effects caused 

by such products: 

(cid:120) 

(cid:120) 

regulatory  authorities  may  require  the  addition  of  labeling  statements,  specific  warnings,  a 
contraindication, or field alerts to physicians and pharmacies; 

regulatory  authorities  may  withdraw  their  approval  of  the  product  and  require  us  to  take  our 
approved product off the market; 

(cid:120)  we may be required to change the way the product is administered, conduct additional clinical trials, 

or change the labeling of the product; 

(cid:120)  we may have limitations on how we promote our products; 

(cid:120) 

sales of products may decrease significantly; 

(cid:120)  we may be subject to litigation or product liability claims; and 

(cid:120) 

our reputation may suffer. 

Any of these events could prevent us from achieving or maintaining market acceptance of the affected product or 
could substantially increase our commercialization costs and expenses, which in turn could delay or prevent us from 
generating significant revenues from its sale. 

Our inability to meet regulatory quality standards applicable to our manufacturing and quality processes and to 
address quality control issues in a timely manner could delay the production and sale of our products or result in 
recalls of products. 

Manufacturing or design defects, unanticipated use of our products, or inadequate disclosure of risks relating to 
the  use  of our products  could  lead  to injury  or  other  adverse  events.    These  events  could  lead  to recalls  or  safety 
alerts relating to our products (either voluntary or required by governmental authorities) and could result, in certain 
cases, in the removal of a product from the market.  Any recall could result in significant costs as well as negative 
publicity that could reduce demand for our products.  Personal injuries relating to the use of our products can also 
result in product liability claims being brought against us.  In some circumstances, such adverse events could also 
cause delays in new product approvals. 

We are committed to providing high quality products to our customers, and we plan to meet this commitment by 
working  diligently  to  continue  implementing  updated  and  improved  quality  systems  and  concepts  throughout  our 
organization.  We cannot assure you that we will not have quality control issues in the future, which may result in 
warning letters and citations from the FDA.  If we receive any warning letters from the FDA in the future, there can 
be no assurances regarding the length of time or cost it will take us to resolve such quality issues to our satisfaction 
and to the satisfaction of the FDA.  If our remedial actions are not satisfactory to the FDA, we may have to devote 
additional financial and human resources to our efforts, and the FDA may take further regulatory actions against us 
including,  but  not  limited  to,  assessing  civil  monetary  penalties  or  imposing  a  consent  decree  on  us,  which  could 
result in further regulatory constraints, including the governance of our quality system by a third party.  Our inability 
to resolve these issues or the taking of further regulatory action by the FDA may weaken our competitive position 
and have a material adverse effect on our business, results of operations and financial condition. 

We manufacture pharmaceutical products in Ireland, Mexico, Spain, and Israel.  We also prepare necessary test 
reagents and assemble and package the cassettes for our point-of-care diagnostic system at our facility in Woburn, 

33 

 
 
Massachusetts.  Any quality control issues at our facilities may weaken our competitive position and have a material 
adverse effect on our business results of operations and financial condition. 

As  a  medical  device  manufacturer,  we  are  required  to  register  with  the  FDA  and  are  subject  to  periodic 
inspection  by  the  FDA  for  compliance  with  its  Quality  System  Regulation  (“QSR”)  requirements,  which  require 
manufacturers  of  medical  devices  to  adhere  to  certain  regulations,  including  testing,  quality  control  and 
documentation procedures.  Compliance with applicable regulatory requirements is subject to continual review and 
is monitored rigorously through periodic inspections by the FDA.  In addition, most international jurisdictions have 
adopted regulatory approval and periodic renewal requirements for medical devices, and we must comply with these 
requirements in order to market our products in these jurisdictions.  In the European Community, we are required to 
maintain certain ISO certifications in order to sell our products and must undergo periodic inspections by notified 
bodies to obtain and maintain these certifications.  Further, some emerging markets rely on the FDA’s Certificate for 
Foreign  Government  (“CFG”)  in  lieu  of  their  own  regulatory  approval  requirements.    Our  failure,  or  our 
manufacturers’  failure  to  meet  QSR  ISO,  or  any  other  regulatory  requirements  or  industry  standards  could  delay 
production  of  our  products  and  lead  to  fines,  difficulties  in  obtaining  regulatory  clearances,  recalls  or  other 
consequences, which could, in turn, have a material adverse effect on our business, results of operations, and our 
financial condition. 

Failure to establish, and perform to, appropriate quality standards to assure that the highest level of quality is 
observed  in  the  performance  of  our  testing  services  could  adversely  affect  the  results  of  our  operations  and 
adversely impact our reputation. 

The  provision of  clinical  testing  services,  including  anatomic  pathology  services,  and  related  services,  and  the 
design,  manufacture  and  marketing  of  diagnostic  products  involve  certain  inherent  risks.    The  services  that  we 
provide and the products that we design, manufacture and market are intended to provide information for healthcare 
providers in providing patient care.  Therefore, users of our services and products may have a greater sensitivity to 
errors than the users of services or products that are intended for other purposes. 

Similarly,  negligence  in  performing  our  services  can  lead  to  injury  or  other  adverse  events.    We  may  be  sued 
under  physician  liability  or  other  liability  law  for  acts  or  omissions  by  our  pathologists,  laboratory  personnel  and 
hospital  employees  who  are  under  the  supervision  of  our  hospital-based  pathologists.    We  are  subject  to  the 
attendant risk of substantial damages awards and risk to our reputation. 

Even  if  we  receive  regulatory  approval  or  clearance  to  market  our  product  candidates,  the  market  may  not  be 
receptive to our products. 

Even  if  our  product  candidates  obtain  marketing  approval  or  clearance,  our  products  may  not  gain  market 
acceptance  among  physicians,  patients,  health  care  payors  and/or  the  medical  community.    We  believe  that  the 
degree of market acceptance will depend on a number of factors, including: 

(cid:120) 

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(cid:120) 

timing of market introduction of competitive products; 

safety and efficacy of our product compared to other products; 

prevalence and severity of any side effects; 

potential advantages or disadvantages over alternative treatments; 

strength of marketing and distribution support; 

price of our products, both in absolute terms and relative to alternative treatments; 

availability of coverage and reimbursement from government and other third-party payors; 

potential product liability claims; 

limitations or warnings contained in a product’s regulatory authority-approved labeling; and 

34 

 
 
(cid:120) 

changes in the standard of care for the targeted indications for any of our product candidates, which 
could reduce the marketing impact of any claims that we could make following applicable regulatory 
authority approval. 

In addition, our efforts to educate the medical community and health care payors on the benefits of our product 
candidates  may  require  significant  resources  and  may  never  be  successful.    If  our  products  do  not  gain  market 
acceptance, it would have a material adverse effect on our business, results of operations, and financial condition. 

If our existing and future product candidates are not covered and eligible for reimbursement from government 
and third party payors, we may not be able to generate significant revenue or achieve or sustain profitability. 

The coverage and reimbursement status of newly approved or cleared drugs, diagnostic and laboratory tests is 
uncertain,  and  failure  of  our  pharmaceutical  products,  diagnostic  tests  or  laboratory  to  be  adequately  covered  by 
insurance and eligible for adequate reimbursement could limit our ability to market any future product candidates 
we may develop and decrease our ability to generate revenue from any of our existing and future product candidates 
that  may  be  approved  or  cleared.    The  commercial  success  of  our  existing  and  future  product  candidates  in  both 
domestic and international markets will depend in part on the availability of coverage and adequate reimbursement 
from third-party payors, including government payors, such as the Medicare and Medicaid programs, managed care 
organizations,  and  other  third-party  payors.    The  government  and  other  third-party  payors  are  increasingly 
attempting to contain health care costs by limiting both insurance coverage and the level of reimbursement for new 
drugs  and  diagnostic  tests  and,  as  a  result,  they  may  not  cover  or  provide  adequate  payment  for  our  product 
candidates.    These  payors  may  conclude  that  our  product  candidates  are  less  safe,  less  effective,  or  less  cost-
effective  than  existing  or  later-introduced  products.    These  payors  may  also  conclude  that  the  overall  cost  of  the 
procedure  using  one  of  our  devices  exceeds  the  overall  cost  of  the  competing  procedure  using  another  type  of 
device,  and  third-party  payors  may  not  approve  our  product  candidates  for  insurance  coverage  and  adequate 
reimbursement. 

The failure to obtain coverage and adequate or any reimbursement for our product candidates, or health care cost 
containment  initiatives  that  limit  or  restrict  reimbursement  for  our  product  candidates,  may  reduce  any  future 
product revenue.  Even though a drug (not administered by a physician) may be approved by the FDA, this does not 
mean that a Prescription Drug Plan (“PDP”), a private insurer operating under Medicare Part D, will list that drug on 
its formulary or will set a reimbursement level.  PDPs are not required to make every FDA-approved drug available 
on their formularies.  If our drug products are not listed on sufficient number of PDP formularies or if the PDPs’ 
levels  of  reimbursement  are  inadequate,  our  business,  results  of  operations,  and  financial  condition  could  be 
materially adversely affected. 

Additionally,  our  failure  to  comply  with  applicable  Medicare,  Medicaid  and  other  governmental  payor  rules 
could result in our inability to participate in a governmental payor program, our returning funds already paid to us, 
civil monetary penalties, criminal penalties and/or limitations on the operational function of our laboratory.  If we 
were unable to receive reimbursement under a governmental payor program, a substantial portion of our revenues 
would be lost, which would adversely affect our results of operations and financial condition. 

As we evolve from a company primarily involved in development to a company also involved in commercialization 
of  our  pharmaceutical  and  diagnostic  products  as  well  as  our  laboratory  testing  services,  we  may  encounter 
difficulties in managing our growth and expanding our operations successfully. 

As  we  advance  our  product  candidates  and  expand  our  business,  we  will  need  to  expand  our  development, 
regulatory  and  commercial  infrastructure.    As  our  operations  expand,  we  expect  that  we  will  need  to  manage 
additional relationships with various third parties, collaborators and suppliers.  Maintaining these relationships and 
managing  our  future  growth  will  impose  significant  added  responsibilities  on  members  of  our  management.    We 
must be able to: manage our development efforts and operations effectively; manage our clinical trials effectively; 
hire,  train  and  integrate  additional  management,  administrative  and  sales  and  marketing  personnel;  improve  our 
managerial, development, operational and finance systems; implement and manage an effective marketing strategy; 
and expand our facilities, all of which may impose a strain on our administrative and operational infrastructure. 

Furthermore, we may acquire additional businesses, products or product candidates that complement or augment 
our existing business.  Integrating any newly acquired business or product could be expensive and time-consuming.  
We  may  not  be  able  to  integrate  any  acquired  business  or  product  successfully  or  operate  any  acquired  business 
profitably.    Our  future  financial  performance  will  depend,  in  part,  on  our  ability  to  manage  any  future  growth 

35 

 
 
effectively and our ability to integrate any acquired businesses.  We may not be able to accomplish these tasks, and 
our failure to accomplish any of them could prevent us from successfully growing our company, which would have 
a material adverse effect on our business, results of operations and financial condition. 

Our success is dependent to a significant degree upon the involvement and efforts of our Chairman and Chief 
Executive Officer, Phillip Frost, M.D. 

Our success is dependent to a significant degree upon the efforts of our Chairman and Chief Executive Officer, 
Phillip Frost, M.D., who is essential to our business.  The departure of our CEO for whatever reason or the inability 
of  our  CEO  to  continue  to  serve  in  his  present  capacity  could  have  a  material  adverse  effect  upon  our  business, 
financial condition, and results of operations.  Our CEO has a highly regarded reputation in the pharmaceutical and 
medical  industry  and  attracts  business  opportunities  and  assists  both  in  negotiations  with  acquisition  targets, 
investment targets, and potential joint venture partners.  Our CEO has also provided financing to the Company, both 
in terms of a credit agreement and equity investments.  If we lost his services, our relationships with acquisition and 
investment  targets,  joint  ventures,  and  investors  may  suffer  and  could  cause  a  material  adverse  impact  on  our 
operations, financial condition, and the value of our Common Stock. 

If  we  fail  to  attract  and  retain  key  management  and  scientific  personnel,  we  may  be  unable  to  successfully 
operate our business and develop or commercialize our product candidates. 

We will need to expand and effectively manage our managerial, operational, sales, financial, development, and 
other  resources  in  order  to  successfully  operate  our  business  and  pursue  our  research,  development,  and 
commercialization efforts for our product candidates.  Our success depends on our continued ability to attract, retain, 
and  motivate  highly  qualified  management  and  pre-clinical  and  clinical  personnel.    The  loss  of  the  services  or 
support of any of our senior management, particularly Dr. Phillip Frost, our Chairman of the Board and CEO, could 
delay or prevent the development and commercialization of our product candidates. 

If  the  FDA  or  other  applicable  regulatory  authorities  approve  generic  products  that  compete  with  any  of  our 
products or product candidates, the sale of our products or product candidates may be adversely affected. 

Once  an  NDA  is  approved,  the  product  covered  thereby  becomes  a  “listed  drug”  which,  in  turn  can  be  relied 
upon  by  potential  competitors  in  support  of  an  approval  of  an  abbreviated  new  drug  application,  or  ANDA,  or 
505(b)(2)  application.    U.S.  laws  and  other  applicable  policies  provide  incentives  to  manufacturers  to  create 
modified, non-infringing versions of a drug to facilitate the approval of an ANDA or other application for a generic 
substitute.  These manufacturers might only be required to conduct a relatively inexpensive study to show that their 
product has the same active ingredient(s), dosage form, strength, route of administration, and conditions of use, or 
labeling,  as  our  product  or  product  candidate  and  that  the  generic  product  is  bioequivalent  to  ours,  meaning  it  is 
absorbed in the body at the same rate and to the same extent as our product or product candidate.  These generic 
equivalents,  which  must  meet  the  same  quality  standards  as  branded  pharmaceuticals,  would  be  significantly  less 
costly than ours to bring to market and companies that produce generic equivalents are generally able to offer their 
products at lower prices.  Thus, after the introduction of a generic competitor, a significant percentage of sales of 
any branded product is typically lost to the generic product.  Accordingly, competition from generic equivalents to 
our products or product candidates would materially adversely impact our revenues, profitability and cash flows and 
substantially limit our ability to obtain a return on the investments that we have made in our product candidates. 

If  we  fail  to  acquire  and  develop  other  products  or  product  candidates  at  all  or  on  commercially  reasonable 
terms, we may be unable to diversify or grow our business. 

We intend to continue to rely on acquisitions and in-licensing as a source of our products and product candidates 
for development and commercialization.  The success of this strategy depends upon our ability to identify, select, 
and  acquire  pharmaceutical  and  diagnostic  products,  drug  delivery  technologies,  and  medical  device  product 
candidates.    Proposing,  negotiating,  and  implementing  an  economically  viable  product  acquisition  or  license  is  a 
lengthy  and  complex  process.    We  compete  for  partnering  arrangements  and  license  agreements  with 
pharmaceutical, biotechnology and medical device companies, and academic research institutions.  Our competitors 
may  have  stronger  relationships  with  third  parties  with  whom  we  are  interested  in  collaborating  and/or  may  have 
more established histories of developing and commercializing products. 

Most of our competitors also have substantially greater financial and other resources than us.  As a result, our 
competitors may have a competitive advantage in entering into partnering arrangements with such third parties, as 
such partnering arrangements are often decided in an auction process in which the highest bidder wins.  In addition, 

36 

 
 
even  if  we  find  promising  product  candidates,  and  generate  interest  in  a  partnering  or  strategic  arrangement  to 
acquire such product candidates, we may not be able to acquire rights to additional product candidates or approved 
products on terms that we find acceptable, or at all. 

We  expect  that  any  product  candidate  to  which  we  acquire  rights  will  require  additional  development  efforts 
prior to commercial sale, including extensive clinical testing and approval or clearance by the FDA and other non-
U.S.  regulatory  authorities.    All  product  candidates  are  subject  to  the  risks  of  failure  inherent  in  pharmaceutical, 
diagnostic test or medical device product development, including the possibility that the product candidate will not 
be shown to be sufficiently safe and effective for approval by regulatory authorities.  Even if the product candidates 
are  approved  or  cleared  for  marketing,  we  cannot  be  sure  that  they  would  be  capable  of  economically  feasible 
production  or  commercial  success.    If  we  fail  to  acquire  or  develop  other  product  candidates  that  are  capable  of 
economically feasible production and commercial success, our business, results of operations and financial condition 
and cash flows may be materially adversely affected. 

We rely on third parties to manufacture and supply our pharmaceutical and diagnostic product candidates. 

If our manufacturing partners are unable to produce our products in the amounts that we require, we may not be 
able to establish a contract and obtain a sufficient alternative supply from another supplier on a timely basis and in 
the quantities we require.  We expect to continue to depend on third-party contract manufacturers for the foreseeable 
future. 

Our product candidates require precise, high quality manufacturing.  Any of our contract manufacturers will be 
subject to ongoing periodic unannounced inspection by the FDA and other non-U.S. regulatory authorities to ensure 
strict  compliance  with  QSR  regulations  for  devices  or  cGMPs  for  drugs,  and  other  applicable  government 
regulations  and  corresponding  standards  relating  to  matters  such  as  testing,  quality  control,  and  documentation 
procedures.  If our contract manufacturers fail to achieve and maintain high manufacturing standards in compliance 
with QSR or cGMPs, we may experience manufacturing errors resulting in patient injury or death, product recalls or 
withdrawals, delays or interruptions of production or failures in product testing or delivery, delay or prevention of 
filing or approval of marketing applications for our products, cost overruns, or other problems that could seriously 
harm our business. 

Any  performance  failure  on  the  part  of  our  contract  manufacturers  could  delay  clinical  development  or 
regulatory approval or clearance of our product candidates or commercialization of our future product candidates, 
depriving us of potential product revenue and resulting in additional losses.  In addition, our dependence on a third 
party  for  manufacturing  may  adversely  affect  our  future  profit  margins.    Our  ability  to  replace  an  existing 
manufacturer may be difficult because the number of potential manufacturers is limited and the FDA must approve 
any  replacement  manufacturer  before  it  can  begin  manufacturing  our  product  candidates.    Such  approval  would 
result  in  additional  non-clinical  testing  and  compliance  inspections.    It  may  be  difficult  or  impossible  for  us  to 
identify and engage a replacement manufacturer on acceptable terms in a timely manner, or at all. 

Independent  clinical  investigators  and  contract  research  organizations  that  we  engage  to  conduct  our  clinical 
trials may not be diligent, careful or timely. 

We depend on independent clinical investigators to conduct our clinical trials.  Contract research organizations 
may also assist us in the collection and analysis of data.  These investigators and contract research organizations will 
not be our employees, and we will not be able to control, other than by contract, the amount of resources, including 
time, that they devote to products that we develop.  If independent investigators fail to devote sufficient resources to 
the  development  of  product  candidates  or  clinical  trials,  or  if  their  performance  is  substandard,  it  will  delay  the 
marketing approval or clearance and commercialization of any products that we develop.  Further, the FDA requires 
that  we  comply  with  standards,  commonly  referred  to  as  good  clinical  practice,  for  conducting,  recording  and 
reporting clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity, 
and  confidentiality  of  trial  subjects  are  protected.    If  our  independent  clinical  investigators  and  contract  research 
organizations fail to comply with good clinical practice, the results of our clinical trials could be called into question 
and the clinical development of our product candidates could be delayed. 

Failure of clinical investigators or contract research organizations to meet their obligations to us or comply with 
federal  regulations  and  good  clinical  practice  procedures  could  adversely  affect  the  clinical  development  of  our 
product candidates and harm our business, results of operations, and financial condition. 

37 

 
 
If the validity of an informed consent from a subject was to be challenged, it may negatively impact our product 
development efforts. 

We take steps to ensure that all clinical data and genetic and other biological samples are collected from subjects 
who provide informed consent for the data and samples and we work to ensure that the subjects from whom our data 
and  samples  are  collected  do  not  retain  any  proprietary  or  commercial  rights  to  the  data  or  samples  or  any 
discoveries  derived  from  them.    However,  because  we  may  collect  data  and  samples  from  countries  that  are 
governed  by  a  number  of  different  regulatory  regimes,  there  are  many  complex  legal  questions  relating  to  the 
adequacy  of  informed  consent  that  we  must  continually  address.    The  adequacy  of  any  given  subject’s  informed 
consent  may  be  challenged  in  the  future,  and  any  given  informed  consent  may  prove  unlawful  or  otherwise 
inadequate for our purposes.  Any findings against us, or our clinical collaborators, could obligate us to stop using 
some of our clinical samples, which in turn may hinder our product development efforts.  Such a result would also 
likely involve legal challenges that may consume our management and financial resources. 

Failure to timely or accurately bill for our services could have a material adverse effect on our business. 

Billing for laboratory testing services is extremely complicated and is subject to extensive and non-uniform rules 
and administrative requirements.  Depending on the billing arrangement and applicable law, we bill various payors, 
such as patients, insurance companies, Medicare, Medicaid, physicians, hospitals and employer groups.  Changes in 
laws and regulations could increase the complexity and cost of our billing process.  Additionally, in the U.S., third-
party payors generally require billing codes on claims for reimbursement that describe the services provided.  For 
laboratory services, the American Medical Association establishes most of the billing codes using a data code set 
called  Current  Procedural  Terminology,  or  CPT,  codes.    Each  third-party  payor  generally  develops  payment 
amounts  and  coverage  policies  for  their  beneficiaries  or  members  that  ties  to  the  CPT  code  established  for  the 
laboratory  test  and,  therefore,  coverage  and  reimbursement  may  differ  by  payor  even  if  the  same  billing  code  is 
reported for claims filing purposes.  For laboratory tests without a specific billing code, payors often review claims 
on a claim-by-claim basis and there are increased uncertainties as to coverage and eligibility for reimbursement. 

We  intend  to  implement  a  new  billing  system  for  our  laboratory  business  in  2016.    The  adoption  of  the  new 
billing  system,  which  will  replace  the  existing  billing  system,  poses  several  challenges  relating  to,  among  other 
things, training of personnel, communication of new rules and procedures, changes in corporate culture, migration of 
data,  and  the  potential  instability  of  the  new  system.    If  the  remaining  implementation  of  the  billing  system  is 
delayed, in whole or in part, we would continue to use our current systems which may not be sufficient to support 
our planned operations  and significant upgrades  to  the  current  systems  may  be  warranted or  required  to  meet  our 
business needs pending the new billing system implementation. 

Incorrect or incomplete documentation and billing information could result in non-payment for services rendered 
or having to pay back amounts incorrectly billed and collected.  Further, the failure to timely or correctly bill could 
lead to various penalties, including: (1) exclusion from participation in CMS and other government programs; (2) 
asset  forfeitures;  (3)  civil  and  criminal  fines  and  penalties;  and  (4)  the  loss  of  various  licenses,  certificates  and 
authorizations necessary to operate our business, any of which could have a material adverse effect on our results of 
operations or cash flows. 

Failure  in  our  information  technology  systems,  including  by  cybersecurity  attacks  or  other  data  security 
incidents,  could  significantly  increase  testing  turn-around  time  or  billing  processes  and  otherwise  disrupt  our 
operations. 

 Our  operations  depend,  in  part,  on  the  continued  performance  of  our  information  technology  systems.    Our 
information technology systems are potentially vulnerable to physical or electronic break-ins, computer viruses and 
similar  disruptions.    In  addition,  we  are  in  the  process  of  integrating  the  information  technology  systems  of  our 
recently  acquired  subsidiaries,  and  we  may  experience  system  failures  or  interruptions  as  a  result  of  this  process.  
Sustained system failures or interruption of our systems in one or more of our laboratory operations could disrupt 
our ability to process laboratory requisitions, perform testing, provide test results in a timely manner and/or bill the 
appropriate party.  Failure of our information technology systems could adversely affect our business, profitability 
and financial condition. 

Although  we  have  information  technology  security  systems,  a  successful  cybersecurity  attack  or  other  data 
security  incident  could  result  in  the  misappropriation  and/or  loss  of  confidential  or  personal  information,  create 
system interruptions, or deploy malicious software that attacks our systems.  It is possible that a cybersecurity attack 

38 

 
 
might not be noticed for some period of time.  The occurrence of a cybersecurity attack or incident could result in 
business interruptions from the disruption of our information technology systems, or negative publicity resulting in 
reputational  damage  with  our  customers,  shareholders  and  other  stakeholders  and/or  increased  costs  to  prevent, 
respond  to  or  mitigate  cybersecurity  events.    In  addition,  the  unauthorized  dissemination  of  sensitive  personal 
information or proprietary or confidential information could expose us or other third-parties to regulatory fines or 
penalties, litigation and potential liability, or otherwise harm our business. 

Healthcare plans have taken steps to control the utilization and reimbursement of healthcare services, including 
clinical test services. 

We  also  face  efforts  by  non-governmental  third-party  payors,  including  healthcare  plans,  to  reduce  utilization 

and reimbursement for clinical testing services. 

The healthcare industry has experienced a trend of consolidation among healthcare insurance plans, resulting in 
fewer  but  larger  insurance  plans  with  significant  bargaining  power  to  negotiate  fee  arrangements  with  healthcare 
providers, including clinical testing providers.  These healthcare plans, and independent physician associations, may 
demand that clinical testing providers accept discounted fee structures or assume all or a portion of the financial risk 
associated  with  providing  testing  services  to  their  members  through  capped  payment  arrangements.    In  addition, 
some  healthcare  plans  have  been  willing  to  limit  the  PPO  or  POS  laboratory  network  to  only  a  single  national 
laboratory to obtain improved fee-for-service pricing.  There are also an increasing number of patients enrolling in 
consumer driven products and high deductible plans that involve greater patient cost-sharing. 

The increased consolidation among healthcare plans also has increased the potential adverse impact of ceasing to 
be  a  contracted  provider  with  any  such  insurer.    The  Health  Care  Reform  Law  includes  provisions,  such  as  the 
creation of healthcare exchanges, which may encourage healthcare insurance plans to increase exclusive contracting. 

We  expect  continuing  efforts  to  reduce  reimbursements,  to  impose  more  stringent  cost  controls  and  to  reduce 
utilization of clinical test services.  These efforts, including future changes in third-party payor rules, practices and 
policies,  or  ceasing  to  be  a  contracted  provider  to  a  healthcare  plan,  may  have  a  material  adverse  effect  on  our 
business. 

The success of our business may be dependent on the actions of our collaborative partners. 

We have entered into and expect in the future to enter into collaborative arrangements with established multi-
national  pharmaceutical,  diagnostic,  and  medical  device  companies,  which  will  finance  or  otherwise  assist  in  the 
development, manufacture and marketing of products incorporating our technology.  We anticipate deriving some 
revenues  from  research  and  development  fees,  license  fees,  milestone  payments,  and  royalties  from  collaborative 
partners.  Our prospects, therefore, may depend to some extent upon our ability to attract and retain collaborative 
partners and to develop technologies and products that meet the requirements of prospective collaborative partners.  
In  addition,  our  collaborative  partners  may  have  the  right  to  abandon  research  projects,  guide  strategy  regarding 
prosecution of relevant patent applications and terminate applicable agreements, including funding obligations, prior 
to or upon the expiration of the agreed-upon research terms.  There can be no assurance that we will be successful in 
establishing collaborative arrangements on acceptable terms or at all, that collaborative partners will not terminate 
funding  before  completion  of  projects,  that  our  collaborative  arrangements  will  result  in  successful  product 
commercialization, or that we will derive any revenues from such arrangements.  To the extent that we are unable to 
develop  and  maintain  collaborative  arrangements,  we  would  need  substantial  additional  capital  to  undertake 
research, development, and commercialization activities on our own. 

If  we  are  unable  to  obtain  and  enforce  patent  protection  for  our  products,  our  business  could  be  materially 
harmed. 

Our success depends, in part, on our ability to protect proprietary methods and technologies that we develop or 
license under the patent and other intellectual property laws of the U.S. and other countries, so that we can prevent 
others from unlawfully using our inventions and proprietary information.  However, we may not hold proprietary 
rights  to  some  patents  required  for  us  to  commercialize  our  product  candidates.    Because  certain  U.S.  patent 
applications  are  confidential  until  patents  issue,  such  as  applications  filed  prior  to  November 29,  2000,  or 
applications filed after such date for which nonpublication has been requested, third parties may have filed patent 
applications  for  technology  covered  by  our  pending  patent  applications  without  our  being  aware  of  those 
applications, and our patent applications may not have priority over those applications.  For this and other reasons, 
we or our third-party collaborators may be unable to secure desired patent rights, thereby losing desired exclusivity.  

39 

 
 
If licenses are not available to us on acceptable terms, we may not be able to market the affected products or conduct 
the  desired  activities,  unless  we  challenge  the  validity,  enforceability,  or  infringement  of  the  third-party  patent  or 
otherwise circumvent the third-party patent. 

Our  strategy  depends  on  our  ability  to  rapidly  identify  and  seek  patent  protection  for  our  discoveries.    In 
addition, we will rely on third-party collaborators to file patent applications relating to proprietary technology that 
we develop jointly during certain collaborations.  The process of obtaining patent protection is expensive and time-
consuming.    If  our  present  or  future  collaborators  fail  to  file  and  prosecute  all  necessary  and  desirable  patent 
applications at a reasonable cost and in a timely manner, our business will be adversely affected.  Despite our efforts 
and the efforts of our collaborators to protect our proprietary rights, unauthorized parties may be able to obtain and 
use information that we regard as proprietary. 

The  issuance  of  a  patent  does  not  guarantee  that  it  is  valid  or  enforceable.    Any  patents  we  have  obtained,  or 
obtain in the future, may be challenged, invalidated, unenforceable, or circumvented.  Moreover, the U.S. Patent and 
Trademark Office (“USPTO”) may commence interference proceedings involving our patents or patent applications.  
In  addition,  court  decisions  may  introduce  uncertainty  in  the  enforceability  or  scope  of  patents  owned  by 
biotechnology,  pharmaceutical,  and  medical  device  companies.    Any  challenge  to,  finding  of  unenforceability  or 
invalidation or circumvention of, our patents or patent applications would be costly, would require significant time 
and attention of our management, and could have a material adverse effect on our business, results of operations and 
financial condition. 

Our  pending  patent  applications  may  not  result  in  issued  patents.    The  patent  position  of  pharmaceutical, 
biotechnology,  diagnostic,  and  medical  device  companies,  including  ours,  is  generally  uncertain  and  involves 
complex legal and factual considerations.  The standards that the USPTO and its foreign counterparts use to grant 
patents are not always applied predictably or uniformly and can change.  There is also no uniform, worldwide policy 
regarding the subject matter and scope of claims granted or allowable in pharmaceutical, biotechnology, diagnostic, 
or medical device patents.  Accordingly, we do not know the degree of future protection for our proprietary rights or 
the  breadth  of  claims  that  will  be  allowed  in  any  patents  issued  to  us  or  to  others.    The  legal  systems  of  certain 
countries do not favor the aggressive enforcement of patents, and the laws of foreign countries may not protect our 
rights to the same extent as the laws of the U.S.  Therefore, the enforceability or scope of our owned or licensed 
patents in the U.S. or in foreign countries cannot be predicted with certainty, and, as a result, any patents that we 
own or license may not provide sufficient protection against competitors.  We may not be able to obtain or maintain 
patent protection for our pending patent applications, those we may file in the future, or those we may license from 
third parties. 

While we believe that our patent rights are enforceable, we cannot assure you that any patents that have issued, 
that  may  issue,  or  that  may  be  licensed  to  us  will  be  enforceable  or  valid,  or  will  not  expire  prior  to  the 
commercialization of our product candidates, thus allowing others to more effectively compete with us.  Therefore, 
any patents that we own or license may not adequately protect our product candidates or our future products, which 
could have a material adverse effect on our business, results of operations, and financial condition. 

If  we  are  unable  to  protect  the  confidentiality  of  our  proprietary  information  and  know-how,  the  value  of  our 
technology and products could be adversely affected. 

In  addition  to  patent  protection,  we  also  rely  on  other proprietary  rights,  including protection  of  trade  secrets, 
know-how,  and  confidential  and  proprietary  information.    To  maintain  the  confidentiality  of  trade  secrets  and 
proprietary information, we will seek to enter into confidentiality agreements with our employees, consultants, and 
collaborators  upon  the  commencement  of  their  relationships  with  us.    These  agreements  generally  require  that  all 
confidential information developed by the individual or made known to the individual by us during the course of the 
individual’s  relationship  with  us  be  kept  confidential  and  not  disclosed  to  third  parties.    Our  agreements  with 
employees also generally provide that any inventions conceived by the individual in the course of rendering services 
to us shall be our exclusive property. 

However, we may not obtain these agreements in all circumstances, and individuals with whom we have these 
agreements may not comply with their terms.  In the event of unauthorized use or disclosure of our trade secrets or 
proprietary information, these agreements, even if obtained, may not provide meaningful protection, particularly for 
our trade secrets or other confidential information.  To the extent that our employees, consultants, or contractors use 
technology or know-how owned by third parties in their work for us, disputes may arise between us and those third 
parties as to the rights in related inventions. 

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Adequate remedies may not exist in the event of unauthorized use or disclosure of our confidential information.  
The  disclosure  of our  trade  secrets  would  impair  our  competitive  position  and  may  materially  harm  our business, 
financial condition, and results of operations. 

We will rely heavily on licenses from third parties.  Failure to comply with the provisions of these licenses could 
result in the loss of our rights under the license agreements. 

Many of the patents and patent applications in our patent portfolio are not owned by us, but are licensed from 
third parties.  Such license agreements give us rights for the commercial exploitation of the patents resulting from 
the respective patent applications, subject to certain provisions of the license agreements.  Failure to comply with 
these provisions could result in the loss of our rights under these license agreements.  Our inability to rely on these 
patents and patent applications, which are the basis of our technology, would have a material adverse effect on our 
business, results of operations and financial condition. 

We license patent rights to certain of our technology from third-party owners.  If such owners do not properly 
maintain or enforce the patents underlying such licenses, our competitive position and business prospects will be 
harmed. 

We have obtained licenses from, among others, INEOS Healthcare, Washington University, UT Southwestern, 
the President and Fellows of Harvard College, The Scripps Research Institute, Arctic Partners, and Academia Sinica, 
among others, that are necessary or useful for our business.  In addition, we intend to enter into additional licenses of 
third-party  intellectual  property  in  the  future.    Although  our  goal  is  to  obtain  exclusivity  in  our  licensing 
transactions, we cannot guarantee that no third parties will step forward and assert inventorship or ownership in our 
in-licensed patents.  In some cases, we may rely on the assurances of our licensors that all ownership rights have 
been secured and that all necessary agreements are intact or forthcoming. 

Our  success  will  depend  in  part  on  our  ability  or  the  ability  of  our  licensors  to  obtain,  maintain,  and  enforce 
patent  protection  for  our  licensed  intellectual  property  and,  in  particular,  those  patents  to  which  we  have  secured 
exclusive rights in our field.  We or our licensors may not successfully prosecute the patent applications which are 
licensed to us.  Even if patents issue in respect of these patent applications, we or our licensors may fail to maintain 
these  patents,  may  determine  not  to  pursue  litigation  against  other  companies  that  are  infringing  these  patents,  or 
may  pursue  such  litigation  less  aggressively  than  we  would.    Without  protection  for  the  intellectual  property  we 
have  licensed,  other  companies  might  be  able  to  offer  substantially  identical  products  for  sale,  which  could 
adversely  affect  our  competitive  business  position  and  harm  our  business,  results  of  operations  and  financial 
condition. 

Our commercial success depends significantly on our ability to operate without infringing the patents and other 
proprietary rights of third parties. 

Other  entities  may  have  or  obtain  patents  or  proprietary  rights  that  could  limit  our  ability  to  develop, 
manufacture,  use,  sell,  offer  for  sale  or  import  products,  or  impair  our  competitive  position.    In  addition,  other 
entities  may  have  or  obtain  patents  or  proprietary  rights  that  cover  our  current  research  and  preclinical  studies.  
While there are statutory exemptions to patent infringement for those who are using third party patented technology 
in the process of pursuing FDA regulatory approval, the U.S. case law pertaining to such exemptions changes over 
time.    Lawsuits  involving  such  exemptions  are very fact intensive  and  it  is  currently  unclear under U.S.  case  law 
whether preclinical studies would always qualify for such an exemption, and whether such exemptions would apply 
to research tools.  To the extent that our current research and preclinical studies may be covered by the patent rights 
of  others,  the  risk  of  suit  may  continue  after  such  patents  expire  because  the  statute  of  limitations  for  patent 
infringement  runs  for  six  years.    To  the  extent  that  a  third  party  develops  and  patents  technology  that  covers  our 
products, we may be required to obtain licenses to that technology, which licenses may not be available or may not 
be available on commercially reasonable terms, if at all.  If licenses are not available to us on acceptable terms, we 
will not be able to market the affected products or conduct the desired activities, unless we challenge the validity, 
enforceability or infringement of the third-party patent, or circumvent the third-party patent, which would be costly 
and would require significant time and attention of our management.  Third parties may have or obtain by license or 
assignment valid and enforceable patents or proprietary rights that could block us from developing products using 
our technology.  Our failure to obtain a license to any technology that we require may materially harm our business, 
financial condition, and results of operations. 

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If  we  become  involved  in  patent  litigation  or  other  proceedings  related  to  a  determination  of  rights,  we  could 
incur  substantial  costs  and  expenses,  substantial  liability  for  damages  or  be  required  to  stop  our  product 
development and commercialization efforts. 

Third  parties  may  sue  us  for  infringing  their  patent  rights.    Likewise,  we  may  need  to  resort  to  litigation  to 
enforce a patent issued or licensed to us or to determine the scope and validity of proprietary rights of others.  In 
addition,  a  third-party  may  claim  that  we  have  improperly  obtained  or  used  its  confidential  or  proprietary 
information.    Furthermore,  in  connection  with  our  third-party  license  agreements,  we  generally  have  agreed  to 
indemnify the licensor for costs incurred in connection with litigation relating to intellectual property rights.  The 
cost to us of any litigation or other proceeding relating to intellectual property rights, even if resolved in our favor, 
could  be  substantial,  and  the  litigation  would  divert  our management’s  efforts.    Some  of  our  competitors  may  be 
able to sustain the costs of complex patent litigation more effectively than we can because they have substantially 
greater resources.  Uncertainties resulting from the initiation and continuation of any litigation could limit our ability 
to  continue  our  operations.    Our  involvement  in  patent  litigation  and  other  proceedings  could  have  a  material 
adverse effect on our business, results of operations, and financial condition. 

If  any  parties  successfully  claim  that  our  creation  or  use  of  proprietary  technologies  infringes  upon  their 
intellectual  property  rights,  we  might  be  forced  to  pay  damages,  potentially  including  treble  damages,  if  we  are 
found to have willfully infringed on such parties’ patent rights.  In addition to any damages we might have to pay, a 
court could require us to stop the infringing activity or obtain a license.  Any license required under any patent may 
not be made available on commercially acceptable terms, if at all.  In addition, such licenses are likely to be non-
exclusive and, therefore, our competitors may have access to the same technology licensed to us.  If we fail to obtain 
a required license and are unable to design around a patent, we  may be unable to effectively  market some of our 
technology  and  products,  which  could  limit  our  ability  to  generate  revenues  or  achieve  profitability  and  possibly 
prevent us from generating revenue sufficient to sustain our operations. 

We  have  faced,  and  may  in  the  future  face,  intellectual  property  infringement  claims  that  could  be  time-
consuming  and  costly  to defend, and  could  result  in  our  loss  of  significant  rights  and  the assessment  of  treble 
damages. 

We  may  from  time  to  time  receive  notices  of  claims  of  infringement  and  misappropriation  or  misuse  of  other 
parties’ proprietary rights.  Some of these additional claims may also lead to litigation.  We cannot assure you that 
we will prevail in such actions, or that other actions alleging misappropriation or misuse by us of third-party trade 
secrets, infringement by us of third-party patents and trademarks or the validity of our patents, will not be asserted or 
prosecuted against us. 

We may also initiate claims to defend our intellectual property or to seek relief on allegations that we use, sell, or 
offer to sell technology that incorporates third party intellectual property.  Intellectual property litigation, regardless 
of outcome, is expensive and time-consuming, could divert management’s attention from our business and have a 
material negative effect on our business, operating results or financial condition.  If there is a successful claim of 
infringement against us, we may be required to pay substantial damages (including treble damages if we were to be 
found to have willfully infringed a third party’s patent) to the party claiming infringement, develop non-infringing 
technology, stop selling our tests or using technology that contains the allegedly infringing intellectual property or 
enter into royalty or license agreements that may not be available on acceptable or commercially practical terms, if 
at all.  Our failure to develop non-infringing technologies or license the proprietary rights on a timely basis could 
harm our business. 

It  is  possible  that  a  third  party  or  patent  office  might  take  the  position  that  one  or  more  patents  or  patent 
applications constitute prior art in the field of genomic-based diagnostics.  In such a case, we might be required to 
pay royalties, damages and costs to firms who own the rights to these patents, or we might be restricted from using 
any of the inventions claimed in those patents. 

We may become subject to product liability for our diagnostic tests, clinical trials, pharmaceutical products and 
medical device products. 

Our  success  depends  on  the  market’s  confidence  that  we  can  provide  reliable,  high-quality  pharmaceuticals, 
medical devices, and diagnostics tests.  Our reputation and the public image of our products or technologies may be 
impaired if our products fail to perform as expected or our products are perceived as difficult to use.  Our products 
are complex and may develop or contain undetected defects or errors.  Furthermore, if a future product candidate 

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harms people, or is alleged to be harmful, we may be subject to costly and damaging product liability claims brought 
against  us  by  clinical  trial  participants,  consumers,  health  care  providers,  corporate  partners  or  others.    We  have 
product  liability  insurance  covering  commercial  sales  of  current  products  and  our  ongoing  clinical  trials.    Any 
defects or errors could lead to the filing of product liability claims, which could be costly and time-consuming to 
defend and result in substantial damages.  If we experience a sustained material defect or error, this could result in 
loss  or  delay  of  revenues,  delayed  market  acceptance,  damaged  reputation,  diversion  of  development  resources, 
legal claims, increased insurance costs or increased service and warranty costs, any of which could materially harm 
our business.  We cannot assure you that our product liability insurance would protect our assets from the financial 
impact of defending a product liability claim.  A product liability claim could have a serious adverse effect on our 
business, financial condition and results of operations. 

Adverse results in material litigation matters or governmental inquiries could have a material adverse effect upon 
our business and financial condition. 

We may from time to time become subject in the ordinary course of business to material legal action related to, 
among other things, intellectual property disputes, professional liability, contractual and employee-related matters, 
as  well  as  inquiries  from  governmental  agencies  and  Medicare  or  Medicaid  carriers  requesting  comment  and 
information on allegations of billing irregularities and other matters that are brought to their attention through billing 
audits, third parties or other sources.  The health care industry is subject to substantial federal and state government 
regulation  and  audit.    Legal  actions  could  result  in  substantial  monetary  damages  as  well  as  damage  to  the 
Company’s reputation with customers, which could have a material adverse effect upon our results of operations and 
financial position. 

RISKS RELATED TO REGULATORY COMPLIANCE 

Our ability to successfully operate our laboratories and develop and commercialize certain of our diagnostic tests 
and  LDTs  will  depend on our  ability  to  maintain  required  regulatory  licensures and comply  with  all  the  CLIA 
requirements. 

In order to successfully operate our laboratory business and offer certain of our diagnostic tests and LDTs, we 
must maintain our CLIA certification and comply with all the CLIA requirements.  CLIA is designed to ensure the 
quality  and  reliability  of  clinical  laboratories  by  mandating  specific  standards  in  the  areas  of  personnel 
qualifications,  administration  and  participation  in  proficiency  testing,  patient  test  management,  quality  control, 
quality assurance and inspections.  The sanction for failure to comply with CLIA requirements may be suspension, 
revocation  or  limitation  of  a  laboratory’s  CLIA  certificate,  which  is  necessary  to  conduct  business,  as  well  as 
significant  fines  and/or  criminal  penalties.    Laboratories  must  undergo  on-site  surveys  at  least  every  two  years, 
which may be conducted by the Federal CLIA program or by a private CMS approved accrediting agency such as 
CAP,  among  others.    Our  laboratories  are  also  subject  to  regulation  of  laboratory  operations  under  state  clinical 
laboratory laws as will be any new CLIA-certified laboratory that we establish or acquire.  State clinical laboratory 
laws  may  require  that  laboratories  and/or  laboratory  personnel  meet  certain  qualifications,  specify  certain  quality 
controls or require maintenance of certain records.  Certain states, such as California, Florida, Maryland, New York, 
Pennsylvania and Rhode Island, require that laboratories obtain licenses to test specimens from patients residing in 
those states and additional states may require similar licenses in the future.  If we are unable to obtain and maintain 
licenses from states where required, we will not be able to process any samples from patients located in those states.  
Only Washington and New York States are exempt under CLIA, as these states have established laboratory quality 
standards at least as stringent as CLIA’s.  Potential sanctions for violation of these statutes and regulations include 
significant fines and the suspension or loss of various licenses, certificates and authorizations, which could adversely 
affect our business and results of operations. 

If we fail to comply with CLIA requirements, HHS or state agencies could require us to cease diagnostic testing.  
Even  if  it  were  possible  for  us  to  bring  our  laboratories  back  into  compliance  after  failure  to  comply  with  such 
requirements,  we  could  incur  significant  expenses  and  potentially  lose  revenues  in  doing  so.    Moreover,  new 
interpretations  of  current  regulations  or  future  changes  in  regulations  under  CLIA  may  make  it  difficult  or 
impossible  for  us  to  comply  with  the  CLIA  classification,  which  would  significantly  harm  our  business  and 
materially adversely affect our financial condition. 

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The  regulatory  approval  process  is  expensive,  time  consuming  and  uncertain  and  may  prevent  us  or  our 
collaboration  partners  from  obtaining  approvals  for  the  commercialization  of  some  or  all  of  our  product 
candidates. 

The  research,  testing,  manufacturing,  labeling,  approval,  selling,  marketing,  and  distribution  of  drug  products, 
diagnostic  products,  or  medical  devices  are  subject  to  extensive  regulation  by  the  FDA  and  other  non-U.S. 
regulatory authorities, which regulations differ from country to country.  In general, we are not permitted to market 
our  product  candidates  in  the  U.S.  until  we  receive  approval  of  a  NDA,  a  clearance  letter  under  the  premarket 
notification process, or 510(k) process, or an approval of a PMA from the FDA.  We have only submitted one NDA 
to  date,  which  has  not  yet  been  approved.  We  have  not received  marketing approval  or  clearance  for  any  of our 
diagnostic product candidates, other than a CE Mark for our point-of-care PSA test and a CE Mark for our 4Kscore 
test.  Obtaining approval of a NDA or PMA can be a lengthy, expensive, and uncertain process.  With respect to 
medical devices, while the FDA reviews and clears a premarket notification in as little as three months, there is no 
guarantee that our products will qualify for this more expeditious regulatory process, which is reserved for Class I 
and II devices, nor is there any assurance that even if a device is reviewed under the 510(k) process that the FDA 
will review it expeditiously or determine that the device is substantially equivalent to a lawfully marketed non-PMA 
device.  If the FDA fails to make this finding, then we cannot market the device.  In lieu of acting on a premarket 
notification, the FDA may seek additional information or additional data which would further delay our ability to 
market the product.  Furthermore, we are not permitted to make changes to a device approved through the PMA or 
510(k)  which  affects  the  safety  or  efficacy  of  the  device  without  first  submitting  a  supplement  application  to  the 
PMA and obtaining FDA approval or cleared premarket notification for that supplement.  In some cases, the FDA 
may require clinical trials to support a supplement application.  In addition, failure to comply with FDA, non-U.S. 
regulatory  authorities,  or  other  applicable  U.S.  and  non-U.S.  regulatory  requirements  may,  either  before  or  after 
product  approval  or  clearance,  if  any,  subject  our  company  to  administrative  or  judicially  imposed  sanctions, 
including, but not limited to the following: 

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restrictions on the products, manufacturers, or manufacturing process; 

adverse inspectional observations (Form 483), warning letters, or non-warning letters incorporating 
inspectional observations; 

civil and criminal penalties; 

injunctions; 

suspension or withdrawal of regulatory approvals or clearances; 

product seizures, detentions, or import bans; 

voluntary or mandatory product recalls and publicity requirements; 

total or partial suspension of production; 

imposition of restrictions on operations, including costly new manufacturing requirements; and 

refusal to approve or clear pending NDAs or supplements to approved NDAs, applications or pre-
market notifications. 

Regulatory approval of an NDA or NDA supplement, PMA, PMA supplement or clearance pursuant to a pre-
market notification is not guaranteed, and the approval or clearance process, as the case may be, is expensive and 
may,  especially  in  the  case  of  an  NDA  or  PMA  application,  take  several  years.    The  FDA  also  has  substantial 
discretion in the drug and medical device approval and clearance process.  Despite the time and expense exerted, 
failure can occur at any stage, and we could encounter problems that cause us to abandon clinical trials or to repeat 
or  perform  additional pre-clinical  studies  and  clinical  trials.    The number of  pre-clinical  studies  and  clinical  trials 
that will be required for FDA approval or clearance varies depending on the drug or medical device candidate, the 
disease or condition that the drug or medical device candidate is designed to address, and the regulations applicable 
to any particular drug or medical device candidate.  The FDA can delay, limit or deny approval or clearance of a 
drug or medical device candidate for many reasons, including: 

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a drug candidate may not be deemed safe or effective; 

a medical device candidate may not be deemed to be substantially equivalent to a lawfully marketed 
non-PMA device, in the case of a premarket notification; 

the FDA may not find the data from pre-clinical studies and clinical trials sufficient; 

the FDA may not approve our or our third-party manufacturer’s processes or facilities; or 

the FDA may change its approval or clearance policies or adopt new regulations. 

