ACM SmmemTLEMVCUTM ty=f
`
`EYLEA® (aflibercept) Injection: The sal VEGF Inhibitor Approvedfor
`
`eS
`
` r Safety and efficacy were assessed in two randomized, multicenter,
`n double-masked, active-controlled (ranibizumab) studies (VIEW 1 and VIEW 2)
`
`VIEW 1 and VIEW 2 Study Design
`
`VIEW1N=1210;VIEW2N=1202 -—~”
`
`1:1:1:1
`
`ci
`
`
`
`Aeee Le
`
`CR eope tes
`
`;
`
`Ranibizumab ——»
`
`0.5 mg every 4 weeks
`
`_ *Following 3 initial monthly doses
`tAdditional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks
`tEYLEA 0.5 mg is not an approved dose
`
`Clinical Endpoints at 52 Weeks
`= Primary Endpoint:
`Proportion of patients who maintained visual acuity (%) (losing <15 letters of Best-Corrected
`Visual Acuity [BCVA])
`= Key Secondary Endpoints:
`Mean change in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
`letter score from baseline
`Number of patients who gained at least 15 letters of vision from baseline
`Important Safety Information from the EYLEA Prescribing Information
`= EYLEA® (aflibercept) Injection is contraindicated in patients with ocular or periocular infections,
`active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the
`excipients in EYLEA
`
`Exhibit 2137
`
`Page 16 of 30
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8S weeks.
`
`EYLEA is indicated for the treatment of
`patients with Macular Edemafollowing
`Central Retinal Vein Occlusion (CRVOQ).
`The recommended dose for EYLEA is
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`
`IMPORTANT SAFETY INFORMATION
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
`
`
`EYLEA
`(aflibercept) phat ,
`
`
`Exhibit 2137
`Page 16 of 30
`
`

`

`
`
`ARCOReC
`ACM SmmemTLEMVCUTM ty=f
`
`eS
`
`I
`[~
`
`VIEW 1 and VIEW 2 Dosing Schedule
`|
`WEEKS
`|
`
`2 mg every
`EYLEA 8 aa (298)
`
`2 mg
`every
`EYLEA 4 weeks (294)
`
`0.5 mg every
`EYLEA 4 oe8 (0.304)
`
`as
`0.5 mg every
`ranibizumab 4 weeks(rad)
`
`Patient Demographics
`= 2412 patients with predominantly classic, minimally classic, or occult neovascular Age-related
`Macular Degeneration were treated and evaluated?
`= All patients had a baseline ETDRS BCVAscore of 73 to 25 letters (Snellen equivalent of 20/40
`to 20/320 vision)?
`= Patient ages ranged from 49 to 99 years with a mean of /6 years
`Important Prescribing Information for EYLEA
`= The recommended dose for EYLEAfor the treatment of wet AMD is 2 mg administered by
`intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by
`2 mg once every 8 weeks (2 months)
`= Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional
`efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every
`8 weeks
`
`Exhibit 2137
`
`Page 17 of 30
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8S weeks.
`
`EYLEA is indicated for the treatment of
`patients with Macular Edemafollowing
`Central Retinal Vein Occlusion (CRVOQ).
`The recommended dose for EYLEA is
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`
`IMPORTANT SAFETY INFORMATION
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
`
`
`EYLEA
`(aflibercept) oo
`
`
`Exhibit 2137
`Page 17 of 30
`
`

