Copyright © Elix, Inc. All rights reserved. ෼ࢠߏ଄ੜ੒Ϟσϧͷ ΫΠοΫϨϏϡʔ גࣜձࣾ&MJY ϦαʔνΤϯδχΞ Ҫ্ وԝ

Copyright © Elix, Inc. All rights reserved. 2 ҩༀ඼Λ͸͡Ίͱ͢ΔػೳੑԽ߹෺ͷߏ଄ઃܭʹ͸ࢼߦࡨޡ͕ඞཁͰɺ࣌ؒͱίετ͕͔͔Δ ➔ ߏ଄ઃܭͷखॱΛޮ཰ԽͰ͖Δͱศར ػೳੑԽ߹෺ͷ։ൃϓϩηε ੒ޭ ߏ଄ઃܭ ߹੒ ࢼݧ ࣦഊʜʜ

Copyright © Elix, Inc. All rights reserved. 3 ߏ଄ੜ੒ث͋Δछͷߏ଄ੜ੒نଇΛ༻͍ͯίϯϐϡʔλ্Ͱ෼ࢠߏ଄Λൃੜͤ͞ΔϓϩάϥϜ ߏ଄ੜ੒ثΛ༻͍Δ͜ͱͰଟ਺ͷ෼ࢠߏ଄Λੜ੒Ͱ͖Δ ଟ਺ͷ෼ࢠߏ଄ΛؚΉੜ੒ߏ଄܈͔Βɺॴ๬ͷੑ࣭Λ࣋ͭͱظ଴͞ΕΔ༗๬ͳԽ߹෺܈Λநग़͢Δ ➔ ༗๬Խ߹෺܈ʹରͯ͠ࢼݧ͢Δ͜ͱͰɺߏ଄ઃܭͷखॱΛޮ཰ԽͰ͖Δͱظ଴͞ΕΔ ߏ଄ੜ੒ث ߏ଄ੜ੒ث ੜ੒ߏ଄܈ ༗๬ߏ଄܈ நग़ ੜ੒

Copyright © Elix, Inc. All rights reserved. 4 ༩͑ΒΕͨσʔληοτ͔Βࣗಈநग़͞Εͨ ֬཰Ͱදݱ͞ΕΔ ߏ଄ੜ੒نଇΛ༻͍ͨਂ૚ੜ੒Ϟσϧ ෼ࢠߏ଄ͷݱΕ΍͢͞ σʔλੜ੒෼෍ Λදݱ͢Δ ྫ һ؀ͱһ؀Ͱ͸ɺһ؀ͷํ͕ݱΕ΍͍͢ $ݪࢠͱ4ݪࢠͰ͸ɺ$ݪࢠͷํ͕෼ࢠ಺ʹଟؚ͘·Ε͍ͯΔ ෼ࢠߏ଄ͷಛ௃ʹ͸Ұఆͷ܏޲͕͋Δ ➔ ݱΕ΍͍͢෼ࢠߏ଄ʹରͯ͠ɺߴ͍֬཰஋ׂ͕Γ౰ͯΒΕ͍ͯΔ ➔ ܇࿅ࡁΈϞσϧ͔ΒͷαϯϓϦϯάͰɺ܇࿅αϯϓϧΒ͍͠ ෼ࢠߏ଄Λੜ੒Ͱ͖Δ Ҏ߱Ͱ͸ɺਂ૚ߏ଄ੜ੒ثͷछྨ΍Ԡ༻ʹ͍ͭͯ ؆୯ʹϨϏϡʔ͢Δ ਂ૚ߏ଄ੜ੒ث ߏ଄ੜ੒نଇ ੜ੒ ੜ੒ߏ଄܈ ਂ૚ߏ଄ੜ੒ث ෼ࢠߏ଄ σʔληοτ نଇͷநग़

