Diagnostics & Pharmaceuticals

for Large Markets with

Unmet Needs

FEBRUARY 2016

NYSE: OPK

FORWARD-LOOKING STATEMENTS

This presentation contains “forward-looking statements,” as that term is defined under the Private Securities Litigation Reform Act of 1995 (PSLRA), which statements may be identified by words such as “expects,” “plans,” “projects,” “will,” “may,” “anticipates,” “believes,” “should,” “intends,” “estimates,” “potential,” and other words of similar meaning, including statements regarding our estimated revenues and financial projections, our ability to achieve high levels of growth, the potential for our products under development, the potential of the 4Kscore® to reduce prostate biopsies by 60% and predict the risk of aggressive prostate cancer within twenty years, our ability to develop, test and launch new products, the expected timing of the clinical studies and regulatory approval for our products under development, the outcome of our clinical trials and validation studies and that such outcomes will support commercialization, the expected market penetration and size of the market for our products under development, including without limitation, Rolapitant, Rayaldee™, hGH-CTP, the 4Kscore, Factor VIIa-CTP, oxyntomodulin, and our point-of-care diagnostic products, the potential benefits of our products under development, including whether the 4Kscore will predict the risk of distant metastases and result in 40-55% cost savings, the expected submission dates for the PMA for PSA and 510k for testosterone and expected launch date for each, that MOD-6031 will provide superior long-term therapy for obesity and Type II diabetes patients, our ability to successfully commercialize our product candidates such as Rolapitant, the 4Kscore, hGH-CTP and Rayaldee and whether Rayaldee will take significant market share in stage 3 and 4 CKD patients with SHPT, whether Rayaldee will raise serum total 25-hydroxyvitamin D (25D) more effectively than any over-the-counter (OTC) or prescription (Rx) products currently marketed without the risk of hypercalcemia, whether we can reach more than half of the CKD population with a small sales force, our ability to establish a sales and marketing and clinical support infrastructure for Rayaldee and the timeline for doing so, the expected PDUFA date and launch date for Rayaldee, our ability to develop Rayaldee for new indications including stage 5 CKD, institutionalized elderly, osteoporosis, and cancer, our ability to execute an ex-U.S. licensing agreement during 2016 for Rayaldee, expectations regarding patent coverage, the expected timing for commencing, completing and obtaining results for our clinical trials, the timing for release of trial data and seeking and obtaining FDA and European regulatory approvals as well as reimbursement coverage, the timing of commercial launch of our product candidates, and expectations about near term profitability. These forward-looking statements are only predictions and reflect our views as of the date they were made, and we undertake no obligation to update such statements. Such statements are subject to many risks and uncertainties that could cause our activities or actual results to differ materially from the activities and results anticipated in forward looking statements, including integration challenges with Bio-Reference, risks inherent in funding, developing and obtaining regulatory approvals of new, commercially viable and competitive products and treatments, the success of our collaboration with Pfizer, general market factors, competitive product development, product availability, federal and state regulations and legislation, and integration issues arising from the transactions, delays associated with development of novel technologies, unexpected difficulties and delays in validating and testing product candidates, the regulatory process for new products and indications, manufacturing issues that may arise, the cost of funding lengthy research programs, the need for and availability of additional capital, the possibility of infringing a third party’s patents or other intellectual property rights, the uncertainty of obtaining patents covering our products and processes and in successfully enforcing them against third parties, and the possibility of litigation, among other factors, including all of the risks identified under the heading Risk Factors in our Annual Report on Form 10-K and other filings with the Securities and Exchange Commission.

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OPKO Health is a multinational biopharmaceutical and diagnostics company that seeks to establish industry-leading positions in large growth markets by leveraging its

discovery, development and commercialization expertise.

