Results of one year of EYLEA Phase 3 positive studies on diabetic retinopathy presented at the symposium on angiogenesis

The trial confirmed that moderately severe and severe non-proliferative diabetic retinopathy was not a benign condition, patients with a high risk of rapid progression to events threatening vision. In patients not treated with severe NPDR, 53% developed these events at one year. Most importantly, treatment with EYLEA has prevented about 74% of these complications.

The main year-long data presented at the meeting are summarized below:

DRSS = severity scale of diabetic retinopathy
^a p <0.0001 versus simulacrum
^b Vision-threatening events defined as vision-threatening complications (VTC, proliferative diabetic retinopathy or anterior segment neovascularization) or central diabetic macular edema (CI-DME)
^c P nominal = 0.0019 against simulacrum
^re P nominal <0.0001 versus simulacrum

The one-year PANORAMA Topline results have already been reported in October 2018.

"PANORAMA provides high quality data to inform NPDR treatment without an EMR, as it is the first prospective trial involving these high-risk patients since the 1980s ETDRS historical trial, where the laser was the only treatment option, "said Charles C. Wykoff, M.D., Ph.D., PANORAMA investigator, retinal surgeon and ophthalmologist with Retina Consultants of Houston. "Without treatment, a significant percentage of patients participating in the trial developed a proliferative disease and an IC-EMR in the first year, and treatment with EYLEA reduced the risk of these events by approximately 74% compared to a simulated injection, thus highlighting the potential importance of early treatment with EYLEA VEGF therapy This efficacy was found even after treatment every 16 weeks after dosing, which is a management approach realistic in the real world. "

The adverse events were consistent with the known profile of EYLEA. Serious ocular ocular adverse effects related to ocular treatment occurring in the study eye occurred in 0 and 1 patient in the EYLEA treatment groups and 1 patient in the simulated injection group. Ocular inflammation occurred in 1 patient in each EYLEA treatment group and in 0 patients in the simulated injection group. Anti-platelet collaboration (APTC) arterial thromboembolism-related events occurred in 4 and 2 patients in the EYLEA treatment groups and 5 patients in the simulated injection group.

An application for an additional biologic product license (sBLA) for EYLEA in the treatment of diabetic retinopathy has been accepted for review by the US FDA, with a target action date of May 13, 2019.

The safety and effectiveness of EYLEA in diabetic retinopathy in patients without EMRs have not been fully evaluated by any regulatory authority.

About the PANORAMA trial
PANORAMA is a clinical trial underway, pivot, double mask, randomized, involving 402 patients. It is designed to examine EYLEA for the improvement of moderately severe to severe NPDR in patients without an EMR, compared to simulated injections. The details on the design of the test include:

• Three treatment arms – A simulated injection observation group and two EYLEA treatment groups. EYLEA was administered every 8 weeks (after five initial monthly doses) or every 16 weeks (after three initial monthly doses and an 8-week interval).
• Main criterion – The primary endpoint was the proportion of patients who showed improvement in two or more stages of the DRSS compared to baseline for the EYLEA combined treatment groups at week 24 and for each EYLEA treatment group separately (each group of 8 weeks and each group of 16 weeks). week) at week 52. The DRSS is a systematic rating scale for badessing the severity of diabetic retinopathy from photographs of the retina following a dilated view.
• Secondary endpoints – This includes evaluating whether EYLEA reduces VTC (defined as proliferative diabetic retinopathy and anterior segment neovascularization) or the development of EMR-EMR, as well as its impact on other anatomical effects. , improving visual acuity and safety.

A separate ongoing trial, sponsored by the Diabetic Retinopathy Clinical Research Network, called the W Protocol, is also evaluating EYLEA for the treatment of NPDR in patients without an EMR.

