What changed in this filing

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Item 8. Financial Statements and Supplementary Data

2022-03-01 compared with 2021-02-18 · 342 added, 306 removed, 1347 unchanged (32% of the section changed)

FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA

Reports of Independent Registered Certified Public Accounting Firm

Reports of Independent Registered Certified Public Accounting Firm (PCAOB ID No.

Consolidated Balance Sheets

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generally accepted accounting principles.

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company's internal control over financial reporting as of December 31, 2020, 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 18, 2021 expressed an unqualified opinion thereon.

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company's internal control over financial reporting as of December 31, 2021, based on criteria established in Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) and our report dated March 1, 2022 expressed an unqualified opinion thereon.

Basis for Opinion

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Critical Audit Matters

(1) relate to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective or complex judgments.

The critical audit matters communicated below are matters arising from the current period audit of the financial statements that were communicated or required to be communicated to the audit committee and that (1) relate to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective, or complex judgments.

The communication of critical audit matters does not alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matters below, providing separate opinions on the critical audit matters or on the accounts or disclosures to which they relate.

Valuation of Goodwill for Rayaldee

Description of the Matter At December 31, 2020, the Company’s goodwill was $680.6 million, and goodwill assigned to the Rayaldee reporting unit was $93.4 million.

As discussed in Note 2 to the consolidated financial statements, 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.

To determine the estimated fair value of the Rayaldee reporting unit, management considers both market and income valuation approaches.

Auditing management’s annual impairment test of goodwill included in the Rayaldee reporting unit was complex and highly judgmental due to the significant assumptions used in the determination of guideline companies, market transactions and market multiples, as well as the discount rate and revenue growth rates used to estimate future cash flows, which are affected by expectations about future market or economic conditions.

How We Addressed the Matter in Our Audit We obtained an understanding, evaluated the design and tested the operating effectiveness of controls over the Company’s annual goodwill impairment review process, including controls over management’s review of the significant assumptions in the Rayaldee analysis described above.

To test the estimated fair value of the Rayaldee reporting unit, we performed audit procedures that included, among others, assessing methodologies and testing the significant assumptions discussed above and the underlying data used by the Company in its analysis.

We compared the significant assumptions used by management to current industry and economic trends, changes to the Company’s business model and other relevant factors.

We involved valuation specialists to assist with assessing the methodologies and evaluating certain significant assumptions, such as the determination of guideline companies, market transactions, market multiples and the discount rate.

We assessed the historical accuracy of management’s projected financial information and performed sensitivity analyses on significant assumptions to evaluate the changes in the fair value that would result from changes in the assumptions .

Valuation of Goodwill and IPR&D for Rayaldee and Biologics

Description of the Matter At December 31, 2021, the Company’s goodwill was $520.6 million, and indefinite lived in-process research and development assets (IPR&D) was $590.2 million.

Included in the Rayaldee reporting unit was $86.6 million of goodwill.

Included in the Biologics reporting unit was $139.8 million and $590.2 million of goodwill and IPR&D, respectively.

As discussed in Note 3 to the consolidated financial statements, goodwill and indefinite lived IPR&D are 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.

To determine the estimated fair value of their reporting units and their intangible assets included within them, management considers both market and income valuation approaches.

Auditing management’s annual impairment tests for the goodwill and intangible assets in these reporting units was complex and highly judgmental due to the significant assumptions used in the determination of guideline companies, market transactions and market multiples, as well as the expected timing and amount of market revenue share and the discount rate used to estimate future cash flows, which are affected by expectations about future development of IPR&D, market, or economic conditions.

How We Addressed the Matter in Our Audit We obtained an understanding, evaluated the design, and tested the operating effectiveness of controls over the Company’s annual goodwill and intangible assets impairment review process, including controls over management’s review of the significant assumptions in the Rayaldee and Biologics analysis described above.

To test the estimated fair value of the reporting units and the intangible assets included within them, we performed audit procedures that included, among others, assessing methodologies and testing the significant assumptions discussed above and the underlying data used by the Company in its analyses.

We compared the significant assumptions used by management to current market and economic trends and other relevant factors.

We assessed the historical accuracy of management’s estimates and performed sensitivity analyses on significant assumptions to evaluate the changes in the fair value that would result from changes in the assumptions.

Variable Consideration in Determining Revenue from Services

Description of the Matter For the year ended December 31, 2021, the Company recorded revenue from services of $1,607.1 million.

As discussed in Note 15 to the consolidated financial statements, revenue from services includes amounts due under third-party and government payer programs, net of estimates

for explicit and implicit price concessions and other elements of variable consideration.

As discussed in Note 15 to the consolidated financial statements, revenue from services includes amounts due under third-party and government payer programs, net of estimates for explicit and implicit price concessions and other elements of variable consideration.

The Company estimates variable consideration by evaluating, among other factors, recent collections experience as well as changes in reimbursement regulations, claims processing and coverage determinations.

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Miami, Florida

February 18, 2021

March 1, 2022

Report of Independent Registered Public Accounting Firm

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In our opinion, OPKO Health, Inc, and subsidiaries (the Company) maintained, in all material respects, effective internal control over financial reporting as of December 31, 2021, based on the COSO criteria.

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the 2020 consolidated financial statements of the Company and our report dated February 18, 2021 expressed an unqualified opinion thereon.

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the 2021 consolidated financial statements of the Company and our report dated March 1, 2022 expressed an unqualified opinion thereon.

Basis for Opinion

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Miami, Florida

February 18, 2021

March 1, 2022

OPKO Health, Inc.

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Other current assets and prepaid expenses 27,170 32,313

Assets held for sale 314,994 —

Total current assets 823,013 523,179

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Current maturities of operating leases 11,624 9,028

Liabilities associated with assets held for sale 28,156 —

Current portion of lines of credit and notes payable 14,695 24,703

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690,082,283 and 670,585,576 shares issued at December 31, 2021 and 2020, respectively

Treasury Stock, - 549,907 shares at December 31, 2020 and 2019, respectively

Treasury Stock, - 8,655,082 and 549,907 shares at December 31, 2021 and 2020, respectively

( 1,791 ) ( 1,791 )

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Asset impairment charges — — 92,399

Gain on sale of assets ( 31,508 ) — —

Total costs and expenses 1,755,968 1,377,699 1,175,987

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Income (loss) before income taxes and investment losses ( 14,026 ) 48,683 ( 304,965 )

Income tax benefit (provision) ( 17,617 ) ( 7,060 ) 38,726

Income tax provision ( 15,489 ) ( 17,617 ) ( 7,060 )

Net income (loss) before investment losses ( 29,515 ) 31,066 ( 312,025 )

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Change in foreign currency translation and other comprehensive income (loss) ( 26,270 ) 17,845 ( 1,939 )

Reclassification adjustments due to adoption of ASU 2016-01 — — ( 4,876 )

Comprehensive income (loss) $ ( 56,413 ) $ 48,431 $ ( 316,864 )

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Adoption of ASU 2018-07 — — — — ( 926 ) — 926 —

Private placement 26,504,298 265 — — 92,235 — — 92,500

2025 convertible notes including share lending agreement 29,250,000 293 — — 50,559 — — 50,852

Sale of common stock 54,227,749 542 — — 75,520 — — 76,062

Net loss — — — — — — ( 314,925 ) ( 314,925 )

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Exercise of common stock options and warrants 206,875 2 — — 754 — — 756

Adoption of ASU 2018-07 — — — — ( 926 ) — 926 —

2025 convertible notes including share lending agreement 29,250,000 293 — — 50,559 — — 50,852

Sale of common stock 54,227,749 542 — — 75,520 — — 76,062

Net loss — — — — — — ( 314,925 ) ( 314,925 )

Other comprehensive loss — — — — — ( 1,939 ) — ( 1,939 )

Adoption of ASC 326 — — — — — — ( 1,342 ) ( 1,342 )

Net income — — — — — — 30,586 30,586

Other comprehensive income — — — — — 17,845 — 17,845

Balance at December 31, 2020 670,585,576 $ 6,706 ( 549,907 ) $ ( 1,791 ) $ 3,152,694 $ ( 4,225 ) $ ( 1,481,833 ) $ 1,671,551

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Exercise of common stock options and warrants 445,437 5 — — 1,076 — — 1,081

Adoption of ASC 326 — — — — — — ( 1,342 ) ( 1,342 )

Net income — — — — — — 30,586 30,586

Conversion of 2025 convertible notes 19,051,270 190 ( 8,105,175 ) — 55,085 — — 55,275

Net loss — — — — — — ( 30,143 ) ( 30,143 )

Other comprehensive loss — — — — — ( 26,270 ) — ( 26,270 )

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Asset impairment charges — — 92,399

Realized loss (gain) on disposal of fixed assets and sales of equity securities and other ( 10,681 ) 739 46

Change in fair value of equity securities and derivative instruments and other ( 101 ) 8,748 ( 6,524 )

Non-cash revenue from the transfer of intellectual property ( 3,801 ) — —

Realized loss (gain) on disposal of fixed assets and sales of equity securities ( 33,922 ) ( 10,681 ) 739

Loss on conversion of the 2025 Notes 11,111 — —

Change in fair value of equity securities and derivative instruments 3,967 ( 101 ) 8,748

Change in fair value of contingent consideration ( 1,703 ) ( 3,989 ) ( 14,854 )

Deferred income tax provision (benefit) 15,640 4,324 ( 35,133 )

Deferred income tax provision 10,159 15,640 4,324

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

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Proceeds from sale of investments 8,079 15,110 —

Acquisition of businesses, net of cash acquired ( 4,000 ) — —

Proceeds from the sale of property, plant and equipment 66,026 245 671

Capital expenditures ( 32,156 ) ( 33,682 ) ( 12,741 )

Net cash used in investing activities ( 18,327 ) ( 13,270 ) ( 26,119 )

Net cash provided by (used in) investing activities 35,949 ( 18,327 ) ( 13,270 )

Cash flows from financing activities:

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2016-02 $ — $ — $ 39,703

Operating lease right-of-use assets obtained in exchange for lease obligations $ 6,493 $ — $ —

Non-cash financing:

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Our diagnostics business includes BioReference Laboratories, Inc.

(“BioReference”), one of the nation’s largest full service laboratories with a core genetic testing business and an almost 300 -person sales and marketing team focused on driving growth and leveraging new products, including the 4Kscore test.

Our pharmaceutical business features Rayaldee , an FDA-approved treatment for secondary hyperparathyroidism (“SHPT”) in adults with stage 3 or 4 chronic kidney disease (“CKD”) and vitamin D insufficiency (launched in November 2016) and a pipeline of products in various stages of development.

(“BioReference”), one of the nation’s largest full service laboratories with an almost 250 -person sales and marketing team to drive growth and leverage new products.

Our pharmaceutical business features Rayaldee , a U.S.

Food and Drug Administration (“FDA”) approved treatment for secondary hyperparathyroidism (“SHPT”) in adults with stage 3 or 4 chronic kidney disease (“CKD”) and vitamin D insufficiency and a pipeline of products in various stages of development.

Our leading product in development is Somatrogon (hGH-CTP), a once-weekly human growth hormone for which we have partnered with Pfizer, Inc.

(“Pfizer”) and successfully completed a phase 3 study in August 2019, and for which the FDA has accepted the initial BLA for filing and we have submitted a New Drug Application (an “NDA”) with the Ministry of Health, Labour and Welfare in Japan.

(“Pfizer”) and successfully completed a phase 3 study in August 2019.

Regulatory applications for Somatrogon have been submitted to several countries around the world for review.

In February 2022, the European Commission granted marketing authorization in the European Union for Somatrogon under the brand name NGENLA® to treat children and adolescents from as young as 3 years of age with growth disturbance due to insufficient secretion of growth hormone.

In January 2022, the Ministry of Health, Labour and Welfare in Japan approved NGENLA® (Somatrogon) for the long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone.

In October 2021, Health Canada approved NGENLA® for the long-term treatment of pediatric patients who have growth hormone deficiency, and Australia’s Therapeutic Goods Administration approved NGENLA® for the long-term treatment of pediatric patients with growth disturbance due to insufficient secretion of growth hormone.

We also submitted the initial Biologics License Application (“BLA”) with the FDA for approval of Somatrogon (hGH-CTP) in the United States and Pfizer received a Complete Response Letter in January 2022.

Pfizer and OPKO are evaluating the FDA’s comments and will work with the agency to determine the best path forward for Somatrogon (hGH-CTP) in the United States.

We are incorporated in Delaware, and our principal executive offices are located in leased offices in Miami, Florida.

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Our research and development activities are primarily performed at facilities in Woburn, MA, Waterford, Ireland, Kiryat Gat, Israel, and Barcelona, Spain.

On January 18, 2022, Sema4 Holdings Corp.

