Item 1. BUSINESS

This Annual Report on Form 10-K contains forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (where applicable, together with its subsidiaries, "Regeneron," "Company," "we," "us," and "our"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of our products, product candidates, and research and clinical programs now underway or planned, including without limitation EYLEA® (aflibercept) Injection, Dupixent® (dupilumab) Injection, Praluent® (alirocumab) Injection, Kevzara® (sarilumab) Injection, cemiplimab, fasinumab, and evinacumab; the likelihood and timing of achieving any of our anticipated clinical development milestones; unforeseen safety issues resulting from the administration of products and product candidates in patients, including serious complications or side effects in connection with the use of our product candidates in clinical trials; the likelihood and timing of possible regulatory approval and commercial launch of our late-stage product candidates and new indications for marketed products, including without limitation EYLEA, Dupixent, Praluent, Kevzara, cemiplimab, fasinumab, and evinacumab; the extent to which the results from the research and development programs conducted by us or our collaborators may be replicated in other studies and lead to therapeutic applications; ongoing regulatory obligations and oversight impacting our marketed products (such as EYLEA, Dupixent, Praluent, and Kevzara), research and clinical programs, and business, including those relating to patient privacy; determinations by regulatory and administrative governmental authorities which may delay or restrict our ability to continue to develop or commercialize our products and product candidates; competing drugs and product candidates that may be superior to our products and product candidates; uncertainty of market acceptance and commercial success of our products and product candidates; our ability to manufacture and manage supply chains for multiple products and product candidates; the ability of our collaborators, suppliers, or other third parties to perform filling, finishing, packaging, labeling, distribution, and other steps related to our products and product candidates; coverage and reimbursement determinations by third-party payers, including Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; our ability to meet any of our financial projections or guidance, including without limitation capital expenditures, and changes to the assumptions underlying those projections or guidance; the potential for any license or collaboration agreement, including our agreements with Sanofi, Bayer, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), to be cancelled or terminated without any further product success; and risks associated with intellectual property of other parties and pending or future litigation relating thereto, including without limitation the patent litigation proceedings relating to Dupixent and Praluent described further in Note 17 to our Consolidated Financial Statements included in this report. These statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any such statements. In evaluating such statements, shareholders and potential investors should specifically consider the various factors identified under Part I, Item 1A. "Risk Factors," which could cause actual events and results to differ materially from those indicated by such forward-looking statements. We do not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events, or otherwise.

General

Regeneron Pharmaceuticals, Inc. is a fully integrated biotechnology company that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious diseases. Our commercialized medicines and product candidates in development are designed to help patients with eye disease, allergic and inflammatory diseases, heart disease, pain, cancer, and infectious and other serious medical conditions.

Our significant 2017 business highlights include:

•

EYLEA (aflibercept) Injection, which is approved by the U.S. Food and Drug Administration (FDA), European Union (EU), Japan, and certain other countries for use in retinal indications, delivered net sales growth of 11.4% over 2016 in the United States and net sales growth of 18.9% outside the United States. In December 2017, the supplemental Biologics License Application (sBLA) for a 12-week dosing interval of EYLEA in patients with neovascular age-related macular degeneration (wet AMD) was filed with the FDA, with a target action date of August 11, 2018. A Phase 3 study for the treatment of non-proliferative diabetic retinopathy (NPDR) in patients without diabetic macular edema (DME) completed enrollment.

•

Dupixent (dupilumab) for the treatment of adults with moderate-to-severe atopic dermatitis received regulatory approval in the United States and EU. We also reported positive results from two additional pivotal Phase 3 studies of dupilumab for the treatment of asthma, and recently submitted an sBLA with the FDA. We reported positive results in the Phase 2 study in eosinophilic esophagitis (EoE). Phase 3 studies in patients (12-17 years of age and 6-11 years of age) with atopic dermatitis and pediatric patients (6-11 years of age) with asthma were initiated.

•

The Phase 3 cardiovascular outcomes study of Praluent has recently been completed, and a Phase 3 study for the treatment of homozygous familial hypercholesterolemia (HoFH) was initiated. The U.S. Court of Appeals for the Federal Circuit ordered a new trial on the issues of written description and enablement and vacated the permanent injunction in the ongoing PCSK9 litigation. The sBLA for use of Praluent with apheresis was filed with the FDA, with a target action date of August 24, 2018.

•	Kevzara for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) received regulatory approval in the United States, EU, and Japan.

•

We reported positive top-line results from a pivotal Phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma (CSCC). We have commenced a rolling BLA submission to the FDA and expect to complete the submission in the first quarter of 2018. The FDA granted Breakthrough Therapy designation to cemiplimab for the treatment of adults with metastatic CSCC and adults with locally advanced and unresectable CSCC. A Phase 3 study as a first-line treatment for non-small cell lung cancer (NSCLC) and a Phase 3 study in cervical cancer were initiated. A potentially pivotal Phase 2 study in basal cell carcinoma (BCC) was also initiated.

•	Phase 3 efficacy studies of fasinumab in osteoarthritis of the knee or hip were initiated, while the Phase 3 long-term safety study in osteoarthritis continued patient enrollment. A Phase 3 study in chronic low back pain in patients with concomitant osteoarthritis of the knee and hip was also initiated.

•	The FDA granted Breakthrough Therapy designation for evinacumab for the treatment of hypercholesterolemia in patients with HoFH.

•	We advanced one new product candidate (REGN3918, an antibody to complement 5 (C5)) into Phase 1 clinical development.

•

We entered into significant new research and development license and collaboration arrangements, including agreements with the Biomedical Advanced Research Development Authority (BARDA) of the U.S. Department of Health and Human Services (HHS) to develop new treatments to combat infectious diseases; Decibel Therapeutics, Inc. to discover and develop new potential therapeutics to protect, repair, and restore hearing; and ISA Pharmaceuticals B.V. to develop ISA101, an immunotherapy targeting human papillomavirus type 16 (HPV16)-induced cancer, in combination with cemiplimab.

•	From a growth perspective, we hired our 6,000th employee, completed a new lease financing for our laboratory and office facilities in Tarrytown, New York, continued to expand our bulk drug product manufacturing operations in Rensselaer, New York, and continued build-out and validation activities at our Limerick, Ireland commercial manufacturing facility.

•	We were named the top employer in the global biotech and pharmaceutical industry by Science magazine. We have been ranked first for five of the past seven years, with second-place rankings in 2015 and 2011.

Our total revenues were $5,872.2 million in 2017, compared to $4,860.4 million in 2016 and $4,103.7 million in 2015. Our net income was $1,198.5 million, or $10.34 per diluted share, in 2017, compared to $895.5 million, or $7.70 per diluted share, in 2016, and $636.1 million, or $5.52 per diluted share, in 2015. Refer to Part II, Item 7. "Management's Discussion and Analysis of Financial Condition and Results of Operations - Results of Operations" below for further details of our financial results, including amounts incurred related to research and development activities.

We currently have six products that have received marketing approval:

•

EYLEA (aflibercept) Injection, known in the scientific literature as VEGF Trap-Eye, is available in the United States, EU, Japan, and certain other countries outside the United States for the treatment of wet AMD, DME, macular edema following retinal vein occlusion (RVO), which includes macular edema following central retinal vein occlusion (CRVO) and macular edema following branch retinal vein occlusion (BRVO). EYLEA is also available in the EU, Japan, and certain other countries outside the United States for the treatment of myopic choroidal neovascularization (mCNV) and in the United States for the treatment of diabetic retinopathy in patients with DME.

We are collaborating with Bayer on the global development and commercialization of EYLEA outside the United States. Bayer markets, and records revenue from sales of EYLEA outside the United States, where, for countries other than Japan, the companies share equally the profits and losses from sales of EYLEA. In Japan, we are entitled to receive a percentage of the sales of EYLEA. We maintain exclusive rights to EYLEA in the United States and are entitled to all profits from such sales.

•

Dupixent (dupilumab) Injection. On March 28, 2017, the FDA approved Dupixent for the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. The launch of Dupixent commenced in March following the FDA approval. In September 2017, the European Commission granted marketing authorization for Dupixent for use in adults with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and in January 2018, the Ministry of Health, Labor and Welfare (MHLW) in Japan approved Dupixent for the treatment of atopic dermatitis in adults not adequately controlled with existing therapies.

We are collaborating with Sanofi on the global development and commercialization of Dupixent. Sanofi records product sales for Dupixent, and we and Sanofi share profits and losses from sales of Dupixent. We have exercised our option to co-promote Dupixent in the United States and thus far have not exercised any of our options to co-promote Dupixent outside the United States.

•

Praluent (alirocumab) Injection is available in the United States where it is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of high low-density lipoprotein (LDL) cholesterol. Praluent is also available in certain European countries and in Japan. In April 2017, the FDA approved the sBLA for a once-monthly (every four weeks), 300 mg dose of Praluent. In July 2017, the FDA approved the sBLA for Praluent's time out of refrigeration, which was increased from 24 hours to 30 days. The effect of Praluent on cardiovascular morbidity and mortality has not been determined.

Sanofi records product sales for Praluent, and we and Sanofi share profits and losses from sales of Praluent. We have exercised our option to co-promote Praluent in the United States and thus far have not exercised any of our options to co-promote Praluent outside the United States.

See Note 17 to our Consolidated Financial Statements for information regarding the patent infringement proceedings relating to Praluent, which may impact Praluent's commercial availability in certain jurisdictions.

•

Kevzara (sarilumab) Solution for Subcutaneous Injection. In January 2017, Health Canada approved Kevzara for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have an inadequate response to or intolerance to one or more biologic or non-biologic disease modifying anti-rheumatic drugs (DMARDs). This was the first approval of Kevzara worldwide. On May 22, 2017, the FDA approved Kevzara for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have an inadequate response or intolerance to one or more DMARDs. In June 2017, the European Commission granted marketing authorization for Kevzara in combination with methotrexate (MTX) for the treatment of moderately to severely active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs; Kevzara may be used as monotherapy in case of intolerance to MTX or when treatment with MTX is inappropriate. In September 2017, the MHLW in Japan approved Kevzara for the treatment of adult patients with rheumatoid arthritis who have had an inadequate response to conventional treatments.

Sanofi records product sales for Kevzara, and we and Sanofi share profits and losses from sales of Kevzara. We have exercised our option to co-promote Kevzara in the United States and thus far have not exercised any of our options to co-promote Kevzara outside the United States.

•

ARCALYST® (rilonacept) Injection for Subcutaneous Use is available in the United States for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), in adults and children 12 years and older. CAPS are a group of rare, inherited, auto-inflammatory conditions characterized by life-long, recurrent symptoms of rash, fever/chills, joint pain, eye redness/pain, and fatigue. Intermittent, disruptive exacerbations or flares can be triggered at any time by exposure to cooling temperatures, stress, exercise, or other unknown stimuli.

•

ZALTRAP® (ziv-aflibercept) Injection for Intravenous Infusion, known in the scientific literature as VEGF Trap, is available in the United States, EU, and certain other countries for treatment, in combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. Pursuant to a 2015 amended and restated ZALTRAP agreement, Sanofi is solely responsible for the development and commercialization of ZALTRAP, and Sanofi pays us a percentage of aggregate net sales of ZALTRAP.

Marketed Products

Net Product Sales of Regeneron-Discovered Products(1)		Year Ended December 31,
(In millions)		2017				2016				2015
EYLEA in the United States		$	3,701.9			$	3,323.1			$	2,676.0
ARCALYST		16.5				15.3				13.5
Net product sales recorded by Regeneron		$	3,718.4			$	3,338.4			$	2,689.5
EYLEA outside of the United States(1)		$	2,226.9			$	1,872.3			$	1,413.3
EYLEA global		$	5,928.8			$	5,195.4			$	4,089.3
Global net product sales recorded by Sanofi(1):
Praluent in the United States		$	131.4			$	94.4			$	9.5
Praluent outside of the United States		63.3				21.9				1.0
Praluent global		194.7				116.3				10.5
Dupixent		256.5				—				—
Kevzara		13.3				—				—
ZALTRAP		83.8				72.3				85.7
Net product sales recorded by Sanofi		$	548.3			$	188.6			$	96.2
(1) As described in the "General" section above, Bayer records net product sales of EYLEA outside the United States and Sanofi records global net product sales of Praluent, Dupixent, Kevzara, and ZALTRAP.