About Diabetic Retinopathy (DR)
About eight million people live with DR, a disease characterized by microvascular damage to the retinal blood vessels often caused by poor blood sugar control in people with diabetes. The disease usually starts as NPDR and often has no warning signs or symptoms. NPDR can progress to proliferative diabetic retinopathy (PDR), a phase of the disease in which abnormal blood vessels develop on the surface of the retina and in the vitreous cavity, potentially leading to severe vision loss.

The MDG can occur at any stage of R & D because the blood vessels in the retina become more and more fragile and leak fluid that can cause visual impairment. In the United States, about 1.5 million adults have been diagnosed with an EMR, while about 3.5 million people have an RD without an EMR.

About EYLEA^® (aflibercept) Injection
Eylea^® (aflibercept) Injection is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eyes. It is designed to block the growth of new blood vessels and reduce the ability of the fluid to cross the blood vessels (vascular permeability) of the eye by blocking VEGF-A and Placental Growth Factor (PLGF), two factors of growth involved in angiogenesis. In the United States, EYLEA is the FDA-approved, market-leading anti-VEGF treatment for approved indications. It is supported by a solid body of research including seven pivotal phase 3 trials.

IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTIONS

• Eylea^® (aflibercept) Injection is contraindicated in patients with ocular or periocular infection, active intraocular inflammation or known hypersensitivity to aflibercept or any of the excipients of EYLEA.
• Intravitreal injections, including those badociated with EYLEA, have been badociated with endophthalmitis and retinal detachments. The aseptic injection technique should always be used when administering EYLEA. Patients should be informed of any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be appropriately managed. Intraocular inflammation has been reported with the use of EYLEA.
• Acute increases in intraocular pressure were observed within 60 minutes after intravitreal injection, including with EYLEA. Sustained increases in intraocular pressure have also been reported following repeated intravitreous doses with VEGF inhibitors. Intraocular pressure and perfusion of the optic nerve head should be monitored and managed appropriately.
• There is a potential risk of arterial thromboembolic events (ATEs) as a result of intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as non-fatal strokes, non-fatal myocardial infarctions, or vascular death (including deaths of unknown cause). In the first year, the incidence of thromboembolic events reported in wet AMD studies was 1.8% (32 of 1824) in the combined group of EYLEA-treated patients, compared to 1.5% ( 9 of 595) in patients treated with ranibizumab; over 96 weeks, the incidence was 3.3% (60 out of 1824) in the EYLEA group, compared to 3.2% (19 out of 595) in the ranibizumab group. The incidence in the EMR studies between the beginning of the week and week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA, compared to 2.8% (8 out of 287) in the control group; between baseline and week 100, the incidence was 6.4% (37 of 578) in the combined group of EYLEA-treated patients compared to 4.2% (12 of 287) in the control group. No thromboembolic events have been reported in patients treated with EYLEA during the first six months of RVO studies.
• Serious adverse reactions related to the injection procedure were observed in less than 0.1% of intravitreal EYLEA injections, including endophthalmitis and retinal detachment.
• The most commonly reported adverse events (≥ 5%) in patients treated with EYLEA were conjunctival hemorrhage, ocular pain, cataract, vitreous detachment, vitreous congestion, and increased intraocular pressure. -ocular.

INDICATIONS
Eylea^® (aflibercept) Injection is indicated in the treatment of patients with neovascular (wet) age-related macular degeneration (AMD), macular edema secondary to retinal venous occlusion (OVR), d. Diabetic macular edema (DME) and diabetic retinopathy (DR) in patients with EMR.

Please visit www.EYLEA.us to view the complete prescription information for EYLEA.

Sure Regeneron Pharmaceuticals, Inc.
Regeneron (NASDAQ: REGN) is a leading biotech company that invents life-transforming drugs for people with serious illnesses. Founded and directed for 30 years by medical scientists, our unique ability to translate science repeatedly and consistently into medicine has led to seven FDA-approved treatments and numerous product candidates in development, all developed in our labs. Our drugs and pipeline are designed to help patients with eye diseases, heart disease, allergic and inflammatory diseases, pain, cancer, infectious diseases and rare diseases.

