Thu Feb 19 2004 09:46:45 EST
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`Biogen Exhibit 2309
`Coalition v. Biogen
`IPR2015-01993
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`From:
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`Biogen Exhibit 2309
`Coalition v. Biogen
`IPR2015-01993
`
`
`
`Subject:
`
`SLIDES ATIACHED: Ad Hoc CTRB Meeting - BG12 MS, Thursday, February 19, 2004, lO(cid:173)
`ll am EST in Room 4124 Auditorium
`
`Hello everyone-
`
`Attached, please find the slides for today's meeting.
`
`**Please note that handouts will be distributed in the Cambridge Office**
`
`..
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`Thank you!
`
`on 02/ 19/2004 08:4!2 AM -----
`
`----- Forwarded by
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`-18-Feb-2004 08:51AM
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`Subject: REMINDER: Ad Hoc CTRB Meeting- BG12 MS, Thursday, February 19, 2004, 10-
`llam EST in Room 4124 Auditorium
`
`Hello everyone-
`
`There will be an Ad Hoc CTRB Meeting regarding BG 12 MS on Thursday, February 19, 2004
`from 10:00-ll:OOam EST I 3:00-4:00pm UK in Room 4124 Auditorium, Bio 4, 12th Floor.
`
`Attached, please find the protocol concept and table of additional concept options for your
`review and comments.
`
`WebEx Details
`
`Topic: Ad Hoc CTRB Meeting - BG12 MS
`Date:
`19, 2004
`
`Meeting number(cid:173)
`Host: Carmen Bozic
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`Teleconference Details
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`Chairperson: Catmen Bozic
`
`For more information on CTRB Meetings, please visit our website:
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`Thank you!
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`Thank you!Thank you!
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`BG’12 in MS
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`CTRB Meeting
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`Gilmore O’Neil|
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`19”‘ February 2004
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`Summary of Dosing options.
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`Dosing Regimes
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`120 mgiday
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`Single dose
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`120 mgfday
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`Single dose
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`240 mgfday 360 mgfday 480 mgfday 720 mglday
`2 div dose
`3 div dose
`2 div dose
`3 div dose
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`360 mgfday 480 mgfday 720 mgfday
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`3 div dose
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`2 div dose
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`3 div dose
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`360 mgfday
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`3 div dose
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`720 mgfday
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`3 div dose
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`720 mgiday
`3 div dose
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`9 November '13, 2iI|D3
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`Impact of Constraints on Options.
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`Constraints
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`Option 1 Option 2 Option 3 Option 4
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`Deliver data by Q3 '05
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`Dosing is in multiples
`of 120 mg
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`Safety concerns
`above 720 mg
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`Psoriasis already
`established 720 mg
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`Adequate Dose
`determination for
`regulatory
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`'
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`'-1'
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`'-1'
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`'-1'
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`X
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`'-1'
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`\ }
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`A
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`10 November 13, 2003
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`Lead Option (Option 1) Treatment
`Schedule
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`233 patients randomised in 59:44:-44:44:44 patients
`
`— Primary objective is to determine the effectiveness
`of4 dosing regimes of BGOO012 on brain lesion
`activity as measured by MRI in patients with
`relapsing remitting MS when compared to placebo.
`— Placebo, BG’12120m bid, BG'12120mtid, BG’12 240m
`E, BG"12 240m tid.
`
`Initial treatment period 24 weeks (Dose escalation
`after one week in treatment and extension phase)
`
`Followed by 24 week extension phase
`— Patients on active treatment will remain on the same dose
`
`— Placebo patients will receive BG"12 240mg tid
`
`11 No~.'en1lJer 13, 2003
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`Critique of Option 1 concept.
`
`• Scientific:
`- Confirms efficacy of BG'12 in MS.
`- Dose ranging study.
`- Minimum efficacious dose.
`- Determine roles of Cmax, Cmax frequency and/or total daily
`exposure in influencing therapeutic effect.
`• Regulatory:
`- Low risk: ie Regulatory agencies will determine that dose
`determination is adequate.
`• Commercial:
`- Endorses option 2.
`
`15 November 13. 2003
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`Option 2 Treatment Schedule
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`- 233 patients randomised in 59:44:44:44:44
`ratio
`
`— Primar ob'ective is to determine the effectiveness
`of four doses of BGOO012 on brain lesion activity
`as measured by MRI in patients with relapsing
`remitting MS when compared to placebo.
`
`— Placebo, BG"l2 ‘l20m g, BG’12 120m tid,
`BG'12 240m bid, BG’12 240m tid
`
`-
`
`Initial treatment period 24 weeks
`
`- Followed by 24 week extension phase
`— Patients on active treatment will remain on the
`
`same dose
`
`— Placebo patients will receive BG’12 240mg tid
`
`1E‘. November 13, 2003
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`Critique of Option 2 concept.
`
`• Scientific:
`- Confirms efficacy of BG'12 in MS.
`- Optimal dose for Phase Il l study.
`- Risk that 120mg qd will not show efficacy.
`- BUT will not determine roles of Cmax, Cmax frequency and/or
`total daily exposure in influencing therapeutic effect
`• Regulatory:
`- Lowest dose selected may not be accepted by Regulatory
`agenc1es.
`• Commercial:
`- Prefers this option.
`
`17 November 13. 2003
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`Option 3 Treatment Schedule
`
`• 236 patients randomized in 1:1:1:1 ratio (59
`patients per arm).
`- Primary objective is to determine the effectiveness
`of three doses of BGOOO 12 on brain lesion activity
`as measured by MRI in patients w ith relapsing
`remitting MS when compared to placebo.
`-Placebo, BG'12 120m
`d, BG'12 120m
`tid
`BG'12 240m
`• Initial treatment period 24 weeks
`• Fallowed by 24 week extension phase
`- Patients on active treatment will remain on the
`same dose
`- Placebo patients w ill receive BG'12 240mg tid
`
`tid,
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`18 November 13, 2003
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`Critique of Option 3 concept.
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`Scientific:
`- Confi rms efficacy of BG'12 in MS.
`- Optimal dose for Phase Ill study.
`- Minimum efficacious dose.
`- Does not explore BID dosing.
`- And will not determine roles of Cmax, Cmax freq uency and/or total
`daily exposure in influencing therapeutic effect
`Regulatory:
`- Risk that regulators would feel that dose determ ination is
`inadequate.
`Commerc ial:
`- Preferred over option 1.
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`19 November 13. 2003
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`Budget Considerations
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`- 1st Pass 2004 Annual Plan: Ph Ilb with 2 F/U
`
`visits
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`- New Designs:
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`— Phase Ilb with 1 F/U visit
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`— Separate extension study
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`— Combined total for separate studies
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`— Phase Ilb and safety extension combined
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`E No~.'en1lJer 13, 2003
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`Phase llb study design
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`§creening
`Randomizeg
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`1°
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`Open label Safety
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`Game Go for
`Phase Ill
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`Go.-‘No Go for
`Phase III
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`0 1'“ endpoint at 24 weeks
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`2? No~.'en1lJer 13, 2003
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