Programs in Clinical Development

All 15 of our product candidates in clinical development were discovered in our research laboratories and are summarized below. We used our VelocImmune® technology to generate each of the antibodies in the table below. There are numerous uncertainties associated with drug development, including uncertainties related to safety and efficacy data from each phase of drug development (including any post-approval studies), uncertainties related to the enrollment and performance of clinical trials, changes in regulatory requirements, and changes in the competitive landscape affecting a product candidate. Refer to Part I, Item 1A, "Risk Factors" for a description of these and other risks and uncertainties that may affect our clinical programs.

Phase 1			Phase 2			Phase 3
Cemiplimab (REGN2810)(a)			Dupilumab(a)			EYLEA
Antibody to programmed cell death protein 1 (PD-1)(h)			Antibody to the interleukin-4 receptor (IL-4R) alpha subunit			Ÿ	NPDR in patients without DME
Ÿ	Solid tumors and advanced hematologic malignancies		Ÿ	EoE(c)		Dupilumab(a)
REGN3767(a)			Sarilumab(a)			Ÿ	Atopic dermatitis in adolescents and pediatrics (6–17 years of age)
Antibody to Lymphocyte Activation Gene 3 (LAG-3) protein			Antibody to the interleukin-6 receptor (IL-6R)			Ÿ	Atopic dermatitis in pediatrics (6 months–5 years of age) (Phase 2/3)
Ÿ	Advanced malignancies (administered alone or in combination with cemiplimab)		Ÿ	Polyarticular-course juvenile idiopathic arthritis (pcJIA)		Ÿ	Asthma in adults and adolescents
				Ÿ	Asthma in pediatrics (6–11 years of age)
REGN1979			Cemiplimab(a)			Ÿ	Nasal polyps
Bispecific antibody against CD20 and CD3			Ÿ	Metastatic or locally advanced and unresectable CSCC (pivotal study)(d)		Praluent(a)
Ÿ	Certain B-cell malignancies (monotherapy and in combination cemiplimab)(c)		Ÿ	BCC (potentially pivotal study)		Antibody to PCSK9
		Evinacumab (REGN1500)(f)			Ÿ	LDL cholesterol reduction and prevention of cardiovascular events
REGN3470-3471-3479(g)			Antibody to angiopoietin-like protein 3 (ANGPTL3)			Ÿ	HoFH(c)
Multi-antibody therapy to Ebola virus			Ÿ	HoFH(c)(d)		Cemiplimab(a)
Ÿ	Ebola virus infection(c)		Ÿ	Refractory hypercholesterolemia (both HeFH and non-FH)		Ÿ	First-line treatment for NSCLC
REGN1908-1909(f)					Ÿ	Cervical cancer
Multi-antibody therapy to Feld1						Fasinumab (REGN475)(b)(f)
Ÿ	Allergic disease					Ÿ	Osteoarthritis of knee and hip
REGN3500(a)						Ÿ	Chronic low back pain in patients with concomitant osteoarthritis of the knee and hip
Antibody to interleukin-33 (IL-33). Studied as monotherapy and in combination with dupilumab.
				Evinacumab (REGN1500)(f)
Ÿ	Asthma					Ÿ	HoFH(c)(d)
Trevogrumab (REGN1033)(f)
Antibody to myostatin (GDF8)
Ÿ	Muscle wasting diseases (in combination with REGN2477)
REGN2477(f)
Antibody to Activin A
Ÿ	Fibrodysplasia ossificans progressiva (FOP)(c)(e)
Ÿ	Muscle-wasting diseases (in combination with trevogrumab)
REGN3918(f)
Antibody to complement 5 (C5)
Ÿ	Paroxysmal nocturnal hemoglobinuria (PNH)

(a) In collaboration with Sanofi
(b) In collaboration with Teva and Mitsubishi Tanabe Pharma
(c) FDA granted orphan drug designation
(d) FDA granted Breakthrough Therapy designation
(e) FDA granted Fast Track designation
(f) Sanofi did not opt-in to or elected not to continue to co-develop the product candidate. Under the terms of our agreement, Sanofi is entitled to receive royalties on any future global sales of the product candidate.
(g) Sanofi did not opt-in to the product candidate. Under the terms of our agreement, Sanofi is entitled to receive royalties on any future sales of the product candidate. We and BARDA of the HHS are parties to agreements (including an agreement executed in September 2017 - see "Other Programs" below for further information) whereby HHS provides certain funding to support research, development, and manufacturing of an antibody therapy for the treatment of Ebola virus infection.
(h) Studied as monotherapy and in combination with other antibodies and treatments

In the third quarter of 2017, we reported that a Phase 3 study evaluating suptavumab (REGN2222), an antibody to the Respiratory Syncytial Virus-F (RSV-F) protein, did not meet its primary endpoint of preventing medically-attended RSV infections in infants. Suptavumab did show signs of efficacy in a subgroup of patients. Adverse events were generally balanced between suptavumab and placebo. We have discontinued further clinical development of suptavumab.

In the fourth quarter of 2017, we reported that results from two Phase 2 studies that added the angiopoietin2 (Ang2) antibody nesvacumab to EYLEA did not provide sufficient differentiation to warrant Phase 3 development. The RUBY study evaluated patients with DME and the ONYX study evaluated patients with wet AMD. EYLEA results were consistent with findings in previous clinical studies, and there were no new safety signals in these studies. Results from RUBY and ONYX will be further analyzed and will be submitted for presentation at a future medical congress.

Our core business strategy is to maintain a strong foundation in basic scientific research and discovery-enabling technologies, and to build on that foundation with our clinical development, manufacturing, and commercial capabilities. Our objective is to continue to be an integrated, multi-product biopharmaceutical company that provides patients and medical professionals with important options for preventing and treating human diseases.

We believe that our ability to develop product candidates is enhanced by the application of our VelociSuite® technology platforms. Our discovery platforms are designed to identify specific proteins of therapeutic interest for a particular disease or cell type and validate these targets through high-throughput production of genetically modified mice using our VelociGene® technology to understand the role of these proteins in normal physiology, as well as in models of disease. Our human antibody technology (VelocImmune) and cell line expression technologies (VelociMab®) may then be utilized to discover and produce new product candidates directed against the disease target. Our antibody product candidates currently in clinical trials were developed using VelocImmune. We continue to invest in the development of enabling technologies to assist in our efforts to identify, develop, manufacture, and commercialize new product candidates.

Trap-based Clinical Program - Ophthalmologic Diseases

EYLEA (aflibercept) - Ophthalmologic Diseases

Overview

EYLEA is a recombinant fusion protein, consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 and formulated as an iso-osmotic solution for intravitreal administration. EYLEA acts as a soluble decoy receptor that binds VEGF-A and placental growth factor (PlGF) and thereby can inhibit the binding and activation of these cognate VEGF receptors. EYLEA is specially purified and contains iso-osmotic buffer concentrations, which optimizes it for injection into the eye.

Diabetic Retinopathy

Diabetic retinopathy is a complication of diabetes mellitus characterized by microvascular damage to the blood vessels in the retina. It can progress to proliferative diabetic retinopathy (PDR), where new, abnormal vessels that are susceptible to hemorrhage grow initially from the retina and/or optic disc and extend beyond the internal limiting membrane. PDR can subsequently lead to various vision-threatening complications such as vitreous hemorrhage, traction macular detachment, and Neovascular Glaucoma (NVG). Patients are often observed until disease progresses sufficiently to warrant intraocular surgery (vitrectomy) or, more commonly, extensive laser treatment (panretinal photocoagulation (PRP)). PRP is utilized with the intent of preserving function of the central retina, but is inherently destructive to the peripheral retina and may result in loss of peripheral vision.

A Phase 3 study (PANORAMA) to assess the efficacy and safety of intravitreal aflibercept in patients with moderately severe to severe NPDR without DME has completed enrollment.

Late-Stage Antibody-based Clinical Programs

Dupixent (dupilumab; IL-4R Antibody) for allergic and inflammatory conditions

Overview

IL-4R is required for signaling by the cytokines IL-4 and IL-13. Both of these cytokines are critical mediators of Type 2 inflammation, which drives the formation of Immunoglobulin E (IgE) antibodies and allergic diseases like atopic dermatitis (eczema), asthma, nasal polyps, and eosinophilic esophagitis. Dupilumab is a fully human monoclonal antibody generated using our VelocImmune technology and is designed to bind to IL-4R alpha subunit to block signaling from both IL-4 and IL-13.

Atopic Dermatitis

Phase 3 Studies in Adolescent and Pediatric Patients. In the first quarter of 2017, a Phase 3 study in adolescent patients (12–17 years of age) with moderate-to-severe atopic dermatitis was initiated, and in the fourth quarter of 2017, a Phase 3 study in pediatric patients (from six years to 11 years of age) with severe atopic dermatitis was also initiated. Additionally, in the first quarter of 2018, we initiated a Phase 2/3 study in younger pediatric patients (from six months to five years of age) with severe atopic dermatitis.

In 2016, the FDA granted Breakthrough Therapy designation for dupilumab for the treatment of moderate-to-severe (12 to less than 18 years of age) and severe (6 months to less than 12 years of age) atopic dermatitis in patients who are not adequately controlled with, or who are intolerant to, topical medication.

Other Phase 3 Studies. The Phase 3 LIBERTY AD CAFÉ study of Dupixent investigated two dose regimens of Dupixent (300 mg weekly and 300 mg every two weeks) with concomitant topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis who are inadequately controlled with or intolerant to the broad immunosuppressant drug cyclosporine A (CSA), or when this treatment is medically inadvisable. The primary endpoint of this study was the proportion of patients with a 75% or greater improvement from baseline in their Eczema Area and Severity Index (EASI-75) score at 16 weeks. In April 2017, we and Sanofi announced that the results of the LIBERTY AD CAFÉ study were positive and demonstrated an acceptable safety profile. These results were submitted to the EMA and in September 2017, we and Sanofi presented the results at the European Academy of Dermatology and Venereology (EADV) Congress.

In March 2017, at the Annual Meeting of the American Academy of Dermatology, we and Sanofi presented additional detailed results from the Phase 3 LIBERTY AD CHRONOS study. This study met its primary and secondary endpoints, with patients receiving Dupixent along with topical corticosteroids (TCS) achieving significantly improved measures of overall disease severity at 16 and 52 weeks, compared to TCS alone in adults with uncontrolled moderate-to-severe atopic dermatitis.

Asthma

Phase 3 Program. LIBERTY ASTHMA QUEST is a Phase 3 study that evaluated dupilumab in adult and adolescent patients with uncontrolled persistent asthma. It is a global, placebo-controlled Phase 3 study that enrolled more than 1,900 patients. Patients were randomized into four groups: dupilumab 200 mg every other week with a loading dose of 400 mg, dupilumab 300 mg every other week with a loading dose of 600 mg, and two separate placebo groups. Patients were randomized in a 2:1 fashion to active drug versus placebo. The two primary endpoints of the study were the annualized rate of severe exacerbation events at 52 weeks and the absolute change from baseline in a standard measure of lung function known as pre-bronchodilator forced expiratory volume over one second (FEV1) at 12 weeks. The pre-specified primary analysis included hierarchical evaluation of these endpoints in the overall population, in patients with 150 eosinophilic cells/microliter or greater, and in patients with 300 eosinophilic cells/microliter or greater. In the study, approximately 50% of patients had 300 eosinophilic cells/microliter or greater and approximately 70% of patients had 150 eosinophilic cells/microliter or greater. Higher eosinophil counts are generally thought to be associated with poorer asthma control and higher rates of exacerbations, as was observed in the placebo patients in this study.

In the third quarter of 2017, we and Sanofi announced that the LIBERTY ASTHMA QUEST study met its two primary endpoints. Dupilumab, when added to standard therapies, reduced severe asthma attacks (exacerbations) and improved lung function. At 52 weeks, in the 300 mg dose group, dupilumab reduced severe asthma attacks by 46% in the overall population, 60% in patients with 150 eosinophilic cells/microliter or greater, and 67% in patients with 300 eosinophilic cells/microliter or greater (p<0.001 for all groups). At 12 weeks, in the 300 mg dupilumab dose group, mean improvement in lung function over placebo as assessed by FEV1 was 130 mL (9%) in the overall population, 150 mL (11%) in patients with 150 eosinophilic cells/microliter or greater, and 240 mL (18%) in patients with 300 eosinophilic cells/microliter or greater (p<0.001 for all groups). Changes in FEV1 of 100 to 200 mL are considered clinically relevant.