Beyond  these  risks,  there  is  also  a  possibility  that  our  licensees  or  collaborators  could  decide  to  discontinue  a 

study at any time for commercial, scientific or other reasons. 

Regulation  by  governmental  authorities  in  the  U.S.  and  other  countries may  be  a  significant  factor  in  how  we 
develop,  test,  produce  and  market  our  diagnostic  test  products.    Diagnostic  tests  like  ours  may  not  fall  squarely 
within the regulatory approval process for pharmaceutical or device products as described above, and the regulatory 
pathway  is  not  as  clear.    It  is  possible  that  the  diagnostic  products  developed  by  us  or  our  collaborators  will  be 
regulated  as  medical  devices  by  the  FDA  and  comparable  agencies  of  other  countries  and  require  either  PMA  or 
510(k)  clearance  from  the  FDA  prior  to  marketing.    Some  companies  that  have  successfully  commercialized 
diagnostic tests for various conditions and disease states have not sought clearance or approval for such tests through 
the  traditional  510(k)  or  PMA  processes,  and  have  instead  utilized  a  process  involving  LDTs  through  a  CLIA- 
certified  laboratory.    CLIA  is  a  federal  law  that  regulates  clinical  laboratories  that  perform  testing  on  specimens 
derived from humans for the purpose of providing information for diagnostic, preventative or treatment purpose.  In 
such  instances,  the  CLIA  lab  is  solely  responsible  for  the  development,  validation  and  commercialization  of  the 
assay. 

Such LDT testing is currently under the purview of CMS and state agencies that provide oversight of the safe 
and  effective  use  of  LDTs.    However,  the  FDA  has  consistently  asserted  that  it  has  the  regulatory  authority  to 
regulate  LDTs  despite  historically  exercising  enforcement  discretion.    In  furtherance  of  that  position,  the  FDA 
issued  two  draft  guidance  documents  in  October  2014:  Framework  for  Regulatory  Oversight  of  Laboratory 
Developed  Tests  (the  “Framework  Guidance”);  and  (2)  FDA  Notification  and  Medical  Device  Reporting  for 
Laboratory Developed Tests (the “Notification Guidance”).  The Framework Guidance outlines the FDA’s plan to 
adopt  over  time  a  risk-based  approach  to  regulating  LDTs  whereby  different  classifications  of  LDTs  would  be 
subject to different levels of FDA oversight and enforcement, including, for example, prohibitions on adulteration 
and misbranding, establishment registration and device listing, premarket notification, banned devices, records and 
reports,  good  manufacturing  practices,  adverse  event  reporting,  premarket  review  of  safety,  effectiveness,  and 
clinical  validity,  and  quality  system  requirements.    The Notification  Guidance  is  intended  to  explain  how  clinical 
laboratories  should  notify  the  FDA  of  the  LDTs  they  develop  and  how  to  satisfy  Medical  Device  Reporting 
requirements.  If finalized, the Framework Guidance and the Notification Guidance may have a materially adverse 
effect on the time, cost, and risk associated with the Company’s development and commercialization of LDTs for 
the U.S. market, and there can be no assurance that clearances or approvals sought by the Company will be granted 
and maintained.  However, the FDA’s authority to regulate LDTs continues to be challenged, and the timeline and 
process  for  finalizing  the  draft  guidance  documents  is  unknown.    We  will  continue  to  monitor  changes  to  all 
domestic and international LDT regulatory policy so as to ensure compliance with the current regulatory scheme. 

Even  if  we  obtain  marketing  approvals  or  clearances  for  our  product  candidates,  the  terms  of  approvals  and 
ongoing  regulation of our products  may  limit  how  we  manufacture  and  market our product  candidates,  which 
could materially impair our ability to generate anticipated revenues. 

Once  regulatory  approval  has  been  granted  to  market  a  product,  the  approved  or  cleared  product  and  its 
manufacturer  are  subject  to  continual  review.    Any  approved  or  cleared  product  may  only  be  promoted  for  its 
indicated  uses.    In  addition,  if  the  FDA  or  other  non-U.S.  regulatory  authorities  approve  any  of  our  product 
candidates for marketing, the labeling, packaging, adverse event reporting, storage, advertising, and promotion for 
the product will be subject to extensive regulatory requirements.  We and the manufacturers of our products are also 
required  to  comply  with  current  Good  Manufacturing  Practices  (“cGMP”)  regulations  or  the  FDA’s  QSR 
regulations,  which  include  requirements  relating  to  quality  control  and  quality  assurance  as  well  as  the 
corresponding maintenance of records and documentation.  Moreover, device manufacturers are required to report 
adverse events by filing Medical Device Reports with the FDA, which reports are publicly available. 

45 

 
 
Further, regulatory agencies must approve manufacturing facilities before they can be used to manufacture our 
products, and these facilities are subject to ongoing regulatory inspection.  If we fail to comply with the regulatory 
requirements  of  the  FDA  and  other  non-U.S.  regulatory  authorities,  or  if  previously  unknown  problems  with  our 
products,  manufacturers,  or  manufacturing  processes  are  discovered,  we  could  be  subject  to  administrative  or 
judicially imposed sanctions.  Furthermore, any limitation on indicated uses for a product candidate or our ability to 
manufacture  and  promote  a  product  candidate  could  significantly  and  adversely  affect  our  business,  results  of 
operations, and financial condition. 

In  addition,  the  FDA  and  other  non-U.S.  regulatory  authorities  may  change  their  policies  and  additional 
regulations may be enacted that could prevent or delay marketing approval or clearance of our product candidates.  
We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or 
administrative action, either in the U.S. or abroad.  If we are not able to maintain regulatory compliance, we would 
likely  not  be  permitted  to  market  our  future  product  candidates  and  we  may  not  achieve  or  sustain  profitability, 
which would materially impair our ability to generate anticipated revenues. 

If  we  fail  to  comply  with  complex  and  rapidly  evolving  laws  and  regulations,  we  could  suffer  penalties,  be 
required to pay substantial damages or make significant changes to our operations. 

We are subject to numerous federal and state regulations, including, but not limited to: 

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federal and state laws applicable to billing and claims payment; 

federal and state laboratory anti-mark-up laws; 

federal and state anti-kickback laws; 

physician self-referral law; 

federal and state false claims laws; 

federal self-referral and financial inducement prohibition laws, commonly known as the Stark Law, 
and the state equivalents; 

federal and state laws governing laboratory licensing and testing, including CLIA; 

federal and state laws governing the development, use and distribution of LDTs; 

(cid:120)  HIPAA, along with the revisions to HIPPA as a result of the HITECH Act, and analogous state laws; 

(cid:120) 

(cid:120) 

federal, state and foreign regulation of privacy, security, electronic transactions and identity theft;  

federal,  state  and  local  laws  governing  the  handling,  transportation  and  disposal  of  medical  and 
hazardous waste; 

(cid:120)  Occupational Safety and Health Administration rules and regulations; 

(cid:120) 

(cid:120) 

changes to laws, regulations and rules as a result of the Health Care Reform Law; and 

changes to other federal, state and local laws, regulations and rules, including tax laws. 

If  we  fail  to  comply  with  existing  or  future  applicable  laws  and  regulations,  we  could  suffer  civil  or  criminal 
penalties, including the loss of our licenses to operate our laboratories and our ability to participate in federal and 
state  healthcare  programs.    Although we believe  that  we  are  substantially  compliant  with  all  existing  statutes  and 
regulations  applicable  to  our  business,  different  interpretations  and  enforcement  policies  of  these  laws  and 
regulations could subject our current practices to allegations of impropriety or illegality, or could require us to make 
significant changes to our operations.  In addition, we cannot predict the impact of future legislation and regulatory 
changes on our  business or  assure  that  we  will  be  able  to  obtain or  maintain  the  regulatory  approvals  required  to 
operate our business. 

46 

 
 
As a result of political, economic, and regulatory influences, the healthcare delivery industry in the U.S. is under 
intense scrutiny and subject to fundamental changes.  We cannot predict which reform proposals will be adopted, 
when they may be adopted, or what impact they may have on us.  The costs associated with complying with federal 
and state regulations could be significant and the failure to comply with any such legal requirements could have a 
material adverse effect on our financial condition, results of operations, and liquidity. 

Failure  to maintain  the  security  of  patient-related  information  or  compliance  with  security  requirements  could 
damage  our  reputation  with  customers,  cause  us  to  incur  substantial  additional  costs  and  become  subject  to 
litigation. 

Pursuant  to  HIPAA,  and  certain  similar  state  laws,  we  must  comply  with  comprehensive  privacy  and  security 
standards with respect to the use and disclosure of protected health information.  Under the HITECH amendments to 
HIPAA,  HIPAA  was  expanded  to  require  certain  data  breach  notification,  to  extend  certain  HIPAA  privacy  and 
security standards directly to business associates, to heighten penalties for noncompliance, and enhance enforcement 
efforts. 

In March 2014 CareEvolve, Bio-Reference’s wholly-owned connectivity subsidiary, became aware that there had 
been a HIPAA breach with regard to one of its servers managed at an internet service provider site called XAND.  
CareEvolve immediately identified and resolved the breach issue, but in the meantime an Internet data googlebot, a 
data  collection  “robot”  operated  by  Google,  Inc.  had  briefly  acquired  data  from  a  server  and  made  it  available  to 
Internet searches.  To the best of our knowledge, there were no known disclosures of this Patient Health Information 
(“PHI”) to unauthorized parties and Bio-Reference took immediate steps to have the PHI removed from the Internet.  
Bio-Reference self-reported this incident to the appropriate government agency, the Office of Civil Rights (“OCR”) 
and is awaiting further discussions, investigation and action by OCR. 

 We  receive  certain  personal  and  financial  information  about  our  clients  and  their  patients.    In  addition,  we 
depend upon the secure transmission of confidential information over public networks.  While we take all reasonable 
and prudent steps to protect this protected information, a compromise in our security systems that results in client or 
patient  personal  information  being  obtained  by  unauthorized  persons  or  our  failure  to  comply  with  security 
requirements for financial transactions could adversely affect our reputation with our clients and result in litigation 
against  us  or  the  imposition  of  penalties,  all  of  which  may  adversely  impact  our  results  of  operations,  financial 
condition and liquidity. 

Failure  to  comply  with  environmental,  health  and  safety  laws  and  regulations,  including  the  Federal 
Occupational  Safety  and  Health  Administration  Act,  the  Needlestick  Safety  and  Prevention  Act  and  the 
Comprehensive  Medical  Waste  Management  Act,  could result  in  fines  and penalties  and  loss  of  licensure, and 
have a material adverse effect upon our business. 

We  are  subject  to  licensing  and  regulation  under  federal,  state  and  local  laws  and  regulations  relating  to  the 
protection of the environment and human health and safety, including laws and regulations relating to the handling, 
transportation and disposal of medical specimens, infectious and hazardous waste and radioactive materials, as well 
as  regulations  relating  to  the  safety  and  health  of  laboratory  employees.    The  Federal  Occupational  Safety  and 
Health  Administration  has  established  extensive  requirements  relating  to  workplace  safety  for  health  care 
employers, including clinical laboratories, whose workers may be exposed to blood-borne pathogens such as HIV 
and  the  hepatitis  B  virus.    These  requirements,  among  other  things,  require  work  practice  controls,  protective 
clothing  and  equipment,  training,  medical  follow-up,  vaccinations  and  other  measures  designed  to  minimize 
exposure  to,  and  transmission  of, blood-borne pathogens.    In  addition,  the  Needlestick  Safety  and  Prevention Act 
requires, among other things, that we include in our safety programs the evaluation and use of engineering controls 
such as safety needles if found to be effective at reducing the risk of needlestick injuries in the workplace. 

Waste  management  is  subject  to  federal  and  state  regulations  governing  the  transportation  and  disposal  of 
medical  waste  including  bodily  fluids.    Federal  regulations  require  licensure  of  interstate  transporters  of  medical 
waste.  In New Jersey, we are subject to the Comprehensive Medical Waste Management Act (“CMWMA”), which 
requires us to register as a generator of special medical waste.  All of our medical waste is disposed of by a licensed 
interstate hauler.  The hauler provides a manifest of the disposition of the waste products as well as a certificate of 
incineration, which is retained by us.  These records are audited by the State of New Jersey on a yearly basis.  We 
are also subject to the Federal Hazardous materials transportation law, 49 U.S.C. 5101 et seq., and the Hazardous 
Materials Regulations (“HMR”), 49 CFR parts 171-180.  The federal government has classified hazardous medical 
waste as hazardous materials for the purpose of regulation.  These regulations preempt state regulation, which must 

47 

 
 
be “substantively the same,” “the non-federal requirement must conform “in every significant respect to the federal 
requirement.  Editorial and other similar de minimis changes are permitted,” 49 CFR 107.202(d). 

Failure to comply with such federal, state and local laws and regulations could subject us to denial of the right to 
conduct  business,  fines,  criminal  penalties  and/or  other  enforcement  actions,  any  of  which  could  have  a  material 
adverse effect on our business.  In addition, compliance with future legislation could impose additional requirements 
us, which may be costly. 

Our  failure  or  the  failure  of  third-party  payors  or  physicians  to  comply  with  ICD-10-CM  Code  Set,  and  our 
failure to comply with other emerging electronic transaction standards could adversely impact our business. 

We  are  within  the  assessment  and  inventory  phase  to  adopt  the  ICD-10-CM  Code  Set  issued  by  HHS  on 
January 16, 2009.  Compliance with the ICD-10-CM Code Set was required to be in place by October 1, 2015.  The 
Company will continue its assessment of information systems, applications and processes for compliance with these 
requirements.  Clinical laboratories are typically required to submit health care claims with diagnosis codes to third 
party payors.  The diagnosis codes must be obtained from the ordering physician.  Our failure or the failure of third 
party  payors  or  physicians  to  transition  within  the  required  timeframe  could  have  an  adverse  impact  on 
reimbursement, days sales outstanding and cash collections. 

Also,  the  failure  of  our  IT  systems  to  keep  pace  with  technological  advances  may  significantly  reduce  our 
revenues  or  increase  our  expenses.    Public  and  private  initiatives  to  create  healthcare  information  technology 
(“HCIT”)  standards  and  to  mandate  standardized  clinical  coding  systems  for  the  electronic  exchange  of  clinical 
information, including test orders and test results, could require costly modifications to our existing HCIT systems.  
While we do not expect HCIT standards to be adopted or implemented without adequate time to comply, if we fail 
to adopt or delay in implementing HCIT standards, we could lose customers and business opportunities. 

Failure to comply with complex federal and state laws and regulations related to submission of claims for clinical 
laboratory services could result in significant monetary damages and penalties and exclusion from the Medicare 
and Medicaid programs. 

We  are  subject  to  extensive  federal  and  state  laws  and  regulations  relating  to  the  submission  of  claims  for 
payment  for  clinical  laboratory  services,  including  those  that  relate  to  coverage  of  our  services  under  Medicare, 
Medicaid  and  other  governmental  health  care  programs,  the  amounts  that  may  be  billed  for  our  services  and  to 
whom  claims  for  services  may  be  submitted.    These  rules  may  also  affect  the  Company  in  light  of  the  practice 
management products that we market, to the extent that these products are considered to affect the manner in which 
our customers’ submit their own claims for services.  Submission of our claims is particularly complex because we 
provide  both  anatomic  pathology  services  and  clinical  laboratory  tests,  which  generally  are  paid  using  different 
reimbursement principles.  The clinical laboratory tests are often paid under a clinical laboratory fee schedule, and 
the anatomic pathology services are often paid under a physician fee schedule. 

Our failure to comply with applicable laws and regulations could result in our inability to receive payment for 
our services or result in attempts by third-party payors, such as Medicare and Medicaid, to recover payments from 
us that have already been made.  Submission of claims in violation of certain statutory or regulatory requirements 
can  result  in  penalties,  including  substantial  civil  money  penalties  for  each  item  or  service  billed  to  Medicare  in 
violation  of  the  legal  requirement,  and  exclusion  from  participation  in  Medicare  and  Medicaid.    Government 
authorities may also assert that violations of laws and regulations related to submission or causing the submission of 
claims violate the federal False Claims Act (“FCA”) or other laws related to fraud and abuse, including submission 
of claims for services that were not medically necessary.  Violations of the FCA could result in enormous economic 
liability.  The FCA provides that all damages are trebled, and each false claim submitted is subject to a penalty of up 
to $11,000.  For example, we could be subject to FCA liability if it was determined that the services we provided 
were  not  medically  necessary  and  not  reimbursable,  particularly  if  it  were  asserted  that  we  contributed  to  the 
physician’s referrals of unnecessary services to us.  It is also possible that the government could attempt to hold us 
liable under fraud and abuse laws for improper claims submitted by an entity for services that we performed if we 
were found to have knowingly participated in the arrangement that resulted in submission of the improper claims. 

Changes in regulation and policies, including increasing downward pressure on health care reimbursement, may 
adversely affect reimbursement for diagnostic services and could have a material adverse impact on our business. 

Reimbursement  levels  for  health  care  services  are  subject  to  continuous  and  often  unexpected  changes  in 
policies,  and  we  face  a  variety  of  efforts  by  government  payors  to  reduce  utilization  and  reimbursement  for 

48 

 
 
diagnostic  testing  services.    Changes  in  governmental  reimbursement  may  result  from  statutory  and  regulatory 
changes,  retroactive  rate  adjustments,  administrative  rulings,  competitive  bidding  initiatives,  and  other  policy 
changes. 

The U.S. Congress has considered, at least yearly in conjunction with budgetary legislation, changes to one or 
both  of  the  Medicare  fee  schedules  under  which  we  receive  reimbursement,  which  include  the  physician  fee 
schedule  for  anatomical  pathology  services,  and  the  clinical  laboratory  fee  schedule  for  our  clinical  laboratory 
services.    For  example,  currently  there  is  no  copayment  or  coinsurance  required  for  clinical  laboratory  services, 
although there is for our physician services.  However, Congress has periodically considered imposing a 20 percent 
coinsurance on laboratory services.  If enacted, this would require us to attempt to collect this amount from patients, 
although in many cases the costs of collection would exceed the amount actually received. 

Our  reimbursement  for  our  pathology  services  is  paid primarily  under  the  physician  fee  schedule  of  Medicare 
and Medicaid and is therefore governed by a complex formula, referred to as the Sustainable Growth Rate, or SGR.  
As  the  use  of  this  formula  could  result  in  a  significant  reduction  in  reimbursement  for  all  physician  services, 
Congress usually acts each year to prevent the full amount of such reductions from taking effect.  In 2011, Congress 
acted to prevent reductions in for 2012, and on January 1, 2013, Congress acted to prevent significant reductions for 
2013.  The SGR has currently been postponed until March 2014 and Congress continues to work on both a short 
term and a long term fix to this annual problem.  If Congress fails to take such action in the future, implementation 
of this formula could adversely affect our business. 

The Center for Medicare and Medicaid Services (“CMS”) pays laboratories on the basis of a fee schedule that is 
reviewed and re-calculated on an annual basis.  CMS may change the fee schedule upward or downward on billing 
codes that we submit for reimbursement on a regular basis.  Our revenue and business may be adversely affected if 
the reimbursement rates associated with such codes are reduced.  Even when reimbursement rates are not reduced, 
policy changes add to our costs by increasing the complexity and volume of administrative requirements.  Medicaid 
reimbursement,  which  varies  by  state,  is  also  subject  to  administrative  and  billing  requirements  and  budget 
pressures.  Recently, state budget pressures have caused states to consider several policy changes that may impact 
our  financial  condition  and  results  of  operations,  such  as  delaying  payments,  reducing  reimbursement,  restricting 
coverage eligibility and service coverage, and imposing taxes on our services. 

Change in the billing and/or reimbursement procedures by the federal government could affect our ability to be 
paid as we have in the past for services rendered. 

CMS has changed or discussed making changes to certain types of reimbursement which could affect our rate of 
reimbursement.  Certain cases are comprised of both a technical component (“TC”) and a professional component 
(“PC”).  In certain specified areas of testing, primarily in the area of anatomic pathology, CMS has determined that 
some  providers  have  over-utilized  these  testing  procedures  and  CMS  has  introduced  changes  in  reimbursement 
policies to discourage over-utilization.  While we do not currently over-utilize services for self-gain, we are always 
subject to review by CMS and cannot be certain that CMS won’t interpret our practices differently than we do. 

CMS has announced planned changes in the area of Molecular Diagnostics’ reimbursement, primarily designed 
to  improve  transparency  in  billing.    Molecular  Diagnostics  is  a  rapidly  changing  and  evolving  area  of  clinical 
testing.    Whereas  other  areas  of  clinical  testing  are  well  vetted  and  established  with  specific  codes  for 
reimbursement,  Molecular  Diagnostics  has  moved  at  a  faster  pace  than  CMS  can  proceed.    Clinical  laboratories 
accordingly use a process called cross-walking to get reimbursed by CMS.  Cross-walking requires that the clinical 
laboratory  identify  the  individual  processes  used  to  process  the  patient’s  specimen  and  identify  diagnostic  results 
that are already reimbursed in established tests.  CMS seeks to specifically identify the testing routine being done 
and  reimburse  providers  universally  for  the  test  actually  being  performed.    CMS  has  not  established  all  of  the 
molecular diagnostic tests that will be included in this revised schedule for reimbursement and it has not determined 
how  much  will  be  reimbursed  to  providers  for  these  tests.    We  expect  CMS  to  implement  fair  and  reasonable 
reimbursement  for  such  tests,  but  until  such  pricing  decisions  are  disclosed  we  cannot  be  certain  what  CMS  will 
finally implement. 

Effective  July 1,  2012,  CMS  eliminated  an  exemption  that  had  been  in  place  since  1999,  which  allowed 
commercial laboratories to bill for certain diagnostic tests performed on in-patient and certain outreach recipients by 
commercial laboratories.  From 1999 through July 1, 2012, commercial laboratories were allowed to bill CMS for 
such tests despite the fact that the recipient was a hospital patient as long as the hospital had been submitting such 
tests for diagnosis to commercial laboratories prior to 1999.  Upon termination of the exemption, we were required 

49 

 
 
to find out from the hospital submitting the test whether the recipient’s bill for diagnostic testing will be reimbursed 
by the hospital or should be billed to CMS.  We have systems in place to manage this change, but these systems are 
dependent upon our getting proper information from the hospital clients. 

The federal government is faced with significant economic decisions in the coming years.  Some solutions being 
offered  in  the  government  could  substantially  change  the  way  laboratory  testing  is  reimbursed  by  government 
entities.  We cannot be certain what or how any such government changes may affect our business. 

Medicare legislation and future legislative or regulatory reform of the health care system may affect our ability to 
sell our products profitably. 

In  the  U.S.,  there  have  been  a  number  of  legislative  and  regulatory  initiatives,  at  both  the  federal  and  state 
government  levels,  to  change  the  healthcare  system  in  ways  that,  if  approved,  could  affect  our  ability  to  sell  our 
products  and  provide  our  laboratory  services  profitably.    While  many  of  the  proposed  policy  changes  require 
congressional approval to implement, we cannot assure you that reimbursement payments under governmental and 
private third party payor programs will remain at levels comparable to present levels or will be sufficient to cover 
the  costs  allocable  to  patients  eligible  for  reimbursement  under  these  programs.    Any  changes  that  lower 
reimbursement rates under Medicare, Medicaid or private payor programs could negatively affect our business. 

Most  significantly,  on  March 23,  2010,  President  Obama  signed  into  law  both  the  Patient  Protection  and 
Affordable Care Act (the “Affordable Care Act”) and the reconciliation law known as Health Care and Education 
Affordability  Reconciliation  Act  (the  “Reconciliation  Act”)  and,  combined  we  refer  to  both  Acts  as  the  “2010 
Health Care Reform Legislation.”  The constitutionality of the 2010 Health Care Reform Legislation was confirmed 
on  June 28,  2012  by  the  Supreme  Court  of  the  United  States  (the  “Supreme  Court”).    Specifically,  the  Supreme 
Court upheld the individual mandate and includes changes to extend medical benefits to those who currently lack 
insurance coverage.  Extending coverage to a large population could substantially change the structure of the health 
insurance  system  and  the  methodology  for  reimbursing  medical  services,  drugs  and  devices.    These  structural 
changes could entail modifications to the existing system of third-party payors and government programs, such as 
Medicare and Medicaid, the creation of a government-sponsored healthcare insurance source, or some combination 
of both, as well as other changes.  Additionally, restructuring the coverage of medical care in the U.S. could impact 
the reimbursement for diagnostic tests.  If reimbursement for our diagnostic tests is substantially less than we or our 
clinical  laboratory  customers  expect,  or  rebate  obligations  associated  with  them  are  substantially  increased,  our 
business could be materially and adversely impacted. 

Beyond coverage and reimbursement changes, the 2010 Health Care Reform Legislation subjects manufacturers 
of medical devices to an excise tax of 2.3% on certain U.S. sales of medical devices in January 2013.  This excise 
tax will likely increase our expenses in the future. 

Further,  the  2010  Health  Care  Reform  Legislation  includes  the  Physician  Payments  Sunshine  Act,  which,  in 
conjunction with its implementing regulations, requires manufacturers of certain drugs, biologics, and devices that 
are covered by Medicare and Medicaid to record all transfers of value to physicians and teaching hospitals starting 
on August 1, 2013 and to begin reporting the same for public disclosure to the Centers for Medicare and Medicaid 
Services  by  March 31,  2014.    Several  other  states  and  a  number  of  countries  worldwide  have  adopted  or  are 
considering the adoption of similar transparency laws.  The failure to report appropriate data may result in civil or 
criminal fines and/or penalties. 

Additionally,  the  2010  Health  Care  Reform  Legislation  includes  significant  new  fraud  and  abuse  measures, 
including  required  disclosures  under  Physician  Payments  Sunshine  Act  described  above,  lower  thresholds  for 
violations and increasing potential penalties for such violations.  Federal funding available for combating health care 
fraud and abuse generally has increased.  While we seek to conduct our business in compliance with all applicable 
laws  and  regulations,  many  of  the  laws  and  regulations  applicable  to  our  business,  particularly  those  relating  to 
billing and reimbursement of tests and those relating to relationships with physicians, hospitals and patients, contain 
language that has not been interpreted by courts.  We must rely on our interpretation of these laws and regulations 
based  on  the  advice  of  our  counsel  and  regulatory  or  law  enforcement  authorities  may  not  agree  with  our 
interpretation  of  these  laws  and  regulations  and  may  seek  to  enforce  legal  remedies  or  penalties  against  us  for 
violations.    From  time  to  time  we  may  need  to  change  our  operations,  particularly  pricing  or  billing  practices,  in 
response  to  changing  interpretations  of  these  laws  and  regulations  or  regulatory  or  judicial  determinations  with 
respect to these laws and regulations.  These occurrences, regardless of their outcome, could damage our reputation 
and harm important business relationships that we have with healthcare providers, payors and others.  Furthermore, 

50 

 
 
if a regulatory or judicial authority finds that we have not complied with applicable laws and regulations, we could 
be required to refund amounts that were billed and collected in violation of such laws and regulations.  In addition, 
we  may  voluntarily  refund  amounts  that  were  alleged  to have been  billed  and  collected  in  violation  of  applicable 
laws and regulations.  In either case, we could suffer civil and criminal damages, fines and penalties, exclusion from 
participation in governmental healthcare programs and the loss of licenses, certificates and authorizations necessary 
to operate our business, as well as incur liabilities from third-party claims, all of which could harm our operating 
results and financial condition.  Moreover, regardless of the outcome, if we or physicians or other third parties with 
whom we do business are investigated by a regulatory or law enforcement authority we could incur substantial costs, 
including legal fees, and our management may be required to divert a substantial amount of time to an investigation. 

To  enhance  compliance  with  applicable  health  care  laws,  and  mitigate  potential  liability  in  the  event  of 
noncompliance, regulatory authorities, such as the United States Health and Human Services Department Office of 
Inspector  General  (“OIG”),  have  recommended  the  adoption  and  implementation  of  a  comprehensive  health  care 
compliance program that generally contains the elements of an effective compliance and ethics program described in 
Section  8B2.1  of  the  United  States  Sentencing  Commission  Guidelines  Manual,  and  for  many  years  the  OIG  has 
made available a model compliance program targeted to the clinical laboratory industry.  In addition, certain states, 
such  as  New  York,  requires  that  health  care  providers,  such  as  clinical  laboratories,  that  engage  in  substantial 
business under the state Medicaid program have a compliance program that generally adheres to the standards set 
forth in the Model Compliance Program.  Also, under the Health Care Reform Law, the U.S. Department of Health 
and  Human  Services,  or  HHS,  will  require  suppliers,  such  as  the  Company,  to  adopt,  as  a  condition  of  Medicare 
participation, compliance programs that meet a core set of requirements.  While we have adopted U.S. healthcare 
compliance and ethics programs that generally incorporate the OIG’s recommendations, and train our employees in 
such compliance, having such a program can be no assurance that we will avoid any compliance issues. 

Regulations under the 2010 Health Care Reform Legislation are expected to continue being drafted, released and 
finalized throughout the next several years.  Pending the promulgation of these regulations, we are unable to fully 
evaluate the impact of the 2010 Health Care Reform Legislation. 

RISKS RELATED TO INTERNATIONAL OPERATIONS 

Failure  to  obtain  regulatory  approval  outside  the  U.S.  will  prevent  us  from  marketing  our  product  candidates 
abroad. 

We  intend  to  market  certain  of  our  existing  and  future  product  candidates  in  non-U.S.  markets.    In  order  to 
market our existing and future product candidates in the European Union and many other non-U.S. jurisdictions, we 
must obtain separate regulatory approvals.  We have had limited interactions with non-U.S. regulatory authorities, 
the  approval  procedures  vary  among  countries  and  can  involve  additional  testing,  and  the  time  required  to  obtain 
approval  may  differ from  that  required  to  obtain  FDA  approval  or  clearance.   Approval  or  clearance  by  the FDA 
does  not  ensure  approval  by  regulatory  authorities  in  other  countries,  and  approval  by  one  or  more  non-U.S. 
regulatory authority does not ensure approval by other regulatory authorities in other countries or by the FDA.  The 
non-U.S.  regulatory  approval  process  may  include  all  of  the  risks  associated  with  obtaining  FDA  approval  or 
clearance.  We may not obtain non-U.S. regulatory approvals on a timely basis, if at all.  We may not be able to file 
for non-U.S. regulatory approvals and may not receive necessary approvals to commercialize our existing and future 
product candidates in any market, which would have a material adverse effect on our business, results of operations 
and financial condition. 

Non-U.S. governments often impose strict price controls, which may adversely affect our future profitability. 

We intend to seek approval to market certain of our existing and future product candidates in both the U.S. and 
in non-U.S. jurisdictions.  If we obtain approval in one or more non-U.S. jurisdictions, we will be subject to rules 
and  regulations  in  those  jurisdictions  relating  to  our  product.    In  some  countries,  particularly  countries  of  the 
European  Union,  each  of  which  has  developed  its  own  rules  and  regulations,  pricing  is  subject  to  governmental 
control.  In these countries, pricing negotiations with governmental authorities can take considerable time after the 
receipt of marketing approval for a drug or medical device candidate.  To obtain reimbursement or pricing approval 
in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our existing 
and  future  product  candidates  to  other  available  products.    If  reimbursement  of  our  future  product  candidates  is 
unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, we may be unable to generate 
revenues and achieve or sustain profitability, which would have a material adverse effect on our business, results of 
operations and financial condition. 

51 

 
 
Potential political, economic and military instability in the State of Israel, where we have office, laboratory and 
manufacturing operations, may adversely affect our results of operations. 

We  maintain  office,  laboratory  and  manufacturing  facilities  in  the  State  of  Israel.    Political,  economic  and 
military  conditions  in  Israel  may  directly  affect  our  ability  to  conduct  business.    Since  the  State  of  Israel  was 
established in 1948, a number of armed conflicts have occurred between Israel and its neighbors.  Any hostilities 
involving  Israel  or  the  interruption  or  curtailment  of  trade  between  Israel  and  its  present  trading  partners,  or  a 
significant  downturn  in  the  economic  or  financial  condition  of  Israel,  could  affect  adversely  our  operations.  
Ongoing and revived hostilities or other Israeli political or economic factors could harm our operations and product 
development and cause our revenues to decrease. 

Due to the international scope of our business activities, our results of operations may be significantly affected by 
currency fluctuations. 

We derive a significant portion of our consolidated net revenues from international sales, subjecting us to risks 
relating to fluctuations in currency exchange rates.  Currency variations can adversely affect margins on sales of our 
products in countries outside of the U.S. and margins on sales of products that include components obtained from 
suppliers located outside of the U.S.  Through our subsidiaries, we operate in a wide variety of jurisdictions.  Certain 
countries  in  which  we  operate  or  may  operate  have  experienced  geopolitical  instability,  economic  problems  and 
other uncertainties from time to time.  To the extent that world events or economic conditions negatively affect our 
future  sales  to  customers  in  these  and  other  regions  of  the  world,  or  the  collectability  of  receivables,  our  future 
results of operations, liquidity and financial condition may be adversely affected.  Although we do not speculate in 
the  foreign  exchange  market,  we  may  manage  exposures  arising  in  the  normal  course  of  business  related  to 
fluctuations  in  foreign  currency  exchange  rates  by  entering  into  offsetting  positions  through  the  use  of  foreign 
exchange  forward  contracts.    Certain  firmly  committed  transactions  are  hedged  with  foreign  exchange  forward 
contracts whereby exchange rates change, gains and losses on the exposed transactions are partially offset by gains 
and losses related to the hedging contracts.  However, our subsidiaries receive their income and pay their expenses 
primarily  in  their  local  currencies.    To  the  extent  that  transactions  of  these  subsidiaries  are  settled  in  their  local 
currencies,  a  devaluation  of  those  currencies  versus  the  U.S.  dollar  could  reduce  the  contribution  from  these 
subsidiaries to our consolidated results of operations as reported in U.S. dollars.  For financial reporting purposes, 
such  depreciation  will  negatively  affect  our  reported  results  of  operations  since  earnings  denominated  in  foreign 
currencies would be converted to U.S. dollars at a decreased value.  While we have employed economic cash flow 
and fair value hedges to minimize the risks associated with these exchange rate fluctuations, the hedging activities 
may  be  ineffective  or  may  not  offset  more  than  a portion  of  the  adverse  financial  impact  resulting from  currency 
variations.  Accordingly, we cannot assure you that fluctuations in the values of the currencies of countries in which 
we operate will not materially adversely affect our future results of operations. 

We may be exposed to liabilities under the Foreign Corrupt Practices Act, and any determination that we violated 
the Foreign Corrupt Practices Act could have a material adverse effect on our business. 

We  are  subject  to  the  Foreign  Corrupt  Practice  Act  (“FCPA”)  and  other  laws  that  prohibit  U.S.  companies  or 
their agents and employees from providing anything of value to a foreign official or political party for the purposes 
of  influencing  any  act  or  decision  of  these  individuals  in  their  official  capacity  to  help  obtain  or  retain  business, 
direct  business  to  any  person  or  corporate  entity  or  obtain  any  unfair  advantage.    We  have  operations  and 
agreements  with  third  parties  and  we  generate  sales  internationally.    Our  international  activities  create  the  risk  of 
unauthorized and illegal payments or offers of payments by our employees, consultants, sales agents or distributors, 
even though they may not always be subject to our control.  We discourage these practices by our employees and 
agents.  However, our existing safeguards and any future improvements may prove to be less than effective, and our 
employees, consultants, sales agents or distributors may engage in conduct for which we might be held responsible.  
Any  failure  by  us  to  adopt  appropriate  compliance  procedures  and  ensure  that  our  employees  and  agents  comply 
with the FCPA and applicable laws and regulations in foreign jurisdictions could result in substantial penalties or 
restrictions on our ability to conduct business in certain foreign jurisdictions. 

Violations  of  the  FCPA  may  result  in  severe  criminal  or  civil  sanctions,  and  we  may  be  subject  to  other 
liabilities, which could negatively affect our business, operating results and financial condition.  In addition, the U.S. 
government may seek to hold our Company liable for successor liability FCPA violations committed by companies 
in which we invest or that we acquire. 

52 

 
 
We are subject to risks associated with doing business globally. 

Our operations,  both within  and outside  the  U.S.,  are  subject  to  risks  inherent  in  conducting business  globally 
and  under  the  laws,  regulations  and  customs  of  various  jurisdictions  and  geographies.    These  risks  include 
fluctuations in currency exchange rates, changes in exchange controls, loss of business in government tenders that 
are held annually in many cases, nationalization, increasingly complex labor environments, expropriation and other 
governmental actions, changes in taxation, including legislative changes in U.S. and international taxation of income 
earned  outside  of  the  U.S.,  importation  limitations,  export  control  restrictions,  violations  of  U.S.  or  local  laws, 
including  the  FCPA,  dependence  on  a  few  government  entities  as  customers,  pricing  restrictions,  economic 
destabilization, political and economic instability, disruption or destruction in a significant geographic region - due 
to the location of manufacturing facilities, distribution facilities or customers - regardless of cause, including war, 
terrorism,  riot,  civil  insurrection  or  social  unrest,  or  natural  or  man-made  disasters,  including  famine,  flood,  fire, 
earthquake,  storm  or  disease.    Failure  to  comply  with  the  laws  and  regulations  that  affect  our  global  operations, 
could have an adverse effect on our business, financial condition or results of operations. 

RISKS RELATED TO ACQUISITIONS AND INVESTMENTS 

Acquisitions,  investments  and  strategic  alliances  that  we  have  made  or  may  make  in  the  future  may  use 
significant  resources,  result  in disruptions  to our business  or  distractions  of  our  management,  may  not  proceed  as 
planned, and could expose us to unforeseen liabilities.  We intend to continue to expand our business through the 
acquisition  of,  investments  in  and  strategic  alliances  with  companies,  technologies,  products,  and  services.  
Acquisitions, investments and strategic alliances involve a number of special problems and risks, including, but not 
limited to: 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

difficulty  integrating  acquired  technologies,  products,  services,  operations,  and  personnel  with  the 
existing businesses; 

diversion  of  management’s  attention  in  connection  with  both  negotiating  the  acquisitions  and 
integrating the businesses; 

strain on managerial and operational resources as management tries to oversee larger operations and 
investments; 

difficulty  implementing  and  maintaining  effective  internal  control  over  financial  reporting  at 
businesses  that  we  acquire  or  invest  in,  particularly  if  they  are  not  located  near  our  existing 
operations; 

exposure to unforeseen liabilities of acquired companies or companies in which we invest; 

potential costly and time-consuming litigation, including stockholder lawsuits; 

potential issuance of securities to equity holders of the company being acquired with rights that are 
superior to the rights of holders of our Common Stock, or which may have a dilutive effect on our 
stockholders; 

the need to incur additional debt or use cash; and 

the  requirement  to  record  potentially  significant  additional  future  operating  costs  for  the 
amortization of intangible assets. 

As  a  result  of  these  or  other  problems  and  risks,  businesses  we  acquire  or  invest  in  may  not  produce  the 
revenues, earnings, or business synergies that we anticipated, and acquired products, services, or technologies might 
not  perform  as  we  expected.    As  a  result,  we  may  incur  higher  costs  and  realize  lower  revenues  than  we  had 
anticipated.    We  may  not  be  able  to  successfully  address  these  problems  and  we  cannot  assure  you  that  the 
acquisitions  or  investments  will  be  successfully  identified  and  completed  or  that,  if  completed,  the  acquired 
businesses, investments, products, services, or technologies will generate sufficient revenue to offset the associated 
costs or other negative effects on our business. 

53 

 
 
Any of these risks can be greater if an acquisition or investment is large relative to our size.  Failure to manage 
effectively  our  growth  through  acquisitions  could  adversely  affect  our  growth  prospects,  business,  results  of 
operations, financial condition and cash flows. 

We may fail to realize the anticipated benefits of the merger with Bio-Reference. 

The success of the merger will depend on, among other things, our ability to combine our business with that of 
Bio-Reference in a manner that facilitates growth opportunities and realizes synergies and cost savings.  We believe 
that the merger will provide an opportunity for revenue growth.  However, we must successfully combine our and 
Bio-Reference’s businesses in a manner that permits these benefits to be realized.  In addition, we must achieve the 
anticipated growth and cost savings without adversely affecting current revenues and investments in future growth.  
If we are not able to successfully achieve these objectives, the anticipated benefits of the merger may not be realized 
fully, or at all, or may take longer to realize than expected. 

The  failure  to  integrate  successfully  the  business  and  operations  of  Bio-Reference  in  the  expected  time  frame 
may adversely affect our future results. 

Historically, we and Bio-Reference have operated as independent companies.  There can be no assurances that 
our and Bio-Reference’s businesses can be integrated successfully.  It is possible that the integration process could 
result in the loss of our or Bio-Reference’s key employees, the loss of customers, the disruption of either company’s 
or both companies’ ongoing businesses or in unexpected integration issues, higher than expected integration costs 
and  an  overall  post-completion  integration  process  that  takes  longer  than  originally  anticipated.    Specifically,  the 
following issues, among others, must be addressed in integrating our operations with Bio-Reference’s operations in 
order to realize the anticipated benefits of the merger so we perform as expected: 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

combining  the  companies’  operations  and  corporate  functions,  as  well  as  obtaining  anticipated 
synergies; 

combining our business with Bio-Reference’s business and meeting the capital requirements of the 
combined  company,  in  a  manner  that  permits  us  to  achieve  the  cost  savings  or  revenue  synergies 
anticipated to result from the merger, the failure of which would result in the anticipated benefits of 
the merger not being realized in the time frame currently anticipated or at all;  

integrating the companies’ technologies; 

integrating and unifying the offerings and services available to customers; 

identifying and eliminating redundant and underperforming functions and assets; 

harmonizing  and/or  addressing  differences  in  the  companies’  operating  practices,  employee 
development  and  compensation  programs,  internal  controls  and  other  policies,  procedures  and 
processes; 

(cid:120)  maintaining  existing  agreements  with  customers,  distributors,  providers  and  vendors  and  avoiding 
delays  in  entering  into  new  agreements  with  prospective  customers,  distributors,  providers  and 
vendors; 

(cid:120) 

(cid:120) 

(cid:120) 

addressing  possible  differences  in  business  backgrounds,  corporate  cultures  and  management 
philosophies; 

consolidating the companies’ administrative and information technology infrastructure; 

coordinating distribution and marketing efforts; 

(cid:120)  managing the movement of certain positions to different locations; 

(cid:120) 

(cid:120) 

coordinating geographically dispersed organizations; and 

effecting actions that may be required in connection with obtaining regulatory approvals.   

54 

 
 
In  addition,  at  times  the  attention  of  our  management  and  resources  may  be  focused  on  the  integration  of  the 
businesses of the two companies and diverted from day-to-day business operations, which may disrupt our ongoing 
business. 

Funding  may  not  be  available  for  us  to  continue  to  make  acquisitions,  investments  and  strategic  alliances  in 
order to grow our business. 

We  have  made  and  anticipate  that  we  may  continue  to  make  acquisitions,  investments  and  strategic  alliances 
with complementary businesses, technologies, products and services to expand our business.  Our growth plans rely, 
in part, on the successful completion of future acquisitions.  At any particular time, we may need to raise substantial 
additional  capital  or  to  issue  additional  equity  to  finance  such  acquisitions,  investments,  and  strategic  alliances.  
There is no assurance that we will be able to secure additional funding on acceptable terms, or at all, or obtain the 
stockholder  approvals  necessary  to  issue  additional  equity  to  finance  such  acquisitions,  investments,  and  strategic 
alliances.  If we are unsuccessful in obtaining the financing, our business would be adversely impacted. 

We have a large amount of goodwill and other intangible assets as a result of acquisitions and a significant write-
down of goodwill and/or other intangible assets would have a material adverse effect on our reported results of 
operations and net worth. 

We have a large amount of goodwill and other intangible assets and we are required to perform an annual, or in 
certain situations a more frequent, assessment for possible impairment for accounting purposes.  At December 31, 
2015, we have goodwill and other intangible assets of $2.2 billion, or approximately 78% of our total assets.  If we 
do  not  achieve  our  planned  operating  results,  we  may  be  required  to  incur  a  non-cash  impairment  charge.    Any 
impairment  charges  in  the  future  will  adversely  affect  our  results  of  operations.    A  significant  write  down  of 
goodwill and/or other intangible assets would have a  material adverse effect on our reported results of operations 
and net worth. 

RISKS RELATED TO OWNERSHIP OF OUR COMMON STOCK 

The market price of our Common Stock may fluctuate significantly. 

The  market  price  of  our  Common  Stock  may  fluctuate  significantly  in  response  to  numerous  factors,  some  of 

which are beyond our control, such as: 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

(cid:120) 

the announcement of new products or product enhancements by us or our competitors; 

results of our clinical trials and other development efforts; 

developments concerning intellectual property rights and regulatory approvals; 

variations in our and our competitors’ results of operations; 

changes in earnings estimates or recommendations by securities analysts, if our Common Stock is 
covered by analysts; 

developments in the biotechnology, pharmaceutical, diagnostic, and medical device industry; 

the results of product liability or intellectual property lawsuits; 

future issuances of our Common Stock or other securities, including debt; 

purchases and sales of our Common Stock by our officers, directors or affiliates; 

the addition or departure of key personnel; 

announcements by us or our competitors of acquisitions, investments, or strategic alliances; and 

general  market  conditions  and  other  factors,  including  factors  unrelated  to  our  operating 
performance. 

55 

 
 
Further, the stock market in general, and the market for biotechnology, pharmaceutical, diagnostic, and medical 
device companies in particular, has experienced extreme price and volume fluctuations in recent years.  Continued 
market fluctuations could result in extreme volatility in the price of our Common Stock, which could cause a decline 
in the value of our Common Stock. 

Directors,  executive  officers,  principal  stockholders  and  affiliated  entities  own  a  substantial  amount  of  our 
capital stock, and they may make decisions that you do not consider to be in the best interests of our stockholders. 

As  of  February 16,  2016,  our  directors,  executive  officers,  principal  stockholders,  and  affiliated  entities 
beneficially owned, in the aggregate 40.73% of our outstanding voting securities.  Frost Gamma Investments Trust 
(“Gamma Trust”), of which Phillip Frost, M.D., the Company’s Chairman and CEO, is the sole trustee, is deemed to 
beneficially own in the aggregate approximately 32.8% of our Common Stock as of February 16, 2016.  As a result, 
Dr. Frost acting with other members of management, would have the ability to significantly impact the election of 
our Board of Directors, the adoption or amendment of provisions in the Company’s Certificate of Incorporation, the 
approval of mergers and other significant corporate transactions, and the outcome of issues requiring approval by 
our stockholders.  This concentration of ownership may also have the effect of delaying or preventing a change in 
control  of  our  company  that  may  be  favored  by  other  stockholders.    This  could  prevent  transactions  in  which 
stockholders might otherwise recover a premium for their shares over current market prices. 

A significant short position in our stock could have a substantial impact on the trading price of our stock. 

Historically,  there  has  been  a  significant  “short”  position  in  our  common  stock.    As  of  February 12,  2016, 
investors held a short position of approximately 65,465,949 million shares of our common stock which represented 
approximately 20.15% of our public float.  The anticipated downward pressure on our stock price due to actual or 
anticipated sales of our stock by some institutions or individuals who engage in short sales of our common stock 
could  cause  our  stock  price  to  decline.    Such  stock  price  decrease  could  encourage  further  short-sales  that  could 
place  additional  downward  pressure  on  our  stock  price.    This  could  lead  to  further  increases  in  the  already  large 
short position in our common stock and cause volatility in our stock price. 

The volatility of our stock may cause the value of a stockholder’s investment to decline rapidly.  Additionally, if 
our stock price declines, it may be more difficult for us to raise capital and may have other adverse effects on our 
business. 

Failure  to  maintain  effective  internal  controls  in  accordance  with  Section  404  of  the  Sarbanes-Oxley  Act, 
including  with  respect  to  companies  we  acquire,  could  have  a  material  adverse  effect  on  our  business  and 
operating  results.    In  addition,  current  and  potential  stockholders  could  lose  confidence  in  our  financial 
reporting, which could have a material adverse effect on the price of our Common Stock. 

Section 404 of the Sarbanes-Oxley Act of 2002 requires annual management assessments of the effectiveness of 
our internal control over financial reporting and a report by our independent registered public accounting firm on the 
effectiveness  of  internal  control  over  financial  reporting  as  of  year  end.    We  are  required  to  report,  among  other 
things,  control  deficiencies  that  constitute  material  weaknesses  or  changes  in  internal  control  that,  or  that  are 
reasonably  likely  to,  materially  affect  internal  control  over  financial  reporting.    A  “material  weakness”  is  a 
significant deficiency or combination of significant deficiencies that results in more than a remote likelihood that a 
material misstatement of the annual or interim financial statements will not be prevented or detected. 

We have identified and remediated control deficiencies in the past, and we cannot assure you that we will at all 
times in the future be able to report that our internal controls are effective.  In addition, material weaknesses in the 
design  and  operation  of  the  internal  control  over  financial  reporting  of  companies  that  we  acquire  could  have  a 
material adverse effect on our business and operating results.  Our acquisition of Bio-Reference and possible future 
acquisitions may increase this risk by expanding the scope and nature of operations over which we must develop and 
maintain internal control over financial reporting.  If we cannot provide reliable financial reports or prevent fraud, 
our  results  of  operation  could  be  harmed.    Our  failure  to  maintain  the  effective  internal  control  over  financial 
reporting  could  cause  the  cost  related  to  remediation  to  increase  and  could  cause  our  stock  price  to  decline.    In 
addition, we may not be able to accurately report our financial results, may be subject to regulatory sanction, and 
investors may lose confidence in our financial statements. 

