CELLTRION- EXHIBIT 1055
`
`A Phase 2, Randomized, Controlled
`Dose- and Interval-Ranging Study
`of Intravitreal VEGF Trap-Eye
`in Patients With Neovascular,
`Age-Related Macular Degeneration
`
`Presented at 2008 Retina Society Meeting
`Scottsdale, Arizona
`September28, 2008
`
`CELLTRION - EXHIBIT 1055
`
`
`
`A Phase 2, Randomized, Controlled
`Dose- and Interval-Ranging Study
`of Intravitreal VEGF Trap-Eye
`in Patients With Neovascular,
`Age-Related Macular Degeneration
`
`Presented at 2008 Retina Society Meeting
`Scottsdale, Arizona
`September28, 2008
`
`CELLTRION - EXHIBIT 1055
`
`
`
`Anti-VEGF therapy has dramatically changed the treatment
`paradigm for wet AMD
`
`Improvementin visual acuity is now an achievable goal of treatment
`
`Durability of response with PRN (as-needed) dosing out to 1 year
`
`A potential limitation of anti-VEGF therapy is the unpredictable
`durability of vision gain initially achieved with monthly dosing
`whenthe treatment interval is prolonged
`
`VEGF Trap-Eye is a novel anti-VEGF therapy with high binding
`affinity for VEGF-A and placental growth factor (PIGF)
`
`CLEAR-IT 2 was designed to assess:
`
`Response at 12 weeks to a range of doses administered monthly and
`quarterly
`
`
`
`RTONEAPCele
`
`Randomized, multicenter,
`double-maskedtrial
`N=159
`
`y
`
`Patients were re-dosed at week 12; PRN dosing started at week 16
`
`Secondary endpoint:
`:
`:
`:
`Primary endpoint:
`
`Changein Central Retinal/Lesion !xed dosing to week 12 (primary—Bact-Corrected ETDRS
`Thickness (CRILT)
`endpoint)
`Visual Acuity (BCVA)
`$
`PRN dosing to 1 year
`
`Whacs
`
`EX
`
`Fo Tee CT»
`
`xy
`
`xy
`
`
`
`Weeks
`
`0
`
`P|
`
`0.5 mg q4 wks = 2
`
`0.5 mg q12 wks -
`
`2 mg g4 wks a =
`
`PCA=Car PERVscl rets
`
`~ 0.5 mg q4 wks VEGFTrap
`WM 0.5 mg g12 wks VEGF Trap
`
`2 mg q12 wks
`
`4 mg q12 wks a
`
`2 mg q12 wks VEGF Trap
`
`Primary and Secondary
`titel foalt
`
`
`
`te
`
`)
`
`r
`
`8
`
`0.5 mg q4 wks = = a
`
`4 mandatory doses
`
`PCA=Car PERVscl rets
`
`2 mg 94 wks - - -
`
`0.5 mg q12 wks -
`
`2 mg q12 wks
`
`4 mg q12 wks =
`
`4 mandatory doses
`
`~ 0.5 mg q4 wks VEGFTrap
`WM 0.5 mg g12 wks VEGF Trap
`
`2 mg q12 wks VEGF Trap
`
`ee eeeat
`titel foalt
`
`
`
`Weeks
`
`0
`
`P|
`
`0.5 mg q4 wks = 2
`
`0.5 mg q12 wks -
`
`2 mg g4 wks i =
`
`PCA=Car PERVscl rets
`
`el
`WM 0.5 mg g12 wks VEGF Trap
`
`2 mg q12 wks
`
`4 mg q12 wks =
`
`relat
`
`2 mg q12 wks VEGF Trap
`
`Primary and Secondary
`titel foalt
`
`
`
`(n=157*)Trenst:ee
`
`*N=159 randomized; n=15/7 treated
`
`Lesion Size (mean+SD)in disc areas
`
`Lesion Type: number(%)
`
`Classic
`
`Predominantly Classic
`
`Minimally Classic
`
`Occult Lesions
`
`Disease Status
`
`Central Retinal/Lesion Thickness
`
`Foveal Thickness
`