`

`AU
`
`EYLEA® (aflibercept) Injection: The sal VEGF Inhibitor Approvedfor
`
`
`
`EYLEA 2 mg every 2 months (following 3 initial monthly doses) demonstrated
`Clinically equivalent efficacy to monthly ranibizumab in the proportion of
`patients who maintained vision at week 52°
`
`Primary Endpoint: Maintenanceof Vision (<15 Letters Lost) Based on BCVA as Measured by ETDRS at 52 Weeksvs Baseline
`
`
`
`ACM SmmemTLEMVCUTM ty=f
`EkeOS
`
`
`
`VIEW 1
`
`
`
`VIEW 2
`
`
`
`
`
`STUDY
`biel
`
`EYLEA
`2 mgevery2 months*
`
`ranibizumab
`0.5 mg every month
`
`EYLEA
`2 mgevery2 months*
`
`ranibizumab
`0.5 mg every month
`
`monthly doses
`
`*Following 3 initial
`
`= The proportion of patients dosed with EYLEA, 2 mg once every 4 weeks (monthly), losing fewer
`than 15 letters of vision at 52 weeks was 95% in VIEW 1 and 95% In VIEW 2
`= The recommended dose for EYLEAfor the treatment of Wet AMD is 2 mg administered by
`intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by
`2 mg once every 8 weeks (2 months)
`= Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional
`efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every
`8 weeks
`
`Important Safety Information from the EYLEA Prescribing Information
`= The most common adverse reactions (>5%) reported in patients receiving EYLEA were
`conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and
`increased intraocular pressure
`
`Exhibit 2137
`
`Page 18 of 30
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8S weeks.
`
`EYLEA Is indicated for the treatmentof
`patients with Macular Edemafollowing
`Central Retinal Vein Occlusion (CRVOQ).
`The recommended dose for EYLEA is
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`
`IMPORTANT SAFETY INFORMATION
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
`
`
`EYLEA
`(aflibercept) ae
`
`
`Exhibit 2137
`Page 18 of 30
`
`

`

`FOR THE TREATMENT OF WET AMD
`
`ARCOReC
`
`EYLEA 2 mg every 2 months (following 3 initial monthly doses) demonstrated
`non-inferior and clinically equivalent efficacy to monthly ranibizumab in the
`proportion of patients who maintained vision at week 52
`
`Absolute Difference* in Proportion of Patients Maintaining Vision (<15 Letters Lost) Based on BCVA
`
`as Measured by ETDRS with EYLEA Relative to Monthly Ranibizumab
`
`=hee
`
`ACM SmmemTLEMVCUTM ty=f
`Enno
`
`2 mg every 2 months’
`
`Non-inferiority region
`
`VIEW 1
`EYLEA
`2 mg every 2 months’
`
`VIEW 2
`EYLEA
`
`10%
`5%
`0
`5%
`-10%
`eel
`
`*EYLEA group minus ranibizumab group
`"Following 3 initial monthly doses
`
`= The specified requirement for non-inferiority was that the upper limit of the 95.1% confidence
`interval (Cl) of the difference between EYLEA and ranibizumab be above -10%°
`= Actual upperlimits in the per protocol set for all EYLEA doses compared to ranibizumab
`0.5 mg monthly were above -10% (non-inferiority) and within +5% (clinically equivalent) for
`the primary endpoint?
`Important Safety Information from the EYLEA Prescribing Information
`= EYLEA® (aflibercept) Injection is contraindicated in patients with ocular or periocular infections,
`active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the
`excipients in EYLEA
`
`Exhibit 2137
`
`Page 19 of 30
`
`al ©)
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8S weeks.
`
`EYLEAis indicated for the treatment of
`patients with Macular Edemafollowing
`Central Retinal Vein Occlusion (CRVO).
`The recommended dose for EYLEA Is
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`
`IMPORTANT SAFETY INFORMATION
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
`
`
`EYLEA
`(aflibercept)oa
`
`
`Exhibit 2137
`Page 19 of 30
`
`

