US Ophthalmology
`
`l.!, NOVARTI S
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718202
`
`Novartis Exhibit 2172.001
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`YY,l_YY-'-Y-'-YY
`Y,l_YY,l_YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY-'-Y-'-YY
`Y ,l_ YY ,l_ YYYY )-
`
`Y,l_YY-'-YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y-'-YY-'-YYYY )(cid:173)
`YY ,l_ YY ,l_ Y ,l_ YY
`Y,l_YY,l_YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y ,l_ YY-'-YYYY )(cid:173)
`YY ,l_ YY ,l_ Y ,l_ YY
`Y-'-YY ,l_ YYYY )(cid:173)
`yy ;._ yy ;._ y ;._ yy
`YJ..YYJ..YYYY)(cid:173)
`yy;._yy;._y;._yy
`Y J.. YY ,l_ YYYY )(cid:173)
`yy )._ yy )._ y )._ yy
`y )._ yy )._ yyyy )_
`yy )._ yy )._ y )._ yy
`y )._ yy )._ yyyy )_
`YYJ..YY,l_YJ..YY
`y;._yy;._yyyy,1-
`yy).. YY).. Y J.. YY
`y;._yy;._yyyy,1-
`yy )._ yy )._ y )._ yy
`y )._ yy )._ yyyy )_
`YYJ..YYJ..YJ..YY
`Y J.. YY ,l_ YYYY )(cid:173)
`yy )._ yy )._ y )._ yy
`Y J.. YY-'-YYYY )(cid:173)
`YY-'-YY).. Y J.. YY
`YJ..YYJ..YYYY)(cid:173)
`yy;._yy;._y;._yy
`
`Oliver, Catherine , Amit,
`Source Text Box to eve
`
`RTH Situation Assessment
`
`Christine Wong
`Amit Kumar Goyal
`Oliver Bock
`Catherine Becker
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718203
`
`Novartis Exhibit 2172.002
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Executive Summary
`
`US Ophthalmology
`
`l.!, NOVARTI S
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718204
`
`Novartis Exhibit 2172.003
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Wet AMD is 57% of total aVEGF sales ($6 B),
`but is growing more slowly than total aVEGF
`market growth rate
`
`Sales Split by Indication for Branded
`aVEGF Sales (2018)
`
`Total wetAMD aVEGF Sales($ M)
`
`• Eylea •
`
`Lucentis
`
`____ ...,@-_______ ,.
`
`2,965
`
`3,033
`
`3,032
`
`3,299
`
`13% annual growth rate
`from 2014-2018
`
`2014
`
`2015
`
`2016
`
`2017
`
`2018
`
`%of
`aVEGF 76%
`sales:
`
`70%
`
`64%
`
`59%
`
`57%
`
`Source EvaluatePharma
`
`US Ophthalmology
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718205
`
`Novartis Exhibit 2172.004
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Avastin leads the market: 46% total treatment share
`A vastin maintains dominance in naive patient share, though
`Eylea continues to grow
`
`wAMD Treatment Share
`
`Eylea
`-
`- Avastin
`-
`Lucentis - Others
`
`---------------------....:::.46%
`
`38%
`
`70%
`60%
`50%
`40%
`30%
`20%
`10%
`0%
`
`100%
`90%
`80%
`70%
`60%
`50%
`
`Continuing Patient Share
`
`15%
`
`44%
`
`~ ---
`
`~
`
`----
`
`-=:-.._:::-
`
`;%
`
`·------.111- %
`
`Naive Patient Sha.,_re~ - - - -~
`Avastin leads naive
`00%
`patient share
`90%
`80%
`70%
`60%
`50%
`40%
`30%
`20%
`10%
`
`67%
`
`US Ophthalmology Time penod of data Jan' 10 to Jul'17
`Data Source IQVIA claims data
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718206
`
`Novartis Exhibit 2172.005
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`43 practices account for 30°/o of all
`branded aVEGF procedures
`
`Account Concentration Curve
`
`100%
`
`90%
`
`0
`
`"O
`
`80%
`"'
`~ 70%
`~ 60%
`ct
`50%
`u_
`(.')