56 

 
 
Compliance  with  changing  regulations  concerning  corporate  governance  and  public  disclosure  may  result  in 
additional expenses. 

There  have  been  changing  laws,  regulations,  and  standards  relating  to  corporate  governance  and  public 
disclosure,  including  the  Sarbanes-Oxley  Act  of  2002,  the  Dodd-Frank  Act,  regulations  promulgated  by  the 
Securities  and  Exchange  Commission  and  rules  promulgated  by  the  NYSE  and  the  other  national  securities 
exchanges.  These new or changed laws, regulations, and standards are subject to varying interpretations in many 
cases  due  to  their  lack  of  specificity,  and,  as  a  result,  their  application  in  practice  may  evolve  over  time  as  new 
guidance  is  provided  by  regulatory  and  governing  bodies,  which  could  result  in  continuing  uncertainty  regarding 
compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.  As a 
result,  our  efforts  to  comply  with  evolving  laws,  regulations,  and  standards  are  likely  to  continue  to  result  in 
increased  general  and  administrative  expenses  and  a  diversion  of  management  time  and  attention  from  revenue-
generating activities to compliance activities.  Our board members, Chief Executive Officer, Chief Financial Officer, 
and  Principal  Accounting  Officer  could  face  an  increased  risk  of  personal  liability  in  connection  with  the 
performance of their duties.  As a result, we may have difficulty attracting and retaining qualified board members 
and  executive  officers,  which  could  harm  our  business.    If  our  efforts  to  comply  with  new  or  changed  laws, 
regulations, and standards differ from the activities intended by regulatory or governing bodies, we could be subject 
to  liability  under  applicable  laws  or  our  reputation  may  be  harmed,  which  could  materially  adversely  affect  our 
business, results of operations and financial condition. 

The  conversion  and  redemption  features  of  our  2033  Senior  Notes  are  classified  as  embedded  derivatives  and 
may continue to result in volatility in our financial statements, including having a material impact on our results 
of operations and the derivative liability recorded. 

The conversion rights and redemption options of our 2033 Senior Notes are classified as embedded derivatives 
and  as  a  result,  are  marked-to-market  to  reflect  their  fair  value  at  each  reporting  period.    The  fair  value  of  the 
embedded  derivatives  is  influenced  by  a  variety  of  factors,  including  the  actual  and  anticipated  behavior  of  the 
holders of the 2033 Senior Notes, the expected volatility of our Common Stock price and our Common Stock price 
as of the fair value measurement date.  Some of these factors are outside of our control.  As a result, changes in these 
factors  may  have  a  material  impact  on  our  results  of  operations  and  the  derivative  liability  recorded  in  our 
Consolidated Balance Sheets.  Consequently, our financial statements may vary periodically, based on factors other 
than our revenues and expenses. 

ITEM 1B.  UNRESOLVED STAFF COMMENTS. 

None. 

ITEM 2.  PROPERTIES. 

Our principal corporate office is located at 4400 Biscayne Blvd, Miami, Florida.  We lease this space from Frost 
Real Estate Holdings, LLC (“Frost Real Estate”), an entity which is controlled by Dr. Phillip Frost, our Chairman of 
the Board and Chief Executive Officer.  Pursuant to the lease agreement with Frost Real Estate Holdings, we lease 
approximately 25,000 square feet, which encompasses space for our corporate offices and administrative services.  
Effective  May 28,  2015,  we  entered  into  an  amendment  to  our  lease  agreement  with  Frost  Real-Estate  Holdings.  
The lease, as amended, is for a five-year term.  The lease provides for payments of approximately $66 thousand per 
month in the first year increasing annually to $75 thousand per month in the fifth year, plus applicable sale tax. 

57 

 
 
The  table  below  summarizes  certain  information  as  to  our  most  significant  physical  properties  as  of 

December 31, 2015: 

Location 

Miami, FL 

  Segment and Purpose 

  Type of Occupancy

  Diagnostics & Pharmaceutical: Corporate Headquarters 

  Leased 

Elmwood Park, NJ 
Gaithersburg, MD 
Nes Ziona, Israel 
Woburn, MA 
Nesher, Israel 
Guadalajara, Mexico 
Banyoles, Spain 
Barcelona, Spain 
Waterford, Ireland 
Santiago, Chile 

  Diagnostics: Main Laboratory 
  Diagnostics: Genetics Laboratory 
  Pharmaceutical: Research and Development, CTP 
  Diagnostics 
  Pharmaceuticals: API Manufacturing 
  Pharmaceuticals: Pharmaceutical Manufacturing 
  Pharmaceuticals: Pharmaceutical Manufacturing 
  Pharmaceuticals: Research and Development 
  Pharmaceuticals: Pharmaceutical Manufacturing 
  Pharmaceuticals: Office; Warehouse 

  Leased 
  Leased 
  Leased 
  Leased 
  Leased 
  Owned 
  Owned 
  Leased 
  Leased 
  Leased 

ITEM 3.  LEGAL PROCEEDINGS. 

Following the announcement of entry into an agreement and plan of merger with Bio-Reference, four putative 
class  action  complaints  challenging  the  merger were  filed  in  the  Superior  Court of New  Jersey  in Bergen  County 
(the “Court”).  The parties subsequently executed a stipulated consent order that the actions would be consolidated 
for all purposes, including trial, in the Chancery Division under Docket No. C-207-15, bearing the caption In re Bio-
Reference Laboratories, Inc.  Shareholder Litigation.  The complaints name Bio-Reference, OPKO, a wholly-owned 
merger  subsidiary  of  OPKO  (“Merger  Sub”)  and  members  of  the  Bio-Reference  board  as  defendants.    The 
complaints generally allege, among other things, that members of the Bio-Reference board breached their fiduciary 
duties  to  Bio-Reference’s  shareholders  by  agreeing  to  sell  Bio-Reference  for  an  inadequate  price  and  agreeing  to 
inappropriate deal protection provisions in the merger agreement that may preclude Bio-Reference from soliciting 
any  potential  acquirers  and  limit  the  ability  of  the  Bio-Reference  board  to  act  with  respect  to  investigating  and 
pursuing  superior  proposals  and  alternatives.    The  complaints  also  allege  that  Bio-Reference,  OPKO  and  Merger 
Sub have aided and abetted the Bio-Reference board members’ breaches of their fiduciary duties.  In August, the 
parties executed a memorandum of understanding reflecting terms of a settlement, which was replaced in September 
2015 by a stipulation and agreement of compromise, settlement and release resolving all matters between them.  In 
January 2016, the  Court  entered  an  order  finally  approving  the  settlement. The settlement did not have  a  material 
impact on our business, financial condition, results of operations or cash flows. 

On December 18, 2013, Bio-Reference filed an action in the Superior Court of New Jersey against Horizon Blue 
Cross  Blue  Shield  of  New  Jersey  (“Horizon”),  captioned  Bio-Reference  Laboratories, Inc.  v.  Horizon  Healthcare 
Services, Inc. d/b/a Horizon Blue Cross Blue Shield of New Jersey, Docket No. BER L-009748-13 (N.J. Super. Ct. 
Bergen  Cnty.).   Bio-Reference  has  been  an  in-network  provider  to  Horizon’s  preferred  provider  organization 
(“PPO”)  members  for  more  than  20  years  and  filed  the  lawsuit  after  attempts  to  resolve  its  dispute  with  Horizon 
were unsuccessful. 

Bio-Reference  currently  provides  services  to  Horizon  pursuant  to  an  Ancillary  Services  Provider  Agreement 
entered  into  in  2003  and  amended  in  2007.   The  central  claims  in  the  lawsuit  arise  from  Bio-Reference’s 
performance  of  laboratory  services  since  at  least  2008  for  members  of  Horizon’s  NJ  DIRECT  plan,  who  receive 
benefits under a program that Horizon has bid, promoted, and represented to be a PPO product for New Jersey state, 
county,  and  municipal  workers  and  teachers.   The  lawsuit  alleges  that,  despite  these  representations,  Horizon  has 
been  improperly  treating  NJ  DIRECT  as  a  Managed  Care  program  in  its  dealings  with  Bio-Reference,  thereby 
costing Bio-Reference more than $20,000,000 in unreimbursed services and depriving state beneficiaries of valuable 
rights  and  benefits  to  which  they  are  entitled.   The  lawsuit  alleges  that  Horizon  furthered  its  fraud  against  Bio-
Reference by means of a sham Request for Proposal issued in 2011 and through false and incorrect communications 
to  Bio-Reference  and  other  providers.   Bio-Reference  asserts  claims  for  breach  of  contract,  breach  of  the  implied 
covenant  of  good  faith  and  fair  dealing,  and  fraud  against  Horizon.   In  addition  to  compensatory  damages,  Bio-

58 

 
 
 
 
 
 
 
 
 
 
 
 
Reference seeks to recover punitive damages from Horizon due to Horizon’s intentional and malicious misconduct.  
Bio-Reference also seeks declaratory and injunctive relief. 

Bio-Reference and Horizon have completed discovery, and Horizon has filed a motion for summary judgment, 
which Bio-Reference is opposing, and which will be argued before the Court on March 18, 2016.  Trial in the matter 
is currently set for April 2016.  Bio-Reference intends to vigorously prosecute its claims against Horizon. 

ITEM 4.  MINE SAFETY DISCLOSURES. 

Not applicable.

59 

 
 
PART II 

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

MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES. 

Our  Common  Stock  is  traded  publicly  on  the  New  York  Stock  Exchange  (“NYSE”)  and  the  Tel  Aviv  Stock 

Exchange under the symbol “OPK”. 

The following table sets forth for the periods indicated the high and low sales prices per share of our Common 

Stock during each of the quarters set forth below as reported on the NYSE: 

High 

Low 

2015 

First Quarter ........................................................    $ 15.23 
Second Quarter.................................................... 
  19.20 
  17.51 
Third Quarter ...................................................... 
Fourth Quarter ..................................................... 
  11.49 

  $  9.81 
  13.71 
  8.23 
  8.20 

2014 

First Quarter ........................................................    $ 10.25 
Second Quarter.................................................... 
  9.83 
Third Quarter ...................................................... 
  9.62 
Fourth Quarter ..................................................... 
  10.16 

  $  7.32 
  7.82 
  8.09 
  8.02 

As of February 16, 2016, there were approximately 628 holders of record of our Common Stock. 

We  have  not  declared  or  paid  any  cash  dividends  on  our  Common  Stock.    No  cash  dividends  have  been 

previously paid on our Common Stock and none are anticipated in fiscal 2016. 

60 

 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stock Performance Graph 

 The  following  graph  compares  the five-year  cumulative  total  return  of our  Common  Stock  with  the  S&P 500 
Index  and  the  NASDAQ  Biotechnology  Index.    The  graph  assumes  $100  invested  on  December 31,  2010  in  our 
Common Stock and in each of the foregoing indices.  The stock price performance reflected in the graph below is 
not necessarily indicative of future price performance. 

12/31/2010 

12/31/2011 

12/31/2012 

12/31/2013 

12/31/2014 

OPKO Health, Inc. ..............$ 
S&P 500 ..............................
NASDAQ Biotechnology ...

100.00  $ 
100.00 
100.00 

133.51 $ 
102.11
113.92

131.06 $ 
118.45
153.97

229.97 $ 
156.82
263.29

272.21    $ 
178.29   
348.49   

12/31/2015 
273.84

180.75
369.06

Recent Sales of Unregistered Securities 

None. 

61 

 
 
 
 
 
 
 
   
ITEM 6.  SELECTED FINANCIAL DATA. 

The  following  selected  historical  consolidated  statement  of  operations  data  for  the  years  ended  December 31, 
2015, 2014, 2013, 2012, and 2011 and the consolidated balance sheet data as of December 31, 2015, 2014, 2013, 
2012,  and  2011,  below  are  derived  from  our  audited  consolidated  financial  statements  and  related  notes  thereto.  
This data should be read in conjunction with our “Management’s Discussion and Analysis of Financial Condition 
and Results of Operation” and our consolidated financial statements and the related notes thereto

(In thousands, except share and per share information)  
Statement of operations data: 
Revenues ........................................................................  $
Costs and expenses: 

Cost of revenue .......................................................... 
Operating expenses .................................................... 
Total costs and expenses ................................................ 
Operating loss from continuing operations .................... 
Other income and (expense), net.................................... 
Income tax benefit (provision) ....................................... 
Loss from continuing operations.................................... 
Net loss attributable to common shareholders ...............  $
Loss per share, basic and diluted: 

2015 

For the years ended December 31, 
2013 

2012 

2014 

2011 

491,738    $

91,125    $

96,530    $

47,044    $

27,979 

235,239   
354,980   
590,219   
(98,481)  
(39,517)  
113,675   
(31,428)  
(30,028)   $

48,009   
188,931   
236,940   
(145,815)  
(25,212)  
(24)  
(174,638)  
(171,666)   $

48,860   
127,302   
176,162   
(79,632)  
(24,586)  
(1,672)  
(117,346)  
(114,827)   $

27,878   
56,435   
84,313   
(37,269)  
165   
9,626   
(29,540)  
(31,288)   $

17,243 
33,925 
51,168 
(23,189)
(1,044)
19,358 
(6,464)
(3,662)

Loss from continuing operations ................................  $

(0.06)   $

(0.41)   $

(0.32)   $

(0.11)   $

(0.03)

Weighted average number of common shares 

outstanding basic and diluted: ....................................  488,065,908

  422,014,039

  355,095,701

  295,750,077

280,673,122

Balance sheet data: 
Total assets ....................................................................  $
Long-term liabilities ......................................................  $
Series D Preferred Stock ................................................  $
Total shareholders’ equity .............................................  $

2,799,614    $
567,918    $
—    $
1,979,794    $

1,267,664    $
348,812    $
—    $
835,741    $

1,391,516    $
426,687    $
—    $
872,979    $

289,830   $
34,168   $
24,386   $
178,894   $

229,489 
25,443 
24,386 
160,882 

62 

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

RESULTS OF OPERATIONS. 

This Annual Report on Form 10-K contains certain forward-looking statements within the meaning of the Private 
Securities Litigation Reform Act of 1995 (“PSLRA”), Section 27A of the Securities Act of 1933, as amended, (the 
“Securities  Act”),  and  Section 21E  of  the  Securities  Exchange  Act  of  1934,  as  amended,  (the  “Exchange  Act”), 
about  our  expectations,  beliefs,  or  intentions  regarding  our  product  development  efforts,  business,  financial 
condition, results of operations, strategies, or prospects.  You can identify forward-looking statements by the fact 
that  these  statements  do  not  relate  strictly  to  historical  or  current  matters.    Rather,  forward-looking  statements 
relate to anticipated or expected events, activities, trends, or results as of the date they are made.  Because forward-
looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and 
uncertainties that could cause our actual results to differ materially from any future results expressed or implied by 
the forward-looking statements.  Many factors could cause our actual activities or results to differ materially from 
the activities and results anticipated in forward-looking statements.  These factors include those contained in “Item 
1A — Risk Factors” of this Annual Report on Form 10-K.  We do not undertake any obligation to update forward-
looking  statements.    We  intend  that  all  forward-looking  statements  be  subject  to  the  safe  harbor  provisions  of 
PSLRA.  These forward-looking statements are only predictions and reflect our views as of the date they are made 
with respect to future events and financial performance. 

OVERVIEW 

We are a diversified healthcare company that seeks to establish industry-leading positions in large and rapidly 
growing medical markets.  Our diagnostics business includes Bio-Reference Laboratories, the nation’s third-largest 
clinical laboratory with a core genetic testing business and a 420-person salesforce to drive growth and leverage new 
products,  including  the  4Kscore  prostate  cancer  test  and  the  Claros1  in-office  immunoassay  platform.    Our 
pharmaceutical  operations  feature  Rayaldee,  a  treatment  for  secondary  hyperparathyroidism  (“SHPT”)  in  patients 
with stage 3 or 4 chronic kidney disease (“CKD”) and vitamin D insufficiency (March 29, 2016 PDUFA date) and 
VARUBI™  for  chemotherapy-induced  nausea  and  vomiting  (launched  by  partner  TESARO  in  November  2015).  
Our  pharmaceutical  business  includes  OPKO  Biologics,  which  features  hGH-CTP,  a  once-weekly  human  growth 
hormone injection (in Phase 3 and partnered with Pfizer), and a once-daily Factor VIIa drug for hemophilia (Phase 
2a). 

We  operate  established  pharmaceutical  platforms  in  Spain,  Ireland,  Chile  and  Mexico,  which  are  generating 
revenue and from which we expect to generate positive cash flow and facilitate future market entry for our products 
currently in development.  EirGen, our specialty pharmaceutical manufacturing and development site in Ireland, is 
focused on the development and commercial supply of high potency, high barrier to entry pharmaceutical products.  
In  addition,  we  operate  a  specialty  active  pharmaceutical  ingredients  (“APIs”)  manufacturer  in  Israel,  which  we 
expect will facilitate the development of our pipeline of molecules and compounds for our proprietary products. 

RECENT DEVELOPMENTS 

In August 2015, we completed the acquisition of Bio-Reference, the third largest full service clinical laboratory 
in  the  United  States,  known  for  its  innovative  technological  solutions  and  pioneering  leadership  in  the  areas  of 
genomics and genetic sequencing.  Holders of Bio-Reference common stock received 76,566,147 shares of OPKO 
Common  Stock  for  the  outstanding  shares  of  Bio-Reference  common  stock.    The  transaction  was  valued  at 
approximately $950.1 million, based on a closing price per share of our Common Stock of $12.38 as reported by the 
New York Stock Exchange on the closing date, or $34.05 per share of Bio-Reference common stock.  Included in 
the  transaction  value  is  $2.3  million  related  to  the  value  of  replacement  stock  option  awards  attributable  to  pre-
merger service. 

In May 2015, we entered into a series of purchase agreements to acquire all of the issued and outstanding shares 
of EirGen, a specialty pharmaceutical company incorporated in Ireland focused on the development and commercial 
supply  of  high  potency,  high  barrier  to  entry  pharmaceutical  products,  for  $133.8  million  in  the  aggregate.    We 
acquired the outstanding shares of EirGen for approximately $100.2 million in cash and delivered 2,420,487 shares 
of our Common Stock valued at approximately $33.6 million based on the closing price per share of our Common 
Stock as reported by the New York Stock Exchange on the closing date of the acquisition, $13.88 per share.   

TESARO’s  NDA  for  approval  of  oral  VARUBI™,  an  investigational  neurokinin-1  receptor  antagonist  in 
development for the prevention of chemotherapy-induced nausea and vomiting, was approved by the U.S. FDA in 
September 2015, and in November 2015, TESARO announced the commercial launch of VARUBI™ in the United 
States.  Under the terms of the TESARO license, TESARO is obligated to pay us tiered royalties on annual net sales 
63 

 
of licensed products achieved in the United States and Europe at percentage rates that range from the low double 
digits to the low twenties, and outside of the United States and Europe at low double-digit percentage rates. 

We  have  been  granted  a  Category  I  CPT  code  by  the  AMA  for  our  4Kscore  test,  which  will  be  published  in 
August 2016 and effective January 1, 2017.  This upgrades the 4Kscore test from a Category III Administrative code 
to a Category I CPT code, a designation reserved for established diagnostic tests.  CPT codes are used by insurance 
companies  and  government  payers  to  describe  health  care  services  and  procedures,  and  having  a  Category  I  CPT 
code  is  critical  to  facilitate  reimbursement  in  government  programs  such  as  Medicare  and  Medicaid,  as  well  as 
private  insurance  programs.    We  believe  having  the  Category  I  CPT  code  will  help  facilitate  obtaining  broader 
coverage from payers for the 4Kscore test and allow greater access to the test for a broader group of patients across 
the U.S. 

RESULTS OF OPERATIONS 

For The Years Ended December 31, 2015 and December 31, 2014 

Revenues.  Revenues for the year ended December 31, 2015 increased $400.6 million compared to the prior year.  
Our  acquisition  of  Bio-Reference  in  August  2015  accounted  for  $321.9  million  of  the  year-over-year  revenue 
growth.  Revenues for the years ended December 31, 2015 and 2014 were as follows: 

Revenues 

(In thousands) 

For the year ended December 31, 

2015 

2014 

Change 

Revenue from services .......................................................$
Revenue from products .......................................................
Revenue from transfer of intellectual property and other ...

329,739   $
80,146  
81,853  

Total revenues ....................................................................$

491,738   $

8,666    $ 
76,983   
5,476   
91,125    $ 

321,073
3,163
76,377

400,613

The increase in Revenue from services is attributable to the acquisition of Bio-Reference in August 2015.  The 
increase in Revenue from products principally reflects $12.1 million of revenue from EirGen, which we acquired in 
May  2015,  which  was  partially  offset by  the  unfavorable  impact  of  foreign exchange rates  of  approximately  $8.7 
million, and decreased revenue from SciVac Therapeutics Inc. (“STI”), a VIE we deconsolidated in July 2015.  The 
increase  in  Revenue  from  transfer  of  intellectual  property  principally  reflects  $65.5  million  of  revenue  from  the 
transfer  of  intellectual  property  related  to  the  Pfizer  Transaction  and  $15.0  million  of  revenue  from  a  milestone 
payment  from  our  licensee  TESARO  in  the  fourth  quarter  of  2015  compared  to  $5.0  million  of  revenue  from  a 
milestone  payment  from  our  licensee  TESARO  in  2014.    We  are  recognizing  the  non-refundable  $295.0  million 
upfront payments received in the Pfizer Transaction on a straight-line basis over the expected performance period.  
The performance period is expected to continue through 2019, when we anticipate completing the various research 
and development services that are specified in the Pfizer Transaction.   

Costs of revenue.  Costs of revenue for the year ended December 31, 2015 increased $187.2 million compared to 
the prior year.  Our acquisition of Bio-Reference in August 2015 accounted for $183.3 million of the year-over-year 
cost of revenue growth.  Cost of revenue for the years ended December 31, 2015 and 2014 were as follows: 

Cost of Revenue 

(In thousands) 

For the year ended December 31, 

2015 

2014 

Change 

Cost of service revenue ......................................................$
Cost of product revenue ......................................................

193,305   $
41,934  

Total cost of revenue ..........................................................$

235,239   $

9,372    $ 
38,637  
48,009    $ 

183,933
3,297

187,230

The increase in cost of service revenue is attributable to the acquisition of Bio-Reference in August 2015.  The 
increase  in  cost  of  product  revenue  principally  reflects  cost  of  revenue  of  $6.8  million  from  EirGen,  which  we 

64 

 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
   
 
acquired  in  May  2015,  which  was  partially  offset  by  the  impact  of  foreign  exchange  rates  of  approximately  $5.2 
million and the deconsolidation of STI in July 2015.   

Selling, general and administrative expenses.  Selling, general and administrative expenses for the years ended 
December 31, 2015 and 2014 were $196.6 million and $57.9 million, respectively.  The increase in selling, general 
and  administrative  expenses  for  the  year  ended  December 31,  2015  was  primarily  due  to  the  acquisitions  of  Bio-
Reference  and  EirGen  in  2015,  which  recognized  $118.1  million  and  $1.8  million  of  selling,  general  and 
administrative expenses in 2015, respectively, increased personnel expenses as we expand our sales, marketing and 
administrative  staff  and  add  infrastructure,  and  an  increase  in  professional  fees  attributable  to  our  acquisitions  of 
Bio-Reference and EirGen.  Selling, general and administrative expenses during the years ended December 31, 2015 
and 2014, include bad debt expense of $24.6 million and $0.7 million, respectively, and equity-based compensation 
expense of $17.4 million and $9.7 million, respectively.  The increase in bad debt expense is due to the acquisition 
of Bio-Reference.  The increase in equity-based compensation expense is due to additional options grants made in 
2015 and fluctuations in the price of our common stock. 

Research  and  development  expenses.    Research  and  development  expenses  for  the  years  ended  December 31, 
2015  and  2014  were  $99.5  million  and  $83.6  million,  respectively.    Research  and  development  costs  include 
external  and  internal  expenses,  partially  offset  by  third-party  grants  and  funding  arising  from  collaboration 
agreements.    External  expenses  include  clinical  and  non-clinical  activities  performed  by  contract  research 
organizations,  lab  services,  purchases  of  drug  and  diagnostic  product  materials  and  manufacturing  development 
costs.  We track external research and development expenses by individual program for phase 3 clinical trials for 
drug approval and PMA’s (pre-market approval) for diagnostics tests, if any.  Internal expenses include employee-
related  expenses  including  salaries,  benefits  and  stock-based  compensation  expense.    Other  internal  research  and 
development  expenses  are  incurred  to  support  overall  research  and  development  activities  and  include  expenses 
related to general overhead and facilities. 

The following table summarizes the components of our research and development expenses: 

External expenses: 

Phase 3 clinical trials ................................................................... $
Manufacturing expense for biological products ........................... 
Earlier-stage programs ................................................................. 
Research and development employee-related expenses ...................
Other internal research and development expenses ..........................
Third-party grants and funding from collaboration agreements .......
Total research and development expenses .............................. $

For the years ended 
December 31, 

2015 

2014 

12,178    $ 
22,674   
6,900   
27,363   
32,689   
(2,316)  
99,488    $ 

14,512
18,692
9,093
21,642
21,982
(2,350)
83,571

The increase in research and development expenses during the year ended December 31, 2015, is primarily due 
to a $16.7 million increase in research and development expenses related to hGH-CTP, a long acting human growth 
hormone which was outlicensed to Pfizer in 2015, including manufacturing expense for biological products, and the 
recognition  of  $2.3  million  of  expense  for  our  NDA  submission  to  the  FDA  for  oral  Rayaldee  in  May  2015.  
Research  and  development  expenses  for  the  year  ended  December 31,  2015  also  include  $4.1  million  from  the 
acquisitions of Bio-Reference and EirGen in August 2015 and May 2015, respectively.  This was partially offset by 
decreased expenses incurred by OPKO Renal related to phase 3 clinical trials for Rayaldee, which were completed 
in 2014.  In addition, during the year ended December 31, 2015 and 2014, we recorded, as an offset to research and 
development  expenses,  $2.3  million  and  $2.4  million,  respectively,  related  to  research  and  development  grants 
received from our collaboration and funding agreements.  Research and development expenses for the year ended 
December 31,  2015  and  2014  include  equity-based  compensation  expense  of  $7.9  million  and  $5.0  million, 
respectively.  We expect our research and development expense to increase as we continue to expand our research 
and development of potential future products. 

In-Process Research and Development.  In May 2014, we acquired Inspiro in a stock for stock transaction.  We 
recorded the transaction as an asset acquisition and recorded the assets and liabilities at fair value, and as a result, we 
recorded  $10.1  million  of  acquired  in-process  research  and  development  expense.    In  addition,  pursuant  to  our 
agreement with Merck & Co. (“Merck”), we were required to make a $2.0 million payment upon the achievement of 

65 

 
 
 
 
 
 
   
 
 
     
a milestone for VARUBI™ which was achieved in the fourth quarter of 2014.  The agreement was accounted for as 
an  asset  acquisition  and  the  entire  $2.0  million  milestone  payment  was  allocated  to  in-process  research  and 
development  expense.    No  In-process  research  and  development  expense  was  incurred  during  the  year  ended 
December 31, 2015.   

Contingent consideration.  Contingent consideration expenses for the years ended December 31, 2015 and 2014, 
were  $5.0  million  and  $24.4  million,  respectively.    The  decrease  in  contingent  consideration  expense  was 
attributable to OPKO Renal resulting from an increase in the fair value of our contingent obligations to OPKO Renal 
in 2014 due to changes in assumptions regarding probabilities of successful achievement of future milestones driven 
by the two successful phase 3 trials of Rayaldee in 2014.  The contingent consideration liabilities at December 31, 
2015  relate  to  potential  amounts  payable  to  former  stockholders  of  CURNA,  OPKO  Diagnostics,  OPKO  Health 
Europe and OPKO Renal pursuant to our acquisition agreements in January 2011, October 2011, August 2012 and 
March 2013, respectively. 

Amortization  of  intangible  assets.    Amortization  of  intangible  assets  was  $28.0  million  and  $10.9  million, 
respectively, for the years ended December 31, 2015 and 2014.  Amortization expense reflects the amortization of 
acquired  intangible  assets  with  defined  useful  lives.    Amortization  of  intangible  assets  for  the  year  ended 
December 31, 2015 includes $14.6 million and $1.7 million from Bio-Reference and EirGen which we acquired in 
August  2015  and  May  2015,  respectively.    Our  IPR&D  assets  will  not  be  amortized  until  the  underlying 
development programs are completed.  Upon obtaining regulatory approval by the U.S. FDA, the IPR&D assets will 
then be accounted for as a finite-lived intangible asset and amortized on a straight-line basis over its estimated useful 
life.   

Grant repayment.  During the year ended December 31, 2015, we made a payment of $25.9 million to the Office 
of  the  Chief  Scientist  of  the  Israeli  Ministry  of  Economy  (“OCS”)  in  connection  with  repayment  obligations 
resulting from grants previously made by the OCS to OPKO Biologics to support development of hGH-CTP and the 
outlicense of the technology outside of Israel.   

Interest income.  Interest income for the years ended December 31, 2015 and 2014, was not significant as our 

cash investment strategy emphasizes the security of the principal invested and fulfillment of liquidity needs. 

Interest expense.  Interest expense for the years ended December 31, 2015 and 2014, was $8.4 million and $12.3 
million, respectively.  Interest expense is principally related to interest incurred on the 2033 Senior Notes and the 
amortization of related deferred financing costs.  The decrease in interest expense for the year ended December 31, 
2015 compared to 2014 is due to a decrease in the principal amount of 2033 Senior Notes outstanding from $87.6 
million  at  December 31,  2014  to  $32.2  million  as  of  December 31,  2015.    This  was  partially  offset  by  interest 
expense of $1.9 million from Bio-Reference due to outstanding debt under their credit facility.  Interest expense for 
the  years  ended  December 31,  2015  and  2014  also  reflect non-cash  write-offs  of  deferred  financing  costs  of  $1.0 
million and $1.5 million as interest expense related to exchange or conversion of $55.4 million and $70.4 million 
principal of 2033 Senior Notes during the years ended December 31, 2015 and 2014, respectively. 

Fair value changes of derivative instruments, net.  Fair value changes of derivative instruments, net for the years 
ended  December 31,  2015  and  2014,  were  $39.1  million  and  $10.6  million  of  expense,  respectively.    Fair  value 
changes of derivative instruments, net principally related to non-cash expense related to the changes in the fair value 
of  the  embedded  derivatives  in  the  2033  Senior  Notes  of  $36.6  million  and  $12.2  million  for  the  years  ended 
December 31, 2015 and 2014, respectively.   

Other income and (expense), net.  Other income and (expense), net for the years ended December 31, 2015 and 
2014, were $7.7 million of income and $(3.1) million of expense, respectively.  The increase in other income and 
(expense),  net  for  the  year  ended  December 31,  2015  compared  to  2014  is  primarily  due  to  a  $15.9  million  gain 
recognized on the deconsolidation of STI in the third quarter of 2015.  This was partially offset by a $7.3 million 
other-than-temporary  impairment  charge  to  write  our  investment  in  RXi  Pharmaceuticals  Corporation  down  to  its 
fair  value  of  $0.9  million  as  of  December 31,  2015  compared  to  a  $1.4  million  other-than-temporary  impairment 
charge to our investment in ARNO Therapeutics in 2014. 

Income tax benefit (provision).  Our income tax benefit is due to a $93.4 million release of OPKO’s valuation 
allowance on our U.S. deferred tax assets as a result of the merger with Bio-Reference.  This was partially offset by 
expense recognized on taxable income from the Pfizer Transaction during the year ended December 31, 2015.  In 

66 

 
 
addition,  our  income  tax  benefit  (provision)  reflects  the  projected  income  tax  payable  in  the  U.S.,  Ireland,  Israel, 
Chile, Spain, Mexico, and Luxembourg. 

Loss from investments in investees.  We have made investments in other early stage companies that we perceive 
to have valuable proprietary technology and significant potential to create value for us as a shareholder or member.  
We  account  for  these  investments  under  the  equity  method  of  accounting,  resulting  in  the  recording  of  our 
proportionate  share  of  their  losses  until  our  share  of  their  loss  exceeds  our  investment.    Until  the  investees’ 
technologies  are  commercialized,  if  ever,  we  anticipate  they  will  continue  to  report  a  net  loss.    Loss  from 
investments  in  investees  was  $7.1  million  and  $3.6  million  for  the  years  ended  December 31,  2015  and  2014, 
respectively.  In the third quarter of 2015 we deconsolidated STI, and account for our retained interest in STI as an 
equity method investment. 

For The Years Ended December 31, 2014 and December 31, 2013 

Revenues.  Revenues for the year ended December 31, 2014, were $91.1 million, compared to $96.5 million for 
the year ended December 31, 2013.  The decrease in revenue principally reflects non-recurring, non-cash revenue 
related to the transfer of technology under the RXi Asset Purchase Agreement of $12.5 million in 2013, which was 
partially offset by (i) a milestone payment of $5.0 million from TESARO during the year ended December 31, 2014, 
which  we  recognized  in  Revenue  from  transfer  of  intellectual  property  and  (ii)  a  14%  increase  in  pharmaceutical 
product  revenue  principally  from  FineTech  of  $6.2  million  for  the  year  ended  December 31,  2014.    In  addition, 
pharmaceutical  product  revenue  from  our  European  and  Mexican  operations  increased  by  $2.5  million  and  $1.6 
million, respectively, during the year ended December 31, 2014, primarily due to increased sales by OPKO Health 
Europe and an increase in government tenders in Mexico.  Revenue related to OPKO Lab decreased $2.9 million 
during  the  year  ended  December 31,  2014,  compared  to  the  year  ended  December 31,  2013,  primarily  related  to 
decreased reimbursement rates from government payors and decreased specimen volume, partially offset by revenue 
from the launch of our 4Kscore test and a price increase to non-government payors initiated in June 2014. 

Costs  of  revenue.    Costs  of  revenue  for  the  year  ended  December 31,  2014,  were  $48.0  million,  compared  to 
$48.9  million  for  the  year  ended  December 31,  2013.    Costs  of  revenue  for  the  year  ended  December 31,  2014 
decreased  principally  due  to  decreased  revenue  at  OPKO  Lab,  which  has  a  lower  margin  than  pharmaceutical 
product sales.  In addition, inventory obsolescence charges decreased $0.9 million for the year ended December 31, 
2014  compared  to  2013.    This  was  partially  offset  by  increased  cost  of  revenue  due  to  increased  pharmaceutical 
product sales. 

Selling, general  and administrative  expenses.   Selling, general  and  administrative  expenses  for  the year  ended 
December 31,  2014  were  $57.9  million,  compared  to  $55.3  million  for  the  year  ended  December 31,  2013.    The 
increase  in  selling,  general  and  administrative  expenses  for  the  year  ended  December 31,  2014  was  a  result  of 
increased personnel expenses including equity based compensation as well as sales and marketing activities related 
to the launch of our 4Kscore test in the U.S. in March 2014 and Europe in September 2014.  These increases were 
partially  offset  by  decreased  professional  fees  as  the  2013  period  included  expenses  related  to  the  acquisitions  of 
OPKO  Renal  and  OPKO  Biologics.    Selling,  general  and  administrative  expenses  during  the  years  ended 
December 31,  2014  and  2013,  include  equity-based  compensation  expense  of  $9.7  million  and  $7.3  million, 
respectively. 

Research  and  development  expenses.    Research  and  development  expenses  for  the  year  ended  December 31, 
2014  were  $83.6  million,  compared  to  $53.9  million  for  the  year  ended  December 31,  2013.    Research  and 
development costs include external and internal expenses, partially offset by third-party grants and funding arising 
from collaboration agreements.  External expenses include clinical and non-clinical activities performed by contract 
research  organizations,  lab  services,  purchases  of  drug  and  diagnostic  product  materials  and  manufacturing 
development  costs.    We  track  external  research  and  development  expenses  by  individual  program  for  phase  3 
clinical  trials  for  drug  approval  and  PMA’s  (pre-market  approval)  for  diagnostics  tests,  if  any.    Internal  expenses 
include  employee-related  expenses  including  salaries,  benefits  and  stock-based  compensation  expense.    Other 
internal research and development expenses are incurred to support overall research and development activities and 
include expenses related to general overhead and facilities. 

67 

 
 
The following table summarizes the components of our research and development expenses: 

External expenses: 

Phase 3 clinical trials ................................................................... $
CMC expense for biological products ......................................... 
Earlier-stage programs .................................................................
Research and development employee-related expenses ...................
Other internal research and development expenses ..........................
Third-party grants and funding from collaboration agreements .......
Total research and development expenses .............................. $

For the years ended 
December 31, 

2014 

2013 

14,512    $ 
18,692   
9,093   
21,642   
21,982   
(2,350)  
83,571    $ 

13,078
1,765
4,599
17,215
18,998
(1,753)
53,902

The increase in research and development expenses during the year ended December 31, 2014, as compared to 
the  year  ended  December 31,  2013,  principally  resulted  from  $38.6  million  of  costs  related  to  OPKO  Biologics 
which we acquired in August 2013 and an increase related to research and development expenses incurred by OPKO 
Renal related to the external costs of two pivotal phase 3 clinical trials for Rayaldee which were completed in 2014, 
and  a  third  open-label  phase  3  trial  completed  in  2015.    OPKO  Biologics  principally  incurred  development  and 
clinical  manufacturing  costs  (“CMC”)  related  to  hGH-CTP,  a  long  acting  human  growth  hormone  which  was 
outlicensed  to  Pfizer  in  2015.    Research  and  development  expenses  for  the  years  ended  December 31,  2014  and 
2013  include  equity-based  compensation  expense  of  $5.0  million  and  $3.6  million,  respectively.    Research  and 
development  expenses  for  the  year  ended  December 31,  2013,  includes  an  offset  to  research  and  development 
expenses of $2.7 million related to the correction of an error related to equity awards granted to non-employees with 
performance based vesting. 

Contingent consideration.  Contingent consideration expenses for the years ended December 31, 2014 and 2013, 
were $24.4 million and $6.9 million, respectively.  The increase in contingent consideration expense was primarily 
attributable to an increase in the fair value of our contingent obligations to the former stockholders of OPKO Renal 
due to changes in assumptions regarding probabilities of successful achievement of future milestones driven by the 
two successful  phase  3  trials  of  Rayaldee  in 2014.    The contingent  consideration  liabilities  at  December 31, 2014 
relate to potential amounts payable to former stockholders of CURNA, OPKO Diagnostics, OPKO Health Europe 
and OPKO Renal pursuant to our acquisition agreements in January 2011, October 2011, August 2012 and March 
2013, respectively. 

Amortization  of  intangible  assets.    Amortization  of  intangible  assets  was  $10.9  million  and  $11.1  million, 
respectively, for the years ended December 31, 2014 and 2013.  Amortization expense reflects the amortization of 
acquired intangible assets with defined useful lives.  The acquisitions of OPKO Renal and OPKO Biologics resulted 
in principally acquiring IPR&D assets which will not be amortized until the underlying development programs are 
completed.  Upon obtaining regulatory approval by the FDA, the IPR&D asset will then be accounted for as a finite-
lived intangible asset and amortized on a straight-line basis over its estimated useful life. 

In-Process  Research  and  Development.    In  May  2014,  we  acquired  Inspiro,  a  privately  held  company  that  is 
developing  the  Inspiromatic,  a  “smart”  easy-to-use  dry  powder  inhaler  with  several  advantages  over  existing 
devices.  We recorded the transaction as an asset acquisition and recorded the assets and liabilities at fair value.  As 
the asset had no alternative future use, we recorded $10.1 million of acquired in-process research and development 
expense.    In  addition,  pursuant  to  our  agreement  with  Merck,  we  were  required  to  make  a  $2.0  million  payment 
upon  the  achievement  of  a  milestone  for  rolapitant  which  was  achieved  in  the  fourth  quarter  of  2014.    The 
agreement was accounted for as an asset acquisition and the entire $2.0 million milestone payment was allocated to 
in-process  research  and  development  expense.    We  did  not  have  any  such  activity  during  the  year  ended 
December 31, 2013. 

We record expense for in-process research and development projects accounted for as asset acquisitions which 
have  not  reached  technological  feasibility  and  which  have  no  alternative  future  use.    Inspiromatic  and  rolapitant 
have not reached a stage of technological feasibility and have no alternative future use. 

Other income and (expense), net.  Other income and (expense), net for the years ended December 31, 2014 and 
2013 was ($25.2) million and $24.6 million of expense, respectively.  During the year ended December 31, 2014, we 

68 

 
 
 
 
 
 
   
 
 
     
recorded  $12.2  million  non-cash  other  charge,  net,  related  to  the  changes  in  the  fair  value  of  the  embedded 
derivatives in the 2033 Senior Notes, and a $2.7 million gain as the result of the exchange of $70.4 million principal 
of 2033 Senior Notes in June 2014.  Other income and (expense), net, for the year ended December 31, 2014, also 
included $12.3 million of interest expense principally related to interest incurred on the 2033 Senior Notes and the 
amortization of related deferred financing costs.  Other income and (expense), net for the year ended December 31, 
2014,  includes  a  $1.4  million  other-than-temporary  impairment  charge  to  write  our  investment  in  ARNO 
Therapeutics down to its fair value of $0.6 million as of December 31, 2014. 

For the year ended December 31, 2013, we recorded a $52.7 million non-cash charge, net, related to the changes 
in  the  fair value  of  the  embedded derivatives  in  the 2033  Senior Notes,  partially  offset  by  a  $1.0 million  gain on 
early partial conversion of the 2033 Senior Notes, income of $6.5 million related to changes in the fair value of the 
Pharmsynthez  Note  Receivable,  a  certain  Pharmsynthez  purchase  option,  warrants  and  options  received  in 
connection with our investment in Neovasc and ARNO, and by a gain of $29.9 million on the sale of certain of our 
strategic investments.  Other income and (expense), net, for the year ended December 31, 2013, also included $13.8 
million  of  interest  expense  primarily  related  to  the  2033  Senior  Notes  and  the  amortization  of  related  deferred 
financing  costs.    The  decrease  in  interest  expense  for  the  year  ended  December 31,  2014  compared  to  the  same 
period  in  2013  is  due  to  the  exchange  of  $70.4  million  principal  of  2033  Senior  Notes  in  June  2014,  which  was 
partially  offset  by  a  non-cash  write-off  of  deferred  financing  costs  of  $1.5  million  as  interest  expense  related  to 
exchange of the 2033 Senior Notes in June 2014. 

Income  tax  benefit  (provision).    Our  income  tax  provision  reflects  the  projected  income  tax  payable  in  Israel, 
Chile,  Spain,  Mexico,  Canada  and  SciVac  Ltd,  a  consolidated  variable  interest  entity.    We  have  recorded  a  full 
valuation allowance against our deferred tax assets in the U.S. 

Loss from investments in investees.  We have made investments in other early stage companies that we perceive 
to have valuable proprietary technology and significant potential to create value for us as a shareholder.  We account 
for these investments under the equity method of accounting, resulting in the recording of our proportionate share of 
their  losses  until  our  share  of  their  loss  exceeds  our  investment.    Until  the  investees’  technologies  are 
commercialized, if ever, we anticipate they will continue to report a net loss.  Loss from investments in investees 
was $3.6 million and $11.5 million for the years ended December 31, 2014 and 2013, respectively.  The decrease in 
loss  from  investments  in  investees  is  primarily  due  to  decreased  losses  at  RXi  Pharmaceuticals  Corporation  and 
Cocrystal Pharma, Inc.  During the third quarter of 2014, we discontinued applying the equity method of accounting 
for RXi and account for our investment in RXi as an available for sale investment. 

LIQUIDITY AND CAPITAL RESOURCES 

At December 31, 2015, we had cash and cash equivalents of approximately $193.6 million.  Cash provided by 
operations  during  2015  principally  reflects  the  $295.0  million  upfront  payments  received  from  the  Pfizer 
Transaction, partially offset by a payment of $25.9 million to the OCS for obligations from grants previously made 
by  the  OCS  to  OPKO  Biologics,  expenses  related  to  selling,  general  and  administrative  activities  related  to  our 
corporate  operations,  research  and  development  activities  and  our  operations  at  Bio-Reference,  OPKO  Biologics, 
OPKO Renal and OPKO Diagnostics.  We recognized $65.5 million of revenue related to the $295.0 million upfront 
payments  received  from  Pfizer  during  the  year  ended  December 31,  2015,  and  will  recognize  the  remainder  as 
revenue on a straight-line basis over the expected performance period.  Cash used in investing activities includes the 
net cash used in acquisitions of $79.0 million, which reflects cash used to acquire EirGen, net and cash provided by 
the Bio-Reference acquisition.  Cash provided by financing activities primarily reflects $25.9 million received from 
Common Stock option and Common Stock warrant exercises.  During the year ended December 31, 2015, we also 
satisfied  a  $20.0  million  contingent  payment  to  the  former  owners  of  OPKO  Renal  through  the  issuance  of 
1,194,337  shares  of  our  common  stock  in  the  third  quarter  of  2015.    Since  our  inception,  we  have  not  generated 
gross margins sufficient to offset our operating and other expenses and our primary source of cash has been from the 
public and private placement of stock, the issuance of the 2033 Senior Notes and credit facilities available to us. 

In  January  2015,  we  partnered  with  Pfizer  through  a  worldwide  agreement  for  the  development  and 
commercialization of our long-acting hGH-CTP for the treatment of growth hormone deficiency (“GHD”) in adults 
and  children,  as  well  as  for  the  treatment  of  growth  failure  in  children  born  small  for  gestational  age  (“SGA”).  
Under the terms of the agreements with Pfizer, we received non-refundable and non-creditable upfront payments of 
$295.0 million in the first quarter of 2015 and are eligible to receive up to an additional $275.0 million upon the 
achievement  of  certain  regulatory  milestones.    Pfizer  received  the  exclusive  license  to  commercialize  hGH-CTP 
worldwide.    In  addition,  we  are  eligible  to  receive  initial  tiered  royalty  payments  associated  with  the 

69 

 
 
commercialization of hGH-CTP for Adult GHD with percentage rates ranging from the high teens to mid-twenties.  
Upon the launch of hGH-CTP for Pediatric GHD in certain major markets, the royalties will transition to regional, 
tiered gross profit sharing for both hGH-CTP and Pfizer’s Genotropin®. 

We  will  lead  the  clinical  activities  and  will  be  responsible  for  funding  the  development  programs  for  the  key 
indications,  which  includes  Adult  and  Pediatric  GHD  and  Pediatric  SGA.    Pfizer  will  be  responsible  for  all 
development costs for additional indications as well as all post-marketing studies.  In addition, Pfizer will fund the 
commercialization  activities  for  all  indications  and  lead  the  manufacturing  activities  covered  by  the  global 
development plan. 

   In August 2015, we completed the acquisition of Bio-Reference, the third largest full service clinical laboratory 
in  the  United  States,  known  for  its  innovative  technological  solutions  and  pioneering  leadership  in  the  areas  of 
genomics and genetic sequencing.  Holders of Bio-Reference common stock received 76,566,147 shares of OPKO 
Common  Stock  for  the  outstanding  shares  of  Bio-Reference  common  stock.    The  transaction  was  valued  at 
approximately $950.1 million, based on a closing price per share of our Common Stock of $12.38 as reported by the 
New York Stock Exchange on the closing date, or $34.05 per share of Bio-Reference common stock.  Included in 
the  transaction  value  is  $2.3  million  related  to  the  value  of  replacement  stock  option  awards  attributable  to  pre-
merger service. 

In May 2015, we entered into a series of purchase agreements to acquire all of the issued and outstanding shares 
of EirGen, a specialty pharmaceutical company incorporated in Ireland focused on the development and commercial 
supply  of  high  potency,  high  barrier  to  entry  pharmaceutical  products,  for  $133.8  million  in  the  aggregate.    We 
acquired the outstanding shares of EirGen for approximately $100.2 million in cash and delivered 2,420,487 shares 
of our Common Stock valued at approximately $33.6 million based on the closing price per share of our Common 
Stock as reported by the New York Stock Exchange on the closing date of the acquisition, $13.88 per share.   

Our  licensee,  TESARO,  received  approval  by  the  U.S.  FDA  in  September  2015  for  oral  VARUBI™,  a 
neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting.  In November 
2015, TESARO announced the commercial launch of VARUBI™ in the United States.  We are eligible to receive 
milestone payments of up to $30.0 million (of which $20.0 million has been received to date) upon achievement of 
certain  regulatory  and  commercial  sale  milestones  and  additional  commercial  milestone  payments  of  up  to  $85.0 
million if specified levels of annual net sales are achieved.  During the years ended December 31, 2015 and 2014, 
$15.0  million  and  $5.0  million  of  revenue,  respectively,  has  been  recognized  related  to  the  achievement  of  the 
milestones under the TESARO License.  TESARO is also obligated to pay us tiered royalties on annual net sales 
achieved  in  the  United  States  and  Europe  at  percentage  rates  that  range  from  the  low  double  digits  to  the  low 
twenties, and outside of the United States and Europe at low double-digit percentage rates.   

Under  the  terms  of  our  agreement  with  Merck,  upon  approval  by  the  FDA  of  the  TESARO’s  NDA  for  oral 
VARUBI™, which occurred in September 2015, we were required to pay Merck a $5.0 million milestone payment.  
In addition, $5.0 million will be due and payable each year thereafter for the next four (4) years on the anniversary 
date of the NDA approval.  We recognized the present value of the milestone payments on FDA approval of $23.0 
million as an intangible asset which will be amortized to expense over the expected useful life of the asset, which is 
approximately 13 years.  The present value of the future payments to Merck of $18.2 million at December 31, 2015 
is recorded as a liability in our Consolidated Balance Sheet with $5.0 million in Accrued expenses and $13.2 million 
in Other long-term liabilities. 

