バイオベンチャーの現状と課題 - METI

1 - . - . - . 2.. 10 .. 8PJ .. VC .. 27 471 3. M&A .. 30 6 30 17 . DATA BOOK 2017 4.. PMDA PMDA. Phase3 .. 5.. / . 1900 . ~50 . 1899 .. ~10 . 1982 .. ~10 . 2001 .. ~1000 . 1983 /Phase1 .. Exondys51 . ~10 Sarepta . DNA/RNA 2016 . Kymriah/Yescarta Kite . ~500 . 2017 Gilead . ~10 Luxturna Spark . DNA 2018 .. 6.. FDA 2016 . Active Ingredient Approval Date Approval Year . Nusinersen 12/23/2016 2016 Ionis Pharmaceuticals . Rucaparib 12/19/2016 2016 Pfizer . Crisaborole 12/14/2016 2016 Anacor Pharmaceuticals . Bezlotoxumab 10/21/2016 2016 Bristol-Myers Squibb . Olaratumab 10/19/2016 2016 ImClone Systems . Eteplirsen 9/19/2016 2016 Sarepta Therapeutics . Lixisenatide 7/27/2016 2016 Zealand Pharma . lifitegrast ophthalmic solution 7/11/2016 2016 Sunesis Pharmaceuticals . sofosbuvir and velpatasvir 6/28/2016 2016 Gilead Sciences . obeticholic acid 5/27/2016 2016 C2N Diagnostics . Daclizumab 5/27/2016 2016 PDL BioPharma.

2 Atezolizumab 5/18/2016 2016 Genentech . Pimavanserin 4/29/2016 2016 ACADIA Pharmaceuticals . Venetoclax 4/11/2016 2016 Abbott Laboratories/Roche . defibrotide sodium 3/30/3016 2016 Crinos . Reslizumab 3/23/2016 2016 Cel-Sci . Ixekizumab 3/22/2016 2016 Eli Lilly . Obiltoxaximab 3/18/2016 2016 EluSys Therapeutics . Brivaracetam 2/18/2016 2016 UCB . elbasvir and grazoprevir 1/28/2016 2016 Merck . 2016 FDA 20 5 15 . 7.. 4 .. 10 4 6. 2017 10 .. 2017 7 . 8.. 900.. 782. 800 * . 700 * . 582. 600. 500. 532. 400 336. 300 372 250. 191 210. 200 136 276. 60. 100 171. 131 5 20. 0. Phase 1 Phase 2 Phase 3 . * 1 . 2010 2011 . 5~20% / .. SM Paul et al., How to improve R&D productivity: the pharmaceutical industry s grand challenge , Nature Review Drug Discovery 9, 203-214 (2010) 9. M&A IPO . NASDAQ IPO M&A . [$M] 29,734. 30,000. IPO . M&A . 25,000. 22,422. 20,000. 15,000. 10,000 8,753. 6,245 6,902. 6,222. 4,485 4,197.

3 5,000 3,081 2,596. 1,894 2,178. 363 833. 0. 2009 2010 2011 2012 2013 2014 2015. 2009 2010 2011 2012 2013 2014 2015. IPO 4 11 13 21 36 70 53. M&A 103 117 94 112 103 126 85. IPO M&A M&A 1 . IPO . Industry Eye 15 , . (2015) 10.. 2008 2014 / . 343 755. 71. 76 57 28%. 86 . 51% 51 Phase3. 73 Phase2. Phase1. 47 . 187 . 28. 72%. 63. 49%. 281. 78.. 11.. 5 (11 -16 ) FDA . (104 ) (81 ).. 66 38 37 44.. 44 22 18 19.. 53 51 30 51.. 12.. 2016 . 16% . (2006-16 ). Biogen 37% +584%. Celgene 82% +402%. BioMarin +505%. 100%.. 13.. Gilead Sciences . 25,000,000 Sovaldi/Harvoni Kite CAR-T.. 20,000,000. Truvada HIV. Vistide AIDS Hepsera B . CMV Emtriva HIV Sovaldi/Harvoni C.. 15,000,000. [$M]. Tamiflu Roche Pharmasset . Tamiflu Sovaldi . 1B . 10,000,000. Viread Truvada .. 5,000,000 . 0. M&A .. Gilead Sciences, Inc. 14.. NBI Top10 3 20 .. 20,000,000. 15,000,000. ( Genentech).. 10,000,000. 5,000,000. 0. Amgen Celgene Gilead Biogen Regeneron Shire Vertex Alexion Incyte Illumina (Genentech).

