20231129_华创证券_医药行业创新药系列研究：CAR_T为系统性红斑狼疮带来治愈曙光_29页.pdf

2009 1210 2023 11 28 CAR-T SLE 100 SLE 780 20-40 SLE SLE 10 0.4%SLE SLE CAR-T SLE SLE B CAR-T B SLE B 13 7 SLE CAR-T SLE 1 CAR-T CRS ICANS 2 80%SLEDAI-2K 0 3 4/SLE 44 4 3 SLE CAR-T CAR-T SLE 23 4 IND 2024 CD19/BCMA CAR-T SLE IIT BMS CD19 CAR-T I Cabaletta Bio CD19 CAR-T SLE I/II FDA Fate therapeutics iPSC CAR-T 7 CAR-T SLE S0360520120002%()475 0.06()72,856.71 8.20()58,047.99 8.43%1M 6M 12M 5.6%-3.2%-2.9%6.8%5.4%2.9%CAR-T 2022-10-14 CAR-T 2021-11-02-14%-5%4%13%22/11 23/02 23/04 23/07 23/09 23/112022-11-282023-11-28 300 2009 1210 CAR-T SLE SLE CAR-T B CAR-T SLE SLE SLE CAR-T SLE WUCXuNnQsRmNpRsRtOrOoP8O9R7NtRpPoMtQkPnMoPlOtRuN9PrQmPxNtOmMxNmMoO 2009 1210 3.6.6.7.9 CAR-T.12 CAR-T SLE B.12.14 CAR-T.16 CAR-T.18.18 CAR-T SLE.18 CD19/BCMA.19 BMS CD19 NEX T.20 T-Charge SLE.22 Cabaletta Bio CAR.23 Fate therapeutics iPSC CAR-T SLE.24.25.26 2009 1210 4 1 SLE.6 2 SLE.6 3 SLE.7 4 SLE.7 5 SLE.7 6 SLE.7 7 SLE.8 8 SLE.8 9.9 10 SLE.9 11 SLE.9 12 SLE.10 13 SLE.10 14 SLE.11 15 SLE.11 16 BLISS-52.12 17 BLISS-76.12 18 SLE.12 19 B.13 20 CAR-T SLE B.13 21 CAR-T SLE B.14 22 CAR-T SLE SLEDAI.14 23 5 rSLE CAR-T.15 24 CAR-T 7 rSLE.15 25 CAR-T SLE.17 26 SLE.17 27 CAR-T B.18 28 SLE.19 29 SLE IIT.19 30 GC012F SLE IIT.20 31 BMS.21 32 BMS-986353.21 33 BMS-986353 SLE.22 2009 1210 5 34 BMS-986353.22 35 T-ChargeTM.22 36 YTB323 SLE I/II.23 37 YTB323 SLE SLEDAI.23 38 Cabaletta Bio.23 39 CABA-201.24 40 CABA-201 SLE I/II.24 41 FT819.24 42 FT819 B.24 43 FT819 SLE I.25 44 SLE.25 2009 1210 6 systemic lupus erythematosus SLE SLE SLE 20-40 SLE 30/10 70/10 100 SLE SLE 2020 SLE 780 1 SLE 2 SLE George C.Tsokos,Systemic Lupus Erythematosus.Jingru Tian,et al.,Global epidemiology of systemic lupus erythematosus:a comprehensive systematic analysis and modelling study CDC 2020 2018 SLE 2009(Chinese SLE Treatment and Research group CSTAR)SLE SLE 01020304050 02004006008001,000 2009 1210 7 3 SLE 4 SLE 2020 SLE 2020 SLE SLE SLE 10 97%25-30 30%SLE 5 SLE 6 SLE 2020 2020 SLE 2020 SLE 0%10%20%30%40%50%10.89%1.17%0.85%0.84%0.80%0.69%0%10%20%30%40%50%60%70%80%0%5%10%15%20%25%30%35%40%SLE 2009 1210 8 SLE SLE SLE SLE disease activity index SLEDAI 9 24:8 4 2 1 BILAG 2004 9 97 A B C D E PGA SLE 03 7 SLE SLEDAI PGA 6 0.5 PGA 1 9%712 1 PGA 2 12 2 PGA 3 20 109/L TTP 2020 Matteo Piga,et al.,Physician Global Assessment International Standardisation COnsensus in Systemic Lupus Erythematosus:the PISCOS study SLE remission 2016 APLC LLDAS LLDAS SLE 2021 Definition of remission in SLE DORIS DORIS 8 SLE SLEDAI-2K DORIS DORIS 2021 0 0.5 5mg/d LLDAS-4 1 7.5mg/d DORIS(2021)APLC(2016)SRI-4 BICLA SRI-4 II III BICLA CD22 epratuzumab 2009 1210 9 9 SLEDAI BILAG-2004 PGA SLE 4 SRI-4 4 A 2 B 0.3 BILAG BICLA A B A 1 B 0.3 Koichiro Ohmura,et al.,Which is the best SLE activity index for clinical trials?CSTAR 0.76%SLE 1982 2.5%2019 16%CSTAR SLE 2.47%SLE 2014 2.1%2019 22.9%3040%/LLDAS 5/LLDAS 2307 SLE 27 10 0.4%SLE 10 SLE 11 SLE 2020 Chiara Tani.EULAR 2021 Virtual Congress Oral Presentation at 2nd Jun SLE 