`

`al 2
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for thefirst
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8 weeks.
`
`EYLEA is indicated for the treatment of
`patients with Macular Edemafollowing
`Central Retinal Vein Occlusion (CRVOQ).
`The recommended dose for EYLEA is
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`
`IMPORTANT SAFETY INFORMATION
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
`AS eSemvt
`
`AEGrem Cee sal VEGF Inhibitor Approvedfor
`Initial Monthly Doses"
`
`AU
`
`EYLEA 2 mg every 2 months (following 3 initial monthly doses) and monthly
`| ranibizumab achieved similar improvements in and maintenanceof visual acuity°
`
`DESIGN
`[~
`Mean Changein Best-Corrected Visual Acuity As Measured by ETDRS Over 52 WeeksvsBaseline
`VIEW 1
`
`See)
`
`a
`
`» "
`
`w”
`ce
`
`5
`
`
`
`se 8 g & @
`
`EYLEA 2 mg every
`ranibizumab
`—@ 0.5 mg monthly (n=304) ~~ 2 months* (n-301)
`
`9
`
`4
`
`64 2.22 es SS
`
`6S
`
`oO
`
`UmektlC CO
`
`'
`
`10
`
`5
`
`0
`
`0
`
`VIEW 2
`
`
`
`ranibizumab
`0.5 mg monthly (n=291)
`
`EYLEA 2 mg every
`2 months* (n=306)
`
`4
`
`8
`
`12
`
`16 2 24
`
`£=2
`
`32
`
`3%
`
`40 4 +;|(48
`
`52 Wks
`
`*Following 3 initial
`monthly doses
`
`5
`
`>w
`
`n<—
`
`= The mean change in BCVA versus baseline for patients dosed with EYLEA 2 mg onceevery 4
`weeks (month) was 10.9 and 7.6 in VIEW 1 and VIEW 2, respectively
`Important Safety Information from the EYLEA Prescribing Information
`= Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis
`and retinal detachments
`= Acute increases in intraocular pressure have been seen within 60 minutesofintravitreal
`injection, including with EYLEA. Sustained increases in intraocular pressure have also been
`reported after repeated intravitreal dosing with VEGF inhibitors
`
`Exhibit 2137
`
`Page 20 of 30
`
` CYEYLEA
`(aflibercept) Injection
`For Intravitreal
`
`
`Exhibit 2137
`Page 20 of 30
`
`

`

`AU
`
`EYLEA® (aflibercept) Injection: The sal VEGF Inhibitor Approvedfor
`
`
`
`EYLEA 2 mg every 2 months (following 3 initial monthly doses) and monthly
`ranibizumab achieved similar proportions of patients who gained at least 15
`letters of vision at 52 weeks?
`
`ACM SmmemTLEMVCUTM ty=f
`Hekeoe
`
`Proportion of Patients Gaining 15 Letters of Best-Corrected Visual Acuity as Measured by ETDRS at 52 Weeksvs Baseline
`
`DESIGN
`
`yeti ei
`
`
`
`VIEW 1
`
`
`
`VIEW 2
`
`
`
`EYLEA
`2 mg every 2 months*
`
`ranibizumab
`0.5 mg every month
`
`EYLEA
`2 mg every 2 months*
`
`ranibizumab
`0.5 mg every month
`
`
`
`Last Observation Carried Forward (LOCF): full analysis set
`*Following 3 initial monthly doses
`
`= Among patients dosed with EYLEA 2 mg onceevery 4 weeks (monthly), 38% and 29% gained
`>15 letters versus baseline in VIEW 1 and VIEW 2, respectively
`= Anatomic measures of disease activity improved similarly in all treatment groups from baseline
`to week 52. Anatomic data were not used to influence treatment decisions
`
`Warnings and Precautions from the EYLEA Prescribing Information
`= There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal
`VEGF inhibitors, including EYLEA, defined as nonfatal stroke, nonfatal myocardial infarction, or
`vascular death (including deaths of unknown cause). The incidence of ATEs in the VIEW 1 and
`VIEW 2 wet AMD studies in patients treated with EYLEA was 1.8% during the first year. The
`incidence of ATEs in the COPERNICUS and GALILEO CRVO studies was 0% in patients treated
`with EYLEA compared with 1.4% in patients receiving sham control during the first six months
`
`Exhibit 2137
`
`Page 21 of 30
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8S weeks.
`
`EYLEA Is indicated for the treatmentof
`patients with Macular Edemafollowing
`Central Retinal Vein Occlusion (CRVOQ).
`The recommended dose for EYLEA is
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`
`IMPORTANT SAFETY INFORMATION
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
`
`
`EYLEA
`(aflibercept) Injection
`
`For Intravitreal |
`
`
`Time BetweenTi
`
`
`Exhibit 2137
`Page 21 of 30
`
`