2033 Senior Notes.  In January 2013, we issued $175.0 million of the 2033 Senior Notes.  The 2033 Senior Notes 
were  sold  in  a  private  placement  in  reliance  on  exemptions  from  registration  under  the  Securities  Act.    Net  cash 
proceeds from the offering totaled $170.2 million.  Holders of the 2033 Senior Notes may require us to repurchase 
the 2033 Senior Notes for 100% of their principal amount, plus accrued and unpaid interest, on February 1, 2019, 
February 1,  2023  and  February 1,  2028,  or  following  the  occurrence  of  a  fundamental  change  as  defined  in  the 
indenture governing the 2033 Senior Notes.   

In  August  2013  and  June  2014,  holders  exchanged  or  converted  $16.9  million  and  $70.4  million  principal 

amount of 2033 Senior Notes, respectively. 

On April 1, 2015, we announced that our 2033 Senior Notes were convertible through June 2015 by holders of 
such  notes.    This  conversion  right  was  triggered  because  the  closing  price  per  share  of  our  Common  Stock  had 
exceeded $9.19, or 130% of the initial conversion price of $7.07, for at least 3 of 30 consecutive trading days during 

70 

 
 
the period ending on March 31, 2015.  Our 2033 Senior Notes continued to be convertible by holders of such notes 
for the remainder of 2015 and the first quarter of 2016.  During 2015, pursuant to the conversion right or through 
exchange agreements we entered with certain holders of our 2033 Senior Notes, holders of our 2033 Senior Notes 
converted or exchanged $55.4 million in aggregate principal amount of 2033 Senior Notes for 8,118,062 shares of 
the Company’s Common Stock.  At December 31, 2015, $32.2 million principal amount of 2033 Senior Notes was 
outstanding. 

In connection with our acquisitions of CURNA, OPKO Diagnostics, OPKO Health Europe and OPKO Renal, we 
agreed  to  pay  future  consideration  to  the  sellers  upon  the  achievement  of  certain  events,  including  up  to  an 
additional $19.1 million in shares of our Common Stock to the former stockholders of OPKO Diagnostics upon and 
subject  to  the  achievement  of  certain  milestones;  and  up  to  an  additional  $150.0  million  in  either  shares  of  our 
Common Stock or cash, at our option subject to the achievement of certain milestones, to the former shareholders of 
OPKO Renal.   

As of December 31, 2015, the total availability under our Credit Agreement with JPMorgan Chase Bank, N.A. 
(“CB”)  and  our  lines  of  credit  with  financial  institutions  in  Chile  and  Spain  was  $189.8  million,  of  which  $82.7 
million was used and outstanding at December 31, 2015.  The weighted average interest rate on these lines of credit 
is approximately 4.3%.  These lines of credit are short-term and are used primarily as a source of working capital.  
The  highest  balance  at  any  time  during  the  year  ended  December 31,  2015,  was  $91.5  million.    We  intend  to 
continue to enter into these lines of credit as needed.  There is no assurance that these lines of credit or other funding 
sources will be available to us on acceptable terms, or at all, in the future. 

On November 5, 2015, Bio-Reference and certain of its subsidiaries entered into a credit agreement with CB, as 
lender and administrative agent (the “Credit Agreement”), which replaced Bio-Reference’s existing Credit Facility 
with  PNC  Bank,  National  Association  (“PNC”).    The  Credit  Agreement  provides  for  a  $175.0  million  secured 
revolving credit facility and includes a $20.0 million sub-facility for swingline loans and a $20.0 million sub-facility 
for  the  issuance  of  letters  of  credit.    Bio-Reference  may  increase  the  credit  facility  to  up  to  $275.0  million  on  a 
secured  basis,  subject  to  the  satisfaction  of  specified  conditions.    The  Credit  Agreement  matures  on  November 5, 
2020 and is guaranteed by all of Bio-Reference’s domestic subsidiaries.  The Credit Agreement is also secured by 
substantially all assets of Bio-Reference and its domestic subsidiaries, as well as a non-recourse pledge by us of our 
equity interest in Bio-Reference.  Availability under the Credit Agreement is based on a borrowing base comprised 
of eligible accounts receivables of Bio-Reference and certain of its subsidiaries, as specified therein.  The proceeds 
of  the  new  credit  facility  were  used  to  refinance  existing  indebtedness,  including  amounts  outstanding  under  the 
credit  facility  with  PNC  which  was  terminated  in  2015  in  accordance  with  its  terms,  to  finance  working  capital 
needs and for general corporate purposes of Bio-Reference and its subsidiaries. 

We expect to continue to incur losses from operations.  We expect to incur substantial research and development 
expenses, including expenses related to the hiring of personnel and additional clinical trials.  We expect that selling, 
general and administrative expenses will also increase as we expand our sales,  marketing and administrative staff 
and add infrastructure. 

We believe that the cash and cash equivalents on hand at December 31, 2015, and the amounts available to be 
borrowed under our lines of credit are sufficient to meet our anticipated cash requirements for operations and debt 
service  beyond  the  next  12  months.    We  based  this  estimate  on  assumptions  that  may  prove  to  be  wrong  or  are 
subject to change, and we may be required to use our available cash resources sooner than we currently expect.  If 
we  acquire  additional  assets  or  companies,  accelerate  our  product  development  programs  or  initiate  additional 
clinical  trials,  we  will  need  additional  funds.    Our  future  cash  requirements  will  depend  on  a  number  of  factors, 
including our relationship with Pfizer, our merger with Bio-Reference, possible acquisitions, the continued progress 
of  research  and  development  of  our  product  candidates,  the  timing  and  outcome  of  clinical  trials  and  regulatory 
approvals, the costs involved in preparing, filing, prosecuting, maintaining, defending, and enforcing patent claims 
and  other  intellectual  property  rights,  the  status  of  competitive  products,  the  availability  of  financing,  and  our 
success  in  developing  markets  for  our  product  candidates.    If  we  are  not  able  to  secure  additional  funding  when 
needed, we may have to delay, reduce the scope of, or eliminate one or more of our clinical trials or research and 
development programs or possible acquisitions. 

71 

 
 
The following table provides information as of December 31, 2015, with respect to the amounts and timing of 

our known contractual obligation payments due by period. 

Contractual obligations 
(In thousands) 

2016 

2017 

2018 

2019 

2020 

  Thereafter 

Total 

15,830

Open purchase orders ......................................    $  48,258 $
Operating leases ...............................................    
Capital leases ...................................................    
2033 Senior Notes ...........................................    
Deferred payments...........................................    
Mortgages and other debts payable .................    
Lines of credit ..................................................    
Interest commitments ......................................    
Total .................................................................    $  161,944 $

83,250

2,493

1,351

5,762

5,000

—

— $

— $

— $

10,749

3,951

—

5,000

293

—

7,862

2,607

—

5,000

245

—

1,031

1,020

6,558

1,386

32,200

5,000

236

—

207

21,024 $

16,734 $

45,587 $

—    $ 

3,208   
603   
—   
—   
234   
—   
32   
4,077    $ 

—  $

7,525 
794 
— 
— 
955 
— 
60 

48,258

51,732

15,103

32,200

20,000

4,456

83,250

3,701
9,334  $ 258,700

The  preceding  table  does  not  include  information  where  the  amounts  of  the  obligations  are  not  currently 

determinable, including the following: 

-  Contractual  obligations  in  connection  with  clinical  trials,  which  span  over  two  years,  and  that  depend  on 
patient enrollment.  The total amount of expenditures is dependent on the actual number of patients enrolled 
and as such, the contracts do not specify the maximum amount we may owe. 

-  Product license agreements effective during the lesser of 15 years or patent expiration whereby payments and 

amounts are determined by applying a royalty rate on uncapped future sales. 

-  Contingent  consideration  that  includes  payments  upon  achievement  of  certain  milestones  including  meeting 
development milestones such as the completion of successful clinical trials, NDA approvals by the FDA and 
revenue  milestones  upon  the  achievement  of  certain  revenue  targets  all  of  which  are  anticipated  to  be  paid 
within the next seven years and are payable in either shares of our Common Stock or cash, at our option, and 
that may aggregate up to $189.6 million. 

CRITICAL ACCOUNTING POLICIES AND ESTIMATES 

Accounting  estimates.    The  preparation  of  financial  statements  in  conformity  with  accounting  principles 
generally  accepted  in  the  United  States  requires  management  to  make  estimates  and  assumptions  that  affect  the 
reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the date of the financial 
statements  and  the  reported  amounts  of  revenues  and  expenses  during  the  reporting  period.    Actual  results  could 
differ significantly from these estimates. 

Goodwill  and  Intangible  Assets.    Goodwill  represents  the  difference  between  the  purchase  price  and  the 
estimated  fair  value  of  the  net  assets  acquired  when  accounted  for  by  the  acquisition  method  of  accounting.  
Goodwill  and  other  intangible  assets,  including  IPR&D,  acquired  in  business  combinations,  licensing  and  other 
transactions  was  $2.2  billion  and  $1.1  billion  at  both  December 31,  2015  and  2014,  respectively,  representing 
approximately 78% and 85% of total assets, respectively. 

Assets acquired and liabilities assumed in business combinations, licensing and other transactions are generally 
recognized  at  the  date  of  acquisition  at  their  respective  fair  values.    Any  excess  of  the  purchase  price  over  the 
estimated fair values of the net assets acquired is recognized as goodwill.  We determined the fair value of intangible 
assets,  including  IPR&D,  using  the  “income  method.”    This  method  starts  with  a  forecast  of  net  cash  flows,  risk 
adjusted for estimated probabilities of technical and regulatory success (for IPR&D) and adjusted to present value 
using an appropriate discount rate that reflects the risk associated with the cash flow streams.  All assets are valued 
from  a  market  participant  view  which  might  be  different  than  our  specific  views.    The  valuation  process  is  very 
complex and requires significant input and judgment using internal and external sources.  Although the valuations 
are required to be finalized within a one-year period, it must consider all and only those facts and evidence which 

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existed at the acquisition date.  The most complex and judgmental matters applicable to the valuation process are 
summarized below: 

(cid:120)  Unit of account – Most intangible assets are valued as single global assets rather than multiple assets 
for  each  jurisdiction  or  indication  after  considering  the  development  stage,  expected  levels  of 
incremental costs to obtain additional approvals, risks associated with further development, amount 
and  timing  of  benefits  expected  to  be  derived  in  the  future,  expected  patent  lives  in  various 
jurisdictions and the intention to promote the asset as a global brand. 

(cid:120)  Estimated  useful  life  –  The  asset  life  expected  to  contribute  meaningful  cash  flows  is  determined 
after  considering  all  pertinent  matters  associated  with  the  asset,  including  expected  regulatory 
approval  dates  (if  unapproved),  exclusivity  periods  and  other  legal,  regulatory  or  contractual 
provisions  as  well  as  the  effects  of  any  obsolescence,  demand,  competition,  and  other  economic 
factors, including barriers to entry. 

(cid:120)  Probability of Technical and Regulatory Success (“PTRS”) Rate – PTRS rates are determined based 
upon  industry  averages  considering  the  respective  programs  development  stage  and  disease 
indication and adjusted for specific information or data known at the acquisition date.  Subsequent 
clinical results or other internal or external data obtained could alter the PTRS rate and materially 
impact the estimated fair value of the intangible asset in subsequent periods leading to impairment 
charges. 

(cid:120)  Projections  –  Future  revenues  are  estimated  after  considering  many  factors  such  as  initial  market 
opportunity,  pricing,  sales  trajectories  to  peak  sales  levels,  competitive  environment  and  product 
evolution.  Future costs and expenses are estimated after considering historical market trends, market 
participant synergies and the timing and level of additional development costs to obtain the initial or 
additional  regulatory  approvals,  maintain  or  further  enhance  the  product.    We  generally  assume 
initial  positive  cash  flows  to  commence  shortly  after  the  receipt  of  expected  regulatory  approvals 
which typically may not occur for a number of years.  Actual cash flows attributed to the project are 
likely to be different than those assumed since projections are subjected to multiple factors including 
trial results and regulatory matters which could materially change the ultimate commercial success 
of the asset as well as significantly alter the costs to develop the respective asset into commercially 
viable products. 

(cid:120)  Tax  rates  –  The  expected  future  income  is  tax  effected  using  a  market  participant  tax  rate.    Our 
recent  valuations  typically  use  a  U.S.  tax  rate  (and  applicable  state  taxes)  after  considering  the 
jurisdiction  in  which  the  intellectual  property  is  held  and  location  of  research  and  manufacturing 
infrastructure.    We  also  considered  that  any  repatriation  of  earnings  would  likely  have  U.S.  tax 
consequences. 

(cid:120)  Discount  rate  –  Discount  rates  are  selected  after  considering  the  risks  inherent  in  the  future  cash 
flows;  the  assessment  of  the  asset’s  life  cycle  and  the  competitive  trends  impacting  the  asset, 
including consideration of any technical, legal, regulatory, or economic barriers to entry, as well as 
expected changes in standards of practice for indications addressed by the asset. 

Goodwill was $743.3 million and $224.3 million, respectively, at December 31, 2015 and 2014.  The increase in 
goodwill from December 31, 2014 to 2015 is due to goodwill recognized from the acquisitions of Bio-Reference and 
EirGen in August 2015 and May 2015, respectively.  Goodwill is tested at least annually for impairment or when 
events or changes in circumstances indicate that the carrying amount of such assets may not be recoverable, on an 
enterprise  level  by  assessing  qualitative  factors  or  performing  a  quantitative  analysis  in  determining  whether  it  is 
more likely than not that its fair value exceeds the carrying value.  Examples of qualitative factors include our share 
price,  our  financial  performance  compared  to  budgets,  long-term  financial  plans,  macroeconomic,  industry  and 
market conditions as well as the substantial excess of fair value over the carrying value of net assets from the annual 
impairment  test  previously  performed.    We  recorded  $87,000  of  goodwill  impairment  during  the  year  ended 
December 31,  2015  as  a  result  of  our  testing.    No  goodwill  impairment  was  recorded  for  the  year  ended 
December 31, 2014 as a result of our testing.   

The  estimated  fair  value  of  a  reporting  unit  is  highly  sensitive  to  changes  in  projections  and  assumptions; 
therefore,  in  some  instances  changes  in  these  assumptions  could  potentially  lead  to  impairment.    We  perform 

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sensitivity analyses around our assumptions in order to assess the reasonableness of the assumptions and the results 
of our testing.  Ultimately, future potential changes in these assumptions may impact the estimated fair value of a 
reporting  unit  and  cause  the  fair  value  of  the  reporting  unit  to  be  below  its  carrying  value.    We  believe  that  our 
estimates  are  consistent  with assumptions  that  marketplace  participants would use  in  their  estimates  of  fair  value.  
However,  if  actual  results  are  not  consistent  with  our  estimates  and  assumptions,  we  may  be  exposed  to  an 
impairment charge that could be material. 

Intangible assets were $1.4 billion and $855.8 million, including IPR&D of $792.3 million and $793.2 million, 
respectively, at December 31, 2015 and 2014.  The increase in intangible assets from December 31, 2014 to 2015 is 
due  to  intangible  assets  recognized  from  the  acquisitions  of  Bio-Reference  and  EirGen  in  August  2015  and  May 
2015,  respectively.    Intangible  assets  are  tested  for  impairment  whenever  events  or  changes  in  circumstances 
indicate that the carrying amount of such assets may not be recoverable, although IPR&D is required to be tested at 
least annually until the project is completed or abandoned.  Upon obtaining regulatory approval, the IPR&D asset is 
then accounted for as a finite-lived intangible asset and amortized on a straight-line basis over its estimated useful 
life.  If the project is abandoned, the IPR&D asset is charged to expense.   

Intangible  assets  are  highly  vulnerable  to  impairment  charges,  particularly  newly  acquired  assets  for  recently 
launched  products  or  IPR&D.    These  assets  are  initially  measured  at  fair  value  and  therefore  any  reduction  in 
expectations used in the valuations could potentially lead to impairment.  Some of the more common potential risks 
leading  to  impairment  include  competition,  earlier  than  expected  loss  of  exclusivity,  pricing  pressures,  adverse 
regulatory changes or clinical trial results, delay or failure to obtain regulatory approval and additional development 
costs, inability to achieve expected synergies, higher operating costs, changes in tax laws and other macro-economic 
changes.  The complexity in estimating the fair value of intangible assets in connection with an impairment test is 
similar to the initial valuation. 

Considering  the  high  risk  nature  of  research  and  development  and  the  industry’s  success  rate  of  bringing 
developmental compounds to market, IPR&D impairment charges are likely to occur in future periods.  IPR&D is 
closely monitored and assessed each period for impairment. 

We  amortize  intangible  assets  with  definite  lives  on  a  straight-line  basis  over  their  estimated  useful  lives, 
currently  ranging  from  3  to  20  years.    We  use  the  straight-line  method  of  amortization  as  there  is  no  reliably 
determinable  pattern  in  which  the  economic  benefits  of  our  intangible  assets  are  consumed  or  otherwise  used  up.  
Amortization  expense  was  $28.0  million  and  $10.9  million  for  the  years  ended  December 31,  2015  and  2014, 
respectively. 

Revenue recognition.  Revenue for laboratory services is recognized at the time test results are reported, which 
approximates  when  services  are  provided.    Services  are  provided  to  patients  covered  by  various  third-party  payer 
programs including various managed care organizations, as well as the Medicare and Medicaid programs.  Billings 
for  services  under  third-party  payer  programs  are  included in  revenue  net  of  allowances  for  contractual  discounts 
and allowances for differences between the amounts billed and estimated program payment amounts.  Adjustments 
to the estimated payment amounts based on final settlement with the programs are recorded upon settlement as an 
adjustment to revenue.  For the years ended December 31, 2015 and 2014, approximately 9% and 5%, respectively, 
of our revenues were derived directly from the Medicare and Medicaid programs.  The increase in revenues from 
laboratory  services,  including  revenue  from  Medicare  and  Medicaid  programs,  is  due  to  the  acquisition  of  Bio-
Reference in August 2015. 

Generally, we recognize revenue from product sales when goods are shipped and title and risk of loss transfer to 
our  customers.    Our  estimates  for  sales  returns  and  allowances  are  based  upon  the  historical  patterns  of  product 
returns and allowances taken, matched against the sales from which they originated, and management’s evaluation 
of specific factors that may increase or decrease the risk of product returns. 

Revenue  from  transfer  of  intellectual  property  includes  revenue  related  to  the  sale,  license  or  transfer  of 
intellectual  property  such  as  upfront  license  payments,  license  fees  and  milestone  payments  received  through  our 
license,  collaboration  and  commercialization  agreements.    We  analyze  our  multiple-element  arrangements  to 
determine whether the elements can be separated and accounted for individually as separate units of accounting. 

Non-refundable license fees for the out-license of our technology are recognized depending on the provisions of 
each agreement.  We recognize non-refundable upfront license payments as revenue upon receipt if the license has 
standalone  value  and  qualifies  for  treatment  as  a  separate  unit  of  accounting  under  multiple-element  arrangement 

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guidance.  License fees with ongoing involvement or performance obligations that do not have standalone value are 
recorded  as  deferred  revenue,  included  in  Accrued  expenses  or  Other  long-term  liabilities,  when  received  and 
generally are recognized ratably over the period of such performance obligations only after both the license period 
has commenced and we have delivered the technology. 

The assessment of our obligations and related performance periods requires significant management judgment.  
If  an  agreement  contains  research  and  development  obligations,  the  relevant  time  period  for  the  research  and 
development phase is based on management estimates and could vary depending on the outcome of clinical trials 
and the regulatory approval process.  Such changes could materially impact the revenue recognized, and as a result, 
management reviews the estimates related to the relevant time period of research and development on a quarterly 
basis. 

Revenue  from  milestone  payments  related  to  arrangements  under  which  we  have  continuing  performance 
obligations is recognized as Revenue from transfer of intellectual property upon achievement of the milestone only 
if  all  of  the  following  conditions  are  met:  the  milestone  payments  are  non-refundable;  there  was  substantive 
uncertainty  at  the  date  of  entering  into  the  arrangement  that  the  milestone  would  be  achieved;  the  milestone  is 
commensurate with either our performance to achieve the milestone or the enhancement of the value of the delivered 
item  by  us;  the  milestone  relates  solely  to  past  performance;  and  the  amount  of  the  milestone  is  reasonable  in 
relation  to  the  effort  expended  or  the  risk  associated  with  the  achievement  of  the  milestone.    If  any  of  these 
conditions are not met, the milestone payments are not considered to be substantive and are, therefore, deferred and 
recognized as Revenue from transfer of intellectual property over the term of the arrangement as we complete our 
performance obligations. 

Concentration of Credit Risk and Allowance for doubtful accounts.  Financial instruments that potentially subject 
us  to  concentrations  of  credit  risk  consist  primarily  of  accounts  receivable.    Substantially  all  of  our  accounts 
receivable are with companies in the health care industry and individuals.  However, concentrations of credit risk are 
limited due to the number of our clients as well as their dispersion across many different geographic regions. 

While  we  have  receivables  due  from  federal  and  state  governmental  agencies,  we  do  not  believe  that  such 
receivables  represent  a  credit  risk  since  the  related  health  care  programs  are  funded  by  federal  and  state 
governments, and payment is primarily dependent upon submitting appropriate documentation.  Accounts receivable 
balances (prior to allowance for doubtful accounts and net of contractual adjustments) from Medicare and Medicaid 
were $26.1 million and $0.6 million at December 31, 2015 and 2014, respectively. 

The  portion  of  our  accounts  receivable  due  from  patients  comprises  the  largest  portion  of  credit  risk.    At 
December 31,  2015  and  2014,  receivables  due  from  patients  represent  approximately  7.5%  and  0.5%  of  our 
consolidated accounts receivable (prior to allowance for doubtful accounts and net of contractual adjustments). 

We assess the collectability of accounts receivable balances by considering factors such as historical collection 
experience,  customer  credit  worthiness,  the  age  of  accounts  receivable  balances,  regulatory  changes  and  current 
economic conditions and trends that may affect a customer’s ability to pay.  Actual results could differ from those 
estimates.    Our  reported  net  income  (loss)  is  directly  affected  by  our  estimate  of  the  collectability  of  accounts 
receivable.  The allowance for doubtful accounts recognized in our Consolidated Balance Sheets was $25.2 million 
and $1.9 million at December 31, 2015 and 2014, respectively. 

Income  Taxes.    Income  taxes  are  accounted  for  under  the  asset-and-liability  method.    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  the  respective  tax  bases  and  operating  loss  and  tax  credit 
carryforwards.  Deferred tax assets and liabilities are measured using enacted tax rates expected to apply to taxable 
income  in  the  years  in  which  those  temporary  differences  are  expected  to  be  recovered  or  settled.    The  effect  on 
deferred tax assets and liabilities of a change in tax rates is recognized in operations in the period that includes the 
enactment  date.    We  periodically  evaluate  the  realizability  of  our  net  deferred  tax  assets.    Our  tax  accruals  are 
analyzed periodically and adjustments are made as events occur to warrant such adjustment. 

Equity-based compensation.  We measure the cost of employee services received in exchange for an award of 
equity  instruments  based  on  the  grant-date  fair  value  of  the  award.    That  cost  is  recognized  in  the  Consolidated 
Statement of Operations over the period during which an employee is required to provide service in exchange for the 
award.  We record excess tax benefits, realized from the exercise of stock options as a financing cash inflow and as a 
reduction of taxes paid in cash flow from operations.  Equity-based compensation arrangements to non-employees 

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are recorded at their fair value on the measurement date.  The measurement of equity-based compensation to non-
employees is subject to periodic adjustment as the underlying equity instruments vest.  We estimate the grant-date 
fair  value  of  our  stock  option  grants  using  a  valuation  model  known  as  the  Black-Scholes-Merton  formula  or  the 
“Black-Scholes Model.”  The Black-Scholes Model requires the use of several variables to estimate the grant-date 
fair  value  of  stock  options  including  expected  term,  expected  volatility,  expected  dividends  and  risk-free  interest 
rate.  We perform analyses to calculate and select the appropriate variable assumptions used in the Black-Scholes 
Model and to estimate forfeitures of equity-based awards.  We are required to adjust our forfeiture estimates on at 
least an annual basis based on the number of share-based awards that ultimately vest.  The selection of assumptions 
and estimated forfeiture rates is subject to significant judgment and future changes to our assumptions and estimates 
which may have a material impact on our Consolidated Financial Statements. 

Inventories.  Inventories are valued at the lower of cost or market (net realizable value).  Cost is determined by 
the first-in, first-out method.  We consider such factors as the amount of inventory on hand, estimated time required 
to  sell  such  inventories,  remaining  shelf-life,  and  current  market  conditions  to  determine  whether  inventories  are 
stated  at  the  lower  of  cost  or  market.    Inventories  at  our  diagnostics  segment  consist  primarily  of  purchased 
laboratory supplies, which is used in our testing laboratories. 

Pre-launch  inventories.    We  may  accumulate  commercial  quantities  of  certain  product  candidates  prior  to  the 
date we anticipate that such products will receive final U.S. FDA approval.  The accumulation of such pre-launch 
inventories involves the risk that such products may not be approved for marketing by the FDA on a timely basis, or 
ever.  This risk notwithstanding, we may accumulate pre-launch inventories of certain products when such action is 
appropriate in relation to the commercial value of the product launch opportunity.  In accordance with our policy, 
this pre-launch inventory is expensed. 

Contingent  consideration.    Each  period  we  revalue  the  contingent  consideration  obligations  associated  with 
certain acquisitions to their fair value and record increases in the fair value as contingent consideration expense and 
decreases  in  the  fair  value  as  contingent  consideration  income.    Changes  in  contingent  consideration  result  from 
changes  in  the  assumptions  regarding  probabilities  of  successful  achievement  of  related  milestones,  the  estimated 
timing  in  which  the  milestones  are  achieved  and  the  discount  rate  used  to  estimate  the  fair  value  of  the  liability.  
Contingent consideration may change significantly as our development programs progress, revenue estimates evolve 
and additional data is obtained, impacting our assumptions.  The assumptions used in estimating fair value require 
significant judgment.  The use of different assumptions and judgments could result in a materially different estimate 
of fair value which may have a material impact on our results from operations and financial position. 

RECENT ACCOUNTING PRONOUNCEMENTS 

In  May  2014,  the  FASB  issued  Accounting  Standards  Update  (“ASU”),  ASU  No.  2014-09,  “Revenue  from 
Contracts  with  Customers.”    ASU  No.  2014-09  clarifies  the  principles  for  recognizing  revenue  and  develops  a 
common revenue standard for GAAP and International Financial Reporting Standards that removes inconsistencies 
and  weaknesses  in  revenue  requirements,  provides  a  more  robust  framework  for  addressing  revenue  issues, 
improves  comparability  of  revenue  recognition  practices  across  entities,  industries,  jurisdictions,  and  capital 
markets,  provides  more  useful  information  to  users  of  financial  statements  through  improved  disclosure 
requirements and simplifies the preparation of financial statements by reducing the number of requirements to which 
an entity must refer. ASU No. 2014-09 is effective for fiscal years, and interim periods within those years, beginning 
after December 15, 2017.  Companies can choose to apply the ASU using either the full retrospective approach or a 
modified  retrospective  approach.    We  are  currently  evaluating  both  methods  of  adoption  and  the  impact  that  the 
adoption of this ASU will have on our Consolidated Financial Statements. 

In June 2014, the FASB issued ASU No. 2014-12, “Accounting for Share-Based Payments When the Terms of 
an Award Provide That a Performance Target Could Be Achieved after the Requisite Service Period (a consensus of 
the FASB Emerging Issues Task Force).”  ASU No. 2014-12 requires that a performance target that affects vesting 
and that could be achieved after the requisite service period be treated as a performance condition. ASU No. 2014-
12 is effective for fiscal years, and interim periods within those years, beginning after December 15, 2015.  Earlier 
adoption is permitted.  The amendments can be applied either prospectively to all awards granted or modified after 
the effective date or retrospectively to all awards with performance targets that are outstanding as of the beginning 
of the earliest annual period presented in the financial statements and to all new or modified awards.  We expect to 
apply  the  ASU  prospectively  and  do  not  expect  the  adoption  to  have  an  impact  on  our  Consolidated  Financial 
Statements. 

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In August 2014, the FASB issued ASU No. 2014-15, “Disclosure of Uncertainties about an Entity’s Ability to 
Continue as a Going Concern,” to provide guidance on management’s responsibility in evaluating whether there is 
substantial  doubt  about  a  company’s  ability  to  continue  as  a  going  concern  and  to  provide  related  footnote 
disclosures.    ASU  2014-15  is  effective  for  annual  periods  ending  after  December 15,  2016  with  early  adoption 
permitted.  We do not believe the impact of our pending adoption of ASU 2014-15 on our Consolidated Financial 
Statements will be material. 

In  February 2015,  the  FASB  issued  ASU  No. 2015-02,  “Consolidation  (Topic  810):  Amendments  to  the 
Consolidation Analysis,” which amends current consolidation guidance including changes to both the variable and 
voting interest models used by companies to evaluate whether an entity should be consolidated.  The requirements 
from  ASU  2015-02  are  effective  for  interim  and  annual  periods  beginning  after  December 15,  2015,  with  early 
adoption permitted.  We do not believe the impact of our pending adoption of ASU 2015-02 on our Consolidated 
Financial Statements will be material. 

In  July  2015,  the  FASB  issued  ASU  No. 2015-11,  “Inventory  (Topic  330):  Simplifying  the  Measurement  of 
Inventory,” which  changes  the  measurement  principle  for  entities  that  do not  measure  inventory  using  the  last-in, 
first-out (“LIFO”) or retail inventory method from the lower of cost or market to lower of cost and net realizable 
value.    ASU  2015-11  is  effective  for  fiscal  years  beginning  after  December 15,  2016,  including  interim  periods 
within  those  fiscal  years,  with  early  adoption  permitted.    We  are  currently  evaluating  the  impact  of  this  new 
guidance on our Consolidated Financial Statements. 

In September 2015, the FASB issued ASU No. 2015-16, “Business Combinations (Topic 805): Simplifying the 
Accounting  for  Measurement-Period  Adjustments,”  which  replaces  the  requirement  that  an  acquirer  in  a  business 
combination  account  for  measurement  period  adjustments  retrospectively  with  a  requirement  that  an  acquirer 
recognize adjustments to the provisional amounts that are identified during the measurement period in the reporting 
period in which the adjustment amounts are determined.  ASU 2015-16 requires that the acquirer record, in the same 
period’s  financial  statements,  the  effect  on  earnings  of  changes  in  depreciation,  amortization,  or  other  income 
effects,  if  any,  as  a  result  of  the  change  to  the  provisional  amounts,  calculated  as  if  the  accounting  had  been 
completed  at  the  acquisition  date.    ASU  2015-16  is  effective  for  fiscal  years  beginning  after  December 15,  2015, 
including interim periods within those fiscal years.  The guidance is to be applied prospectively to adjustments to 
provisional  amounts  that  occur  after  the  effective  date  of  the  guidance,  with  earlier  application  permitted  for 
financial statements that have not been issued.  Our early adoption of ASU 2015-16 in the third quarter of 2015 did 
not have a material impact on our Consolidated Financial Statements. 

In  November  2015,  the  FASB  issued  ASU  No. 2015-17,  “Income  Taxes  (Topic  740):  Balance  Sheet 
Classification of Deferred Taxes,” which requires deferred tax liabilities and assets to be classified as noncurrent in 
a  classified  statement  of  financial  position.   ASU  2015-17  is  effective  for  financial  statements  issued  for  annual 
periods beginning after December 15, 2016, and interim periods within those annual periods.  Earlier application is 
permitted for all entities as of the beginning of an interim or annual reporting period.  We adopted the provisions of 
this  ASU  prospectively  in  the  fourth  quarter  of  2015,  and  did  not  retrospectively  adjust  the  prior  periods.   The 
adoption  of  this  ASU  will  simplify  the  presentation  of  deferred  income  taxes  and  reduce  complexity  without 
decreasing the usefulness of information provided to users of financial statements.  The adoption of ASU 2015-17 
did not have a significant impact on our financial position, results of operations and cash flows. 

ITEM 7A.  QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK. 

In the normal course of doing business, we are exposed to the risks associated with foreign currency exchange 

rates and changes in interest rates. 

Foreign Currency Exchange Rate Risk – We operate globally and, as such, we are subject to foreign exchange 
risk in our commercial operations as a significant portion of our revenues are exposed to changes in foreign currency 
exchange rates, primarily the Chilean peso, the Mexican peso, the Euro and the New Israeli shekel. 

Although we do not speculate in the foreign exchange market, we may from time to time manage exposures that 
arise  in  the  normal  course  of  business  related  to  fluctuations  in  foreign  currency  exchange  rates  by  entering  into 
offsetting positions through the use of foreign exchange forward contracts.  Certain firmly committed transactions 
may  be  hedged  with  foreign  exchange  forward  contracts.    As  exchange  rates  change,  gains  and  losses  on  the 
exposed  transactions  are  partially  offset  by  gains  and  losses  related  to  the  hedging  contracts.    Both  the  exposed 

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transactions and the hedging contracts are translated and fair valued, respectively, at current spot rates, with gains 
and losses included in earnings. 

Our derivative activities, which consist of foreign exchange forward contracts, are initiated to hedge forecasted 
cash flows that are exposed to foreign currency risk.  The foreign exchange forward contracts generally require us to 
exchange local currencies for foreign currencies based on pre-established exchange rates at the contracts’ maturity 
dates.    As  exchange  rates  change,  gains  and  losses  on  these  contracts  are  generated  based  on  the  change  in  the 
exchange rates that are recognized in the Consolidated Statement of Operations and offset the impact of the change 
in exchange rates on the foreign currency cash flows that are hedged.  If the counterparties to the exchange contracts 
do  not  fulfill  their  obligations  to  deliver  the  contracted  currencies,  we  could  be  at  risk  for  currency  related 
fluctuations.    We  had  $6.2  million  in  foreign  exchange  forward  contracts  outstanding  at  December 31,  2015, 
primarily to hedge Chilean-based operating cash flows against U.S. dollars.  If Chilean pesos were to strengthen or 
weaken in relation to the U.S. dollar, our loss or gain on hedged foreign currency cash-flows would be offset by the 
derivative contracts, with a net effect of zero. 

We do not engage in trading market risk sensitive instruments or purchasing hedging instruments or “other than 
trading” instruments that are likely to expose us to significant market risk, whether interest rate, foreign currency 
exchange, commodity price, or equity price risk. 

Interest Rate Risk – Our exposure to interest rate risk relates to our cash and investments and to our borrowings.  
We  maintain  an  investment  portfolio  of  money  market  funds.    The  securities  in  our  investment  portfolio  are  not 
leveraged, and are, due to their very short-term nature, subject to minimal interest rate risk.  We currently do not 
hedge  interest  rate  exposure.    Because  of  the  short-term  maturities  of  our  investments,  we  do  not  believe  that  a 
change  in  market  interest  rates  would have  a  significant negative  impact  on  the  value  of our  investment  portfolio 
except for reduced income in a low interest rate environment. 

At  December 31,  2015,  we  had  cash  and  cash  equivalents  and  marketable  securities  of  $193.6  million.    The 
weighted average interest rate related to our cash and cash equivalents for the years ended December 31, 2015 was 
0%.  As of December 31, 2015, the principal outstanding balance under our Credit Agreement with JPMorgan Chase 
Bank,  N.A.  and  our  Chilean  and  Spanish  credit  lines  was  $82.7  million  in  the  aggregate  at  a  weighted  average 
interest rate of approximately 4.3%.   

Our $32.2 million aggregate principal amount of our 2033 Senior Notes has a fixed interest rate, and therefore is 

not subject to fluctuations in market interest rates. 

The  primary  objective  of  our  investment  activities  is  to  preserve  principal  while  at  the  same  time  maximizing 
yields without significantly increasing risk.  To achieve this objective, we invest our excess cash in debt instruments 
of  the  U.S.  Government  and  its  agencies,  bank  obligations,  repurchase  agreements  and  high-quality  corporate 
issuers, and money market funds that invest in such debt instruments, and, by policy, restrict our exposure to any 
single corporate issuer by imposing concentration limits.  To minimize the exposure due to adverse shifts in interest 
rates, we maintain investments at an average maturity of generally less than three months. 

Equity  Price  Risk  –  We  are  subject  to  equity  price  risk  related  to  the  (i)  rights  to  convert  into  shares  of  our 
Common  Stock,  including  upon  a  fundamental  change;  and  (ii)  a  coupon  make-whole  payment  in  the  event  of  a 
conversion  by  the  holders  of  the  2033  Senior  Notes  on  or  after  February 1,  2017  but  prior  to  February 1,  2019.  
These  terms  are  considered  to  be  embedded  derivatives.    On  a  quarterly  basis,  we  are  required  to  record  these 
embedded derivatives at fair value with the changes being recorded in our Consolidated Statement of Operations.  
Accordingly, our results of operations are subject to exposure associated with increases or decreases in the estimated 
fair value of our embedded derivatives. 

78 

 
 
ITEM 8.  FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA. 

Reports of Independent Registered Certified Public Accounting Firm 

Consolidated Balance Sheets 

Consolidated Statements of Operations 

Consolidated Statements of Comprehensive Loss 

Consolidated Statements of Equity 

Consolidated Statements of Cash Flows 

Notes to Consolidated Financial Statements 

Page 

80 

82 

83 

84 

85 

88 

90 - 130 

79 

 
 
 
Report of Independent Registered Certified Public Accounting Firm 

The Board of Directors and Shareholders of OPKO Health, Inc. and subsidiaries 

We  have  audited  the  accompanying  consolidated  balance  sheets  of  OPKO  Health,  Inc.  and  subsidiaries  as  of 
December 31, 2015 and 2014, and the related consolidated statements of operations, comprehensive loss, equity and 
cash flows for each of the three years in the period ended December 31, 2015.  These financial statements are the 
responsibility  of  the  Company’s  management.    Our  responsibility  is  to  express  an  opinion  on  these  financial 
statements based on our audits. 

We conducted our audits in accordance with the standards of the Public Company Accounting Oversight Board 
(United States).  Those standards require that we plan and perform the audit to obtain reasonable assurance about 
whether  the  financial  statements  are  free  of  material  misstatement.    An  audit  includes  examining,  on  a  test  basis, 
evidence supporting the amounts and disclosures in the financial statements.  An audit also includes assessing the 
accounting  principles  used  and  significant  estimates  made  by  management,  as  well  as  evaluating  the  overall 
financial statement presentation.  We believe that our audits provide a reasonable basis for our opinion. 

In our opinion, the financial statements referred to above present fairly, in all material respects, the consolidated 
financial  position  of  OPKO  Health,  Inc.  and  subsidiaries  at  December 31,  2015  and  2014,  and  the  consolidated 
results of their operations and their cash flows for each of the three years in the period ended December 31, 2015, 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),  OPKO  Health,  Inc.  and  subsidiaries’  internal  control  over  financial  reporting  as  of  December 31, 
2015, 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 29, 2016 expressed an 
unqualified opinion thereon.  

/s/ Ernst & Young LLP 

Miami, Florida 
February 29, 2016

80 

 
 
 
Report of Independent Registered Certified Public Accounting Firm 

The Board of Directors and Shareholders of OPKO Health, Inc. and subsidiaries 

We  have  audited  OPKO  Health,  Inc.  and  subsidiaries’  internal  control  over  financial  reporting  as  of 
December 31, 2015, 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”).    OPKO 
Health,  Inc.  and  subsidiaries’  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 conducted our audit in accordance with the standards of the Public Company Accounting Oversight Board 
(United States).  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. 

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. 

As indicated in the accompanying Management’s Annual Report on Internal Control Over Financial Reporting, 
management’s assessment of and conclusion on the effectiveness of internal control over financial reporting did not 
include the internal controls of Bio-Reference Laboratories, Inc. and EirGen Pharma Limited, which are included in 
the  December 31,  2015  consolidated  financial  statements  of  OPKO  Health,  Inc.  and  subsidiaries  and  constituted 
15%  of  consolidated  total  assets,  as  of  December 31,  2015  and  68%  of  consolidated  revenues,  for  the  year  then 
ended.    Our  audit  of  internal  control  over  financial  reporting  of  OPKO  Health,  Inc.  and  subsidiaries  also  did  not 
include an evaluation of the internal control over financial reporting of Bio-Reference Laboratories, Inc. or EirGen 
Pharma Limited. 

In our opinion, OPKO Health, Inc. and subsidiaries maintained, in all material respects, effective internal control 

over financial reporting as of December 31, 2015, based on the COSO criteria. 

We  also  have  audited,  in  accordance  with  the  standards  of  the  Public  Company  Accounting  Oversight  Board 
(United States), the consolidated balance sheets of OPKO Health, Inc. and subsidiaries as of December 31, 2015 and 
2014, and the related consolidated statements of operations, comprehensive loss, equity and cash flows for each of 
the three years in the period ended December 31, 2015 of OPKO Health, Inc. and subsidiaries and our report dated 
February 29, 2016 expressed an unqualified opinion thereon.  

/s/ Ernst & Young LLP 

Miami, Florida 
February 29, 2016

81 

 
 
 
 
OPKO Health, Inc. and Subsidiaries 
CONSOLIDATED BALANCE SHEETS 
 (In thousands, except share and per share data) 

ASSETS 
Current assets: 

Cash and cash equivalents...................................................................................$
Accounts receivable, net .....................................................................................
Inventory, net ......................................................................................................
Prepaid expenses and other current assets ..........................................................
Total current assets ..........................................................................................
Property, plant and equipment, net .........................................................................
Intangible assets, net ...............................................................................................
In-process research and development .....................................................................
Goodwill .................................................................................................................
Investments, net ......................................................................................................
Other assets .............................................................................................................

Total assets ..........................................................................................................$

LIABILITIES AND EQUITY 
Current liabilities: 

Accounts payable ................................................................................................$
Accrued expenses................................................................................................
Current portion of lines of credit and notes payable ...........................................
Total current liabilities ....................................................................................

2033 Senior Notes, net of discount and estimated fair value of embedded 

derivatives ...........................................................................................................
Deferred tax liabilities, net .....................................................................................
Other long-term liabilities, principally deferred revenue .......................................
Total long-term liabilities ................................................................................
Total liabilities ....................................................................................................

Equity: 

Common Stock - $0.01 par value, 750,000,000 shares authorized; 

546,188,516 and 433,421,677 shares issued at December 31, 2015 and 
2014, respectively ............................................................................................

Treasury Stock, at cost - 1,120,367 and 1,245,367 shares at December 31, 

2015 and 2014, respectively ............................................................................
Additional paid-in capital....................................................................................
Accumulated other comprehensive loss ..............................................................
Accumulated deficit ............................................................................................
Total shareholders’ equity attributable to OPKO ............................................
Noncontrolling interests .........................................................................................
Total shareholders’ equity ............................................................................... 
Total liabilities and equity ..................................................................................$

December 31, 

2015 

2014 (1) 

193,598    $ 
193,875   
39,681   
26,904   
454,058   
131,798   
638,152   
792,275   
743,348   
34,716   
5,267   
2,799,614    $ 

72,535 $$ 
167,899
11,468
251,902

49,412
226,036
292,470
567,918
819,820

96,907
19,969
16,604
9,389
142,869
16,411
62,649
793,152
224,292
22,453
5,838
1,267,664

8,744
60,912
13,455
83,111

131,454
167,153
50,205
348,812
431,923

5,462    

4,334

(3,645 )  
2,705,385    
(22,537)  
(704,871)  
1,979,794   
—   

2,799,614    $ 

(4,051)
1,529,096
(12,392)
(674,843)
842,144
(6,403)
835,741
1,267,664

(1)  As of December 31, 2014, total assets include $7.6 million and total liabilities include $12.1 million related to SciVac Ltd (“SciVac”).  

SciVac was a consolidated variable interest entity which we deconsolidated in July 2015.  Refer to Note 4.  SciVac’s consolidated assets 
were owned by SciVac and SciVac’s consolidated liabilities had no recourse against us. 

The accompanying Notes to Consolidated Financial Statements are an integral part of these statements 

 82 

 
 
 
 
 
   
 
   
 
   
 
   
 
 
 
   
 
 
 
OPKO Health, Inc. and Subsidiaries 
CONSOLIDATED STATEMENTS OF OPERATIONS 
 (In thousands, except share and per share data) 

For the years ended December 31, 
2014 

2015 

2013 

Revenues: 

Revenue from services ...........................................................$
Revenue from products ..........................................................
Revenue from transfer of intellectual property and other .......
Total revenues .....................................................................

329,739 $
80,146
81,853
491,738

8,666    $ 

76,983   
5,476   
91,125   

Costs and expenses: 

Costs of service revenue .........................................................
Cost of product revenue .........................................................
Selling, general and administrative ........................................
Research and development .....................................................
In-process research and development .....................................
Contingent consideration ........................................................
Amortization of intangible assets ...........................................
Grant repayment .....................................................................
Total costs and expenses .............................................................
Operating loss .............................................................................
Other income and (expense), net: 

Interest income .......................................................................
Interest expense ......................................................................
Fair value changes of derivative instruments, net ..................
Other income (expense), net ...................................................
Other income and (expense), net ................................................
Loss before income taxes and investment losses ........................
Income tax benefit (provision) ....................................................
Loss before investment losses .....................................................
Loss from investments in investees ............................................
Net loss .......................................................................................
Less: Net loss attributable to noncontrolling interests ................
Net loss attributable to common shareholders before 
  preferred stock dividend .........................................................
Preferred stock dividend .............................................................
Net loss attributable to common shareholders ............................$
Loss per share, basic and diluted: 

193,305
41,934
196,576
99,488
—
5,050
27,977
25,889
590,219
(98,481)

255
(8,419)
(39,083)
7,730
(39,517)
(137,998)
113,675
(24,323)
(7,105)
(31,428)
(1,400)

9,372   
38,637   
57,940   
83,571   
12,055   
24,446   
10,919   
—   
236,940   
(145,815)  

771   
(12,263)  
(10,632)  
(3,088)  
(25,212)  
(171,027)  
(24)  
(171,051)  
(3,587)  
(174,638)  
(2,972)  

(30,028)
—
(30,028) $

(171,666)  
—   

(171,666)   $ 

11,658
68,161
16,711
96,530

10,419
38,441
55,320
53,902
—
6,947
11,133
—
176,162
(79,632)

376
(13,802)
(45,942)
34,782
(24,586)
(104,218)
(1,672)
(105,890)
(11,456)
(117,346)
(2,939)

(114,407)
(420)
(114,827)

Net loss per share ...................................................................$

(0.06) $

(0.41)   $ 

(0.32)

Weighted average number of common shares outstanding, 
  basic and diluted .....................................................................

488,065,908

422,014,039   

355,095,701

The accompanying Notes to Consolidated Financial Statements are an integral part of these statements 

 83 

 
 
 
 
 
 
   
 
 
   
 
 
   
 
 
   
 
 
OPKO Health, Inc. and Subsidiaries 
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS 
(In thousands) 

For the years ended December 31, 
2014 

2013 

2014 

Net loss ........................................................................$ 
Other comprehensive income (loss), net of tax: 

Change in foreign currency translation and other 
comprehensive income (loss) from equity 
investments ..........................................................

Available for sale investments: 

Change in unrealized gain (loss), net of tax .........
Less: reclassification adjustments for (gains)  

(31,428) $

(174,638)   $ 

(117,346)

(15,074)

(8,088)  

(1,825)

(2,378)

(8,044)  

2,467

losses included in net loss, net of tax ...............
Comprehensive loss ..................................................... 

7,307
(41,573)  

322   
(190,448)    

(4,580)
(121,284)

Less: Comprehensive loss attributable to 

noncontrolling interest 

Comprehensive loss attributable to common 

shareholders before preferred stock dividend ........... 
Preferred stock dividend .............................................. 
Comprehensive loss attributable to common 

(1,400)  

(2,972)    

(2,939)

(40,173)  
—  

(187,476)    
—     

(118,345)
(420)

shareholders .............................................................$ 

(40,173) $

(187,476)   $ 

(118,765)

The accompanying Notes to Consolidated Financial Statements are an integral part of these statements 

 84 

 
 
 
 
 
   
 
 
 
 
 
 
 
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T

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
OPKO Health, Inc. and Subsidiaries 
CONSOLIDATED STATEMENTS OF CASH FLOWS 
 (In thousands) 

Cash flows from operating activities: 
Net loss ......................................................................................................................$
Adjustments to reconcile net loss to net cash used in operating activities: 

Depreciation and amortization ..............................................................................
Non-cash interest on 2033 Senior Notes ...............................................................
Amortization of deferred financing costs ..............................................................
Losses from investments in investees ...................................................................
Equity-based compensation – employees and non-employees ..............................
Provision for bad debts .........................................................................................
Provision for inventory obsolescence ...................................................................
Revenue from receipt of equity .............................................................................
Realized gain (loss) on equity securities ...............................................................
Gain on conversion of 3.00% convertible senior notes .........................................
Loss on sale of property, plant and equipment ......................................................
Change in fair value of derivative instruments .....................................................
In-process research and development ...................................................................
Change in fair value of contingent consideration ..................................................
Gain on deconsolidation of SciVac .......................................................................
Deferred income tax (benefit) provision ...............................................................