`w 40%
`>
`"' 0 30%
`#-
`20%
`
`-
`
`-
`
`Branded aVEGFs
`
`AllaVEGFs
`
`-------- , -----.- -------------------------------------------------------------------------------------
`
`10%
`
`0%
`
`Number of Practices
`
`Time period of data Jan-Dec 2016
`Data Source IQVIA claims data + CMS Data CareSet Affiliations
`
`US Ophthalmology
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718207
`
`Novartis Exhibit 2172.006
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`HCPs treating nAMD are highly concentrated
`with 35% treating 80% of all patients
`
`100%
`
`HCP Concentration Curve
`
`80'¾
`
`Q)
`
`f
`~ 60%
`Q_
`0
`2
`1
`#-
`
`40%
`
`20%
`
`0%
`0%
`
`10%
`
`20%
`
`30%
`
`40%
`
`50%
`
`60%
`
`70%
`
`80%
`
`90%
`
`100%
`
`% HCPs
`322 Retinal Specialists (15%) drive 50% of nAMD treatments
`759 Retinal Specialists (35%) drive 80%
`
`Time period of data Aug'16 to Jul'17
`Data Source IQVIA claims data HCP (# AMD patients> 10) N = 2145
`
`US Ophthalmology
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718208
`
`Novartis Exhibit 2172.007
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Retina Landscape - Near Term Highlights
`
`o ... - .. ~,_.,..,,Q-. o._,,,..,..,., ◊­
`
`•-• • .. ..., ...... --•-•.,.. •~· •"""'·
`
`l.!, NOVARTI S
`
`Last Update: Feb19
`
`US Ophthalmology
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718209
`
`Novartis Exhibit 2172.008
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Retina Biosimilar Landscape
`(Advanced stage products only)
`
`Last Update: Jan19
`
`US Ophthalmology
`
`l.!, NOVARTI S
`
`Notes:
`
`*ONS501 O: The first clinical study for ONS-501 O is being conducted outside
`of the U.S. and is designed to serve as the first of two adequate and well
`controlled studies for wet AMO. The U.S. portion of the second study is
`scheduled to begin in early 2019 upon the submission of an IND application.
`Oncobiologics' wet AMO clinical program was reviewed at a successful end of
`Phase II meeting held with the U.S. FDA conducted earlier in 2018. If the
`program is successful , it will support the Company's plans to submit for
`regulatory approval in multiple markets in 2020. The Company is developing
`ONS-5010 as an innovative therapy and not using the biosimilar drug
`development pathway. Previously, ONS-5010 met the primary and secondary
`endpoints in a 3-arm single-dose PK Phase I clinical trial. All of the PK
`endpoints met the bio equivalency criteria of the geometric mean ratios within
`90% confidence interval of 80-125% when compared to both U.S. and EU
`sourced Avastin reference products (https://oncobiologics.com/programs/novel(cid:173)
`therapeutics/)
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718210
`
`Novartis Exhibit 2172.009
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Annually, 200 K new nAMD patients, at
`high diagnosed and treated rate: 86%
`
`Naive Patients on Treatment
`
`Continuing Patients on Treatment
`
`TOTAL Patients
`TOTAL Eyes·
`
`2019
`
`182K
`
`316K
`498K
`610K
`
`US Ophthalmology
`
`l.!, NOVARTI S
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718211
`
`Novartis Exhibit 2172.0010
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`. ~ . .
`
`t
`
`.
`
`I
`
`•
`
`..
`. . .
`
`Patient's first contact with
`the PCP, OD, or GO
`
`••
`• . .
`
`Lack of
`clarity
`
`8.
`
`•
`
`I
`
`Trea
`1s1mt1at
`
`•
`
`• •
`. .
`
`Treatment
`
`RS makes diagnosis and
`explains the condition/treatment
`
`The PCP, OD, or GO
`refers patientto the RS
`
`•
`
`a Undersranding A Fear
`
`u
`J l
`
`~ Boththe
`prognosis a~d
`t~eatm~ntp an
`( mtrav1treal
`injections) terrify
`the patient.
`
`Loss of ■
`Gaps
`independence
`Increase need for a
`caregiver
`
`Between
`reality and
`expectations.
`
`Inability to drive
`
`fu NOVARTIS
`
`What is
`happening?
`
`What is
`nAMD?
`
`What are its
`implications?