In the LIBERTY ASTHMA QUEST study, the exacerbations and FEV1 results for the 200 mg and 300 mg dupilumab dose groups were generally comparable. The extent of patient response correlated with allergic or atopic status as reflected by blood eosinophils and other markers. Less activity was observed in patients with less than 150 eosinophilic cells/microliter. The overall

rates of adverse events, deaths, infections, conjunctivitis, herpes, and discontinuations were comparable between the dupilumab and placebo groups. Injection site reactions were more common in the dupilumab groups (17%) compared to placebo (8%). All patients continued throughout the study on a medium or high dose inhaled corticosteroid (ICS) and up to two additional controller medicines. Eosinophil subgroups were classified based on baseline levels. Detailed results from this study will be submitted for presentation at a future medical congress.

In the fourth quarter of 2017, we and Sanofi announced that LIBERTY ASTHMA VENTURE, a randomized Phase 3 study examining the ability of dupilumab to reduce oral corticosteroid use in adults and adolescents with severe steroid-dependent asthma, met its primary endpoint and key secondary endpoints. Patients with severe chronic asthma have compromised lung function. In VENTURE, baseline FEV1 was approximately 52% of predicted normal. Oral corticosteriods (OCS) are typically prescribed to improve lung function and reduce asthma attacks in these severe patients. The VENTURE study enrolled 210 patients (103 in the dupilumab group and 107 in the placebo group) with severe asthma and regular use of OCS in the six months prior to enrollment. This Phase 3 trial enrolled severe steroid-dependent asthma patients without regard to baseline eosinophil levels or other biomarkers. The results showed improvements compared to placebo on lung function and exacerbations across patient subgroups - those with baseline eosinophil counts above 300 cells/microliter, above 150 cells/microliter, and below 150 cells/microliter.

For the primary endpoint, at 24 weeks in the overall population, dupilumab added to standard therapies significantly reduced the use of maintenance OCS by 70% on average (median reduction of 100%) compared to 42% with placebo (median reduction of 50%) (p<0.0001). In prespecified analyses of patients with baseline eosinophil counts greater than or equal to 300 cells/microliter, adding dupilumab significantly reduced OCS use by 80% on average (median reduction of 100%) compared to 43% for placebo (median reduction of 50%) (nominal p=0.0001). At 24 weeks, despite the reduced use of OCS, patients treated with dupilumab had 59% fewer attacks (exacerbations) in the overall population (p<0.0001) and 71% fewer attacks in patients with eosinophil counts greater than or equal to 300 cells/microliter. In addition to reducing exacerbations while reducing oral steroid dependence, dupilumab also improved lung function. At 24 weeks, the placebo-adjusted improvement in FEV1 on dupilumab was 220 mL (15%) in the overall population (p=0.0007) and 320 mL (25%) in patients with eosinophil counts greater than or equal to 300 cells/microliter (nominal p=0.0049).

The safety and tolerability profile of dupilumab in the LIBERTY ASTHMA VENTURE study was consistent with previous studies. There were more injection-site reactions reported with dupilumab (9%) vs. placebo (4%). There were more dupilumab-treated patients with an increase in eosinophil counts (14% dupilumab vs. 1% placebo), most of which were mild and the vast majority of which resolved. Overall rates of adverse events, including infections, conjunctivitis, and herpes, were comparable between the dupilumab and placebo groups.

Based on discussions with the FDA, our previously reported and published Phase 2b LIBERTY ASTHMA QUEST study served as the second required pivotal efficacy study for the sBLA for asthma. The results from the LIBERTY ASTHMA VENTURE study were also included in the sBLA for asthma, which was submitted with the FDA in the fourth quarter of 2017.

The TRAVERSE study, a long-term safety extension study, is also included in the LIBERTY ASTHMA clinical development program.

Phase 3 Study in Pediatric Patients. In the second quarter of 2017, a Phase 3 study in pediatric patients (from six to 11 years of age) with uncontrolled persistent asthma was initiated.

Nasal Polyps

Phase 3 Study. In 2017, we completed enrollment in two Phase 3 studies, as part of the LIBERTY NP SINUS program, in adult patients with bilateral nasal polyps on a background therapy with intranasal corticosteroids.

Eosinophilic Esophagitis

Phase 2 Study. EoE is a chronic allergic inflammatory disease manifested by tissue injury and pain and difficulty swallowing. People with EoE may also have allergies, asthma, atopic dermatitis, and chronic respiratory disease.

In the second quarter of 2017, we and Sanofi announced positive results from a 12-week Phase 2 proof-of-concept study of dupilumab in patients with active, moderate-to-severe EoE. In the fourth quarter of 2017, we and Sanofi presented these results at the World Congress of Gastroenterology. The study showed that compared to placebo, patients who received dupilumab weekly reported a significant improvement in the ability to swallow. The primary endpoint of the study was the change from baseline to week 10 in the Straumann Dysphagia Instrument (SDI) score, a 0–9 point patient-reported measure of swallowing difficulty, with 9 indicating more severe symptoms. A total of 47 patients were randomized to dupilumab 300 mg weekly following a 600 mg loading dose or placebo. Mean baseline SDI score was 6.4 in each group. At week 10, patients who received dupilumab reported a significant improvement in the ability to swallow with a three point reduction in their SDI score (45% improvement) compared to 1.3 points (19% improvement) for those patients who received placebo (p=0.0304).

Secondary endpoints of the study included endoscopic and histopathologic measures of disease severity, as well as other symptoms. The results include:

•

The mean change in the Eosinophilic Esophagitis Endoscopic Reference Score (EoE-EREFS) at 12 weeks was significantly reduced by 1.9 points from baseline (48% improvement) in patients who received dupilumab compared to 0.3 points (7% improvement) for those who received placebo (p=0.0006). EoE-EREFS is a visual measure of disease severity (inflammation and fibrosis in the esophagus) on a 0–8 point scale, with 8 indicating more severe disease. The mean baseline score was 3.9 for dupilumab and 4.3 for placebo.

•	The mean percent change in overall peak intraepithelial eosinophil count from baseline to 12 weeks was significantly reduced by 93% in patients who received dupilumab compared to an increase of 14% in those who received placebo (p<0.0001).

•	The mean percent change in a composite measure of symptoms and quality of life, as measured by Eosinophilic Esophagitis Symptom Activity Index (EEsAI), was numerically improved at 10 weeks (although not statistically significant) by 35% in patients who received dupilumab compared to an 11% improvement for those who received placebo (p=0.085).

There were no new significant safety concerns in this study. Compared to placebo, higher rates of injection site reactions were observed on dupilumab.

In the third quarter of 2017, the FDA granted orphan drug designation to dupilumab for the treatment of EoE.

Praluent for LDL cholesterol reduction

Overview

Elevated LDL cholesterol ("bad cholesterol") level is a validated risk factor leading to cardiovascular disease. Statins are a class of drugs that lower LDL cholesterol (LDL-C) through inhibition of HMG-CoA, an enzyme regulating the early and rate-limiting step in cholesterol biosynthesis that ultimately results in an increase in LDL receptors to increase the uptake of plasma LDL lipoproteins. Similar to statins, PCSK9 impacts the number of available LDL receptors and therefore plays a key role in modulating LDL-C levels in the body. PCSK9 is a secreted protein that binds to and induces the destruction of the LDL receptor, thereby interfering with cellular uptake and increasing circulating levels of LDL cholesterol. In a landmark study published in The New England Journal of Medicine in March 2006, patients with lower than normal PCSK9 levels due to a genetic abnormality not only had significantly lower levels of LDL-C, but also a significant reduction in the risk of coronary heart disease (CHD). We used our VelocImmune technology to generate a fully human monoclonal antibody inhibitor of PCSK9, called Praluent, which lowers LDL cholesterol.

Clinical Program

The potential of Praluent to reduce cardiovascular events is being prospectively assessed in the 18,000-patient ODYSSEY OUTCOMES study (with data expected in the first quarter of 2018). To be entered into the ODYSSEY OUTCOMES study, patients had to have had a heart attack or unstable angina requiring hospitalization within the previous year, and inadequately controlled LDL cholesterol despite receiving maximally-tolerated statins and potentially other lipid-lowering therapies.

A Phase 4 randomized, placebo-controlled, long-term study that prospectively evaluates the effect of Praluent on neurocognitive function remains ongoing. This is a post-marketing commitment we made to the FDA.

In the second quarter of 2017, we and Sanofi presented positive results from two Phase 3b/4 studies (ODYSSEY-INSULIN and ODYSSEY-DYSLIPIDEMIA) that evaluated Praluent in patients with diabetes. A majority of patients in both trials reached their lipid goals on Praluent 75 mg administered every two weeks. The overall safety profile was consistent with observations in the ODYSSEY Phase 3 program.

The sBLA for use of Praluent with apheresis has been filed with the FDA, with a target action date of August 24, 2018.

In the fourth quarter of 2017, a Phase 3 study in HoFH was initiated.

Kevzara (sarilumab; IL-6R Antibody) for inflammatory diseases

Overview

IL-6 is a key cytokine driving inflammation and joint destruction in RA. Sarilumab, generated using our VelocImmune technology, is a fully human monoclonal antibody to IL-6R.

Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA)

A Phase 2 study of sarilumab in pcJIA was initiated in 2016.

Cemiplimab (REGN2810; PD-1 Antibody) for cancer

Overview

The PD-1 immune checkpoint pathway has emerged as a major mechanism by which cancers evade immune destruction. Several drugs blocking either PD-1 or PD-L1 (one of the two ligands bound by PD-1) have been approved. Cemiplimab is a fully-human high-affinity anti-PD-1 antibody that was generated using the Velocimmune platform. We are developing cemiplimab as a foundation for a diverse and comprehensive immuno-oncology portfolio. Our initial approval strategy is focused on monotherapy in selected indications. Subsequent development activities are expected to include combinations with other anti-cancer agents.

Clinical Program

Cemiplimab is in Phase 1 clinical development in a variety of malignancies, both as monotherapy and in combination with other antibodies or treatments. In 2016, we initiated a pivotal Phase 2 study for the treatment of metastatic or locally advanced and unresectable CSCC. In the second quarter of 2017, we initiated a Phase 3 study in first-line treatment for NSCLC and a potentially pivotal Phase 2 study in BCC. In the third quarter of 2017, we also initiated a Phase 3 study in cervical cancer.

In June 2017, we and Sanofi announced positive preliminary results in patients with advanced CSCC. We presented data at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting from 26 patients pooled from two expansion cohorts of the cemiplimab Phase 1 study. Ten patients with distantly metastatic CSCC were enrolled in one expansion cohort and 16 patients with inoperable (unresectable) locally or regionally advanced CSCC were enrolled in a second expansion cohort. Treatment with cemiplimab led to an investigator-assessed overall response rate (ORR) of 46.2% and a disease control rate (DCR) of 69.2%. The median progression-free survival and overall survival were not reached at the data cutoff date with a median follow up of 6.9 months (range: 1.1 to 13.8 months; ongoing). One patient experienced progressive disease following an initial response to cemiplimab, and two patients were not evaluable for response due to death, which was considered unrelated to cemiplimab. The most common treatment-related adverse event of any grade was fatigue (23.1%). Grade 3 or higher adverse events included arthralgia (3.8%), maculopapular rash (3.8%), asthenia (3.8%), aspartate aminotransferase (AST) elevation (3.8%), and alanine aminotransferase (ALT) elevation (3.8%). We found no apparent association between the treatment response and level of PD-L1 (programmed death ligand 1) expression.

In the third quarter of 2017, the FDA granted cemiplimab Breakthrough Therapy designation for the treatment of adults with metastatic CSCC and adults with locally advanced and unresectable CSCC.

In December 2017, we and Sanofi announced positive top-line results from the pivotal Phase 2 EMPOWER-CSCC 1 study of cemiplimab in 82 patients with advanced CSCC. Cemiplimab demonstrated an ORR of 46.3%, determined by independent review. The median duration of response (DOR) had not yet been reached at the data cut-off point (32 of 38 responses were ongoing). At the time of this analysis, all patients had a minimum follow up of 6 months. The safety profile in the study was generally consistent with approved anti-PD-1 agents. These pivotal data will form the basis of a rolling BLA submission to the FDA, which we have initiated.