4 15.. - . - . - . 16. 3 .. 30 .. 2 .. 15 .. 17.. / / .. PSS .. HD . DWTI .. HMT . JCR . DNA .. 30 UMN .. J-TEC 3D .. 2015 6 18.. 10 / . 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017.. 1 4974 20,982 -215 20,278 560 18,913 426 19,325 553 18,737 1,097 19,578 1,547 20,564 1,691 23,905 1,954 25,969 2,302 29,729 2,667 29,375 3,202. 2 4587 - - - - - - - - - - 269 -18 678 160 818 201 2,474 1,391 4,328 2,548 4,895 2,490. 3 4565 740 -6,651 709 -6,270 152 -3,667 919 -1,854 716 -1,876 862 -1,962 1,958 853 2,069 756 3,671 1,043 8,151 1,075 18,901 12,389. 4 4592 - - - - - - - - - - - - - - 204 -584 3,229 2,248 1,174 -1,125 949 -1,932. 5 7774 J-TEC 103 -973 111 -1,071 114 -1,102 211 -1,067 351 -1,145 473 -1,107 563 -1,103 1,008 -1,025 1,321 -688 1,430 -722 2,135 312. 6 4564 804 -1,349 1,973 -385 3,327 27 5,257 318 5,361 223 6,223 1,184 3,277 -1,113 1,017 -3,785 769 -1,962 266 -2,980 286 -3,004. 7 4571 103 -717 262 -452 353 -531 117 -492 84 -519 346 -333 373 -526 472 -1,123 675 -1,108 243 -2,082 218 -2,712.

5 8 7777 - - - - - - - - 158 -482 1,107 354 32 -999 107 -1,518 99 -1,903 141 -1,814 615 -1,240. 9 2160 274 -1,285 204 -949 81 -442 272 -269 90 -457 161 -464 183 -785 474 -378 1,016 -633 1,306 -276 - - 10 4585 - - - - - - - - 1,000 -1,075 108 -2,072 93 -4,421 1,108 -3,942 202 -3,207 71 -3,564 - - 11 4596 - - - - - - - - - - - - - - - - - - 870 -4,121 - - 12 4583 - - - - - - 463 -231 633 -7 324 -413 434 -708 186 -820 280 -1,269 252 -1,042 - - 13 2191 269 42 546 109 974 233 1,145 144 1,322 71 1,544 221 1,539 23 1,865 -293 1,909 -601 1,801 -621 - - 14 2370 1,606 -823 1,838 -667 2,900 293 3,202 334 2,674 -303 2,190 -711 2,110 -877 1,843 -1,407 1,674 -1,741 1,909 -1,681 - - 15 4576 - - - - - - - - 20 -351 112 -257 80 -208 80 -196 61 -290 168 -319 - - 16 4591 - - - - - - - - - - - - - - 151 -414 479 6 121 -532 93 -785. 17 4875 ( - - - - - - - - - - 803-10,945 6,003 -4,021 0 -9,223 0 -8,822 0-10,881 - - 18 4563 1,720 -2,040 951 -2,685 585 -2,610 286 -2,010 243 -2,100 444 -1,785 491 -1,363 909 -2,273 430 -4,171 514 -4,763 - - 19 4572 - - 500 -296 687 -344 571 -398 592 -393 510 -457 771 -300 611 -634 1,569 472 811 -423 - - 20 4582 - - - - - - 1,449 -612 1,882 -2,066 1,955 -1,700 1,532 -1,680 1,955 -1,303 1,933 -2,551 2,368 -2,127 - - 21 4586 - - - - - - - - 741 -434 87 -567 68 -604 26 -1,003 37 -999 22 -1,342 - - 22 4584 - - - - - - - - - - 207 -316 60 -358 301 -512 321 -824 1,160 -820 1,089 -1,184.)