Copyright © Elix, Inc. All rights reserved. 5 ෼ࢠߏ଄ͷओͳදݱํ๏ CC(=O)Nc1cccc1 ਂ૚ߏ଄ੜ੒ثͷೖग़ྗʹར༻͞ΕΔ෼ࢠߏ଄ͷදݱํ๏͸ɺओʹछྨ͋Δ • จࣈྻʹΑΔදݱ • ෼ࢠάϥϑʹΑΔදݱ • ࣍ݩ࠲ඪʹΑΔදݱ ҎԼɺͦΕͧΕͷಛ௃ʹ͍ͭͯ֓આ͢Δ

Copyright © Elix, Inc. All rights reserved. 6 • จࣈྻτʔΫϯͱݺ͹ΕΔ࠷খͷߏ੒୯Ґ͕ฒΜͩ΋ͷ ◦ τʔΫϯ͸ࣗવݴޠʹ͓͚Δ୯ޠʹ૬౰ ◦ 4.*-&4จࣈྻͰ͸ݩૉ͝ͱʹҰͭͷτʔΫϯΛͳ͢ͱߟ͑Δ͜ͱ͕ଟ͍ • ෼ࢠߏ଄Λग़ྗ͢Δͷʹѻ͍΍͍͢ ◦ طʹಘΒΕͨจࣈྻʹଓ͘τʔΫϯΛ֬཰తʹग़ྗ ݴޠϞσϧ • ଟ͘ͷϞσϧͰར༻͞Ε͍ͯΔͷ͸4.*-&4จࣈྻ ◦ Ұఆͷจ๏ʹैͬͯτʔΫϯ͕ฒΜͰ͍Δ • 4.*-&4ͷจ๏ʹैΘͳ͍จࣈྻ͸ɺ෼ࢠߏ଄Λදݱ͠ͳ͍ແޮͳจࣈྻ ➔ 4.*-&4จࣈྻͷ୅ΘΓʹ4&-'*&4<>Λ༻͍ͨΓɺจ๏ΛߟྀͰ͖ΔϞσϧ FH (SBNNBS7"&<> 4%7"&<> Λར༻͢ΔͳͲͷ޻෉͕ͳ͞Ε͍ͯΔ จࣈྻʹΑΔදݱ CC(=O)Nc1cccc1 <>.,SFOO FUBM.BDI-FBSO4DJ5FDIOPM <>.+,VTOFS FUBM*$.- 1.-3 <>)%BJ FUBM*$-3

Copyright © Elix, Inc. All rights reserved. 7 • ෼ࢠάϥϑݪࢠɾ݁߹Λ௖఺ɾลʹରԠͤͯ͞Ͱ͖Δ ࿈݁ͳ άϥϑ ◦ ࣮ମ͸ɺྡ઀ߦྻͱݪࢠɾ݁߹ͷछྨΛද͢ଟ࣍ݩ഑ྻͷ૊ ◦ ؀΍ࢬ෼͔Εͱ͍ͬͨߏ଄ͷ৘ใΛ໌ࣔతʹදݱͰ͖Δ • ෼ࢠάϥϑͷग़ྗํ๏ ◦ Ұׅੜ੒ྡ઀ߦྻͳͲͷ਺஋σʔλΛੜ੒ ◦ ஞ࣍ੜ੒طʹಘΒΕͨ෦෼άϥϑʹݪࢠɾ݁߹Λ֬཰తʹ௥Ճ͠ͳ͕Βੜ੒ • ෼ࢠάϥϑͷ֤௖఺͸Ձ਺੍໿Λຬͨ͢ඞཁ͕͋Δ ◦ Ұׅੜ੒Ձ਺੍໿Λຬͨ͞ͳ͍ແޮͳάϥϑ͕ੜ੒͠΍͍͢ ◦ ஞ࣍ੜ੒௥Ճ͢Δݪࢠɾ݁߹ʹ੍໿Λ͔͚Δ͜ͱͰ༗ޮͳάϥϑΛ ੜ੒͠΍͍͢ ෼ࢠάϥϑʹΑΔදݱ CC(=O)Nc1cccc1