`
`US Ophthalmology
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718212
`
`Novartis Exhibit 2172.0011
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Majority of patients are diagnosed with nAMD in
`both eyes but are only treated early enough to
`save one eye
`
`Monocular, Binocular Diagnosed Patients
`
`Treatment Adherence (mean)
`
`100%
`
`"' Cl)
`>, w ... 0
`
`-;J.
`
`0%
`
`48%
`
`Monocular nAMD, Di agnosed
`and treated ea~y
`
`22%
`
`Binocular nAM D, Diagnosed
`and treated ea~y
`
`11 %
`
`-----------}
`
`Monocular nAMD, Diagnosed too
`late to treat/save vis ion
`Binocular nAMD, Diagnosed too
`late to treat/save vision
`Binocular , Only a ble to treat
`early enough to save vision in one eye
`
`I
`I
`I
`I
`
`US Opht halmology
`
`30% too late
`75% of
`patients wrrh
`binocular
`nAMD are
`diagnosed in
`both eyes on
`the same day
`Yet, <50%
`wrrh binocular
`wAMD are
`treated in both
`eyes
`
`•
`
`Adherent to treat ment D Not adherent
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718213
`
`Novartis Exhibit 2172.0012
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`US Ophthalmology
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)0071821 4
`
`Novartis Exhibit 2172.0013
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Each physician segment type impacts the in
`treatment prescription drivers and their proc
`preferences
`
`Font size too small. W
`the so-what of this pa
`Keep only the primary
`on the page
`
`SCICNCCSAM
`'ln-.16<1-'•W~
`
`More tenured intelectualy
`curiOus retila exi,erts who
`pride themselves on
`Jldividuaized patient treatment
`-they thrive on making
`treatment decisions based on
`a patient's pathology combll'led
`with thel"ex1ensive knowledge
`and experience
`
`Price is the least mportant
`treatment choice motrvator for
`this group, instead tis B
`pathology driven decision
`pnortizing patient outcomes,
`visual acuiy and branded
`optJons for safety
`
`-US Ophthalmology
`
`% of
`physicia ns in
`each segnent
`
`. ,_ . ..,.
`
`SINCLC BRAND BLAKC
`
`• They are less tenured non-~
`partnered retll'la experts who
`are focused on treatment '
`efficacyand efficiencyoftheir
`practice. The cost of stocking
`in.tectable drugs is a concern ,
`t>ecause ofthel' high volume
`• They are early adopters of new
`treatments. They are sightly
`less colaborat1Ve with their
`patients alld focus on treating
`the disease rather than the i
`patient. ,
`No productsareoffwrvt for
`many and they are motivated to
`try the newest even if outcomes '
`for a new treatment therapy
`aren't completely dear. 92% of
`this segment agreed that cost 1
`effectiveness is fartess :···_ · _,
`important than efficacy, which
`
`ranks high with thlS group -
`
`.,.,._.,.._ .. ,,,_ ....
`
`PRAGMATIC PAT
`
`Less tenured reMa experts
`who pride themselves on
`curilg patients defintively(cid:173)
`they aclively engage
`patients in the treatment
`decision favorilg unlicensed
`bevacizumab as a
`financially practical and
`efficacious first me therapy
`but they switch rapidly to
`Eylea if a patient responds
`poorly to early injections of
`un~cense-d bevacizumab
`Patient convenience is
`centralto influencing
`treatment choice
`Safetyandtolerability are
`strong treatment choice
`motivators forth is group,
`wanting to ultimately
`maximize comfortto
`patients in the treatment
`
`expenence -
`
`STAac.Hm SP[NCEA
`'7.dltbofl\'111111,-...,,,,..,..,,, •
`
`More tenured retl\a experts
`who Like to feel they are
`helping others, they are
`driven to cure patients and
`engage in the most pro bono
`work. Toey often operate in
`smaaer practices where cost
`effectiveness is as important
`as efficacy, making
`unlicensed bevacizumabthe
`preferred treatment therapy
`TIiey are slower to adopt
`new technology and are
`most skeptical of
`pharmaceutical companies
`Ease and amount of
`reUT1bursemenl are strong
`treatment choice motivators
`for this group making
`unlicensed bevacizumabthe
`
`clear fav orite -fu NOVARTIS
`
`$0\/Kle : !UH LllfnellfJ.p.ntrA ~ - lkKlnHy&cornp.iy
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718215
`
`Novartis Exhibit 2172.0014
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`"Extremely Important".
