..
`
`Date:
`Wednesday, April 4 2007 06:05 PM
`Subject:
`Summary of issues for call: AMO P3 Planning
`From:
`George Yancopoulos
`To:
`Darlene Jody <Darlene_Jody@berlex.com>;
`Attachments: Jody Call_040407.doc
`
`please see enclosed outline for our discussions ....
`
`EXHIBIT
`
`:;J)X
`i
`
`0/lt..1
`
`CONFIDENTIAL
`
`RGN-EYLEA-MYLAN-00526319
`
`DTX 0228.0001
`
`Regeneron v. Mylan
`DTX 0228
`
`(22-cv-61 NDWV)
`
`Regeneron Pharmaceuticals, Inc. Exhibit 2009 Page 1
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
`
`

`

`Darlene Jody Call / April 4, 2007
`
`Dear Darlene:
`
`Just a quick (albeit belated) pre-summary for our call - it has to do with planning for our AMD Phase 3
`program.
`
`Here at REGN, we like a top-down approach, in vvhich major decisions are made by our Senior Management
`Team (follov.-ing intense data review), and then "·sold" down. We find this avoids a lot of unnecessary busy
`work and discord at the team level, which ultimately has a high chance of being obviated by the Senior
`Mgmt perspective anyway.
`
`In this regard, after carefully reviewing the P2 data (as well as all prior Pl data, which is also quite relevant),
`our entire Senior Management Team is strongly united on the follmving AMD P3 program:
`
`Two identical 1200 patient studies (the first led by REGN, the second by BHS), each with the same 4 anns ,
`powered for NI to Lucentis control :
`
`Lucentis Control (0.5q4w)
`VT 0.5q4w
`VT 2.0q4w
`VT 2.0q8w (dose somewhat still undecided)
`
`The rationale for this is that the data suggests that:
`l. The higher dose ( 4. 0) does not clearly provide further benefit at this time, so we wou ld not use it
`unless something strongly changes with the maturing P2 data; we are a bit still strnggling with the
`high dose to be used for the q8w interval
`2. The quarterly dose groups slip more at 12w than at 8w, making NI a significant risk at 12w
`3. Our commercial group assures us that the community wou ld viev.- a fixed dose regimen at 8w as a
`real big ,vin in the marketplace, and that you are much better off having a strong 8w number than a
`In fact, any fixed dose regimen greater than every 4 weeks that doesn ·t
`weaker 12vv number.
`require interim monitoring for visual acuity is seen as desirable among physicians.
`4. The 0.5 and 2.0 monthly regimens provide best opportunity for best absolute efficacy, and also
`provide real opportunity for improved absolute efficacy compared to Lucentis (numerically if not
`statistically) which could convince physicians that our drng is the definitive better agent to be used
`regardless of dosing regimen and interval
`(there is minor concern about tox coverage for the 2q4 group - while 10-fold tox coverage is standard,
`for 2q4w we have 6-fold coverage but have already given this to 30 humans in the P2, and can
`provide the additional tox during the P3 study, which we think is little risk since nothing has been
`seen tox-wise at the 4q4w in monkeys, and new study would be at 4q2w - we have previously
`negotiated similar solutions with the regulatory agencies)
`
`I know there has been extensive discussion at the team level about the second study being a NI study using
`doses of VT q 12w versus the Lucentis PIER regimen, which might suffice for EMEA and also
`simultaneously serve as a second study for the FDA based on using a separate Superiority analysis. Our
`view on this is that while such a second study is indeed likely to be NI to Lucentis PIER regimen, it is at high
`risk for not achieving Superiority and thus not being useful for the US approval in any way, and thus at high
`risk of seriously hanning the global brand perception. Wiley has also told us in writing that he wants the
`labeled '·optimal dose and regimen., reproduced, so even achieving Superiority in such a second study would
`probably not suffice for US approval. Finally, such a dosing regimen is unlikely to produce a benefit that
`favorably compares with monthly Lucentis dosing or unlabelled but published PRN approaches (which arc
`being widely adopted as current standard of care), to which we are likely to be compared by physicians.
`
`CONFIDENTIAL
`
`RGN-EYLEA-MYLAN-00526320
`
`DTX 0228.0002
`
`Regeneron Pharmaceuticals, Inc. Exhibit 2009 Page 2
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
`
`

`

`To summarize, 2 identical studies as suggested above provide full support for the TPP and global
`registration, as well as best chance of producing optimal data for VT, whereas a 4 arm + PIER design may
`provide an inferior label (and hence a weaker version of the TPP) AND unlikely to allow registration in the
`us
`
`There is also an issue of which formulation to use in the first study, which we can discuss as ,veil.
`
`Best,
`George
`
`CONFIDENTIAL
`
`RG N-EYLEA-MYLAN-00526321
`
`DTX 0228.0003
`
`Regeneron Pharmaceuticals, Inc. Exhibit 2009 Page 3
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
`
`

`

`J
`
`DTX 0228.0004
`
`Regeneron Pharmaceuticals, Inc. Exhibit 2009 Page 4
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
`
`