Cemiplimab is also being studied by other companies in combination with their proprietary assets. For example, in the second quarter of 2017, we and Inovio Pharmaceuticals, Inc. entered into a clinical and supply agreement for a Phase 1b/2a immuno-oncology study that will be conducted by Inovio in patients with newly-diagnosed glioblastoma multiforme (GBM) and will evaluate cemiplimab in combination with Inovio's INO-5401 T cell activating immunotherapy encoding multiple antigens and INO-9012, an immune activator encoding IL-12. Also in the second quarter of 2017, we and SillaJen, Inc. entered into a clinical and supply agreement for a Phase 1b dose-escalation study in renal cell carcinoma (RCC), or kidney cancer. The study will evaluate cemiplimab in combination with SillaJen's oncolytic vaccinia virus, Pexa-Vec, in patients with previously treated metastatic or unresectable renal cell carcinoma.

In the fourth quarter of 2017, we and ISA Pharmaceuticals entered into a collaboration agreement to develop ISA101, an immunotherapy targeting HPV16-induced cancer, in combination with cemiplimab. We and ISA will jointly fund and conduct clinical trials of the combination treatment in cervical cancer and head-and-neck cancer.

Fasinumab (REGN475; NGF Antibody) for pain due to osteoarthritis and chronic low back pain

Overview

Pain is among the most common reasons people see the doctor and why analgesics, including opioids, are among the most commonly prescribed drugs. Pain is a major cause of work disability and impaired quality of life. Targeting NGF is a potential new way to manage pain without resorting to opiods. NGF expression is elevated in many acute and chronic painful conditions and NGF blockade has demonstrated efficacy in clinical trials. Fasinumab is a fully human monoclonal antibody to NGF, generated using our VelocImmune technology.

The fasinumab clinical development program is expected to comprise approximately 10,000 patients treated with fasinumab.

Osteoarthritis

We initiated a Phase 3 long-term safety study in patients with pain due to osteoarthritis of the knee or hip in 2016 and a Phase 3 efficacy study in patients with pain due to osteoarthritis of the knee or hip in the second quarter of 2017. In the third quarter of 2017, we initiated a Phase 3 efficacy study of fasinumab compared to placebo or naproxen in patients with pain due to osteoarthritis of the knee or hip and in the fourth quarter of 2017 we initiated a Phase 3 efficacy study with multiple nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with pain due to osteoarthritis.

As previously reported, in our Phase 2/3 clinical study in osteoarthritis, the incidence of adjudicated arthropathies in patients on fasinumab was found to be potentially dose-dependent. The ongoing fasinumab osteoarthritis pain pivotal Phase 3 program excludes higher doses associated with a higher incidence of arthropathy.

Chronic Low Back Pain

A Phase 3 study in chronic low back pain in patients with concomitant osteoarthritis was initiated in the fourth quarter of 2017.

Evinacumab (REGN1500; Antibody to ANGPTL3) for cardiovascular and metabolic disease

Overview

ANGPTL3 is a protein secreted by the liver. ANGPTL3 inhibition lowers plasma levels of triglycerides, LDL-C, and high-density lipoprotein cholesterol (HDL-C). Evinacumab is a fully human monoclonal antibody and a specific inhibitor of ANGPTL3. We are investigating the use of evinacumab in patients with dyslipidemias.

HoFH

A Phase 2 study for the treatment of HoFH is fully enrolled and ongoing. A Phase 3 study in HoFH was initiated in the first quarter of 2018.

Refractory Hypercholesterolemia

A Phase 2 study in refractory hypercholesterolemia (both HeFH and non-FH) was initiated in the fourth quarter of 2017 .

Other Programs

Our preclinical research programs include the areas of oncology and immuno-oncology, angiogenesis, ophthalmology, metabolic and related diseases, muscle diseases and disorders, inflammation and immune diseases, bone and cartilage, pain and neurobiology, cardiovascular diseases, and infectious diseases.

In 2015, we and BARDA of the HHS entered into an agreement to develop, test, and manufacture an antibody therapy (REGN3470-3471-3479) for the treatment of Ebola virus infection. Under the terms of the agreement, HHS provides funding to support our preclinical development, antibody manufacturing, and for a Phase 1 study in healthy volunteers, and has the option to provide additional funding for further manufacturing and development studies. In September 2017, we and BARDA entered into an additional agreement whereby HHS provides additional funding for the continued development of REGN3470-3471-3479, a potential BLA filing, and initial procurement of the therapy for national security preparedness. In addition, in 2016, we and BARDA entered into an agreement whereby HHS will provide certain funding to manufacture and study two antibody therapies for the potential treatment of Middle East Respiratory Syndrome (MERS).

In September 2017, we and BARDA also entered into an agreement to discover, research, develop, and manufacture a portfolio of antibodies targeting up to 10 pathogens, starting with Influenza virus, that pose significant risk to public health. The emerging pathogens treatment portfolio will be pursued using an Other Transaction Agreement (OTA), which provides a funding and collaboration vehicle for HHS to promote innovation in technology for advanced research and development. Under the OTA,

which has a term of 10 years, HHS will fund 80% of our costs for research, development, and manufacturing activities for antibodies that are selected to move forward.

Research and Development Technologies

Many proteins that play an important role in biology and disease are secreted by cells or located on the cell surface. Moreover, cells communicate through secreted factors and surface molecules. Our scientists have developed two different technologies to make protein therapeutics that potently and specifically block, activate, or inhibit the action of specific cell surface or secreted molecules. The first technology fuses receptor components to the constant region of an antibody molecule to make a class of drugs we call "Traps". EYLEA, ZALTRAP, and ARCALYST are drugs generated using our Trap technology. VelociSuite is our second technology platform. It is used for discovering, developing, and producing fully human antibodies that can address both secreted and cell-surface targets.

VelociSuite. VelociSuite consists of VelocImmune, VelociGene, VelociMouse®, VelociMab, and other related technologies. The VelocImmune mouse platform is utilized to produce fully human antibodies. VelocImmune was generated by exploiting our VelociGene technology (see below), in a process in which six megabases of mouse immune gene loci were replaced, or "humanized," with corresponding human immune gene loci. VelocImmune mice can be used efficiently to generate fully human antibodies to targets of therapeutic interest. VelocImmune and our entire VelociSuite offer the potential to increase the speed and efficiency through which human antibody therapeutics may be discovered and validated, thereby improving the overall efficiency of our early stage drug development activities. We are utilizing the VelocImmune technology to produce our next generation of drug candidates for preclinical and clinical development.

Our VelociGene platform allows custom and precise manipulation of very large sequences of DNA to produce highly customized alterations of a specified target gene, or genes, and accelerates the production of knock-out and transgenic expression models without using either positive/negative selection or isogenic DNA. In producing knock-out models, a color or fluorescent marker may be substituted in place of the actual gene sequence, allowing for high-resolution visualization of precisely where the gene is active in the body during normal body functioning as well as in disease processes. For the optimization of preclinical development and pharmacology programs, VelociGene offers the opportunity to humanize targets by replacing the mouse gene with the human homolog. Thus, VelociGene allows scientists to rapidly identify the physical and biological effects of deleting or over-expressing the target gene, as well as to characterize and test potential therapeutic molecules.

Our VelociMouse technology platform allows for the direct and immediate generation of genetically altered mice from embryonic stem cells (ES cells), thereby avoiding the lengthy process involved in generating and breeding knockout mice from chimeras. Mice generated through this method are normal and healthy and exhibit a 100% germ-line transmission. Furthermore, mice developed using our VelociMouse technology are suitable for direct phenotyping or other studies. We have also developed our VelociMab platform for the rapid screening of antibodies and rapid generation of expression cell lines for our Traps and our VelocImmune human antibodies.

We have utilized our VelociSuite technologies to develop a class of potential drug candidates, known as bi-specific antibodies. In the area of immunotherapies in oncology, we are exploring the use of bi-specific antibodies that target tumor antigens and the CD3 receptor on T-cells to harness the oncolytic properties of T-cells. Our first such bi-specific antibody, REGN1979, targets CD20 and CD3. We are exploring additional indications and applications for our bi-specific technologies, such as bi-specific antibodies to mucin 16 (MUC16) and B-cell maturation antigen (BCMA).

Regeneron Genetics Center®. In 2014, we launched a new human genetics initiative via a wholly owned subsidiary, Regeneron Genetics Center LLC (RGC). RGC leverages de-identified clinical, genomic, and molecular data from human volunteers to identify medically relevant associations in a blinded fashion designed to preserve patients' privacy. The objective of RGC is to expand the use of human genetics for discovering and validating genetic factors that cause or influence a range of diseases where there are major unmet medical needs, with the prospect of improving the drug discovery and development process. RGC is undertaking multiple approaches, including large population-based efforts as well as family- and founder-based approaches. RGC utilizes laboratory automation and innovative approaches to cloud computing to achieve high-quality throughput.

Central to the work of RGC is a collaboration with the Geisinger Health System of Pennsylvania. Geisinger collects samples from consented patient volunteers, while RGC performs sequencing and genotyping to generate de-identified genomic data. In addition, RGC has expanded on its foundational population-based collaboration with Geisinger with a growing number of other organizations worldwide.

In January 2018, we, along with AbbVie Inc., Alnylam Pharmaceuticals Inc., AstraZeneca PLC, Biogen Inc., and Pfizer Inc., announced the formation of a consortium to fund the generation of genetic exome sequence data from 500,000 volunteer participants who make up the UK Biobank health resource. The other companies will each commit up to $10.0 million in funding for Regeneron to sequence the UK Biobank's samples, which will be performed at the RGC facility. Consortium members will have a limited period of exclusive access to the sequencing data, before the data will be made available to other health researchers by UK Biobank.

License Agreements

In September 2017, we entered into a license agreement with a third party, which grants the third party the right to develop and commercialize new indications for ARCALYST in certain jurisdictions, including the United States. We currently maintain exclusive rights to ARCALYST in the United States for existing indications, and are entitled to all profits from such sales. Commencing with the receipt of marketing approval by the third party for the first new indication in the United States, we will grant commercial rights to ARCALYST for our existing indications to the third party.

Collaboration Agreements

Collaborations with Sanofi

Antibodies. Our Discovery and Preclinical Development Agreement (Antibody Discovery Agreement) with Sanofi ended on December 31, 2017 without any extension. Praluent, Dupixent, Kevzara, cemiplimab, REGN3500, and REGN3767 were discovered and initially developed under the Antibody Discovery Agreement. Praluent, Dupixent, Kevzara, and REGN3500 will continue to be developed, and commercialized as applicable, with Sanofi under the Antibody License and Collaboration Agreement (LCA). Cemiplimab and REGN3767 will continue to be developed with Sanofi under the immuno-oncology collaboration. We have the right to develop or continue to develop other product candidates discovered under the Antibody Discovery Agreement independently or with other collaborators.

Under the terms of the LCA, development costs for the drug candidate are shared between the companies, with Sanofi generally funding these costs as they are incurred by us, except that following receipt of the first positive Phase 3 trial results for a co-developed drug candidate, subsequent Phase 3 trial-related costs for that drug candidate are shared 80% by Sanofi and 20% by us. We are generally responsible for reimbursing Sanofi for half of the total development costs for all collaboration antibody products from our share of profits from commercialization of collaboration products to the extent they are sufficient for this purpose. We are obligated to use commercially reasonable efforts to supply clinical requirements of each drug candidate under the collaboration until commercial supplies of that drug candidate are being manufactured.

Effective January 7, 2018, we and Sanofi entered into a letter agreement (Letter Agreement) amending the LCA in connection with, among other matters, the allocation of additional funds to certain proposed activities relating to the development of dupilumab and REGN3500 and non-approval trials of dupilumab (collectively, the Dupilumab/REGN3500 Eligible Investments). Pursuant to the Letter Agreement, we have agreed to allow Sanofi to satisfy in whole or in part its funding obligations with respect to the Dupilumab/REGN3500 Eligible Investments for the quarterly periods commencing on January 1, 2018 and ending on September 30, 2020 by selling up to 600,000 shares of our Common Stock directly or indirectly owned by Sanofi. Refer to the "Immuno-Oncology" section below for further details regarding the Letter Agreement.