(“Sema4”) and OPKO announced they had signed an Agreement and Plan of Merger and Reorganization (the “GeneDx Merger Agreement”) with Sema4 Holdings Corp., a Delaware corporation (“Sema4”), pursuant to which Sema4 has agreed to acquire OPKO’s wholly owned subsidiary, GeneDx, Inc.

(“GeneDx”), subject to satisfaction of customary closing conditions (the “GeneDx Transaction”).

The GeneDx Transaction is expected to close in the second quarter of 2022.

Under the terms of the GeneDx Merger Agreement, Sema4 has agreed to acquire GeneDx for an upfront payment of $ 150 million in cash plus 80.0 million shares in Sema4, with up to an additional $ 150 million revenue-based milestones over the next two years (which will be payable in cash or Sema4 shares at Sema4’s discretion).

Based on the closing stock price of Sema4 as of January 14, 2022, the total upfront consideration represents approximately $ 473 million, and the total aggregate consideration including potential milestones is approximately $ 623 million.

As of December 31, 2021, GeneDx met the held-for-sale accounting criteria and the related assets and liabilities are classified as held for sale in the consolidated balance sheet.

Depending upon the value Sema4 shares upon closing of the transaction, an impairment charge may be incurred.

GeneDx was included in our diagnostics segment as of December 31, 2021.

In June 2021, EirGen Pharma Limited (“EirGen”), our wholly owned subsidiary, entered into a definitive agreement to sell one of its facilities in Waterford, Ireland to Horizon Therapeutics plc for $ 65 million in cash less certain assumed and accrued liabilities relating to transferred employees.

The facility, which was formerly included in our pharmaceutical segment, housed EirGen’s sterile-fill-finish business and was no longer a core component of our ongoing operations and business strategy.

The transaction closed in the third quarter of 2021.

We recognized a gain on the sale of the facility in the third quarter of 2021 of $ 31.5 million.

Note 2 Impact of COVID-19

As the disease caused by SARS-CoV-2, a novel strain of coronavirus, COVID-19 continues to spread and severely impact the economy of the U.S.

and other countries around the world, we are committed to being a part of the coordinated public and private sector response to this unprecedented challenge.

In response to the COVID-19 pandemic, BioReference is accepting specimens from U.S.

healthcare providers, clinics and health and hospital systems for two types of COVID-19 testing, diagnostic molecular testing and serology antibody testing, which is intended to promote earlier diagnosis of the coronavirus, assess a patient’s immune response to the virus and aid in limiting the spread of infection.

We have put preparedness plans in place at our facilities to maintain continuity of operations, while also taking steps to keep our employees and customers healthy and safe.

In line with recommendations to reduce large gatherings and increase social distancing, we have, where practical, transitioned many office-based employees to a remote work environment.

As the disease caused by SARS-CoV-2, a novel strain of coronavirus, COVID-19 continues to spread and severely impact the U.S.

economy and economies of other countries around the world, we continue to be a part of the coordinated public and private sector response to this unprecedented challenge as the COVID-19 pandemic continues.

There continues to be a high level of uncertainty relating to how the pandemic will evolve, how governments and consumers will react, progress on the distribution of vaccines and whether the pandemic will have a longer-term effect on the healthcare industry and patient habits.

In response to the COVID-19 pandemic, BioReference is providing COVID-19 solutions, including diagnostic molecular testing and serology antibody testing, to meet the testing needs of its numerous customer verticals, including physicians, health systems, long-term care facilities, governments, schools, employers, professional sports teams and entertainment venues, as well as the general public through relationships with retail pharmacy chains.

Revenue from services for the year ended December 31, 2021 increased by $ 344.9 million as compared to 2020 due to COVID-19 testing volumes.

however we are unable to predict how long the demand will continue for our COVID-19 related testing, or whether pricing and reimbursement policies for testing will sustain, and accordingly, the sustainability of our COVID-19 testing volumes is uncertain.

Additionally, beginning in March 2020, BioReference experienced, and continues to experience, a decline in routine clinical and genomics testing volumes due to the COVID-19 pandemic.

Excluding COVID-19 test volumes, for the year ended December 31, 2020, volumes in our diagnostics segment declined 17 % as compared to volumes for the year ended December 31, 2019.

We are unable to predict how long the demand will continue for our COVID-19 related testing, or whether pricing and reimbursement policies for testing will sustain.

In addition, in the second half of 2021, overall demand for COVID-19 testing has declined, and accordingly, the sustainability of our COVID-19 testing volumes is uncertain.

Additionally, beginning in March 2020, BioReference experienced a decline in testing volumes due to the COVID-19 pandemic;

however as stay at home orders and other restrictions have been lifted, we have seen our routine clinical and genomic testing volumes trending towards normalization with prior periods.

Should stay at home orders or other restrictions be reenacted, we could see our routine testing levels decline.

Excluding COVID-19 test volumes, for the year ended December 31, 2021, genomic and routine clinical test volume increased 26.4 % and 6.9 % as compared to volumes for the year ended December 31, 2020.

Additionally, sales of Rayaldee have not increased in accordance with its expected growth trajectory as a result of challenges in onboarding new patients due to the COVID-19 pandemic.

Federal, state and local governmental policies and initiatives designed to reduce the transmission of COVID-19 have resulted in, among other things, a significant reduction in physician office visits, the cancellation of elective medical procedures, customers closing or severely curtailing their operations (voluntarily or in response to government orders), and the adoption of work-from-home or shelter-in-place policies.

As stay at home orders and other restrictions have been lifted, we have seen our routine clinical and genomic testing volumes trending towards normalization with prior periods;

however should stay at home orders or other

restrictions be reenacted, we could see our routine testing levels decline.

We also continue to see a substantial need for COVID-19 testing by our existing clients and expect new clients as infection rates for the virus continue to increase across the country.

In March 2020, in response to the COVID-19 pandemic, the Coronavirus Aid, Relief, and Economic Security (CARES) Act was signed into law.

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We have received, or expect to receive a number of benefits under the CARES Act including, but not limited to:

• During the year ended December 31, 2020, we received approximately $ 14 million under The Centers for Medicare & Medicaid Services (CMS) Accelerated and Advance Payment Program, which provides accelerated payments to Medicare providers/suppliers working to provide treatment to patients and combat the COVID-19 pandemic, and such amounts advanced to us are loans which will be offset against future claims and must be repaid in 2021;

• During the year ended December 31, 2020, we received approximately $ 14 million under The Centers for Medicare & Medicaid Services (CMS) Accelerated and Advance Payment Program, which provides accelerated payments to Medicare providers/suppliers working to provide treatment to patients and combat the COVID-19 pandemic, and the amounts advanced are loans which will be offset against future claims and were repaid in 2021.

These loans are initially recorded as contract liabilities included in Accrued expenses and are reduced as the amounts are recouped by CMS;

• We are eligible to defer depositing the employer’s share of Social Security taxes for payments due from March 27, 2020 through December 31, 2020, interest-free and penalty-free;

• We received approximately $ 16.2 million during the year ended December 31, 2020 from the funds that were distributed to healthcare providers for related expenses or lost revenues that are attributable to the COVID-19 pandemic;

• We received approximately $ 16.2 million during 2020 from the funds that were distributed to healthcare providers for related expenses or lost revenues that are attributable to the COVID-19 pandemic.

We recognized the $ 16.2 million grant in other revenues for the year ended December 31, 2020;

Department of Health and Human Services (HHS), will provide claims reimbursement to healthcare providers generally at Medicare rates for testing uninsured patients;

• Clinical laboratories are provided a one-year reprieve from the reporting requirements under the Protecting Access to Medicare Act (“PAMA”) as well as a one-year delay of reimbursement rate reductions for clinical laboratory services provided under Medicare that were scheduled to take place in 2021.

In October 2020, the U.S.

Department of Health & Human Services issued new reporting requirements for the CARES Act funding.

Due to these new reporting requirements and various interpretations, there is a reasonable possibility that amounts recorded under CARES Act funding will change in future periods.

Since the pandemic began in the U.S., we have invested in testing capabilities and infrastructure to meet demand for our molecular and antibody testing for COVID-19.

In 2021, we kicked off company-wide lab operations specimen acquisition, logistics, procurement, customer service, cost reduction initiatives to rightsize our cost structure to match the declining COVID testing volumes and to drive efficiency gains in our core clinical lines of business.

Three vaccines for COVID-19 have received approval or emergency authorization and have had increasingly widespread acceptance.

However, we believe that, based on our experience with the pandemic, the high medical need for efficient and widespread testing for COVID-19 will extend beyond the current phase of the pandemic.

Our belief is supported by the unprecedented healthcare and economic impact of the pandemic thus far, the uneven and incomplete rollout of vaccines and the fact that significant portions of the U.S.

population may never be vaccinated, and the continued likelihood of surges of COVID-19 including from new strains of SARS-CoV-2 with uncertain susceptibility to the current vaccines.

We believe that these factors have greatly magnified the need for more effective therapeutics, and the need for efficient and widespread testing, with properties targeted to the disease processes caused by serious viral infections.

Note 3 Summary of Significant Accounting Policies

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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 and net realizable value.

Inventories at our diagnostics segment consist primarily of purchased laboratory supplies, which is used in our testing laboratories.

Inventory obsolescence expense for the years ended December 31, 2020 and 2019 was $ 4.4 million and $ 2.3 million, respectively.

Inventories at our diagnostics segment consist primarily of purchased laboratory supplies, which are used in our testing laboratories.

Inventory obsolescence expense for the years ended December 31, 2021, 2020 and 2019 was $ 6.5 million, $ 4.4 million and $ 2.3 million, respectively.

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.

We may accumulate commercial quantities of certain product candidates prior to the date we anticipate that such products will receive final FDA approval.

The accumulation of such pre-launch inventories exposes us to the risk that such products may not be approved for marketing by the FDA on a timely basis, or ever;

however, we may accumulate pre-launch inventories depending on the commercial value of the applicable product launch opportunity.

In accordance with our policy, we expense this pre-launch inventory.

Goodwill and intangible assets.

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Goodwill was $ 520.6 million and $ 680.6 million, respectively, at December 31, 2021 and 2020.

In addition, at December 31, 2021, Assets held for sale includes $ 151.8 million of goodwill related to GeneDx.

Estimating the fair value of a reporting unit for goodwill impairment is highly sensitive to changes in projections and assumptions and changes in assumptions could potentially lead to impairment.

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Ultimately, potential changes in these assumptions may impact the estimated fair value of a reporting unit and result in an impairment if the fair value of such reporting unit is less than its carrying value.

Net intangible assets other than goodwill were $ 1.1 billion, including IPR&D of $ 590.2 million, at both December 31, 2020 and 2019.

Net intangible assets at December 31, 2021 and 2020, other than goodwill were $ 911.9 million and $ 1.1 billion, respectively, including IPR&D of $ 590.2 million.

Intangible assets are highly vulnerable to impairment charges, particularly newly acquired assets for recently launched products and IPR&D.

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If the carrying amount of an asset exceeds its estimated undiscounted future cash flows, then an impairment charge is recognized for the amount by which the carrying amount of the asset exceeds the fair value of the asset.

No impairment charges were recognized for the year ended December 31.

2021 and December 31, 2020.

Impairment charges for the year ended December 31, 2019 were $ 92.4 million and consisted of a goodwill impairment charge of $ 26.2 million to write the carrying amount of the OPKO Diagnostics, CURNA and Transition Therapeutics reporting units down to their estimated fair value, an impairment charge of $ 44.8 million to write our IPR&D assets for OPK88003 and CURNA’s platform technology for oligonucleotide therapeutics down to their estimated fair value, and an impairment charge of $ 20.7 million to write our intangible asset for the Claros Analyzer down to its estimated fair value as a result of our testing.

These impairment charges for the year ended December 31, 2019, resulted from liquidity constraints, longer than expected development timelines and changes in the competitive landscape, which resulted in changes to our estimates and assumptions of the expected future cash flows of the reporting units focused on the development of the Claros Analyzer, OPK88003 and CURNA’s platform technology.

We recorded a goodwill impairment charge of $ 11.7 million in Asset impairment charges in our Consolidated Statement of Operations for the year ended December 31, 2018 to write the carrying amount of the FineTech reporting unit down to its estimated fair value.

We recorded an impairment charge of $ 10.1 million in Asset impairment charges in our Consolidated Statement of Operations for the year ended December 31, 2018 to write our IPR&D assets for Alpharen and OPK88004 down to their estimated fair value as a result of our testing.

We believe that our estimates and assumptions are reasonable and otherwise consistent with assumptions that marketplace participants would use in their estimates of fair value.

However, if future results are not consistent with our estimates and assumptions, including as a result of the COVID-19 global pandemic, then we may be exposed to an impairment charge, which could be material.

We believe that our estimates and assumptions in testing goodwill and other intangible assets, including IPR&D, for impairment are reasonable and otherwise consistent with assumptions that marketplace participants would use in their estimates of fair value.