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INVESTMENT HIGHLIGHTS

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Acquired Bio-Reference Laboratories 3Q 2015, >$800 million fiscal 2014 revenues 420-person salesforce drives higher-margin esoteric testing, ~70% of revenues Facilitates uptake of 4Kscore® prostate cancer test and Claros® 1 in-office platform

Rayaldee™ addresses unmet need in ~$12 billion CKD market, ~9 million patients VARUBI™ (Tesaro) $95 million in milestones, double-digit royalty, ~$1 billion market Long-term focus on high-value products including orphan diseases

hGH-CTP (Pfizer) 1x/week hGH, $570 million total pre-commercialization milestones; double-digit royalties on adult sales, profit-sharing on pediatric sales, ~$3 billion growing market

Once-daily Factor VIIa-CTP Phase 2a currently enrolling, ~$1.7 billion market Platform technologies for extending circulating time of biologics

Diagnostics

Biologics

Pharmaceuticals

Execution

Near-term Milestones

Rayaldee PDUFA, Launch March 29, 2016, 2H 2016 4Kscore reimbursement On-going Factor VIIa Phase 2a 1Q 2016 Oxyntomodulin Phase 1 initiation 1Q 2016 hGH-CTP topline Phase 3 data 2H 2016 (adults)

Management team with a track record of success and access to capital Commitment to opportunistic business development Production and distribution assets worldwide, multiple strategic investments

Strategy and Execution

BIO-REFERENCE LABS: NEAR-TERM OPPORTUNITIES

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LEVERAGING ESTABLISHED CHANNELS TO ACCELERATE ADOPTION OF NEW TESTS AND PRODUCTS

Bio-Reference Labs is the third largest full-service reference laboratory in the U.S. Strategic rationale: Leverage the national marketing, sales and distribution resources to drive

rapid and widespread uptake of OPKO’s diagnostic platforms ~420 sales and marketing personnel ~5,000 people working together to support the needs of clients and patients ~180+ patient service centers located throughout the U.S.

Leveraging Bio-Reference Commercial Infrastructure for 4Kscore Validated the 4Kscore test in blood serum at Bio-Reference’s Elmwood Park, NJ facility BioReference sales training completed for ~200 sales representatives 4Kscore test reimbursement continues to expand

4KSCORE TEST: MINIMALLY INVASIVE ALTERNATIVE TO BIOPSY

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MORE THAN 2 MILLION PROSTATE BIOPSIES PER YEAR WORLDWIDE

4Kscore is the only blood test that accurately identifies risk for aggressive prostate cancer

Clinical utility is based on decades of biomarker research and more than 20,000 men tested in Europe and the U.S.

Long term outcomes data shows 4Kscore predicts 20 year metastasis-free survival for the individual patient

Inclusion in NCCN Guidelines and Category I CPT published and effective January 1, 2017

More than 1,500 urologists have used the 4Kscore in routine practice

Primary care physicians beginning to order test

Health economics study shows a 40–55% cost savings to avoid unnecessary MRI, prostate biopsies, and add treatment or monitoring of indolent cancer

Clinical utility study completed

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Clinical Utility Study was designed to assess the influence of the 4Kscore Test on the decision to perform prostate biopsy at 35 urology clinics with a total of 611 men referred due to abnormal PSA and/or DRE

Reduces prostate biopsy procedures by over 60%

Influences 89% of decisions about performing a prostate biopsy

Konety B. et al. Rev. Urol. 2015 17(4) 231-240

4KSCORE INFLUENCES CLINICAL DECISIONS – REDUCES BIOPSIES

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Before you ordered the 4Kscore Test, were you considering a prostate biopsy for this patient?

After you received the 4Kscore Test results, did the patient either a) have performed by you, b) get scheduled for, or c) get referred by you, to have a prostate biopsy within 90 days of the 4Kscore Test result?

Do you feel the 4Kscore Test influenced the decision for the patient to have (or not have) a prostate biopsy?