6 23 4579 - - - - - - 1,186 -1,345 684 -1,916 28 -2,636 228 -2,137 153 -2,183 145 -1,864 705 -759 - - 24 4575 - - - - 161 -245 148 -480 0 -1,420 0 -1,103 0 -651 0 -483 60 -283 105 -399 109 -406. 25 7776 - - - - 87 -785 66 -1,204 86 -1,418 75 -846 105 -534 86 -601 193 -568 100 -1,413 - - 26 4588 - - - - - - - - - - - - 1 -665 28 -827 121 -951 178 -861 - - 27 4552 JCR 8,544 -163 11,871 281 12,082 546 14,387 2,007 14,457 1,407 12,845 1,089 14,099 1,150 15,705 1,545 16,855 2,014 17,438 2,152 18,085 2,362. 28 4593 - - - - - - - - - - - - - - 279 -568 98 -1,060 77 -3,507 - - 29 4594 - - - - - - - - - - - - - - - - 821 -492 822 -988 529 -1,113. 30 4597 - - - - - - - - - - - - - - - - - - - - - - 19.. / . 4,000 2,000 . 156 (Top4 ) Agios Pharma Impax Laboratories 8%. 18%. 24%. 24% 14%. 15% 60% 26% 55%. 77%. 81 Swedish Orphan Evotec 26% 21%. 30%. 66% 3% 69% 2% 76%. 42 Medy-Tox 12% 2%. 37%. 60% . 15% 61%.

7 85%. 2%. 30 . 10%. 18%. 0%. 6%. 75%. 89%.. NBI Growth INDEX Value/YIELD/GARP Others 20.. 1-Year Revenue Growth Aggressive Growth . 40 Growth . Growth P/E P/E 40 . Growth . Growth 1-Year Revenue Growth 75 . Aggressive Aggressive Growth P/E . Growth P/E 50 Aggressive Growth . / . Index Index . P/B Yield Deep Value . P/B 70 Value . Value P/E P/E 70 . Value . Value Price-to-Book (P/B) Yield P/B. 90 Deep Value . Deep Value Price-to-Earnings (P/E) P/E 90 . Deep Value . 90% . Yield Yield ( ) . Index GARP . GARP / . GARP GARP. / .. Others Others . Factset . 21.. (%). 0%. 5%. 20%. 25%. 10%. 15%. 30%. 35%. 40%. 45%. 50%. (30 ).. * .. (HV)* 2012 .. 22. / .. 2014 1Q 23 . 2014 2Q 0 0 . A . 2015 3Q 14 . 2017 1Q . 2005 1 .. 2 .. B *.. 1b .. - 10 . 2017 17/3 . - . - . * . 23. IPO( ) PO( ) . IPO PO 2011 15 ). 50% 50% IPO PO.. 17% 83%. ( ). *1 = 110 . 24.. Ticker ($m) ($m) EBITDA($m) ($m). 2017/9/6 Insmed Inc INSM (Common Stock) 403 / - -180 -188.