`ETDRS BCVA(letters)
`
`186-1316 um
`
`116-1081 um
`
`27-83
`
`
`
`Patient Disposition
`
`aTT
`[SSORCC
`
`TX
`
`CCAA
`Se
`Oc
`YT
`Padre||||+||106%)
`roTT
`OcOY
`creYT
`AYe
`
`
`
`At 12 weeks VEGF Trap-Eye:
`
`Significantly improved mean visual acuity
`
`Significantly reduced central retinal thickness
`
`adverse events
`
`Maintained effect on visual acuity with a single dose to 8
`Voto) es
`
`Groups dosed at Baseline and at Week 12 showed
`improved visual acuity and retinal thickness
`
`Effect was not as robust as with monthly dosing
`
`Was generally well tolerated with no drug-related serious
`
`
`
`
`
`
`
`Increase in central retinal thickness of>100um as
`measured by OCT,or:
`A loss of>5 ETDRSletters in conjunction with
`recurrentfluid as indicated by OCT,or:
`
`New macular hemorrhage
`
`New or persistent leak on FA,or;
`
`Persistent fluid as indicated by OCT, or:
`
`New onset classic neovascularization, or;
`
`
`
`Re-Treatment Outcome
`
`Number of injections over PRN phase*
`
`All patients, n=152
`
`ee
`
`* After the week 12 injection through week 52
`
`
`
`Re-Treatment Outcome
`
`VEGF Trap-Eye
`
`Viean number of|Median number
`Mean number of
`days to first
`of daystofirst
`injections over
`injection over
`injection over
`PRN phase
`PRN phase
`PRN phase
`(week 12 — 52)
`(week 12 — 52)
`(week 12 — 52)
`
`
`
`
`
`Percentof patients receiving an injection analyzed by numberof injections, n=152
`
`Number of Injections
`
`”~”ae
`‘=
`
`®_C
`
`y)
`OW
`
`S
`
`
`
`
`
`Timeto 1st re-injection
`— 0.5q12
`coleman Foye 3
`== 2.0q12
`2.0q4
`4.0q12
`x Censored
`
`Median # of days to 1*tre-injection
`
`V4, in 2.0q4 group = 150
`
`”)a
`
`= aa
`
`) ©
`
`OW
`_—
`Cc
`Lo)
`Ss
`0)
`OW
`
`
`
`Last Observation Carried Forward (LOCF) analysis; paired t-test; 0.5q4 : n=32; 2q4: n=31
`
`16 20 24 28 32 36 40 44 48 52
`
`x >
`
`)
`bh
`—)
`Oo
`<x
`
`i —
`
`)a> — ®(
`
`o))
`
`8
`
`12
`
`c ©
`
`is
`O
`
`—®-0.5 mg q4
`
`a eA LL? me(|
`
`oanlih
`+P = 0.085
`
`Fixed-dosing
`
`PRN-dosing Phase
`
`ry
`
`= ®—
`
`_
`—_
`
`
`
`LOCF analysis; paired t-test; 0.5q4 and 0.5912: n=32; 2q4, 2q12, and 4q12: n=31
`
`*P < 0.0001
`**P- = 0.0154
`**P = 0.0412
`TP = 0.085
`TTP = 0.344
`
`x >
`
`)
`bh
`—)
`Oo
`<x
`
`i —
`
`)a> — ®(
`
`o))
`
`0
`
`4
`
`8
`
`12 16 20 24 28 32 36 40 44 48 52
`
`c ©
`
`is
`O
`
`—©@-0.5q4 —-2q4
`
`-*#-0.5q12
`
`2q12
`
` ~<4q12—
`
`Fixed-dosing
`
`PRN-dosing Phase
`
`ry
`
`= ®—
`
`_
`—_
`
`
`
`Posterior Pole Scans; LOCF analysis; 0.5q4 and 0.5q12: n=32; 2q4, 2q12, and 4q12: n=31
`
`ee
`th
`* Se ee enog-125* 0.594
`
`Zu\-e
`eK
`maeEP
`
`PRN-dosing Phase
`Week
`24 28 32
`
`40
`
`36
`
`16
`
`20
`
`||
`
`12
`
`Fixed-dosing
`
`4
`
`8
`
`0
`
`es
`
`aC
`
`c
`je)Som
`
`2= -
`
`44 48
`
`52
`
`—
`
`*P < 0.0001