Changes in assets and liabilities, net of the effects of acquisitions: 

Accounts receivable ..............................................................................................
Inventory ...............................................................................................................
Prepaid expenses and other current assets .............................................................
Other assets ...........................................................................................................
Accounts payable ..................................................................................................
Foreign currency measurement .............................................................................
Deferred revenue...................................................................................................
Accrued expenses and other liabilities ..................................................................
Net cash provided by (used in) operating activities ...................................................
Cash flows from investing activities: 

Investments in investees .......................................................................................
Proceeds from sale of equity securities .................................................................
Acquisition of businesses, net of cash acquired ....................................................
Acquisition of intangible assets ............................................................................
Purchase of marketable securities .........................................................................
Maturities of short-term marketable securities ......................................................
Proceeds from the sale of property, plant and equipment .....................................
Capital expenditures .............................................................................................
Net cash provided by (used in) investing activities ....................................................
Cash flows from financing activities: 

Issuance of 2033 Senior Notes, net, including related parties ...............................
Payment of Series D dividends, including related parties .....................................
Proceeds from the exercise of Common Stock options and warrants ....................
Cash from non-controlling interest .......................................................................
Contingent consideration payments ......................................................................
Borrowings on lines of credit ................................................................................
Repayments of lines of credit ................................................................................
Net cash provided by financing activities ..................................................................
Effect of exchange rate on cash and cash equivalents ................................................
Net increase (decrease) in cash and cash equivalents ................................................
Cash and cash equivalents at beginning of period .....................................................
Cash and cash equivalents at end of period ...............................................................$

For the years ended December 31, 
2014 
2015 

2013 

(31,428)   $ 

(174,638)   $ 

(117,346)

42,248   
2,612   
1,212   
7,105   
26,074   
24,548   
926   
(140)  
7,091   
(943)  
—   
39,083   
—   
5,050   
(15,940)  
(123,536)  

(29,393)  
(5,879)  
(4,391)  
(305)  
(18,122)  
979   
227,671   
9,502   
164,024   

(4,375)  
—   
(79,000)  
(5,000)  
—   
—   
—   
(10,846)  
(99,221)  

14,927   
5,662   
2,007   
3,587   
14,779   
646   
1,082   
(240)  
167   
(2,668)  
—   
10,632   
12,055   
24,446   
—   
1,017   

(3,919)  
(1,752)  
3,182   
(3,378)  
(3,852)  
945   
—   
4,934   
(90,379)  

(589)  
1,331   
(1,683)  
—   
—   
—   
—   
(4,734)  
(5,675)  

—   
—   
25,921   
100   
—   
261,339   
(254,355)  
33,005   
(1,117)  
96,691   
96,907   
193,598    $ 

—   
—   
12,928   
2,696   
(6,435)  
26,443   
(28,369)  
7,263   
(100)  
(88,891)  
185,798   
96,907    $ 

15,216 
5,980 
1,170 
11,456 
10,983 
979 
2,015 
(12,740)
(29,881)
(972)
60 
45,942 
— 
6,947 
— 
599 

754 
1,892 
(1,131)
(544)
1,829 
(2,386)
— 
3,525 
(55,653)

(17,441)
30,556 
20,528 
— 
(50,027)
50,027 
636 
(3,962)
30,317 

170,184 
(3,015)
23,425 
— 
(2,539)
34,577 
(38,997)
183,635 
138 
158,437 
27,361 
185,798 

The accompanying Notes to Consolidated Financial Statements are an integral part of these statements 

 88 

 
 
 
 
 
 
   
   
 
 
 
   
 
   
 
   
OPKO Health, Inc. and Subsidiaries 

CONSOLIDATED STATEMENTS OF CASH FLOWS (continued) 
 (In thousands) 

For the years ended December 31, 
2014 
2015 

2013 

SUPPLEMENTAL INFORMATION: 

Interest Paid ..........................................................................................................$
Income taxes paid, net ...........................................................................................$
RXi common stock received .................................................................................$
Pharmsynthez common stock received .................................................................$
Non-cash financing: 

4,572    $ 
4,879    $ 
—    $ 
—    $ 

6,276 
954 
— 
6,264 

Assets acquired under capital leases 
Shares issued upon the conversion of: 

Series D Preferred Stock ...............................................................................$
2033 Senior Notes .........................................................................................$
Common Stock options and warrants, surrendered in net exercise ...............$

—    $ 
120,299    $ 
14,369    $ 

Issuance of capital stock to acquire or contingent consideration settlement: 

Bio-Reference Laboratories, Inc. ..................................................................$  
EirGen Pharma Limited ................................................................................$
OPKO Biologics ...........................................................................................$
OPKO Renal .................................................................................................$
OPKO Brazil .................................................................................................$
OPKO Health Europe ...................................................................................$
OPKO Uruguay Ltda. ...................................................................................$
Inspiro ...........................................................................................................$

950,148    $ 
33,569    $ 
—    $ 
20,113    $ 
—    $ 
1,813    $ 
—    $ 
—    $ 

— 
95,665 
3,494 

— 
— 
— 
21,155 
— 
— 
159 
8,566 

 $
 $
 $
 $

 $
 $
 $

 $
 $
 $
 $
 $
 $
 $
 $

3,407 
1,321 
12,500 
— 

24,386 
20,839 
815 

— 
— 
586,643 
146,902 
436 
4,404 
— 
— 

The accompanying Notes to Consolidated Financial Statements are an integral part of these statements 

 89 

 
 
 
 
 
 
   
 
     
 
  
 
 
     
 
  
 
 
     
 
  
 
 
     
 
  
 
OPKO Health, Inc. and Subsidiaries 
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS 

Note 1 Business and Organization 

We are a diversified healthcare company that seeks to establish industry-leading positions in large and rapidly 
growing medical markets.  Our diagnostics business includes Bio-Reference Laboratories, the nation’s third-largest 
clinical  laboratory with  a  core  genetic  testing  business  and  a 420-person  sales force  to drive growth  and  leverage 
new  products,  including  the  4Kscore  prostate  cancer  test  and  the  Claros  1  in-office  immunoassay  platform.    Our 
pharmaceutical  business  features  Rayaldee,  a  treatment  for  secondary  hyperparathyroidism  (“SHPT”)  in  patients 
with stage 3 or 4 chronic kidney disease (“CKD”) and vitamin D insufficiency (March 29, 2016 PDUFA date) and 
VARUBI™  for  chemotherapy-induced  nausea  and  vomiting  (launched  by  partner  TESARO  in  November  2015).  
Our  pharmaceutical  business  includes  OPKO  Biologics,  which  features  hGH-CTP,  a  once-weekly  human  growth 
hormone injection (in Phase 3 and partnered with Pfizer), and a once-daily Factor VIIa drug for hemophilia (Phase 
2a).   We  are  incorporated  in  Delaware  and  our  principal executive  offices  are  located in  leased offices  in  Miami, 
Florida. 

  In August 2015, we completed the acquisition of Bio-Reference, the third largest full service clinical laboratory 
in  the  United  States,  known  for  its  innovative  technological  solutions  and  pioneering  leadership  in  the  areas  of 
genomics and genetic sequencing.  Holders of Bio-Reference common stock received 76,566,147 shares of OPKO 
Common  Stock  for  the  outstanding  shares  of  Bio-Reference  common  stock.    The  transaction  was  valued  at 
approximately $950.1 million, based on a closing price per share of our Common Stock of $12.38 as reported by the 
New York Stock Exchange on the closing date, or $34.05 per share of Bio-Reference common stock.  Included in 
the  transaction  value  is  $2.3  million  related  to  the  value  of  replacement  stock  option  awards  attributable  to  pre-
merger service. 

Through our acquisition of Bio-Reference, we provide laboratory testing services, primarily to customers in the 
larger  metropolitan  areas  across  New  York,  New  Jersey,  Maryland,  Pennsylvania,  Delaware,  Washington  DC, 
Florida, California, Texas, Illinois and Massachusetts as well as to customers in a number of other states.  We offer a 
comprehensive  list  of  clinical  diagnostic  tests  including  blood  and  urine  analysis,  blood  chemistry,  hematology 
services,  serology,  radio-immuno  analysis,  toxicology  (including  drug  screening),  pap  smears,  tissue  pathology 
(biopsies) and other tissue analysis.  We perform cancer cytogenetic testing at our leased facilities in Elmwood Park, 
NJ, Smithtown, NY, Clarksburg, MD, Milford, MA, Miami, FL, and Campbell, CA and genetic testing at our leased 
facility in Gaithersburg, MD, as well as at our Elmwood Park facility.  We perform cytology testing at our leased 
facilities Frederick, MD, Milford, MA, Columbus, OH, Houston, TX and at our Elmwood Park facility.  We market 
our  laboratory  testing  services  directly  to  physicians,  geneticists,  hospitals,  clinics,  correctional  and  other  health 
facilities. 

In  May  2015,  we  acquired  all  of  the  issued  and  outstanding  shares  of  EirGen  Pharma  Limited  (“EirGen”),  a 
specialty  pharmaceutical  company  incorporated  in  Ireland  focused  on  the  development  and  commercial  supply  of 
high potency, high barrier to entry pharmaceutical products, for $133.8 million in the aggregate.  We acquired the 
outstanding  shares  of  EirGen  for  approximately  $100.2  million  in  cash  and  delivered  2,420,487  shares  of  our 
Common Stock valued at approximately $33.6 million based on the closing price per share of our Common Stock as 
reported by the New York Stock Exchange on the closing date of the acquisition, $13.88 per share. 

We  operate  established  pharmaceutical  platforms  in  Ireland,  Chile,  Spain,  and  Mexico,  which  are  generating 
revenue  and  which  we  expect  to  facilitate  future  market  entry  for  our  products  currently  in  development.    In 
addition,  we  have  a  development  and  commercial  supply  pharmaceutical  company  and  a  global  supply  chain 
operation  and  holding  company  in  Ireland.    We  own  a  specialty  active  pharmaceutical  ingredients  (“APIs”) 
manufacturer in Israel, which we expect will facilitate the development of our pipeline of molecules and compounds 
for our molecular diagnostic and therapeutic products. 

Our  research  and  development  activities  are  primarily  performed  at  leased  facilities  in  Jupiter  and  Miramar, 

Florida, Woburn, Massachusetts, Waterford, Ireland, Nes Ziona, Israel, and Barcelona, Spain. 

90 

 
 
Note 2 Summary of Significant Accounting Policies 

Basis of presentation.  The accompanying Consolidated Financial Statements have been prepared in accordance 
with accounting principles generally accepted in the U.S. and with the instructions to Form 10-K and of Regulation 
S-X. 

Principles  of  consolidation.    The  accompanying  Consolidated  Financial  Statements  include  the  accounts  of 
OPKO  Health,  Inc.  and  of  our  wholly-owned  subsidiaries.    All  intercompany  accounts  and  transactions  are 
eliminated in consolidation. 

Use  of  estimates.    The  preparation  of  financial  statements  in  conformity  with  accounting  principles  generally 
accepted  in  the  United  States  requires  management  to  make  estimates  and  assumptions  that  affect  the  reported 
amounts  of  assets  and  liabilities  and  disclosure  of  contingent  assets  and  liabilities  at  the  date  of  the  financial 
statements  and  the  reported  amounts  of  revenues  and  expenses  during  the  reporting  period.    Actual  results  could 
differ significantly from these estimates. 

Cash  and  cash  equivalents.    Cash  and  cash  equivalents  include  short-term,  interest-bearing  instruments  with 
original maturities of 90 days or less at the date of purchase.  We also consider all highly liquid investments with 
original maturities at the date of purchase of 90 days or less as cash equivalents.  These investments include money 
markets, bank deposits, certificates of deposit and U.S. treasury securities. 

Inventories.  Inventories are valued at the lower of cost or market (net realizable value).  Cost is determined by 
the first-in, first-out method.  We consider such factors as the amount of inventory on hand, estimated time required 
to  sell  such  inventories,  remaining  shelf-life,  and  current  market  conditions  to  determine  whether  inventories  are 
stated  at  the  lower  of  cost  or  market.    Inventories  at  our  diagnostics  segment  consist  primarily  of  purchased 
laboratory supplies, which is used in our testing laboratories. 

Pre-launch  inventories.    We  may  accumulate  commercial  quantities  of  certain  product  candidates  prior  to  the 
date we anticipate that such products will receive final U.S. FDA approval.  The accumulation of such pre-launch 
inventories involves the risk that such products may not be approved for marketing by the FDA on a timely basis, or 
ever.  This risk notwithstanding, we may accumulate pre-launch inventories of certain products when such action is 
appropriate in relation to the commercial value of the product launch opportunity.  In accordance with our policy, 
this pre-launch inventory is expensed.  At December 31, 2015 and 2014, there were no pre-launch inventories. 

Goodwill and intangible assets.  Goodwill represents the difference between the purchase price and the estimated 
fair value of the net assets acquired when accounted for by the acquisition method of accounting and arose from our 
acquisitions.    Refer  to  Note  5.    Goodwill,  in-process  research  and  development  (“IPR&D”)  and  other  intangible 
assets  acquired  in  business  combinations,  licensing  and  other  transactions  at  December 31,  2015  and  2014,  were 
$2.2 billion and $1.1 billion, respectively. 

Assets acquired and liabilities assumed in business combinations, licensing and other transactions are generally 
recognized  at  the  date  of  acquisition  at  their  respective  fair  values.    We  determined  the  fair  value  of  intangible 
assets, including IPR&D, using the “income method.” 

Goodwill is tested at least annually for impairment, or when events or changes in circumstances indicate that the 
carrying amount of such assets may not be recoverable, by assessing qualitative factors or performing a quantitative 
analysis in determining whether it is more likely than not that its fair value exceeds the carrying value. 

Intangible  assets  are  tested  for  impairment  whenever  events  or  changes  in  circumstances  indicate  that  the 
carrying amount of such assets may not be recoverable, although IPR&D is required to be tested at least annually 
until  the  project  is  completed  or  abandoned.    Upon  obtaining  regulatory  approval,  the  IPR&D  asset  is  then 
accounted for as a finite-lived intangible asset and amortized on a straight-line basis over its estimated useful life.  If 
the project is abandoned, the IPR&D asset is charged to expense. 

We  amortize  intangible  assets  with  definite  lives  on  a  straight-line  basis  over  their  estimated  useful  lives, 
currently  ranging  from  3  to  20  years.    We  use  the  straight-line  method  of  amortization  as  there  is  no  reliably 
determinable  pattern  in  which  the  economic  benefits  of  our  intangible  assets  are  consumed  or  otherwise  used  up.  
Amortization expense was $28.0 million, $10.9 million and $11.1 million for the years ended December 31, 2015, 
2014 and 2013, respectively.  Amortization expense from operations for our intangible assets is expected to be $51.3 
million,  $50.8  million,  $47.7  million,  $44.2  million  and  $42.9  million  for  the  years  ended  December 2016,  2017, 
2018, 2019 and 2020, respectively. 

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Fair value measurements.  The carrying amounts of our cash and cash equivalents, accounts receivable, accounts 
payable  and  short-term  debt  approximate  their  fair  value  due  to  the  short-term  maturities  of  these  instruments.  
Investments that are considered available for sale as of December 31, 2015 and 2014 are carried at fair value. 

In evaluating the fair value information, considerable judgment is required to interpret the market data used to 
develop the estimates.  The use of different market assumptions and/or different valuation techniques may have a 
material effect on the estimated fair value amounts.  Accordingly, the estimates of fair value presented herein may 
not be indicative of the amounts that could be realized in a current market exchange.  Refer to Note 17. 

Contingent  consideration.    Each  period  we  revalue  the  contingent  consideration  obligations  associated  with 
certain prior acquisitions to their fair value and record increases in the fair value as contingent consideration expense 
and  decreases  in  the  fair  value  as  a  reduction  in  contingent  consideration  expense.    Changes  in  contingent 
consideration  result  from  changes  in  the  assumptions  regarding  probabilities  of  successful  achievement  of  related 
milestones, the estimated timing in which the milestones are achieved and the discount rate used to estimate the fair 
value  of  the  liability.    Contingent  consideration  may  change  significantly  as  our  development  programs  progress, 
revenue  estimates  evolve  and  additional  data  is  obtained,  impacting  our  assumptions.    The  assumptions  used  in 
estimating fair value require significant judgment.  The use of different assumptions and judgments could result in a 
materially  different  estimate  of  fair  value  which  may  have  a  material  impact  on  our  results  from  operations  and 
financial position. 

Derivative financial instruments.  We record derivative financial instruments on our Consolidated Balance Sheet 
at their fair value and recognize the changes in the fair value in our Consolidated Statement of Operations when they 
occur,  the  only  exception  being  derivatives  that  qualify  as  hedges.    For  the  derivative  instrument  to  qualify  as  a 
hedge, we are required to meet strict hedge effectiveness and contemporaneous documentation requirements at the 
initiation  of  the  hedge  and  assess  the  hedge  effectiveness  on  an  ongoing  basis  over  the  life  of  the  hedge.    At 
December 31,  2015  and  2014,  our  forward  contracts  for  inventory  purchases  did  not  meet  the  documentation 
requirements to be designated as hedges.  Accordingly, we recognize all changes in the fair values of our derivatives 
instruments, net, in our Consolidated Statement of Operations.  Refer to Note 18. 

Property, Plant and Equipment.  Property, plant and equipment are recorded at cost.  Depreciation is provided 
using the straight-line method over the estimated useful lives of the assets, generally five to ten years and includes 
amortization  expense  for  assets  capitalized  under  capital  leases.    The  estimated  useful  lives  by  asset  class  are  as 
follows: software - 3 years, machinery, medical and other equipment - 5-8 years, furniture and fixtures - 5-10 years, 
leasehold improvements - the lesser of their useful life or the lease term, buildings and improvements - 10-40 years, 
automobiles and aircraft - 5-7 years.  Expenditures for repairs and maintenance are charged to expense as incurred.  
Depreciation expense was $14.2 million, $4.0 million and $4.1 million for the years ended December 31, 2015, 2014 
and 2013, respectively.  Assets held under capital leases are included within Property, plant and equipment, net in 
our Consolidated Balance Sheet and are amortized over the shorter of their useful lives or the term of their related 
leases. 

Impairment  of  Long-Lived  Assets.    Long-lived  assets,  such  as  property  and  equipment,  are  reviewed  for 
impairment whenever events or changes in circumstances indicate that the carrying amount of an asset may not be 
recoverable.  Recoverability of assets to be held and used is measured by a comparison of the carrying amount of an 
asset to estimated undiscounted future cash flows expected to be generated by the asset.  If the carrying amount of 
an asset exceeds its estimated future cash flows, then an impairment charge is recognized for the amount by which 
the carrying amount of the asset exceeds the fair value, or carrying amount for cost basis assets, of the asset. 

Income  Taxes.    Income  taxes  are  accounted  for  under  the  asset-and-liability  method.    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  the  respective  tax  bases  and  operating  loss  and  tax  credit 
carryforwards.  Deferred tax assets and liabilities are measured using enacted tax rates expected to apply to taxable 
income  in  the  years  in  which  those  temporary  differences  are  expected  to  be  recovered  or  settled.    The  effect  on 
deferred tax assets and liabilities of a change in tax rates is recognized in operations in the period that includes the 
enactment  date.    We  periodically  evaluate  the  realizability  of  our  net  deferred  tax  assets.    Our  tax  accruals  are 
analyzed periodically and adjustments are made as events occur to warrant such adjustment. 

Income  tax  benefit  for  the  year  ended  December 31,  2015  was  primarily  due  to  a  $93.4  million  release  of  a 
valuation allowance on our U.S. deferred tax assets due to a change in the assessment of recoverability following the 
merger  with  Bio-Reference  in  August  2015.    This  was  partially  offset  by  expense  recognized  on  taxable  income 

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from  the  Pfizer  Transaction  during  the  year  ended  December 31,  2015.    Refer  to  Note  14  for  a  discussion  of  the 
Pfizer Transaction. 

Included in income tax benefit is an accrual of $2.3 million related to uncertain tax positions involving income 
recognition.  We recognize that local tax law is inherently complex and the local taxing authorities may not agree 
with certain tax positions taken.  Consequently, it is reasonably possible that the ultimate resolution of tax matters in 
any jurisdiction may be significantly  more or less than estimated.  We evaluated the estimated tax exposure for a 
range of current likely outcomes to be from $0 to approximately $50.0 million and recorded our accrual to reflect 
our best expectation of ultimate resolution. 

Revenue recognition.  Revenue for laboratory services is recognized at the time test results are reported, which 
approximates  when  services  are  provided.    Services  are  provided  to  patients  covered  by  various  third-party  payer 
programs including various managed care organizations, as well as the Medicare and Medicaid programs.  Billings 
for  services  under  third-party  payer  programs  are  included in  revenue  net  of  allowances  for  contractual  discounts 
and allowances for differences between the amounts billed and estimated program payment amounts.  Adjustments 
to the estimated payment amounts based on final settlement with the programs are recorded upon settlement as an 
adjustment to revenue.  For the years ended December 31, 2015 and 2014, approximately 9% and 5%, respectively, 
of our revenues were derived directly from the Medicare and Medicaid programs.  The increase in revenues from 
laboratory  services,  including  revenue  from  Medicare  and  Medicaid  programs,  is  due  to  the  acquisition  of  Bio-
Reference in August 2015. 

Generally, we recognize revenue from product sales when goods are shipped and title and risk of loss transfer to 
our  customers.    Our  estimates  for  sales  returns  and  allowances  are  based  upon  the  historical  patterns  of  product 
returns and allowances taken, matched against the sales from which they originated, and management’s evaluation 
of specific factors that may increase or decrease the risk of product returns. 

Revenue  from  transfer  of  intellectual  property  includes  revenue  related  to  the  sale,  license  or  transfer  of 
intellectual  property  such  as  upfront  license  payments,  license  fees  and  milestone  payments  received  through  our 
license,  collaboration  and  commercialization  agreements.    We  analyze  our  multiple-element  arrangements  to 
determine whether the elements can be separated and accounted for individually as separate units of accounting. 

Non-refundable license fees for the out-license of our technology are recognized depending on the provisions of 
each agreement.  We recognize non-refundable upfront license payments as revenue upon receipt if the license has 
standalone  value  and  qualifies  for  treatment  as  a  separate  unit  of  accounting  under  multiple-element  arrangement 
guidance.  License fees with ongoing involvement or performance obligations that do not have standalone value are 
recorded  as  deferred  revenue,  included  in  Accrued  expenses  or  Other  long-term  liabilities,  when  received  and 
generally are recognized ratably over the period of such performance obligations only after both the license period 
has commenced and we have delivered the technology. 

The assessment of our obligations and related performance periods requires significant management judgment.  
If  an  agreement  contains  research  and  development  obligations,  the  relevant  time  period  for  the  research  and 
development phase is based on management estimates and could vary depending on the outcome of clinical trials 
and the regulatory approval process.  Such changes could materially impact the revenue recognized, and as a result, 
management reviews the estimates related to the relevant time period of research and development on a quarterly 
basis.  For the years ended December 31, 2015, 2014 and 2013 we recorded $81.9 million, $5.5 million and $16.7 
million of revenue from the transfer of intellectual property, respectively.  For the year ended December 31, 2015, 
revenue  from  the  transfer  of  intellectual  property  included  $15.0  million  related  to  a  milestone  payment  that 
TESARO, Inc.  (“TESARO”) paid us under our license agreement with them and $65.5 million related to the Pfizer 
Transaction.  Refer to Note 14.  For the year ended December 31, 2014, $5.0 million related to a milestone payment 
that TESARO paid us under our license agreement with them.  For the year ended December 31, 2013, $12.5 million 
related  to  the  sale  of  substantially  all  of  our  assets  in  the  field  of  RNA  interference  to  RXi  Pharmaceuticals 
Corporation  (“RXi”)  and  $3.8  million  related  to  the  rights  granted  to  OAO  Pharmsynthez  (“Pharmsynthez”)  for 
certain technologies. 

Revenue  from  milestone  payments  related  to  arrangements  under  which  we  have  continuing  performance 
obligations are recognized as Revenue from transfer of intellectual property upon achievement of the milestone only 
if  all  of  the  following  conditions  are  met:  the  milestone  payments  are  non-refundable;  there  was  substantive 
uncertainty  at  the  date  of  entering  into  the  arrangement  that  the  milestone  would  be  achieved;  the  milestone  is 
commensurate with either our performance to achieve the milestone or the enhancement of the value of the delivered 
item  by  us;  the  milestone  relates  solely  to  past  performance;  and  the  amount  of  the  milestone  is  reasonable  in 

93 

 
relation  to  the  effort  expended  or  the  risk  associated  with  the  achievement  of  the  milestone.    If  any  of  these 
conditions are not met, the milestone payments are not considered to be substantive and are, therefore, deferred and 
recognized as Revenue from transfer of intellectual property over the term of the arrangement as we complete our 
performance obligations. 

Total deferred revenue included in Accrued expenses and Other long-term liabilities was $232.9 million and $6.7 
million at December 31, 2015 and 2014, respectively.  The deferred revenue balance at December 31, 2015 relates 
primarily to the Pfizer Transaction.  Refer to Note 14. 

Concentration of Credit Risk and Allowance for doubtful accounts.  Financial instruments that potentially subject 
us  to  concentrations  of  credit  risk  consist  primarily  of  accounts  receivable.    Substantially  all  of  our  accounts 
receivable are with companies in the health care industry and individuals.  However, credit risk is limited due to the 
number of our clients as well as their dispersion across many different geographic regions. 

While  we  have  receivables  due  from  federal  and  state  governmental  agencies,  we  do  not  believe  that  such 
receivables  represent  a  credit  risk  since  the  related  health  care  programs  are  funded  by  federal  and  state 
governments, and payment is primarily dependent upon submitting appropriate documentation.  Accounts receivable 
balances (prior to allowance for doubtful accounts and net of contractual adjustments) from Medicare and Medicaid 
were $26.1 million and $0.6 million at December 31, 2015 and 2014, respectively. 

The  portion  of  our  accounts  receivable  due  from  patients  comprises  the  largest  portion  of  credit  risk.    At 
December 31,  2015  and  2014,  receivables  due  from  patients  represent  approximately  7.5%  and  0.5%  of  our 
consolidated accounts receivable (prior to allowance for doubtful accounts and net of contractual adjustments). 

We assess the collectability of accounts receivable balances by considering factors such as historical collection 
experience,  customer  credit  worthiness,  the  age  of  accounts  receivable  balances,  regulatory  changes  and  current 
economic conditions and trends that may affect a customer’s ability to pay.  Actual results could differ from those 
estimates.    Our  reported  net  income  (loss)  is  directly  affected  by  our  estimate  of  the  collectability  of  accounts 
receivable.  The allowance for doubtful accounts recognized in our Consolidated Balance Sheets was $25.2 million 
and $1.9 million at December 31, 2015 and 2014, respectively. 

Equity-based compensation.  We measure the cost of employee services received in exchange for an award of 
equity  instruments  based  on  the  grant-date  fair  value  of  the  award.    That  cost  is  recognized  in  the  Consolidated 
Statement of Operations over the period during which an employee is required to provide service in exchange for the 
award.  We record excess tax benefits, realized from the exercise of stock options as a financing cash inflow and as a 
reduction of taxes paid in cash flow from operations.  Equity-based compensation arrangements to non-employees 
are recorded at their fair value on the measurement date.  The measurement of equity-based compensation to non-
employees  is  subject  to  periodic  adjustment  as  the  underlying  equity  instruments  vest.    During  the  years  ended 
December 31, 2015, 2014  and  2013,  we recorded  $26.1 million, $14.8 million  and $11.0  million, respectively,  of 
equity-based compensation expense.   

Research  and  development  expenses.    Research  and  development  expenses  include  external  and  internal 
expenses,  partially  offset  by  third-party  grants  and  fundings  arising  from  collaboration  agreements.    External 
expenses  include  clinical  and  non-clinical  activities  performed  by  contract  research  organizations,  lab  services, 
purchases  of  drug  and  diagnostic  product  materials  and  manufacturing  development  costs.    Research  and 
development  employee-related  expenses  include  salaries,  benefits  and  stock-based  compensation  expense.    Other 
internal research and development expenses are incurred to support overall research and development activities and 
include expenses related to general overhead and facilities.  We expense these costs in the period in which they are 
incurred.   We estimate  our  liabilities  for research  and development  expenses  in  order to  match  the  recognition  of 
expenses to the period in which the actual services are received.  As such, accrued liabilities related to third party 
research  and  development  activities  are  recognized  based  upon  our  estimate  of  services  received  and  degree  of 
completion of the services in accordance with the specific third party contract. 

We record expense for in-process research and development projects acquired as asset acquisitions which have 
not  reached  technological  feasibility  and  which  have  no  alternative  future  use.    For  in-process  research  and 
development  projects  acquired  in  business  combinations,  the  in-process  research  and  development  project  is 
capitalized and evaluated for impairment until the development process has been completed.  Once the development 
process has been completed the asset will be amortized over its remaining useful life. 

Segment  reporting.    Our  chief  operating  decision-maker  (“CODM”)  is  Phillip  Frost,  M.D.,  our  Chairman  and 
Chief  Executive  Officer.    Our  CODM  reviews  our  operating  results  and  operating  plans  and  makes  resource 
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allocation decisions on a Company-wide or aggregate basis.  We currently manage our operations in two reportable 
segments, pharmaceutical and diagnostics.  The pharmaceutical segment consists of our pharmaceutical operations 
we  acquired  in  Chile,  Mexico,  Ireland,  Israel  and  Spain  and  our  pharmaceutical  research  and  development.    The 
diagnostics segment primarily consists of our clinical laboratory operations we acquired through the acquisitions of 
Bio-Reference and OPKO Lab and our point-of-care operations.  There are no significant inter-segment sales.  We 
evaluate the performance of each segment based on operating profit or loss.  There is no inter-segment allocation of 
interest expense and income taxes.   

Shipping  and  Handling  Costs.    We  do  not  charge  customers  for  shipping  and  handling  costs.    Shipping  and 

handling costs are classified as Cost of revenues in the Consolidated Statements of Operations. 

Foreign Currency Translation.  The financial statements of certain of our foreign operations are measured using 
the local currency as the functional currency.  The local currency assets and liabilities are generally translated at the 
rate of exchange to the United States (“U.S.”) dollar on the balance sheet date and the local currency revenues and 
expenses  are  translated  at  average  rates  of  exchange  to  the  U.S.  dollar  during  the  reporting  periods.    Foreign 
currency transaction gains (losses) have been reflected as a component of Other income (expense), net within the 
Consolidated  Statements  of  Operations  and  foreign  currency  translation  gains  (losses)  have  been  included  as  a 
component  of the  Consolidated  Statements  of  Comprehensive  Loss.    During  the  years ended  December 31,  2015, 
2014  and  2013,  we  recorded  $(2.4)  million,  $(4.8)  million  and  $(0.3)  million,  respectively  of  transaction  gains 
(losses). 

Variable interest entities.  The consolidation of variable interest entities (“VIE”) is required when an enterprise 
has  a  controlling  financial  interest.    A  controlling  financial  interest  in  a  VIE  will  have  both  of  the  following 
characteristics:  (a)  the  power  to  direct  the  activities  of  a  VIE  that  most  significantly  impact  the  VIE’s  economic 
performance and (b) the obligation to absorb losses of the VIE that could potentially be significant to the VIE.  In 
July 2015, we deconsolidated SciVac Therapeutics Inc., (“STI”), and account for our retained interest in STI as an 
equity method investment.  Refer to Note 4. 

Investments.  We have made strategic investments in development stage and emerging companies.  We record 
these  investments  as  equity  method  investments  or  investments  available  for  sale  based  on  our  percentage  of 
ownership and whether we have significant influence over the operations of the investees.  Investments for which it 
is  not  practical  to  estimate  fair  value  and  which  we  do  not  have  significant  influence  are  accounted  for  as  cost 
method investments.  For investments classified under the equity method of accounting, we record our proportionate 
share of their losses in Losses from investments in investees in our Consolidated Statement of Operations.  Refer to 
Note 4.  For investments classified as available for sale, we record changes in their fair value as unrealized gain or 
loss in Other comprehensive income (loss) based on their closing price per share at the end of each reporting period.  
Refer to Note 4. 

Recent  accounting  pronouncements.    In  May  2014,  the  FASB  issued  Accounting  Standards  Update  (“ASU”), 
ASU  No.  2014-09,  “Revenue  from  Contracts  with  Customers.”    ASU  No.  2014-09  clarifies  the  principles  for 
recognizing  revenue  and  develops  a  common  revenue  standard  for  GAAP  and  International  Financial  Reporting 
Standards that removes inconsistencies and weaknesses in revenue requirements, provides a more robust framework 
for  addressing  revenue  issues,  improves  comparability  of  revenue  recognition  practices  across  entities,  industries, 
jurisdictions,  and  capital  markets,  provides  more  useful  information  to  users  of  financial  statements  through 
improved disclosure requirements and simplifies the preparation of financial statements by reducing the number of 
requirements  to  which  an  entity  must  refer.    ASU  No.  2014-09  is  effective  for  fiscal  years,  and  interim  periods 
within those years, beginning after December 15, 2017.  Companies can choose to apply the ASU using either the 
full  retrospective  approach  or  a  modified  retrospective  approach.    We  are  currently  evaluating  both  methods  of 
adoption and the impact that the adoption of this ASU will have on our Consolidated Financial Statements. 

In June 2014, the FASB issued ASU No. 2014-12, “Accounting for Share-Based Payments When the Terms of 
an Award Provide That a Performance Target Could Be Achieved after the Requisite Service Period (a consensus of 
the FASB Emerging Issues Task Force).”  ASU No. 2014-12 requires that a performance target that affects vesting 
and that could be achieved after the requisite service period be treated as a performance condition.  ASU No. 2014-
12 is effective for fiscal years, and interim periods within those years, beginning after December 15, 2015.  Earlier 
adoption is permitted.  The amendments can be applied either prospectively to all awards granted or modified after 
the effective date or retrospectively to all awards with performance targets that are outstanding as of the beginning 
of the earliest annual period presented in the financial statements and to all new or modified awards.  We expect to 
apply  the  ASU  prospectively  and  do  not  expect  the  adoption  to  have  an  impact  on  our  Consolidated  Financial 
Statements. 

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In August 2014, the FASB issued ASU No. 2014-15, “Disclosure of Uncertainties about an Entity’s Ability to 
Continue as a Going Concern,” to provide guidance on management’s responsibility in evaluating whether there is 
substantial  doubt  about  a  company’s  ability  to  continue  as  a  going  concern  and  to  provide  related  footnote 
disclosures.    ASU  2014-15  is  effective  for  annual  periods  ending  after  December 15,  2016  with  early  adoption 
permitted.  We do not believe the impact of our pending adoption of ASU 2014-15 on our Consolidated Financial 
Statements will be material. 

In  February 2015,  the  FASB  issued  ASU  No. 2015-02,  “Consolidation  (Topic  810):  Amendments  to  the 
Consolidation Analysis,” which amends current consolidation guidance including changes to both the variable and 
voting interest models used by companies to evaluate whether an entity should be consolidated.  The requirements 
from  ASU  2015-02  are  effective  for  interim  and  annual  periods  beginning  after  December 15,  2015,  with  early 
adoption permitted.  We do not believe the impact of our pending adoption of ASU 2015-02 on our Consolidated 
Financial Statements will be material. 

In  July  2015,  the  FASB  issued  ASU  No. 2015-11,  “Inventory  (Topic  330):  Simplifying  the  Measurement  of 
Inventory,” which  changes  the  measurement  principle  for  entities  that  do not  measure  inventory  using  the  last-in, 
first-out (“LIFO”) or retail inventory method from the lower of cost or market to lower of cost and net realizable 
value.    ASU  2015-11  is  effective  for  fiscal  years  beginning  after  December 15,  2016,  including  interim  periods 
within  those  fiscal  years,  with  early  adoption  permitted.    We  are  currently  evaluating  the  impact  of  this  new 
guidance on our Consolidated Financial Statements. 

In September 2015, the FASB issued ASU No. 2015-16, “Business Combinations (Topic 805): Simplifying the 
Accounting  for  Measurement-Period  Adjustments,”  which  replaces  the  requirement  that  an  acquirer  in  a  business 
combination  account  for  measurement  period  adjustments  retrospectively  with  a  requirement  that  an  acquirer 
recognize adjustments to the provisional amounts that are identified during the measurement period in the reporting 
period in which the adjustment amounts are determined.  ASU 2015-16 requires that the acquirer record, in the same 
period’s  financial  statements,  the  effect  on  earnings  of  changes  in  depreciation,  amortization,  or  other  income 
effects,  if  any,  as  a  result  of  the  change  to  the  provisional  amounts,  calculated  as  if  the  accounting  had  been 
completed  at  the  acquisition  date.    ASU  2015-16  is  effective  for  fiscal  years  beginning  after  December 15,  2015, 
including interim periods within those fiscal years.  The guidance is to be applied prospectively to adjustments to 
provisional  amounts  that  occur  after  the  effective  date  of  the  guidance,  with  earlier  application  permitted  for 
financial statements that have not been issued.  Our early adoption of ASU 2015-16 in the third quarter of 2015 did 
not have a material impact on our Consolidated Financial Statements. 

In  November  2015,  the  FASB  issued  ASU  No. 2015-17,  “Income  Taxes  (Topic  740):  Balance  Sheet 
Classification of Deferred Taxes,” which requires deferred tax liabilities and assets to be classified as noncurrent in 
a  classified  statement  of  financial  position.   ASU  2015-17  is  effective  for  financial  statements  issued  for  annual 
periods beginning after December 15, 2016, and interim periods within those annual periods.  Earlier application is 
permitted for all entities as of the beginning of an interim or annual reporting period.  We adopted the provisions of 
this  ASU  prospectively  in  the  fourth  quarter  of  2015,  and  did  not  retrospectively  adjust  the  prior  periods.   The 
adoption  of  this  ASU  will  simplify  the  presentation  of  deferred  income  taxes  and  reduce  complexity  without 
decreasing the usefulness of information provided to users of financial statements.  The adoption of ASU 2015-17 
did not have a significant impact on our financial position, results of operations and cash flows. 

Note 3 Loss Per Share 

Basic loss per share is computed by dividing our net loss by the weighted average number of shares outstanding 
during  the  period.    For  diluted  earnings  per  share,  the  dilutive  impact  of  stock  options,  warrants  and  bifurcated 
conversion option of the 2033 Senior Notes is determined by applying the “treasury stock” method.  In the periods 
in  which  their  effect  would  be  antidilutive,  no  effect  has  been  given  to  outstanding  options,  warrants  or  the 
potentially  dilutive  shares  issuable  pursuant  to  the  2033  Senior  Notes  (defined  in  Note  6)  in  the  dilutive 
computation. 

A total of 14,269,717, 28,456,149 and 32,105,859 potential shares of Common Stock have been excluded from 
the calculation of diluted net loss per share for the years ended December 31, 2015, 2014 and 2013, respectively, 
because their inclusion would be antidilutive.   

During the year ended December 31, 2015, 25,686,153 Common Stock options and Common Stock warrants to 
purchase shares of our Common Stock were exercised, resulting in the issuance of 24,466,106 shares of Common 
Stock.    Of  the  25,686,153  Common  Stock  options  and  Common  Stock  warrants  exercised,  1,220,047  shares  of 
Common Stock were surrendered in lieu of a cash payment via the net exercise feature of the agreements.   

96 

 
During the year ended December 31, 2014, 5,787,983 Common Stock options and Common Stock warrants to 
purchase  shares  of  our  Common  Stock  were  exercised,  resulting  in  the  issuance  of  5,392,741  shares  of  Common 
Stock.  Of the 5,787,983 Common Stock options and Common Stock warrants exercised, 426 shares of Common 
Stock were surrendered in lieu of a cash payment via the net exercise feature of the agreements.   

During  the  year  ended  December 31,  2013,  10,881,570  Common  Stock  options  and  Common  Stock  warrants  to 
purchase shares of our Common Stock were exercised, resulting in the issuance of 10,732,745 shares of Common 
Stock.    Of  the  10,881,570  Common  Stock  options  and  Common  Stock  warrants  exercised,  148,825  shares  of 
Common Stock were surrendered in lieu of a cash payment via the net exercise feature of the agreements. 

Note 4 Acquisitions, Investments, and Licenses 

Bio-Reference acquisition 

In August 2015, we completed the acquisition of Bio-Reference, the third largest full service clinical laboratory 
in  the  United  States,  known  for  its  innovative  technological  solutions  and  pioneering  leadership  in  the  areas  of 
genomics and genetic sequencing.  Holders of Bio-Reference common stock received 76,566,147 shares of OPKO 
Common  Stock  for  the  outstanding  shares  of  Bio-Reference  common  stock.    The  transaction  was  valued  at 
approximately $950.1 million, based on a closing price per share of our Common Stock of $12.38 as reported by the 
New York Stock Exchange on the closing date, or $34.05 per share of Bio-Reference common stock.  Included in 
the  transaction  value  is  $2.3  million  related  to  the  value  of  replacement  stock  option  awards  attributable  to  pre-
merger service. 

The following table summarizes the preliminary purchase price allocation and the estimated fair value of the net 
assets acquired and liabilities assumed in the acquisition of Bio-Reference at the date of acquisition.  The purchase 
price  allocation  for  Bio-Reference  is  preliminary  pending  completion  of  the  fair  value  analysis  of  acquired  assets 
and liabilities: 

97 

 
(In thousands) 
Purchase price: 

Bio-Reference 

Value of OPKO Common Stock issued to Bio-Reference shareholders .................................. $ 
Value of replacement stock options awards to holders of Bio-Reference stock options ......... 

Total purchase price ............................................................................................................ $ 

947,889
2,259
950,148

Preliminary value of assets acquired and liabilities assumed: 
Current assets 

Cash and cash equivalents ....................................................................................................... $ 
Accounts receivable ................................................................................................................. 
Inventory .................................................................................................................................. 
Other current assets, principally deferred tax assets ................................................................ 
Total current assets ............................................................................................................... 
Property, plant and equipment ................................................................................................. 

Intangible assets: 

Trade name .............................................................................................................................. 
Customer relationships ............................................................................................................ 
Technology .............................................................................................................................. 
Total intangible assets .......................................................................................................... 
Goodwill .................................................................................................................................. 
Investments .............................................................................................................................. 
Other assets .............................................................................................................................. 

Total assets ........................................................................................................................... $ 

Accounts payable ..................................................................................................................... 
Accrued expenses .................................................................................................................... 
Income taxes payable ............................................................................................................... 
Lines of credit and notes payable ............................................................................................ 
Capital lease obligations .......................................................................................................... 
Deferred tax liability (non-current) .......................................................................................... 

Total purchase price ............................................................................................................. $ 

15,800
168,164
19,674
61,135
264,773
112,457

47,100
395,200
100,600
542,900
441,158
5,326
13,265
1,379,879
(77,908)
(30,848)
(437)
(65,701)
(18,293)
(236,544)
950,148

During the fourth quarter of 2015, we continued to finalize our purchase price allocation during the measurement 
period  and  obtained  new  fair  value  information  related  to  certain  assets  acquired  and  liabilities  assumed  of  Bio-
Reference.  As a result, in the fourth quarter of 2015 we adjusted the purchase price allocation initially recorded in 
the third quarter of 2015 by increasing accounts receivable by $5.2 million, decreasing Inventory by $0.2 million, 
increasing  Other  current  assets  by  $7.0  million,  increasing  Property,  plant  and  equipment  by  $6.2  million, 
decreasing intangible assets by $6.9 million, decreasing Goodwill by $31.6 million, increasing Other assets (long-
term) by $1.1 million, decreasing Accounts payable by $1.5 million, increasing accrued expenses by $1.6 million, 
decreasing  Income  taxes  payable  by  $20.0  million  and  increasing  Deferred  tax  liability  by  $0.5  million.    These 
adjustments did not have a significant impact on our fourth quarter results of operations or cash flows. 

Goodwill  from  the  acquisition  of  Bio-Reference  principally  relates  to  intangible  assets  that  do  not  qualify  for 
separate  recognition  (for  instance,  Bio-Reference’s  assembled  workforce),  our  expectation  to  develop  and  market 
new products, and the deferred tax liability generated as a result of the transaction.  Goodwill is not tax deductible 
for income tax purposes and was assigned to the diagnostics reporting segment. 

Revenue  and  Net  loss  in  the  Consolidated  Statement  of  Operations  for  the  year  ended  December 31,  2015 
includes  revenue  and  net  income  of  Bio-Reference  from  the  date  of  acquisition  to  December 31,  2015  of  $321.9 
million and $3.2 million, respectively. 

The preliminary amortization periods for intangible assets acquired are 5 years for trade name, 10-20 years for 

customer relationships, 8-12 years for technology and 3 years for internally developed software.   

We recognized $6.2 million of acquisition related costs for the acquisition of Bio-Reference that were expensed 

in the current period as a component of Selling, general and administrative expense. 

Pro forma disclosure for Bio-Reference acquisition 

The pro forma information has been prepared utilizing period ends that differ by less than 93 days, as permitted 
by  Regulation  S-X.    We  are  a  registrant  with  a  fiscal  year  that  ends  on  December 31  and  Bio-Reference  was  a 
98 

 
 
 
 
 
 
registrant with a fiscal year that ended on October 31.  The pro forma results for the years ended December 31, 2015 
and  2014  combines  the  results  of  operations  of  OPKO  and  Bio-Reference,  giving  effect  to  the  merger  as  if  it 
occurred on January 1, 2014, and are based on the individual consolidated statement of operations of OPKO as of 
December 31, 2015 and 2014 and Bio-Reference as of October 31, 2015 and 2014. 

(In thousands) 
Revenues .................................................................................................$
Net loss ....................................................................................................$
Net loss attributable to common shareholders .........................................$

2015 
1,052,462 

  $ 
(19,456)    $ 
(18,055)    $ 

2014 
923,407 
(140,854) 
(137,881) 

For the year ended December 31, 

The pro forma financial information is presented for information purposes only.  The financial information may 
not  necessarily  reflect  our  future  results  of  operations  or  what  the  results  of  operations  would  have  been  had  we 
owned and operated Bio-Reference as of the beginning of the period presented. 

EirGen Pharma Limited acquisition 

In  May  2015,  we  acquired  all  of  the  issued  and  outstanding  shares  of  EirGen,  a  specialty  pharmaceutical 
company incorporated in Ireland focused on the development and commercial supply of high potency, high barrier 
to entry pharmaceutical products, for $133.8 million in the aggregate.  We acquired the outstanding shares of EirGen 
for  approximately  $100.2  million  in  cash  and  delivered  2,420,487  shares  of  our  Common  Stock  valued  at 
approximately  $33.6  million  based  on  the  closing  price  per  share  of  our  Common  Stock  as  reported  by  the  New 
York Stock Exchange on the closing date of the acquisition, $13.88 per share.   

The following table summarizes the preliminary purchase price allocation and the estimated fair value of the net 
assets acquired and liabilities assumed in the acquisition of EirGen at the date of acquisition.  The purchase price 
allocation for EirGen is preliminary pending completion of the fair value analysis of acquired assets and liabilities: 

(In thousands) 
Current assets(1) ..................................................................................$
Intangible assets: 

EirGen 

11,795 

IPR&D assets .................................................................................
Customer relationships ..................................................................
Currently marketed products .........................................................
Total intangible assets ................................................................
Goodwill ........................................................................................
Property, plant and equipment .......................................................
Other assets ....................................................................................
Accounts payable and other liabilities ...........................................
Deferred tax liability ......................................................................

Total purchase price ...................................................................$

560 
34,155 
3,919 
38,634 
83,373 
8,117 
1,232 
(6,254) 
(3,131) 
133,766 

(1)  Current  assets  include  cash,  accounts  receivable,  inventory  and  other  assets  of  $5.5  million,  $2.7
million, $2.2 million and $1.4 million, respectively, related to the EirGen acquisition.  The fair value of
the accounts receivable equals the gross contractual amount at the date of acquisition.   

During the fourth quarter of 2015, we continued to finalize our purchase price allocation during the measurement 
period  and  obtained  new  fair  value  information  related  to  certain  assets  acquired  of  EirGen.    As  a  result,  in  the 
fourth quarter of 2015 we adjusted the purchase price allocation initially recorded in the third quarter of 2015 by 
decreasing  IPR&D  assets  by  $19.0  million,  increasing  Goodwill  by  $16.6  million  and  decreasing  Deferred  tax 
liability by $2.5 million. 

Goodwill from the acquisition of EirGen principally relates to intangible assets that do not qualify for separate 
recognition (for instance, EirGen’s assembled workforce), our expectation to develop and market new products, and 
the deferred tax liability generated as a result of this being a partial stock transaction.  Goodwill is not tax deductible 
for income tax purposes and was assigned to the pharmaceutical reporting segment. 

Revenue  and  Net  loss  in  the  Consolidated  Statement  of  Operations  for  the  year  ended  December 31,  2015 
includes revenue and net income of EirGen from the date of acquisition to December 31, 2015 of $13.5 million and 
$1.4 million, respectively. 

99 

 
 
 
 
 
 
 
 
 
 
 
Our  IPR&D  assets  will  not  be  amortized  until  the  underlying  development  programs  are  completed.    Upon 
obtaining  regulatory  approval,  the  IPR&D  assets  are  then  accounted  for  as  finite-lived  intangible  assets  and 
amortized on a straight-line basis over its estimated useful life.  We amortize intangible assets with definite lives on 
a straight-line basis over their estimated useful lives, currently ranging from 3 to 20 years. 

We recognized $0.5 million of acquisition related costs for the acquisition of EirGen that were expensed in the 

current period as a component of Selling, general and administrative expense. 

Pro forma disclosure for EirGen acquisition 

The  following  table  includes  the  pro  forma  results  for  the  years  ended  December 31,  2015  and  2014  of  the 
combined  companies  as  though  the  acquisition  of  EirGen  had  been  completed  as  of  the  beginning  of  the  period 
presented. 

(In thousands) 
Revenues .................................................................................................$
Net loss ....................................................................................................$
Net loss attributable to common shareholders .........................................$

2015 
495,993 
  $ 
(32,481)    $ 
(31,081)    $ 

2014 
105,973 
(176,563) 
(173,590) 

For the year ended December 31, 

The  pro  forma  financial  information  is  presented  for  information  purposes  only.    The  unaudited  pro  forma 
financial  information  may  not  necessarily  reflect  our  future results  of operations or what  the  results  of  operations 
would have been had we owned and operated EirGen as of the beginning of the period presented. 