Copyright © Elix, Inc. All rights reserved. 8 • ෼ࢠΛߏ੒͢Δ֤ݪࢠͷछྨͱҐஔ ࣍ݩ࠲ඪ Λه࿥ͨ͠఺܈σʔλ ◦ ෼ࢠߏ଄ͷίϯϑΥϝʔγϣϯͳͲɺཱମతͳ৘ใΛදݱ͠΍͍͢ • ࣍ݩ࠲ඪͷग़ྗํ๏ ◦ Ұׅੜ੒఺܈ΛҰ౓ʹੜ੒ ◦ ஞ࣍ੜ੒طʹಘΒΕͨ఺܈σʔλʹ৽ͨͳݪࢠΛ֬཰తʹ௥Ճ͠ͳ͕Βੜ੒ • ఺Ͳ͏͠ͷڑ཭Λར༻ͯ͠ɺ఺܈σʔλ͔Β෼ࢠάϥϑΛߏ੒Ͱ͖Δ ◦ ఺܈σʔλ͔Βߏ੒ͨ͠෼ࢠάϥϑ͸Ձ਺੍໿Λຬͨ͢ඞཁ͕͋Δ ࣍ݩ࠲ඪʹΑΔදݱ CC(=O)Nc1cccc1

Copyright © Elix, Inc. All rights reserved. 9 ਂ૚ߏ଄ੜ੒ثͰར༻͞Ε͍ͯΔయܕతͳϞσϧͷछྨ͸ҎԼͷͱ͓Γ • ࣗݾճؼܕϞσϧ • ม෼ΦʔτΤϯίʔμ 7"& • ఢରతੜ੒ωοτϫʔΫ ("/ • ϑϩʔϕʔεϞσϧ • ֦ࢄϞσϧ • ΤωϧΪʔϕʔεϞσϧ ҎԼɺ۩ମతͳਂ૚ߏ଄ੜ੒ثΛڍ͛ͳ͕Β֓ཁΛ঺հ͢Δ ϞσϧͷछྨʹΑΔਂ૚ߏ଄ੜ੒ثͷ෼ྨ

Copyright © Elix, Inc. All rights reserved. 10 • ݱࡏͷঢ়ଶΛೖྗ͢Δͱɺঢ়ଶΛमਖ਼͢Δૢ࡞ͷ֬཰Λࢉग़Ͱ͖ΔϞσϧ ➔ αϯϓϦϯάͨ͠ૢ࡞Ͱݱࡏͷঢ়ଶΛ܁Γฦ͠मਖ਼͢Δ͜ͱͰੜ੒ • ྫ ◦ จࣈྻ$IFN54<> 3&*/7&/5<> ▪ 4.*-&4ݴޠϞσϧ ڧԽֶशͰॴ๬ͷ෺ੑɾ׆ੑΛ࣋ͭ ෼ࢠΛੜ੒ ◦ ෼ࢠάϥϑ%(.(<> ▪ ݪࢠछͷαϯϓϦϯάͱ݁߹छɾҐஔͷαϯϓϦϯάΛ܁Γฦ͢ ◦ ࣍ݩ࠲ඪ(4DI/FU<> ▪ ݪࢠछͷαϯϓϦϯάͱ഑ஔ͢ΔҐஔͷαϯϓϦϯάΛ܁Γฦ͢ ࣗݾճؼܕϞσϧ Cl c 1 c c c c ೖྗ ੜ੒్த ࣗݾճؼܕ Ϟσϧ c: 40 % C: 7 % n: 10 % ộ [EOS]: 0.2% ग़ྗ ֤ૢ࡞ͷબ୒֬཰ Cl c 1 c c c c c मਖ਼͞Εͨೖྗ αϯϓϦϯά <>9:BOH FUBM4DJ5FDIOPM"EW.BUFS r <>.0MJWFDSPOB FUBM+$IFNJOGPSN r <>:-J FUBMBS9JW QSFQSJOU BS9JW <>/(FCBVFS FUBM/FVS*14