Under our collaboration agreement, Sanofi records product sales for commercialized products, and Regeneron has the right to co-promote such products on a country-by-country basis. We have exercised our option to co-promote Dupixent, Praluent, and Kevzara in the United States. We have not exercised any of our options to co-promote these antibodies outside the United States; however, we retain the right to do so at a future date subject to the terms of the collaboration agreement. We and Sanofi will equally share profits and losses from sales within the United States. We and Sanofi share profits outside the United States on a sliding scale based on sales starting at 65% (Sanofi)/35% (us) and ending at 55% (Sanofi)/45% (us), and share losses outside the United States at 55% (Sanofi)/45% (us). In addition to profit sharing, we are entitled to receive up to $250.0 million in sales milestone payments, with milestone payments commencing after aggregate annual sales outside the United States exceed $1.0 billion on a rolling 12-month basis.

Immuno-Oncology. In July 2015, we and Sanofi entered into a global strategic collaboration to discover, develop, and commercialize antibody-based cancer treatments in the field of immuno-oncology (the IO Collaboration). The IO Collaboration is governed by an Immuno-oncology Discovery and Development Agreement (IO Discovery Agreement), and an Immuno-oncology License and Collaboration Agreement (IO License and Collaboration Agreement). In connection with the IO Discovery Agreement, Sanofi made a $265.0 million non-refundable up-front payment to us. Pursuant to the IO Discovery Agreement, we will spend up to $1,090.0 million (IO Discovery Budget) to identify and validate potential immuno-oncology targets and develop therapeutic antibodies against such targets through clinical proof-of-concept. Sanofi will reimburse us for up to $825.0 million (IO Discovery Funding) of these costs, subject to certain annual limits. The term of the IO Discovery Agreement will continue through the later of five years from the effective date of the IO Collaboration or the date the IO Discovery Budget is exhausted, subject to Sanofi's option to extend it for up to an additional three years for the continued development (and funding) of selected ongoing programs. Pursuant to the IO Discovery Agreement, we will be primarily responsible for the design and conduct of all research activities, including target identification and validation, antibody development, preclinical activities, toxicology studies, manufacture of preclinical and clinical supplies, filing of Investigational New Drug Applications (INDs), and clinical development through proof-of-concept. We will reimburse Sanofi for half of the development costs they funded that are attributable to clinical development of antibody product candidates under the IO Discovery Agreement from our share of future profits, if any, from commercialized

IO Collaboration products to the extent they are sufficient for this purpose. With regard to product candidates for which proof-of-concept is established, Sanofi will have the option to license rights to the product candidate pursuant to the IO License and Collaboration Agreement (as further described below).

In connection with the IO License and Collaboration Agreement, Sanofi made a $375.0 million non-refundable up-front payment to us. If Sanofi exercises its option to license rights to a product candidate thereunder, it will co-develop the drug candidate with us through product approval. Principal control of development of each product candidate that enters development under the IO License and Collaboration Agreement will alternate between us and Sanofi on a candidate-by-candidate basis. Sanofi will fund drug candidate development costs up front for the candidates for which it is the principal controlling party and we will reimburse half of the total development costs for all such candidates from our share of future IO Collaboration profits to the extent they are sufficient for this purpose. In addition, we and Sanofi will share equally, on an ongoing basis, the development costs for the drug candidates for which we are the principal controlling party. The party having principal control over the development of a product candidate will also lead the commercialization activities for such product candidate in the United States. We are obligated to use commercially reasonable efforts to supply clinical requirements of each drug candidate under the IO License and Collaboration Agreement until commercial supplies of that IO drug candidate are being manufactured. For all products commercialized under the IO License and Collaboration Agreement, Sanofi will lead commercialization activities outside of the United States. Each party will have the right to co-promote licensed products in countries where it is not the lead commercialization party. The parties will share equally in profits and losses in connection with the commercialization of collaboration products.

Under the terms of the IO License and Collaboration Agreement, the parties will also co-develop our antibody product candidate targeting PD-1 (cemiplimab). We have principal control over the development of cemiplimab, and the parties share equally, on an ongoing basis, development expenses for cemiplimab. Pursuant to the January 7, 2018 Letter Agreement with Sanofi, the cemiplimab development budget has been increased to a total of $1.640 billion, $990.0 million over the budget originally set forth in the IO License and Collaboration Agreement. Under the Letter Agreement, we have also agreed to allow Sanofi to satisfy in whole or in part its funding obligation with respect to cemiplimab development costs for the quarterly periods commencing on October 1, 2017 and ending on September 30, 2020 by selling up to 800,000 shares of our Common Stock directly or indirectly owned by Sanofi.

If Sanofi desires to sell shares of our Common Stock during the term of the Letter Agreement to satisfy a portion or all of its funding obligations for the cemiplimab development and/or, as noted above, Dupilumab/REGN3500 Eligible Investments, we may elect to purchase, in whole or in part, such shares from Sanofi. If we do not elect to purchase such shares, Sanofi may sell the applicable number of shares (subject to certain daily and quarterly limits) in one or more open-market transactions.

With regard to cemiplimab, we will lead commercialization activities in the United States, while Sanofi will lead commercialization activities outside of the United States and the parties will equally share profits from worldwide sales. Sanofi has exercised its option to co-promote cemiplimab in the United States. We will be entitled to a milestone payment of $375.0 million in the event that global sales of certain licensed products targeting PD-1 (including cemiplimab), together with sales of any other products licensed under the IO License and Collaboration Agreement and sold for use in combination with any of such licensed products targeting PD-1, equal or exceed $2.0 billion in any consecutive twelve-month period.

Collaborations with Bayer

EYLEA outside the United States. Since October 2006, we and Bayer have been parties to a license and collaboration agreement for the global development and commercialization outside the United States of EYLEA. Under the agreement, we and Bayer collaborate on, and share the costs of, the development of EYLEA. Bayer markets EYLEA outside the United States, where, for countries other than Japan, the companies share equally in profits and losses from sales of EYLEA. In Japan, we are entitled to receive a tiered percentage of between 33.5% and 40.0% of EYLEA net sales.

Commencing with the first commercial sale of EYLEA in a major market country outside the United States, we became obligated to reimburse Bayer for 50% of the development costs that it has incurred under the agreement from our share of the collaboration profits (including payments to us based on sales in Japan). The reimbursement payment in any quarter will equal 5% of the then outstanding repayment obligation, but never more than our share of the collaboration profits in the quarter unless we elect to reimburse Bayer at a faster rate. As a result, we expect that a portion of our share of EYLEA profits outside the United States will be used to reimburse Bayer for this repayment obligation.

Within the United States, we retain exclusive commercialization rights to EYLEA and are entitled to all profits from any such sales.

Ang2 antibody outside the United States. In March 2016, we entered into an agreement with Bayer governing the joint development and commercialization outside the United States of nesvacumab, an antibody product candidate to Ang2, including REGN910-3 (nesvacumab in combination with aflibercept), for the treatment of ocular diseases or disorders. In connection with the agreement, Bayer made a $50.0 million non-refundable up-front payment to us and is obligated to pay 25% of global development costs and 50% of development costs exclusively for the territory outside the United States.

In the fourth quarter of 2017, we reported that results from two Phase 2 studies that added nesvacumab to EYLEA did not provide sufficient differentiation to warrant Phase 3 development.

Collaboration with Mitsubishi Tanabe Pharma

Fasinumab. In September 2015, we entered into a collaboration agreement with Mitsubishi Tanabe Pharma Corporation (MTPC) providing MTPC with development and commercial rights to fasinumab in Japan, South Korea, Taiwan, Indonesia, Thailand, the Philippines, Malaysia, Singapore, Vietnam, Myanmar, and Sri Lanka (the MTPC Territories). In connection with the agreement, MTPC made a $10.0 million non-refundable up-front payment in 2015, and in 2016, MTPC made additional payments totaling $60.0 million to us. In the second quarter of 2017, we earned a $30.0 million development milestone from MTPC, and in the fourth quarter of 2017, MTPC made additional payments totaling $25.0 million to us related to development milestones achieved by MTPC. We are entitled to receive up to an aggregate of $100.0 million in additional development milestone and other contingent payments.

Under the agreement, we are obligated to manufacture and supply MTPC with clinical and commercial supplies of fasinumab. If fasinumab is commercialized in the MTPC Territories, we will supply the product to MTPC at a tiered purchase price, which ranges from 30% to 50% of net sales of the product (subject to adjustment in certain circumstances), and are eligible for additional payments up to an aggregate of $100.0 million upon the achievement of specified annual net sales amounts starting at $200.0 million.

Collaboration with Teva

Fasinumab. In September 2016, we entered into a collaboration agreement with Teva to develop and commercialize fasinumab globally, excluding certain Asian countries that are subject to our collaboration agreement with MTPC (as described above). In connection with the agreement, Teva made a $250.0 million non-refundable up-front payment in 2016. We will lead global development activities, and the parties will share equally, on an ongoing basis, development costs under a global development plan. During 2017, we earned $25.0 million and $35.0 million development milestones from Teva, and we are entitled to receive up to an aggregate of $400.0 million in additional development milestones and up to an aggregate of $1,890.0 million in contingent payments upon achievement of specified annual net sales amounts. We are responsible for the manufacture and supply of fasinumab globally.

Within the United States, we will lead commercialization activities, and the parties will share equally in any profits or losses in connection with commercialization of fasinumab. In the territory outside of the United States, Teva will lead commercialization activities and we will supply product to Teva at a tiered purchase price, which is calculated as a percentage of net sales of the product (subject to adjustment in certain circumstances).

Manufacturing

We currently manufacture bulk drug materials at our manufacturing facilities in Rensselaer, New York, which consists of approximately 565,000 square feet of owned research, manufacturing, office, and warehouse space. We currently have approximately 101,000 liters of cell culture capacity, and are approved by the FDA and other regulatory agencies to manufacture our marketed products at these facilities.

We also own an approximately 445,000 square foot facility in Limerick, Ireland, which we acquired in 2014 and subsequently renovated to accommodate and support our growth and expand our manufacturing capacity. The facility has received certain manufacturing approvals by regulatory agencies, including the FDA, and is in the process of further validation, as required by regulatory authorities, for the manufacture of our bulk drug products.

Certain raw materials or other products necessary for the manufacture and formulation of our products and product candidates are provided by single-source unaffiliated third-party suppliers. In addition, we rely on certain third parties to perform packaging, filling, finishing, labeling, distribution, laboratory testing, and other services related to the manufacture of our products and product candidates, and to supply various raw materials and other products. See Part I, Item 1A. "Risk Factors - Risks Related to Manufacturing and Supply" for further information.

Among the conditions for regulatory marketing approval of a medicine is the requirement that the prospective manufacturer's quality control and manufacturing procedures conform to the good manufacturing practice (GMP) regulations of the health authority. In complying with standards set forth in these regulations, manufacturers must continue to expend time, money, and effort in the

areas of production and quality control to ensure full technical compliance. Manufacturing establishments, both foreign and domestic, are also subject to inspections by or under the authority of the FDA and by other national, federal, state, and local agencies.

Sales and Marketing

We have a New Products Marketing and Planning group, a Market Research group, and a Market Access group to evaluate commercial opportunities for our targets and drug candidates, assess the competitive environment, and analyze the commercial potential of our product portfolio, and prepare for market launch of new products. These groups are fully functional to support our product and product candidates that we are independently developing and/or commercializing, and also work closely with our collaborators for co-developed products to develop marketing plans and forecasts and to develop and execute pre-launch market development programs.

We also have a full-service commercialization group to handle various aspects of our commercial programs. The group includes experienced professionals in the fields of marketing, communications, professional education, patient education and advocacy, reimbursement and market access, trade and distribution, commercial operations, commercial analytics, market research, and forecasting. Moreover, for our marketed products, we have hired, trained, and deployed a field-based organization including regional directors, medical specialists, and reimbursement managers, each typically with a number of years of experience in the biopharmaceutical industry in a variety of therapeutic areas including oncology, ophthalmology, immunology, and inflammation. We have approximately 600 field-based employees in the United States.