However, if future results are not consistent with our estimates and assumptions, including as a result of the COVID-19 global pandemic, then we may be exposed to additional impairment charges, which could be material.

Our 2021 impairment test of the OPKO Biologics reporting unit, including IPR&D related to Somatrogon, indicated an excess of estimated fair value over the carrying amount of approximately 19 %.

We submitted the initial BLA with the FDA for approval of Somatrogon (hGH-CTP) in the United States and Pfizer received a Complete Response Letter in January 2022.

Pfizer and OPKO are evaluating the FDA’s comments and will work with the agency to determine the best path forward for Somatrogon in the United States.

If we are unable to successfully commercialize Somatrogon in the U.S., or changes in projections and assumptions negatively impact our forecast of net cash flows, we may be exposed to a material impairment charge related to the IPR&D for Somatrogon.

We amortize intangible assets with definite lives on a straight-line basis over their estimated useful lives, ranging from 3 to 20 years.

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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.

Long-lived assets, such as property and equipment and assets held for sale, 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.

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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.

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.

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deferred tax assets are established, because realization of these tax benefits through future taxable income does not meet the more-likely-than-not threshold.

On December 22, 2017, the Tax Act was enacted into law and the new legislation contains several key tax provisions, including a reduction of the corporate income tax rate from 35% to 21% effective January 1, 2018 and a one-time mandatory transition tax on accumulated foreign earnings, among others.

We were required to recognize the effect of the tax law changes in the period of enactment, such as remeasuring our U.S.

deferred tax assets and liabilities, as well as reassessing the net realizability of our deferred tax assets and liabilities.

Effective January 1, 2018, the Tax Act provides for a new GILTI provision.

Under the GILTI provision, certain foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary’s tangible assets are included in U.S.

taxable income.

The Company currently estimates GILTI will be immaterial for the years ended December 31, 2020, 2019 and 2018, although interpretive guidance continues to be issued and future guidance may impact this analysis.

The Company has not recorded any deferred taxes for future GILTI inclusions as any future inclusions are expected to be treated as a period expense and offset by net operating loss carryforwards in the U.S.

We operate in various countries and tax jurisdictions globally.

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In connection with an examination of a 2014 and 2015 tax return in a foreign jurisdiction, the taxing authority has issued an initial income tax assessment of approximately $ 66 million (including interest).

We are protesting this assessment as we believe that it is without technical merit.

We are protesting this

assessment as we believe that it is without technical merit.

We expect to exhaust all administrative and judicial remedies necessary to resolve the matter, which could be a lengthy process.

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For a complete discussion of accounting for Revenues from services, Revenues from products and Revenue from transfer of intellectual property and other , refer to Note 15.

Concentration of credit risk and allowance for doubtful accounts .

Concentration of credit risk and allowance for credit losses .

Financial instruments that potentially subject us to concentrations of credit risk consist primarily of accounts receivable.

Substantially all of our accounts receivable are with either companies in the health care industry or patients.

Substantially all of our accounts receivable are with either companies in the healthcare industry or patients.

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 healthcare programs are funded by federal and state governments, and payment is primarily dependent upon submitting appropriate documentation.

While we have receivables due from federal and state governmental agencies, we do not believe that such receivables represent a credit risk because the related healthcare programs are funded by federal and state governments, and payment is primarily dependent upon submitting appropriate documentation.

At December 31, 2021 and 2020, receivable balances (net of explicit and implicit price concessions) from Medicare and Medicaid were 8 % and 6 %, respectively, of our consolidated Accounts receivable, net.

At December 31, 2020, receivable balances (net of explicit and implicit price concessions) due directly from states, cities and other municipalities, specifically related to our real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) assay to detect COVID-19, were 6.3 % of our consolidated accounts receivable, net.

At December 31, 2021 and 2020, receivable balances (net of explicit and implicit price concessions) due directly from states, cities and other municipalities, specifically related to our real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) assay to detect COVID-19, were 4.1 % and 6.3 % of our consolidated accounts receivable, net.

The portion of our accounts receivable due from individual patients comprises the largest portion of credit risk.

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The allowance for credit losses was $ 1.8 million and $ 2.1 million at December 31, 2021 and 2020, respectively.

The credit loss expense for the years ended December 31, 2020 and 2019 was $ 0.2 million and $ 0.5 million, respectively.

The credit loss expense for the years ended December 31, 2021, 2020 and 2019 was $ 0.4 million, $ 0.2 million and $ 0.5 million, respectively.

Equity-based compensation.

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The pharmaceutical segment consists of our pharmaceutical operations in Chile, Mexico, Ireland, Israel and Spain, Rayaldee product sales and our pharmaceutical research and development.

The diagnostics segment primarily consists of clinical laboratory operations through BioReference and point-of-care operations.

The diagnostics segment primarily consists of clinical and genomics laboratory operations through BioReference and point-of-care operations.

There are no significant inter-segment sales.

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We record these investments as equity method investments or as equity securities based on our percentage of ownership and whether we have significant influence over the operations of the investees.

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.

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 5.

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Refer to Note 5.

Recently adopted accounting pronouncements .

In June 2016, the FASB issued ASU No.

2016-13, “Financial Instruments - Credit Losses (Topic 326):

Measurement of Credit Losses on Financial Instruments,” which amends the impairment model by requiring entities to use a forward-looking approach based on expected losses rather than incurred losses to estimate credit losses on certain types of financial instruments, including trade receivables.

This may result in the earlier recognition of allowances for losses.

The ASU is effective for public entities for fiscal years beginning after December 15, 2019, with early adoption permitted.

The adoption of ASU 2016-13 on January 1, 2020, did not have a significant impact on our Consolidated Financial Statements.

Pending accounting pronouncements .

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The dilutive impact of the 2033 Senior Notes, the 2023 Convertible Notes and the 2025 Notes (each, as defined and discussed in Note 7) has been considered using the “if converted” method.

For periods in which their effect would be antidilutive, no effect is given to outstanding options, warrants or the potentially dilutive shares issuable pursuant to the 2033 Senior Notes, the 2023 Convertible Notes and the 2025 Notes in the dilutive computation.

For periods in which their effect would be antidilutive, no effect is given to Common Stock issuable under outstanding options or warrants or the potentially dilutive shares issuable pursuant to the 2033 Senior Notes, the 2023 Convertible Notes and the 2025 Notes in the dilutive computation.

A total of 62,204,391 , 70,029,480 and 67,765,380 potential shares of Common Stock have been excluded from the calculation of diluted net income (loss) per share for the years ended December 31, 2021, 2020 and 2019, respectively, because their inclusion would be antidilutive.

A full presentation of diluted earnings per share has not been provided because the required adjustments to the numerator and denominator resulted in diluted earnings per share equivalent to basic earnings per share.

During the year ended December 31, 2020, an aggregate of 206,875 options and warrants to purchase shares of our Common Stock were exercised, resulting in the issuance of 206,875 shares of Common Stock.

Of the 206,875 Common Stock options and Common Stock warrants exercised, 0 shares of Common Stock were surrendered in lieu of a cash payment via the net exercise feature of the applicable option and warrant agreements.

During the year ended December 31, 2019, an aggregate of 24,877 options and warrants to purchase shares of our Common Stock were exercised, resulting in the issuance of 19,232 shares of Common Stock.

Of the 24,877 Common Stock options and Common Stock warrants exercised, 5,645 shares of Common Stock were surrendered in lieu of a cash payment via the net exercise feature of the applicable option and warrant agreements.

During the year ended December 31, 2018, an aggregate of 540,000 options and warrants to purchase shares of our Common Stock were exercised, resulting in the issuance of 353,677 shares of Common Stock.

Of the 540,000 Common Stock options and Common Stock warrants exercised, 186,323 shares of Common Stock were surrendered in lieu of a cash payment via the net exercise feature of the applicable option and warrant agreements .

During the year ended December 31, 2021, 445,437 Common Stock options to purchase shares of our Common Stock were exercised, resulting in the issuance of 445,437 shares of Common Stock.

Of the 445,437 Common Stock options exercised, 0 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, 2020, 206,875 Common Stock options to purchase shares of our Common Stock were exercised, resulting in the issuance of 206,875 shares of Common Stock.

Of the 206,875 Common Stock options exercised, 0 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, 2019, 24,877 Common Stock options to purchase shares of our Common Stock were exercised, resulting in the issuance of 19,232 shares of Common Stock.

Of the 24,877 Common Stock options exercised, 5,645 shares of Common Stock were surrendered in lieu of a cash payment via the net exercise feature of the agreements .

Note 5 Investments

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(“Xenetic”) ( 1 %).

The aggregate total assets, liabilities, and net losses of our equity method investees as of and for the year ended December 31, 2020 were $ 90.9 million, $ 28.4 million, and $ 75.4 million, respectively.

The aggregate amount of assets, liabilities, and net losses of our equity method investees as of and for the year ended December 31, 2021 were $ 223.6 million, $ 37.9 million, and $ 69.4 million, respectively.

The aggregate total assets, liabilities, and net losses of our equity method investees as of and for the year ended December 31, 2020 was $ 90.9 million, $ 28.4 million, and $ 75.4 million, respectively.

We have determined that we and/or our related parties can significantly influence the control of our equity method investments through our board representation and/or voting power.

Accordingly, we account for our investment in these entities under the equity method and record our proportionate share of their respective losses in Loss from investments in investees in our Consolidated Statement of Operations.

Included in Loss from investments in investees for the year ended December 31, 2018 is a charge of $ 2.9 million to write our investment in InCellDx, Inc.

down to its fair value as of December 31, 2018.

We have determined that we and/or our related parties can significantly influence control of our equity method investments through our board representation and/or voting power.

Accordingly, we account for our investment in these entities under the equity method and 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 respective shares of common stock and the number of shares held by us as of December 31, 2021 and 2020 was $ 4.5 million and 7.5 million, respectively.

Investments in Equity securities

Our equity securities consist of investments in Phio Pharmaceuticals (“Phio”) ( 0.01 %), VBI Vaccines Inc.

(“VBI”) ( 1 %), ChromaDex Corporation ( 0.1 %), MabVax Therapeutics Holdings, Inc.

(“MabVax”) ( 1 %), and Eloxx Pharmaceuticals, Inc.

(“Eloxx”) ( 3 %).

Our equity securities consist of investments in Phio Pharmaceuticals (“Phio”) (ownership 0.01 %), VBI Vaccines Inc.

(“VBI”) ( 1 %), ChromaDex Corporation (“ChromaDex”) ( 0.1 %), Eloxx Pharmaceuticals, Inc.

(“Eloxx”) ( 2 %), CAMP4 Therapeutics Corporation (“CAMP4”) ( 4.58 %), and HealthSnap, Inc.

We have determined that our ownership, along with that of our related parties, does not provide us with significant influence over the operations of these investments.

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Net gains and (losses) recognized during the period on equity securities $ ( 1,832 ) $ 10,376 $ ( 7,443 )

Net gains and losses realized during the period on equity securities ( 10,324 ) — 113

Net gains realized during the period on equity securities ( 2,981 ) ( 10,324 ) —

Unrealized net gains and losses recognized during the period on equity securities still held at the reporting date $ ( 4,813 ) $ 52 $ ( 7,443 )

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Warrants and options

In addition to our equity method investments and equity securities, we hold options to purchase 47 thousand additional shares of BioCardia, all of which were vested as of December 31, 2020, and 33 thousand, 0.7 million, 40 thousand and 404 warrants to purchase additional shares of COCP, InCellDx, Inc., Xenetic and Phio, respectively.

In addition to our equity method investments and equity securities, we hold options to purchase 47 thousand additional shares of BioCardia, all of which were vested as of December 31, 2021 and 2020, and 33 thousand, 0.7 million to purchase additional shares of COCP and InCellDx, Inc., 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 Statement of Operations.

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Investments in variable interest entities

We have determined that we hold variable interests in Detect Genomix, LLC (“Detect Genomix”) and Zebra Biologics, Inc.

We have determined that we hold variable interests in LeaderMed Health Group Limited (“LeaderMed”), Detect Genomix, LLC (“Detect Genomix”) and Zebra Biologics, Inc.

We made this determination as a result of our assessment that they do not have sufficient resources to carry out their principal activities without additional financial support.

On September 14, 2021, we and LeaderMed Health Group Limited (“LeaderMed”), a pharmaceutical development company with operations based in Asia, announced the formation of a joint venture to develop, manufacture and commercialize two of OPKO’s clinical stage, long-acting drug products in Greater China and eight other Asian territories.

Under the terms of the agreements, we have granted the joint venture exclusive rights to develop, manufacture and commercialize (a) OPK88003, an oxyntomodulin analog being developed for the treatment of obesity and diabetes, and (b) Factor VIIa-CTP, a novel long-acting coagulation factor being developed to treat hemophilia, in exchange for 4,703 shares 47 % ownership interest in the joint venture.