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718216
`
`Novartis Exhibit 2172.0015
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Eylea is considered to outperform others on majority of
`attributes, OOP costs and reimbursement confidence drive
`highest Avastin levels
`Comparative Product Performance- T2B (rated 81-100)- Total Level
`
`■11ihiiit■---
`
`- - - - - - - - - - - - - - -
`
`ltmpor- Attribute
`ance
`
`1111 rmproving visual acuity - mean change in BCVA
`1111 Helps achieve regression of neovascularization
`1111 ls a product I can trust
`1111 Longer duration of efficacy
`1111 Confidence in product quality
`1111 Flattens/thins central subfield thickness
`
`67% Positive experience with the product
`
`67% Reimbursement confidence
`
`64% Resolves IRF/SRF fastest
`
`64% Out of pocket cots patient
`
`63% Maximizes treat and extend dosing interval
`
`62%
`Injection frequency
`ti~~ t l -~WPW~ Anti-VEGF therapies for
`s~
`3~ M0v,w~~/tJ'vlOJ,1arW~sst~~ing to again show y
`2sW0~"1iUk,-<VQ1iteWr ay,t!Mate how well ( or how poor
`13% Patient/caregiver support services & education
`Using the scale below, p1Era1S~ate each An~ ~therapy for the treatment of
`us~~il~~ AMO (Wet AMO) anywhere from Does Not Pertd&n .VAffll[R>
`Performs Extremely Well for the statement shown. To do so, click on each
`treatment and drag it to the rating you would like to give for that Anti-VEGF
`therapy for the treatment of Neovascular AMO (Wet AMO).
`
`i&
`ai
`>
`0
`Cl
`C
`"ii
`Ill
`a,
`ti
`£
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718217
`
`Novartis Exhibit 2172.0016
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Physician-perceived strengths and weaknesses of
`current nAMD treatments are clear, across all
`segment types
`
`AVASTIN
`
`Low cost / well
`reimbursed
`
`[±l Similar efficacy to
`
`Lucentis
`Lower economic risk to
`practice
`
`G
`LUCENTIS
`
`RANIBIZUMAB INJECTION
`
`Longer market experience
`Pre-filled Syringe
`Preferred for patients with
`recent cardiovascular
`disease
`She~ life
`Gives rebates to big users
`
`ro•s
`1
`
`Off label use
`Preparation requires
`compounding pharmacy
`Dosing frequency
`Short she~ life
`
`Reimbursement for
`patients with suboptimal
`insurance
`Lower perceptions of
`efficacy vs Eylea
`Dosing frequency
`
`Barring financial /
`insurance concerns,
`physicians prefer Eylea
`Perceived longer duration
`of action
`Reducing side effects
`Dosing advantage
`She~ life
`
`Reimbursement for
`patients with suboptimal
`insurance
`
`US Ophthalmology
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718218
`
`Novartis Exhibit 2172.0017
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`In the past 12 months 7% patients had their
`treatment switched; During Eylea launch year
`the switch rate had increased to 17%
`
`PatientMixin nAMD
`
`Product Share of Switching nAMD Patients
`
`100%
`
`80%
`
`60%
`
`40%
`
`20%
`
`0%
`
`■ Off-label
`beva
`■ Lucentis
`
`■ Eylea
`
`■ Naive
`
`■ Switch ■ Continuing
`
`Time period of data Aug'16 toJu1'17
`Data Source IQVIA claims data
`
`US Ophthalmology
`
`Products Switched To (from
`Eylea , Lucentis, Off-label beva)
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718219
`
`Novartis Exhibit 2172.0018
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Is this slide % of
`AMIT:
`patients or% of eyes? itching happens early in treatment
`when MDs are assessing patients' response
`
`Switching - Eye Level
`(n=22k)
`
`29%
`
`13%
`
`11 %
`
`8%
`
`5%
`
`5%
`
`---- - ◄€- ----
`
`25%
`
`30%
`
`"'
`C:
`Q) 'i
`a.
