20200803 成長可能性に関する説明資料 final...2020/08/03 · spk-9001: vnhb spk-8011,...
TRANSCRIPT
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2020 8
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5.
• Appendix
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Modalis Therapeutics CRISPR
5
2016 1
CEO
16-5 Y’s 4F
Modalis Therapeutics Inc. (51 Moulton st. Cambridge MA)
CRISPR
1,300,000
41.1
25,100,000 ( 2,903,200 )
17 ( 2020 5 31 PhD 7[ ]4 [ ]13
J-STARTUP 2018
2016 1
2016 4 EdiGENE Inc.Modalis Therapeutics Inc.
2017 4 CRISPR-GNDM
2017 12
2017 12
2018 6 J-Startup
2019 1
2019 3
2019 3
2019 8
Modalis Therapeutics Corporation
EdiGENE Inc. Modalis Therapeutics Inc.
2019 9 2
2019 11 CRISPR-GNDM
2020 4 Editas Medicine, Inc. CRISPR/Cas9
-
Modalis Therapeutics 6
6
next big thing••
CRISPR
••
• 3• 2 380
•• 2019.12
•• 5 2
•
-
)
7
• ••
• ( ),
•PRISM
BioLab
CEO
• ( ) CEO, ( ) , ( PwC Strategy &),
( ) •
••
MD PhD: SVP, Chief Technology Officer
• ,
• Joslin Diabetes Center( ),
• Medical Patent Research ( )• ) ( )
, ( )
MBA: SV, Chief Financial Officer
• ( ), ()(CFO), Argenes( ), ,
•
Joseph S. McCracken• Roche , Genentech,
Sanofi-Aventis
-
8
*1: P21*2:
GNDM GNDMGMP
12 24 3 10
*2
*2
*1
-
9
MDL-201
MDL-202
MDL-204
MDL-205
MDL-206
*I II IIIIND
MDL-101
MDL-102
MDC1A
*:
380
-
10
-
0 1865
645
46
141
213
146
2016/12 2017/12 2018/12 2019/12
2
6
10131
1
4
2016/12 2017/12 2018/12 2019/12
2019
11
US
)PhD7
(JP
)PhD5)PhD7)PhD2
33 109
218
304
2016/12 2017/12 2018/12 2019/12
(
-
12
( ) 2018/12 2019/12 2020/12 1Q1,214,738 3,874,974 3,703,9381,205,143 3,857,235 3,682,880
757 48,954 51,7639,011 14,499 14,199
1,224,508 3,938,428 3,769,90122,728 95,885 45,44650,000 1,300,000 1,300,000
1,371,735 2,621,735 2,621,735219,640 79,112 197,398
1,202,094 3,842,623 3,724,3361,201,779 3,842,542 3,724,4551,224,508 3,938,428 3,769,901
( ) 2018/12 2019/12 2020/12 1Q65,297 644,500 13,000
279,420 487,305 129,164217,927 303,680 81,317
61,493 183,625 47,846214,123 157,194 116,164
983 1,119 98250 11,962 858
213,390 146,351 116,924213,390 146,351 116,924
O 4,518 5,823 1,362217,909 140,528 118,286217,909 140,528 118,286
( )
( )
A
:
42%
2%8%
O O12%
VC36%
A
:
37%
2%
8%
O O11%
VC32%
10%
-
13
-
=10,000* 7,000# 80%†
14
A B C D95%† ¶
600
4 ¶
: *21st Century Cure Act, #NIH GARD †innovation.org ¶GlobalGenes.orgActive therapeutics of 491 NME, 106 BLA, 17 cellular and gene therapy products @FDA as of 2019.7.22 Source from KEGG
-
2 ON/OFF
15
A
B
X Y Z• 37
• 200
DNA
• 30 DNA2
ONOFF
-
16
AAGTCAACTAGC
ON OFF
OFF ON
-
DNA DNA
17
AAGTCAACTAGC AAGTCATCTAGC
-
DNA
18
AAGTCAACTAGC AAGTCATCTAGC
AAGTCATCTAGC
DNA
-
Monogenic Diseases( )Monogenic Disease
19
Monogenic Disease =1
1
2
3
4
5
6
Monogenic Diseases
-
20
7,000
3,500
2,200
(1989~ )
: Discovery Medicine Modalis Tx
TAM
: The Journal of Gene Medicine (2019) Modalis Tx
66.8%11.7%
Cancer diseases
Monogenic diseases