In addition, we received an upfront payment of $ 1.0 million and will be reimbursed for clinical trial material and technical support we provide the joint venture.

In order to determine the primary beneficiary of the joint venture, we evaluated our investment and our related parties’ investment, as well as our investment combined with the related parties’ investment to identify if we had the power to direct the activities that most significantly impact the economic performance of the joint venture.

Based on the capital structure, governing documents and overall business operations of the joint venture, we determined that, while a VIE, we do not have the power to direct the activities that most significantly impact the joint venture’s economic performance and do not have an obligation to fund expected losses.

We did determine, that we can significantly influence control of the joint venture through our board representation and voting power.

Therefore, we have the ability to exercise significant influence over the joint venture’s operations and account for our investment in the joint venture under the equity method.

In August 2020, GeneDx, Inc., a subsidiary of BioReference, announced that it had entered into an agreement with Pediatrix Medical Group (“Pediatrix”), a provider of maternal-fetal, and pediatric medical and surgical subspecialty physician services, to offer genomic sequencing to support clinical diagnosis in neonatal intensive care units staffed by Pediatrix’s affiliated neonatologists.

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We have not made any other investments in or loans to Detect Genomix through December 31, 2021.

In January 2022, the Detect Genomix agreement was terminated.

In order to determine the primary beneficiary of Detect Genomix, we evaluated our investment to identify if we had the power to direct the activities that most significantly impact the economic performance of Detect Genomix.

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Therefore, we have the ability to exercise significant influence over Detect Genomix’s operations and account for our investment in Detect Genomix under the equity method.

The joint venture was dissolved in January 2022.

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, 2021 and 2020).

Zebra is a privately held biotechnology company focused on the discovery and development of biosuperior antibody therapeutics and complex drugs.

Richard Lerner, M.D., a member of our Board of Directors, is a founder of Zebra and, along with Dr.

Richard Lerner, M.D., a former member of our Board of Directors, was a founder of Zebra.

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 parties’ investment to identify if we had the power to direct the activities that most significantly impact the economic performance of Zebra.

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 and have no obligation to fund expected losses.

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 and have no obligation to fund expected losses.

We did determine, however, that we can significantly influence control of Zebra through our board representation and voting power.

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Other current assets and prepaid expenses

Taxes recoverable $ 13,440 $ 19,808

Other receivables 2,502 3,262

Prepaid supplies $ 10,641 $ 7,259

Prepaid insurance 4,383 3,803

Taxes recoverable 5,598 13,440

Other receivables 353 2,502

Other 6,195 5,309

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Employee benefits 45,939 43,300

Contract liabilities 15,783 19,196

Commitments and contingencies 27,819 15,454

Clinical trials 4,867 7,112

Professional fees 4,985 1,333

Finance leases short-term 2,257 2,453

Professional fees 2,121 4,985

Contingent consideration 487 1,188

Contract liabilities 258 15,783

Other 69,299 78,434

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Other long-term liabilities:

Line of credit $ — $ 44,749

Contract liabilities 595 2,571

Contingent consideration 4,507 7,308

Finance leases long-term $ 2,924 $ 2,805

Contingent consideration 2,350 4,507

Mortgages and other debts payable 2,224 3,837

Contract liabilities 208 595

Other 7,356 25,328

$ 15,062 $ 37,072

Our intangible assets and goodwill relate principally to our completed acquisitions of OPKO Renal, OPKO Biologics, EirGen Pharma Limited (“EirGen”) and BioReference.

Our intangible assets and goodwill relate principally to our completed acquisitions of OPKO Renal, OPKO Biologics, EirGen and BioReference.

We amortize intangible assets with definite lives on a straight-line basis over their estimated useful lives.

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Our goodwill is not tax deductible for income tax purposes in any jurisdiction in which we operate.

As of December 31, 2021, GeneDx met the held-for-sale accounting criteria and the related assets and liabilities are recognized at the lower of carrying value or fair value less costs to sell in the consolidated balance sheet.

In addition, at December 31, 2021, Assets held for sale includes $ 151.8 million of goodwill related to GeneDx.

The changes in value of the intangible assets and goodwill during the year ended December 31, 2020, are primarily due to foreign currency fluctuations between the Chilean Peso, the Euro and the Shekel against the U.S.

The changes in value of the intangible assets and goodwill during the year ended December 31, 2019 are primarily due to an impairment charge of $ 44.8 million to write our IPR&D assets for OPK88003 and CURNA’s platform technology for oligonucleotide therapeutics down to their estimated fair value, a goodwill impairment charge of $ 26.2 million to write the carrying amount of the OPKO Diagnostics, CURNA and Transition Therapeutics reporting units down to their estimated fair value, and an impairment charge of $ 20.7 million to write our intangible asset for the Claros Analyzer down to its estimated fair value.

The changes in value of the intangible assets during the year ended December 31, 2018 are primarily due to an impairment charge of $ 10.1 million to write our IPR&D assets for Alpharen and OPK88004 down to their estimated fair value.

The changes in value of our intangible assets and goodwill for the years ended December 31, 2019 and 2018 were also affected by foreign currency fluctuations between the Chilean Peso, the Euro and the Shekel against the U.S.

The following table reflects the changes in the allowance for doubtful accounts, provision for inventory reserve and tax valuation allowance accounts:

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balance Charged

expense Written-off Ending

expense Written-off Charged

to other Ending

Allowance for doubtful accounts $ ( 2,055 ) ( 369 ) 585 — $ ( 1,839 )

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The following table summarizes the changes in Goodwill by reporting unit during the years ended December 31, 2021 and 2020.

(In thousands) Gross goodwill at January 1 Cumulative impairment at January 1 Goodwill impairment Foreign exchange and other Balance at December 31st Gross goodwill at January 1 Cumulative impairment at January 1 Goodwill impairment Foreign exchange and other Balance at December 31

Pharmaceuticals

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$ 718,625 $ ( 38,023 ) $ — $ ( 160,002 ) $ 520,601 $ 709,963 $ ( 38,023 ) $ — $ 8,662 $ 680,602

Foreign exchange and other amounts for the year ended December 31, 2021 includes amounts related to GeneDx which is included as Assets held for sale at December 31, 2021.

As of December 31, 2021 and 2020, our debt consists of the following:

For the years ended December 31,

(In thousands) 2020 2019

(In thousands) As of December 31, 2021 As of December 31, 2020

2025 Notes $ 119,360 $ 156,163

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Current portion of lines of credit and notes payable 14,695 24,703

JP Morgan Chase and LT notes payable included in long-term liabilities 4,513 49,473

LT notes payable included in long-term liabilities 2,642 4,513

Total $ 205,272 $ 251,205

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Frost, pursuant to which the lender committed to provide us with an unsecured line of credit in the amount of $ 100 million.

Borrowings under the line of credit will bear interest at a rate of 11 % per annum and may be repaid and reborrowed at any time.

The credit agreement includes various customary remedies for the lender following an event of default, including the acceleration of repayment of outstanding amounts under line of credit.

The line of credit matures on February 25, 2025.

The line of credit also calls for a commitment fee equal to 0.25 % per annum of the unused portion of the line.

As of December 31, 2020, no funds were borrowed under the line of credit.

The line of credit called for a commitment fee equal to 0.25 % per annum of the unused portion of the line.

No funds were borrowed under this line of credit and we terminated this line of credit in June 2021.

In February 2019, we issued $ 200.0 million aggregate principal amount of Senior Convertible Notes due 2025 (the “2025 Notes”) in an underwritten public offering.

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We may not redeem the 2025 Notes prior to February 15, 2022.

We may redeem for cash any or all of the notes, at our option, on or after February 15, 2022, if the last reported sale price of our Common Stock has been at least 130 % of the then current conversion price for the notes for at least 20 trading days (whether or not consecutive) during any 30 consecutive

trading day period (including the last trading day of such period) ending on, and including, the trading day immediately preceding the date on which we provide notice of redemption at a redemption price equal to 100 % of the principal amount of the notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

preceding the date on which we provide notice of redemption at a redemption price equal to 100 % of the principal amount of the notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

No sinking fund is provided for the 2025 Notes.

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and structurally junior to all indebtedness and other liabilities (including trade payables) of our current or future subsidiaries.

In May 2021, we entered into exchange agreements with certain holders of the 2025 Notes pursuant to which the holders exchanged $ 55.4 million in aggregate principal amount of the outstanding 2025 Notes for 19,051,270 shares of our Common Stock (the “Exchange”).

We recorded an $ 11.1 million non-cash loss related to the Exchange.

In conjunction with the issuance of the 2025 Notes, we agreed to loan up to 30,000,000 shares of our Common Stock to affiliates of the underwriter in order to assist investors in the 2025 Notes to hedge their position.

As of December 31, 2020 and 2019, a total of 29,250,000 shares were issued under the share lending arrangement.

Following consummation of the Exchange, the number of outstanding borrowed shares of Common Stock was reduced by 8,105,175 shares.

As of December 31, 2021 and 2020, a total of 21,144,825 and 29,250,000 shares were issued under the share lending arrangement, respectively.

We will not receive any of the proceeds from the sale of the borrowed shares, but we received a one-time nominal fee of $ 0.3 million for the newly issued shares.

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Amortization of debt discount and debt issuance costs — 6,639 723 7,362

Conversion ( 55,420 ) 10,151 1,104 ( 44,165 )

Balance at December 31, 2021 $ 144,580 $ ( 22,747 ) $ ( 2,473 ) $ 119,360

On November 8, 2018, we entered into a credit agreement with an affiliate of Dr.

Frost, pursuant to which the lender committed to provide us with an unsecured line of credit in the aggregate principal amount of $ 60 million.

The credit agreement was terminated on or around February 20, 2019 and we repaid the $ 28.8 million outstanding thereunder from the proceeds of the 2025 Notes offering.

In February 2018, we issued a series of 5 % Convertible Promissory Notes (the “2023 Convertible Notes”) in the aggregate principal amount of $ 55.0 million.

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The 2033 Senior Notes mature on February 1, 2033, unless earlier repurchased, redeemed or converted.

Upon a fundamental change as defined in the indenture, 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 related fundamental change repurchase date.

Upon a fundamental change as defined in the indenture, 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 related fundamental change repurchase date.

From 2013 to 2016, holders of the 2033 Senior Notes converted $ 143.2 million in aggregate principal amount into an aggregate of 21,539,873 shares of Common Stock.

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In 2017, certain terms of the embedded derivatives expired pursuant to the original agreement and the embedded derivatives no longer met the criteria to be separated from the host contract and, as a result, the embedded derivatives were no longer required to be valued separate and apart from the 2033 Senior Notes and were reclassified to additional paid in capital.

In November 2015, BioReference and certain of its subsidiaries entered into a credit agreement, as amended from time to time, with JPMorgan Chase Bank, N.A.

In November 2015, BioReference and certain of its subsidiaries entered into a credit agreement with JPMorgan Chase Bank, N.A.

(“CB”), as lender and administrative agent, as amended (the “Credit Agreement”).

The Credit Agreement provides for a $ 75.0 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.

The Credit Agreement matures on November 5, 2021 and is guaranteed by all of BioReference’s domestic subsidiaries.

The Credit Agreement is also secured by substantially all assets of BioReference and its domestic subsidiaries, as well as a non-recourse pledge by us of our equity interest in BioReference.

Availability under the Credit Agreement is based on a borrowing base comprised of eligible accounts receivables of BioReference and certain of its subsidiaries, as specified therein.

On August 30, 2021, the Credit Agreement was amended and restated (the “A&R Credit Agreement”).

The A&R Credit Agreement is guaranteed by all of BioReference’s domestic subsidiaries.

The A&R Credit Agreement is also secured by substantially all assets of BioReference and its domestic subsidiaries, as well as a non-recourse pledge by us of our equity interest in BioReference.

Availability under the A&R Credit Agreement is based on a borrowing base composed of eligible accounts receivables of BioReference and certain of its subsidiaries, as specified therein.

As of December 31, 2021, $ 64.8 million remained available for borrowing under the Credit Agreement.

Principal under the Credit Agreement is due upon maturity on November 5, 2021.

At BioReference’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.

Principal under the Credit Agreement is due upon maturity on August 30, 2024.

At BioReference’s option, borrowings under the A&R Credit Agreement (other than swingline loans) 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 0.75 % or (ii) the LIBOR rate (adjusted for statutory reserve requirements for Eurocurrency liabilities) plus an applicable margin of 1.75 %.

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.

As of December 31, 2020 and 2019, $ 7.1 million and $ 44.7 million, respectively, was outstanding under the Credit Agreement.