`

` eS
`
`ARCOReC
`Initial Monthly Doses'
`Every 2-Months Dosing Following
`
`| Most CommonAdverse Reactions (21%) in Phase 3 Studies*
`
`
`
`
`
`EY LEA (N=1824)
`
`ranibizumab (N=595)
`
`25%
`
`28%
`
`9%
`7%
`
`6%
`
`6%
`
`5%
`4%
`
`4%
`
`3%
`
`3%
`3%
`
`3%
`
`2%
`
`2%
`
`2%
`
`1%
`1%
`
`1%
`
`9%
`7%
`
`6%
`
`7%
`
`7%
`8%
`
`5%
`
`3%
`
`3%
`4%
`
`1%
`
`2%
`
`3%
`
`1%
`
`2%
`2%
`
`1%
`
`Hl
`
`EEREEEe
`
`Adverse reactions
`
`Conjunctival hemorrhage
`
`Eye pain
`Cataract
`
`Vitreous detachment
`
`Vitreous floaters
`
`Intraocular pressure increased
`Conjunctival hyperemia
`
`Corneal erosion
`
`Detachmentof the retinal pigment epithelium
`
`Injection site pain
`Foreign body sensation in eyes
`
`Lacrimation increased
`
`Vision blurred
`
`Intraocular inflammation
`
`Retinal pigment epithelium tear
`
`Injection site hemorrhage
`Eyelid edema
`
`Corneal edema
`
`= Less common serious adverse reactions reported in less than 1% of the patients treated with
`EYLEA wereretinal detachment, retinal tear, and endophthalmitis. Hypersensitivity has also
`been reported in less than 1% of patients treated with EYLEA
`
`Exhibit 2137
`
`Page 22 of 30
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8S weeks.
`
`EYLEAIs indicated for the treatment of
`patients with Macular Edemafollowing
`Central Retinal Vein Occlusion (CRVOQ).
`The recommended dose for EYLEAis
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`
`IMPORTANT SAFETY INFORMATION
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
`
`
`EYLEA
`(aflibercept)ae
`
`
`Exhibit 2137
`Page 22 of 30
`
`

`

`hEnHhRREAE
`
`IMPORTANT PRESCRIBING INFORMATION FOR EYLEA® (aflibercept) INJECTION
`= EYLEA® (aflibercept) Injection is indicated for the treatment of patients with neovascular (Wet) Age-related Macular
`Degeneration (AMD). The recommended dose for EYLEA is 2 mg administered by intravitreal injection every 4 weeks
`(monthly) for the first 12 weeks (3 months), followed by 2 mg once every 8 weeks (2 months). Although EYLEA may be
`dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated when EYLEA was
`dosed every 4 weeks compared to every 8 weeks
`
`= EYLEAIs indicated for the treatment of patients with Macular Edema following Central Retinal Vein Occlusion (CRVQ).
`The recommended dose for EYLEA is 2 mg administered by intravitreal injection every 4 weeks (monthly)
`
`IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION
`= EYLEA® (aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular
`inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA
`
`= Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal
`detachments. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be
`instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be
`managed appropriately. Intraocular inflammation has been reported with the use of EYLEA
`
`= Acute Increases in intraocular pressure have been seen within 60 minutesof intravitreal injection, including with
`EYLEA. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with
`VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed
`appropriately
`
`= There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors,
`including EYLEA, defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of
`unknown cause). The incidence of ATEs in the VIEW 1 and VIEW 2 wet AMD studies in patients treated with EYLEA
`was 1.8% during the first year. The incidence of ATEs in the COPERNICUS and GALILEO CRVO studies was 0% In
`patients treated with EYLEA compared with 1.4% in patients receiving sham control during the first six months
`
`= The most common adverse reactions (>5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye
`pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure
`
`=™ Serious adverse reactions related to the injection procedure have occurred in <O.1% of intravitreal injections with
`EYLEA including endophthalmitis, traumatic cataract, increased intraocular pressure, and vitreous detachment
`
`= Please see the full Prescribing Information for EYLEA
`
`Exhibit 2137
`
`Page 23 of 30
`
`
`
`Exhibit 2137
`Page 23 of 30
`
`