Cardiovascular diseases
Infectious diseases
Others
Healthy volunteers
Neurological diseases
Gene marking
Ocular diseases
Inflammatory diseases
-
GTx PoP PoC
21
(Proof of Mechanism)
(Proof of Principal)
(Proof of Concept)
PhIIb
PhIIa
PhI
pre
clinic
al
CRISPR-GNDM
pre
clinic
al PhI
: Nature Biotechnology volume 30, p596–599 (2012) Modalis Tx
GTx
-
GTxGTx
22
: Evaluate Ltd 2019 8 CAGR 2018 2024 2019 2024
27 4441,371
3,060
5,820
10,062
14,906
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
2018 2019 2020 2021 2022 2023 2024
CAGR 185.7%14.9 Billion$
(2024 )
2,0402,693
3,4964,336
5,795
8,051
10,651
0
2,000
4,000
6,000
8,000
10,000
12,000
2018 2019 2020 2021 2022 2023 2024
120,563135,722
149,757163,136
176,325187,211
197,215
0
50,000
100,000
150,000
200,000
250,000
2018 2019 2020 2021 2022 2023 2024
399,725399,874
416,784 444,066475,819 508,220
545,585
0
100,000
200,000
300,000
400,000
500,000
600,000
2018 2019 2020 2021 2022 2023 2024
CAGR 31.7%10.7 Billion$
(2024 )
CAGR 8.5%197.2 Billion$
(2024 )
CAGR 5.3%545.6 Billion$
(2024 )
US $ (mln)
US $ (mln) US $ (mln) US $ (mln)
Gene Therapy
(DNA&RNA therapeutics) (Monoclonal antibody) (Small molecule chemistry)
GTx
-
GTx M&A2018 2019 M&A /
23
/ /
2019/12 3.0 billion$AT132: X (XLMTM)AT845:AT702, AT751, AT753: (DMD)
2019/10 3.0 billion$( )SPIRO-2101: SPIRO-2102:
2019/6 1.0 billion$ (DMD)1 (DM1)
2019/3 165 million$ MYO-101: 2E (LGMD 2E)MYO-102: 2D (LGMD 2D)
2019/3 800 million$NSR-REP1: NSR-RPGR: X (XLRP)NSR-ABCA4:
2019/2 4.3 billion$SPK-9001: BSPK-8011, SPK-8016: A SPK-7001: ( )
2018/5 8.7 billion$ AVXS-101 IT : SMA Type 2AVXS-201: RTTAVXS-301: ALS
: ModalisTx
GTx M&A
VERTEX
SAREPTA Tx
Biogen
Roche
NOVARTIS
AUDENTES Tx
ROIVANT
Exonics Tx
Myonexus Tx
Nightstar Tx
Spark Tx
AveXis
-
CRISPRRNA
24
CRISPR
ZFN TALENCas9
gRNA
ZFN TALEN
RNA DNA( )
CRISPR
DNA( )
-
0
10
20
30
40
50
60
70
80
90
100
Jan-
04
Jan-
05
Jan-
06
Jan-
07
Jan-
08
Jan-
09
Jan-
10
Jan-
11
Jan-
12
Jan-
13
Jan-
14
Jan-
15
Jan-
16
Jan-
17
Jan-
18
Jan-
19
CRISPR
25
RNAi
iPS
CRISPR
67%
23%
10%
86%
7%7% JPNUS
RNAi Oct 2006
iPS Oct 2012s
Google ( ) 3 (2005-2015)
CRISPR
: Google Trends ModalisTx: iPS 2012 10 100
iPS CRISPR RNAi
-
CRISPR = CRISPR-GNDM
26
CRISPR-GNDM (Guide Nucleotide-Directed Modulation) platform
dCas9( )
ON/OFFgRNA
CRISPR-GNDM
-
CRISPR-GNDMAAV
27
1 2 3
AAV
AAV GNDM
4
U6 Cas9gRNA pA
+GNDM
-GNDM
GNDM
CRISPR-GNDM
-
GNDMgRNA
28
gRNA
ON
OFF
dCas9
CRISPR-GNDM
-
• : 1 / 30,000*• : • : • :
••
• : LAMA2
MDC1A( 1A )LAMA2
: Flores et al, Frontiers in Molecular Neuroscience vol 13 (2020) *Ophanet
MDL-101
29
-
GNDM MDC1ALAMA1 ON
dCas9
CRISPR-GNDM-a targeting LAMA1
RNA
LAMA2
MDL-101
ON
LAMA1
30
-
Small 3.5kb Large
780
520 /siRNA/ASO
GNDMGTx
31
A
B
C
Gain ofMalfunction
Loss ofFunction
400
: Discovery Medicine Modalis Tx
GNDM
3,500
GNDM2,200
GNDM
1
CRISPR-GNDM
-
32
-
Modalis
33
e.g.
e.g.
