April 28, 2008
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`Regeneron and Bayer HealthCare Announce Encouraging 32-Week Follow-Up Results from
`a Phase 2 Study of VEGF Trap-Eye in Age-Related Macular Degeneration
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`Gains in visual acuity achieved in initial 12-week fixed dosing phase of study maintained in PRN (as-
`needed) dosing phase
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`TARRYTOWN, N.Y. & LEVERKUSEN, Germany--(BUSINESS WIRE)--April 28, 2008--Regeneron Pharmaceuticals, Inc. (Nasdaq:
`REGN) and Bayer HealthCare AG today announced that VEGF Trap-Eye dosed on a PRN (as-needed) dosing schedule
`maintained the statistically significant gain in visual acuity achieved after an initial, 12-week, fixed-dosing phase of a Phase 2
`study in the neovascular form of Age-related Macular Degeneration (wet AMD). A full analysis of the 32-week results of the
`Phase 2 study will be presented today at the 2008 Association for Research in Vision and Ophthalmology (ARVO) meeting in
`Fort Lauderdale, Florida. The data being reported at the meeting are available on the Regeneron website
`(www.regeneron.com on the Investor Relations page, under the Presentations heading).
`
`Study results showed that across all dose groups in the study population, the 6.6 mean letter gain in visual acuity achieved
`versus baseline at the week 16 evaluation visit, following 12 weeks of fixed dosing, was maintained out to week 32 (a 6.7 mean
`letter gain versus baseline; p less than 0.0001) using a PRN dosing schedule (where dosing frequency was determined by the
`physician's assessment of pre-specified criteria). The decrease in retinal thickness, an anatomical measure of treatment effect
`achieved with a fixed-dose schedule was also maintained for all dose groups combined at week 32 (a 137 micron mean
`decrease versus baseline, p less than0.0001).
`
`In this double-masked, prospective, randomized, multi-center Phase 2 trial, 157 patients were randomized to five dose groups
`and treated with VEGF Trap-Eye in one eye. Two groups initially received monthly doses of 0.5 or 2.0 milligrams (mg) of VEGF
`Trap-Eye for 12 weeks and three groups received quarterly doses of 0.5, 2.0, or 4.0 mg of VEGF Trap-Eye (at baseline and
`week 12). Following the initial 12-week fixed-dose phase of the trial, patients continued to receive therapy at the same dose on
`a PRN dosing schedule based upon the physician assessment of the need for re-treatment in accordance with pre-specified
`criteria. Patients were monitored for safety, retinal thickness, and visual acuity. These data represent the week 32 analysis
`from the 52-week study, which is continuing to follow patients.
`
`Patients receiving monthly doses of VEGF Trap-Eye, either 0.5 or 2.0 mg, for 12 weeks followed by PRN dosing thereafter
`achieved mean improvements in visual acuity of 8.0 (p less than0.01 versus baseline) and 10.1 letters (p less than0.0001
`versus baseline), respectively, and mean decreases in retinal thickness of 141 (p less than0.0001 versus baseline) and 162
`microns (p less than0.0001 versus baseline) at week 32, respectively. While PRN dosing also maintained the improvements in
`retinal thickness and visual acuity achieved versus baseline following a fixed dosing regimen utilizing quarterly dosing at
`baseline and week 12, the results achieved with a quarterly fixed dosing regimen were generally not as robust as obtained with
`initial fixed monthly dosing.
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`VEGF Trap-Eye was generally safe and well tolerated and there were no drug-related serious adverse events. There was one
`reported case of culture-negative endophthalmitis/uveitis in the study eye, which was deemed not to be drug-related. The most
`common adverse events were those typically associated with intravitreal injections.
`
`After the last fixed-dose administration at week 12, patients from all dose groups combined required, on average, only one
`additional injection over the following 20 weeks to maintain the visual acuity gain established during the fixed-dosing period.
`Notably, 55 percent of the patients who received 2.0 mg monthly for 12 weeks did not require any additional treatment
`throughout the next 20-week PRN dosing period. Moreover, 97 percent of the patients who received 2.0 mg monthly for 12
`weeks did not require re-dosing at the week 16 evaluation visit, indicating that an 8-week dosing schedule may be feasible.
`
`"Due to its high affinity for all isoforms of VEGF-A and PlGF, potent mediators of blood vessel overgrowth in wet AMD, as well
`as its long residence time in the eye, it is anticipated that VEGF Trap-Eye may be able to be dosed at a frequency less than
`once monthly, especially on a chronic basis, without compromising visual acuity," stated Quan Dong Nguyen, M.D., M.Sc.,*
`Assistant Professor of Ophthalmology, Wilmer Ophthalmological Institute, the Johns Hopkins University School of Medicine,
`Baltimore, MD and a primary investigator in the Phase 2 study. "These emerging Phase 2 clinical data seem to support the
`concept of durability of VEGF Trap-Eye."
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`In this study, treatment with VEGF Trap-Eye was associated with a reduction in the size of the choroidal neovascular membrane
`(CNV), the lesion that is the underlying cause of vision loss due to wet AMD. Patients initially treated with a 0.5 mg or 2.0 mg
`monthly fixed dose for 12 weeks, followed by PRN dosing thereafter, experienced 1.55 mm(2) and 2.52 mm(2) reductions in
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`Mylan Exhibit 1012
`Mylan v. Regeneron, IPR2021-00880
`Page 1
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`Joining Petitioner: Apotex
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`mean CNV size at 24 weeks (the most recently available analysis from the independent reading center) versus baseline,
`respectively. Patients treated initially with fixed quarterly dosing also experienced an overall reduction in CNV size.