Customers

We sell EYLEA in the United States to several distributors and specialty pharmacies. We sell ARCALYST in the United States to two specialty pharmacies. Under these distribution models, the distributors and specialty pharmacies generally take physical delivery of product. For EYLEA, the distributors and specialty pharmacies generally sell the product directly to healthcare providers, whereas for ARCALYST, the specialty pharmacies sell the product directly to patients. We had sales to three customers (Besse Medical, a subsidiary of AmerisourceBergen Corporation; McKesson Corporation; and Curascript SD Specialty Distribution, a subsidiary of Express Scripts) that each accounted for more than 10% of total gross product revenue for the year ended December 31, 2017. On a combined basis, our product sales to these customers accounted for approximately 99% of our gross product revenue for the year ended December 31, 2017. We are also a party to collaboration agreements with Bayer and Sanofi, whereby our collaborator is responsible for recording product sales of EYLEA outside the United States and global sales of Dupixent, Praluent, and Kevzara, respectively.

Competition

We face substantial competition from pharmaceutical, biotechnology, and chemical companies. Many of our competitors have substantially greater research, preclinical, and clinical product development, manufacturing capabilities, and financial, marketing, and human resources than we do. Competition from smaller competitors may also be or become more significant if those competitors acquire or discover patentable inventions, form collaborative arrangements, or merge with large pharmaceutical companies. Even if we are able to commercialize additional product candidates, one or more of our competitors may have brought a competitive product to market earlier than us or may have obtained or obtain patent protection that dominates or adversely affects our activities or products. Our ability to compete depends, to a great extent, on how fast we can develop safe and effective product candidates, complete clinical testing and approval processes, and supply commercial quantities of the product to the market. Competition among product candidates approved for sale is based on efficacy, safety, reliability, availability, price, patent position, and other factors.

EYLEA. The following table provides an overview of the competitive landscape for EYLEA:

Competitor Product/Product Candidate		Commercial or Development Status		Competitor		Indication		Territory
Lucentis® (ranibizumab)		Approved		Novartis AG and Genentech/Roche		Wet AMD, DME, macular edema following RVO (including CRVO and BRVO), diabetic retinopathy in patients with DME, and mCNV		Worldwide
Avastin® (bevacizumab) (off-label)		Used to treat wet AMD, DME, and macular edema following RVO		Genentech/Roche		Wet AMD, DME, and macular edema following RVO		Worldwide
Ozurdex® (dexamethasone intravitreal implant)		Approved		Allergan, PLC		DME, RVO		Worldwide
Iluvien® (fluocinolone acetonide intravitreal implant)		Approved		Alimera Sciences, Inc.		DME		United States, EU
Conbercept		Approved in China for wet AMD In development for other eye indications		Chengdu Kanghong Pharmaceutical Group		Wet AMD		China
Brolucizumab (RTH258), a single chain antibody fragment directed against VEGF-A		In development (two non-inferiority Phase 3 trials comparing RTH258 and EYLEA met their primary endpoint in June 2017)		Novartis		Wet AMD		—
Abicipar pegol (anti-VEGF-A-DARPin®)		In development (non-inferiority Phase 3 trial initiated in 2015 comparing dosing regimens of abicipar pegol and Lucentis)		Allergan		Wet AMD and related conditions		—
RG7716, a bi-specific antibody targeting anti-VEGF and Ang2		In development (Phase 2)		Genentech/Roche		Wet AMD, DME		—
Lucentis port delivery system		In development (Phase 2)		Genentech/Roche		Wet AMD and related conditions		—
X-82, an orally administered small molecule tyrosine kinase inhibitor in development for use in combination with EYLEA or Lucentis		In development (Phase 2)		Tyrogenex		Wet AMD and related conditions		—
DE-122, an anti-endoglin antibody in development for use in combination with EYLEA or Lucentis		In development (Phase 2)		Santen Pharmaceuticals Co. Ltd./ TRACON Pharmaceuticals, Inc.		Wet AMD and related conditions		—
GB-102, an intravitreally administered depot formulation of the small molecule tyrosine kinase inhibitor, sunitinib		In development (Phase 2)		Graybug Vision, Inc.		Wet AMD and related conditions		—

EYLEA (continued):
Competitor Product/Product Candidate		Commercial or Development Status		Competitor		Indication		Territory
OPT-302, a VEGFR-3 large molecule trap in development for use in combination with EYLEA or Lucentis		In development (Phase 2b)		Opthea Limited		Wet AMD and related conditions		—
M710, a biosimilar to EYLEA		In development (Phase 3)		Momenta Pharmaceuticals, Inc. (in partnership with Mylan N.V.)		Wet AMD and related conditions		—
CHS-3351, a biosimilar to Lucentis		In development (Phase 1)		Coherus BioSciences, Inc.		Wet AMD and related conditions		—
PF582, a biosimilar to Lucentis		In development (Phase 1/2 completed in August 2016)		Pfenex Inc.		Wet AMD and related conditions		—
FYB201, a biosimilar to Lucentis		In development (Phase 3)		Formycon AG (in collaboration with Bioeq GmbH)		Wet AMD and related conditions		—
SB11, a biosimilar to Lucentis		In development (Phase 3)		Samsung Bioepis Co., Ltd.		Wet AMD and related conditions		—
Razumab, a biosimilar to Lucentis		Approved in India for wet AMD and related conditions		Intas Phamaceuticals Limited		Wet AMD and related conditions		India

The table above is not exhaustive. For additional information regarding the substantial competition EYLEA faces, see also Part I, Item 1A. "Risk Factors - Risks Related to Commercialization of EYLEA - The commercial success of EYLEA is subject to strong competition" and Part I, Item 1A. "Risk Factors - Risks Related to Commercialization of Products - Our product candidates or new indications for our marketed products, if any are approved for marketing, may face significant competition."

Dupixent. The following table provides an overview of the competitive landscape for Dupixent:

Competitor Product/Product Candidate		Commercial or Development Status		Competitor		Indication		Territory
Eucrisa® (crisaborole)		Approved		Pfizer		Mild-to-moderate atopic dermatitis		United States
Xolair® (omalizumab)		Approved		Roche/Novartis		Asthma		Worldwide
Nucala® (mepolizumab)		Approved for asthma In development (Phase 2) for atopic dermatitis		GlaxoSmithKline (GSK)		Asthma and atopic dermatitis		Worldwide
Cinqair® (reslizumab)		Approved		Teva		Asthma		Worldwide
Fasenra® (benralizumab)		Approved		AstraZeneca		Asthma		United States, EU
Tralokinumab, an anti-IL-13 antibody		In development (Phase 3)		AstraZeneca/ LEO Pharma Inc.		Atopic dermatitis		—
Baricitinib, an orally administered JAK inhibitor		In development (Phase 3)		Eli Lilly and Company/Incyte Corporation		Atopic dermatitis		—
PF-04965842, an orally administered JAK inhibitor		In development (Phase 3)		Pfizer		Atopic dermatitis		—
Upadacitinib, an orally administered JAK inhibitor		In development (Phase 3)		AbbVie		Atopic dermatitis		—
Fevipiprant, an orally administered CRTH2 antagonist		In development (Phase 3)		Novartis		Asthma		—
Tezepelumab, an anti-TSLP antibody		In development (Phase 3)		Amgen Inc./AstraZeneca		Asthma		—
ANB-020, an anti-IL-33 antibody		In development (Phase 2)		AnaptysBio, Inc.		Asthma and atopic dermatitis		—
Lebrikizumab, an anti-IL-13 antibody		In development (Phase 2)		Dermira, Inc./Roche		Atopic dermatitis		—
Nemolizumab, an anti-IL-31R antibody		In development (Phase 2)		Galderma S.A.		Atopic dermatitis		—
CNTO7610, an anti-ST2 antibody		In development (Phase 2 for asthma and Phase 1 for atopic dermatitis)		Johnson & Johnson		Asthma and atopic dermatitis		—
RG6149, an anti-ST2 antibody		In development (Phase 2)		Roche		Asthma		—
MEDI-9314, an anti-IL-4R antibody		In development (Phase 1)		AstraZeneca		Atopic dermatitis		—
PRS-060, an inhaled anticalin targeting IL-4R		In development (Phase 1)		AstraZeneca/ Pieris Pharmaceuticals, Inc.		Asthma		—

The table above is not exhaustive. For additional information regarding the substantial competition Dupixent faces, see also Part I, Item 1A. "Risk Factors - Risks Related to Commercialization of Our Antibody-based Products (Dupixent, Praluent, and Kevzara) - The commercial success of Dupixent, Praluent, and Kevzara is subject to strong competition."

Praluent. The following table provides an overview of the competitive landscape for Praluent:

Competitor Product/Product Candidate		Commercial or Development Status		Competitor		Indication		Territory
Repatha® (evolocumab)		Approved		Amgen		(1) Reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease, (2) primary hyperlipidemia, and (3) HoFH		Worldwide
Inclisiran (ALN-PCSsc)		In development (Phase 2)		Alnylam Pharmaceuticals (in collaboration with The Medicines Company)		RNAi molecule against PCSK9 (injectable, small molecule)		—
ETC-1002 (bempedoic acid)		In development (Phase 3)		Esperion Therapeutics, Inc.		ACL-inhibitor (oral, small molecule)		—
Gemcabene		In development (Phase 2)		Gemphire Therapeutics Inc.		Cholesterol synthesis inhibitor (oral, small molecule)		—

The table above is not exhaustive. For additional information regarding the substantial competition Praluent faces, see also Part I, Item 1A. "Risk Factors - Risks Related to Commercialization of Our Antibody-based Products (Dupixent, Praluent, and Kevzara) - The commercial success of Dupixent, Praluent, and Kevzara is subject to strong competition."

Kevzara. The following table provides an overview of the competitive landscape for Kevzara:

Competitor Product/Product Candidate		Commercial or Development Status		Competitor		Indication		Territory
Actemra® (tocilizumab)		Approved		Roche		Rheumatoid arthritis		Worldwide
Orencia® (abatacept)		Approved		Bristol-Myers Squibb Company		Rheumatoid arthritis		Worldwide
Xeljanz® (tofacitinib)		Approved		Pfizer		Rheumatoid arthritis		Worldwide
Olumiant® (baricitinib)		Approved		Eli Lilly/Incyte		Rheumatoid arthritis		EU
Olokizumab, an anti-IL-6 antibody		In development (Phase 3)		R-Pharm		Rheumatoid arthritis		—
Upadacitinib, an orally administered JAK inhibitor		In development (Phase 3)		AbbVie		Rheumatoid arthritis		—
Filgotinib, an orally administered JAK inhibitor		In development (Phase 3)		Gilead Sciences, Inc./ Galapagos NV		Rheumatoid arthritis		—
Peficitinib, an orally administered JAK inhibitor		In development (Phase 3)		Astellas Pharma Inc.		Rheumatoid arthritis		—
Clazakizumab, an anti-IL-6 antibody		In development (Phase 2)		Vitaeris Inc.		Rheumatoid arthritis		—
Vobarilizumab, an anti-IL-6R antibody fragment		In development (Phase 2)		Ablynx NV		Rheumatoid arthritis		—
Gerilimzumab, an anti-IL-6 antibody		In development (Phase 1)		Bird Rock Bio, Inc.		Rheumatoid arthritis		—

The table above is not exhaustive. For additional information regarding the substantial competition Kevzara faces, see also Part I, Item 1A. "Risk Factors - Risks Related to Commercialization of Our Antibody-based Products (Dupixent, Praluent, and Kevzara) - The commercial success of Dupixent, Praluent, and Kevzara is subject to strong competition."

Antibodies in Development. Our clinical candidates in development are all fully human antibodies which were generated using our VelocImmune technology. Our antibody generation technologies and clinical candidates face competition from many pharmaceutical and biotechnology companies using various technologies. Numerous other companies are developing therapeutic antibody products. Companies have generated therapeutic products that are currently in development or on the market that are derived from recombinant DNA that comprise human antibody sequences. Astellas has licensed our VelocImmune technology to use it as part of their internal antibody development programs.

