screws Sept 2009
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`Page 3. of2
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`' item;
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`-_ scrnrrvrs acre '
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`ecrnrms 2013
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`The European Committee for Treatment and Research in MS held their annual
`meeting from September 9-12. Here are some of the presentations that!
`found interesting.
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`3. Active Clinical Trials at UT .
`_ 201s
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`Z
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`3
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`.
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`..
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`'
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`- scrnlrvis 2017
`Acrnrrvrs Forum 2017'
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`,
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`scrnnvrs 201s
`Téctldoroupdatc
`' 5eptember.2_018
`.'
`screams 2015'
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`'
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`..Anrv2015
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`5 swarms-screws 2014 "
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`AAN 2014 I
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`'
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`_. Current Treatments -'
`(updated‘r‘ii'flal
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`'
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`ilerlyo (updated aracnorzr'
`Tysabriand PML '. _
`A'mpyro
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`'
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`it reduced relapse rate by
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`Treatment
`There were reports on a number of clinical trials, mainly of oral agents which are summarized below.
`Fingolimod: Further results from the TRANSFORMS study were reported. The initial results were
`reported at AAN earlierthis year. This was a targe study with over 400 patients per arm, and
`fingolimod was compared to interferon rather than using a placebo control. The effectiveness looks
`good with over a 50% reduction in relapse rate. Safety is a concern, since there were 2 fatst virus
`infections in the treatment group.
`. Oral ciadribine, further results from the CLARITY study. Again. the initial results of this study
`"
`.‘ were reported at the AAN, and it was a large study with over 400 patients in each group,
`with cladn‘bine compared to placebo. The retapse rate was reduced 58%. and MRI activity
`decreased 83%. No safety concerns were identified, but they remain a concern with a cytotoxic
`drug like this.
`' BG12 or tumarate: This agent is earlier in the clinical trial process.
`about 30% compared to placebo.
`Laquinimod: they reported safety results which look promising.
`Terifiunomide: This is another orai agent with immunomcdulatory effects. This was a phase ii
`study with around 49 patients per arm, and the drug was used as an add-on to interferon. MRI
`activity decreased by about 80%.
`Atorvastatin in early MS: this is a cholesterol lowering drug. which may also be useful in MS.
`They didn't enroll as many patients as they planned with only 82 total patients, and there wasn't any
`obvious benefit.
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`
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`Recent and. current
`research
`.Old meetings ..
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`I'
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`New diagnosis of MS I
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`'
`
`Information
`1 ”WP"? Edema 8°“ '
`.
`Into damn versus
`Giotiramer--updale 11m?
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`Dimcotide: This is a peptide from myelin basic protein, and it was used in a study with over 500
`- secondary progressive MS patients. There was no benefit.
`in summary, there are a number of oral treatments in development. some of which may be more
`effective than our current standard treatments. The combination of increased effectiveness and
`'. safety is elusive. The single trial in progressive MS was negative. but it is good to see treatments
`3 being tried in progressive disease since the majority of drugs are for relapsing MS.
`
`3 alk on stem certs-arrows
`About Dr. Lindsey _
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`.-
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`Research Interests
`_ MapiDirections__ _-
`Links
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`Contact Us
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`3 Science
`
`l heard several presentations of some fresh ideas. One ofthe keynote lectures was given by Dr.
`':_ Prineas. a pathologist, who has some different ideas on the cause of MS. Most researchers focus on
`the role of autoimmunity in damaging myelin and oligodendrocytes. Dr. Prineas suggested that the
`. primary problem in MS is that oltgodendrocytes die off first. and then the immune cells come in to
`clean up the myelin debris. He thinks the primary problem may be with the astrocytes. one of the
`cells in the brain that provides support to the other cells.
`l'm not sure he has a convincing story yet.
`. but he definitety has interesting ideas and a different approach.
`-' Dr. Derfuss from Dr. Meinl's group gave an excellent talk on the proteins neurofascin and contactin
`.. as possible targets of the autoimmune attack in MS. These are relatively minor proteins, but they
`.' are located at the junction where the myetin binds to the axon. These proteins were first identified
`. by finding myelin proteins that were recognized by antibodies from MS patients. and they have gone
`.- on to do experimental work to demonstrate that immune attack on these proteins can cause
`-. demyelination. We definitely need to think beyond myelin basic protein and proteolipid protein as
`the targets of immune attack, and I think this is a step in the right direction.
`Epstein-Barr virus continues to be controversial. Some investigators can find it in the brain, and
`-_ others cannot.
`i think it will be a while before that issue is settled.
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`http:/Iwwwjiwindscyrud.comiid69.html
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`Biogen Exhibit 2228
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`Mylan v. Biogen
`IPR 2018-01403
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`Page 1 of 2
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`Biogen Exhibit 2228
`Mylan v. Biogen
`IPR 2018-01403
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`

`

`ECTRIMS 394312009
`
`J. William Lindsey. MD
`University of Texas Multipie Sclemsis Research Group
`Houston. Texas
`
`copyright 2007-2020 John Wililam Lindsey
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