`eas
`
`tp=
`
`_—
`
`!—
`
`||1 |
`
`\4
`
`aO = c
`
`o)
`fey)
`Cc
`©
`nos
`O
`
`ers elLP
`
`||
`
`
`
`Visual Acuity at Week 52
`
`LOCF analysis; 0.594 and 0.5q12: n=32; 2q4, 2q12, and 4q12: n=31
`
`<15 letters lost
`
`2 0 letter gain
`
`2 15 letter gain
`
`0.5q4
`
`=2q4
`
`80.5q12
`
`=2q12
`
`= 4q12
`
`29%
`
`29%
`
`22%
`
`oSll
`q)
`ed
`
`= ©
`
`ar]
`oJ
`al
`
`
`
`Proportion of Patients
`With >20/40 Vision
`
`LOCF analysis; 0.594 and 0.5q12: n=32; 2q4, 2q12, and 4q12: n=31; BL=baseline;
`
`BL Wk52
`
`BL Wk52
`
`BL Wk52
`
`BL Wk52
`
`BL Wk52
`
`2q4 Le
`
`Ps
`
`rTP
`
`Wey.
`
`Dose Groups
`
`>20/40Vision—
`
`bam
`
`
`
`o
`
`oS
`~”—_
`
`aad
`4°]
`oa
`
`
`
`a}
`
`10:20 FA
`
`
`
`Total Lesion Size
`
`Measurementof entire lesion including the classic and occult neo-
`vascular component as well as contiguous areas of blood and/or blocked
`fluorescence and/or serous pigment epithelial detachment (PED)
`Total Active CNV Size
`
`Area of visible CNV (classic and/or occult) which demonstrates
`angiographic evidence of late leakage or pooling of dye
`Classic CNV
`
`vascular PED to account for leakage)
`
`Area of bright, well-demarcated hyper-fluorescence in early phase, with
`progressive dye leakage into overlying sub-sensory retinal spacein late
`phase of angiogram (not a measurementof area of leakage, but rather
`extent of the classic neo-vascular complex)
`Occult CNV
`
`Angiogram showsstaining or leakage from fibro-vascular PED or hyper-
`fluorescent leakage at level of RPE that represents late leakage of
`undetermined source (leakage in late phase without classic CNV or fibro-
`
`
`
`Mandatory FA only; LOCF analysis; 0.5q4 and 0.5q12: n=32; 2q4, 2q12, and 4q12: n=31
`
`0.85t 0.5q12
`FE |
`
`36
`
`48
`
`Week
`
`“© 0.594
`Lesion Size at Baseline (mm2)
`4.9
`
`-Me2q4
`ae)
`
`-*0.5q12
`5S
`
`rh Pin
`7.6
`
`aot CLP
`6.5
`
`Fixed-dosing
`
`PRN-dosing Phase
`
`-1.00t 4q12
`
`Lee
`
`2=
`
`cS
`
`ra
`
`=@m
`
`7
`Cs
`faa)
`
`=©
`
`re
`
`ra
`
`D = Gr
`
`fO
`
`
`
`TP=ns
`
`*P < 0.001
`
`—@&4q12
`*P<0.05
`
`
`
`—©-0.5q4 -<2q49-*0.5q12 rx 2
`
`CNV Size at baseline (mm2)
`
`4.6
`
`6.9
`
`a
`
`6.8
`
`5.6
`
`Mandatory FA only; LOCF analysis; 0.5q4 and 0.5q12: n=32; 2q4, 2q12, and 4q12: n=31
`
`Fixed-dosing
`
`PRN-dosing Phase
`
`0
`
`4
`
`12
`
`24
`
`36
`
`nT
`
`Week
`
`-1.35t 05q12
`-1.42** 0.5q4
`
`-2.59** 4q12
`
`xCele
`
`a=£ ®=7
`
`)
`m7
`OY
`fea
`
`=°—
`
`_
`re
`
`®D= oxO
`
`
`
`Mandatory FA only; LOCF analysis; 0.5q4 and 0.5q12: n=32; 2q4, 2q12, and 4q12: n=31
`
`a =°:=
`
`®D c ocO
`
`i:)All P values < 0.013
`
`-2.0
`PeeTONSEE “©-0.5q4
`Ela stele at
`1.2
`
`fe 2q4
`1.2
`
`=*t0.5q12
`1.8
`
`2q12
`1.8
`
` -®4q12
`i)
`
`|
`
`Fixed-dosing
`r
`
`PRN-dosing Phase
`|
`ery 36
`
`rn
`
`0)
`
`Oy
`
`Oe.