The following table provides an overview of the competitive landscape for our antibody programs that are in late-stage clinical development:

Regeneron Antibody Program		Competitor		Competitor Product/Product Candidate		Commercial or Development Status		Target
Cemiplimab (Phase 2/3) Target: PD-1		Bristol-Myers Squibb		Opdivo® (nivolumab)		Approved		Antibody against PD-1
		Merck & Co., Inc.		Keytruda® (pembrolizumab)		Approved		Antibody against PD-1
		Pfizer/ Merck		Bavencio® (avelumab)		Approved		Antibody against PDL-1
		Roche		Tecentriq® (atezolizumab)		Approved		Antibody against PDL-1
		AstraZeneca		Imfinzi® (durvalumab)		Approved		Antibody against PDL-1
		Novartis		PDR001		In development (Phase 3)		Antibody against PD-1
		Celgene Corporation/ BeiGene Ltd.		BGB-A317		In development (Phase 3)		Antibody against PD-1
		Agenus Inc.		AGEN2034		In development (Phase 1)		Antibody against PD-1
		TESARO, Inc./AnaptysBio		TSR-042		In development (Phase 1)		Antibody against PD-1
		Pfizer		PFE-06801591		In development (Phase 1)		Antibody against PD-1 (Subcutaneous Formulation)
Fasinumab (Phase 3) Target: NGF		Pfizer/Eli Lilly		Tanezumab		In development (Phase 3)		Antibody against NGF
Evinacumab (Phase 3) Target: ANGPTL3		Ionis Pharmaceuticals, Inc./Akcea Therapeutics, Inc.		AKCEA-ANGPTL3-LRx		In development (Phase 2)		Ligand conjugated antisense drug against ANGPTL3

The table above is not exhaustive and focuses on antibody competitors. We are also aware of several companies developing or marketing small molecules that may compete with our antibody product candidates in various indications, if such product candidates obtain regulatory approval in those indications.

For additional information regarding our antibody programs and the substantial competition they face, see Part I, Item 1A. "Risk Factors - Risks Related to Commercialization of Products - Our product candidates or new indications for our marketed products, if any are approved for marketing, may face significant competition."

Other Areas. Many pharmaceutical and biotechnology companies are attempting to discover new therapeutics for indications in which we invest substantial time and resources. In these and related areas, intellectual property rights have been sought and certain rights have been granted to competitors and potential competitors of ours, and we may be at a substantial competitive disadvantage in such areas as a result of, among other things, our lack of experience, trained personnel, and expertise. A number of corporate and academic competitors are involved in the discovery and development of novel therapeutics that are the focus of other research or development programs we are now conducting. Some of these competitors are currently conducting advanced preclinical and clinical research programs in these areas. These and other competitors may have established substantial intellectual property and other competitive advantages.

If any of these or other competitors announces a successful clinical study involving a product that may be competitive with one of our product candidates or the grant of marketing approval by a regulatory agency for a competitive product, such developments may have an adverse effect on our business, operating results, financial condition, cash flows, or future prospects.

We also compete with academic institutions, governmental agencies, and other public or private research organizations, which conduct research, seek patent protection, and establish collaborative arrangements for the development and marketing of products that would provide royalties or other consideration for use of their technology. These institutions are becoming more active in seeking patent protection and licensing arrangements to collect royalties or other consideration for use of the technology they have developed. Products developed in this manner may compete directly with products we develop. We also compete with others in acquiring technology from these institutions, agencies, and organizations.

Patents, Trademarks, and Trade Secrets

Our success depends, in part, on our ability to obtain patents, maintain trade secret protection, and operate without infringing on the proprietary rights of third parties (see Part I, Item 1A. "Risk Factors - Risks Related to Intellectual Property and Market Exclusivity - We may be restricted in our development, manufacturing, and/or commercialization activities by patents or other proprietary rights of others, and could be subject to damage awards if we are found to have infringed such patents or rights"; and Note 17 to our Consolidated Financial Statements). Our policy is to file patent applications to protect technology, inventions, and improvements that we consider important to our business and operations. We hold an ownership interest in a number of issued patents in the United States and foreign countries with respect to our products and technologies. In addition, we hold an ownership interest in hundreds of patent applications in the United States and foreign countries.

Our patent portfolio includes granted patents and pending patent applications covering our VelociSuite technologies, including our VelocImmune mouse platform which produces fully human antibodies. Our issued patents covering these technologies generally expire between 2020 and 2030. However, we continue to file patent applications directed to improvements to these technology platforms.

Our patent portfolio also includes issued patents and pending applications relating to commercialized products and our product candidates in clinical development. These patents cover the proteins and DNA encoding the proteins, manufacturing patents, method of use patents, and pharmaceutical compositions.

The following table describes our U.S. patents and European patents (EP) that we currently consider of primary importance to our marketed products, including the territory, patent number, general subject matter class, and expected expiration dates. The noted expiration dates include any patent term adjustments. Certain of these patents may also be entitled to term extensions. We continue to pursue additional patents and patent term extensions in the United States and other jurisdictions covering various aspects of our products that may, if issued, extend exclusivity beyond the expiration of the patents listed in the table below. One or more patents with the same or earlier expiry date may fall under the same "general subject matter class" for certain products and are not separately listed.

Product		Molecule		Territory		Patent No.		General Subject Matter Class		Expiration
EYLEA		aflibercept		US		7,070,959		Composition of Matter		June 16, 2023*
				US		8,092,803		Formulation		June 21, 2027
				US		9,254,338		Methods of Treatment		May 22, 2032
				EP		1183353		Composition of Matter		May 23, 2025**
				EP		2364691		Formulation		June 14, 2027
				EP		1544299		Methods of Treatment		May 23, 2020
Dupixent		dupilumab		US		7,608,693		Composition of Matter		October 2, 2027
				US		8,945,559		Formulation		October 17, 2032
				US		8,075,887		Methods of Treatment		April 17, 2028
				US		8,337,839		Methods of Treatment		October 2, 2027
				US		9,290,574		Methods of Treatment		July 10, 2034
				US		9,574,004		Methods of Treatment		December 22, 2033
				EP		2356151		Composition of Matter		October 27, 2029
Praluent***		alirocumab		US		8,062,640		Composition of Matter		December 15, 2029
				US		8,795,669		Formulation		July 27, 2032
				US		8,357,371		Methods of Treatment		December 21, 2029
				US		9,550,837		Methods of Treatment		December 15, 2029
				US		9,724,411		Methods of Treatment		January 15, 2031
				EP		2358756		Composition of Matter		December 15, 2029
Kevzara		sarilumab		US		7,582,298		Composition of Matter		January 4, 2028
				US		9,173,880		Formulation		December 6, 2031
				US		8,080,248		Methods of Treatment		June 1, 2027
				EP		2041177		Composition of Matter		June 1, 2027
				EP		2766039		Methods of Treatment		October 10, 2032
* A patent term extension has been granted by the U.S. Patent and Trademark Office, extending the original patent term (May 23, 2020), insofar as it covers EYLEA, to June 16, 2023.
** Supplementary protection certificates have been granted in 14 European countries, extending the original patent term (May 23, 2020) in those countries to May 23, 2025, and are pending in nine additional European countries.
*** See Note 17 to our Consolidated Financial Statements for information regarding the patent infringement proceedings relating to Praluent, which may impact Praluent's commercial availability in the United States and other jurisdictions.

In addition, in the United States and certain other countries, our competitive position may be enhanced due to the availability of market exclusivity under relevant law (for additional information regarding market exclusivity, see Part I, Item 1A. "Risk Factors - Risks Related to Intellectual Property and Market Exclusivity - Loss or limitation of patent rights, and new regulatory pathways for biosimilar competition, could reduce the duration of market exclusivity for our products"). The effect of expiration of a patent relating to a particular product also depends upon other factors, such as the nature of the market and the position of the product in it, the growth of the market, the complexities and economics of the process for manufacture of the active ingredient of the product, and the requirements of new drug provisions of the Federal Food, Drug and Cosmetic Act or similar laws and regulations in other countries.

We also are the nonexclusive licensee of a number of additional patents and patent applications. These include fully paid-up and royalty-free licenses to certain patents relating to VEGF receptor proteins, known as the Davis-Smyth patents, and other related technology patents for the prevention or treatment of human eye diseases and eye disorders through administration of EYLEA to the eye.

Patent law relating to the patentability and scope of claims in the biotechnology field is evolving and our patent rights are subject to this additional uncertainty. The degree of patent protection that will be afforded to our products in the United States and other important commercial markets is uncertain and is dependent upon the scope of protection decided upon by the patent offices, courts, and governments in these countries. There is no certainty that our existing patents or others, if obtained, will provide us protection from competition or provide commercial benefit.

Others may independently develop similar products or processes to those developed by us, duplicate any of our products or processes or, if patents are issued to us, design around any products and processes covered by our patents. We expect to continue, when appropriate, to file product and process applications with respect to our inventions. However, we may not file any such applications or, if filed, the patents may not be issued. Patents issued to or licensed by us may be infringed by the products or processes of others.

Defense and enforcement of our intellectual property rights is expensive and time consuming, even if the outcome is favorable to us. It is possible that patents issued or licensed to us will be successfully challenged, that a court may find that we are infringing validly issued patents of third parties, or that we may have to alter or discontinue the development of our products or pay licensing fees to take into account patent rights of third parties (see Part I, Item 1A. "Risk Factors - Risks Related to Intellectual Property and Market Exclusivity - We may be restricted in our development, manufacturing, and/or commercialization activities by patents or other proprietary rights of others, and could be subject to damage awards if we are found to have infringed such patents or rights"; and Note 17 to our Consolidated Financial Statements).

Government Regulation

Regulation by government authorities in the United States and foreign countries is a significant factor in the research, development, manufacture, and marketing of our products and our product candidates. A summary of regulatory requirements that are relevant to our business is provided below. These include (i) preclinical requirements; (ii) product approval requirements; (iii) post-approval regulation; (iv) pricing and reimbursement requirements; and (v) other applicable requirements. For a description of material regulatory risks we face, please also refer to Part I, Item 1A. "Risk Factors."

Preclinical Requirements

The activities required before a product candidate may be marketed in the United States begin with preclinical tests. Preclinical tests include laboratory evaluations and animal studies to assess the potential safety and efficacy of the product candidate and its formulations. Preclinical trials must comply with the FDA's Good Laboratory Practices (GLPs) and the U.S. Department of Agriculture's Animal Welfare Act. The results of these studies must be submitted to the FDA as part of an IND, which must be reviewed by the FDA before proposed clinical testing can begin. In other countries, the data are reviewed by regulatory authorities as part of our clinical trial applications. The FDA or other regulatory authorities may ask for additional data in order to begin a clinical study. In addition, based on safety data that emerge from our studies, such regulatory authorities may put a study or an entire clinical development program on hold pending receipt of additional data. These actions by the FDA or other regulatory authorities can result in a delay or termination of a clinical development program.

Product Approval

All of our product candidates will require regulatory approval before they can be commercialized. In particular, human therapeutic products are subject to rigorous preclinical and clinical trials and other pre-market approval requirements by the FDA and foreign authorities. The structure and substance of the FDA and foreign pharmaceutical regulatory practices evolve over time as government priorities change. The ultimate outcome and impact of such developments cannot be predicted.

Typically, clinical testing involves a three-phase process. In Phase 1, trials are typically conducted with a small number of healthy volunteers to determine the early safety profile of the product candidate for treatment of the relevant disease. In Phase 2, clinical trials are conducted with subjects afflicted with a specific disease or disorder to provide enough data to evaluate the preliminary safety, tolerability, and efficacy of different potential doses of the product candidate. In Phase 3, large-scale clinical trials are conducted with patients afflicted with the specific disease or disorder in order to provide enough data to understand the efficacy and safety profile of the product candidate, as required by the FDA. If concerns arise about the safety of the product candidate, the FDA can stop clinical trials by placing them on a "clinical hold." The results of the preclinical and clinical testing of a biologic product candidate are then submitted to the FDA in the form of a BLA for evaluation to determine whether the product candidate may be approved for commercial sale under the Public Health Service Act. Under the Prescription Drug User Fee Act, we must pay fees to the FDA for review of any BLA, which can exceed $2 million. In responding to a BLA, the FDA may grant marketing approval, request additional information, or deny the application. Before approving a new drug or biologic product, the FDA also requires that the facilities at which the product will be manufactured or advanced through the supply chain be in compliance with current Good Manufacturing Practices, or cGMP, requirements and regulations governing the manufacture, shipment, and storage of the product. The FDA also can audit the sponsor of the BLA to determine if the clinical studies were conducted in compliance with current Good Clinical Practice, or cGCP, requirements.

Any approval required by the FDA for any of our product candidates may not be obtained on a timely basis, or at all. The designation of a clinical trial as being of a particular phase is not necessarily indicative that such a trial will be sufficient to satisfy the parameters of a particular phase, and a clinical trial may contain elements of more than one phase notwithstanding the designation of the trial as being of a particular phase. The results of preclinical studies or early stage clinical trials may not predict long-term safety or efficacy of our compounds when they are tested or used more broadly in humans.