The Credit Agreement contains customary covenants and restrictions, including, without limitation, covenants that require BioReference 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 BioReference 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 BioReference 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 BioReference and its subsidiaries are restricted from sale, transfer, lease, disposal or

distributions to the Company, subject to certain exceptions.

As of December 31, 2020, BioReference and its subsidiaries had net assets of approximately $ 1.0 billion, which included goodwill of $ 434.8 million and intangible assets of $ 329.5 million.

In addition to the Credit Agreement with CB, we had line of credit agreements with eleven other financial institutions as of December 31, 2020 and 2019 in the U.S., Chile and Spain.

The A&R Credit Agreement also calls for other customary fees and charges, including an unused commitment fee of 0.375 % if the average quarterly availability is 50% or more of the revolving commitment, or 0.25 % if the average quarterly availability is less than or equal to 50% of the revolving commitments.

As of December 31, 2021 and 2020, no amount and $ 7.1 million, respectively, was outstanding under the A&R Credit Agreement.

The A&R Credit Agreement contains customary covenants and restrictions, including, without limitation, covenants that require BioReference 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 BioReference 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 A&R Credit Agreement, notwithstanding the ability of BioReference to meet its debt service obligations.

The A&R 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 A&R Credit Agreement and execution upon the collateral securing obligations under the A&R Credit Agreement.

Substantially all the assets of BioReference and its subsidiaries are restricted from sale, transfer, lease, disposal or distributions to the Company, subject to certain exceptions.

As of December 31, 2021, BioReference and its subsidiaries had net assets of approximately $ 1,103.6 million, which included goodwill of $ 283.0 million and intangible assets of $ 204.4 million.

In addition to the A&R Credit Agreement with CB, we had line of credit agreements with eleven other financial institutions as of December 31, 2021 and 2020 in the U.S., Chile and Spain.

These lines of credit are used primarily as a source of working capital for inventory purchases.

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BICE Bank 5.50 % 2,500 850 1,166

BBVA Bank 5.50 % 3,250 — 11

Security Bank 5.50 % 1,400 1,111 262

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Scotiabank 5.50 % 4,500 567 1,829

BCI Bank 5.00 % 2,515 2,515 —

Corpbanca 5.00 % 2,935 2,935 3,641

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Banco Bilbao Vizcaya 1.82 % 567 — —

Santander Bank 1.82 % 613 — —

Total $ 103,359 $ 13,672 $ 22,954

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Sales of Common Stock

On October 29, 2019, we issued 50 million shares of our Common Stock at a price of $ 1.50 per share in an underwritten public offering (the “Offering”), resulting in net proceeds to the Company of approximately $ 70 million, after deducting underwriting commissions and offering expenses.

In November 2019, pursuant to an option the Company granted the underwriters, we issued an additional 4,227,749 shares at $ 1.50 per share, less underwriting discounts and commissions, resulting in net proceeds of approximately $ 6 million.

On October 29, 2019, we issued 50 million shares of our Common Stock at a price of $ 1.50 per share in an underwritten public offering (the “2019 Stock Offering”), resulting in net proceeds to the Company of approximately $ 70 million, after deducting underwriting commissions and offering expenses.

In November 2019, pursuant to an option the Company granted the underwriters, we issued an additional 4,227,749 shares at $ 1.50 per share, less underwriting discounts and commissions,

resulting in net proceeds of approximately $ 6 million.

Frost and Hsiao and Mr.

Steven Rubin, members of OPKO’s senior management purchased an aggregate of 2,415,000 shares in the Offering.

On November 8, 2018, we entered into stock purchase agreements with certain investors pursuant to which we agreed to sell to such investors in private placements exempt from registration under the Securities Act an aggregate of approximately 26.5 million shares of Common Stock at a purchase price of $ 3.49 per share, which was the closing bid price per share of Common Stock on the NASDAQ Global Select Market (“NASDAQ”) on such date, for an aggregate purchase price of $ 92.5 million.

Investors in the offering included an affiliate of Dr.

Phillip Frost, our Chairman and Chief Executive Officer ($ 70 million), and Dr.

Jane Hsiao, our Vice Chairman and Chief Technical Officer ($ 2 million).

Steven Rubin, members of OPKO’s senior management purchased an aggregate of 2,415,000 shares in the 2019 Stock Offering.

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.

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Balance at December 31, 2020 $ ( 4,225 )

Other comprehensive income 17,845

Other comprehensive loss ( 26,270 )

Balance at December 31, 2021 $ ( 30,495 )

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Balance at December 31, 2019 $ ( 22,070 )

Other comprehensive loss ( 1,939 )

Other comprehensive income 17,845

Balance at December 31, 2020 $ ( 4,225 )

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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 2016 Equity Incentive Plan

are exercisable for a period of up to 10 years from the date of grant.

Equity awards granted under our 2016 Equity Incentive Plan are exercisable for a period of up to 10 years from the date of grant.

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 the Modigene Plan are exercisable for a period of up to 10 years from date of grant.

Equity awards granted under the

Modigene Plan are exercisable for a period of up to 10 years from date of grant.

Vesting periods range from immediate to 5 years.

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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

BioReference, which reflected various vesting schedules, including monthly vesting to employees and non-employee consultants.

We assumed stock options to grant Common Stock as part of the mergers with Acuity Pharmaceuticals, Inc., Froptix, Inc., OPKO Biologics and BioReference, which reflected various vesting schedules, including monthly vesting to employees and non-employee consultants.

A summary of option activity under our stock option plans as of December 31, 2021, and the changes during the year is presented below:

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Operating lease liability ( 14,554 ) ( 9,842 )

Investment in subsidiaries ( 42,140 ) —

Fixed assets ( 2,592 ) ( 2,736 )

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Net deferred income tax liabilities $ ( 142,709 ) $ ( 131,933 )

Net deferred income tax liability balance includes $ 5.3 million recorded to Other Assets on the Consolidated Balance Sheet.

Net deferred income tax liability balance includes $ 4.3 million recorded to Other Assets and $ 1.5 million recorded to Assets Held for Sale on the Consolidated Balance Sheet.

As of December 31, 2021, we have federal, state and foreign net operating loss carryforwards of approximately $ 470.2 million, $ 774.1 million and $ 86.8 million, respectively, that expire at various dates through 2041 unless indefinite in nature.

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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 Section 338 Approach (IRS approved methodology for determining recognized Built-In Gain).

This limitation may be increased under the IRC Section 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.

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During 2020, we conducted a study to determine whether any ownership changes occurred from 2009 through 2020.

As a result, we have concluded that the annual utilization of our NOLs and tax credits is not subject to a limitation pursuant to Internal Revenue Code Section 382.

In 2021, the study has been updated and we have concluded that the annual utilization of our NOLs and tax credits is not subject to a limitation pursuant to Internal Revenue Code Section 382.

We file federal income tax returns in the U.S.

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taxable income.

The Company currently estimates GILTI will be immaterial for the year ended December 31, 2020, although interpretive guidance continues to be issued and future guidance may impact this analysis.

The Company’s GILTI inclusion is immaterial for the year ended December 31, 2021.

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Research and development tax credits 2.3 % ( 1.0 ) % 0.3 %

Non-Deductible components of Convertible Debt — % — % ( 0.2 ) %

Valuation allowance 235.4 % 227.7 % ( 17.9 ) %

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Imputed interest ( 6.3 ) % 2.5 % 0.5 %

Investment in subsidiaries ( 287.6 ) % — % — %

Other 9.7 % 3.2 % 0.1 %

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Under the terms of the Beneficiary Enterprise program, beneficiary income that is attributable to our operations in Kiryat Gat, Israel will be exempt from income tax through 2023.

This tax incentive has an immaterial impact on our earnings per share for the year ended December 31, 2020.

The impact of the tax holiday on a per share basis for the year ended December 31, 2021 was a benefit of $ 0.02 per share.

The following table reconciles our income (loss) before income taxes between U.S.

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Total $ ( 14,655 ) $ 48,203 $ ( 307,865 )

Prior to the enactment of the Tax Act, the Company regularly determined certain foreign earnings to be indefinitely reinvested outside the U.S.

Our intent is to permanently reinvest these funds outside the U.S.

and our current plans do not demonstrate a need to repatriate cash to fund U.S.

However, if funds were repatriated, we would be required to accrue and pay applicable U.S.

taxes (if any) and withholding taxes payable to foreign tax authorities.

In 2021, we revised our position regarding unrepatriated foreign earnings to a partially reinvested assertion.

We assert that all foreign earnings will be indefinitely reinvested, with the exception of certain foreign investments in which earnings and cash generation are in excess of local needs.

With the passage of the Tax Act, dividends of earnings from non-U.S.

operations are generally no longer subject to U.S.

We continue to analyze and adjust the estimated impact of the non-U.S.

income and withholding tax liabilities based on the source of these earnings, as well as the expected means through which those earnings may be taxed.

We have accrued a withholding tax estimate of $ 1.8 million related to earnings that are not deemed to be permanently reinvested.

Note 12 Related Party Transactions

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Frost for the HSR filing fee.

In August 2020, GeneDx, Inc., a subsidiary of BioReference, entered into an agreement with Mednax Services, Inc.

In August 2020, GeneDx entered into an agreement with Mednax Services, Inc.

(“Mednax Services”), a subsidiary of MEDNAX, Inc., (“MEDNAX”) pursuant to which the parties formed a joint venture under the brand Detect Genomix.

GeneDx’s initial capital investment in Detect Genomix was $ 245,000 for which GeneDx received a 49 % ownership interest in Detect Genomix, and Mednax Services contributed $ 255,000 .

Adam Logal, the

Company’s CFO, is the chair and sits on the Board of Managers of the joint venture.

Mednax Services provides administrative services to the joint venture pursuant to an administrative services agreement.

GeneDx provides laboratory services to the joint venture.

Roger Medel, a director of the Company as of December 18, 2020, is the former Chief Executive Officer of MEDNAX and Mednax Services.

GeneDx’s initial capital investment in Detect Genomix was $ 245,000 for which GeneDx received a 49 % ownership interest in Detect Genomix, and Mednax Services contributed $ 255,000 in exchange for a 51 % ownership interest in Detect Genomix.

Adam Logal, the Company’s CFO, was the chair and sat on the Board of Managers of the joint venture.

Mednax Services provided administrative services to the joint venture pursuant to an administrative services agreement.

GeneDx provided laboratory services to the joint venture.

Roger Medel, a director of the Company, is the former Chief Executive Officer of MEDNAX and Mednax Services.

Medel continues to serve on the board of MEDNAX.

The joint venture was dissolved in January 2022.

On February 25, 2020, we entered into a credit agreement with an affiliate of Dr.

Frost, pursuant to which the lender committed to provide us with an unsecured line of credit in the amount of $ 100 million.

Borrowings under the line of credit will bear interest at a rate of 11 % per annum and may be repaid and reborrowed at any time.

The credit agreement includes various customary remedies for the lender following an event of default, including the acceleration of repayment of outstanding amounts under this line of credit.

This line of credit matures on February 25, 2025.

This line of credit also calls for a commitment fee equal to 0.25 % per annum of the unused portion of the line.

As of December 31, 2020, no funds were borrowed under this line of credit.

This line of credit called for a commitment fee equal to 0.25 % per annum of the unused portion of the line.

We terminated this line of credit in June 2021 and as of December 31, 2021, no amount was outstanding thereunder.

On October 29, 2019, we issued 50 million shares of our Common Stock at a price of $ 1.50 per share in the 2019 Stock Offering, resulting in net proceeds to the Company of approximately $ 70 million, after deducting underwriting commissions and offering expenses.

In November 2019, pursuant to an option the Company granted the underwriters, we issued an additional 4,227,749 shares at the public offering price, less underwriting discounts and commissions, resulting in net proceeds to the Company of approximately $ 6 million.

Frost and Hsiao and Mr.

Steven Rubin, members of OPKO’s senior management purchased an aggregate of 2,415,000 shares of Common Stock in the Offering.

On March 1, 2019, OPKO Pharmaceuticals, LLC entered into an assignment agreement with Xenetic Biosciences, Inc., as amended from time to time (the “Assignment Agreement”), pursuant to which Xenetic acquired all of OPKO Pharmaceuticals’ right, title and interest in and to that certain Intellectual Property License Agreement (the “IP License Agreement”), entered into between The Scripps Research Institute and OPKO Pharmaceuticals, regarding certain patents for novel CAR T platform technology and through which the Scripps Research Institute granted an exclusive royalty-bearing license in exchange for royalties, subject to the terms of the IP License Agreement.

Steven Rubin, members of OPKO’s senior management purchased an aggregate of 2,415,000 shares of Common Stock in the 2019 Stock Offering.

technology and through which the Scripps Research Institute granted an exclusive royalty-bearing license in exchange for royalties, subject to the terms of the IP License Agreement.

Under the Assignment Agreement and the IP License Agreement, Xenetic issued to OPKO Pharmaceuticals 164,062 shares of Xenetic common stock (the “OPKO Transaction Shares”).