Regeneron speeds up and enhances the development process of traditional medicines with our patented system VelociSuite^® technologies, such as VelocImmune^® which produces fully human optimal antibodies and ambitious research initiatives such as the Regeneron Genetics Center, which is leading one of the world's largest sequencing efforts.

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Regeneron's Forward-Looking Statements and the Use of Digital Media
This press release contains forward-looking statements that involve risks and uncertainties relating to future events and future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"). Actual events or results may differ materially from these events. statements to search. Terms such as "anticipate", "expect", "intend", "plan", "believe", "search", "estimate", variations of these words and similar expressions purpose of identifying these forward-looking statements, although not all forward-looking statements contain these identifying words. These statements relate, and these risks and uncertainties include, among others, the nature, timing, as well as the possible therapeutic successes and applications of Regeneron products, product candidates and ongoing or planned research and clinical programs, including, without limitation, EYLEA^® (aflibercept) Injection; unanticipated safety issues resulting from the administration of products and patient-candidate products, including serious complications or side effects related to the use of Regeneron's product candidates in clinical trials; the likelihood and timing of any regulatory approval and commercial launch of Regeneron 's advanced product candidates and new indications for marketed products, including, without limitation, any potential regulatory approvals of the product; EYLEA for patients: diabetic retinopathy; the impact of the recent and potential closures of the US government on the timing of the US Food and Drug Administration's decision on EYLEA's additional biologics license application for diabetic retinopathy mentioned in this news release; the extent to which the results of research and development programs conducted by Regeneron or its collaborators can be replicated in other studies and lead to therapeutic applications; regulatory requirements and ongoing monitoring affecting Regeneron's marketed products (such as EYLEA), research and clinical programs, and commercial activities, including those relating to patient privacy; decisions by regulatory and administrative governmental authorities that may delay or limit Regeneron's ability to continue to develop or market its products and product candidates; competing drug candidates and products that may be superior to Regeneron products and product candidates; uncertainty of market acceptance and commercial success of Regeneron products and product candidates and the impact of studies (whether conducted by Regeneron or others and that they are mandatory or voluntary) on the commercial success of Regeneron products and product candidates; Regeneron's ability to manufacture and manage supply chains for several product and product candidates; the ability of Regeneron's employees, suppliers or other third parties to perform (where applicable) the manufacture, filling, finishing, packaging, labeling, distribution and other stages relating to Regeneron products and product candidates; the availability and extent of reimbursement of the Company's products (such as EYLEA) by third-party payers, including health care and private payer insurance programs, health maintenance organizations , drug benefit management companies, and government programs such as Medicare and Medicaid; determination of the payor's coverage and repayment and new policies and procedures adopted by these payers; unforeseen expenses; the costs of developing, producing and selling products; Regeneron's ability to meet its financial forecasts or forecasts and to modify the underlying badumptions; the possibility that any licensing or collaboration agreement, including Regeneron's agreements with Sanofi, Bayer and Teva Pharmaceutical Industries Ltd. (or their respective affiliates, if applicable), be canceled or terminated without further success of the product; and the intellectual property risks of other parties and pending or future litigation involving them, including, without limitation, the patent litigation procedures relating to EYLEA, Dupixent^® (dupilumab) Injection and Praluate^® (Injurocumab) Injection, the end result of such litigation proceedings, as well as the consequences that the foregoing may have on Regeneron's business, prospects, results of operations and financial condition. A more complete description of these and other significant risks can be found in Regeneron's filings with the US Securities and Exchange Commission, including Form 10-K for the year ended the 31st of December2018. All forward-looking statements are made based on current beliefs and beliefs of management, and readers are cautioned not to rely on Regeneron's forward-looking statements. Regeneron undertakes no obligation to publicly update forward-looking statements, including, without limitation, any projections or financial forecasts, whether as a result of new information, future events or otherwise.