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`
`SENJU EXHIBIT 2304
`LUPIN v SENJU
`IPR2015-01105
`
`

`
`2912016
`Miami.
`
`EP Valzlp - Vatage Pa'rt—As Eliqis limps on Xadlo rhniraes mi flood llimers
`
`‘They otter tremendous benefit over warfari_n — they have less bleeding risk, they are easier to
`use, they have less drug and food interactions. But it takes time for this to penetrate down,
`particularly to the community practitioner,’ he says.
`
`Despite al this many analysts were still expecting glquis to stop &rLelt_o in its tracks. But
`prescription data suggests that the impact has been negligible and as such the consensus
`view of the market for these oral thinners has shifted dramatically this year, with numbers for
`gcareltq climbing back up and Q5‘uis falling, producing the picture in the table below.
`
`Changing outlook for the oral anticoagulants
`Company Cunent
`%
`Current
`%
`%change in First
`2018
`change
`2014
`change
`2014
`launch
`sales
`overlast
`sales
`overlast
`forecast
`in major
`forecast
`12
`forecast
`12
`since
`market
`(Sm)
`months
`($m)
`months
`launch
`2,667
`54%
`1 ,353
`60%
`1 10%
`
`Bristol-
`Myers
`filfl
`
`gohnson
`33. Johnson
`
`_[)aiichi
`$3419
`
`_Lixiang
`
`2,631
`
`-37%
`
`491
`
`1 ,B39
`
`50%
`
`1 ,005
`
`350
`
`65%
`
`94
`
`Jul 201 1
`(US)
`
`Jul 2011
`U393")
`
`gm.’
`The big gap in this picture is Boehringer lngelheinfs Pradaxa which reached the main markets
`frst. The company being privately owned, consensus sales forecasts are not available;
`floehringer reported global sales of S1.43bn last year.
`
`US prescription data indicate that Pltfi lost market share on the arrival of gay in July
`2011 and contiiues to do so, while grgltg demand is still climbing strongly. Elgrfi was only
`launched in March, and has so far captured only 1.1% of the market, according to data 15
`presented at an investor conference this week; Earelto is on 19.3% to fla_d1a_'s 15.4%, the
`company said.
`
`In part, this will be thanks to Xarelt_o's broad label, the widea of all three blood thinners with
`seven approved indications — Pradaxa and lEIiguis_ are only approved in stroke prevention in
`the US.
`
`The J8-Jgyg pill is also approved to treat deep vein thrombosis and pulmonary emboisms,
`and to prevent deep vein thrombosis in patients undergoing knee or hip replacement surgery.
`On top of this 5&5! has generated some positive data in acute coronary syndromes, a
`severely il patient population in which _Elg‘uis faied and poehringer declined to test Eradaxg in
`phase III.
`
`European regulators allowed marketing in this setting earlier this year and alhough the US has
`so far declined to grant approval, evidence of utility in a very hard-to—treat population can only
`have helped the dmg's reputation (Q/l'L'lO!fLafl for new blood thinners in acute
`goronam smdrome March 5, 2013).
`
`liliguis is due to hear on approval in the albeit smaller pre-surgery setting in the US in May
`next year — it has already sold for this use in Europe — and this could help bump up demand.
`
`Once vs twice
`
`Dosing is likely to be another factor favouring Xarelto. Whie both Egg and Pradfi pills
`need to be taken twice a day in stroke prevention, Xarelto is once daily. Tim Race, pharma
`analyst at Deutsche Bank, reckons this couki be providing an edge.
`
`‘These patients are on many other drugs and once daily fits in best. Also, doctors don't trust
`patients to take their pills, so is [Eggs] really better in the real world if you miss a dose?‘ he
`says.
`
`figyg is convinced that dosing is playing a major part in grelt_o's success. ‘Physician surveys
`have shown that they use §arelto_ over other agents because of its breadth of indications at
`launch and once daiy dosing,‘ Dr Kemal Mal k, head of development and chief medical oflicer,
`said at figs presentation yesterday.
`
`Dr Sacco, who was involved in one of the pivotal trials testing §l_igu_i§, agrees that _Xarelt9_'s
`litp1Iwww.epvaIa_)e.canILIriversdMamspx?lype=Stuy&id=461m18JsEFNaIu;e=yes
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`2190016
`schedule can be an advantage.
`
`EP Vantage - Vantage Point—As Eliquis limps on Xarelto dominates oral blood thinners
`
`“Once a day often improves compliance." But whether any of these drugs is truly better is "the
`million dollar question", he adds, as there have been no head-to-heads, and comparing trials
`results is fraught with the usual caveats.
`
`‘It's really hard to choose between them. Ultimately it comes down to what the physician is
`most comfortable using," he says.
`
`Inertia
`
`This stance will naturally favour an incumbent, and helps explain §ig_ui_s’s struggles to get off
`the ground, despite being perceived as the safest. As such, it is too early write off the drug as
`an also-ran, although if it still does have market-leading potential it seems this will longer than
`expected to fulfil.
`
`And there is another cloud on the horizon for Eggs, in the shape of a fourth oral contender —
`_gixiana_ or §doxat3a_n from _[_)aiichi Sankyg. Like _E£;_uls_ and xareltqthis is a _l1ct_o_rla_ inhibitor —
`_Prada)g is a thrombin inhibitor — and is also being tested as a once—a—day medicine.
`
`Phase III data released earlier this year, in patients with deep vein or lung blood clots, found
`the project non—inferior to warfarirl at preventing the recurrence of clots and superior to
`vvartarifl at preventing bleeding. Superiority on both measures would have been a huge win for
`the Japanese company, but results in the all-important stroke prevention indication will be the
`real measure of edoxabi. Those data are I kely to emerge at the AHA conference in
`N°Vembe' (§§.9.:..Q<:*E’1LL’£'S_fle.2%2fl2<l’£'J£'Lm9_CfllV.ifl.99§fl!§£z‘E£'1¢£1£,
`September 2, 2013).
`
`Of course, a strong showing in stroke prevention will mark once—a—day edoxafl as a strong
`competitor to all of the anticoagulants. Although _Daiich_i still has to get the drug to market — the
`FDA did not give )_(a_rrell>_ or gigifi an easy ride — and then battle in an even more crowded
`market place.
`
`And E)/gr and J&J will not let their lead go without a fight — the German company set out
`plans yesterday to recruit another 30,000 patients in trials in additional clotting settings and a
`wider atrial f brtllation population, to broaden the label further.
`
`It is undoubtedly early days for §ligu_is, and Bristol-Myers and @453 have laid out plans for a
`big marketing push to reinvigorate the launch. But its third-to-market handicap and twice-a—day
`dosing disadvantage, which were brushed off by the companies and bullish analysts before
`launch, will take time to overcome.
`
`To contact the miter of this story email Amy Brown in London at §mZB@_e‘pi/antage_con_i
`or follow _@mzEPL/:ita_q§ on Twitter
`
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