BG-12 MS
`Clinical Development Team
`
`Ratna
`
`Pri mary Endpoint: Will be switched to ARR
`Dose: 480 mg arm will be added
`Open Label Rescue Trcaunen1: Per FDA request that we prov ide. an "approved MS
`therapy". the protocols will be revised to include Avonex after 48 weeks for patients
`who (a) have 2 conJ1nncd relapses at any time during the trial, or (b) experience
`protocol-defined disease progression (EDSS ~ 1.0 increase sustained or L5 increase
`of Baseline EDSS=), sustained x 12 weeks).
`Pk testing wil l be added to 302 (uot 301)
`Study Durarion: EndofSwdy decreased from 104 weeks w tOO weeks.
`Add SF36 and EQ5D to Unscheduled Relapse Assessment Visit.
`= Question: Can we add Pharmacoeconomic analysis section to the protocol? Specific.
`team members will review docmncm from UBC and decide.
`= Availability of dmg for FPI in Dec-Oo: Decision stlJ I pending. Team ,viJi movc
`forward assuming we can meet goal. Primary focus will be on 30 I. Documents required
`for 302 stan-up will be delayed approximately 2-4 weeks following 302 (timeline
`pending).
`=US Regulatory remir.ds \IS that we will need to send the Phase 3 protocols to FDA
`prior to FPL Tanuny recottunends the following plan:
`(a) We provide I'DA with a chan summarizing major chaogcs to tbc pro tocol.
`(b) Cover leiter, Sununary cbarl outliniug cbauges aud protocols are sent together
`wiOl request for t'ccdback.
`(c) Tammy will call to see if this format is acceptable, itnd if so, when can we
`expect fc.edback on the protocols. (NOTE: We wi ll submit for AUS/NZ at risk
`without FDA buy·in).
`(d) Tammy will comacl fDA to inquire if they are accepting our EOP2 Meeting
`Minutes as final minutes. or if they are sending another version. If so. when
`
`What is required to start US (9 rno tox. linal ordrafl rcpo•i?}
`What is the timeline for having this available?
`Canada?
`=> Pos t-CDT update: P:ogram Team discussion on 7-Scpt regarding wh;~ is required for
`toxicology. Final answer regarding repo11 availallilily and timeline pending unt il 14-
`Sept. EU and US Regulatory met oft~li ne with Canada to develop a plan for assessing
`Canadian requirements. Initial assessment: Formal meeting not fe(jUired. Will prepare
`
`bas confirmed previous advice received regarding tile slim cbar,ce of placebo(cid:173)
`-
`controlled trials being approved in mese countries. -
`has also advised us that
`negative feedback from regulatory agencies in these countries may have a much
`greater negative impact in the litture (since their regulations slate they do not
`approve placebo-con!rolled trials, they are uot pleased wbcu companies submit
`them). -
`will discuss with country affiliates.
`recommend these
`countries be removed from the lists so that we can give these slots to other sites we
`
`Page 112
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`regarding Nortb
`American site panicipalion in
`Phase 3
`
`Recomn•eodations
`regarding Brazil and I
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`Biogeo Exhibit 2228
`Coalition v. Biogeo
`IPR2015-01993
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