Inspiro Medical Ltd. acquisition 

In May 2014, we acquired 100% of the issued and outstanding share capital of Inspiro Medical Ltd. (“Inspiro”), 
an  Israeli  medical  device  company  developing  a  new  platform  to  deliver  small  molecule  drugs  such  as 
corticosteroids and beta agonists and larger molecules to treat respiratory diseases.   

In connection with the transaction, we paid $1.5 million in cash and delivered 999,556 shares of our Common 

Stock valued at $8.6 million. 

Inspiro’s Inspiromatic is a “smart” easy-to-use dry powder inhaler with several advantages over existing devices.  
We anticipate that this innovative device will play a valuable role in the improvement of therapy for asthma, chronic 
obstructive  pulmonary  disease,  cystic  fibrosis  and  other  respiratory  diseases.    We  recorded  the  transaction  as  an 
asset acquisition and recorded the assets and liabilities at fair value.  As the asset had no alternative future use, we 
recorded  $10.1  million  of  acquired  in-process  research  and  development  expenses.    We  record  expense  for  in-
process research and development projects accounted for as asset acquisitions which have not reached technological 
feasibility and which have no alternative future use. 

Investments 

The  following  table  reflects  the  accounting  method,  carrying  value  and  underlying  equity  in  net  assets  of  our 

unconsolidated investments as of December 31, 2015: 

(In thousands) 

Investment type 
Equity method investments .........................................   $
Variable interest entity, equity method ........................  
Available for sale investments .....................................  
Warrants and options ...................................................  
Total carrying value of investments ............................   $

Investment 
Carrying Value 
24,495 
1,268 
3,615 
5,338 
34,716 

Underlying Equity
in Net Assets 
24,488 
91 

  $

Equity Method Investments 

Our  equity  method  investments  consist  of  investments  in  Pharmsynthez  (ownership  17%),  Cocrystal  Pharma, 
Inc.  (“COCP”)  (8%),  Sevion  Therapeutics,  Inc.  (“Sevion”)  (3%),  Non-Invasive  Monitoring  Systems,  Inc.  (1%), 
Neovasc Inc. (4%), STI (25%) and InCellDx, Inc. (27%).  The total assets, liabilities, and net losses of our equity 

100 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
method investees as of and for the years ended December 31, 2015 were $383.1 million, $61.6 million, and $73.3 
million, respectively.  We have determined that we and/or our related parties can significantly influence the success 
of our equity method investments through our board representation and voting power.  Accordingly, we account for 
our  investment  in  these  entities  under  the  equity  method.    For  investments  classified  under  the  equity  method  of 
accounting,  we  record  our  proportionate  share  of  their  losses  in  Loss  from  investments  in  investees  in  our 
Consolidated Statement of Operations.  The aggregate value of our equity method investments based on the quoted 
market price of their common stock and the number of shares held by us as of December 31, 2015 is $89.6 million.   

Available for Sale Investments 

Our  available  for  sale  investments  consist  of  investments  in  RXi  Pharmaceuticals  Corporation  (“RXi”) 
(ownership  3%),  ChromaDex  Corporation  (2%),  MabVax  Therapeutics  Holdings,  Inc.  (“MabVax”)  (1%)  and 
ARNO Therapeutics, Inc. (“ARNO”) (4%).  We have determined that our ownership, along with that of our related 
parties,  does  not  provide  us  with  significant  influence  over  the  operations  of  our  available  for  sale  investments.  
Accordingly, we account for our investment in these entities as available for sale, and we record changes in these 
investments as an unrealized gain or loss in Other comprehensive income (loss) each reporting period.   

Based on our evaluation of the value of our investment in RXi, including RXi’s decreasing stock price during the 
year ended December 31, 2015, we determined that the decline in fair value of our RXi common shares was other-
than-temporary  and  recorded  an  impairment  charge  of  $7.3  million  in  Other  income  (expense),  net  in  our 
Consolidated  Statement  of  Operations  for  the  year  ended  December 31,  2015  to  write  our  investment  in  RXi 
common  shares  down  to  its  fair  value  of  $0.9  million  as  of  December 31,  2015.    Based  on  our  evaluation  of  the 
value of our investment in ARNO, including ARNO’s decreasing stock price during the year ended December 31, 
2014,  we  determined  that  the  decline  in  fair  value  of  our  ARNO  common  shares  was  other-than-temporary  and 
recorded  an  impairment  charge  of  $1.4  million  in  Other  income  (expense),  net  in  our  Consolidated  Statement  of 
Operations for the year ended December 31, 2014 to write our investment in ARNO common shares down to its fair 
value  of  $0.6  million  as  of  December 31,  2014.    Refer  to  Note  17  for  further  discussion  of  the  fair  value  of  our 
available for sale investments. 

Sales of Investments 

Gains (losses) included in earnings from sales of our investments for the years ended December 31, 2015, 2014 
and  2013  were  $0.0  million,  $1.3  million  and  $29.9  million,  respectively,  and  were  recorded  in  Other  income 
(expense),  net  in  our  Consolidated  Statement  of  Operations.    The  cost  of  securities  sold  is  based  on  the  specific 
identification method. 

Warrants and Options 

In addition to our equity method investments and available for sale investments, we hold options to purchase 1.0 
million additional shares of Neovasc, which are fully vested as of December 31, 2015, and 1.0 million, 0.8 million, 
0.5  million  and  1.8  million  warrants  to  purchase  additional  shares  of  COCP,  ARNO,  Sevion  and  MabVax, 
respectively.    We  recorded  the  changes  in  the  fair  value  of  the  options  and  warrants  in  Fair  value  changes  of 
derivative instruments, net in our Consolidated Statements of Operations.  We record the fair value of the options 
and  warrants  in  Investments,  net  in  our  Consolidated  Balance  Sheets.    See  further  discussion  of  the  Company’s 
options and warrants in Note 17 and Note 18. 

Investments in variable interest entities 

We  have  determined  that  we  hold  variable  interests  in  Zebra  Biologics,  Inc.  (“Zebra”).    We  made  this 
determination as a result of our assessment that Zebra does not have sufficient resources to carry out its principal 
activities without additional financial support. 

We own 1,260,000 shares of Zebra Series A-2 Preferred Stock and 900,000 shares of Zebra restricted common 
stock  (ownership  29%  at  December 31,  2015).    Zebra  is  a  privately  held  biotechnology  company  focused  on  the 
discovery and development of biosuperior antibody therapeutics and complex drugs.  Dr. Richard Lerner, M.D., a 
member of our Board of Directors, is a founder of Zebra and, along with Dr. Frost, serves as a member of Zebra’s 
Board of Directors.   

In  order  to  determine  the  primary  beneficiary  of  Zebra,  we  evaluated  our  investment  and  our  related  parties’ 
investment, as well as our investment combined with the related party group’s investment to identify if we had the 
power to direct the activities that most significantly impact the economic performance of Zebra.  We determined that 
101 

 
we  do  not  have  the  power  to  direct  the  activities  that  most  significantly  impact  Zebra’s  economic  performance.  
Based on the capital structure, governing documents and overall business operations of Zebra, we determined that, 
while  a  VIE,  we  do  not  have  the  power  to  direct  the  activities  that  most  significantly  impact  Zebra’s  economic 
performance.    We  did  determine,  however,  that  we  can  significantly  influence  the  success  of  Zebra  through  our 
board representation and voting power.  Therefore, we have the ability to exercise significant influence over Zebra’s 
operations and account for our investment in Zebra under the equity method. 

Investment in SciVac 

In June 2012, we acquired a 50% stock ownership in SciVac from FDS Pharma LLP (“FDS”).  SciVac was a 
privately-held Israeli company that produced a third-generation hepatitis B-vaccine.  From November 2012 through 
June 2015, we loaned to SciVac a combined $7.9 million for working capital purposes.  We determined that we held 
variable interests in SciVac based on our assessment that SciVac did not have sufficient resources to carry out its 
principal activities without financial support.  We had also determined we were the primary beneficiary of SciVac 
through our representation on SciVac’s board of directors.  SciVac’s board of directors consisted of 5 members, of 
which 3 members had been appointed by us, representing 60% of SciVac’s board.  As a result of this conclusion, we 
consolidated the results of operations and financial position of SciVac through June 2015 and recorded a reduction 
of equity for the portion of SciVac we do not own. 

On July 9, 2015, SciVac Therapeutics Inc., formerly Levon Resources Ltd. (“STI”) completed a reverse takeover 
transaction  (the  “Arrangement”)  pursuant  to  which  STI  acquired  all  of  the  issued  and  outstanding  securities  of 
SciVac.  As a result of this transaction, OPKO’s ownership in STI decreased to 24.5%.   

Upon completion of the Arrangement, we determined that STI was not a VIE.  We also determined that we do 
not  have  the  power  to  direct  the  activities  that  most  significantly  impact  the  economic  performance  of  STI  that 
would  require  us  to  consolidate  STI.    STI’s  board  of  directors  consists  of  7  members,  of  which  3  independent 
members are initially members of our management.  We do not have any rights to appoint members to STI’s board.  
STI’s  board  members  are  approved  by  a  vote  of  the  shareholders.    We  recorded  a  $15.9  million  gain  on  the 
deconsolidation of SciVac in Other income (expense), net in our Consolidated Statement of Operations for the year 
ended December 31, 2015.  The recognized gain was primarily due to the fair value of the retained interest in STI 
based on Levon’s cash contribution of approximately $21.2 million under the Arrangement.   

Following  the  deconsolidation,  we  account  for  our  investment  in  STI  under  the  equity  method  as  we  have 
determined that we and/or our related parties can significantly influence STI through our board representation and 
voting  power.    STI  is  considered  a  related  party  as  a  result  of  our  board  representation  in  STI  and  executive 
management’s ownership interests in STI. 

In  October  2015,  STI  announced  it  entered  into  an  agreement  and  plan  of  merger  pursuant  to  which  a  newly-
formed wholly-owned subsidiary of STI will merge with and into VBI Vaccines Inc. (“VBI”) with VBI surviving 
the  merger  as  a  wholly-owned  subsidiary  of  STI,  and  STI  will  change  its  name  to  VBI  Vaccines  Inc.    At  the 
effective time of the merger, each share of VBI common stock will be converted into the right to receive 20.808356 
common shares of STI (the “Exchange Ratio”).  Upon closing of the transaction in 2016, holders of VBI’s securities 
will  receive  shares,  options  and  warrants  of  STI  representing  approximately  46%  of  the  fully  diluted  outstanding 
shares of the combined company. 

102 

 
The  following  table  represents  the  consolidated  assets  and  non-recourse  liabilities  related  to  SciVac  as  of 

December 31, 2014.  These assets were owned by, and these liabilities were obligations of, SciVac, not us. 

(In thousands) 
Assets 
Current assets: 

December 31, 
2014 

Cash and cash equivalents .....................................................$ 
Accounts receivable, net ........................................................
Inventories, net ......................................................................
Prepaid expenses and other current assets .............................
Total current assets ............................................................
Property, plant and equipment, net ............................................
Intangible assets, net ..................................................................
Goodwill ....................................................................................
Other assets ................................................................................

Total assets .....................................................................$ 

393  
316  
1,649  
718  
3,076  
1,725  
875  
1,553  
384  
7,613  

Liabilities 
Current liabilities: 

Accounts payable...................................................................$ 
Accrued expenses ..................................................................
Notes payable ........................................................................
Total current liabilities .......................................................
Other long-term liabilities ..........................................................

Total liabilities ................................................................$ 

445  
4,446  
5,189  
10,080  
2,042  
12,122  

103 

 
 
 
  
 
 
 
Note 5 Composition of Certain Financial Statement Captions 

(In thousands) 
Accounts receivable, net: 

Accounts receivable ................................................................................$ 
Less: allowance for doubtful accounts ................................................

$ 

Inventories, net: 

Consumable supplies ..............................................................................$ 
Finished products ....................................................................................
Work in-process ......................................................................................
Raw materials .........................................................................................
Less: inventory reserve ........................................................................

$ 

Prepaid expenses and other current assets: 

Other receivables ....................................................................................$ 
Prepaid supplies ......................................................................................
Taxes recoverable ...................................................................................
Prepaid insurance ....................................................................................
Other .......................................................................................................

$ 

Property, plant and equipment, net: 

Machinery, medical and other equipment ...............................................$ 
Leasehold improvements ........................................................................
Furniture and fixtures ..............................................................................
Automobiles and aircraft ........................................................................
Software ..................................................................................................
Building ..................................................................................................
Land ........................................................................................................
Construction in process ...........................................................................
Less: accumulated depreciation ...........................................................

$ 

Intangible assets, net: 

Customer relationships ...........................................................................$ 
Technologies ...........................................................................................
Trade names ............................................................................................
Covenants not to compete .......................................................................
Licenses ..................................................................................................
Product registrations ...............................................................................
Other .......................................................................................................
Less:  accumulated amortization .........................................................

$ 

Accrued expenses: 

Deferred revenue.....................................................................................$ 
Employee benefits...................................................................................
Taxes payable .........................................................................................
Contingent consideration ........................................................................
Clinical trials ...........................................................................................
Capital leases short-term .........................................................................
Milestone payment ..................................................................................
Professional fees .....................................................................................
Other .......................................................................................................

$ 

70,246 
29,751 
7,605 
22,164 
2,505 
5,373 
5,000 
1,506 
23,749 
167,899 

Other long-term liabilities: 

Deferred revenue.....................................................................................$ 
JP Morgan Chase line of credit ...............................................................

162,634 
72,107 

  $ 

  $ 

  $ 

104 

For the years ended 
December 31, 

2015 

2014 

219,043 
(25,168)   
193,875 

  $ 

  $ 

  $ 

22,265 
13,404 
1,215 
3,848 
(1,051)   
39,681 

  $ 

21,875 
(1,906) 
19,969 

— 
12,116 
1,011 
4,116 
(639) 
16,604 

11,946 
8,773 
3,076 
2,206 
903 
26,904 

  $ 

  $ 

669 
1,123 
2,417 
968 
4,212 
9,389 

  $ 

89,936 
27,949 
11,403 
10,271 
10,497 
5,965 
2,394 
425 
(27,042)   
131,798 

449,972 
151,709 
50,416 
8,612 
23,432 
7,512 
5,600 
(59,101)   
638,152 

  $ 

  $ 

  $ 

13,710 
3,592 
2,148 
— 
1,695 
3,171 
2,391 
225 
(10,521) 
16,411 

22,108 
52,508 
3,483 
8,639 
— 
8,763 
1,079 
(33,931) 
62,649 

4,185 
4,127 
77 
27,352 
8,643 
— 
— 
1,860 
14,668 
60,912 

2,526 
— 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(In thousands) 

Contingent consideration ........................................................................
Capital leases long-term ..........................................................................
Mortgages and other debts payable .........................................................
Other .......................................................................................................

$ 

For the years ended 
December 31, 

2015 

32,258 
9,285 
2,523 
13,663 
292,470 

  $ 

2014 
44,215 
— 
2,434 
1,030 
50,205 

The  following  table  summarizes  the  fair  values  assigned  to  our  major  intangible  asset  classes  upon  each 

acquisition: 

(In thousands) 
Bio-Reference ........$ 
CURNA .................

Technologies  

In-process 
research and 
development   

Customer 
relationships

Product 
registrations

Covenants 
not to 
compete  Tradenames   Other 

100,600   $

—   $ 

—  

10,000  

395,200 $
—

— $
—

— $
—

47,100  $ 
—  

EirGen ...................
FineTech ................
OPKO Biologics ....
OPKO Chile ...........
OPKO  
  Diagnostics ........
OPKO Health 

Europe ...............
OPKO Lab .............
OPKO Renal ..........
Weighted average 
amortization 
period .................

—  
2,700  
—  
—  

560  
—  
590,200  
—  

44,400  

—  

3,017  
1,370  
—  

1,459  
—  
191,530  

34,155
14,200
—
3,945

—

436
3,860
—

—
—
—
5,829

—

2,930
—
—

—
1,500
—
—

—

187
6,900
—

Total 
identified 
intangible 
assets 

10,290

Goodwill
—    $ 542,900 $ 441,158
290  
4,827
3,919  
—  
—  
—  

38,634
18,800
590,200
10,806

83,373
11,623
139,784
5,441

—  
400  
—  
1,032  

—  

—  

44,400

17,977

349  
1,830  
—  

—  
70  
210  

8,378
14,030
191,740

8,062
29,629
2,411

8-12 years 

Indefinite 

6-20 years

9 years

5 years

4-5 years  3-10 years   

Indefinite

All of the intangible assets and goodwill acquired relate to our acquisitions of principally OPKO Renal, OPKO 
Biologics, EirGen and Bio-Reference.  We do not anticipate capitalizing the cost of product registration renewals, 
rather we expect to expense these costs, as incurred.  Our goodwill is not tax deductible for income tax purposes in 
any jurisdiction we operate in. 

At  December 31,  2015,  the  changes  in  value  of  the  intangible  assets  and  goodwill  are  primarily  due  to  the 
acquisitions  of  Bio-Reference  and  EirGen  and  foreign  currency  fluctuations  between  the  Chilean  and  Mexican 
pesos, the Euro and the Shekel against the U.S. dollar.  At December 31, 2014, the changes in value of the intangible 
assets and goodwill are primarily due to foreign currency fluctuations between the Chilean and Mexican pesos, the 
Euro and the Shekel against the U.S. dollar.   

The following table reflects the changes in the allowance for doubtful accounts, provision for inventory reserve 

and tax valuation allowance accounts: 

(In thousands) 
2015 

Beginning
balance 

Charged 
to 

expense  Written-off

Charged 
to other 

Ending 
balance 

(1,906)
Allowance for doubtful accounts ..........$
Inventory reserve ...................................$
(639)
Tax valuation allowance .......................$ (131,931)

2014 

Allowance for doubtful accounts ..........$
Inventory reserve ...................................$
Tax valuation allowance .......................$

(1,884)
(777)
(85,370)

(24,548)
(926)
—

(646)
(1,082)
—

928 
435 
— 

321 
1,028 
— 

358    $ (25,168)
(1,051)
89,784    $ (42,147)

79    $

303    $
192    $

(1,906)
(639)
(46,561)   $ (131,931)

105 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
   
 
The following table summarizes the changes in Goodwill during the year ended December 31, 2015. 

2015 

Balance at 
January 1 

  Acquisitions

Foreign 
exchange, 
other 

Balance at 
December 31 

Balance at 
January 1  Acquisitions   

Foreign 
exchange, 
other 

Balance at 
December 31

2014 

(In thousands) 
Pharmaceuticals 

CURNA ................$
EirGen 
FineTech ...............
OPKO Biologics ...
OPKO Chile .........
OPKO Health 

Europe ................
OPKO Mexico ......
OPKO Renal .........
SciVac ..................

4,827   $ 
—  
11,698  
139,784  
5,283  

8,013  
100  
2,069  
1,553  

—   $ 

—    $ 

4,827    $

83,373  
—  
—  
—  

—  
—  
—  
—  

(2,234)  
—   
—   
(766)  

(822)  
(100)  
—   
(1,553)  

81,139   
11,698   
139,784   
4,517   

7,191   
—   
2,069   
—   

4,827    $
—   
11,698   
139,784   
6,102   

9,075   
114   
2,069   
1,739   

—    $

—    $

—   
—   
—   

—   
—   
—   
—   

— 
— 
(819)

(1,062) 
(14)
— 
(186)

4,827 
— 
11,698 
139,784 
5,283 

8,013  
100 
2,069 
1,553 

Diagnostics 

Bio-Reference .......
OPKO 

Diagnostics ........
OPKO Lab ............

Note 6 Debt 

—  

441,158  

—   

441,158   

—   

—   

— 

— 

17,977  
32,988  
224,292   $ 

$

—  
—  

524,531   $ 

—   
—   
(5,475)   $ 

17,977   
32,988   

17,977   
32,988   

743,348    $ 226,373    $

—   
—   
—    $

— 
— 
(2,081)   $

17,977 
32,988 
224,292 

In January 2013, we entered into note purchase agreements (the “2033 Senior Notes”) with qualified institutional 
buyers  and  accredited  investors  (collectively,  the  “Purchaser”)  in  a  private  placement  in  reliance  on  exemptions 
from registration under the Securities Act of 1933, (the “Securities Act”).  The Purchasers of the 2033 Senior Notes 
include  Frost  Gamma  Investments  Trust,  a  trust  affiliated  with  Dr. Frost,  and  Hsu  Gamma  Investment,  L.P.,  an 
entity affiliated with Dr. Jane H. Hsiao, our Vice Chairman and Chief Technology Officer.  The 2033 Senior Notes 
were issued on January 30, 2013.  The 2033 Senior Notes, which totaled $175.0 million, bear interest at the rate of 
3.00% per  year,  payable  semiannually  on  February 1  and  August 1  of  each  year,  beginning  August 1,  2013.    The 
2033  Senior  Notes  will  mature  on  February 1,  2033,  unless  earlier  repurchased,  redeemed  or  converted.    Upon  a 
fundamental change as defined in the instruments governing the 2033 Senior Notes, subject to certain exceptions, 
the holders may require us to repurchase all or any portion of their 2033 Senior Notes for cash at a repurchase price 
equal to 100% of the principal amount of the 2033 Senior Notes being repurchased, plus any accrued and unpaid 
interest to but not including the fundamental change repurchase date. 

The following table sets forth information related to the 2033 Senior Notes which is included our Consolidated 

Balance Sheets as of December 31, 2015: 

(In thousands) 
Balance at December 31, 2014 .................................$
Amortization of debt discount ..................................
Change in fair value of embedded derivative ...........
Conversion ................................................................
Balance at December 31, 2015 .................................$

Embedded 
conversion option

2033 Senior 
Notes 

Discount 

65,947 $
—
36,587
(78,797)
23,737 $

87,642 $
—
—
(55,442)
32,200 $

(22,135)   $ 
2,613   
—   
12,997   
(6,525)   $ 

106 

Total 
131,454
2,613
36,587
(121,242)
49,412

 
 
 
 
   
   
   
   
   
   
   
   
 
 
 
 
 
 
 
 
 
    
   
     
     
     
     
     
 
 
 
 
 
 
     
The following table sets forth information related to the 2033 Senior Notes which is included our Consolidated 

Balance Sheets as of December 31, 2014: 

(In thousands) 
Balance at December 31, 2013 .................................$
Amortization of debt discount ..................................
Change in fair value of embedded derivative ...........
Conversion ................................................................
Balance at December 31, 2014 .................................$

Embedded 
conversion option

2033 Senior 
Notes 
158,064 $
—
—
(70,422)
87,642 $

101,087 $
—
12,213
(47,353)
65,947 $

Discount 

(47,239)   $ 
5,662   
—   
19,442   
(22,135)   $ 

Total 
211,912
5,662
12,213
(98,333)
131,454 

The  2033  Senior  Notes  will  be  convertible  at  any  time  on  or  after  November 1,  2032,  through  the  second 
scheduled trading day immediately preceding the maturity date, at the option of the holders.  Additionally, holders 
may  convert  their  2033  Senior  Notes  prior  to  the  close  of  business  on  the  scheduled  trading  day  immediately 
preceding  November 1,  2032,  under  the  following  circumstances:  (1) conversion  based  upon  satisfaction  of  the 
trading  price  condition  relating  to  the  2033  Senior  Notes;  (2) conversion  based  on  the  Common  Stock  price; 
(3) conversion based upon the occurrence of specified corporate events; or (4) if we call the 2033 Senior Notes for 
redemption.  The 2033 Senior Notes will be convertible into cash, shares of our Common Stock, or a combination of 
cash  and  shares  of  Common  Stock,  at  our  election  unless  we  have  made  an  irrevocable  election  of  net  share 
settlement.    The  initial  conversion  rate  for  the  2033  Senior  Notes  will  be  141.48  shares  of  Common  Stock  per 
$1,000 principal amount of 2033 Senior Notes (equivalent to an initial conversion price of approximately $7.07 per 
share of Common Stock), and will be subject to adjustment upon the occurrence of certain events.  In addition, we 
will,  in  certain  circumstances,  increase  the  conversion  rate  for  holders  who  convert  their  2033  Senior  Notes  in 
connection with a make-whole fundamental change (as defined in the Indenture) and holders who convert upon the 
occurrence  of  certain  specific  events  prior  to  February 1,  2017  (other  than  in  connection  with  a  make-whole 
fundamental  change).   Holders of  the 2033  Senior Notes may  require  us  to repurchase  the 2033  Senior  Notes for 
100%  of  their  principal  amount,  plus  accrued  and  unpaid  interest,  on  February 1,  2019,  February 1,  2023  and 
February 1, 2028, or  following  the  occurrence of  a fundamental  change  as defined  in the  indenture governing  the 
2033 Senior Notes.  See further discussion in Note 20. 

We may not redeem the 2033 Senior Notes prior to February 1, 2017.  On or after February 1, 2017 and before 
February 1, 2019, we may redeem for cash any or all of the 2033 Senior Notes but only if the last reported sale price 
of our Common Stock exceeds 130% of the applicable conversion price for at least 20 trading days during the 30 
consecutive  trading  day  period  ending  on  the  trading  day  immediately  prior  to  the  date  on  which  we  deliver  the 
redemption notice.  The redemption price will equal 100% of the principal amount of the 2033 Senior Notes to be 
redeemed, plus any accrued and unpaid interest to but not including the redemption date.  On or after February 1, 
2019, we may redeem for cash any or all of the 2033 Senior Notes at a redemption price of 100% of the principal 
amount of the 2033 Senior Notes to be redeemed, plus any accrued and unpaid interest up to but not including the 
redemption date. 

The  terms  of  the  2033  Senior  Notes,  include,  among  others:  (i)  rights  to  convert  into  shares  of  our  Common 
Stock, including upon a fundamental change; and (ii) a coupon make-whole payment in the event of a conversion by 
the  holders  of  the  2033  Senior  Notes  on  or  after  February 1,  2017  but  prior  to  February 1,  2019.    We  have 
determined that these specific terms are considered to be embedded derivatives.  Embedded derivatives are required 
to  be  separated  from  the  host  contract,  the  2033  Senior  Notes,  and  carried  at  fair  value  when:  (a)  the  embedded 
derivative possesses economic characteristics that are not clearly and closely related to the economic characteristics 
of the host contract; and (b) a separate, stand-alone instrument with the same terms would qualify as a derivative 
instrument.  We have concluded that the embedded derivatives within the 2033 Senior Notes meet these criteria and, 
as  such,  must  be  valued  separate  and  apart  from  the  2033  Senior  Notes  and  recorded  at  fair  value  each  reporting 
period. 

For  accounting  and  financial  reporting  purposes,  we  combine  these  embedded  derivatives  and  value  them 
together  as one  unit  of  accounting.   At  each  reporting  period, we  record  these  embedded derivatives  at  fair  value 
which is included as a component of the 2033 Senior Notes on our Consolidated Balance Sheets. 

On August 30, 2013, one of the conversion rights in the 2033 Senior Notes was triggered.  Holders of the 2033 
Senior  Notes  converted  $16.9  million  principal  amount  into  2,396,145  shares  of  our  Common  Stock  at  a  rate  of 
141.48 shares of Common Stock per $1,000 principal amount of 2033 Senior Notes.  We recorded a $1.0 million 
non-cash gain related to the conversion.  The gain on exchange is included within Other income (expense) on our 
Consolidated Statement of Operations.   

107 

 
 
 
 
 
 
     
In  June  2014,  we  entered  into  an  exchange  agreement  with  a  holder  of  the  Company’s  2033  Senior  Notes 
pursuant  to  which  such  holder  exchanged  $70.4  million  in  aggregate  principal  amount  of  Notes  for  10,974,431 
shares  of  the  Company’s  Common  Stock  and  approximately  $0.8  million  in  cash  representing  accrued  interest 
through the date of completion of the exchange.  We recorded a $2.7 million non-cash gain related to the exchange.   

On April 1, 2015, we announced that our 2033 Senior Notes are convertible by holders of such notes.  We have 
elected  to  satisfy  our  conversion  obligation  under  the  2033  Senior  Notes  in  shares  of  our  Common  Stock.    This 
conversion  right  was  triggered  because  the  closing  price  per  share  of  our  Common  Stock  has  exceeded  $9.19,  or 
130% of the initial conversion price of $7.07, for at least 3 of 30 consecutive trading days during the period ending 
on March 31, 2015.  The 2033 Senior Notes were convertible until June 30, 2015, and may be convertible thereafter, 
if one or more of the conversion conditions specified in the Indenture, dated as of January 30, 2013, by and between 
the  Company  and  Wells  Fargo  Bank  N.A.,  is  satisfied  during  future  measurement  periods.    Pursuant  to  the 
Indenture, a holder who elects to convert the 2033 Senior Notes will receive 141.4827 shares of our Common Stock 
plus such number of additional shares as is applicable on the conversion date per $1,000 principal amount of 2033 
Senior  Notes  based  on  the  early  conversion  provisions  in  the  Indenture.    On  July 1,  2015,  October 1,  2015  and 
January 5,  2016,  we  announced  that  our  2033  Senior  Notes  continue  to  be  convertible  by  holders  of  such  notes 
during the third quarter of 2015, the fourth quarter of 2015 and the first quarter of 2016, respectively. 

During 2015, pursuant to the conversion right or through exchange agreements we entered with certain holders 
of  our  2033  Senior  Notes,  holders  of  our  2033  Senior  Notes  converted  or  exchanged  $55.4  million  in  aggregate 
principal amount of 2033 Senior Notes for 8,118,062 shares of the Company’s Common Stock.  We recorded a $0.9 
million non-cash gain related to the conversion and exchanges.  The gain is included within Other income (expense) 
in our Consolidated Statement of Operations. 

We  used  a  binomial  lattice  model  in  order  to  estimate  the  fair  value  of  the  embedded  derivative  in  the  2033 
Senior Notes.  A binomial lattice model generates two probable outcomes — one up and another down —arising at 
each point in time, starting from the date of valuation until the maturity date.  A lattice model was initially used to 
determine  if  the  2033  Senior  Notes  would  be  converted,  called  or  held  at  each  decision  point.    Within  the  lattice 
model,  the  following  assumptions  are  made:  (i)  the  2033  Senior  Notes  will  be  converted  early  if  the  conversion 
value is greater than the holding value; or (ii) the 2033 Senior Notes will be called if the holding value is greater 
than both (a) the redemption price (as defined in the Indenture) and (b) the conversion value plus the coupon make-
whole payment at the time.  If the 2033 Senior Notes are called, then the holder will maximize their value by finding 
the optimal decision between (1) redeeming at the redemption price and (2) converting the 2033 Senior Notes. 

Using this lattice model, we valued the embedded derivatives using the “with-and-without method,” where the 
value of the 2033 Senior Notes including the embedded derivatives is defined as the “with,” and the value of the 
2033 Senior Notes excluding the embedded derivatives is defined as the “without.”  This method estimates the value 
of  the  embedded  derivatives  by  looking  at  the  difference  in  the  values  between  the  2033  Senior  Notes  with  the 
embedded derivatives and the value of the 2033 Senior Notes without the embedded derivatives. 

The lattice model requires the following inputs: (i) price of our Common Stock; (ii) Conversion Rate (as defined 
in the Indenture); (iii) Conversion Price (as defined in the Indenture); (iv) maturity date; (v) risk-free interest rate; 
(vi) estimated stock volatility; and (vii) estimated credit spread for the Company. 

The following table sets forth the inputs to the lattice model used to value the embedded derivative: 

Stock price ........................................................
Conversion rate .................................................
Conversion price ...............................................
Maturity date ..................................................... February 1, 2033 
Risk-free interest rate ........................................
Estimated stock volatility ..................................
Estimated credit spread ..................................... 1,142 basis points 

December 31, 2015 December 31, 2014    December 31, 2013
$9.99 
141.4827 
$7.07 
February 1, 2033 
1.40% 
39% 
1,081 basis points 

$8.44 
141.4827 
$7.07 
  February 1, 2033 
1.78% 
55% 

$10.05 
141.4827 
$7.07 

  828 basis points 

1.33% 
50% 

108 

 
 
 
 
 
 
 
 
 
 
 
 
The following table sets forth the fair value of the 2033 Senior Notes with and without the embedded derivatives, 
and the fair value of the embedded derivatives at December 31, 2015, 2014 and 2013.  At December 31, 2015, 2014 
and  2013,  the  principal  amount  of  the  2033  Senior  Notes  was  $32.2  million,  $87.6  million  and  $158.1  million, 
respectively: 

(In thousands) 
Fair value of 2033 Senior Notes: 

December 31, 
2015 

December 31, 
2014 

December 31, 
2013 

With the embedded derivatives ..................................... $
Without the embedded derivatives ............................... $
Estimated fair value of the embedded derivatives ........ $

48,384  $ 
24,647  $ 
23,737  $ 

129,009   $ 
63,062   $ 
65,947   $ 

218,081 
116,994 
101,087 

Changes in certain inputs into the lattice  model can have a significant impact on changes in the estimated fair 
value of the embedded derivatives.  For example, a decrease in our estimated credit spread results in an increase in 
the estimated value of the embedded derivatives.  Conversely, a decrease in the price of our Common Stock results 
in a decrease in the estimated fair value of the embedded derivatives.  For the years ended December 31, 2015 and 
2014, we observed an increase in the market price of our Common Stock which primarily resulted in a $36.6 million 
and $12.2  million  increase, respectively, in  the  estimated  fair  value  of  our  embedded derivatives  recorded  in  Fair 
value changes of derivative instruments, net in our Consolidated Statements of Operations. 

On  November 5,  2015,  Bio-Reference  and  certain  of  its  subsidiaries  entered  into  a  credit  agreement  with 
JPMorgan Chase Bank, N.A. (“CB”), as lender and administrative agent (the “Credit Agreement”), which replaced 
Bio-Reference’s  existing  credit  facility  with  PNC  Bank,  National  Association  (“PNC”).    The  Credit  Agreement 
provides for a $175.0 million secured revolving credit facility and includes a $20.0 million sub-facility for swingline 
loans  and  a  $20.0  million  sub-facility  for the  issuance of  letters  of  credit.    Bio-Reference  may  increase  the  credit 
facility  to  up  to  $275.0  million on  a  secured  basis,  subject  to  the  satisfaction  of  specified  conditions.    The  Credit 
Agreement matures on November 5, 2020 and is guaranteed by all of Bio-Reference’s domestic subsidiaries.  The 
Credit Agreement is also secured by substantially all assets of Bio-Reference and its domestic subsidiaries, as well 
as a non-recourse pledge by us of our equity interest in Bio-Reference.  Availability under the Credit Agreement is 
based  on  a  borrowing  base  comprised  of  eligible  accounts  receivables  of  Bio-Reference  and  certain  of  its 
subsidiaries,  as  specified  therein.    The  proceeds  of  the  new  credit  facility  were  used  to  refinance  existing 
indebtedness,  including  amounts  outstanding  under  the  credit  facility  with  PNC  which  was  terminated  in  2015  in 
accordance with its terms, to finance working capital needs and for general corporate purposes of Bio-Reference and 
its subsidiaries. 

At  Bio-Reference’s  option,  borrowings  under  the  Credit  Agreement  (other  than  swingline  loans)  will  bear 
interest at (i) the CB floating rate (defined as the higher of (a) the prime rate and (b) the LIBOR rate (adjusted for 
statutory reserve requirements for Eurocurrency liabilities) for an interest period of one month plus 2.50%) plus an 
applicable  margin  of  0.35%  for  the  first  12  months  and  0.50%  thereafter  or  (ii)  the  LIBOR  rate  (adjusted  for 
statutory  reserve  requirements  for  Eurocurrency  liabilities)  plus  an  applicable  margin  of  1.35%  for  the  first  12 
months and 1.50% thereafter.  Swingline loans will bear interest at the CB floating rate plus the applicable margin.  
The  Credit  Agreement  also  calls  for  other  customary  fees  and  charges,  including  an  unused  commitment  fee  of 
0.25% of the lending commitments.   

The  Credit  Agreement  contains  customary  covenants  and  restrictions,  including,  without  limitation,  covenants 
that  require  Bio-Reference  and  its  subsidiaries  to  maintain  a  minimum  fixed  charge  coverage  ratio  if  availability 
under the new credit facility falls below a specified amount and to comply with laws, and restrictions on the ability 
of  Bio-Reference  and  its  subsidiaries  to  incur  additional  indebtedness or  to  pay  dividends  and  make  certain  other 
distributions  to  the  Company,  subject  to  certain  exceptions  as  specified  therein.    Failure  to  comply  with  these 
covenants  would  constitute  an  event  of  default  under  the  Credit  Agreement,  notwithstanding  the  ability  of  Bio-
Reference to meet its debt service obligations.  The Credit Agreement also includes various customary remedies for 
the lenders following an event of default, including the acceleration of repayment of outstanding amounts under the 
Credit Agreement and execution upon the collateral securing obligations under the Credit Agreement.  Substantially 
all the assets of Bio-Reference and its subsidiaries are restricted from sale, transfer, lease, disposal or distributions to 
the Company, subject to certain exceptions.  Bio-Reference and its subsidiaries net assets as of December 31, 2015 
was approximately $1.0 billion, which includes goodwill of $441.2 million and intangible assets of $528.3 million. 

We  have  line  of  credit  agreements  with  ten  financial  institutions  as  of  December 31,  2015  and  ten  financial 
institutions as of December 31, 2014 in United States, Chile and Spain.  These lines of credit are used primarily as a 
source of working capital for inventory purchases. 

109 

 
 
 
 
   
 
 
 
 
 
   
 
  
 
 
 
The following table summarizes the amounts outstanding under the Bio-Reference, Chilean and Spanish lines of 

credit: 

(Dollars in thousands) 

Lender 
JP Morgan Chase .................................
Itau Bank .............................................
Bank of Chile .......................................
BICE Bank ..........................................
BBVA Bank ........................................
Penta Bank ...........................................
Security Bank ......................................
Estado Bank .........................................
Santander Bank ....................................
Scotiabank ...........................................
Banco Bilbao Vizcaya .........................

  $

Interest rate 
on borrowings
at  
December 31, 
2015 
3.25% 
6.00% 
5.50% 
5.50% 
5.50% 
7.58% 
6.16% 
5.30% 
5.30% 
5.00% 
2.90% 

Total ................................................  

  $

 Balance Outstanding 

Credit line
capacity 

December 31, 
 2015 

December 31,
2014 

175,000    $
1,500   
2,500   
2,300   
2,300   
—   
150   
2,500   
2,000   
1,300   
273   
189,823    $

72,107    $ 
282   
2,313   
1,502   
1,825   
—   
145   
2,210   
1,345   
939   
—   
82,668    $ 

—
965
1,410
1,249
795
1,008
361
1,870
—
—
—
7,658

At  December 31,  2015  and  2014,  the  weighted  average  interest  rate  on  our  lines  of  credit  was  approximately 

4.3% and 6.1%, respectively. 

At December 31, 2015 and 2014, we had mortgage notes and other debt (excluding the 2033 Senior Notes, the 

Credit Agreement and amounts outstanding under lines of credit) as follows: 

(In thousands) 
Current portion of notes payable ...............................................$
Other long-term liabilities .........................................................
Total mortgage notes and other debt ....................................$

December 31, 

2015 

2014 

1,054   $ 
1,963  
3,017   $ 

608 
2,435 
3,043 

The mortgages and other debts mature at various dates ranging from 2015 through 2024 bearing variable interest 
rates  from  2.4%  up  to  6.3%.    The  weighted  average  interest  rate  on  the  mortgage  notes  and  other  debt  at 
December 31, 2015 and 2014, was 4.3% and 3.4%, respectively.  The mortgages are secured by our office space in 
Barcelona. 

Note 7 Shareholders’ Equity 

Our authorized capital stock consists of 750,000,000 shares of Common Stock, par value $0.01 per share, and 

10,000,000 shares of Preferred Stock, par value $0.01 per share. 

Common Stock 

Subject to the rights of the holders of any shares of Preferred Stock currently outstanding or which may be issued 
in  the future,  the holders  of  the  Common  Stock  are  entitled to  receive dividends from  our  funds  legally  available 
when, as and if declared by our Board of Directors, and are entitled to share ratably in all of our assets available for 
distribution to holders of Common Stock upon the liquidation, dissolution or winding-up of our affairs subject to the 
liquidation preference, if any, of any then outstanding shares of Preferred Stock.  Holders of our Common Stock do 
not have any preemptive, subscription, redemption or conversion rights.  Holders of our Common Stock are entitled 
to one vote per share on all matters which they are entitled to vote upon at meetings of stockholders or upon actions 
taken  by  written  consent  pursuant  to  Delaware  corporate  law.    The  holders  of  our  Common  Stock  do  not  have 
cumulative voting rights, which means that the holders of a plurality of the outstanding shares can elect all of our 
directors.  All of the shares of our Common Stock currently issued and outstanding are fully-paid and nonassessable.  
No dividends have been paid to holders of our Common Stock since our incorporation, and no cash dividends are 
anticipated to be declared or paid on our Common Stock in the reasonably foreseeable future. 

110 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
   
 
 
 
 
 
 
 
 
 
In  addition  to our  equity-based  compensation  plans,  we  have  issued warrants  to purchase  our  Common  Stock.  
Refer  to  Note  9  for  additional  information  on  our  share-based  compensation  plans.    The  table  below  provides 
additional information for warrants outstanding as of December 31, 2015. 

Warrants 

Weighted
average
exercise
price 

Number of
warrants 

Outstanding at December 31, 2014 ....................................  *21,239,213  $
Exercised ............................................................................  (19,034,662)
(30,828)
Expired ............................................................................... 

0.75
0.74  
0.01  

Outstanding and Exercisable at December 31, 2015 ...........

2,173,723  $

0.85

Expiration date 

Various from July 2015 
through March 2017 

Various from 
January 2017 through 
March 2017 

*  Prior year reported amounts adjusted by 190,533 warrants that expired in September 2014. 

Of  the  19,034,662  Common  Stock  warrants  exercised,  1,197,932  shares  were  surrendered  in  lieu  of  a  cash 

payment via the net exercise feature of the warrant agreements. 

Preferred Stock 

Under  our  certificate  of  incorporation,  our  Board  of  Directors  has  the  authority,  without  further  action  by 
stockholders, to designate up to 10 million shares of Preferred Stock in one or more series and to fix or alter, from 
time to time, the designations, powers and rights of each series of Preferred Stock and the qualifications, limitations 
or  restrictions  of  any  series  of  Preferred  Stock,  including  dividend  rights,  dividend  rate,  conversion  rights,  voting 
rights,  rights  and  terms  of  redemption  (including  sinking  fund  provisions),  redemption  price  or  prices,  and  the 
liquidation preference of any wholly issued series of Preferred Stock, any or all of which may be greater than the 
rights of the Common Stock, and to establish the number of shares constituting any such series. 

Of  the  authorized  Preferred  Stock,  4,000,000  shares,  500,000  shares  and  2,000,000  shares  were  designated 
Series A Preferred Stock, Series C Preferred Stock and Series D Preferred Stock, respectively.  As of December 31, 
2015  and  2014,  there  were  no  shares  of  Series A  Preferred  Stock,  Series C  Preferred  Stock  or  Series  D  Preferred 
Stock issued or outstanding. 

Note 8 Accumulated Other Comprehensive Income (Loss) 

For the year ended December 31, 2015, changes in Accumulated other comprehensive income (loss), net of tax, 

were as follows: 

(In thousands) 
Balance at December 31, 2014 .......................................................... $
Other comprehensive income (loss) before reclassifications, net 
of tax(1) ........................................................................................

Amounts reclassified from accumulated other comprehensive 

income (loss), net of tax(1) ...........................................................
Net other comprehensive loss .............................................................
Balance at December 31, 2015 ........................................................  $

(1)  Effective tax rate of 40.13%. 

Foreign 
currency 
translation 

Unrealized 
gain (loss) in 
Accumulated 
OCI 

(6,717 )   $

(5,675)   $

Total 
(12,392)

(15,074)

(2,378)  

(17,452)

—
(15,074)
(21,791 )   $

7,307   
4,929   
(746)   $

7,307
(10,145)
(22,537)

Amounts  reclassified  from  Accumulated  other  comprehensive  income  (loss)  for  the  year  ended  December 31, 
2015  includes  an  other-than-temporary  impairment  charge  on  our  investment  in  RXi  as  discussed  in  Note  4.  
Amounts reclassified for our available for sale investments were based on the specific identification method.   

111 

 
 
 
 
 
 
   
 
   
 
 
 
 
 
 
   
 
For the year ended December 31, 2014, changes in Accumulated other comprehensive income, net of tax, were 

as follows: 

(In thousands) 
Balance at December 31, 2013 .......................................................... $
Other comprehensive income (loss) before reclassifications, net 
of tax(1) ........................................................................................

Amounts reclassified from accumulated other comprehensive 

income, net of tax(1) .....................................................................
Net other comprehensive loss .............................................................
Balance at December 31, 2014 .......................................................... $

(1)  Effective tax rate of 40.13% 

Foreign 
currency 
translation 

Unrealized 
gain (loss) in 
Accumulated 
OCI 

Total 

1,371   $

2,047    $

3,418

(8,088)

(8,044)  

(16,132)

—
(8,088)
(6,717 )   $

322   
(7,722)  
(5,675)   $

322
(15,810)
(12,392)

Amounts  reclassified  from  Accumulated  other  comprehensive  income  (loss)  for  the  year  ended  December 31, 
2014, includes $1.3 million realized gain on the sales of certain of our investments available for sale.  Of the $1.3 
million gain on the sales of our investments available for sale, a $0.9 million gain was reclassified from unrealized 
gains  in  Accumulated  other  comprehensive  income  (loss)  to  Other  income  (expense),  net  for  the  year  ended 
December 31, 2014.  Amounts reclassified from Accumulated other comprehensive income (loss) also includes an 
other-than-temporary impairment charge on our investment in ARNO as discussed in Note 4.  Amounts reclassified 
for our available for sale investments were based on the specific identification method. 

Note 9 Equity-Based Compensation 

We  maintain  five  equity-based  incentive  compensation  plans,  the  Acuity  Pharmaceuticals,  Inc.  2003  Equity 
Incentive Plan, the 2007 Equity Incentive Plan, the 2000 Stock Option Plan, the Bio-Reference Laboratories, Inc. 
2003 Employee Incentive Stock Option Plan, the Modigene Inc. 2005 Stock Incentive Plan and the Modigene Inc. 
2007 Equity Incentive Plan that provide for grants of stock options and restricted stock to our directors, officers, key 
employees  and  certain  outside  consultants.    Equity  awards  granted  under  our  2007  Equity  Incentive  Plan  are 
exercisable for a period of either 7 years or 10 years from the date of grant.  Equity awards granted under our 2000 
Stock Option Plan, 2003 Equity Incentive Plan and the two Modigene Plans are exercisable for a period of up to 10 
years from date of grant.  Vesting periods range from immediate to 5 years.   

We  classify  the  cash  flows  resulting  from  the  tax  benefit  that  arises  when  the  tax  deductions  exceed  the 
compensation cost recognized for those equity awards (excess tax benefits) as financing cash inflows.  There were 
no excess tax benefits for the years ended December 31, 2015, 2014, and 2013. 

Equity-based  compensation  arrangements  to  non-employees  are  accounted  for  at  their  fair  value  on  the 
measurement  date.    The  measurement  of  equity-based  compensation  to  non-employees  is  subject  to  periodic 
adjustment over the vesting period of the equity instruments. 

Valuation and Expense Information 

We recorded equity-based compensation expense of $26.1 million, $14.8 million and $11.0 million for the years 
ended December 31, 2015, 2014, and 2013, respectively, all of which were reflected as operating expenses.  Of the 
$26.1 million of equity based compensation expense recorded in the year ended December 31, 2015, $17.4 million 
was  recorded  as  selling,  general  and  administrative  expenses,  $7.9  million  was  recorded  as  research  and 
development  expenses  and  $0.8  million  was  recorded  as a  cost  of  revenue.    Of  the $14.8  million  of  equity  based 
compensation expense recorded in the year ended December 31, 2014, $9.7 million was recorded as selling, general 
and administrative expense and $5.0 million was recorded as research and development expenses and $0.1 million 
was recorded as a cost of revenue.  Of the $11.0 million of equity based compensation expense recorded in the year 
ended  December 31,  2013,  $7.3  million  was  recorded  as  selling,  general  and  administrative  expense  and  $3.6 
million was recorded as research and development expenses.   

We estimate forfeitures of stock options and recognize compensation cost only for those awards expected to vest.  
Forfeiture rates are determined for all employees and non-employee directors based on historical experience and our 
estimate  of  future  vesting.    Estimated  forfeiture  rates  are  adjusted  from  time  to  time  based  on  actual  forfeiture 
experience. 

112 

 
 
 
   
 
   
 
 
 
 
 
 
   
 
As  of  December 31,  2015,  there  was  $90.8  million  of  unrecognized  compensation  cost  related  to  the  stock 
options granted under our equity-based incentive compensation plans.  Such cost is expected to be recognized over a 
weighted-average period of approximately 3.0 years. 

Stock Options 

We  estimate  the  fair  value  of  each  stock  option  on  the  date  of  grant  using  the  Black-Scholes-Merton  Model 
option-pricing  formula  and  amortize  the  fair  value  to  expense  over  the  stock  option’s  vesting  period  using  the 
straight-line  attribution  approach  for  employees  and  non-employee  directors,  and  for  awards  issued  to  non-
employees  we  recognize  compensation  expense  on  a  graded  basis,  with  most  of  the  compensation  expense  being 
recorded  during  the  initial  periods  of  vesting.    We  apply  the  following  assumptions  in  our  Black-Scholes-Merton 
Model option-pricing formula: 

Expected term (in years) .........
Risk-free interest rate ..............
Expected volatility ..................
Expected dividend yield ..........