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The Company owns approximately 9 % of Pharmsynthez, and Pharmsynthez is Xenetic’s largest and controlling stockholder.

Richard Lerner, a director of the Company, is a co-inventor of Xenetic’s technology and received 31,240 shares of Xenetic upon the closing of the Xenetic transactions described above.

Richard Lerner, a director of the Company until his death on December 2, 2021, was a co-inventor of Xenetic’s technology and received 31,240 shares of Xenetic upon the closing of the Xenetic transactions described above.

Adam Logal, our Senior Vice President and Chief Financial Officer, is a director of Xenetic.

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Frost for the HSR filing fee.

On November 8, 2018, we entered into stock purchase agreements with certain investors pursuant to which we agreed to sell to such investors in private placements an aggregate of approximately 26.5 million shares of our Common Stock at a purchase price of $ 3.49 per share, which was the closing bid price of our Common Stock on the NASDAQ on such date, for an aggregate purchase price of $ 92.5 million.

The investors in the private placements included an affiliate of Dr.

Frost ($ 70 million), and Dr.

Hsiao ($ 2 million).

On November 8, 2018, we entered into a credit agreement with an affiliate of Dr.

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We repaid approximately $ 28.8 million that was borrowed in 2019 and terminated this line of credit on or around February 20, 2019.

In February 2018, we issued the 2023 Convertible Notes in the aggregate principal amount of $ 55.0 million.

Refer to Note 7.

Purchasers of the 2023 Convertible Notes included Dr.

Hsiao and an affiliate of Dr.

We hold investments in Zebra (ownership 29 %), Neovasc ( 1 %), ChromaDex Corporation ( 0 %), MabVax ( 1 %), COCP ( 4 %), NIMS ( 1 %), Eloxx ( 3 %) and BioCardia ( 2 %).

We hold investments in Zebra (ownership 29 %), Neovasc ( 1 %), ChromaDex Corporation ( 0.1 %), COCP ( 3 %), NIMS ( 1 %), Eloxx ( 2 %), BioCardia ( 1 %) and LeaderMed Health Group Limited ( 47 %).

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 5.

In February 2018, we invested an additional $ 1.0 million in COCP for a convertible note, which was converted into 538,544 shares of its common stock in May 2018.

In November 2017, we invested an additional $ 3.0 million in Neovasc for 20,547 shares of its common stock, 20,547 Series A warrants, 20,547 Series B warrants and 8,221 Series C warrants, after adjusting for a 1-for-100 reverse stock split in 2018.

In April 2018, we exercised our Series B warrants in a cashless exercise and received 10,690 shares of Neovasc common stock.

In the first quarter of 2019, we exercised the Series C warrants for $ 1.2 million and exchanged the Series A warrants and received a total of 22,660 additional shares of Neovasc common stock.

In the first quarter of 2019, we exercised Neovasc’s Series C warrants for $ 1.2 million and exchanged the Series A warrants and received a total of 22,660 additional shares of Neovasc common stock.

In November 2016, we entered into a Pledge Agreement with the Museum of Science, Inc.

and the Museum of Science Endowment Fund, Inc.

pursuant to which we will contribute an aggregate of $ 1.0 million over a four-year period for constructing, equipping and the general operation of the Frost Science Museum.

pursuant to which we contributed an aggregate of $ 1.0 million over a four-year period for constructing, equipping and the general operation of the Frost Science Museum.

Frost and Mr.

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As a result, as of December 31, 2021, we recorded $ 2.8 million as contingent consideration, with $ 0.5 million recorded within Accrued expenses and $ 2.3 million recorded within Other long-term liabilities in the accompanying Consolidated Balance Sheets.

In January 2021, the Company settled the ongoing litigation with Claros Diagnostics, Inc.

shareholders and, among other things, agreed to pay $ 1.2 million to the shareholders.

Refer to Note 6.

As previously disclosed, on September 7, 2018, the Securities and Exchange Commission (the “SEC”) filed a lawsuit in the Southern District of New York (the “SEC Complaint”) against a number of individuals and entities (the “Defendants”), including the Company and its CEO and Chairman, Dr.

Phillip Frost.

The SEC alleged, among other things, that the Company (i) aided and abetted an illegal “pump and dump” scheme perpetrated by a number of the Defendants, and (ii) failed to file required Schedules 13D or 13G with the SEC.

The Company and Dr.

Frost entered into settlement agreements with the SEC that resolved the SEC Complaint against each of them.

The settlement agreements were approved by the court in January 2019.

Pursuant to the settlement, and without admitting or denying any of the allegations of the SEC Complaint, the Company is

enjoined from violating Section 13(d) of the Exchange Act and paid a $ 100,000 penalty.

Liability under Section 13(d) can be established without any showing of wrongful intent or negligence.

Following the SEC’s announcement of the SEC Complaint, we were named in several class action lawsuits, more than a dozen derivative suits, and other litigation relating to the allegations in the SEC Complaint among other matters.

On June 26, 2020, The Amitim Funds, the lead plaintiff in the class action lawsuits, filed a Stipulation of Settlement in the Southern District of Florida of behalf of itself and the remainder of the class, which provides for the settlement of and release of the class action claims against the Company and Dr.

Frost for $ 16.5 million.

On September 4, 2020, an Order Preliminarily Approving Settlement was entered and a settlement hearing was held on December 15, 2020.

The settlement remains subject to certain terms and conditions including court approval.

Our insurance carriers have agreed to provide coverage for a significant portion of the currently contemplated settlement amounts in connection with the class action lawsuits.

The derivative suit was settled on November 2, 2020.

The settlement amount of $ 3.1 million was paid by the individual defendants’ insurance company.

In April 2017, the Civil Division of the United States Attorney’s Office for the Southern District of New York (the “SDNY”) informed BioReference that it believed that, from 2008 to 2012, BioReference had, in violation of the False Claims Act, improperly billed Medicare and TRICARE (both are federal government healthcare programs) for clinical laboratory services provided to hospital inpatient beneficiaries at certain hospitals.

On March 1, 2019, the Company received a Civil Investigative Demand (“CID”) from the U.S.

Department of Justice, Washington, DC.

The CID sets forth document requests and interrogatories in connection with allegations that the Company and certain of its affiliates violated the False Claims Act and/or the Anti-Kickback Statute.

On January 13, 2022, the Federal Government notified the U.S.D.C., Middle District Florida, Jacksonville Division, that it is declining to intervene in the matter but retains the right, via the Attorney General, to consent to any proposed dismals of the action by the Court.

On February 9, 2022, the States of Florida, Georgia, and Commonwealth of Massachusetts notified the U.S.D.C., Middle District Florida, Jacksonville Division, that they are declining to intervene in the matter.

Notwithstanding the above declinations, on February 17, 2022, the Company was served with the Relator’s Summons and Complaint (“Complaint”), which had been previously sealed.

The complaint alleges violations of the False Claims Act, the California Fraud Preventions Act, the Florida False Claims Act, the Massachusetts False Claims Act, the Georgia False Medicaid Claims Act, and illegal kickbacks.

The Company is reviewing and assessing the allegations made in the Complaint and, at this point, has not determined whether there is any merit to these claims nor can it determine the extent of any potential liability.

While management cannot predict the outcome of these matters at this time, the ultimate outcome could be material to our business, financial condition, results of operations, and cash flows.

As previously reported, BioReference receives and is routinely required to respond to Civil Investigative Demands (“CID”) in the ordinary course of business.

On November 26, 2019, BioReference received a CID from the U.S.

Department of Justice (“DOJ”).

The CID states that DOJ is investigating whether BioReference paid unlawful remuneration to health care practitioners in violation of the Anti-Kickback Statute or Stark law and thus submitted or caused to be submitted false claims to government health care programs in violation of the False Claims Act.

The time period covered by DOJ’s requests is January 1, 2011 through November 26, 2019.

BioReference has fully cooperated with the DOJ by submitting the requested information and making current employees available for interviews, and DOJ recently made a presentation to BioReference regarding its position.

The parties have reached verbal agreement on the settlement amount, which is anticipated to be approximately $ 10 million, excluding attorney fees.

On April 8, 2019, MabVax Therapeutics Holdings, Inc.

filed a lawsuit in the Superior Court of California, County of San Diego against a number of individuals and entities, including the Company, Dr.

Frost, Steven Rubin, the Company’s Executive Vice President-Administration, and an entity affiliated with Dr.

Frost, based on the allegations raised in the SEC Complaint.

The lawsuit seeks an award for actual and punitive damages, pre- and post-judgment interest;

that the defendants be required to make full disclosure and accounting of their interests and transactions in plaintiff’s securities;

costs of the suit, and reasonable attorney’s fees;

and such other legal and equitable relief as the Court may deem proper under the circumstances.

On January 31, 2022, plaintiffs entered into a confidential mutual release and settlement agreement with the Company, Dr.

Frost, Frost Gamma Investment Trust, and Steve Rubin (the “Settlement Agreement”).

The Settlement Agreement is subject to the approval of United States Bankruptcy Court for the District of Delaware.

On April 5, 2019, former shareholders of Claros Diagnostics, Inc.

filed a complaint in the Chancery Court of Delaware against the Company, alleging among other things, that the Company breached the Agreement and Plan of Merger dated October 13, 2011 by and among the Company, Claros Merger Subsidiary, LLC and Claros Diagnostics, Inc.

(the “Claros Merger Agreement”):

(i) by failing to make a milestone payment of $ 2.375 million (payable in OPKO Common Stock) upon obtaining FDA approval of the Claros PSA test;

and (ii) by repudiating its obligations to make additional future milestone payments as required under the Claros Merger Agreement.

In January 2021, the Company and the shareholder representative entered into a settlement agreement providing, among other things, that the Company pay the shareholders $ 1.2 million, which the Company has paid in full.

services provided to hospital inpatient beneficiaries at certain hospitals.

In April 2019, the SDNY also informed BioReference that it believed that BioReference provided physicians subsidies for electronic health record systems prior to 2012 that violated regulations adopted by HHS in 2006 which allowed laboratories to provide these donations under certain conditions.

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The amount of related attorneys’ fees is currently being negotiated.

On June 3, 2019, BioReference reported that Retrieval-Masters Creditors Bureau, Inc.

d/b/a American Medical Collection Agency (“AMCA”), had notified BioReference about a data security incident involving AMCA (the “AMCA Incident”).

AMCA informed BioReference that an unauthorized user had access to AMCA’s system between August 1, 2018 and March 30, 2019.

AMCA advised that AMCA’s affected system may have included patient name, date of birth, address, phone, date of service, provider, and balance information, as well as credit card information, bank account information (but no passwords or security questions) and email addresses that were provided by the consumer to AMCA.

AMCA advised BioReference that no Social Security Numbers were compromised, and BioReference provided no laboratory results or diagnostic information to AMCA.

BioReference notified patients and provided notice to the Office of Civil Rights of the AMCA Incident.

BioReference had been named in at least two class action lawsuits against AMCA and other defendants in connection with the AMCA Incident.

In April 2020, the class action lawsuits against BioReference were dismissed without prejudice.

The Office of Inspector General and Office for Civil Rights (“OCR”) of the Department of Health and Human Services, as well as the attorney generals’ offices from certain states have contacted BioReference to request additional information relating to the AMCA Incident.

On June 22, 2020 the OCR advised us it was closing its file regarding the AHCA matter and no further action is required of BioReference with respect to this matter.

The resolution with the OCR does not, however, foreclose continued inquiries from attorney generals’ offices from other states.

Accordingly, it is not possible at this time to estimate the amount of loss or range of loss, if any, that might result from adverse judgments, settlements, fines, penalties, or other resolution of these investigations based on the stage of these investigations, and the absence of specific allegations.

On October 11, 2019, GeneDx received a letter from the Centers for Medicare and Medicaid Services (“CMS”), notifying GeneDx of CMS’ determination to suspend Medicare payments to GeneDx, which suspension became effective on September 27, 2019 (the “CMS Letter”).

CMS advised that it suspended payments due to possible overpayments to GeneDx in connection with reimbursement claims for genetic testing services based on a diagnosis of family history of cancer, which testing CMS has alleged is not covered by Medicare under the applicable provisions of the Social Security Act on the basis that such testing is not reasonable and necessary for the diagnosis or treatment of illness or injury.

CMS lifted the suspension on February 3, 2020, and issued an extrapolated overpayment finding of approximately $ 576,332 , which GeneDx paid.

From time to time, we may receive inquiries, document requests, Civil Investigative Demands (“CIDs”) or subpoenas from the Department of Justice, OCR, CMS, various payors and fiscal intermediaries, and other state and federal regulators regarding investigations, audits and reviews.

From time to time, we may receive inquiries, document requests, CIDs or subpoenas from the Department of Justice, OCR, CMS, various payors and fiscal intermediaries, and other state and federal regulators regarding investigations, audits and reviews.