8 2017/8/10 BeiGene Ltd BGNE 175 / - - - 2017/8/9 Radius Health, Inc. RDUS Corporate Convertible 300 1 -225 -224. 2017/8/8 BioMarin Pharmaceutical Inc. BMRN Corporate Convertible 450 1,201 -107 -181. 2017/8/4 Spectrum Pharmaceuticals Inc SPPI (Common Stock) 150- 132 -43 -78. 2017/8/3 Spark Therapeutics Inc ONCE (Common Stock) 403 / 20 - -196. 2017/6/27 Repligen Corp RGEN (Common Stock) 120 / 110 24 13. 2017/6/27 bluebird bio Inc BLUE (Common Stock) 460 / 12 - -276. 2017/5/26 ImmunoGen, Inc. IMGN Corporate Convertible 100 83 -70 -106. 2017/5/23 Alnylam Pharmaceuticals Inc ALNY (Common Stock) 359 / / 59 - -414. 2017/5/17 ARGENX SE AGNX 112 / 16 -22 -23. 2017/5/5 AMAG Pharmaceuticals, Inc. AMAG Corporate Convertible 300 593 238 -45. 2017/4/27 Flexion Therapeutics, Inc. FLXN Corporate Convertible 175 0 -88 -94. 2017/4/25 Flexion Therapeutics, Inc. FLXN Corporate Convertible 201 0 -88 -94. 2017/4/25 Neurocrine Biosciences, Inc.

9 NBIX Corporate Convertible 518 6 -220 -220. 2017/4/25 Neurocrine Biosciences, Inc. NBIX Corporate Convertible 450 6 -220 -220. 2017/4/18 Audentes Therapeutics Inc BOLD (Common Stock) 86 / - - -60. 2017/3/27 Atara Biotherapeutics Inc ATRA (Common Stock) 75- - -79 -79. 2017/3/21 Regenxbio Inc RGNX (Common Stock) 87 / / / 5 -63 -63. 2017/3/17 Editas Medicine Inc EDIT (Common Stock) 104 / 6 - -97. 2017/3/9 BioCryst Pharmaceuticals Inc BCRX (Common Stock) 52 / 26 -48 -55. (Ordinary / Common 2017/3/6 Prothena Corp plc PRTA 179 / . Shares) 1 -157 -160. 2017/3/2 Kite Pharma Inc KITE (Common Stock) 410 / // 22 -259 -267. 2017/2/13 Novavax, Inc. NVAX Corporate Convertible 325 21 -187 -212. 2017/2/8 Coherus Biosciences Inc CHRS (Common Stock) 128 / / 200 -96 -104. 2017/1/23 Cascadian Therapeutics Inc CASC (Common Stock) 77 / / - -85 -76. 2016/12/15 Amicus Therapeutics, Inc. FOLD Corporate Convertible 225 16 -187 -208.

10 2016/12/7 Sangamo BioSciences Inc SGMO (Common Stock) 75- 20 - -76. 2016/12/6 bluebird bio Inc BLUE (Common Stock) 250 / 6 - -239. EBITDA . Ticker ( ). ( ) ( ) ( ). 2017/8/28 4563 / 514 -4,696 -4,776. 2017/8/9 4582 / 2,368 -2,101 -2,313. 2017/6/22 4572 / 811 -402 -289. 2017/6/8 4591 / 93 -749 -646. 2017/4/21 2160 / 1,306 -210 -513. 2017/2/22 4593 / 77 --3,338 -3,433. 2016/12/19 4563 / 430 -4,123 -4,143. 2016/12/9 4588 / 121 -934 -857. 2016/12/1 4570 CB/ 1,388 717 8 -31. 2016/11/4 4585 / 202 -1,682 -3,961. 2016/8/30 4583 / 280 -1,167 -1,282. 2016/8/5 4563 / 430 -4,123 -4,143. 2016/6/14 4586 CB/ 631 37 -923 -878. 2016/5/25 4585 / 202 -1,682 -3,961. 2016/5/24 4594 / 822 -969 -994. 2016/5/24 HMT 6090 356 914 9 -61. 2016/4/6 4582 CB/ 3,000 1,933 -2,527 -2,632. 2016/3/25 4563 / 430 -4,123 -4,143. 2016/2/12 4570 CB/ 200 729 -73 -158. 2015/12/14 4565 4,023 3,671 1,130 568. 2015/11/20 4586 / 26 -950 -1,016.