0.76%2.47%2.50%2.10%16.00%22.90%0%5%10%15%20%25%2020 201943.80%24.30%13.20%5.60%1.20%0.40%0%10%20%30%40%50%120 240 1 2 5 10 2009 1210 10 12 SLE 2020 SLE 13 SLE 5/30%7.5 mg/d SLE 2020 SLE Belimumab 2011 FDA 2019 SLE 2021 SLE 2023 11 III 2009 1210 11 Anifrolumab 2021 7 FDA 2023 1.91 14 SLE GSK SLE SLE SLE SRI-4 BICLA DORIS LLDAS 15 SLE 335 SELENA-SLEDAI 8 6 160 mg 48 52 SRI-4 82.6%vs 38.1%BLISS-52 865 SLEDAI-2K 6 4 1/10 mg/kg 48 52 SRI-4 58%vs 44%BLISS-76 819 48 52 SRI-4 43.2%vs 33.5%TULIP-1 457 150/300 mg 48 52 SRI-4 37.6%vs 40.2%TULIP-2 362 300 mg 48 52 BICLA 47.8%vs 31.5%GSK DORIS LLDAS BLISS-52 BLISS-76 DORIS 5-6%LLDAS 12-15%02468101214162011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023-9M 2009 1210 12 16 BLISS-52 17 BLISS-76 Oon,S.et al.Lupus Low Disease Activity State(LLDAS)discriminates responders in the BLISS-52 and BLISS-76 phase III trials of belimumab in systemic lupus erythematosus Parodis,I.et al.Definitions of remission in systemic lupus erythematosus:a post-hoc analysis of two randomised clinical trials SLE 18 SLE JAK1 52 BICLA anti-CD20 52 SRI-4 BMS TYK2 52 SRI-4 cenerimod/Idorsia S1PR1 12 SLEDAI-2K dapirolizumab pegol/UCB anti-CD40L 48 BICLA ianalumab anti-BAFF-R 52 SRI-4 litifilimab anti-BDCA2 52 SRI-4 MIL62 anti-CD20 52 SRI-4 CAR-T CAR-T SLE B B B SLE SLE antinuclear antibodies ANA DNA RNA B na ve B plasmablast ds-DNA long-lived plasma cell RBP na ve B CD19 BCMA CD19 0%10%20%30%40%50%60%70%SRI-4 LLDASDORIS DORIS 0%10%20%30%40%50%SRI-4 LLDASDORIS DORIS 2009 1210 13 19 B Markus Krumbholz,et al.,B cells and antibodies in multiple sclerosis pathogenesis and therapy.BLyS B off-label CD20 B B B CD20 SLE B CAR-T T B CAR-T CD19 CAR B BCMA CAR B SLE B reset SLE 20 CAR-T SLE B Jane E.Salmon,Arming T cells against B cells in systemic lupus erythematosus 2019 CD19 CAR-T B CD19 CAR-T B 2009 1210 14 CAR-T 2021 Georg Schett CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus 20 CD19 CAR-T WHO IIIA Libman-Sacks B B CD19 CAR-T 1.1 106/kg CD19 CAR-T CAR-T CRS CAR-T B dsDNA C3 C4/2000 mg/g 250 mg/g SLEDAI 16 0 CAR-T SLE CAR-T 21 CAR-T SLE B 22 CAR-T SLE SLEDAI Simon V lkl,et al.,CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus.Simon V lkl,et al.,CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus.2022 9 Georg Schett Nature Medicine 5 SLE CD19 CAR-T 5 22 SLE 4 1 4 SLEDAI 16 1.1 106/kg CD19 CAR-T CAR-T CRS CAR-T B ds-DNA DORIS 5 3 SLE 3 SLEDAI 0 4 0 1 2 0 8 0 B B na ve B B CD19 CAR-T 2009 1210 15 SLE 23 5 rSLE CAR-T Andreas Mackensen,et al.,Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus.2023 5 Georg Schett SLE 7 SLEDAI 10 8-16 7 4-15 ICANS 4 1 CRS 13 4-22 SLEDAI 0 DORIS LLDAS dsDNA SLE 22 CAR-T SLE SLE 24 CAR-T 7 rSLE J.Taubmann,et al.,Long term safety and efficacy of CAR-T cell treatment in refractory systemic lupus erythematosus-data from the first seven patients.2009 1210 16 ASH 2023 15 8 SLE 4 SSc 3 IIM CD19 CAR-T 3 1-20 12 2-28 5 2-14 8 SLE 3 SLEDAI 0 5 14-24 SLE B C3 CAR-T 4 CRS 10 1 CRS 1 2 CRS 1 ICANS 15 6 20 SLE BCMA-CD19 cCAR T 2019 9 1 2023 11 ACR 2023 13 BCMA-CD19 cCAR SLE LN 