Konety B. et al. Rev. Urol. 2015 17(4) 231-240

CLAROS 1 PLATFORM ADDRESSES LARGE TESTING MARKETS

Filing modular PMA with the FDA for rapid PSA test expected in 2016 and expect testosterone 510(k) filing 2H2016

2017 launch expected for both

Claros 1 point-of-care platform will leverage Bio-Reference Labs’ distribution and marketing

Menu expansion following initial FDA filings

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25M PSA TESTS IN THE US ANNUALLY; $625M MARKET FOR A SINGLE TEST

ROBUST LATE-STAGE DRUG PIPELINE

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PRODUCT INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MILESTONE MARKET SIZE

VARUBI (Rolapitant)

CINV

Launched 11/16/2015

$1.0 BN

Rayaldee™ (CTAP101)

SHPT (CKD stage 3-4 patients)

PDUFA date 3/29/2016 $12.0 BN

hGH-CTP

hGH deficiency Phase 3 data

(adults) 2H 2016

$3.0 BN

Alpharen™ (Fermagate)

Hyperphosphatemia (CKD stage 5 patients) $1.2 BN

CTAP201 Mild-to-moderate SHPT (CKD stage 5 patients) $1.1 BN

Factor VIIa-CTP Hemophilia Phase 2a enrolling subjects

$1.7 BN

Oxyntomodulin Diabetes, obesity Phase I trial targeted for

1Q 2016 $15 BN

AntagoNAT Platform

Cancer, CV, metabolic and orphan disease $1.0 BN

Out-licensed to Tesaro

Collaboration with Pfizer

RAYALDEE OVERVIEW

• Product launch estimated 2H 2016 into a ~$12 billion market

• Modified-release oral formulation of 25D3* addresses significant unmet market need

• Indication: Treatment for elevated PTH (SHPT) associated with Vitamin D Insufficency (VDI) (low 25D levels) in stage 3-4 CKD

• Increases serum 25D and reduces plasma PTH

• No adverse effect on serum calcium or phosphorus (key drivers of vascular calcification)

• Existing therapies have efficacy and safety concerns

• Expected to take significant market share in stage 3-4 CKD patients with SHPT & (VDI)

• 9 million patients in the U.S.

• Potential for new indications including stage 5 CKD, institutionalized elderly, osteoporosis and cancer 11 * 25-Hydroxyvitamin D3 or Calcifediol

** 1,25-Dihydroxyvitamin D3 or Calcitriol

PDUFA DATE MARCH 29, 2016; DRUG MET ALL PHASE 3 PRIMARY ENDPOINTS

RAYALDEE MARKET OPPORTUNITY

The CKD patient population is large and growing as a result of:

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Obesity Hypertension Diabetes

% of CKD Patients with

Stage Kidney Function CKD Prevalence Vitamin D Insufficiency (↓25D)

SHPT (↑ PTH)

Hyperphosphatemia (↑ Phosphorus)

3 Moderate impairment 18.7 million* 71% 40% 37%

4 Severe impairment 1.4 million* 83% 82% 50%

5 Failure 0.5 million* 97% 95% 70%

*US Renal Data Service 2013 Annual Data Report Sources: Levin, A et al., Kidney International 2007; 71: pp.31-38; Gonzalez, E et al. Am J Nephrol 2004;24:503-510; LaClair, R et al. Am J Kidney Dis 2005;45:1026-1033; Tentori, F et al., Clin J Am Soc Nephrol 2015; 10:98-109

RAYALDEE VS. ALTERNATIVE THERAPIES

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Effect on blood levels of:

Drug Active Type 25D** Ca iPTH

Rayaldee Calcifediol (25-hydroxyvitamin D3)

Rx Significant Increase

No Change

Significant Decrease

Vitamin D Cholecalciferol/Ergocalciferol (vitamin D3/vitamin D2)

OTC Minor Increase

No Change

Minor Decrease

Drisdol™* Ergocalciferol (vitamin D2)

Rx Minor Increase

No Change

Minor Decrease

Rocaltrol™* Calcitriol (1α,25-dihydroxyvitamin D3)

Rx Decrease Increase Significant Decrease

Hectorol™* Doxercalciferol (1α-hydroxyvitamin D2)

Rx Decrease Increase Significant Decrease

Zemplar™* Paricalcitol (19-nor-1α,25-dihydroxyvitamin D2)