`0
`#-
`
`20%
`
`10%
`
`0%
`
`-
`
`4
`1- - - - 2 - - - - 3 - -
`No of Treatments
`
`5
`
`6
`
`7+
`
`■ A-> L ■ A-> E ■ L-> E ■ L->A ■ E-> A ■ E -> L Total
`
`Time period of data Aug'16 to Ju1'17
`Data Source IQVIA claims data
`
`US Ophthalmology
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718220
`
`Novartis Exhibit 2172.0019
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Lack of efficacy is primary reason for switch, although cost
`plays a role when switching from Eylea and Lucentis
`
`Reasons for Treatm ent Switch
`% selected
`
`Lack of efficacy
`Cost
`Side effects
`Patient request
`
`z
`~ <(
`$
`<i w
`Lack of efficacy
`Cost
`..J >-w
`S1deeffects
`~ Patient request
`'-~ z
`Lack of efficacy
`Cost
`b
`Side effects
`Patient request
`J
`
`t:f~hthatmologyo1-e,•rior, ot ecst _c•hersegrr-er:•so• qC9ficor'1derce eve
`St:iel'•o·e:uect '-' vrQ1,,e5 v
`..,tll'dini.;
`
`l.!, NOVART IS
`
`Q9. Again, please think of your wet AMO patients that you have initiated on
`each of the following agents, and then switched to a different anti-VEGF agent.
`On average, what % patients are switched for each of the following reasons?
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718221
`
`Novartis Exhibit 2172.0020
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`May swap w/ patient adherence report slide
`Approx. 3 in 4 physicians acknow Highlight important stats
`be sufficient, and that the treatment is burdensome to patients
`
`Treatment Needs Addressed by CurrentAnti-VEGF-T2B
`
`Total
`
`Single Brand Blalee
`or Science Sam
`
`Pragmatic Pat
`
`Stretched Spencer
`
`C ,ascuta, AMD (Wet AMO) is a chronic, complex disease
`I ;;;,;~ by multiple pathogenic mechanisms beyond VEGF
`
`Treatment with intrtl'itreal injections of Anti-VEGF c.in be
`burdensome 10 Neovascular AMO ,:,Mel AMO) pa11en1s
`
`Despite optimal Anti.VEGF therapy vision or Ne-ovascular AMO
`Ci/./et AMO) patients maydecli.ne 1n the long-term.
`
`Despite optimal AntiNEGF therapy. vision of Neovascular AMO
`(Wet AMO) patients does not often retum to normal.
`
`Patients response toAntt-VEGf therapy 1s vanable in terms of
`initial gain and maintenance of gain
`
`Optimal outcomes with current Anti-VEGF therapies may not be
`achieved due to requirement for frequent treatmenVmonitoring
`
`Under current Anti-VEGF therapies, only a mmonty of patients
`regain normal '4$ion
`
`Current AntiNEGF the,apies do not modify disease
`progression
`
`US Ophthalmology
`
`Q26.We would now like to present you with a series of statements, can you
`please indicate your level of agreement with each of them, using a scale from
`1 to 7, where 1 = 'Strongly Disagree' and 7 = 'Strongly Agree'? Single code per
`row.
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718222
`
`Novartis Exhibit 2172.0021
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Patients and physicians agree that they need
`Innovative formulations with Prolonged
`duration and a Home-based monitoring
`
`Lessmvasrve
`Preference for topical
`Lower nsk of10fed10n
`
`Higher durat10nthat re<1uces
`the frequencyof111Ject10ns
`
`Offers an endpoint
`Reduce nsk of side effects
`Patient friendly
`
`Higher durnt100 of ad.on
`Less fre,quentdos1ng
`
`[LO
`
`Economic
`Considerations
`
`EYen11i+sen rernbursemertcs
`successluf.~ptOC@SSlJ"90fd.u'r.s
`Gburden!.om,eandthe
`w,prafJCUbil1ty~iestre
`f~jHCU0eS
`
`TOOIS&.Jitalowed pat,erts
`... ~ti."ddi:seas.e ar-:3
`t"Ul~I
`Patoie'llSS..pp0(1:IP'OU~
`
`Education and
`Support
`
`Too,s&.,..at@rial:slOl'l"l.tt!