Copyright © Elix, Inc. All rights reserved. 11 • ௿࣍ݩͷ਺஋ϕΫτϧ જࡏม਺ ͔ΒαϯϓϧΛੜ੒͢ΔϞσϧ ◦ Τϯίʔμαϯϓϧ ➔ જࡏม਺ ◦ σίʔμજࡏม਺ ➔ αϯϓϧ • αϯϓϧ͔ΒٻΊͨજࡏม਺͔Βɺݩͷαϯϓϧ͕࠶ߏ੒͠΍͘͢ͳΔΑ͏܇࿅ ➔ જࡏม਺ʹ܇࿅σʔληοτͷಛ௃͕൓ө͞ΕΔ • ྫ ◦ จࣈྻ$IFNJDBM7"&<> ▪ 4.*-&4จࣈྻΛೖग़ྗʹ༻͍ͨγϯϓϧͳ7"& ◦ ෼ࢠάϥϑ+VODUJPO5SFF7"&<> ▪ ෦෼ߏ଄ͷͭͳ͕ΓΛදݱ͢ΔδϟϯΫγϣϯ໦ͱ෼ࢠάϥϑͦΕͧΕ ʹର͢Δ7"&Ͱߏ଄ੜ੒ ม෼ΦʔτΤϯίʔμ 7"& ೖྗ ࠶ߏ੒͞Εͨ ೖྗ જࡏม਺ Τϯίʔμ σίʔμ <>3(ÓNF[#PNCBSFMMJ FUBM"$4$FOU4DJ r <>8+JO FUBM*$.- 1.-3

Copyright © Elix, Inc. All rights reserved. 12 • ௿࣍ݩͷ਺஋ϕΫτϧ જࡏม਺ ͔ΒαϯϓϧΛੜ੒͢ΔϞσϧ ◦ δΣωϨʔλજࡏม਺ ➔ αϯϓϧ ◦ σΟεΫϦϛωʔλੜ੒αϯϓϧ͔܇࿅αϯϓϧ͔Λ൑ఆ • ೋͭͷωοτϫʔΫΛڝ͍߹ΘͤΔΑ͏ʹ܇࿅ ➔ δΣωϨʔλ͕܇࿅αϯϓϧΒ͍͠ߏ଄Λੜ੒Ͱ͖ΔΑ͏ʹ • ஞ࣍తʹੜ੒͢Δ৔߹͸ڧԽֶशͱซ༻͢Δ͜ͱ͕ଟ͍ • ྫ ◦ จࣈྻ03("/*$<> ▪ ݴޠϞσϧʹΑΔδΣωϨʔλΛڧԽֶशͰ܇࿅ ◦ ෼ࢠάϥϑ($1/<> ▪ ෼ࢠάϥϑੜ੒ͷࣗݾճؼܕϞσϧΛڧԽֶशͰ܇࿅ ఢରతੜ੒ωοτϫʔΫ ("/ જࡏม਺ δΣωϨʔλ ੜ੒ αϯϓϧ ܇࿅ αϯϓϧ ܇࿅ σʔληοτ σΟεΫϦϛωʔλ 0.87 ೖྗ͕ ܇࿅αϯϓϧ Ͱ͋Δ֬཰ <>#4BODIF[-FOHFMJOH FUBM$IFN3YJW QSFQSJOU DIFNSYJWW <>+:PV FUBM/FVS*14