Rx Decrease Increase Significant Decrease

*And generics **25-hydroxyvitamin D

RAYALDEE COMMERCIALIZATION

NDA accepted for full review by FDA July 29, 2015

Build marketing and sales capabilities 1Q-2Q 2016

PDUFA date: March 29, 2016

Launch expected 2H 2016

Execute an ex-U.S. licensing agreement

during 2016

Initial line-extension plans: • Clinical trial planned in stage 5

CKD • Initial clinical trial ongoing for

new oncology indication • Other indications being evaluated

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VARUBI: NEAR-TERM REVENUE DRIVER

• VARUBI (rolapitant) out-licensed to Tesaro in December 2010 • Additional milestone payments of up to $95 million • Double-digit tiered royalties

• Differentiated cancer supportive care product with >$1 billion U.S. market opportunity

• Potent neurokinin-1(NK-1) receptor antagonist for chemotherapy-induced nausea and vomiting (CINV)

• Opportunity to differentiate on convenience, market access and safety • Long-acting, sustained effect • Lack of CYP 3A4 drug-drug interactions • Oral and IV formulations allow full market access

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COMMERCIAL LAUNCH - November 16, 2015

OPKO BIOLOGICS: EXTENDING THE HALF-LIFE OF PROTEINS

• Significant reduction in injection frequency

• CTP technology safety profile is comparable to non-modified active therapeutic agents

• Potential expanded prophylactic uses with longer-half-life agents, in addition to short-term treatment

• Maintain drug bioactivity

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Developing improved long-acting proteins and peptides

Carboxyl Terminal Peptide (CTP) Technology Reversible Pegylation Technology

LONG-ACTING HUMAN GROWTH HORMONE (hGH-CTP)

Terms of global collaboration with Pfizer:

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$295 million in upfront payments to OPKO $275 million to OPKO upon achievement of regulatory milestones

OPKO responsible for funding development program for the key indications:

• Growth hormone deficiency (GHD) – adult & pediatric • Short for gestational age - pediatric

Pfizer responsible for funding: • Development programs for additional indications • All post-marketing studies • All commercialization activities

Initial double-digit tiered royalties on sales of adult GHD Profit sharing commencing upon launch for pediatric GHD encompassing

combined sales for all indications of hGH-CTP and Pfizer’s Genotropin Genotropin represents about 23% of the global market with 2013 annual sales

exceeding $700 million; total global market is ~$3 billion and growing

FINANCIAL

COMMERCIAL

DEVELOPMENT

hGH-CTP COMPETITIVE ADVANTAGES

• New molecular entity (NME) that maintains natural native sequence of growth hormone • A key differentiator is once-weekly injection (current products require daily injections) • Human growth hormone is used for:

• Growth hormone deficient children and adults • SGA, PWS, ISS

• Final presentation: • Refrigerated, liquid, non-viscous formulation • Disposable easy-to-handle pen injection device with a thin needle and low injection volume

• Phase 2 study completed in naive growth hormone deficiency pediatric population • Phase 3 study to be initiated 2H 2016 in naive growth hormone deficiency pediatric population • Orphan drug designation in the U.S. and the EU for children and adults

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PHASE 3 TOP LINE DATA IN ADULTS AVAILABLE 2H 2016

Daily 2013 Daily 2018 Long-acting potentialmarket

hGH MARKET IS ~$3 BILLION, UNDIFFERENTIATED, GROWING

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ESTABLISHED AND GROWING FRAGMENTED

Novo Nordisk (Norditropin)

31%

Pfizer (Genotropin)

23%

Eli Lilly (Humatrope)

12%

Sandoz (Omnitrope)

8%

Merck KGaA (Saizen,

Serostim) 8%

Roche (Nutropin)

12%

Others 6%

~$4B

Pediatric GHD

$3B+

Pediatric GHD

($1.5B)

Adult GHD ISS, Turner syndrome

Other

80%

Projected market growth Competition based on history, service and device innovation

LONG-ACTING FACTOR VIIA-CTP FOR HEMOPHILIA A & B

• Market is growing 7% annually and only 25% of patients are treated

• Current product (NovoSeven®) requires frequent IV doses • 3-4 times a day during bleeding episodes • 1-2 times a day for prophylactic treatment