In addition to the matters discussed in this note, we are currently responding to CIDs, subpoenas, payor audits, and document requests for various matters relating to our laboratory operations.

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Settlements of suits involving the types of issues that we routinely confront may require monetary payments as well as corporate integrity agreements.

Additionally, qui tam or “whistleblower” actions initiated under the civil False Claims Act may be pending but placed under seal by the court to comply

with the False Claims Act’s requirements for filing such suits.

Additionally, qui tam or “whistleblower” actions initiated under the civil False Claims Act may be pending but placed under seal by the court to comply with the False Claims Act’s requirements for filing such suits.

Also, from time to time, we may detect issues of non-compliance with federal healthcare laws pertaining to claims submission and reimbursement practices and/or financial relationships with physicians, among other things.

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Because of the high degree of judgment involved in establishing loss estimates, the ultimate outcome of such matters will differ from our estimates and such differences may be material to our business, financial condition, results of operations, and cash flows.

We have employment agreements with certain employees of BioReference which provide for compensation and certain other benefits and for severance payments under certain circumstances.

During the years ended December 31, 2020, 2019 and 2018, we recognized $ 1.0 million, $ 3.0 million and $ 4.9 million, respectively, of severance costs pursuant to these employment agreements as a component of Selling, general and administrative expense.

At December 31, 2021, we were committed to make future purchases for inventory and other items in 2021 that occur in the ordinary course of business under various purchase arrangements with fixed purchase provisions aggregating approximately $ 255.1 million.

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Reimbursements from government payors are based on fee-for-service schedules set by governmental authorities, including traditional Medicare and Medicaid.

Revenues consist of amounts billed, net of contractual allowances for differences between amounts billed and the estimated consideration we expect to receive from such payors, which considers historical denial and collection experience and the terms of our contractual arrangements.

Revenues consist of amounts billed, net of contractual allowances for differences between amounts billed and the estimated consideration we expect to receive from such payors,

which considers historical denial and collection experience and the terms of our contractual arrangements.

Adjustments to the allowances, based on actual receipts from the government payors, are recorded upon settlement.

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Revenues consist of amounts billed net of discounts provided to uninsured patients in accordance with our policies and implicit price concessions.

Implicit price concessions represent differences between amounts billed and the estimated

consideration that we expect to receive from patients, which considers historical collection experience and other factors including current market conditions.

Implicit price concessions represent differences between amounts billed and the estimated consideration that we expect to receive from patients, which considers historical collection experience and other factors including current market conditions.

Adjustments to the estimated allowances, based on actual receipts from the patients, are recorded upon settlement.

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Actual amounts are adjusted in the period those adjustments become known.

For the year ended December 31, 2020, positive revenue adjustments due to changes in estimates of implicit price concessions for performance obligations satisfied in prior periods of $ 0.3 million were recognized.

For the years ended December 31, 2019 and 2018, revenue reductions due to changes in estimates of implicit price concessions for performance obligations satisfied in prior periods of $ 24.8 million and $ 22.8 million, respectively, were recognized.

For the years ended December 31, 2021, and December 31, 2020, positive revenue adjustments due to changes in estimates of implicit price concessions for performance obligations satisfied in prior periods of $ 40.4 million and $ 0.3 million were recognized, respectively.

For the years ended December 31, 2019, revenue reductions due to changes in estimates of implicit price concessions for performance obligations satisfied in prior periods of $ 24.8 million were recognized.

Third-party payors, including government programs, may decide to deny payment or recoup payments for testing they contend were improperly billed or not medically necessary, against their coverage determinations, or for which they believe they have otherwise overpaid (including as a result of their own error), and we may be required to refund payments already received.

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Allowances are recorded as a reduction of revenue at the time product revenues are recognized.

amounts of consideration ultimately received may differ from our estimates.

The actual amounts of consideration ultimately received may differ from our estimates.

If actual results in the future vary from our estimates, we will adjust these estimates, which would affect Revenue from products in the period such variances become known.

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We assess if these options provide a material right to the licensee and if so, they are accounted for as separate performance obligations at the inception of the contract and revenue is recognized only if the option is exercised and products or services are subsequently delivered or when the rights expire.

If the promise is based on market terms and not considered a material right, the option is

accounted for if and when exercised.

If the promise is based on market terms and not considered a material right, the option is accounted for if and when exercised.

If we are entitled to additional payments when the licensee exercises these options, any additional payments are generally recorded in license or other revenues when the licensee obtains control of the goods, which is upon delivery.

For the years ended December 31, 2020, 2019 and 2018 we recorded $ 53.2 million, $ 73.3 million and $ 69.9 million of revenue from the transfer of intellectual property, respectively.

For the year ended December 31, 2020 and 2019, revenue from the transfer of intellectual property included $ 28.7 million and $ 66.8 million related to the Pfizer Transaction.

For the years ended December 31, 2021, 2020 and 2019 we recorded $ 25.8 million, $ 53.2 million and $ 73.3 million of revenue from the transfer of intellectual property and other, respectively.

For the year ended December 31, 2021, revenue from transfer of intellectual property and other principally reflects $ 10.8 million of revenue related to the Pfizer Transaction, $ 1.0 million related to the LeaderMed joint venture (as defined below), $ 4.9 million related to the CAMP4 Agreement (as defined below) and a $ 5.0 million non-refundable upfront payment received under the Nicoya Agreement (as defined below).

For the years ended December 31, 2020, and 2019 revenue from transfer of intellectual property and other principally reflects $ 28.7 million and $ 66.8 million of revenue related to the Pfizer Transaction.

In addition, revenue from the transfer of intellectual property and other for the year ended December 31, 2020 included $ 16.2 million of grants received by BioReference under the CARES Act and a $ 3 million milestone payment triggered by the first marketing approval of Rayaldee in Europe.

For the year ended December 31, 2018, revenue from the transfer of intellectual property included $ 60.0 million related to the Pfizer Transaction and $ 2.0 million related to a milestone payment from our licensee, Vifor Fresenius Medical Care Renal Pharma Ltd (“VFMCRP”).

Refer to Note 16.

Contract liabilities relate to cash consideration that OPKO receives in advance of satisfying the related performance obligations.

Changes in the contractual liabilities balance for the years ended December 31, 2020 are as follows:

Changes in the contractual liabilities balance for the year ended December 31, 2021 are as follows:

(In thousands)

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Note 16 Strategic Alliances

Japan Tobacco Inc.

On October 12, 2017, EirGen, our wholly-owned subsidiary, and Japan Tobacco Inc.

(“JT”) entered into a Development and License Agreement (the “JT Agreement”) granting JT the exclusive rights for the development and commercialization of Rayaldee in Japan (the “JT Territory”).

The license grant to JT covers the therapeutic and preventative use of the product for (i) SHPT in non-dialysis and dialysis patients with CKD, (ii) rickets, and (iii) osteomalacia (the “JT Initial Indications”), as well as such additional indications as may be added to the scope of the license subject to the terms of the JT Agreement (the JT Additional Indications” and together with the JT Initial Indications, the “JT Field”).

In connection with the license, OPKO received an initial upfront payment of $ 6 million and received another $ 6 million upon the initiation of OPKO’s phase 2 study for Rayaldee in dialysis patients in the U.S.

in September 2018 (the “Initial Consideration”).

OPKO is also eligible to receive up to an additional aggregate amount of $ 31 million upon the achievement of certain regulatory and development milestones by JT for Rayaldee in the JT Territory, and $ 75 million upon the achievement of certain sales based milestones by JT in the JT Territory.

OPKO is also entitled to receive tiered, double digit royalty payments at percentages ranging from low double digits to mid-teens on net sales of Rayaldee within the JT Territory.

JT will, at its sole cost and expense, be responsible for performing all development activities necessary to obtain all regulatory approvals for Rayaldee in Japan and for all commercial activities pertaining to Rayaldee in Japan.

The JT Agreement provides for the following:

(1) an exclusive license in the JT Territory in the JT Field for the development and commercialization of Rayaldee ;

and (2) at JT’s option, EirGen will supply products to support the development, sale and commercialization of the products to JT in the JT Territory.

The Initial Consideration will be recognized over the performance period through 2021, when we anticipate completing the transfer of license materials specified in the JT Agreement and our performance obligation is complete.

Payments received for regulatory, development and sales milestones are non-refundable.

The milestones are payable if and when the associated milestone is achieved and will be recognized as revenue 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 these milestones.

In addition, we received an upfront payment of $ 1 million and will be reimbursed for clinical trial material and technical support we provide the joint venture.

For the year ended December 31, 2021, we recognized the upfront payment of $ 1 million as revenue from transfer of intellectual property and other.

LeaderMed has agreed to be responsible for funding the joint venture’s operations, development and commercialization efforts and, together with its syndicate partners, initially invested $ 11 million in exchange for a 53 % ownership interest.

We retain full rights to oxyntomodulin and Factor VIIa-CTP in all other geographies.

CAMP4 Therapeutics

On July 6, 2021, we entered into an exclusive license agreement (the “CAMP4 Agreement”) with CAMP4, pursuant to which we granted to CAMP4 an exclusive license to develop, manufacture, commercialize or improve therapeutics utilizing the AntagoNAT technology, an oligonucleotide platform developed under OPKO CURNA, which includes the molecule for the treatment of Dravet syndrome, together with any derivative or modification thereof (the “Licensed Compound”) and any pharmaceutical product that comprises or contains the Licensed Compound, alone or in combination with one or more other active ingredients (“Licensed Product”), worldwide.

The CAMP4 Agreement grant covers human pharmaceutical, prophylactic, and therapeutic and certain diagnostic uses.

We received an initial upfront payment of $ 1.5 million and 3,373,008 shares of CAMP4’s Series A Prime Preferred Stock (“Preferred Stock”), which equates to approximately 9 % of the outstanding shares of CAMP4, and we are eligible to receive up to $ 3.5 million in development milestone payments for Dravet syndrome products, and $ 4 million for non-Dravet syndrome products, as well as sales milestones of up to $ 90 million for Dravet syndrome products and up to $ 90 million for non-Dravet syndrome products.

We may also receive double digit royalty payments on the net sales of royalty bearing products, subject to adjustment.

In addition, upon achievement of certain development milestones, we will be eligible to receive equity consideration of up to 5,782,299 shares of Preferred Stock in connection with Dravet syndrome products and up to 1,082,248 shares of Preferred Stock in connection with non-Dravet syndrome products.

In connection with our acquisition of CURNA, we agreed to pay future consideration to the sellers upon the achievement of certain events.

As a result of our execution of the CAMP4 Agreement, we will have to pay a percentage of any payments received under the CAMP4 Agreement to the former CURNA stockholders.

For the three months ended September 30, 2021, we recognized the fair value of the upfront payments of cash and shares of Preferred Stock totaling $ 4.9 million in revenue from transfer of intellectual property and other.

Unless earlier terminated, the CAMP4 Agreement will remain in effect on a Licensed Product-by-Licensed Product and country by-country basis until such time as the royalty term expires for a Licensed Product in a country, and expires in its entirety upon the expiration of the royalty term for the last Licensed Product in the last country.

CAMP4’s royalty obligations expire on the later of (i) the expiration, invalidation or abandonment date of the last patent right in connection with the royalty bearing product, or (ii) ten ( 10 ) years after a royalty bearing product’s first commercial sale in a country.

In addition to termination rights for material breach and bankruptcy, CAMP4 is permitted to terminate the Agreement after a specified notice period.

NICOYA Macau Limited

On June 18, 2021, EirGen, our wholly owned subsidiary, and NICOYA Macau Limited (“Nicoya”), a Macau corporation and an affiliate of NICOYA Therapeutics, entered into a Development and License Agreement (the “Nicoya Agreement”) granting Nicoya the exclusive rights for the development and commercialization of extended release calcifediol (the “Nicoya Product”) in Greater China, which includes mainland China, Hong Kong, Macau, and Taiwan (collectively, the “Nicoya Territory”).

Extended release calcifediol is marketed in the U.S.

by OPKO under the tradename Rayaldee .

The license grant to Nicoya covers the therapeutic and preventative use of the Nicoya Product for SHPT in non-dialysis and hemodialysis chronic kidney disease patients (the “Nicoya Field”).

EirGen has received an initial upfront payment of $ 5 million and is eligible to receive an additional $ 5 million upon the first to occur of (A) a predetermined milestone and (B) the first anniversary of the effective date.

EirGen is also eligible to receive up to an additional aggregate amount of $ 115 million upon the achievement of certain development, regulatory and

sales-based milestones by Nicoya for the Nicoya Product in the Nicoya Territory.

EirGen will also receive tiered, double digit royalty payments at rates in the low double digits on net product sales within the Nicoya Territory and in the Nicoya Field.