Approval of a product candidate by comparable regulatory authorities in foreign countries is generally required prior to commencement of marketing of the product in those countries. The approval procedure varies among countries and may involve additional testing, and the time required to obtain such approval may differ from that required for FDA approval. Approval by a regulatory authority in one jurisdiction does not guarantee approval by comparable regulatory authorities in other jurisdictions.

Various federal, state, and foreign statutes and regulations also govern or influence the research, manufacture, safety, labeling, storage, record keeping, marketing, transport, and other aspects of pharmaceutical product candidates. The lengthy process of seeking these approvals and the compliance with applicable statutes and regulations require the expenditure of substantial resources. Any failure by us or our collaborators or licensees to obtain, or any delay in obtaining, regulatory approvals could adversely affect the manufacturing or marketing of our products and our ability to receive product or royalty revenue.

For additional information regarding U.S. and foreign regulatory approval processes and requirements, see Part I, Item 1A, "Risk Factors - Risks Related to Maintaining Approval of Our Marketed Products and the Development and Obtaining Approval of Our Product Candidates and New Indications for Our Marketed Products - Obtaining and maintaining regulatory approval for drug products is costly, time-consuming, and highly uncertain."

Post-Approval Regulation

The FDA and comparable regulatory authorities in other jurisdictions may also require us to conduct additional clinical trials after granting approval of a product. The FDA has the explicit authority to require postmarketing studies (also referred to as post-approval or Phase 4 studies), labeling changes based on new safety information, and compliance with FDA-approved risk evaluation and mitigation strategies.

Following approval, the FDA regulates the marketing and promotion of our products, which must comply with the Food, Drug, and Cosmetic Act and applicable FDA implementing standards. The FDA's review of promotional activities includes healthcare provider-directed and direct-to-consumer advertising as well as sales representatives' communications. The FDA may take enforcement action for promoting unapproved uses of a product or other violations of its advertising and promotion laws and regulations. See Part I, Item 1A, "Risk Factors - Regulatory and Litigation Risks - If we market and sell approved products in a way that violates federal or state healthcare laws, we may be subject to civil or criminal penalties."

Adverse-event reporting and submission of periodic reports is required following marketing approval. We may be subject to audits by the FDA and other regulatory authorities to ensure that we are complying with the applicable requirements. In addition, we and our third-party providers are required to maintain compliance with cGMPs, and are subject to inspections by the FDA or comparable regulatory authorities in other jurisdictions to confirm such compliance. Changes of suppliers or modifications of methods of manufacturing may require amending our application(s) to the FDA or such comparable foreign regulatory authorities and acceptance of the change by the FDA or such comparable foreign regulatory authorities prior to release of product(s). Prescription drug manufacturers in the U.S. must comply with applicable provisions of the Drug Supply Chain Security Act and provide and receive product tracing information, maintain appropriate licenses, ensure they only work with other properly licensed entities, and have procedures in place to identify and properly handle suspect and illegitimate products. We may also be subject to state regulations related to the manufacturing and distribution of our products.

Failure to comply with these laws and regulations may lead the FDA and comparable regulatory authorities in other jurisdictions to take regulatory action, including suspending manufacturing or withdrawing their approval of a product.

Pricing and Reimbursement

Sales in the United States of our marketed products are dependent, in large part, on the availability and extent of reimbursement from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid. Sales of our marketed products in other countries are dependent, in large part, on coverage and reimbursement mechanisms and programs administered by health authorities in those countries. See Part I, Item 1A, "Risk Factors - Risks Related to Commercialization of Products - The successful commercialization of our marketed products, as well as our late-stage product candidates or new indications for our marketed products, if approved, will depend on obtaining and maintaining coverage and reimbursement for use of these products from third-party payers, including Medicare and Medicaid in the United States, and these payers may not cover or adequately reimburse for use of our products or may do so at levels that make our products uncompetitive and/or unprofitable, which would materially harm our business, prospects, operating results, and financial condition."

Medicaid is a joint federal and state program that is administered by the states for low income and disabled beneficiaries. Under the Medicaid Drug Rebate Program, we are required to pay a rebate for each unit of product reimbursed by the state Medicaid programs. The amount of the rebate is established by law and is adjusted upward if average manufacture price (AMP) increases more than inflation (measured by the Consumer Price Index - Urban). The rebate amount is calculated each quarter based on our report of current AMP and best price for each of our products to CMS. The requirements for calculating AMP and best price are

complex. We are required to report any revisions to AMP or best price previously reported within a certain period, which revisions could affect our rebate liability for prior quarters. In addition, if we fail to provide information timely or we are found to have knowingly submitted false information to the government, the statute governing the Medicaid Drug Rebate Program provides for civil monetary penalties.

Medicare is a federal program that is administered by the federal government that covers individuals age 65 and over as well as those with certain disabilities. Medicare Part B generally covers drugs that must be administered by physicians or other health care practitioners; are provided in connection with certain durable medical equipment; or are certain oral anti-cancer drugs and certain oral immunosuppressive drugs. Medicare Part B pays for such drugs under a payment methodology based on the average sales price (ASP) of the drugs. Manufacturers, including us, are required to provide ASP information to CMS on a quarterly basis. The manufacturer-submitted information is used to calculate Medicare payment rates. If a manufacturer is found to have made a misrepresentation in the reporting of ASP, the governing statute provides for civil monetary penalties. Medicare Part D provides coverage to enrolled Medicare patients for self-administered drugs (i.e., drugs that are not administered by a physician). Medicare Part D is administered by private prescription drug plans approved by the U.S. government and, subject to detailed program rules and government oversight, each drug plan establishes its own Medicare Part D formulary for prescription drug coverage and pricing, which the drug plan may modify from time to time. The prescription drug plans negotiate pricing with manufacturers and pharmacies, and may condition formulary placement on the availability of manufacturer discounts. In addition, manufacturers, including us, are required to provide to CMS a 50% discount on brand name prescription drugs utilized by Medicare Part D beneficiaries when those beneficiaries are in the coverage gap phase of the Part D benefit design.

Our products are subject to discounted pricing when purchased by federal agencies via the Federal Supply Schedule (FSS). FSS participation is required for our products to be covered and reimbursed by the Veterans Administration (VA), Department of Defense, Coast Guard, and Public Health Service (PHS). Coverage under Medicaid, Medicare, and the PHS pharmaceutical pricing program is also conditioned upon FSS participation. FSS pricing is intended not to exceed the price that we charge our most-favored non-federal customer for a product. In addition, prices for drugs purchased by the VA, Department of Defense (including drugs purchased by military personnel and dependents through the TriCare retail pharmacy program), Coast Guard, and PHS are subject to a cap on pricing equal to 76% of the non-federal average manufacturer price (non-FAMP). An additional discount applies if non-FAMP increases more than inflation (measured by the Consumer Price Index - Urban). In addition, if we fail to provide information timely or we are found to have knowingly submitted false information to the government, the governing statute provides for civil monetary penalties.

To maintain coverage of our products under the Medicaid Drug Rebate Program and Medicare Part B, we are required to extend significant discounts to certain covered entities that purchase products under Section 340B of the PHS pharmaceutical pricing program. Purchasers eligible for discounts include hospitals that serve a disproportionate share of financially needy patients, community health clinics, and other entities that receive certain types of grants under the Public Health Service Act. For all of our products, we must agree to charge a price that will not exceed the amount determined under statute (the "ceiling price") when we sell outpatient drugs to these covered entities. In addition, we may, but are not required to, offer these covered entities a price lower than the 340B ceiling price. The 340B discount formula is based on AMP and is generally similar to the level of rebates calculated under the Medicaid Drug Rebate Program.

Private payor healthcare and insurance providers, health maintenance organizations, and pharmacy benefit managers in the United States are adopting more aggressive utilization management techniques and are increasingly requiring significant discounts and rebates from manufacturers as a condition to including products on formulary with favorable coverage and copayment/coinsurance. As a consequence, these payers may not cover or adequately reimburse for use of our products or may do so at levels that disadvantage them relative to competitive products.

Outside the United States, within the EU, our products are paid for by a variety of payors, with governments being the primary source of payment. Government health authorities in the EU determine or influence reimbursement of products, and set prices or otherwise regulate pricing. Negotiating prices with governmental authorities can delay commercialization of our products. Governments may use a variety of cost-containment measures to control the cost of products, including price cuts, mandatory rebates, value-based pricing, and reference pricing (i.e., referencing prices in other countries or prices of competitive products and using those reference prices to set a price). Budgetary pressures in many EU countries are continuing to cause governments to consider or implement various cost-containment measures, such as price freezes, increased price cuts and rebates, and expanded generic substitution and patient cost-sharing.

Other Regulatory Requirements

We are subject to health care "fraud and abuse" laws, such as the federal False Claims Act, the anti-kickback provisions of the federal Social Security Act, and other state and federal laws and regulations. Federal and state anti-kickback laws prohibit, among other things, payments or other remuneration to induce or reward someone to purchase, prescribe, endorse, or recommend a product that is reimbursed under federal or state healthcare programs. Federal false claims laws prohibit any person from knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly making, or causing to be made, a false statement to get a false claim paid. See Part I, Item 1A, "Risk Factors - Regulatory and Litigation Risks - If we market and sell approved products in a way that violates federal or state healthcare laws, we may be subject to civil or criminal penalties."

Our business activities outside of the United States are subject to the Foreign Corrupt Practices Act, or FCPA, and similar anti-bribery or anti-corruption laws, regulations or rules of other countries in which we operate, including the U.K. Bribery Act. See Part I, Item 1A, "Risk Factors - Regulatory and Litigation Risks - Risks from the improper conduct of employees, agents, contractors, or collaborators could adversely affect our reputation and our business, prospects, operating results, and financial condition."

Numerous federal and state laws, including state security breach notification laws, state health information privacy laws, and federal and state consumer protection laws, govern the collection, use, and disclosure of personal information. In addition, most health care providers, including research institutions from which we or our collaborators obtain patient health information, are subject to privacy and security regulations promulgated under the Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act. Although we are not directly subject to HIPAA other than with respect to providing certain employee benefits, we could potentially be subject to criminal penalties if we, our affiliates, or our agents knowingly obtain or disclose individually identifiable health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA. Outside the United States, our clinical trial programs and research collaborations may implicate international data protection laws, including the EU Data Protection Directive and the General Data Protection Regulation (GDPR) that is replacing it. See Part I, Item 1A, "Risk Factors - Regulatory and Litigation Risks - We face potential liability related to the privacy of health information we obtain from clinical trials sponsored by us or our collaborators, from research institutions and our collaborators, and directly from individuals."

In addition to the foregoing, our present business is, and our future business will be, subject to regulation under the United States Atomic Energy Act, the Clean Air Act, the Clean Water Act, the Comprehensive Environmental Response, Compensation and Liability Act, the National Environmental Policy Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act, national restrictions, and other current and potential future local, state, federal, and foreign regulations.

Business Segments

We manage our business as one segment which includes all activities related to the discovery, development, and commercialization of medicines for the treatment of serious medical conditions. For financial information related to our one segment, see Part II, Item 6. "Selected Financial Data" and our Consolidated Financial Statements and related notes.

Employees

As of December 31, 2017, we had approximately 6,200 full-time employees. We believe that we have been successful in attracting skilled and experienced personnel in a highly competitive environment; however, competition for these personnel is intense. None of our personnel are covered by collective bargaining agreements and our management considers its relations with our employees to be good.

Corporate Information

We were incorporated in the State of New York in 1988 and publicly listed in 1991. Our principal executive offices are located at 777 Old Saw Mill River Road, Tarrytown, New York 10591, and our telephone number at that address is (914) 847-7000.

We make available free of charge on or through our Internet website (http://www.regeneron.com) our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and, if applicable, amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act, as soon as reasonably practicable after we electronically file such material with, or furnish it to, the Securities and Exchange Commission (SEC).

Investors and other interested parties should note that we use our media and investor relations website (http://newsroom.regeneron.com) and our social media channels to publish important information about Regeneron, including information that may be deemed material to investors. We encourage investors and other interested parties to review the information we may publish through our media and investor relations website and the social media channels listed on our media and investor relations website, in addition to our SEC filings, press releases, conference calls, and webcasts.