ARBUTUS - EXHIBIT 2023
`Moderna Therapeutics, Inc. v. Arbutus Biopharma Corporation - IPR2019-00554
`
`

`

`|NEWS|IN FOCUS
`
`oe
`
`UPS AND DOWNS
`The biotech firm Alnylam faced several setbacks
`before winning US government approval forits
`first RNA-interference drug,
`2,000 MetPen erreva vauteres sever siveeryrecsesteresttatecnrssneetsersyeraspatsaspen et
`
`
`
`SOURCE:NASDA
`
`
`
`
`
`
`
`Alnylamstackpricechange(9%)
`
`By 2010,large pharmaceutical compa-
`is testing RNAi therapies that target proteins in
`nies werealso losing their appetite for RNAi,
`the kidneys and the eye. Alnylamis develop-
`severing collaborations and ending inter-
`ing waysto target the brain and spinal cord,
`and Arrowhead Pharmaceuticals of Pasadena,
`nal research programmes. “By andlarge, big
`pharmaleft RNAifor dead,” says Fambrough.
`California, is working on an inhalable RNAi
`Safety concerns dealt the field another blow
`treatmentfor cystic fibrosis.
`in 2016, when Alnylam abandonedoneofits
`“T've never been more optimistic about the
`leading RNAi programmesafter finding a pos-
`future of RNAi,” says Fambrough.“All ofthose
`sible link to patient deathsinaclinical trial (see
`tear-your-hair-out days were worth it to get to
`“Ups and downs’).
`today”
`But gradually, some RNAi companies began
`Advances in RNA delivery mightalso benefit
`to iron out the kinksin their delivery systems.
`researchers whoare developing gene-editing
`Alnylam experimented with a numberofdeliv-
`therapies based on the popular technique
`ery routes and target organs, encasing some
`CRISPR-Cas9.That system uses a DNA-cutting
`ofits RNA moleculesin fatty nanoparticles
`protein called Cas9, which is guided to the
`or chemically modifying the RNAsto help
`desiredsite in the genome by an RNA molecule.
`them survive the perilous journey through
`Like RNAi before it, CRISPR-Cas9 has
`the bloodstream.
`become a commontool in genetics labora-
`RNAsprotected in this way and injected
`tories, But it might still face a difficult and
`into the bloodstream tended to accumulate in
`lengthy path to the clinic. Muchlike ordinary
`the kidneys and liver. This led the company
`N. Engl. J. Med. 379, 11-21; 2018). Walking
`drugs, RNAi therapies will break down over
`speed declined in the placebo group,
`to lookat transthyretin, which is produced
`time; a gene edit, however,is intended to be
`mainlyin theliver. In a clinical trial in 225 peo-
`In the future, Alnylam and otherswill be
`permanent, which amplifies safety. concerns.
`ple with hereditary transthyretin amyloidosis
`able to move beyondtheliver, says company
`“L hope they can do it more quickly than
`who showedsigns of nerve damage,average
`co-founder Thomas Tuschl, a biochemist
`wedid it, but I would not expect it to be so
`walking speed significantly improved in those
`at Rockefeller University in New YorkCity.
`smooth,” says Fambrough. “I wish themthe
`best of luck.” =
`Quark Pharmaceuticals of Fremont, California
`whoreceived the treatment (D. Adamsetal.
`
`
`25=
`
`BOO nererereeereeetetnerenneererrrererereerereed
`
`fone cece
`
`bere
`
`2006
`
`2009
`
`2012
`
`2015
`
`2018
`
`Outrage over changesto
`EPA chemical assessments
`
`Critics say US environment agency’s revisionsfavour industry over academic research.
`
`BY JEFF TOLLEFSON
`
`he US Environmental Protection
`Agency is making major changes to
`the way in whichit evaluates chemicals
`for environmental and public-health effects.
`The latest push includes changes to chemical-
`safety guidelines that place greater weight on
`industry-sponsored research, among other
`things, andis a part ofefforts by US President
`Donald Trump’s administration to reshape
`how the agencyuses science to make decisions.
`The Environmental Protection Agency
`(EPA) issuedits chemical-assessment guidance
`in May,andis soliciting public commentsuntil
`16 August. The guidance contains changes
`dictating the kind of data that studies must
`include in order to be considered in the EPAs
`decision-making process. Researchers and
`environmental and public-health advocates
`say that the guidelines provide a non-peer-
`
`required by law to do these evaluations,but the
`guidance defines howofficials conduct them.
`At stake are tens of thousands of chemicals
`destined for public use and governed by the
`1976 Toxic Substances Control Act (TSCA),
`The guidancedovetails with a rule proposed
`in April by then-EPA administrator Scott
`Pruitt, which, if finalized and implemented,
`would reduce the role of published scientific
`studies in decision-making across the agency.
`The changesalso coincide with attacks on the
`EPA'score chemical-assessment programme,
`knownas the Integrated Risk Information
`System (IRIS), by industry and Republican
`politicians overthepast year.
`In a statementto Nature, the EPA says the
`changes are meantto provideclearcriteria to
`help determine the quality ofthe research used
`to evaluate chemicals — and that the guid-
`ance is a work in progressthat can be revised
`in response to new information.Butscientists
`
`JenniferSass, a senior scientist at the Natural
`Resources Defense Council, an advocacy
`group based in New YorkCity, suspects that
`the goals are to promote science from industry
`and changethe calculationsthat the EPA uses
`to develop regulations andestimatesafe expo-
`surelimits for chemicals.
`
`MEETING THE REQUIREMENTS
`The guidelines introduce manydata report-
`ing requirements — including statistical
`analyses that measure whether a study cor-
`rectly identifies the presence of an effect
`— that are standard for industry-funded
`research. But because such criteria vary
`among peer-reviewed journals, many aca-
`demic studies would be disqualified, says
`Tracey Woodruff, who led the development
`of a chemical-evaluation process at the Uni-
`versity of California, San Francisco. “Only
`industry studieswill survive.”
`
`