`st:rseo'tl-,edl¥,lno5tS
`.. ~derstar,d ~.gof prog;r.oslS
`trUl!'l"'i!"t!lr-dexpectabOl"Ji
`
`US Ophthalmology
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718223
`
`Novartis Exhibit 2172.0022
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`2 out of 3 physicians believe there is a need for a
`new nAMD therapy
`Need for New Therapy to Treat nAMD
`
`US Ophthalmology
`
`SiKJlitf~ntdif!erences.@ ) l.!, NOV ART I $
`
`Q24. To what extent do you believe there is a need for a new therapy to treat
`Neovascular AMO (Wet AMO)? Please use a scale of 1 to 7 where 1 means "no
`need" and 7 means "major need".
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718224
`
`Novartis Exhibit 2172.0023
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Q36. And how you would describe your knowledge of these products?
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718225
`
`Novartis Exhibit 2172.0024
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Dosing and efficacy are identified as key advantages;
`While cost is the main disadvantage, over 1 in 10 do
`not see any disadvantages
`
`Advantages or disadvantages perception for RTH
`
`What comes to mind-when--yotJ think of R:EH258/Brol1?i~~~? What ar
`~
`the a'ct'\Pcffi~~ ~gbr disadvantages you perceive for RTH? (P as
`~Vdfic
`.
`.
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718226
`
`Novartis Exhibit 2172.0025
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Need Images
`What Retinal Specialists expect with RTH
`
`US Ophthalmology
`
`l.!, NOVARTI S
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718227
`
`Novartis Exhibit 2172.0026
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718228
`
`Novartis Exhibit 2172.0027
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Q3-8-:-Based on what you know I the-information-yot1--have b~n shown how(cid:173)
`Ii kelf ai'@~'01't'~tJse RTH 258 / Brolucizumab as a treatmen\1o~~¥M\ t 1 1ar
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718229
`
`Novartis Exhibit 2172.0028
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`US Ophthalmology
`
`Q42. Should RJH258/Brolucjzumab become available in the market, assuming
`positive clinical results and assuming that there will be no access challenges,
`how likely would you be to use this product to each type of Wet AMO patients?
`Please select all that apply.
`043. And should RJH258/Brolucjzumab become available in the market,
`assuming positive clinical results and assuming that there will be no additional
`access challenges when compared to other branded, on-label anti-VEGFs, what
`proportion of each of your Neovascular AMO (Wet AMO) patients would you
`treat with this product? Please specify your answer per each of the following
`types of Wet AMO patients.
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)0071 8230
`
`Novartis Exhibit 2172.0029
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718231
`
`Novartis Exhibit 2172.0030
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718232
`
`Novartis Exhibit 2172.0031
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`While physicians see many drivers for RTH
`use, a few key risks to RTH share are present
`
`US Ophthalmology
`1:
`
`l.!, NOVARTI S
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718233
`
`Novartis Exhibit 2172.0032
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Key Insights
`
`US Ophthalmology
`
`l.!, NOVARTI S
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718234
`
`Novartis Exhibit 2172.0033
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Outstanding Questions to Explore
`
`US Ophthalmology
`
`l.!, NOVARTI S
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718235
`
`Novartis Exhibit 2172.0034
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`YY,l_YY-'-Y-'-YY
`Y,l_YY,l_YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY-'-Y-'-YY
`Y ,l_ YY ,l_ YYYY )(cid:173)
`YY ,l_ YY ,l_ Y,l_ YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y ,l_ YY ,l_ YYYY )(cid:173)
`yy ,l_ yy ;_ y ;_ yy
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy)_
`yy;_yy;_y;_yy
`Y,t_YY,l_YYYY)(cid:173)
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy,l_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy)_
`yy;_yy;_y;_yy
`y;_yy,l_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy,l_yyyy,1-
`yy,l_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`
`Thank you
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718236
`
`Novartis Exhibit 2172.0035
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`YY,l_YY-'-Y-'-YY
`Y,l_YY,l_YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY-'-Y-'-YY
`Y ,l_ YY ,l_ YYYY )(cid:173)
`YY ,l_ YY ,l_ Y,l_ YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y ,l_ YY ,l_ YYYY )(cid:173)
`yy ,l_ yy ;_ y ;_ yy
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy)_
`yy;_yy;_y;_yy
`Y,t_YY,l_YYYY)(cid:173)
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy,l_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy)_
`yy;_yy;_y;_yy
`y;_yy,l_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy,l_yyyy,1-
`yy,l_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`
`Supporting Material
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718237
`
`Novartis Exhibit 2172.0036
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`YY,l_YY-'-Y-'-YY
`Y,l_YY,l_YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY-'-Y-'-YY
`Y ,l_ YY ,l_ YYYY )(cid:173)
`YY ,l_ YY ,l_ Y,l_ YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y ,l_ YY ,l_ YYYY )(cid:173)
`yy ,l_ yy ;_ y ;_ yy
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy)_
`yy;_yy;_y;_yy
`Y,t_YY,l_YYYY)(cid:173)
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy,l_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy)_
`yy;_yy;_y;_yy
`y;_yy,l_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy,l_yyyy,1-
`yy,l_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`
`Market Overview
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718238
`
`Novartis Exhibit 2172.0037
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Wet AMD comprises majority (57%) of total
`aVEGF sales, but is growing less rapidly than
`total aVEGF market
`
`Sales Split by Indication for Branded
`aVEGF's (2018)
`
`Total aVEGF Sales in wet AMO in USA ($mn)
`
`• Eylea •
`
`Lucentis
`
`____ ...,@-_______ ,.