Year Ended 
December 31, 
2015 
1.0 - 10.0 
0.26% - 2.42% 
32% - 64% 
0% 

Year Ended 
December 31, 
2014 
1.0 - 10.0 
0.10% - 2.65% 
31% - 72% 
0% 

Year Ended 
December 31, 
2013 
1.0 - 7.0 
0.15% - 2.45% 
31% - 83% 
0% 

Expected Term: The expected term of the stock options granted to employees and non-employee directors was 
calculated  using  the  shortcut  method.    We  believe  this  method  is  appropriate  as  our  equity  shares  have  been 
publicly-traded for a limited period of time and as such we do not have sufficient historical exercise data to provide 
a  reasonable  basis  upon  which  to  estimate  expected  term.    The  expected  term  of  stock  options  issued  to  non-
employee consultants is the remaining contractual life of the options issued. 

Risk-Free  Interest  Rate:  The  risk-free  interest  rate  is  based  on  the  rates  paid  on  securities  issued  by  the  U.S. 

Treasury with a term approximating the expected life of the option. 

Expected Volatility: The expected volatility for stock options with an expected life of 8 years or less was based 
on the historical volatility of our stock.  The expected volatility for stock options with an expected life of 9 years or 
greater  was  based  on  an  average  of  the  volatility  of  a  peer  group  of  publicly-traded  entities  and  the  historical 
volatility of our stock, which we believe will be representative of the volatility over the expected term of the options.  
We believe the use of peer group’s historical volatility is appropriate as our equity shares have not been publicly-
traded for 9 years. 

Expected  Dividend  Yield:  We  do  not  intend  to  pay  dividends  on  Common  Stock  for  the  foreseeable  future.  

Accordingly, we used a dividend yield of zero in the assumptions. 

We  maintain  incentive  stock  plans  that  provide  for  the  grants  of  stock  options  to  our  directors,  officers, 
employees  and  non-employee  consultants.    As  of  December 31,  2015,  there  were  2,056,783  shares  of  Common 
Stock  reserved  for  issuance  under  our  2007  Incentive  Plan.    We  intend  to  issue  new  shares  upon  the  exercise  of 
stock  options.    Stock  options  granted  under  these  plans  have  been  granted  at  an  option  price  equal  to  the  closing 
market value of the stock on the date of the grant.  Stock options granted under these plans to employees typically 
become exercisable over four years in equal annual installments after the date of grant, and stock options granted to 
non-employee directors become exercisable in full one-year after the grant date, subject to, in each case, continuous 
service with us during the applicable vesting period.  We assumed stock options to grant Common Stock as part of 
the mergers with Acuity Pharmaceuticals, Inc., Froptix, Inc., OPKO Biologics and Bio-Reference, which reflected 
various vesting schedules, including monthly vesting to employees and non-employee consultants. 

113 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A summary of option activity under our stock option plans as of December 31, 2015, and the changes during the 

year is presented below: 

Weighted 
average 
exercise 
price 

Weighted 
average 
remaining 
contractual 
term (years)   

Aggregate 
intrinsic value
(in thousands)
104,797

5.4 

  $ 

Options 
Outstanding at December 31, 2014 ....................
Granted ...............................................................
Exercised ............................................................
Forfeited .............................................................
Expired ...............................................................
Outstanding at December 31, 2015 ....................
Vested and expected to vest at December 31, 

2015 ...............................................................
Exercisable at December 31, 2015 .....................

Number of 
options 
23,299,919 $
15,579,500 $
(6,643,991) $
(710,250) $
(238,391) $
31,286,787 $

28,066,315 $
8,779,201 $

5.50  
13.09  
3.93  
9.64  
1.58  
9.55  

9.35  
3.76  

6.97    $ 

63,902

6.82    $ 
3.76    $ 

60,780
41,891

The total intrinsic value of stock options exercised for the years ended December 31, 2015, 2014, and 2013 was 

$69.9 million, $14.6 million and $59.5 million, respectively. 

The  weighted  average  grant  date  fair  value  of  stock  options  granted  for  the  years  ended  December 31,  2015, 
2014, and 2013 was $5.00, $4.64, and $4, respectively.  The total fair value of stock options vested during the years 
ended December 31, 2015, 2014, and 2013 was $13.3 million, $10.9 million and $5.9 million, respectively. 

Restricted Stock 

In 2009, we issued 30,000 shares of restricted Common Stock to one of our independent board members.  The 
restricted stock was granted under our 2007 Equity Incentive Plan with a term of 7 years and vesting occurring 5 
years after the grant date with certain events which would accelerate the vesting of the award.  The restricted stock 
was valued using the grant date fair value which was equivalent to the closing price of our Common Stock on the 
grant date.  We record the cost of restricted stock over the vesting period. 

Note 10 Income Taxes 

We operate and are required to file tax returns in the U.S. and various foreign jurisdictions. 

The benefit (provision) for incomes taxes consists of the following: 

(In thousands) 
Current 

Federal .................................................$
State .....................................................
Foreign .................................................

Deferred 

Federal .................................................
State .....................................................
Foreign .................................................

Total, net ..............................................$

For the years ended December 31, 
2014 

2015 

2013 

430 $

(2,157)
(8,134)
(9,861)

109,286
12,327
1,923
123,536
113,675 $

225 $ 
247
(1,514)
(1,042)

—
(167)
1,185
1,018

(24) $ 

— 
— 
(1,073)
(1,073)

(1,161)
(104)
666 
(599)
(1,672)

114 

 
   
   
   
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Deferred income tax assets and liabilities as of December 31, 2015 and 2014 are comprised of the following: 

(In thousands) 
Deferred income tax assets: 

December 31, 
2015 

December 31, 
2014 

Federal net operating loss ...........................................$
State net operating loss ...............................................
Foreign net operating loss ...........................................
Research and development expense ............................
Research and development tax credit ..........................
Stock options ..............................................................
Accruals ......................................................................
Equity investments ......................................................
Bad debts ....................................................................
Lease liability ..............................................................
Other ...........................................................................
Deferred income tax assets ..............................................
Deferred income tax liabilities: 

Intangible assets ..........................................................
Fixed assets .................................................................
Other ...........................................................................
Deferred income tax liabilities .........................................
Net deferred income tax liabilities ...................................
Valuation allowance ........................................................
Net deferred income tax liabilities ...................................$

71,658    $ 
14,227   
33,701   
5,138   
7,388   
24,756   
7,086   
4,420   
38,809   
7,022   
7,104   
221,309   

63,004 
12,050 
25,825 
9,244 
6,077 
18,422 
1,764 
8,038 
— 
— 
4,702 
149,126 

(386,588)  
(17,072)  
(1,538)  
(405,198)  
(183,889)  
(42,147)  

(226,036)   $ 

(177,074) 
— 
(4,305) 
(181,379) 
(32,253) 
(131,931) 
(164,184) 

The changes in deferred income tax assets, liabilities and valuation allowances at December 31, 2015 reflect the 
acquisition  of  various  legal  entities,  including  the  tax  attributes.    The  acquisitions  were  accounted  for  under  U.S. 
GAAP  as  stock  acquisitions  and  business  combinations.    As  of  December 31,  2015,  we  have  federal,  state  and 
foreign  net  operating  loss  carryforwards  of  approximately  $362.4  million,  $199.9  million  and  $126.6  million, 
respectively, that expire at various dates through 2035.  Included in the foreign net operating losses is $112.9 million 
related to OPKO Biologics.  As of December 31, 2015, we have research and development tax credit carryforwards 
of approximately $7.4 million that expire in varying amounts through 2035.  As of each reporting date, management 
considers new evidence, both positive and negative, that could affect its view of the future realization of deferred tax 
assets.  As a result of the merger with Bio-Reference, OPKO released the full valuation allowance recorded against 
OPKO’s U.S. deferred tax assets, which resulted in an income tax benefit of $93.4 million.   

As  a  result  of  certain  realization  requirements  of  ASC  718,  Compensation  -  Stock  Compensation,  the  table  of 
deferred tax assets and liabilities shown above does not include certain deferred tax assets as of December 31, 2015 
and  2014,  that  arose  directly  from  (or  the  use  of  which  was  postponed  by)  tax  deductions  related  to  equity 
compensation that are greater than the compensation recognized for financial reporting.  Equity will be increased by 
$33.9 million if and when such deferred tax assets are ultimately realized.  The Company uses ASC 740 ordering 
when determining when excess tax benefits have been realized. 

Under Section 382 of the Internal Revenue Code of 1986, as amended, certain significant changes in ownership 
may restrict the future utilization of our income tax loss carryforwards and income tax credit carryforwards in the 
U.S.  The annual limitation is equal to the value of our stock immediately before the ownership change, multiplied 
by the long-term tax-exempt rate (i.e., the highest of the adjusted Federal long-term rates in effect for any month in 
the three-calendar-month period ending with the calendar month in which the change date occurs).  This limitation 
may be increased under the IRC§ 338 Approach (IRS approved methodology for determining recognized Built-In 
Gain).  As a result, federal net operating losses and tax credits may expire before we are able to fully utilize them. 

During  2008,  we  conducted  a  study  to  determine  the  impact  of  the  various  ownership  changes  that  occurred 
during  2007  and  2008.    As  a  result,  we  have  concluded  that  the  annual  utilization  of  our  net  operating  loss 
carryforwards  (“NOLs”)  and  tax  credits  is  subject  to  a  limitation  pursuant  to  Internal  Revenue  Code  section  382.  
Under  the  tax  law,  such  NOLs  and  tax  credits  are  subject  to  expiration  from  15  to  20  years  after  they  were 
generated.    As  a  result  of  the  annual  limitation  that  may  be  imposed  on  such  tax  attributes  and  the  statutory 
expiration period, some of these tax attributes may expire prior to our being able to use them.  There is no current 
impact on these financial statements as a result of the annual limitation.  This study did not conclude as to whether 

115 

 
 
 
 
 
 
 
 
   
 
 
eXegenics’  pre-merger  NOLs  were  limited  under  Section 382.    As  such,  of  the  $362.4  million  of  federal  net 
operating loss carryforwards, at least approximately $50.9 million may not be able to be utilized. 

Uncertain Income Tax Positions 

We  file  federal  income  tax  returns  in  the  U.S.  and  various  foreign  jurisdictions,  as  well  as  with  various  U.S. 
states and the Ontario and Quebec provinces in Canada.  We are subject to routine tax audits in all jurisdictions for 
which  we  file  tax  returns.    Tax  audits  by  their  very  nature  are  often  complex  and  can  require  several  years  to 
complete.    It  is  reasonably  possible  that  some  audits  will  close  within  the  next  twelve  months,  which  we  do  not 
believe would result in a material change to our accrued uncertain tax positions.  Additionally, included in income 
tax expense is an accrual of $2.3 million related to uncertain tax positions involving income recognition from the 
Pfizer Transaction.  We recognize that local tax law is inherently complex and the local taxing authorities may not 
agree  with  certain  tax  positions  taken.    Consequently,  it  is  reasonably  possible  that  ultimate  resolution  of  these 
matters  in  any  jurisdiction  may  be  significantly  more  or  less  than  estimated.    We  evaluated  the  estimated  tax 
exposure  for  a  range  of  current  likely  outcomes  to  be  from  $0  to  approximately  $50.0  million  and  recorded  our 
accrual to reflect our best expectation of ultimate resolution.   

U.S.  Federal:  Under  the  tax  statute  of  limitations  applicable  to  the  Internal  Revenue  Code,  we  are  no  longer 
subject to U.S. federal income tax examinations by the Internal Revenue Service for years before 2012.  However, 
because we are carrying forward income tax attributes, such as net operating losses and tax credits from 2012 and 
earlier tax years, these attributes can still be audited when utilized on returns filed in the future. 

State: Under the statutes of limitation applicable to most state income tax laws, we are no longer subject to state 
income  tax  examinations  by  tax  authorities  for  years  before  2012  in  states  in  which  we  have  filed  income  tax 
returns.  Certain states may take the position that we are subject to income tax in such states even though we have 
not filed income tax returns in such states and, depending on the varying state income tax statutes and administrative 
practices, the statute of limitations in such states may extend to years before 2012. 

Foreign: Under the statutes of limitations applicable to our foreign operations, we are generally no longer subject 

to tax examination for years before 2010 in jurisdictions where we have filed income tax returns. 

Unrecognized Tax Benefits 

As  of  December 31,  2015,  2014,  and  2013,  the  total  amount  of  gross  unrecognized  tax  benefits  was 
approximately $8.6 million, $5.9 million, and $9.2 million, respectively.  As of December 31, 2015, the total gross 
unrecognized tax benefit of $8.6 million consisted of increases of $3.5 million as a result of current year activity, 
and decreases of $0.8 million as a result of the lapse of statutes of limitations.  As of December 31, 2015, the total 
amount of unrecognized tax benefits that, if recognized, would affect our effective income tax rate was $0.7 million.  
We  account  for  any  applicable  interest  and  penalties  on  uncertain  tax  positions  as  a  component  of  income  tax 
expense.  As  of  December 31,  2014  and  2013,  $0.9  million  and  $0.2  million  of  the  unrecognized  tax  benefits,  if 
recognized,  would  have  affected  our  effective  income  tax  rate.    We  believe  it  is  reasonably  possible  that 
approximately $0.1 million of unrecognized tax benefits may be recognized within the next twelve months. 

The following summarizes the changes in our gross unrecognized income tax benefits. 

For the years ended December 31, 
2014 

2013 

2015 

5,890   $
955  
2,543  
(176)  
(617)  
—  
8,595   $

9,231    $ 
524   
193   
(396)  
(472)  
(3,190)  
5,890    $ 

9,245
58
517
(589)
—
—
9,231

(In thousands) 
Unrecognized tax benefits at beginning of period .....................$
Gross increases – tax positions in prior period ..........................
Gross increases – tax positions in current period ......................
Gross decreases – tax positions in prior period .........................
Lapse of statute of limitations ...................................................
Settlements ................................................................................
Unrecognized tax benefits at end of period ...............................$

116 

 
 
 
 
 
 
 
 
   
 
Other Income Tax Disclosures 

The significant elements contributing to the difference between the federal statutory tax rate and the effective tax 

rate are as follows: 

For the years ended December 31, 
2014 

2015 

2013 

Federal statutory rate .............................................................
State income taxes, net of federal benefit ..............................
Foreign income tax ................................................................
Research and development tax credits ...................................
Non-deductible components of convertible debt ...................
Valuation allowance ..............................................................
Other ......................................................................................
Total ..................................................................................

35.0 % 
2.8 % 
(7.8 )% 
— % 
(9.4 )% 
61.1 % 
(1.7 )% 
80.0 % 

35.0 %  
2.5 %  
(10.3 )%  
1.1 %  
(3.8 )%  
(25.3 )%  
0.8 %  
— %  

35.0 %
2.4 %
(7.9 )%
1.0 %
(16.7 )%
(11.4 )%
(3.9 )%
(1.5 )%

The following table reconciles our losses before income taxes between U.S. and foreign jurisdictions: 

(In thousands) 
Pre-tax loss: 

For the years ended December 31, 
2014 

2015 

2013 

U.S. .............................................................................$
Foreign ........................................................................
Total ........................................................................$

(113,612)   $
(30,091)  
(143,703)   $

(84,075)  $ 
(87,567)  
(171,642)   $ 

(74,861)
(37,874)
(112,735)

No  additional  provision  has  been  made  for  U.S.  or  foreign  income  taxes  on  the  undistributed  earnings  of 
subsidiaries  or  for  unrecognized  deferred  tax  liabilities  for  temporary  differences  related  to  investments  in 
subsidiaries, as such earnings are expected to be permanently reinvested. 

Note 11 Related Party Transactions 

In  February  2014,  Dr.  Frost,  our  Chairman  and  Chief  Executive  Officer,  paid  a  filing  fee  of  $280,000  to  the 
Federal Trade Commission (the “FTC”) under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (“HSR 
Act”) in connection with filings made by us and Dr. Frost.  We reimbursed Dr. Frost for the HSR filing fee.   

In  October,  2013,  we  paid  the  $170,000  filing  fee  to  the  FTC  in  connection  with  filings  made  by  us  and  Dr. 

Hsiao, our Vice Chairman of the Board and Chief Technical Officer, under the HSR Act.   

We  hold  investments  in  Zebra  (ownership  29%),  Sevion  (3%),  Neovasc  (4%),  ChromaDex  Corporation  (2%), 
MabVax (1%), and ARNO (4%).  These investments were considered related party transactions as a result of our 
executive management’s ownership interests and/or board representation in these entities.  See further discussion of 
our investments in Note 4.  In July 2015, we made an additional $500 thousand investment in a private placement 
transaction  with  Sevion  pursuant  to  which  we  acquired  66,667  shares  of  Series  C  Convertible  Preferred  Stock 
convertible  into  666,667  shares  of  common  stock  and  warrants  to  purchase  333,333  shares  of  common  stock.    In 
October 2015, we made an additional $375 thousand investment in MabVax pursuant to which we acquired 340,909 
shares of common stock at $1.10 and 170,454 warrants to purchase shares of common stock.  In November 2015, we 
made an additional $1.0 million investment in Zebra pursuant to which we acquired 420,000 shares of Series A-2 
Preferred Stock.   

In  August  2013,  we  acquired  OPKO  Biologics  (formerly  PROLOR)  pursuant  to  an  Agreement  and  Plan  of 
Merger  dated  as  of  April 23,  2013  in  an  all-stock  transaction.   Until  completion  of  the  acquisition,  Dr.  Frost  was 
PROLOR’s Chairman of the Board and a greater than 5% stockholder of PROLOR.  Dr. Hsiao and Mr. Rubin were 
also directors and less than 5% stockholders of PROLOR.   

In January 2013, we sold $175.0 million aggregate principal amount of 2033 Senior Notes in a private placement 
in  reliance  on  exemptions  from  registration  under  the  Securities  Act.    The  Purchasers  of  the  2033  Senior  Notes 
include the Gamma Trust and Hsu Gamma.  The 2033 Senior Notes were issued on January 30, 2013. 

During  the  years  ended  December 31,  2014,  and  2013,  FineTech  recorded  revenue  of  $0.3  million  and  $0.3 
million, respectively, for the sale of APIs to Teva Pharmaceutical Industries, Limited (“Teva”).  Dr. Frost previously 

117 

 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
   
 
served as the Chairman of the Board of Directors of Teva until 2015.  No revenue was recorded for the year ended 
December 31, 2015. 

In 2012, we made a $1.7 million investment in Biozone.  Effective January 2, 2014, Biozone completed a merger 
with Cocrystal Discovery, Inc. (“Cocrystal”), another entity in which we had an equity investment.  The name of the 
issuer  was  changed  to  Cocrystal  Pharma,  Inc.  (“COCP”).    Dr.  Frost  previously  invested  in  both  Biozone  and 
Cocrystal.    Effective  January 16,  2014,  we  invested  an  additional  $0.5  million  in  the  company  as  part  of  a  $2.75 
million  private  placement  and  received  1.0  million  shares  of  common  stock  and  1.0  million  10-year  warrants 
exercisable at $0.50 per share.  At December 31, 2015, we hold an 8% ownership interest in COCP. 

We lease office space from  Frost Real Estate Holdings, LLC (“Frost Holdings”) in Miami, Florida, where our 
principal  executive  offices  are  located.    Effective  May 28,  2015,  we  entered  into  an  amendment  to  our  lease 
agreement with Frost Holdings.  The lease, as amended, is for approximately 25,000 square feet of space.  The lease 
provides  for  payments  of  approximately  $66  thousand  per  month  in  the  first  year  increasing  annually  to  $75 
thousand  per  month  in  the  fifth  year,  plus  applicable  sales  taxes.    The  rent  is  inclusive  of  operating  expenses, 
property taxes and parking.  The rent was reduced by $216 thousand for the cost of tenant improvements. 

Our wholly-owned subsidiary, Bio-Reference purchases and uses certain products acquired from InCellDx, Inc., 

a company in which we hold a 27% minority interest in. 

We reimburse Dr. Frost for Company-related use by Dr. Frost and our other executives of an airplane owned by 
a company that is beneficially owned by Dr. Frost.  Prior to 2015, we reimbursed Dr. Frost in an amount equal to the 
cost of a first class airline ticket between the travel cities for each executive, including Dr. Frost, traveling on the 
airplane for Company-related business.  Beginning in the first quarter of 2015, we reimburse Dr. Frost for out-of-
pocket operating costs for the use of the airplane by Dr. Frost or Company executives for Company-related business.  
We do not reimburse Dr. Frost for personal use of the airplane by Dr. Frost or any other executive.  For the years 
ended December 31, 2015, 2014, and 2013, we recognized approximately $595 thousand, $175 thousand, and $93 
thousand, respectively, for Company-related travel by Dr. Frost and other OPKO executives. 

Note 12 Employee Benefit Plans 

Effective  January 1,  2007,  the  OPKO  Health  Savings  and  Retirement  Plan  (the  “Plan”)  permits  employees  to 
contribute  up  to  100%  of  qualified  pre-tax  annual  compensation  up  to  annual  statutory  limitations.    The 
discretionary company match for employee contributions to the Plan is 100% up to the first 4% of the participant’s 
earnings  contributed  to  the  Plan.    Our  matching  contributions  to  the  Plan  were  approximately  $0.8  million,  $0.6 
million and $0.5 million for the years ended December 31, 2015, 2014, and 2013 respectively. 

Bio-Reference Laboratories, Inc. sponsors a 401(k) Profit-Sharing Plan (the “Plan”).  Employees become eligible 
for  participation  after  attaining  the  age of  eighteen  and  completing  one  year  of  service.   Participants  may  elect  to 
contribute up to 60% of their compensation, as defined in the Plan, to a maximum allowed by the Internal Revenue 
Service.  Bio-Reference makes a matching contribution to the plan for each participant who has elected to make tax-
deferred contributions.  The discretionary company match for employee contributions to the Plan is 100% up to the 
first 3% of the participant’s earnings contributed to the Plan, with an annual maximum match of $1 thousand.   Bio-
Reference Laboratories, Inc. elected to make a matching contribution which amounted to $1.5 million for the year 
ended December 31, 2015. 

GeneDx, Inc. sponsors a 401(k) Profit-Sharing Plan (the “Plan”).  Employees become eligible for participation 
after attaining the age of eighteen and completing one month of service.  Participants may elect to contribute up to 
100%  of  their  compensation,  as  defined  in  the  Plan,  to  a  maximum  allowed  by  the  Internal  Revenue  Service.  
GeneDx, Inc. makes a matching contribution to the plan for each participant who has elected to make tax-deferred 
contributions.  The discretionary company match for employee contributions to the Plan is 100% up to the first 3%, 
plus  50%  of  the  next  2%  of  the  participant’s  earnings  contributed  to  the  Plan.    GeneDx,  Inc.  elected  to  make  a 
matching contribution which amounted to $0.8 million for the year ended December 31, 2015. 

Note 13 Commitments and Contingencies 

In connection with our acquisitions of CURNA, OPKO Diagnostics, OPKO Health Europe and OPKO Renal, we 
agreed  to  pay  future  consideration  to  the  sellers  upon  the  achievement  of  certain  events.    As  a  result,  as  of 
December 31,  2015,  we  recorded  $54.4  million  as  contingent  consideration,  with  $22.2  million  recorded  within 
Accrued expenses and $32.3 million recorded within Other long-term liabilities in the accompanying Consolidated 
Balance  Sheets.    Refer  to  Note  5.    During  the  year  ended  December 31,  2015,  we  satisfied  a  $20.0  million 
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contingent payment to the former owners of OPKO Renal through the issuance of 1,194,337 shares of our common 
stock in the third quarter of 2015. 

In  July  2012,  OPKO  Lab  received  a  letter  from  AdvanceMed  Corporation  (“AdvanceMed”)  regarding  a  post-
payment review conducted by AdvanceMed (the “Post-Payment Review Letter”).  The Post-Payment Review Letter 
originated  with  a  post  payment  review  audit  by  AdvanceMed  of  183  claims  submitted  by  OPKO  Lab  to  the 
Medicare  program.    OPKO  Lab  believes  that  its  billing  practices  were  appropriate  and  it  is  following  the  appeal 
process set forth by Medicare.  OPKO Lab received a partially favorable determination, which reduced the amount 
of the alleged overpayment, and it continues to appeal the remaining alleged overpayments.  No assurances can be 
given about the outcome of the appeal. 

On or around October 21, 2014, we received a Civil Investigative Demand (“Demand”) from the U.S. Attorney’s 
Office  for  the  Middle  District  of  Tennessee  (“Attorney’s  Office”).    The  Demand  concerns  an  investigation  of 
allegations  that  the  Company  or  one  of  its  affiliated  entities  or  other  parties  submitted  false  claims  for  payment 
related to services provided to government healthcare program beneficiaries in violation of the False Claims Act, 31 
U.S.C. Section 3729.  We are fully cooperating with the investigation and are producing documents responsive to 
the Demand.  It is too early to assess the range of loss, if any. 

Following the announcement of entry into an agreement and plan of merger with Bio-Reference, four putative 
class  action  complaints  challenging  the  merger were  filed  in  the  Superior  Court of New  Jersey  in Bergen  County 
(the  “Court”).    The  parties  executed  a  stipulated  consent  order  that  the  actions  would  be  consolidated  for  all 
purposes,  including  trial,  in  the  Chancery  Division  under  Docket  No.  C-207-15,  bearing  the  caption  In  re  Bio-
Reference  Laboratories,  Inc.  Shareholder  Litigation  (the  “Consolidated  Action”).    The  complaints  name  Bio-
Reference, OPKO, a wholly-owned merger subsidiary of OPKO (“Merger Sub”) and members of the Bio-Reference 
board as defendants.  The complaints generally allege, among other things, that members of the Bio-Reference board 
breached their fiduciary duties to Bio-Reference’s shareholders by agreeing to sell Bio-Reference for an inadequate 
price  and  agreeing  to  inappropriate  deal  protection  provisions  in  the  merger  agreement  that  may  preclude  Bio-
Reference from soliciting any potential acquirers and limit the ability of the Bio-Reference board to act with respect 
to investigating and pursuing superior proposals and alternatives.  In August, the parties executed a memorandum of 
understanding  reflecting  terms  of  a  settlement,  which  was  replaced  in  September  2015  by  a  stipulation  and 
agreement of compromise, settlement and release resolving all matters between them.  In January 2016, the Court 
entered  an  order  finally  approving  the  settlement. The  settlement  did  not  have  a  material  impact  on  our  business, 
financial condition, results of operations or cash flows. 

Under a license agreement one of our subsidiaries has with Washington University in St. Louis, we are obligated 
to pay Washington University a single digit percentage of any sublicensing payment we receive in connection with a 
sublicense  of  our  rights  to  Washington  University  patents  subject  to  certain  exceptions.   In  connection  with  the 
Pfizer Transaction, we sublicensed to Pfizer the sole remaining patent licensed to us by Washington University and 
paid  to  Washington  University  the  sublicensing  payment  we  believe  is  due  under  the  license  agreement.  
Washington University has questioned the computation of the sublicense payment and has notified us that it would 
like  to  review  additional  information  relating  to  the  sublicense  and  the  Pfizer  Transaction  to  determine  whether 
additional amounts are owed to it. 

We  accrue  a  liability  for  legal  contingencies  when  we  believe  that  it  is  both  probable  that  a  liability  has  been 
incurred and that we can reasonably estimate the amount of the loss.  We review these accruals and adjust them to 
reflect  ongoing  negotiations,  settlements,  rulings,  advice  of  legal  counsel  and  other  relevant  information.    To  the 
extent  new  information  is  obtained  and  our  views  on  the  probable  outcomes  of  claims,  suits,  assessments, 
investigations  or  legal  proceedings  change,  changes  in  our  accrued  liabilities  would  be  recorded  in  the  period  in 
which such determination is made.  For the matters referenced in the paragraph below, the amount of liability is not 
probable or the amount cannot be reasonably estimated; and, therefore, accruals have not been made.  In addition, in 
accordance  with  the  relevant  authoritative  guidance,  for  matters  which  the  likelihood  of  material  loss  is  at  least 
reasonably possible, we provide disclosure of the possible loss or range of loss; however, if a reasonable estimate 
cannot be made, we will provide disclosure to that effect. 

We are a party to other litigation in the ordinary course of business.  We do not believe that any such litigation 

will have a material adverse effect on our business, financial condition, results of operations or cash flows. 

We  expect  to  incur  substantial  losses as  we continue  the development  of our product  candidates,  continue our 
other  research  and  development  activities,  and  establish  a  pharmaceutical  sales  and  marketing  infrastructure  in 
anticipation  of  the  commercialization  of  our  pharmaceutical  product  candidates.    We  currently  have  limited 

119 

 
pharmaceutical commercialization capabilities, and it is possible that we may never successfully commercialize any 
of our diagnostic and pharmaceutical product candidates.  We do not currently generate significant revenue from any 
of our diagnostic and pharmaceutical product candidates.  Our research and development activities are budgeted to 
expand over a period of time and will require further resources if we are to be successful.  As a result, we believe 
that our operating losses are likely to be substantial over the next several years.  We may need to obtain additional 
funds  to  further  develop  our  research  and  development  programs,  and  there  can  be  no  assurance  that  additional 
capital will be available to us on acceptable terms, or at all. 

We  have  employment  agreements  with  certain  executives  which  provide  for  compensation  and  certain  other 

benefits and for severance payments under certain circumstances. 

At December 31, 2015, we were committed to make future purchases for inventory and other items in 2016 that 
occur  in  the  ordinary  course  of  business  under  various  purchase  arrangements  with  fixed  purchase  provisions 
aggregating $48.3 million. 

Note 14 Strategic Alliances 

Pfizer Inc 

We plan to develop a portfolio of product candidates through a combination of internal development and external 
partnerships.  In December 2014, we entered into an exclusive worldwide agreement with Pfizer Inc. (“Pfizer”) for 
the  development  and  commercialization  of  our  long-acting  hGH-CTP  for  the  treatment  of  growth  hormone 
deficiency (“GHD”) in adults and children, as well as for the treatment of growth failure in children born small for 
gestational age (“SGA”) (the “Pfizer Transaction”). 

The Pfizer Transaction closed in January 2015 following the termination of the waiting period under the Hart-
Scott-Rodino  Act.    Under  the  terms  of  the  Pfizer  Transaction,  we  received  non-refundable  and  non-creditable 
upfront  payments  of  $295.0  million  and  are  eligible  to  receive  up  to  an  additional  $275.0  million  upon  the 
achievement  of  certain  regulatory  milestones.    Pfizer  received  the  exclusive  license  to  commercialize  hGH-CTP 
worldwide.    In  addition,  we  are  eligible  to  receive  initial  tiered  royalty  payments  associated  with  the 
commercialization of hGH-CTP for Adult GHD with percentage rates ranging from the high teens to mid-twenties.  
Upon the launch of hGH-CTP for Pediatric GHD in certain major markets, the royalties will transition to regional, 
tiered gross profit sharing for both hGH-CTP and Pfizer’s Genotropin®. 

The  agreement  with  Pfizer  will  remain  in  effect  until  the  last  sale  of  the  licensed  product,  unless  earlier 
terminated as permitted under the agreement.  In addition to termination rights for material breach and bankruptcy, 
Pfizer is permitted to terminate the Agreement in its entirety, or with respect to one or more world regions, without 
cause after a specified notice period.  If the Agreement is terminated by us for Pfizer’s uncured material breach, or 
by Pfizer without cause, provision has been made for transition of product and product responsibilities to us for the 
terminated regions, as well as continued supply of product by Pfizer or transfer of supply to us in order to support 
the terminated regions. 

We  will  lead  the  clinical  activities  and  will  be  responsible  for  funding  the  development  programs  for  the  key 
indications,  which  includes  Adult  and  Pediatric  GHD  and  Pediatric  SGA.    Pfizer  will  be  responsible  for  all 
development costs for additional indications as well as all post-marketing studies.  In addition, Pfizer will fund the 
commercialization  activities  for  all  indications  and  lead  the  manufacturing  activities  covered  by  the  global 
development plan. 

For  revenue  recognition  purposes,  we  viewed  the  Pfizer  Transaction  as  a  multiple-element  arrangement.  
Multiple-element arrangements are analyzed to determine whether the various performance obligations, or elements, 
can  be  separated  or  whether  they  must  be  accounted  for as  a  single  unit  of  accounting.    We  evaluated  whether  a 
delivered  element  under  an  arrangement  has  standalone  value  and  qualifies  for  treatment  as  a  separate  unit  of 
accounting.    Deliverables  that  do  not  meet  these  criteria  are  not  evaluated  separately  for  the  purpose  of  revenue 
recognition.  For a single unit of accounting, payments received are recognized in a manner consistent with the final 
deliverable.    We  determined  that  the  deliverables  under  the  Pfizer  Transaction,  including  the  licenses  granted  to 
Pfizer, as well as our obligations to provide various research and development services, will be accounted for as a 
single unit of account.  This determination was made because the ongoing research and development services to be 
provided by us are essential to the overall arrangement as we have significant knowledge and technical know-how 
that is important to realizing the value of the licenses granted.  The performance period over which the revenue will 
be recognized is expected to continue from the first quarter of 2015 through 2019, when we anticipate completing 
the  various  research  and  development  services  that  are  specified  in  the  Pfizer  Transaction  and  our  performance 
120 

 
obligations are completed.  We will continue to review the timing of when our research and development services 
will  be  completed  in  order  to  assess  that  the  estimated  performance  period  over  which  the  revenue  is  to  be 
recognized is appropriate.  Any significant changes in the timing of the performance period will result in a change in 
the revenue recognition period. 

We  are  recognizing  the  non-refundable  $295.0  million  upfront  payments  on  a  straight-line  basis  over  the 
performance  period.    We  recognized  $65.5  million  of  revenue  related  to  the  Pfizer  Transaction  in  Revenue  from 
transfer of  intellectual  property  in  our  Consolidated  Statement  of  Operations during  the  year  ended December 31, 
2015,  and had  deferred revenue  related  to the  Pfizer  Transaction of $229.5  million  at December 31,  2015.    As of 
December 31, 2015, $70.6 million of deferred revenue related to the Pfizer Transaction was classified in Accrued 
expenses and $158.9 million was classified in Other long-term liabilities in our Consolidated Balance Sheet.  During 
the  year  ended  December 31,  2015,  we  incurred  $55.3  million  in  research  and  development  expenses  related  to 
hGH-CTP. 

The  Pfizer  Transaction  includes  milestone  payments  of  $275.0  million  upon  the  achievement  of  certain 
milestones.    The  milestones  range  from  $20.0  million  to  $90.0  million  each  and  are  based  on  achievement  of 
regulatory approval in the U.S. and regulatory approval and price approval in other major markets.  We evaluated 
each  of  these  milestone  payments  and  believe  that  all  of  the  milestones  are  substantive  as  (i)  there  is  substantive 
uncertainty  at  the  close  of  the  Pfizer  Transaction  that  the  milestones  would  be  achieved  as  approval  from  a 
regulatory  authority  must  be  received  to  achieve  the  milestones  which  would  be  commensurate  with  the 
enhancement  of  value of  the underlying  intellectual  property,  (ii)  the  milestones relate  solely  to past  performance 
and (iii) the amount of the milestone is reasonable in relation to the effort expended and the risk associated with the 
achievement of the milestone.  The milestone payments will be recognized as revenue in full in the period in which 
the associated milestone is achieved, assuming all other revenue recognition criteria are met.  To date, no revenue 
has been recognized related to the achievement of the milestones. 

In the first quarter of 2015, we made a payment of $25.9 million to the Office of the Chief Scientist of the Israeli 
Ministry of Economy (“OCS”) in connection with repayment obligations resulting from grants previously made by 
the OCS to OPKO Biologics to support development of hGH-CTP and the outlicense of the technology outside of 
Israel.    We  recognized  the  $25.9  million  payment  in  Grant  repayment  expense  in  our  Consolidated  Statement  of 
Operations during the year ended December 31, 2015. 

TESARO 

In  November  2009,  we  entered  into  an  asset  purchase  agreement  (the  “NK-1  Agreement”)  under  which  we 
acquired  VARUBI™  (rolapitant)  and  other  neurokinin-1  (“NK-1”)  assets  from  Merck.    In  December 2010,  we 
entered into an exclusive license agreement with TESARO, in which we out-licensed the development, manufacture, 
commercialization and distribution of our lead NK-1 candidate, VARUBI™ (the “TESARO License”).  Under the 
terms  of  the  license,  we  received  a  $6.0  million  upfront  payment  from  TESARO  and  are  eligible  to  receive 
milestone payments of up to $30.0 million upon achievement of certain regulatory and commercial sale milestones 
(of which $20.0 million has been received to date) and additional commercial  milestone payments  of up to $85.0 
million if specified levels of annual net sales are achieved.  During the years ended December 31, 2015 and 2014, 
$15.0  million  and  $5.0  million  of  revenue,  respectively,  has  been  recognized  related  to  the  achievement  of  the 
milestones under the TESARO License.  TESARO is also obligated to pay us tiered royalties on annual net sales 
achieved  in  the  United  States  and  Europe  at  percentage  rates  that  range  from  the  low  double  digits  to  the  low 
twenties,  and  outside  of  the  United  States  and  Europe  at  low  double-digit  percentage  rates.    TESARO  assumed 
responsibility  for  clinical  development  and  commercialization  of  licensed  products  at  its  expense.    Under  the 
Agreement,  we  will  continue  to  receive  royalties  on  a  country-by-country  and  product-by-product  basis  until  the 
later of the date that all of the patent rights licensed from us and covering VARUBI™ expire, are invalidated or are 
not enforceable and 12 years from the first commercial sale of the product. 

If TESARO elects to develop and commercialize VARUBI™ in Japan through a third-party licensee, TESARO 
will share equally with us all amounts it receives in connection with such activities, subject to certain exceptions and 
deductions.  In addition, we will have an option to market the products in Latin America. 

The term of the license will remain in force until the expiration of the royalty term in each country, unless we 
terminate the license earlier for TESARO’s material breach of the license or bankruptcy.  TESARO has a right to 
terminate the license at any time during the term for any reason on three months’ written notice. 

121 

 
TESARO’s New Drug Application (“NDA”) for approval of oral VARUBI™, a neurokinin-1 receptor antagonist 
in development for the prevention of chemotherapy-induced nausea and vomiting, was approved by the U.S. FDA in 
September 2015, and in November 2015, TESARO announced the commercial launch of VARUBI™ in the United 
States.    Under  the  terms  of  the  NK-1  Agreement,  upon  approval  by  the  FDA  of  the  TESARO’s  NDA  for  oral 
VARUBI™, we were required to pay Merck a $5.0 million milestone payment.  In addition, $5.0 million will be due 
and  payable  each  year  thereafter  for  the  next  four  (4)  years  on  the  anniversary  date  of  the  NDA  approval.    We 
recognized  the  present  value  of  the  milestone  payments  on  FDA  approval  of  $23.0  million  as  an  intangible  asset 
which will be amortized to expense over the expected useful life of the asset, which is approximately 13 years.  The 
present value of the future payments to Merck of $18.2 million at December 31, 2015 is recorded as a liability in our 
Consolidated Balance Sheet with $5.0 million in Accrued expenses and $13.2 million in Other long-term liabilities. 

Pharmsynthez 

In April 2013, we entered into a series of concurrent transactions with Pharmsynthez, a Russian pharmaceutical 
company  traded  on  the  Moscow  Stock  Exchange  pursuant  to  which  we  acquired  an  equity  method  investment  in 
Pharmsynthez (ownership 17%).  We also granted rights to certain technologies in the Russian Federation, Ukraine, 
Belarus, Azerbaijan and Kazakhstan (the “Territories”) to Pharmsynthez and agreed to perform certain development 
activities.  We will receive from Pharmsynthez royalties on net sales of products incorporating the technologies in 
the  Territories,  as  well  as  a  percentage  of  any  sublicense  income  from  third  parties  for  the  technologies  in  the 
Territories.  

In July 2015, we entered into a Note Purchase Agreement with Pharmsynthez pursuant to which we delivered 
$3.0  million  to  Pharmsynthez  in  exchange  for  a  $3.0  million  note  (the  “Pharmsynthez  Note  Receivable”).    The 
Pharmsynthez Note Receivable is due on or before July 1, 2016, and Pharmsynthez  may satisfy the note either in 
cash  or  shares  of  its  capital  stock.    We  recorded  the  Pharmsynthez  Note  Receivable  within  Prepaid  expenses  and 
other current assets in our Consolidated Balance Sheet. 

RXi Pharmaceuticals Corporation 

In March 2013, we completed the sale to RXi of substantially all of our assets in the field of RNA interference 
(the “RNAi Assets”) (collectively, the “Asset Purchase Agreement”).  In accounting for the sale of the RNAi Assets, 
we determined that we did not have any continuing involvement in the development of the RNAi Assets or any other 
future  performance  obligations  and,  as  a  result,  during  the  year  ended  December 31,  2013,  we  recognized  $12.5 
million of Revenue from transfer of intellectual property in our Consolidated Statement of Operations. 

Pursuant  to  the  Asset  Purchase  Agreement,  RXi  will  be  required  to  pay  us  up  to  $50.0  million  in  milestone 
payments  upon  the  successful  development  and  commercialization  of  each  drug  developed  by  RXi,  certain  of  its 
affiliates or any of its or their licensees or sublicensees utilizing patents included within the RNAi Assets (each, a 
“Qualified  Drug”).    In  addition,  RXi  will  also  be  required  to  pay  us  royalties  equal  to:  (a) a  mid  single-digit 
percentage of “Net Sales” (as defined in the Asset Purchase Agreement) with respect to each Qualified Drug sold for 
an ophthalmologic use during the applicable “Royalty Period” (as defined in the Asset Purchase Agreement); and 
(b) a low single-digit percentage of net sales with respect to each Qualified Drug sold for a non-ophthalmologic use 
during the applicable royalty period. 

Other 

We have completed strategic deals with UT Southwestern, Washington University, INEOS Healthcare, TSRI, the 
President  and  Fellows  of  Harvard  College,  and  Academia  Sinica,  among  others.    In  connection  with  these 
agreements, upon the achievement of certain milestones we are obligated to make certain payments and have royalty 
obligations upon sales of products developed under the license agreements.  At this time, we are unable to estimate 
the timing and amounts of payments as the obligations are based on future development of the licensed products. 

Note 15 Leases 

Operating Leases 

We  conduct  certain  of  our  operations  under  operating lease  agreements.    Rent  expense  under  operating  leases 
was approximately $7.8 million, $2.6 million, and $1.9 million for the years ended December 31, 2015, 2014, and 
2013, respectively. 

122 

 
As  of  December 31,  2015,  the  aggregate  future  minimum  lease  payments  under  all  non-cancelable  operating 

leases with initial or remaining lease terms in excess of one year are as follows: 

Year Ending 
2016 ....................................................................... $ 
2017 ....................................................................... 
2018 ....................................................................... 
2019 ....................................................................... 
2020 ....................................................................... 
Thereafter .............................................................. 
Total minimum operating lease commitments ....... $ 

(In thousands) 
15,830
10,749
7,862
6,558
3,208
7,525
51,732

Capital Leases 

We acquired various assets under capital leases in connection with our acquisition of Bio-Reference in August 
2015.  Capital leases are included within Property, plant and equipment, net in our Consolidated Balance Sheet with 
interest rates ranging from 2% to 7% as follows: 

Capital leases 
Medical Equipment ....................................$ 
Automobiles ...............................................
Total ...........................................................
Less: Accumulated Depreciation ...............
Net capital leases in Property, plant and 

Year ended 
December 31, 
2015 

50,139
6,748
56,887
(6,798)

equipment ...............................................$ 

50,089

As of December 31, 2015, the aggregate future minimum lease payments under all non-cancelable capital leases 

with initial or remaining lease terms in excess of one year are as follows:  

Year Ending 
2016 .................................................................... $ 
2017 .................................................................... 
2018 .................................................................... 
2019 .................................................................... 
2020 .................................................................... 
Thereafter ............................................................ 
Total minimum capital lease commitments ........ $ 

(In thousands) 
5,762
3,951
2,607
1,386
603
794
15,103

Less interest ........................................................ $ 

445

Present value of minimum lease payments ......... $ 

14,658

Note 16 Segments 

We  currently  manage  our  operations  in  two  reportable  segments,  pharmaceutical  and  diagnostics.    The 
pharmaceutical segment consists of our pharmaceutical operations we acquired in Chile, Mexico, Ireland, Israel and 
Spain and our pharmaceutical research and development.  The diagnostics segment primarily consists of our clinical 
laboratory operations we acquired through the acquisitions of Bio-Reference and OPKO Lab and our point-of-care 
operations.  There are no significant inter-segment sales.  We evaluate the performance of each segment based on 
operating profit or loss.  There is no inter-segment allocation of interest expense and income taxes. 

123 

 
 
 
 
 
 
 
 
Information  regarding  our  operations  and  assets  for  our  operating  segments  and  the  unallocated  corporate 

operations as well as geographic information are as follows: 

(In thousands) 
Revenue from services: 

For the years ended December 31, 
2014 

2015 

2013 

Pharmaceutical ...........................................................................$
Diagnostics .................................................................................
Corporate ....................................................................................
$

—   $

329,599  
140  
329,739   $

Product revenues: 

Pharmaceutical ...........................................................................$
Diagnostics .................................................................................
Corporate ....................................................................................
$

Revenue from transfer of intellectual property: 

Pharmaceutical ...........................................................................$
Diagnostics .................................................................................
Corporate ....................................................................................
$

Operating (loss) income: 

80,146   $
—  
—  
80,146   $

81,853   $
—  
—  
81,853   $

—    $ 

8,426   
240   
8,666    $ 

76,983    $ 
—  
—  
76,983    $ 

5,285    $ 
191   
—   
5,476    $ 

Pharmaceutical ...........................................................................$
Diagnostics .................................................................................
Corporate ....................................................................................
Less: Operating loss attributable to noncontrolling interests .....
$

(40,395)   $
(10,294)  
(46,512)  
(1,280)  
(98,481)   $

(94,401)   $ 
(21,647)  
(27,725)  
(2,042)  
(145,815)   $ 

Depreciation and amortization: 

Pharmaceutical ...........................................................................$
Diagnostics .................................................................................
Corporate ....................................................................................
$

Net loss from investment in investees: 

Pharmaceutical ...........................................................................$
Diagnostics .................................................................................
Corporate ....................................................................................
$

Revenues: 

United States. .............................................................................$
Ireland ........................................................................................
Chile ...........................................................................................
Spain ...........................................................................................
Israel ...........................................................................................
Mexico .......................................................................................
Other ...........................................................................................
$

10,245   $
31,918  
85  
42,248   $

(7,105)   $
—  
—  
(7,105)   $

344,464   $
78,989  
29,885  
16,622  
18,107  
3,671  
—  

491,738   $

124 

—
10,833
825
11,658

68,161
—
—
68,161

15,160
1,551
—
16,711

(29,809)
(22,199)
(24,473)
(3,151)
(79,632)

8,234
6,833
149
15,216

7,936    $ 
6,894   
97   
14,927    $ 

(3,587)   $ 
—   
—   
(3,587)   $ 

(11,456)
—
—
(11,456)

14,142    $ 
—   
29,154   
21,323   
20,638   
5,807   
61   
91,125    $ 

28,369
—
31,650
18,800
13,252
4,459
—
96,530

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
(In thousands) 
Assets: 

December 31,
 2015 

December 31, 
 2014 

Pharmaceutical .......................................................................... $
Diagnostics ................................................................................  
Corporate ...................................................................................  
$

1,258,011  
1,479,841  
61,762  
2,799,614  

Goodwill: 

Pharmaceutical .......................................................................... $
Diagnostics ................................................................................  
Corporate ...................................................................................  
$

251,225  
492,123  
—  
743,348  

$ 

$ 

$ 

$ 

1,064,498  
108,072  
95,094  
1,267,664  

173,327  
50,965  
—  
224,292  

During the year ended December 31, 2015, revenue recognized under the Pfizer Transaction represented 13% of 
our  total  revenue.    During  the  year  ended  December 31,  2014,  one  customer  of  our  pharmaceutical  segment 
represented 13%  of  our  total  revenue.   During  the  year  ended December 31,  2013,  no  customer  represented  more 
than 10% of our total revenue.  As of December 31, 2015, one customer represented more than 10% of our accounts 
receivable balance.  As of December 31, 2014 and 2013, no customer represented more than 10% of our accounts 
receivable balance.  

The following table reconciles our Property, plant and equipment, net between U.S. and foreign jurisdictions: 

(In thousands) 
PP&E: 

December 31,
 2015 

December 31, 
 2014 

U.S. ........................................................................................... $
Foreign ......................................................................................  
Total ..................................................................................... $

113,307  
18,491  
131,798  

$ 

$ 

4,286  
12,125  
16,411  

Note 17 Fair Value Measurements 

We record fair values at an exit price, representing the amount that would be received to sell an asset or paid to 
transfer  a  liability  in  an  orderly  transaction  between  market  participants.    As  such,  fair  value  is  a  market-based 
measurement that should be determined based on assumptions that market participants would use in pricing an asset 
or liability.   We utilize a three-tier fair value hierarchy, which prioritizes the inputs used in measuring fair value.  
These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets; Level 2, defined 
as  inputs  other  than  quoted  prices  in  active  markets  that  are  either  directly  or  indirectly  observable;  and  Level  3, 
defined as unobservable inputs in which little or no market data exists, therefore requiring an entity to develop its 
own assumptions. 