`

`Aa SOU Se STremTameCEU)mtieee
`
`EYLEA® (aflibercept) Injection: The salCeme
`
`AU
`
`General Dosing Information
`= EYLEA (aflibercept) Injection is indicated for the treatment of patients with neovascular (wet)
`Age-related Macular Degeneration (AMD)
`= EYLEAis contraindicated in patients with ocular or periocular infections, active intraocular
`inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA
`
`Zz
`
`
`= EYLEA IS FOR OPHTHALMIC INTRAVITREAL INJECTION ONLY
`| = The recommended dose for EYLEA is 2 mg administered by intravitreal injection every 4 weeks
`(monthly) for the first 12 weeks (3 months), followed by 2 mg once every 8 weeks (2 months)
`n = Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional
`efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every
`8 weeks
`= No special dosage modification is required for any of the populations that have been studied
`(eg, gender, elderly, renally impaired)
`
`
`NDC 61755-005-02
`
`— "Os KS. Aes PWO.40U™.
`
`
`
`| ae wr ©
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8S weeks.
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`EYLEA Is indicated for the treatmentof
`patients with Macular Edemafollowing
`Central Retinal Vein Occlusion (CRVOQ).
`The recommended dose for EYLEA is
`
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`. In tion SS4
`
`
`For Intravitreal injection
`\EYLEA|
`IMPORTANT SAFETY INFORMATION
`2 mg /0.05 mL
`ro
`Single-useVial a
`
`
`
`Exhibit 2137
`
`Page 24 of 30
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
` CYEYLEA
`Time Between
`
`(aflibercept) Injection
`For Intravitreal
`
`Exhibit 2137
`Page 24 of 30
`
`

`

`Every 2-Months Dosing Following3Initial Monthly Doses'2
`
`
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`Ueee Y
`
`EYLEA® ae TCSRATmeteete my
`
`»)) How Supplied
`= One single-use glass vial to deliver 0.05 mL of 40 mg/mL EYLEA
`ai = One 19-gauge x 14-inch, 5-micron, filter needle for withdrawal of the vial contents
`# One 30-gauge x 42-inch injection needle for intravitreal injection
`Bj = Qne 1-mL syringe for administration
`
`
`
`Important Administration Considerations
`= Immediately following the intravitreal injection, patients should be monitored for elevation in
`intraocular pressure. Appropriate monitoring may consist of a check for perfusion of the optic
`nerve head or tonometry. If required, a sterile paracentesis needle should be available
`= Following intravitreal injection, patients should be instructed to report any symptoms suggestive
`of endophthalmitis or retinal detachment (eg, eye pain, redness of the eye, photophobia,
`blurring of vision) without delay
`
`Exhibit 2137
`
`Page 25 of 30
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA Is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`& weeks.
`
`EYLEA is indicated for the treatment of
`patients with Macular Edema following
`Central Retinal Vein Occlusion (CRVO).
`The recommended dose for EYLEA Is
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`
`IMPORTANT SAFETY INFORMATION
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
` ‘WEYLEA
`(aflibercept) Injection
`
`ForIntravitreal Inj ection
`
`Time Between Treatments?
`
`Exhibit 2137
`Page 25 of 30
`
`

`

`
`
`ans Sag WeyaT sal VEGF Inhibitor Approvedfor
`ACM SmmemTLEMVCUTM ty=f
`
`eS
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`ee
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA wasdosed
`Vascular disorders
`1%
`| %
`every 4 weeks compared to every
`
`_} |__Injury/poisoning/procedural complications 2% 1%
`
`8S weeks.
`EYLEA is indicated for the treatment of
`Musculoskeletal/connective tissue
`0.5%
`1%
`patients with Macular Edemafollowing
`| Gastrointestinal
`1.5%
`1%
`Central Retinal Vein Occlusion (CRVOQ).
`The recommended dose for EYLEA is
`Respiratory/thoracic/mediastinal
`1%
`1%
`2 mg administered by intravitreal
`| General/administration site
`1%
`1%
`injection every 4 weeks (monthly).
`Nervous system
`2%
`0.5%
`
`
`Serious Non-ocular (Systemic) Adverse Reactions Over First 52 Weeks That
`Occurred in at Least 1% of Patients in Either Group'*
` _
`ranibizumab (N=595)
`- Disorder
`EYLEA (N=1824)
`Any serious non-ocular adverse event
`14%
`14%
`Infections/infestations
`2%
`3.5%
`Cardiac
`nu
`3%
`3%
`[— Neoplasms
`2.5%
`2%
`
`
`_]
`
`_
`
`IMPORTANT SAFETY INFORMATION
`
`= There wasa similar overall incidence for EYLEA® (aflibercept) Injection 2 mg every 8 weeksor
`monthly and 0.5 ranibizumab monthly of systemic (nonocular) adverse events, serious systemic
`adverse events (including ATEs) and deaths
`= Among the EYLEAtreatment groups, there was no evidence of a dose responsefor
`adverse events
`Important Safety Information from the EYLEA Prescribing Information
`= The most common adverse reactions (>5%) reported In patients receiving EYLEA were
`conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and
`increased intraocular pressure
`= There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal
`VEGF inhibitors, including EYLEA, defined as nonfatal stroke, nonfatal myocardial infarction, or
`vascular death (including deaths of unknown cause). The incidence of ATEs in the VIEW 1 and
`VIEW 2 wet AMD studies in patients treated with EYLEA was 1.8% during the first year. The
`incidence of ATEs in the COPERNICUS and GALILEO CRVO studies was 0% in patients treated
`with EYLEA compared with 1.4% in patients receiving sham control during the first six months
`
`Exhibit 2137
`
`Page 26 of 30
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
`
`
`EYLEA
`(aflibercept) ae
`
`
`Exhibit 2137
`Page 26 of 30
`
`