• In pharmacological studies in hemophilic mice and dogs, Factor VIIa-CTP:

• Demonstrated potential for subcutaneous administration • Reduced frequency of injection during on-demand therapy • Enabled prophylactic treatment while reducing the injection frequency to 2-3 times a week

• Orphan drug designation in the U.S. and the EU

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PHASE 2a STUDY CURRENTLY ENROLLING SUBJECTS - $1.7 BILLION MARKET

THE MOD-6031 SOLUTION

• Oxyntomodulin is a natural appetite suppressor and a dual GLP-1/ glucagon receptor agonist

• Secreted by the digestive system following food intake and induces satiety in the brain

• Crosses blood-brain barrier to induce satiety

• Increases glucose tolerance in insulin resistant pre-diabetic state associated with obesity

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DEVELOPMENT CHALLENGE Oxyntomodulin has short half-life that necessitates multiple daily injections

OPKO SOLUTION: MOD-6031, a reversible PEG30 formulation, provides for once-weekly dosing

MOD-6031 ADDRESSES SIGNIFICANT UNMET MARKET NEED

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Significantly inhibits food intake and reduces body weight by fat reduction

Improves glycemic control by inducing glucose-dependent insulin secretion (direct mechanism) and by reducing fat

(indirect mechanism)

Improves lipid profile

Expected to provide effective long-term therapy for obese people and for people with type 2 diabetes

MOD-6031 (in animal studies)

MARKET SIZE FOR DIABETES AND OBESITY IS ~$15 BILLION

Phase 1 study to be initiated in 1Q 2016

Phase 1 study will evaluate the safety and PK/PD profile of MOD-6301 in overweight or obese healthy volunteers

A battery of comprehensive toxicological studies has been completed confirming the safety of MOD-6031 following a single injection

SELECT FINANCIAL INFORMATION

Cash, cash equivalents & marketable securities: $212.1 million

Net investments: $34.7 million Current portion of credit and notes payable: $78.5 million Senior notes (net of embedded derivatives): $44.2 million

Common shares outstanding: 545,951,707 Potentially dilutive shares: 29,874,112

Three months ended September 30: $143.0 million vs. $19.8 million Nine months ended September 30: $215.0 million vs. $65.6 million

Balance sheet at 9/30/15

Revenue* 2015 vs. 2014

Capital structure at 9/30/15

* 2015 revenue reflects acquisition of Bio-Reference Laboratories on August 20, 2015

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VALUE-CREATING MILESTONES

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VARUBI oral formulation launched by partner Tesaro (November 2015) Rayaldee PDUFA date (1Q 16) Rayaldee launch (2H 16) Rayaldee ex-U.S. licensing (2016)

Phase 2a study of Factor VIIa-CTP (1Q 16) Start Phase 1 trial of oxynotomodulin for treatment of obesity and diabetes (1Q 16) Phase 3 clinical trial results for hGH-CTP for adults (2H 16) Initiate pediatric Phase 3 clinical trial (2H 16)

Diagnostics

Biologics

Pharmaceuticals

Execution Closed on a new 5-year $175.million secured revolving credit facility with JPMorgan

Chase that replaced and improved upon BRL’s’ previous facility Build Sales and Marketing infrastructure for Renal Division (1Q 16)

Strategy and Execution

Granted Category 1 CPT code for 4Kscore test from AMA Obtain broad reimbursement for the 4Kscore test Leverage BRL sales force to drive 4Kscore test revenue (2016) Modular PMA for PSA with FDA for Claros 1 point-of-care diagnostic platform (2016)

KEY TAKEAWAYS

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Core Base Business with Nearly $1 Billion in Revenue

Solid Financial Position

Advanced Deep Pipeline in Multibillion-Dollar Markets

Execution Experienced Leadership with Strategic Vision and

Ability to Execute

Diagnostics & Pharmaceuticals

for Large Markets with

Unmet Needs