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`"Regression in CNV size is generally not seen when treating wet AMD patients. The reduction in CNV size achieved thus far
`with VEGF Trap-Eye treatment highlights the potential clinical utility of this investigational treatment in patients suffering from
`this devastating condition," stated Jason Slakter, M.D., Clinical Professor of Ophthalmology, New York University School of
`Medicine, New York.
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`"These study results further increase our confidence in the design of our Phase 3 clinical program for VEGF Trap-Eye in wet
`AMD," said George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories. "These studies are
`evaluating the clinical efficacy and safety of VEGF Trap-Eye, using a monthly loading dose of 0.5 mg or 2.0 mg for 12 weeks,
`followed by a nine-month fixed-dosing regimen of 0.5 mg monthly, 2.0 mg monthly, or 2.0 mg every eight weeks. In the second
`year of the studies, all patients will be dosed on a PRN basis."
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`About the Phase 3 Program in Wet AMD
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`Regeneron and Bayer HealthCare initiated a Phase 3 global development program for VEGF Trap-Eye in wet AMD in August
`2007. In two Phase 3 trials, the companies are evaluating VEGF Trap-Eye using four- and eight-week dosing intervals in direct
`comparison with ranibizumab (Lucentis®, a registered trademark of Genentech, Inc.) administered every four weeks according
`to its label during the first year of the studies. PRN dosing will be evaluated during the second year of each study. The VIEW1
`study is currently enrolling patients in the United States and Canada. The VIEW2 study has recently been initiated and will
`enroll patients in up to 200 centers in Europe, Asia Pacific, Japan, and Latin America. The companies are collaborating on the
`global development of VEGF Trap-Eye for the treatment of wet AMD, diabetic eye diseases, and other eye diseases and
`disorders. Bayer HealthCare will market VEGF Trap-Eye outside the United States, where the companies will share equally in
`profits from any future sales of VEGF Trap-Eye. Regeneron maintains exclusive rights to VEGF Trap-Eye in the United States.
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`About VEGF Trap-Eye
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`Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body whose normal role is to trigger
`formation of new blood vessels (angiogenesis) to support the growth of the body's tissues and organs. It has also been
`associated with the abnormal growth and fragility of new blood vessels in the eye, which lead to the development of wet AMD.
`The VEGF Trap-Eye is a fully human, soluble VEGF receptor fusion protein that binds all forms of VEGF-A along with the
`related Placental Growth Factor (PlGF). VEGF Trap-Eye is a specific and highly potent blocker of these growth factors.
`Blockade of VEGF, which can prevent abnormal blood vessel formation and vascular leak, has proven beneficial in the
`treatment of wet AMD and a VEGF inhibitor, ranibizumab, has been approved for treatment of patients with this condition.
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`About Wet AMD
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`Age-related Macular Degeneration (AMD) is a leading cause of acquired blindness. Macular degeneration is diagnosed as
`either dry (nonexudative) or wet (exudative). In wet AMD, new blood vessels grow beneath the retina and leak blood and fluid.
`This leakage causes disruption and dysfunction of the retina creating blind spots in central vision, and it can account for
`blindness in wet AMD patients. Wet AMD is the leading cause of blindness for people over the age of 65 in the U.S. and
`Europe.
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`About Regeneron Pharmaceuticals, Inc.
`
`Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the
`treatment of serious medical conditions. In addition to ARCALYST™ (rilonacept) Injection for Subcutaneous Use, its first
`commercialized product, Regeneron has therapeutic candidates in clinical trials for the potential treatment of cancer, eye
`diseases, and inflammatory diseases, and has preclinical programs in other diseases and disorders. Additional information
`about Regeneron and recent news releases are available on Regeneron's web site at www.regeneron.com.
`
`Forward Looking Statement
`
`This news release discusses historical information and includes forward-looking statements about Regeneron and its products,
`development programs, finances, and business, all of which involve a number of risks and uncertainties, such as risks
`associated with preclinical and clinical development of Regeneron's drug candidates, determinations by regulatory and
`administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize
`its product and drug candidates, competing drugs that are superior to Regeneron's product and drug candidates, uncertainty
`of market acceptance of Regeneron's product and drug candidates, unanticipated expenses, the availability and cost of capital,
`the costs of developing, producing, and selling products, the potential for any collaboration agreement, including Regeneron's
`agreements with the sanofi-aventis Group and Bayer HealthCare, to be canceled or to terminate without any product success,
`risks associated with third party intellectual property, and other material risks. A more complete description of these and other
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`Mylan Exhibit 1012
`Mylan v. Regeneron, IPR2021-00880
`Page 2
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`material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission (SEC), including
`its Form 10-K for the year ended December 31, 2007. Regeneron does not undertake any obligation to update publicly any
`forward-looking statement, whether as a result of new information, future events, or otherwise unless required by law.
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`* The assessment made by Dr. Nguyen does not necessarily imply endorsement by the Johns Hopkins University, the Johns
`Hopkins Hospital, or the Johns Hopkins Medical Institutions.
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`CONTACT: Regeneron Pharmaceuticals, Inc.
`Investor Relations, 914-345-7640
`invest@regeneron.com
`or
`Corporate Communications
`Laura Lindsay, 914-345-7800
`laura.lindsay@regeneron.com
`or
`Media Relations
`Kimberly Chen, 212-845-5634
`kchen@biosector2.com
`
`SOURCE: Regeneron Pharmaceuticals, Inc.
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`Mylan Exhibit 1012
`Mylan v. Regeneron, IPR2021-00880
`Page 3
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`Joining Petitioner: Apotex
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