Copyright © Elix, Inc. All rights reserved. 13 • જࡏม਺ʹෳ਺ͷՄٯͳม਺ม׵Λద༻ͯ͠αϯϓϧΛੜ੒͢ΔϞσϧ ◦ જࡏม਺ͷ෼෍͸ɺαϯϓϧ͠΍͘͢͢ΔͨΊ୯७ͳ΋ͷʹઃఆ ◦ ܇࿅αϯϓϧ͕Ͳͷఔ౓Ϟσϧ͔ΒಘΒΕ΍͍͔͢ ໬౓ Λਖ਼֬ʹܭࢉͰ͖Δ ◦ ม਺ม׵ͷύϥϝʔλʹχϡʔϥϧωοτϫʔΫΛར༻ ◦ ͲͷΑ͏ͳม਺ม׵Λར༻͢Δ͔ʹΑͬͯόϦΤʔγϣϯ͕͋Δ • ܇࿅αϯϓϧʹର͢Δ໬౓Λ࠷େԽ͢ΔΑ͏ʹ܇࿅ • ྫ ◦ ෼ࢠάϥϑ(SBQI/71<> ▪ ݪࢠɾ݁߹ͷछྨΛද͢ଟ࣍ݩ഑ྻΛੜ੒͢ΔछྨͷϑϩʔϕʔεϞσϧ Λ૊Έ߹Θͤͯɺ෼ࢠάϥϑΛҰׅੜ੒ ϑϩʔϕʔεϞσϧ ੜ੒ αϯϓϧ જࡏม਺ ộ ộ Մٯͳ ม਺ม׵ <>,.BEIBXB FUBMBS9JW QSFQSJOUBS9JW

Copyright © Elix, Inc. All rights reserved. 14 • (BVTTܕϊΠζ͔ΒϊΠζΛஞ࣍తʹআڈ͢Δ͜ͱͰαϯϓϧΛੜ੒͢ΔϞσϧ ◦ αϯϓϧʹͩΜͩΜϊΠζ͕ͷΔ ֦ࢄ͢Δ ͜ͱͰ݁Ռతʹ(BVTTܕϊΠζ ͕ಘΒΕͨͱߟ͑Δ ◦ ֦ࢄͷ֤ஈ֊Ͱαϯϓϧʹ͔͔͍ͬͯΔϊΠζͷྔΛਪఆ͢Δͷʹ ωοτϫʔΫΛར༻ • ϊΠζΛఴՃͨ͠܇࿅αϯϓϧ͔ΒɺఴՃ͞ΕͨϊΠζͷྔΛ͏·͘ਪఆ Ͱ͖ΔΑ͏ʹωοτϫʔΫΛ܇࿅ • ྫ ◦ ࣍ݩ࠲ඪ& &%.<> ▪ & ରশੑ ฒਐɾճసɾ൓సʹؔ͢Δରশੑ Λ֦࣋ͬͨࢄϞσϧʹ ΑΓ఺܈Λੜ੒͢Δ͜ͱͰɺ࣍ݩߏ଄ΛҰׅੜ੒ ֦ࢄϞσϧ <>&)PPHFCPPN FUBM*$.- 1.-3 ੜ੒ αϯϓϧ (BVTTܕ ϊΠζ ộ ộ ϊΠζͷ আڈ 𝜺! 𝜺!"# 𝜺#

Copyright © Elix, Inc. All rights reserved. 15 • σʔλੜ੒෼෍ͷ୅ΘΓʹαϯϓϧʹର͢ΔΤωϧΪʔΛωοτϫʔΫ ͰϞσϧԽ͢Δ͜ͱͰɺσʔλੜ੒෼෍Λؒ઀తʹϞσϧԽ͢Δ ◦ ΤωϧΪʔͷ௿͍αϯϓϧ͕ੜ੒͞Ε΍͍͢ ◦ ΤωϧΪʔͷઃܭʹΑͬͯ͸ɺ෺ੑɾ׆ੑͷ୯໨తɾଟ໨త࠷దԽ ΋Մೳ • ੜ੒αϯϓϧʹରͯ͠͸ΤωϧΪʔΛߴ͘͠ɺ܇࿅αϯϓϧʹରͯ͠͸ ΤωϧΪʔΛ௿͘͢ΔΑ͏ʹ܇࿅ ➔ ܇࿅αϯϓϧΒ͍͠ߏ଄͕αϯϓϦϯά͞Ε΍͘͢ͳΔ • ྫ ◦ ෼ࢠάϥϑ(SBQI.<> ▪ ݪࢠɾ݁߹ͷछྨΛද͢ଟ࣍ݩ഑ྻΛੜ੒͢ΔΤωϧΪʔ ϕʔεϞσϧͰ෼ࢠάϥϑΛҰׅੜ੒ ΤωϧΪʔϕʔεϞσϧ <>.-JV FUBMBS9JW QSFQSJOU BS9JW 𝐸 ੜ੒ αϯϓϧ ܇࿅ αϯϓϧ ΤωϧΪʔ ϕʔε Ϟσϧ ΤωϧΪʔ Ҿ্͖͛ ΤωϧΪʔ Ҿ͖Լ͛