A summary of our investments classified as available for sale and carried at fair value, is as follows: 

As of December 31, 2015 

Gross 
unrealized 
gains in 
Accumulated
OCI 

Gross 
unrealized 
losses in 
Accumulated
OCI 

Fair 
value 

Amortized
Cost 

2,978 $
2,978 $

904 $
904 $

(267)
(267)

$
$

3,615 
3,615  

(In thousands) 
Common stock investments,  
  available for sale .............................$ 
Total assets ......................................$ 

125 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
As of December 31, 2014 

Gross 
unrealized 
gains in 
Accumulated
OCI 

Gross 
unrealized 
losses in 
Accumulated
OCI 

Fair 
value 

Amortized
Cost 

10,038 $
10,038 $

293 $
293 $

(4,573)
(4,573)

$
$

5,758 
5,758  

(In thousands) 
Common stock investments,  
  available for sale .............................$ 
Total assets ......................................$ 

Any future fluctuation in fair value related to our available for sale investments that is judged to be temporary, 
and any recoveries of previous write-downs, will be recorded in Accumulated other comprehensive income or loss.  
If  we  determine  that  any  future  valuation  adjustment  was  other-than-temporary,  we  will  record  a  loss  during  the 
period such determination is made.  Any future changes in the fair value of option and warrant instruments will be 
recorded in Fair value changes of derivative instruments, net in our Consolidated Statements of Operations. 

As  of  December 31,  2015,  we  have  money  market  funds  that  qualify  as  cash  equivalents,  forward  foreign 
currency exchange contracts for inventory purchases (Refer to Note 18) and contingent consideration related to the 
acquisitions  of  CURNA,  OPKO  Diagnostics,  OPKO  Health  Europe,  and  OPKO  Renal  that  are  required  to  be 
measured  at  fair  value  on  a  recurring  basis.    In  addition,  in  connection  with  our  investment  and  our  consulting 
agreement with Neovasc, we record the related Neovasc options at fair value as well as the warrants from COCP, 
ARNO, Sevion and MabVax. 

126 

 
 
 
 
 
 
 
 
 
 
  
Our financial assets and liabilities measured at fair value on a recurring basis are as follows: 

Fair value measurements as of December 31, 2015 

Quoted 
prices in 
active 
markets for 
identical 
assets 
(Level 1) 

Significant 
other 
observable 
inputs 
(Level 2) 

Significant 
unobservable 
inputs 
(Level 3) 

84,421  

$

3,615  
—  
—  
88,036  

—  

—  
—  
—  
—  
—  

$

$

$

—   
— 

5,338   
9   
5,347   

—   

—   
—   
—   
—   
—   

$

$

$

$

Total 

84,421
3,615

5,338
9
93,383

—    

$ 

— 
—    
—    
—    

$ 

23,737    

$ 

23,737

411    
12,141    
41,400    
470    
78,159    

$ 

411
12,141
41,400
470
78,159

(In thousands) 
Assets: 

Money market funds ..............................$
Common stock investments, 

available for sale ..............................
Common stock options/warrants ...........
Forward contracts ..................................
Total assets ................................................$
Liabilities: 

Embedded conversion option ................$
Contingent consideration: 

CURNA ...........................................
OPKO Diagnostics ...........................
OPKO Renal ....................................
OPKO Health Europe ......................
Total liabilities ...........................................$

Fair value measurements as of December 31, 2014 

Quoted 
prices in 
active 
markets for 
identical 
assets 
(Level 1) 

Significant 
other 
observable 
inputs 
(Level 2) 

Significant 
unobservable 
inputs 
(Level 3) 

Total 

71,286  

$

—   

$

—    

$ 

71,286

5,758  
—  
—  
77,044  

—  

—  
—  
—  
—  
—  

$

$

$

—
6,314   
36   
6,350   

—   

—   
—   
—   
—   
—   

$

$

$

— 
—    
—    
—    

$ 

5,758
6,314
36
83,394

65,947    

$ 

65,947

440    
13,578    
55,780    
1,769    
137,514    

$ 

440
13,578
55,780
1,769
137,514

(In thousands) 
Assets: 

Money market funds ..............................$
Common stock investments, 

available for sale ..............................
Common stock options/warrants ...........
Forward contracts ..................................
Total assets ................................................$
Liabilities: 

Embedded conversion option ................$
Contingent consideration: 

CURNA ...........................................
OPKO Diagnostics ...........................
OPKO Renal ....................................
OPKO Health Europe ......................
Total liabilities ...........................................$

127 

 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
  
 
 
  
 
 
   
    
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
  
 
 
  
 
 
   
    
The carrying amount and estimated fair value of our 2033 Senior Notes without the embedded conversion option, 
as  well  as  the  applicable  fair  value  hierarchy  tiers,  are  contained  in  the  table  below.    The  fair  value  of  the  2033 
Senior  Notes  is  determined  using  a  binomial  lattice  approach  in  order  to  estimate  the  fair  value  of  the  embedded 
derivative in the 2033 Senior Notes.  Refer to Note 6. 

(In thousands) 
2033 Senior Notes .............................$ 

Carrying 
Value 

Total 
Fair Value 

Level 1 

Level 2 

Level 3 

25,675 $

24,647 $

—   $

—    $

24,647

December 31, 2015 

There have been no transfers between Level 1 and Level 2 and no transfers to or from Level 3 of the fair value 

hierarchy. 

(In thousands) 
2033 Senior Notes .............................$ 

Carrying 
Value 

Total 
Fair Value 

Level 1 

Level 2 

Level 3 

65,507 $

63,062 $

—   $

—    $ 

63,062

December 31, 2014 

There have been no transfers between Level 1 and Level 2 and no transfers to or from Level 3 of the fair value 

hierarchy. 

As of December 31, 2015 and 2014, the carrying value of our other assets and liabilities approximates their fair 

value due to their short-term nature. 

The  following  tables  reconcile  the  beginning  and  ending  balances  of  our  Level  3  assets  and  liabilities  as  of 

December 31, 2015 and 2014: 

December 31, 2015 

(In thousands) 
Balance at December 31, 2014 ..............................$

Contingent
consideration
71,567

Embedded
conversion
option 

$

65,947

Total losses (gains) for the period: 

Included in results of operations ....................
Foreign currency impact ................................
Payments ...........................................................
Conversion ........................................................
Balance at December 31, 2015 ..............................$

5,050
(269)
(21,926)
—
54,422

36,587
—
—
(78,797)
23,737

$

(In thousands) 
Balance at December 31, 2013 ..............................$

December 31, 2014 
Deferred 
acquisition
payments, net
of discount 

Embedded 
conversion 
option 

Contingent
consideration

71,620 $

5,465 $ 101,087 

Total losses (gains) for the period: 

Included in results of operations ....................
Foreign currency impact ................................
Payments ...........................................................
Conversion ........................................................
Balance at December 31, 2014 ..............................$

24,446
(130)
(24,369)
—
71,567 $

(735)
—
(4,730)
—
— $

12,213 
— 
— 
(47,353) 
65,947 

The  estimated  fair  values  of  our  financial  instruments  have  been  determined  by  using  available  market 
information  and  what  we  believe  to  be  appropriate  valuation  methodologies.    We  use  the  following  methods  and 
assumptions in estimating fair value: 

Contingent consideration – We estimate the fair value of the contingent consideration utilizing a discounted cash 
flow model for the expected payments based on estimated timing and expected revenues.  We use several discount 

128 

 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
rates  depending  on  each  type  of  contingent  consideration  related  to  OPKO  Diagnostics,  CURNA,  OPKO  Health 
Europe, OPKO Renal and Merck (VARUBI™) transactions.  If estimated future sales were to decrease by 10%, the 
contingent consideration related to OPKO Renal would decrease by $1.7 million.  As of December 31, 2015, of the 
$54.4  million  of  contingent  consideration,  $22.2  million  is  recorded  in  Accrued  expenses  and  $32.3  million  is 
recorded in Other long-term liabilities.  As of December 31, 2014, of the $71.6 million of contingent consideration, 
$27.4 million is recorded in Accrued expenses and $44.2 million is recorded in Other long-term liabilities. 

Deferred payments – We estimate the fair value of the deferred payments utilizing a discounted cash flow model 

for the expected payments. 

Embedded conversion option – We estimate the fair value of the embedded conversion option related to the 2033 
Senior Notes using a binomial lattice model.  Refer to Note 6 for detail description of the binomial lattice model and 
the fair value assumptions used. 

Note 18 Derivative Contracts 

The following table summarizes the fair values and the presentation of our derivative financial instruments in the 

Consolidated Balance Sheets: 

(In thousands) 
Derivative financial instruments: 

Balance Sheet Component 

December 31, 
 2015 

December 31,
 2014 

Common stock options/warrants ...........Investments, net 
Embedded conversion option ................2033 Senior Notes, net of discount and 

Forward contracts .................................Unrealized gains on forward contracts 

estimated fair value of embedded 
derivatives 

$
$

$

5,338 
23,737 

  $ 
  $ 

6,314
65,947

9 

  $ 

36

are recorded in Prepaid expenses and 
other current assets.  Unrealized 
losses on forward contracts are 
recorded in Accrued expenses. 

We  enter  into  foreign  currency  forward  exchange  contracts  to  cover  the  risk  of  exposure  to  exchange  rate 
differences arising from inventory purchases on letters of credit.  Under these forward contracts, for any rate above 
or  below  the  fixed  rate,  we  receive  or  pay  the  difference  between  the  spot  rate  and  the  fixed  rate  for  the  given 
amount at the settlement date. 

To  qualify  the  derivative  instrument  as  a  hedge,  we  are  required  to  meet  strict  hedge  effectiveness  and 
contemporaneous documentation requirements at the initiation of the hedge and assess the hedge effectiveness on an 
ongoing basis over the life of the hedge.  At December 31, 2015 and 2014, our derivative financial instruments do 
not  meet  the  documentation  requirements  to  be  designated  as  hedges.    Accordingly,  we  recognize  the  changes  in 
Fair  value  of  derivative  instruments,  net  in  our  Consolidated  Statements  of  Operations.    The  following  table 
summarizes the losses and gains recorded for the years ended December 31, 2015 and 2014: 

(In thousands) 
Derivative gain (loss): 

For the years ended December 31, 
2014 

2013 

2015 

Common stock options/warrants ...........................................$
2033 Senior Notes .................................................................
Forward contracts ..................................................................$
Total ...................................................................................$

(2,854) $

(36,588)

359 $
(39,083) $

1,193  $ 

(12,213)  

388  $ 
(10,632)   $ 

6,544
(52,742)
(256)
(45,942)

129 

 
 
 
 
 
 
 
 
 
   
 
Note 19 Selected Quarterly Financial Data (Unaudited) 

(In thousands, except per share data) 
Total revenues .................................................................. $
Total costs and expenses ................................................... 
Net income (loss) .............................................................. 
Net income (loss) attributable to common shareholders ... 
Earnings (loss) per share, basic ........................................  
Earnings (loss) per share, diluted ...................................... $

(In thousands, except per share data) 
Total revenues .................................................................. $
Total costs and expenses ................................................... 
Net loss ............................................................................. 
Net loss attributable to common shareholders .................. 
Earnings (loss) per share, basic ........................................ $
Earnings (loss) per share, diluted ...................................... $

For the 2015 Quarters Ended 

March 31 

June 30 

30,084 $
86,998
(118,037)
(117,112)

(0.26)  
(0.26) $

42,429 $ 
67,838
(43,241)
(42,766)

(0.09)  
(0.09) $ 

September 30   December 31 
276,191 
284,126 
1,603 
1,603 
— 
— 

143,034    $
151,257   
128,247   
128,247   
0.26     
0.18    $

For the 2014 Quarters Ended 

March 31 

June 30 

22,274 $
52,550
(45,088)
(44,548)

(0.11) $
(0.11) $

23,545 $ 
58,429
(26,075)
(25,478)

(0.06) $ 
(0.08) $ 

19,773    $
67,974   
(50,014)  
(48,669)  

September 30   December 31 
25,533 
57,987 
(53,461) 
(52,971) 
(0.12) 
(0.12) 

(0.11)   $
(0.11)   $

For  the  third  quarter  of  2015,  we  previously  reported  diluted  earnings  per  share  (“EPS”)  of  $0.25.    We  have 

corrected the amount to $0.18 to reflect an immaterial adjustment calculation. 

Note 20 Subsequent Events 

On  January 5,  2016,  we  announced  that  our  2033  Senior  Notes  continue  to  be  convertible  by  holders  of  such 
notes.  We have elected to satisfy our conversion obligation under the 2033 Senior Notes in shares of our Common 
Stock.    This  conversion  right  has  been  triggered  because  the  closing  price  per  share  of  our  Common  Stock  has 
exceeded  $9.19,  or  130%  of  the  initial  conversion  price  of  $7.07,  for  at  least  20  of  30  consecutive  trading  days 
during the period ending on December 31, 2015.  The conversion right was previously triggered during the quarters 
ended  March 31,  2015,  June 30,  2015  and  September 30,  2015.    The  2033  Senior  Notes  will  continue  to  be 
convertible  until  March 31,  2016,  and  may  be  convertible  thereafter,  if  one  or  more  of  the  conversion  conditions 
specified in the Indenture, dated as of January 30, 2013, by and between the Company and Wells Fargo Bank N.A., 
is satisfied during future measurement periods.  Pursuant to the Indenture, a holder who elects to convert the 2033 
Senior  Notes  will  receive  141.4827  shares  of  our  Common  Stock  plus  such  number  of  additional  shares  as  is 
applicable on the conversion date per $1,000 principal amount of 2033 Senior Notes based on the early conversion 
provisions in the Indenture. 

We have reviewed all subsequent events and transactions that occurred after the date of our December 31, 2015 

Consolidated Balance Sheet date, through the time of filing this Annual Report on Form 10-K. 

ITEM 9.  CHANGES  IN  AND  DISAGREEMENTS  WITH  ACCOUNTANTS  ON  ACCOUNTING  AND 

FINANCIAL DISCLOSURE. 

None. 

ITEM 9A.  CONTROLS AND PROCEDURES. 

Disclosure Controls and Procedures 

Our  management,  with  the  participation  of  our  Chief  Executive  Officer  and  Chief  Financial  Officer,  have 
evaluated the effectiveness of the Company’s disclosure controls and procedures (as defined in Rules 13a-15(e) and 
15d-15(e) under the Securities Exchange Act of 1934, as amended (the “Exchange Act”)) as of December 31, 2015.  
Our disclosure controls and procedures are designed to provide reasonable assurance that information required to be 
disclosed by us in the reports that we file or submit under the Exchange Act is recorded, processed, summarized and 
reported,  within  the  time  periods  specified  in  the  rules  and  forms  of  the  Securities  and  Exchange  Commission.  
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.  Based on this evaluation, 
management concluded that our disclosure controls and procedures were effective as of December 31, 2015. 

130 

 
 
 
 
 
 
   
 
 
 
 
 
   
Management’s Annual Report on Internal Control Over Financial Reporting 

Our  management  is  responsible  for  establishing  and  maintaining  adequate  internal  control  over  financial 
reporting, as such term is defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as 
amended.    Our  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.    All  internal  control  systems,  no  matter  how  well 
designed,  have  inherent  limitations.    Therefore,  even  those  systems  determined  effective  could  provide  only 
reasonable assurance with respect to financial statement preparation and presentation. 

Our management conducted an evaluation of the effectiveness of our internal control over financial reporting as 
of December 31, 2015, based on the framework in the Internal Control - Integrated Framework (2013) issued by the 
Committee  of  Sponsoring  Organizations  of  the  Treadway  Commission  (the  “2013  Internal  Control-Integrated 
Framework”).  Based on our evaluation under the framework in 2013 Internal Control-Integrated Framework, our 
management concluded that our internal control over financial reporting was effective as of December 31, 2015.  As 
permitted,  our  management’s  assessment  of  and  conclusion  on  the  effectiveness  of  our  internal  control  over 
financial  reporting  did  not  include  the  internal  controls  of  EirGen  Pharma  Limited  (“EirGen”)  or  Bio-Reference 
Laboratories, Inc. (“Bio-Reference”), because they were acquired by us in business combinations in May 2015 and 
August 2015, respectively.  EirGen and Bio-Reference’s assets excluded from the annual assessment process were 
15% of consolidated total assets as of December 31, 2015 and 68% of consolidated revenues for the year then ended 
as a result of the closing of the acquisitions in May 2015 and August 2015. 

The effectiveness of the Company’s internal control over financial reporting as of December 31, 2015 has been 
audited  by  Ernst &  Young  LLP,  our  independent  registered  public  accounting  firm,  who  also  audited  our 
Consolidated  Financial  Statements  included  in  this  Annual  Report  on  Form  10-K,  as  stated  in  their  report  which 
appears with our accompanying Consolidated Financial Statements. 

Changes to the Company’s Internal Control Over Financial Reporting 

In  connection  with  the  acquisitions  of  EirGen  in  May  2015  and  Bio-Reference  in  August  2015,  we  began 
implementing  standards  and  procedures  at  EirGen  and  Bio-Reference,  including  establishing  controls  over 
accounting  systems  and  establishing  controls  over  the  preparation  of  financial  statements  in  accordance  with 
generally accepted accounting principles to ensure that we have in place appropriate internal control over financial 
reporting at EirGen and Bio-Reference.  We are continuing to integrate the acquired operations of EirGen and Bio-
Reference into our overall internal control over financial reporting process. 

These changes to the Company’s internal control over financial reporting that occurred during the most recent 
quarter  ended  December 31,  2015  have  materially  affected,  or  are  reasonably  likely  to  materially  affect,  the 
Company’s internal control over financial reporting. 

ITEM 9B.  OTHER INFORMATION. 

None.

131 

 
PART III 

The  information  required  in  Items  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),  and  Item 14  (Principal  Accounting  Fees  and  Services)  is  incorporated  by  reference  to  the 
Company’s definitive proxy statement for the 2016 Annual Meeting of Stockholders to be filed with the Securities 
and Exchange Commission within 120 days of December 31, 2015.

132 

 
ITEM 15.  EXHIBITS, FINANCIAL STATEMENT SCHEDULES. 

(a)  (1)  Financial Statements:  See Part II, Item 8 of this report. 

PART IV 

(2)  We will file the financial statement schedule entitled “Schedule I - Condensed Financial Information of 
Registrant” by amendment to this Part IV, Item 15 of this Form 10-K within 30 days.  Additionally, the 
financial statement schedule entitled “Schedule II – Valuation and Qualifying Accounts” has been omitted 
since the information required is included in the consolidated financial statements and notes thereto. 

(3)  Exhibits:  See below. 

Exhibit 
Number 
1.1(12) 

2.1(1) 

2.2(3)+ 

2.3(9) 

2.4(14)+ 

2.5(15) 

2.6(17)+ 

2.7(18) 

2.8(19)+ 

2.9(21)+ 

2.10(22)+ 

2.11(23) 

Underwriting Agreement, dated March 9, 2011, by and among OPKO Health, Inc., Jefferies & 
Company, Inc. and J.P. Morgan Securities LLC, as representatives for the underwriters named 
therein. 

Description 

Merger Agreement and Plan of Reorganization, dated as of March 27, 2007, by and among Acuity 
Pharmaceuticals, Inc., Froptix Corporation, eXegenics, Inc., e-Acquisition Company I-A, LLC, and 
e-Acquisition Company II-B, LLC. 

Securities Purchase Agreement, dated May 2, 2008, by and among Vidus Ocular, Inc., OPKO 
Instrumentation, LLC, OPKO Health, Inc., and the individual sellers and noteholders named therein. 

Purchase Agreement, dated February 17, 2010, by and among Ignacio Levy García and José de Jesús 
Levy García, Inmobiliaria Chapalita, S.A. de C.V., Pharmacos Exakta, S.A. de C.V., OPKO Health, 
Inc., OPKO Health Mexicana S. de R.L. de C.V., and OPKO Manufacturing Facilities S. de R.L. de 
C.V. 

Agreement and Plan of Merger, dated January 28, 2011, by and among CURNA Inc., KUR, LLC, 
OPKO Pharmaceuticals, LLC, OPKO CURNA, LLC, and certain individuals named therein. 

Agreement and Plan of Merger, dated October 13, 2011, by and among OPKO Health, Inc., Claros 
Merger Subsidiary, LLC, Claros Diagnostics, Inc., and Ellen Baron, Marc Goldberg and Michael 
Magliochetti on behalf of the Shareholder Representative Committee. 

Stock Purchase Agreement, dated December 20, 2011, by and among FineTech Pharmaceutical Ltd., 
Arie Gutman, OPKO Holdings Israel Ltd., and OPKO Health, Inc. 

Purchase Agreement, dated January 20, 2012, by and among OPKO Health, Inc., OPKO Chile S.A., 
Samuel Alexandre Arama, Inversiones SVJV Limitada, Bruno Sergiani, Inversiones BS Limitada, 
Pierre-Yves LeGoff, and Inversiones PYTT Limitada. 

Stock Purchase Agreement, dated August 2, 2012, by and among Farmadiet Group Holding, S.L., the 
Sellers party thereto, OPKO Health, Inc., and Shebeli XXI, S.L.U. 

Agreement and Plan of Merger, dated October 18, 2012, by and among Prost-Data, Inc. d/b/a 
OurLab, Our Labs, Endo Labs and Gold Lab, Jonathan Oppenheimer, M.D., OPKO Health, Inc., 
OPKO Laboratories Inc., and OPKO Labs, LLC. 

Share Purchase Agreement, dated January 8, 2013, by among Cytochroma Inc., Cytochroma 
Holdings ULC, Cytochroma Canada Inc., Cytochroma Development Inc., Proventiv Therapeutics, 
LLC, Cytochroma Cayman Islands, Ltd., OPKO Health, Inc., and OPKO IP Holdings, Inc. 

Asset Purchase Agreement, dated March 1, 2013, by and between RXi Pharmaceuticals Corporation 
and OPKO Health, Inc. 

133 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.12(24) 

2.13(28)+ 

2.14(28)+ 

2.15(29)+ 

3.1(27) 

3.2(2) 

3.3(7) 

4.1(1) 

4.2(7) 

4.3(25) 

10.1(1) 

10.2(2) 

10.3(2)* 

10.4(26)* 

10.5(3) 

10.6(3) 

10.7(4) 

10.8(5) 

10.9(6) 

Agreement and Plan of Merger, dated April 23, 2013, by and among OPKO Health, Inc., POM 
Acquisition Inc., and PROLOR Biotech, Inc. 

Agreement for the Sale and Purchase of Shares in EirGen Pharma Limited, dated May 5, 2015 by and 
among OPKO Ireland Limited, OPKO Health, Inc. and the Sellers named therein. 

Form of Additional Agreement for the Sale and Purchase of Shares in EirGen Pharma Limited, dated 
May 5, 2015 by and among OPKO Ireland Limited and the Sellers named therein. 

Agreement and Plan of Merger by and among the Company, Bamboo Acquisition, Inc. and Bio-
Reference Laboratories, Inc. dated as of June 3, 2015. 

  Amended and Restated Certificate of Incorporation, as amended. 

  Amended and Restated Bylaws. 

  Certificate of Designation of Series D Preferred Stock. 

  Form of Common Stock Warrant. 

  Form of Common Stock Warrant. 

  Indenture, dated January 30, 2013, between OPKO Health, Inc. and Wells Fargo Bank, National 

Association. 

  Form of Lockup Agreement. 

  Stock Purchase Agreement, dated December 4, 2007, by and between OPKO Health, Inc. and the 

members of The Frost Group, LLC. 

  OPKO Health, Inc. 2007 Equity Incentive Plan. 

  Amendment to OPKO Health, Inc. 2007 Equity Incentive Plan. 

  Form of Director Indemnification Agreement. 

  Form of Officer Indemnification Agreement. 

  Stock Purchase Agreement, dated August 8, 2008 by and between OPKO Health, Inc. and the 

Purchasers named therein. 

  Stock Purchase Agreement, dated February 23, 2009 by and between OPKO Health, Inc. and Frost 

Gamma Investments Trust. 

  Form of Stock Purchase Agreement for transactions between OPKO Health, Inc. and Nora Real 

Estate SA., Vector Group Ltd., Oracle Partners LP, Oracle Institutional Partners, LP., Chung Chia 
Company Limited, Gold Sino Assets Limited, and Grandtime Associates Limited. 

10.10(6) 

  Stock Purchase Agreement, dated June 10, 2009, by and among OPKO Health, Inc. and Sorrento 

Therapeutics, Inc. 

10.11(7) 

10.12(8)* 

  Form of Securities Purchase Agreement for Series D Preferred Stock. 

  Form of Restricted Share Award Agreement for Directors. 

10.13(8) 

  Cocrystal Discovery, Inc. Agreements. 

134 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10.14(11) 

  Stock Purchase Agreement, dated October 1, 2009, by and among the Laboratoria Volta S.A., 

Farmacias Ahumada S.A., FASA Chile S.A., OPKO Chile Limitada and Inversones OPKO Limitada, 
subsidiaries of OPKO Health, Inc. 

10.15(10)+ 

  Asset Purchase Agreement, dated October 12, 2009, by and between OPKO Health, Inc. and Schering 

Corporation. 

10.16(10) 

  Letter Agreement, dated June 29, 2010, by and between OPKO Health, Inc. and Schering 

Corporation. 

10.17(16)+ 

  Exclusive License Agreement by and between TESARO, Inc. and OPKO Health, Inc. dated 

December 10, 2010. 

10.18(13) 

  Third Amended and Restated Subordinated Note and Security Agreement, dated February 22, 2011, 

between OPKO Health, Inc. and The Frost Group, LLC. 

10.19(15)+ 

  Asset Purchase Agreement dated September 21, 2011, by and among Optos plc, Optos Inc., OPKO 
Health, Inc., OPKO Instrumentation, LLC, Ophthalmic Technologies, Inc., and OTI (UK) Limited. 

10.20(20) 

  Form of Note Purchase Agreement, dated as of January 25, 2013, by and among OPKO Health, Inc. 

and each purchaser a party thereto. 

10.21(30)+ 

  Development and Commercialization License Agreement by and between OPKO Ireland, Ltd., a 

subsidiary of OPKO Health, Inc., and Pfizer, Inc. dated December 13, 2014. 

10.22 

  Credit Agreement by and between Bio-Reference Laboratories, Inc. and certain of its subsidiaries and 

JPMorgan Chase Bank, N.A. dated November 5, 2015. 

21 

  Subsidiaries of the Company. 

23.1 

  Consent of Ernst & Young LLP. 

23.2 

31.1 

31.2 

  Consent of MSPC Certified Public Accountants and Advisors, P.C. relating to Bio-Reference 

Laboratories, Inc.’s financial statements. 

  Certification by Phillip Frost, Chief Executive Officer, pursuant to Rule 13a-14(a) and 15d-14(a) of 
the Securities and Exchange Act of 1934 as adopted pursuant to Section 302 of the Sarbanes-Oxley 
Act of 2002 for the quarterly period ended December 31, 2015. 

  Certification by Adam Logal, Chief Financial Officer, pursuant to Rule 13a-14(a) and 15d-14(a) of 
the Securities and Exchange Act of 1934 as adopted pursuant to Section 302 of the Sarbanes-Oxley 
Act of 2002 for the quarterly period ended December 31, 2015. 

32.1 

  Certification by Phillip Frost, Chief Executive Officer pursuant to 18 U.S.C. Section 1350, as adopted 

pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 for the quarterly period ended 
December 31, 2015. 

32.2 

  Certification by Adam Logal, Chief Financial Officer, pursuant to 18 U.S.C. Section 1350, as adopted 

pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 for the quarterly period ended 
December 31, 2015. 

99.1(31) 

  The audited consolidated balance sheets of Bio-Reference Laboratories, Inc. and its subsidiaries as of 

October 31, 2014 and 2013, and the related consolidated statements of operations, shareholders’ 
equity, and cash flows for each of the years in the three-year period ended October 31, 2014, and the 
notes and the independent auditor’s reports thereto. 

99.2(32) 

  The unaudited consolidated balance sheet of Bio-Reference Laboratories, Inc. and its subsidiaries as 

of April 30, 2015, the related unaudited consolidated statements of operations, and statements of cash 
flows for the three and six months ended April 30, 2015, and the notes thereto. 

135 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
99.3(33) 

  The unaudited pro forma condensed combined financial statements of the Company and Bio-

Reference Laboratories, Inc. 

101.INS 

  XBRL Instance Document 

101.SCH 

  XBRL Taxonomy Extension Schema Document 

101.CAL 

  XBRL Taxonomy Extension Calculation Linkbase Document 

101.DEF 

  XBRL Taxonomy Extension Definition Linkbase Document 

101.LAB 

  XBRL Taxonomy Extension Label Linkbase Document 

101.PRE 

  XBRL Taxonomy Extension Presentation Linkbase Document 

* 

+ 

(1) 

(2) 

(3) 

(4) 

(5) 

(6) 

(7) 

(8) 

(9) 

(10) 

(11) 

(12) 

(13) 

(14) 

(15) 

(16) 

(17) 

(18) 

(19) 

(20) 

(21) 

(22) 

(23) 

Denotes management contract or compensatory plan or arrangement.

Certain confidential material contained in the document has been omitted and filed separately with the Securities and Exchange 
Commission. 

Filed with the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on April 2, 2007, and 
incorporated herein by reference. 

Filed with the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 31, 2008 and 
incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 8, 2008 for 
the Company’s three-month period ended June 30, 2008, and incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 12, 2008 
for the Company’s three-month period ended September 30, 2008, and incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 8, 2009 for the 
Company’s three-month period ended March 31, 2009, and incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 7, 2009 for 
the Company’s three-month period ended June 30, 2009, and incorporated herein by reference. 

Filed with the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on September 24, 2009, 
and incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 9, 2009 
for the Company’s three-month period ended September 30, 2009, and incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 10, 2010 for 
the Company’s three-month period ended March 31, 2010, and incorporated herein by reference. 

Filed with the Company’s Amendment to Annual Report on Form 10-K filed with the Securities and Exchange Commission on 
February 3, 2011. 

Filed with the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 17, 2010. 

Filed with the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on March 10, 2011, and 
incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 10, 2011 for 
the Company’s three-month period ended March 31, 2011, and incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q/A filed with the Securities and Exchange Commission on July 5, 2011, and 
incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 9, 2011 
for the Company’s three-month period ended September 30, 2011, and incorporated herein by reference. 

Filed with the Company’s Annual Report on Form 10-K/A filed with the Securities and Exchange Commission on July 28, 2011. 

Filed with the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 15, 2012. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 10, 2012 for 
the Company’s three-month period ended March 31, 2012, and incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 9, 2012 
for the Company’s three-month period ended September 30, 2012, and incorporated herein by reference. 

Filed with the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on January 29, 2013, and 
incorporated herein by reference. 

Filed with the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 18, 2013. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 10, 2013 for 
the Company’s three-month period ended March 31, 2013, and incorporated herein by reference. 

Filed with the Company’s Schedule 13D filed with the Securities and Exchange Commission on March 22, 2013, and incorporated 
herein by reference. 

136 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(24) 

(25) 

(26) 

(27) 

(28) 

(29) 

(30) 

(31) 

(32) 

(33) 

Filed as Annex A to the Company’s Preliminary Joint Proxy Statement/Prospectus, Form S-4, with the Securities Exchange 
Commission on June 27, 2013, as amended, and incorporated herein by reference. 

Filed with the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on February 5, 2013, and 
incorporated herein by reference. 

Filed with the Company’s Current Report on Form 8-K filed with the Securities Exchange Commission on August 30, 2013, and 
incorporated herein by reference. 

Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 12, 2013 
for the Company’s three month period ended September 30, 2013, and incorporated herein by reference. 

 Filed with the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 5, 2015 for 
the Company’s three month period ended June 30, 2015, and incorporated herein by reference. 

Filed with the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on June 4, 2015, and 
incorporated herein by reference. 

Filed with the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 27, 2015, and 
incorporated herein by reference. 

Filed under Part II, Item 8, of the Bio-Reference Laboratories, Inc. Form 10-K filed with the Securities and Exchange Commission on 
January 13, 2015 (File No. 0-15266), and incorporated herein by reference. 

Filed under Part I, Item 1, of the Bio-Reference Laboratories, Inc. Form 10-Q filed with the Securities and Exchange Commission on 
June 9, 2015 (File No. 0-15266), and incorporated herein by reference. 

Filed under the heading “Unaudited Pro Forma Condensed Combined Financial Statements” beginning on page 27 of the Company’s 
Registration Statement on Form S-4/A filed with the Securities and Exchange Commission on July 15, 2015 (File No. 333-205480), 
and incorporated herein by reference. 

137 

 
 
 
 
 
 
 
 
 
SIGNATURES 

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has 

duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized. 

Date:  February 29, 2016 

OPKO HEALTH, INC. 

By:  /s/ Phillip Frost, M.D. 

Phillip Frost, M.D. 
Chairman of the Board and 
Chief Executive Officer 

Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the 

following persons on behalf of the registrant and in the capacities and on the dates indicated. 

Signature 

Title 

Date 

/s/ Phillip Frost, M.D. 
Phillip Frost, M.D. 

Chairman of the Board and Chief Executive 
Officer 
(Principal Executive Officer) 

February 29, 2016 

/s/ Jane H. Hsiao, Ph.D., MBA 
Jane H. Hsiao, Ph.D., MBA 

Vice Chairman and Chief Technical Officer 

February 29, 2016 

/s/ Steven D. Rubin 
Steven D. Rubin 

/s/ Adam Logal 
Adam Logal 

/s/ Robert Baron 
Robert Baron 

/s/ Thomas E. Beier 
Thomas E. Beier 

/s/ Dmitry Kolosov 
Dmitry Kolosov 

/s/ Richard A. Lerner, M.D. 
Richard A. Lerner, M.D. 

/s/ John A. Paganelli 
John A. Paganelli 

/s/ Richard C. Pfenniger, Jr. 
Richard C. Pfenniger, Jr. 

/s/ Alice Lin-Tsing Yu, M.D., Ph.D. 
Alice Lin-Tsing Yu, M.D., Ph.D. 

Director and Executive Vice President – 
Administration 

February 29, 2016 

Senior Vice President and Chief Financial Officer, 
Chief Accounting Officer and Treasurer 
(Principal Financial Officer) 

February 29, 2016 

February 29, 2016 

February 29, 2016 

February 29, 2016 

February 29, 2016 

February 29, 2016 

February 29, 2016 

February 29, 2016 

Director 

Director 

Director 

Director 

Director 

Director 

Director 

138 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EXHIBIT INDEX 

Exhibit 
Number 

10.22 

Description 
Credit Agreement by and between Bio-Reference Laboratories, Inc. and certain of its subsidiaries 
and JPMorgan Chase Bank, N.A. dated November 5, 2015. 

21 

23.1 

23.2 

31.1 

31.2 

32.1 

32.2 

  Subsidiaries of the Company. 

  Consent of Ernst & Young LLP. 

Consent of MSPC Certified Public Accountants and Advisors, P.C. relating to Bio-Reference 
Laboratories, Inc.’s financial statements. 

Certification by Phillip Frost, Chief Executive Officer, pursuant to Rule 13a-14(a) and 15d-14(a) of 
the Securities and Exchange Act of 1934 as adopted pursuant to Section 302 of the Sarbanes-Oxley 
Act of 2002 for the quarterly period ended December 31, 2015. 

Certification by Adam Logal, Chief Financial Officer, pursuant to Rule 13a-14(a) and 15d-14(a) of 
the Securities and Exchange Act of 1934 as adopted pursuant to Section 302 of the Sarbanes-Oxley 
Act of 2002 for the quarterly period ended December 31, 2015. 

Certification by Phillip Frost, Chief Executive Officer pursuant to 18 U.S.C. Section 1350, as 
adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 for the quarterly period ended 
December 31, 2015. 

Certification by Adam Logal, Chief Financial Officer, pursuant to 18 U.S.C. Section 1350, as 
adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 for the quarterly period ended 
December 31, 2015. 

101.INS 

  XBRL Instance Document 

101.SCH 

  XBRL Taxonomy Extension Schema Document 

101.CAL 

  XBRL Taxonomy Extension Calculation Linkbase Document 

101.DEF 

  XBRL Taxonomy Extension Definition Linkbase Document 

101.LAB 

  XBRL Taxonomy Extension Label Linkbase Document 

101.PRE 

  XBRL Taxonomy Extension Presentation Linkbase Document 

139 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SUBSIDIARIES OF OPKO HEALTH, INC. 

Exhibit 21 

NAME 
OPKO Instrumentation, LLC 
OPKO Pharmaceuticals, LLC 
OPKO Diagnostics, LLC 
OPKO Chile, S.A. 
Arama Natural Products Distribuidora, Ltda 
Pharmacos Exakta S.A. de C.V. 
FineTech Pharmaceutical Ltd 
Farmadiet Group Holdings, S.C. 
OPKO Lab, LLC 
OPKO Biologics, Ltd 
OPKO Ireland Global Holdings, Ltd 
OPKO Ireland, Ltd 
OPKO Canada Corp, ULC 
OPKO Renal, LLC 
Curna, Inc. 
Inspiro Medical, Ltd 
OPKO do Brasil Comercio de Produtos Farmaceuticos, Ltda 
OPKO Uruguay, Ltd 
Bio-Reference Laboratories, Inc. 
GeneDX, Inc. 
Genome Diagnostics, Ltd 
EirGen Pharma Limited 

  JURISDICTION OF INCORPORATION 
Delaware 
Delaware 
Delaware 
Chile 
Chile 
Mexico 
Israel 
Spain 
Florida 
Israel 
Ireland 
Ireland 
Canada 
Canada 
Delaware 
Israel 
Brazil 
Uruguay 
New Jersey 
New Jersey 
Canada 
Ireland 

140 

 
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
  
 
  
 
  
 
Exhibit 23.1 

Consent of Independent Registered Public Accounting Firm 

We consent to the incorporation by reference in the following Registration Statements: 

1.  Registration Statement (Form S-8 No. 333-144040) of OPKO Health, Inc. and subsidiaries, 

2.  Registration Statement (Form S-3 No. 333-189369) of OPKO Health, Inc. and subsidiaries,  

3.  Registration Statement (Form S-3 No. 333-190360) of OPKO Health, Inc. and subsidiaries,  

4.  Registration Statement (Form S-8 No. 333-190899) of OPKO Health, Inc. and subsidiaries,  

5.  Registration Statement (Form S-8 No. 333-190900) of OPKO Health, Inc. and subsidiaries, and 

6.  Registration Statement (Form S-8 No. 333-206489) of OPKO Health, Inc. and subsidiaries 

of our reports dated February 29, 2016, with respect to the consolidated financial statements of OPKO Health Inc. 
and  subsidiaries  and  the  effectiveness  of  internal  control  over  financial  reporting  of  OPKO  Health  Inc.  and 
subsidiaries included in this Annual Report (Form 10-K) of OPKO Health Inc. and subsidiaries for the year ended 
December 31, 2015. 

/s/ Ernst & Young LLP 
Certified Public Accountants  

Miami, Florida 
February 29, 2016 

141 

 
 
 
Consent of Independent Registered Public Accounting Firm 

Exhibit 23.2 

February 29, 2016 

OPKO Health, Inc. 
4400 Biscayne Blvd. 
Miami, FL 33137 

We consent to the incorporation by reference in the following Registration Statements: 

1.  Registration Statement on Form S-8 (No. 333-144040) of OPKO Health, Inc. and subsidiaries; 

2.  Registration Statement on Form S-3 (No. 333-189369) of OPKO Health, Inc. and subsidiaries,  

3.  Registration Statement on Form S-3 (No. 333-190360) of OPKO Health, Inc. and subsidiaries, 

4.  Registration Statement on Form S-8 (No. 333-190899) of OPKO Health, Inc. and subsidiaries; 

5.  Registration Statement on Form S-8 (No. 333-190900) of OPKO Health, Inc. and subsidiaries; 

6.  Registration Statement on Form S-8 (No. 333-206489) of OPKO Health, Inc. and subsidiaries; 

of  our  reports  dated  January 13,  2015,  with  respect  to  the  consolidated  financial  statements  and  internal  controls 
over financial reporting of Bio-Reference Laboratories, Inc. and its subsidiaries which is incorporated by reference 
in this Annual Report on Form 10-K of OPKO Health, Inc. 

/s/ MSPC 
MSPC 
Certified Public Accountants and Advisors  
A Professional Corporation 

Cranford, New Jersey  
February 29, 2016 

142 

 
 
 
 
 
 
 
CERTIFICATIONS 

Exhibit 31.1 

I, Phillip Frost, certify that:  

(1) 

I have reviewed this Annual Report on Form 10-K of OPKO Health, Inc.; 

(2)  Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state 
a  material  fact  necessary  to  make  the  statements  made,  in  light  of  the  circumstances  under  which  such 
statements were made, not misleading with respect to the period covered by this report; 

(3)  Based on my knowledge, the financial statements, and other financial information included in this report, 
fairly  present  in  all  material  respects  the  financial  condition,  results  of  operations  and  cash  flows  of  the 
registrant as of, and for, the periods presented in this report; 

(4)  The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure 
controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control 
over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and 
have: 

(a)  Designed such disclosure controls and procedures, or caused such disclosure controls and procedures 
to  be  designed  under  our  supervision,  to  ensure  that  material  information  relating  to  the  registrant, 
including its consolidated subsidiaries, is made known to us by others within those entities, particularly 
during the period in which this report is being prepared; 

(b)  Designed such internal control over financial reporting, or caused such internal control over financial 
reporting  to  be  designed  under  our  supervision,  to  provide  reasonable  assurance  regarding  the 
reliability  of  financial  reporting  and  the  preparation  of  financial  statements  for  external  purposes  in 
accordance with generally accepted accounting principles; 

(c)  Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this 
report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end 
of the period covered by this report based on such evaluation; and 

(d)  Disclosed  in  this  report  any  change  in  the  registrant’s  internal  control  over  financial  reporting  that 
occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the 
case of an annual report) that has materially affected, or is reasonably likely to materially affect, the 
registrant’s internal control over financial reporting; and 

(5)  The  registrant’s  other  certifying  officer(s)  and  I  have  disclosed,  based  on  our  most  recent  evaluation  of 
internal  control  over  financial  reporting,  to  the  registrant’s  auditors  and  the  audit  committee  of  the 
registrant’s board of directors (or persons performing the equivalent functions): 

(a)  All significant deficiencies and material weaknesses in the design or operation of internal control over 
financial  reporting  which  are  reasonably  likely  to  adversely  affect  the  registrant’s  ability  to  record, 
process, summarize and report financial information; and 

(b)  Any  fraud,  whether  or  not  material,  that  involves  management  or  other  employees  who  have  a 

significant role in the registrant’s internal control over financial reporting. 

Date:  February 29, 2016 

 /s/ Phillip Frost, M.D. 
Phillip Frost, M.D. 
Chief Executive Officer 

143 

 
 
 
 
 
 
I, Adam Logal, certify that:  

CERTIFICATIONS 

(1) 

I have reviewed this Annual Report on Form 10-K of OPKO Health, Inc.; 

Exhibit 31.2 

(2)  Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state 
a  material  fact  necessary  to  make  the  statements  made,  in  light  of  the  circumstances  under  which  such 
statements were made, not misleading with respect to the period covered by this report; 

(3)  Based on my knowledge, the financial statements, and other financial information included in this report, 
fairly  present  in  all  material  respects  the  financial  condition,  results  of  operations  and  cash  flows  of  the 
registrant as of, and for, the periods presented in this report; 

(4)  The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure 
controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control 
over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and 
have: 

(a)  Designed such disclosure controls and procedures, or caused such disclosure controls and procedures 
to  be  designed  under  our  supervision,  to  ensure  that  material  information  relating  to  the  registrant, 
including its consolidated subsidiaries, is made known to us by others within those entities, particularly 
during the period in which this report is being prepared; 

(b)  Designed such internal control over financial reporting, or caused such internal control over financial 
reporting  to  be  designed  under  our  supervision,  to  provide  reasonable  assurance  regarding  the 
reliability  of  financial  reporting  and  the  preparation  of  financial  statements  for  external  purposes  in 
accordance with generally accepted accounting principles; 

(c)  Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this 
report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end 
of the period covered by this report based on such evaluation; and 

(d)  Disclosed  in  this  report  any  change  in  the  registrant’s  internal  control  over  financial  reporting  that 
occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the 
case of an annual report) that has materially affected, or is reasonably likely to materially affect, the 
registrant’s internal control over financial reporting; and 

(5)  The  registrant’s  other  certifying  officer(s)  and  I  have  disclosed,  based  on  our  most  recent  evaluation  of 
internal  control  over  financial  reporting,  to  the  registrant’s  auditors  and  the  audit  committee  of  the 
registrant’s board of directors (or persons performing the equivalent functions): 

(a)  (All significant deficiencies and material weaknesses in the design or operation of internal control over 
financial  reporting  which  are  reasonably  likely  to  adversely  affect  the  registrant’s  ability  to  record, 
process, summarize and report financial information; and 

(b)  Any  fraud,  whether  or  not  material,  that  involves  management  or  other  employees  who  have  a 

significant role in the registrant’s internal control over financial reporting. 

Date: February 29, 2016 

/s/ Adam Logal 
Adam Logal
Senior Vice President, Chief Financial Officer, 
Chief Accounting Officer and Treasurer 

144 

 
 
 
 
 
 
 
 
Exhibit 32.1 

Certification Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 

(Subsections (a) and (b) of Section 1350, Chapter 63 of Title 18, United States Code) 

Pursuant  to  18  U.S.C.  Section  1350,  as  adopted  pursuant  section  906  of  the  Sarbanes-Oxley  Act  of  2002,  I, 

Phillip Frost, Chief Executive Officer of OPKO Health, Inc. (the “Company”), hereby certify that: 

The  Annual  Report  on  Form  10-K  for  the  year  ended  December 31,  2015  (the  “Form  10-K”)  of  the 
Company fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 
1934, and the information contained in the Form 10-K fairly presents, in all material respects, the financial 
condition and results of operations of the Company. 

Date:  February 29, 2016 

/s/ Phillip Frost, M.D.  
Phillip Frost, M.D.  
Chief Executive Officer 

145 

 
 
 
Exhibit 32.2 

Certification Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 

(Subsections (a) and (b) of Section 1350, Chapter 63 of Title 18, United States Code) 

Pursuant  to  18  U.S.C.  Section  1350,  as  adopted  pursuant  section  906  of  the  Sarbanes-Oxley  Act  of  2002,  I, 

Adam Logal, Chief Financial Officer of OPKO Health, Inc. (the “Company”), hereby certify that: 

The  Annual  Report  on  Form  10-K  for  the  year  ended  December 31,  2015  (the  “Form  10-K”)  of  the 
Company fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 
1934, and the information contained in the Form 10-K fairly presents, in all material respects, the financial 
condition and results of operations of the Company. 

Date:  February 29, 2016 

/s/ Adam Logal  
Adam Logal  
Senior Vice President, Chief Financial Officer 
Chief Accounting Officer and Treasurer

146 

 
 
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147 

 
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148 

 
Phillip Frost, M.D. 
Chairman & Chief Executive Officer 
OPKO Health, Inc. 

Jane H. Hsiao, Ph.D., MBA 
Vice Chairman & 
Chief Technical Officer 
OPKO Health, Inc. 

OPKO Health, Inc. Board of Directors 

Richard A. Lerner, M.D. 
Institute Professor 
The Scripps Research Institute 

Dmitry Kolosov 
Chief Executive Officer  
Green-G Logistic LLC 

Steven D. Rubin 
Executive Vice President — Administration 
OPKO Health, Inc. 

John Paganelli 
Chairman of the Board 
Pharos Systems International 

Robert Baron 
Entrepreneur 

Richard C. Pfenniger, Jr. 
Former Chairman, Chief Executive Officer and President 
Continucare Corporation 

Thomas E. Beier 
Former Senior Vice President — Finance and 
Chief Financial Officer 
IVAX Corporation 

Alice Lin-Tsing Yu, M.D., Ph.D. 
Distinguished Chair Professor and Co-Director  
The Institute of Stem Cell & Translational Cancer  
Research, Chang Gung Memorial Hospital 

OPKO Health, Inc. Executive Officers 

Phillip Frost, M.D. 
Chief Executive Officer & Chairman of the Board 

Steven D. Rubin 
Executive Vice President — Administration 

Jane H. Hsiao, Ph.D., MBA 
Vice Chairman & Chief Technical Officer 

Adam Logal 
Senior Vice President, Chief Financial Officer 
Chief Accounting Officer and Treasurer 

STOCK AND INVESTOR INFORMATION 

Corporate Headquarters — 
OPKO Health, Inc. 
4400 Biscayne Boulevard 
Miami, FL 33137 
Telephone: (305) 575-4100 

Independent Auditors— 
Ernst & Young, LLP 
201 South Biscayne Blvd. 
Suite 3000 
Miami, FL 33131 

Common Stock Information — 
OPKO Health, Inc. Common Stock, par value $.01, is listed 
on the New York Stock Exchange under the symbol “OPK”. 

Stockholder Service— Stockholders desiring to change the 
name, address, or ownership of stock, report lost certificates, 
or consolidate accounts should contact the Transfer Agent & 
Registrar: 

American Stock Transfer & Trust Company, LLC 
6201 15th Avenue 
Brooklyn, NY 11219 
Telephone:  800.937.5449 (Domestic) 

718.921.8124 (International) 

Annual Report on Form 10-K — 
Stockholders may obtain a copy of OPKO Health, Inc.’s Annual Report on Form 10-K for the year ended December 31, 2015, 
including the financial statements and the financial statement schedules, without charge by sending a request in writing to 
Investor Relations at OPKO’s headquarters, 4400 Biscayne Blvd, Miami, Florida 33137. 

Except for the historical matters contained herein, statements made in this report are forward looking and are made pursuant to 
the safe harbor provisions of the Securities Litigation Reform Act of 1995. Investors are cautioned that forward looking 
statements involve risks and uncertainties that may affect OPKO’s business and prospects, including economic, competitive, 
governmental, technological, and other factors discussed in this report and in OPKO’s filings with the Securities and Exchange 
Commission, including without limitation, the Annual Report on Form 10-K filed with the SEC on February 29, 2016.