`
`2,965
`
`3,033
`
`3,032
`
`3,299
`
`13% annual growth rate
`from 2014-2018
`
`2014
`
`2015
`
`2016
`
`2017
`
`2018
`
`%of
`aVEGF 76%
`sales:
`
`70%
`
`64%
`
`59%
`
`57%
`
`Source EvaluatePharma
`
`US Ophthalmology
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718239
`
`Novartis Exhibit 2172.0038
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`US nAMD patient population is highly
`penetrated
`86% is diagnosed & tre ated; annually, 200K new patients
`
`AMO lnc1denco Rato
`
`01agnos1s & Treatment
`Rates
`
`Naive Pc:ithrnts on
`Treatment
`
`Continuing Patients on
`Traatnutnt
`
`TOTAL Patients
`TOTAL Eyes'
`
`!l
`
`C ! :.
`
`US Ophthalmology
`
`l.!, NOVARTI S
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)0071 8240
`
`Novartis Exhibit 2172.0039
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Avastin leads the market with 46%
`share while Eylea continues to grow
`
`wAMD Treatment Share
`
`----------------46%
`
`38%
`
`15%
`
`70%
`
`60%
`
`50%
`
`40%
`
`30%
`
`20%
`
`10%
`
`0%
`
`#~~~~~~~~~~~~~##~~~~~~~~####~~
`O'~o~~o~\::Y~O'~o~~o'~if~O'~o~~O"~if~O'~o~~o~~.J'~O'~o~~o~~cf'~O'~c§~o~~.J'~O'~o~~o~~.J'~O'~CY?
`
`-
`
`Avastin
`
`-
`
`Eylea
`
`-
`
`Lucentis -Others
`
`Time penod of data Jan'10 to Jul'17
`Data Source IQVIA claims data
`
`US Ophthalmology
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718241
`
`Novartis Exhibit 2172.0040
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Patient share mix differs with naive market
`leader off-label beva at 67% but 44% for
`continuing
`
`Naive Patient Share
`
`Continuing Patient Share
`
`100%
`
`90%
`
`80%
`
`70%
`
`60%
`
`50%
`
`100%
`
`90%
`
`80%
`
`70%
`
`67%
`
`-
`
`Eylea
`
`-
`
`Lucentis
`
`-
`
`Avastin
`
`-
`
`Eylea
`
`-
`
`Lucentis - Avastin
`
`Data Source IQVIA claims data
`
`US Ophthalmology
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718242
`
`Novartis Exhibit 2172.0041
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Avastin is prescribed as an initial
`treatment by a majority
`
`US Ophthalmology
`
`l.!, NOVARTI S
`
`S11 . In what order do you typically prescribe / escalate therapy in wet AMO
`patients (1 for first-line, up to 4 for 4th line)?