Copyright © Elix, Inc. All rights reserved. 16 σʔληοτɾ܇࿅ํ๏ɾϞσϧͷ޻෉Ͱɺੜ੒͞ΕΔ෼ࢠߏ଄͕ద౰ͳ৚݅Λຬͨ͢Α͏ʹ੍ޚͰ͖Δ ੜ੒ߏ଄ͷ੍ޚ <>4;IFOH FUBM+$IFNJOGPSN r • ॴ๬ͷࠎ֨Λ ͋Δఔ౓ ༗͢Δߏ଄ͷੜ੒ ◦ సҠֶशͷར༻ ▪ ॴ๬ͷࠎ֨ΛؚΉσʔληοτͰ ϑΝΠϯνϡʔχϯά͢Δ͜ͱͰ౰֘ͷ ࠎ֨ΛؚΉߏ଄͕૿Ճ<> ◦ ߏ଄ม׵Ϟσϧͷར༻ ▪ ߏ଄Λೖྗ͢Δͱɺม׵͞Εͨߏ଄͕ ग़ྗ͞ΕΔϞσϧ ▪ ڐ༰͞ΕΔೖग़ྗͷύλʔϯΛద੾ʹ ઃఆͯ͠܇࿅͢Ε͹ɺೖྗߏ଄ͷࠎ֨Λ ͋Δఔ౓ݻఆͯ͠ߏ଄ੜ੒Ͱ͖Δ • ॴ๬ͷ෺ੑɾ׆ੑΛ࣋ͭͱ༧૝͞ΕΔߏ଄ͷੜ੒ ◦ ༧ଌϞσϧͷಉ࣌܇࿅ ▪ 7"&ͳͲͰ જࡏม਺͔Β෺ੑɾ׆ੑΛ ༧ଌ͢ΔϞσϧΛར༻ͨ͠જࡏม਺ͷ ࠷దԽ ◦ ڧԽֶशͷར༻ ▪ ࣗݾճؼܕϞσϧͳͲͰ ࠷దԽ͍ͨ͠ ෺ੑɾ׆ੑΛใुͱͯ͠ར༻

Copyright © Elix, Inc. All rights reserved. 17 • ਂ૚ߏ଄ੜ੒ث ෼ࢠߏ଄ͷσʔλੜ੒෼෍ΛχϡʔϥϧωοτϫʔΫͰϞσϧԽͨ͠΋ͷ • ೖग़ྗͷ෼ࢠߏ଄ͷදݱ จࣈྻ ෼ࢠάϥϑ ࣍ݩ࠲ඪ • Ϟσϧͷछྨ ࣗݾճؼܕϞσϧ 7"& ("/ϑϩʔϕʔεϞσϧ ֦ࢄϞσϧ ΤωϧΪʔϕʔεϞσϧ • ੜ੒ߏ଄ͷ੍ޚ ॴ๬ͷ෺ੑɾ׆ੑΛ࣋ͭͱ༧૝͞ΕΔߏ଄ͷੜ੒ ॴ๬ͷࠎ֨Λ ͋Δఔ౓ ؚΉߏ଄ͷੜ੒ ·ͱΊ

Elix, Inc. https://elix-inc.com/ Copyright © Elix, Inc. All rights reserved. 18