:
-
34
+
+**
( )
-
Broad CRISPR
CART
Modalis Tx
GNDM IP
35
Editas Medicine
MIT
Allerganabbvie
JUNO TxBristol-Myers Squibb
Beam Tx
-
DMD2024 3,000
36
Evaluate Ltd Modalis Tx 2019 8 *: Orphanet2019 2024 DMD MDC1A MDC1A DMD 1/3~1/10
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
2018 2019 2020 2021 2022 2023 2024SRP-9001 (AVII) Raxone (SANTH) Exondys 51 (AVII)Golodirsen (AVII) Vamorolone (SANTH) Casimersen (AVII)Translarna (PTC Therapeutics) Suvodirsen (WAVE Life Sciences) Edasalonexent (Catabasis Pharmaceuticals)NS-065 (NIPSH) Other
US $ (mln)
3,000
DMD
: 1/3,500-1/9,300 *
-
$1,484MEDIT-US
CART 3 $25M+ $22M + $700M
LCA105
$90M + MS
$1,099MNTLA-US
CART
$10M + $20M+ $20M+ $230.3M / 1 product+ 15%$13M
& Novartis DDS 14
Option for10& Except some
$75M+ $135M / 1 product+ 10%$50M @ IPO
$3,654MCRSP-US
Option to 6 targets$75M+ $30M+ $420M MS / 1 target +
JV 50:50 & $70M
BAYER CASEBIA$45M + $255M
CASEBIA CRISPR$15M $20M when get IP
CRISPR 3
37
$747M
$293.3M
$260M
$525M
$405M
Modalis Tx 6/12 *
Editas Medicine
Intellia Tx
CRISPR Tx
JUNO TxBristol-Myers Squibb
Allerganabbvie
NOVARTIS
REGENERON
VERTEX
BAYER
CASEBIA
-
CRISPR
38
6/3 B=Billion
Canonical( = )
Non-canonical( )
$3.9B
$1.5B
$1.4B
$1.1B~$1B
~$1B
?
Dx Platformer Tx
CRISPR
Intellia TX
CRISPR Tx
Editas
Beam Tx
KSQ
ExonicsTx
CASEBIA TX
BlueRockTx
VERTEX
BAYER
SHERLOCK BIOSCIENCES
Mammoth Biosciences
-
39
-
40
MDL-201
MDL-202
MDL-101
MDL-102
MDL-204
2,200
MDL-205
100
MDL-206380
-
*
41
*
MDL-201
MDL-202
MDL-204
MDL-205
2019/12 2020/12 2021/12
2019 1Q 2021
IND
2019 3Q 2021
IND
2019 3Q 2020
2019 4Q
CNS
CNS
MDL-206
CNS2020 2Q
380
-
*
42
*
MDL-101
MDL-102
2019/12 2020/12 2021/12
2020 2022
IND
2021
MDC1A( )
CNS
CNS
2021
MDL-103
-
GNDM
••
••
••
43
-
CRISPR
()
( )
44
6 Modalis Tx 6/151990
45876,276
45651,301
HMT
DWTI
Delta-Fly Pharma
GNI
JCR
J TEC
-
Appendix
45
-
Modalis24
46
• 2022 1 US
•
•
-
47
-
DNA( ) DNA( ) ( )
48
-
49
2 strategies for gene therapy1. Ex vivo 2. In vivo
DNA
-
( )
- ZFN TALEN CRISPR CRISPR CRISPR
-
1
AAV/LNP AAV AAV AAV/LNP AAV/LNP AAV
(1 )
~3.5kb
GNDM GTx
50
: ModalisTx
CRISPR-GNDM
AUDENTES TxSpark Tx
AveXisSAREPTA Tx
REGENXBIO
Sangamo TxEditas Medicine
Intellia Tx
CRISPR Tx
Beam Tx
-
1/2
51
Page Word Explanation
P9 MDC1A1A α2 Lama2
P21 GTx Gene Therapy
P24 ZFNDNA
P24 TALENZFN TAL effector TALE
DNA
P24 gRNA RNA CRISPR-Cas RNA
P26 dCas9DNA Cas9 Cas9
P27 AAV
P31 Gain of Malfunction
P31 Loss of function
-
2/2
52
Page Word Explanation
P31 siRNA 21-23 RNA RNA(mRNA)
P31 ASO Antisense oligo( ) DNA RNAsiRNA
P36 Duchenne muscular dystrophy
P41 CNS Central nervous system
P48 () DNA
P48
P49 Ex vivo / In vivo Ex vivoIn vivo