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718243
`
`Novartis Exhibit 2172.0042
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`In the past 12 months 7% patients had their
`treatment switched; During Eylea launch year
`the switch rate had increased to 17%
`
`PatientMixin nAMD
`
`Product Share of Switching nAMD Patients
`
`100%
`
`80%
`
`60%
`
`40%
`
`20%
`
`0%
`
`■ Off-label
`beva
`■ Lucentis
`
`■ Eylea
`
`■ Naive
`
`■ Switch ■ Continuing
`
`Time period of data Aug'16 toJu1'17
`Data Source IQVIA claims data
`
`US Ophthalmology
`
`Products Switched To (from
`Eylea , Lucentis, Off-label beva)
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718244
`
`Novartis Exhibit 2172.0043
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`US Ophthalmology
`
`l.!, NOVARTI S
`
`Q7. Now please think about your wet AMO patients that you have initiated on
`initiated on ________ and then switched to a different anti-VEGF
`agent. For those patients, what percent were switched to the following
`medications on average?
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718245
`
`Novartis Exhibit 2172.0044
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`While initially Eylea took more share from
`Lucentis, at end of Y1 it had taken more share
`from Beva
`
`002)
`-1".~
`<l)"'
`20.7%
`_J _J _JIIODIL
`
`0 >,
`:::, 0
`
`34.6%
`
`21.3'11,
`
`(-9.3% )
`
`Pre-Launch
`
`Aug-Oct '11
`(Pre-Launch)
`
`Time penod of data Aug'11 to Oct'12
`Data Source IQVIA claims data
`
`US Ophthalmology
`
`■ Lucentis ■ Av astin ■ Eylea
`
`Aug-Oct '12
`(12 mths)
`
`Aug-Oct '12
`
`fu NOVARTIS
`
`Lucentis share >60% - Lucentis Loyalist
`Avastin share> 60% -Avastin Loyalist
`Others - Splitters
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718246
`
`Novartis Exhibit 2172.0045
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Retina Biosimilar Landscape
`(Advanced stage products only)
`
`Last Update. Jan19
`
`US Ophthalmology
`
`l.!, NOVARTI S
`
`Notes:
`
`*ONS501 O: The first clinical study for ONS-501 O is being conducted outside
`of the U.S. and is designed to serve as the first of two adequate and well
`controlled studies for wet AMO. The U.S. portion of the second study is
`scheduled to begin in early 2019 upon the submission of an IND application.
`Oncobiologics' wet AMO clinical program was reviewed at a successful end of
`Phase II meeting held with the U.S. FDA conducted earlier in 2018. If the
`program is successful , it will support the Company's plans to submit for
`regulatory approval in multiple markets in 2020. The Company is developing
`ONS-5010 as an innovative therapy and not using the biosimilar drug
`development pathway. Previously, ONS-5010 met the primary and secondary
`endpoints in a 3-arm single-dose PK Phase I clinical trial. All of the PK
`endpoints met the bio equivalency criteria of the geometric mean ratios within
`90% confidence interval of 80-125% when compared to both U.S. and EU
`sourced Avastin reference products (https://oncobiologics.com/programs/novel(cid:173)
`therapeutics/)
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)0071824 7
`
`Novartis Exhibit 2172.0046
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Retina Biosimilar Landscape - Key Highlights
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718248
`
`Novartis Exhibit 2172.0047
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`YY,l_YY-'-Y-'-YY
`Y,l_YY,l_YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY-'-Y-'-YY
`Y ,l_ YY ,l_ YYYY )(cid:173)
`YY ,l_ YY ,l_ Y,l_ YY
`Y-'-YY-'-YYYY)(cid:173)
`YY,l_YY,l_Y,l_YY
`Y ,l_ YY ,l_ YYYY )(cid:173)
`yy ,l_ yy ;_ y ;_ yy
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`YY,l_YY,l_Y,l_YY
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy)_
`yy;_yy;_y;_yy
`Y,t_YY,l_YYYY)(cid:173)
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy,l_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy;_yyyy)_
`yy;_yy;_y;_yy
`y;_yy,l_yyyy,1-
`yy;_yy;_y;_yy
`y;_yy,l_yyyy,1-
`yy,l_yy;_y;_yy
`y;_yy;_yyyy,1-
`yy;_yy;_y;_yy
`
`Patient Journey
`
`fu NOVARTIS
`
`CONTAINS CONFIDENTIAL BUSINESS INFORMATION, SUBJECT TO PROTECTIVE ORDER
`
`NOVITC(US)00718249
`
`Novartis Exhibit 2172.0048
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`. ~ . .
`
`t
`
`.
`
`I
`
`•
`
`..
`. . .
`
`Patient's first contact with
`the PCP, OD, or GO
`
`••
`• . .
`
`