`

`Aa SOU Se STremTameCEU)mtieee
`
`EYLEA® (aflibercept) Injection: The salCeme
`
`eS
`
`_} Pre-Specified Integrated Analysis'*
`
`
`
`Blood Pressure: Systolic
`
`> ranibizumab q4 (Nw595)
`—+— EYLEA 298° (Ne610)
`—@— EYLEA 244 (N=613)
`
`
`
`q 2
`= 1
`=
`
`S41
`©
`.?
`
`3
`
`o=
`
`a
`
`5 *
`°o”CUCCSC aa
`Week
`
`_|
`
`_!
`
`I
`[~
`
`
`
`Blood Pressure: Diastolic
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for thefirst
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8 weeks.
`
`EYLEA is indicated for the treatment of
`3 2
`> ranibizumab q4 (Ne595)
`patients with Macular Edemafollowing
`1
`—wa— EYLEA 248* (N=610)
`Central Retinal Vein Occlusion (CRVOQ).
`—
`~~@— EYLEA 294 (N=613)
`The recommended dose for EYLEA is
`£ 03 -l Pie ———— ————S —
`2 mg administered by intravitreal
`a 2 =ee— :
`
`
`injection every 4 weeks (monthly).
`5
`SS
`IMPORTANT SAFETY INFORMATION
`= 3
`Sa
`4s
`
`eo 5
`
`2
`4a
`Week
`
`£32
`
`6s
`
`0
`
`4
`
`4
`
`32s
`
`* Following 3 initial
`monthly doses
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`Changesin systolic and diastolic blood pressure were similar across all EYLEA® (aflibercept)
`Injection and ranibizumab 0.5 mg monthly study arms over 52 weeks'*
`= The incidence of blood pressure-related serious adverse events was 0.3% with ranibizumab 0.5
`mg every 4 weeks and 0.3% across all EYLEA study arms over 52 weeks®
`Important Safety Information from the EYLEA Prescribing Information
`= There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal
`VEGF inhibitors, including EYLEA, defined as nonfatal stroke, nonfatal myocardial infarction, or
`vascular death (including deaths of unknown cause). The incidence of ATEs in the VIEW 1 and
`VIEW 2 wet AMD studies in patients treated with EYLEA was 1.8% during the first year. The
`incidence of ATEs in the COPERNICUS and GALILEO CRVO studies was 0% in patients treated
`with EYLEA compared with 1.4% in patients receiving sham control during the first six months
`
`Exhibit 2137
`
`Page 27 of 30
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
` GNEYLEA
`Time Between
`
`(aflibercept) Injection
`For Intravitreal
`
`Exhibit 2137
`Page 27 of 30
`
`