`
`-0.6
`
`Oe
`
`A!
`
`-1.2
`
`-1.4
`
`-1.6
`
`cm
`
`=£ ®A
`
`=7m
`
`2
`os
`
`re
`
`
`
`Subject had a history of prior stroke
`
`Ocular Serious Adverse Events in the study eye:
`1 case of culture-negative endophthalmitis / uveitis
`(deemed not related to study drug)
`Systemic Serious Adverse Events:
`None deemedto be drug-related
`2 deaths
`
`Pulmonary hypertension (pre-existing condition)
`Pancreatic carcinoma
`
`Arterial Thromboembolic Events (ATE’s): 1 case of
`hemorrhagic stroke
`
`
`
`Adverse Events
`(Study eye, all groups combined > 5%)
`
`Adverse Event
`
`Number
`
`Percent
`
`Refraction Disorder
`
`18.5
`
`15.9
`
`14.6
`
`Vitreous Detachment
`
`Vitreous Floaters
`
`l|OP=intraocular pressure
`
`(%)
`(Ee Eva)
`Er~SOS~S~S*D2
`
`Conjunctival Hemorrhage
`Siew
`Pee a
`Increased IOP (transient post-injection)
`IeOCOCOtC~S* 88
`rr 8
`Retinal Hemorrhage
`SI 84
`Visual Acuity Reduced (patient reported
`Tr rs
`—_ 8
`Mee
`er [8
`
`[onanPE
`Detachmentof Retinal Pigment Epithelium
`Ee
`Ee
`L=—_ij...
`Blepharitis
`=~=~S*
`ESEac
`
`Stare ke (gare
`
`Visual Disturbance
`
`Cataract nuclear
`
`Subretinal Fibrosis
`
`
`
`Patients received, on average, only two additional injections
`over 40-week PRN-dosing phase(after a 12-week fixed
`dosing period)
`19% received no additional injections after Week 12
`110 days median time to first re-injection
`
`Most common AE’s typical of intravitreal injection
`
`VEGF Trap-Eye achievedclinically meaningful and durable
`vision improvement over 1 year
`Up to +9.0 mean letters gained at week 52
`Up to -161 microns reduction in central retinal lesion thickness at
`week 52 as measured by OCT
`
`Generally well tolerated with no drug-related serious
`adverse events
`
`
`
`29
`
`auecone tL 1 |) |
`ro |)
`Ranibizumab 7 a a a a , , 7
`
`
`
`Primary and Secondary
`aealmt
`
`+ Capped PRN: minimum injection frequency is q12 weeks
`
`0.5 mg VEGF Trap 7 2 mg g4 wksVEGFTrap i 2 mg q8wksVEGFTrap Z 0.5 mg Ranibizumab
`
`a 0
`
`4
`
`8
`
`12 16 20 24 28 32
`
`0.5 mg g4 wks
`
`0.5 mg g4 wks
`
`*Continued dosing at their respective intervals
`uNae loading dose period of 3-months
`
`
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