Nicoya will, at its sole cost and expense, be responsible for performing all development activities necessary to obtain all regulatory approvals for the Nicoya Product in the Nicoya Territory and for all commercial activities pertaining to the Nicoya Product in the Nicoya Territory.

Unless earlier terminated, the Nicoya Agreement will remain in effect until such time as all royalty payment terms and extended payment terms have expired, and Nicoya shall have no further payment obligations to EirGen under the terms of the Nicoya Agreement.

Nicoya’s royalty obligations expire on the later of (i) expiration of the last to expire valid patent claim covering the Nicoya Product sold in the Nicoya Territory, (ii) expiration of all regulatory and data exclusivity applicable to the Nicoya Product in the Nicoya Territory, and (iii) on a product-by-product basis, ten ( 10 ) years after such Nicoya Product’s first commercial sale in the Nicoya Territory.

In addition to termination rights for material breach and bankruptcy, Nicoya is permitted to terminate the Nicoya Agreement after a specified notice period.

Vifor Fresenius Medical Care Renal Pharma Ltd

In May 2016, EirGen and Vifor Fresenius Medical Care Renal Pharma Ltd (“VFMCRP”), entered into a Development and License Agreement (the “VFMCRP Agreement”) for the development and commercialization of Rayaldee (the “Product”) worldwide, except for (i) the U.S., (ii) any country in Central America or South America (excluding Mexico), (iii) Russia, (iv)

China, (v) Japan, (vi) Ukraine, (vii) Belorussia, (viii) Azerbaijan, (ix) Kazakhstan, and (x) Taiwan (the “VFMCRP Territory”).

The license to VFMCRP potentially covers all therapeutic and prophylactic uses of the Product in human patients (the “VFMCRP Field”), provided that initially the license is for the use of the Product for the treatment or prevention of SHPT related to patients with CKD and vitamin D insufficiency/deficiency (the “VFMCRP Initial Indication”).

Effective May 5, 2020, we entered into an amendment to the VFMCRP Agreement (the “VFMCRP Amendment”), pursuant to which the parties agreed to exclude Mexico, South Korea, the Middle East and all of the countries of Africa from the VFMCRP Territory.

Effective May 23, 2021, we entered into an amendment to the VFMCRP Agreement pursuant to which the parties thereto agreed to include Japan as part of the VFMCRP Territory.

Effective May 5, 2020, we entered into an amendment to the VFMCRP Agreement pursuant to which the parties agreed to exclude Mexico, South Korea, the Middle East and all of the countries of Africa from the VFMCRP Territory.

In addition, the parties agreed to certain amendments to the milestone structure and to reduce minimum royalties payable.

As revised, the Company has received a $ 3 million payment triggered by the first marketing approval of Rayaldee in Europe and is eligible to receive up to an additional $ 17 million in regulatory milestones and $ 210 million in milestone payments tied to launch, pricing and sales of Rayaldee , and tiered, double-digit royalties.

Under the terms of the VFMCRP Agreement, as amended, EirGen granted to VFMCRP an exclusive license in the VFMCRP Territory in the VFMCRP Field to use certain EirGen patents and technology to make, have made, use, sell, offer for sale, and import Products and to develop, commercialize, have commercialized, and otherwise exploit the Product.

EirGen received a non-refundable and non-creditable initial payment of $ 50 million, which was recognized in Revenue from the transfer of intellectual property and other in our Consolidated Statement of Operations in 2016.

EirGen also received a $ 2.0 million payment triggered by the approval of Rayaldee in Canada for the treatment of SHPT in adults with stage 3 or 4 CKD and vitamin D insufficiency in July 2018 and a $ 3 million payment triggered by the first marketing approval of Rayaldee in Europe.

EirGen is also eligible to receive up to an additional $ 17 million in Regulatory Milestones and $ 210 million in Sales Milestones tied to launch, pricing and sales of Rayaldee , and will receive tiered royalties on sales of the product at percentage rates that range from the mid-teens to the mid-twenties or a minimum royalty, whichever is greater, upon the commencement of sales of the Product within the VFMCRP Territory and in the VFMCRP Field.

We plan to share responsibility with VFMCRP for the conduct of trials specified within an agreed-upon development plan, with each company leading certain activities within the plan.

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In December 2014, we entered into an exclusive worldwide agreement (the “Pfizer Agreement”) with Pfizer for the development and commercialization of our long-acting Somatrogon (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 (the “Pfizer Transaction”).

In May 2020, we entered into an Amended and Restated Development and Commercialization License Agreement (the “Restated Agreement”) with Pfizer, effective January 1, 2020, pursuant to which the parties agreed, among other things, to share all costs for Manufacturing Activities, as defined in the Restated Agreement, for developing a licensed product for the three indications included in the Restated Agreement.

In early 2022, the European Commission and Ministry of Health, Labour and Welfare in Japan approved the next-generation long-acting recombinant human growth hormone NGENLA (Somatrogon), a once-weekly injection to treat pediatric growth hormone deficiency.

Further, Canada and Australia approved NGENLA in October and November of 2021, respectively.

In January 2022, the FDA issued a Complete Response Letter for the BLA for Somatrogon.

Pfizer and OPKO are evaluating the FDA’s comments and will work with the agency to determine the best path forward for Somatrogon (hGH-CTP) in the United States.

In May 2020, we entered into an Amended and Restated Development and Commercialization License Agreement (the “Restated Pfizer Agreement”) with Pfizer, effective January 1, 2020, pursuant to which the parties agreed, among other things, to share all costs for Manufacturing Activities, as defined in the Restated Pfizer Agreement, for developing a licensed product for the three indications included in the Restated Pfizer Agreement.

On October 21, 2019, we and Pfizer announced that the global phase 3 trial evaluating Somatrogon dosed once-weekly in prepubertal children with GHD met its primary endpoint of non-inferiority to daily Genotropin® (somatropin) for injection, as measured by annual height velocity at 12 months.

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If the Pfizer 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 recognized the non-refundable $ 295.0 million upfront payments as revenue as the research and development services were completed and as of December 31, 2020, we had no contract liabilities related to the Pfizer Transaction.

We recognized the non-refundable $ 295.0 million upfront payments as revenue as the research and development services were completed and as of December 31, 2021 and 2020, we had no contract liabilities related to the Pfizer Transaction.

The Pfizer Transaction includes milestone payments of $ 275.0 million upon the achievement of certain milestones.

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To date, no revenue has been recognized related to the achievement of the milestones.

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 9 %).

We also granted rights to certain technologies in the Russian Federation, Ukraine, Belarus, Azerbaijan and Kazakhstan (the “Pharmsynthez 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 Pharmsynthez Territories, as well as a percentage of any sublicense income from third parties for the technologies in the Pharmsynthez Territories.

We have completed strategic deals with numerous institutions and commercial partners.

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Our leases generally do not provide an implicit interest rate, and we therefore use our incremental borrowing rate as the discount rate when measuring operating lease liabilities.

The incremental borrowing rate represents an estimate of the interest rate we would incur at lease commencement to borrow an amount equal to the lease payments on a collateralized basis over the term of the lease within a particular currency environment.

The incremental borrowing rate represents an estimate of the interest rate we would incur at lease commencement to borrow an amount equal to the lease payments on a collateralized basis

over the term of the lease within a particular currency environment.

We used the incremental borrowing rates as of January 1, 2019 for operating leases that commenced prior to that date.

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We elected the use of permitted practical expedients of not recording leases on our Consolidated Balance Sheet when the leases have terms of 12 months or less, and we elected not to separate nonlease components from lease components and instead account for each separate lease component and the nonlease components associated with that lease component as a single lease component.

The following table presents the lease balances within the Consolidated Balance Sheet as of December 31, 2020:

The following table presents the lease balances within the Consolidated Balance Sheet as of December 31, 2021 and 2020:

(in thousands) Classification on the Balance Sheet December 31, 2021 December 31, 2020

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Total lease liabilities $ 54,658 $ 5,181

Expense under operating leases and finance leases was $ 18.0 million and $ 2.3 million, respectively, for the year ended December 31, 2021, which includes $ 2.5 million of variable lease costs.

Expense under operating leases and finance leases was $ 17.8 million and $ 3.0 million, respectively, for the year ended December 31, 2020, and includes $ 3.0 million of variable lease

Expense under operating leases and finance leases was $ 20.2 million and $ 3.1 million, respectively, for the year ended December 31, 2019, and includes $ 3.4 million of variable lease costs.

Expense under operating leases and finance leases was $ 20.2 million and $ 3.1 million, respectively, for the year ended December 31, 2019, and includes $ 3.4 million of variable lease costs.Operating lease costs and finance lease costs are included within Operating loss in the Consolidated Statement of Operations.

Operating lease costs and finance lease costs are included within Operating loss in the Consolidated Statement of Operations.

Short-term lease costs were not material.

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Common stock options/warrants — 16 — 16

Total assets $ 14,136 $ 74 $ — $ 14,210

Forward contracts — 122 — 122

Total assets $ 4,226 $ 138 $ — $ 4,364

Contingent consideration:

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Common stock options/warrants — 74 — 74

Forward contracts — 133 — 133

Total assets $ 14,136 $ 74 $ — $ 14,210

Forward contracts $ — $ 1,040 $ — $ 1,040

Contingent consideration:

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Balance at December 31, 2020 $ 5,695

Total gains for the period:

Change in fair value:

Included in results of operations ( 1,703 )

Foreign currency impact 7

Payments ( 1,162 )

Balance at December 31, 2021 $ 2,837

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Balance at December 31, 2019 $ 9,684

Total gains for the period:

Change in fair value

Included in results of operations ( 3,989 )

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As of December 31, 2020, of the $ 5.7 million of contingent consideration, $ 1.2 million is recorded in Accrued expenses and $ 4.5 million is recorded in Other long-term liabilities.

As a result of our execution of the CAMP4 Agreement (as defined in Note 16), we will have to pay a percentage of any payments received under the CAMP4 Agreement to the former CURNA stockholders.

Note 20 Derivative Contracts

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Total costs and expenses 252,228 274,028 406,125 445,318

Net loss ( 80,762 ) ( 59,806 ) ( 62,007 ) ( 112,350 )

Loss per share, basic and diluted $ ( 0.14 ) $ ( 0.10 ) $ ( 0.11 ) $ ( 0.18 )

Net income (loss) ( 59,132 ) 33,703 23,717 32,298

Earnings (loss) per share, basic and diluted $ ( 0.09 ) $ 0.05 $ 0.04 $ 0.05

Note 22 Subsequent Events

In February 2022, the European Commission approved the next-generation long-acting recombinant human growth hormone NGENLA (Somatrogon), a once-weekly injection to treat children and adolescents from as young as 3 years of age with growth disturbance due to insufficient secretion of growth hormone.

In January 2022, Pfizer, Inc.

and OPKO announced that the FDA issued a Complete Response Letter for the BLA for Somatrogon.

Somatrogon is an investigational once-weekly long-acting recombinant human growth hormone for the treatment of GHD in pediatric patients.

Pfizer is evaluating the FDA’s comments and will work with the agency to determine an appropriate path forward.

In January 2022, Pfizer, Inc.

and OPKO announced that the long-acting growth hormone injection, NGENLA® (Somatrogon) Inj.

24 mg Pens and 60 mg Pens, has been approved by the Ministry of Health, Labour and Welfare in Japan for the treatment of GHD in pediatric patients.

Somatrogon has also been approved in the Canada and Japan under the brand name NGENLA.

In January 2022, Sema4 and OPKO announced they have signed GeneDx Merger Agreement, pursuant to which Sema4 has agreed to acquire GeneDx, a leader in genomic testing and analysis, from OPKO, subject to satisfaction of customary closing conditions.

The GeneDx Transaction is expected to close in the second quarter of 2022.

Under the terms of the agreement, Sema4 has agreed to acquire GeneDx for an upfront payment of $ 150 million in cash together with 80.0 million shares of Sema4 Common Stock, subject to a customary purchase price adjustment mechanism providing for a normalized level of working capital and that GeneDx be free of debt at closing of the GeneDx Transaction.

Additionally, Sema4 agreed to pay OPKO up to an additional $ 150 million revenue-based milestones over the next two years ( which may be paid in Sema4 Common Stock, cash or a combination thereof in Sema4’s discretion, subject to GeneDx

achieving certain revenue targets ).

Based on the closing stock price of Sema4 as of January 14, 2022, the total upfront consideration is approximately $ 473 million, and the total aggregate consideration including potential milestones is approximately $ 623 million.

As of December 31, 2021, the assets and liabilities of GeneDx are reflected in the consolidated balance sheet as held for sale.

We have reviewed all subsequent events and transactions that occurred after the date of our December 31, 2021 Consolidated Balance Sheet date, through the time of filing this Annual Report on Form 10-K.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 8. Financial Statements and Supplementary Data