`

`Aa SOU Se STremTameCEU)mtieee
`
`EYLEA® (aflibercept) Injection: The Only VEGF Inhibitor Approved for
`
`FOR THE TREATMENT OF WET AMD
`
`| Comprehensive Support for You and Your Patients
`EYLEA
`
`en"a\(U)
`
`
`EYLEA4U is a comprehensive support program designed to meet your patients’ information,
`access, and reimbursement needs
`
`Call 1-855-EYLEA-4U (1-855-395-3248)
`Monday-Friday 9AM-8PM Eastern Time
`
`www.EYLEA.com
`
`=] ©
`
`IMPORTANT PRESCRIBING
`INFORMATION
`
`EYLEA® (aflibercept) Injection is
`indicated for the treatment of patients
`with neovascular (Wet) Age-related
`Macular Degeneration (AMD). The
`recommended dose for EYLEA is 2 mg
`administered by intravitreal injection
`every 4 weeks (monthly) for the first
`12 weeks (3 months), followed by 2 mg
`once every 8 weeks (2 months).
`Although EYLEA may be dosed as
`frequently as 2 mg every 4 weeks
`(monthly), additional efficacy was not
`demonstrated when EYLEA was dosed
`every 4 weeks compared to every
`8S weeks.
`
`EYLEA® (aflibercept) Injection is
`contraindicated in patients with ocular
`
`For additional Important Safety
`Information and full Prescribing
`Information, tap buttons above.
`
` GYEYLEA
`(aflibercept) Injection
`For Intravitreal
`
`
`EYLEAis indicated for the treatment of
`patients with Macular Edemafollowing
`Central Retinal Vein Occlusion (CRVOQ).
`The recommended dose for EYLEAIs
`2 mg administered by intravitreal
`injection every 4 weeks (monthly).
`Product Ordering
`Reimbursement and
`Adverse Events,
`Patient or Caregiver
`Health Care
`
`
`Professional Medical Medical Information Patient Assistance|Assistance ThroughProduct Complaints,
`IMPORTANT SAFETY INFORMATION
`Information Inquiries
`Inquiries
`and Product Returns
`One of Our Distributors
`
`EYLEA, EYLEA4U, and Time Between Treatments are registered trademarks of Regeneron Pharmaceuticals, Inc.
`
`Exhibit 2137
`
`Page 28 of 30
`
`Exhibit 2137
`Page 28 of 30
`
`

`

`
`
`For the treatment of wet AMD*
`
`Q\EYLEA
`
`(aflibercept) Injection
`For Intravitreal Injection
`Time Between Treatments®
`
`‘ii ie
`
`
`
`panda)
`
`,
`
`*Neovascular (wet) Age-related Macular Degeneration (AMD)
`TRecommended dose: 2 mg every 4 weeksforfirst 12 weeks, followed by 2 mg every 8 weeks
`EYLEA Is contraindicated in patients with ocular or periocular infections, active intraocular
`inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA.
`
`Exhibit 2137
`Page 29 of 30
`
`

`

`Cm Aa SUM TmaM LeeBUCAthyte
`
`ARTCCyeete
`
`AU
`
`2.
`
`10.
`
`[~ References
`1. Lucentis® (ranibizumab injection) Prescribing Information, Genentech, Inc.
`Revised Aug 2012.
`Macugen® (pegaptanib sodium injection) Prescribing Information, Eyetech Inc. Revised
`Aug 2008.
`. Data on file. Regeneron Pharmaceuticals, Inc. FDA Briefing Document. June 17, 2011.
`. Bressler SB. Introduction: understanding the role of angiogenesis and antiangiogenic
`agents In age-related macular degeneration. Ophthalmology. 2009;116(suppl 10):S1-S/7.
`. Papadopolos N, Martin J, Ruan Q, et al. Binding and neutralization of vascular endothelial
`growth factor and related ligands by VEGF Trap, ranibizumab and bevacizumab.
`Angiogenesis. 2012;15(2):171-85.
`. Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent
`antitumor effects. Proc Natl Acad Sci USA. 2002;99:11398.
`. Data on file. Regeneron Pharmaceuticals, Inc. BLA Sec. 2.3.8, Drug Substance.
`. Holz FG, Amoaku W, Donate J, et al. Safety and efficacy of a flexible dosing regimen of
`ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study.
`Ophthalmology. 2011;118:663-671.
`. Boyer DS, Helier JS, Brown DM, et al. A Phase IIIb study to evaluate the safety of
`ranibizumab in subjects with neovascular age-related macular degeneration.
`Ophthalmology. 2009;116:1731-1739.
`Rosenfeld PJ, Brown DM, Helier JS, e