13 10 17-59 SLEDAI-2K 10 LN 24 1.7g/1.0 3.9 C3 1.5-3 106/kg CAR-T 1-10 B B 90 40-150 11 1 3 44 LN 6 CAR-T SLE CAR-T SLE CAR-T SLE 1 CAR-T CRS ICANS 2 80%SLEDAI-2K 0 3 4/SLE 44 4 3 SLE 2009 1210 17 25 CAR-T SLE Georg Schett#1#2#3#4#5#6#7#1#2#3#4#5#6#7#8#9#10#11#12#13 22 16 14 13 11 8 4 1-4 44 6 6 6 6 6 6 6 6 SLEDAI-2K 16 16 10 8 9 16 10 8 4 8 10 10 8 12 10 8 12 15 16 8 SLEDAI-2K 0 0 0 0 0 0 0 0 0 0 4*0 4*0 0 0 0-4*0 ANA CRS 0 1 0 1 0 1 1 10 1 CRS ICANS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ACR 2023 1 EULAR 2023 2*6 3/2/3 24 2g 14.3 CAR-T 26 SLE 3-6 24 DNA D aPL 10mg 0.51 mg/kg 1 mg/kg 5001 000 mg/d 3d 5-30d 4-8/CAR-T 2020 1 Yong Yuan,et al.,Novel BCMA-CD19 Compound CAR-T(cCAR)Targets B Cells and Plasma Cells Achieving Immune Reset and Eliminates All Autoantibodies in Systemic Lupus Erythematosus(SLE)and Lupus Nephritis(LN)Patients Resulting in Long-Term,Medication-Free Remission.2 J.Taubmann,et al.,Long term safety and efficacy of CAR-T cell treatment in refractory systemic lupus erythematosus-data from the first seven patients.2009 1210 18 CAR-T CAR-T 37-48 110-130 CAR-T T-/CAR-T CAR-T GvHD CAR-T CD19 CAR-T CAR-T CB-010 PBCAR0191 ORR 100%CAR-T CAR-T 27 CAR-T B BMS Allogene CRISPR Caribou Precision CD19 CAR-T CD19 CAR-T SLE B CAR-T CAR-T CAR-NK CAR-T iPSC CAR-T CAR-T SLE CAR-T SLE CD19 CAR-T B 2023 SLE 2023 2009 1210 19 28 SLE 2023 IIT CRS CAR-T B 29 ds-DNA SELENA-SLEDAI 14 6 29 SLE IIT 2023 2023 2023 4 IND CDE 2024 CAR-T 2024/IIT CD19/BCMA GC012F CD19/BCMA CAR-T CD19 B BCMA 2009 1210 20 2023 11 27 GC012F SLE I/II IND FDA ELISPOT CAR-T CD19/BCMA CAR-T CD19 CAR-T IIT GC012F SLE B 84 B na ve B GC012F B na ve 30 GC012F SLE IIT Corporate Presentation-November 2023 2023 GC012F rSLE IND 2024 IIT BMS CD19 NEX T BMS 2019 1 BMS Celgene Celgen Juno Therapeutics Juno-MSKCC CD19 CAR-T BMS CD19 CAR-T Breyanzi BMS Celgen BlueBird Bio 2seventy bio BCMA CAR-T Abecma 2023 BMS CD19 NEX T BMS Editas CRISPR CAR-T BMS gentibio IBD Treg 2009 1210 21 31 BMS BMS 2023 R&D Day BMS-986353 BMS NEX T CD19 CAR-T Breyanzi CAR NEX T CAR-T Breyanzi BMS-986353 32 BMS-986353 BMS 2023 R&D Day BMS BMS-986353 SLE I 2024 BMS B I 2009 1210 22 33 BMS-986353 SLE 34 BMS-986353 BMS 2023 R&D Day BMS 2023 R&D Day T-Charge SLE CAR-T Kymriah CD19 B B B 2022 5.36 CAR-T T-ChargeTM 24 CAR-T 1-2 2 T-ChargeTM T na ve T T T T-ChargeTM CAR-T CAR-T 10-50 35 T-ChargeTM Novartis R&D Day 2021 T-ChargeTM CD19 CAR-T YTB323 Kymriah CAR B II SLE I/II 2023 2 27 YTB323 2023 ACR YTB323 SLE ICANS 1 2 1 2 CRS 3 SLEDAI PhGA dsDNA 2009 1210 23 36 YTB323 SLE I/II 37 YTB323 SLE SLEDAI Clinicaltrials ACR 2023 3 Cabaletta Bio CAR Cabaletta Bio T CAR-T CABA CARTA CABA-201 4-1BB CD19-CAR T CAR-T CAART DSG3-CAART MuSK MuSK-CAART 2022 10 11 Cabaletta Bio CD19 CAR CAR-T 1.62 Cabaletta 38 Cabaletta Bio Cabaletta Bio Corporate Presentation-November 2023 CABA-201 CD19 CAR-T SLE I/II FDA I/II 3Josefina Cort s Hern ndez,et al.,An Open-label,Multicenter,Phase 1/2 Study to Assess Safety,Efficacy and Cellular Kinetics of YTB323,a Rapid Manufacturing CAR-T Cell Therapy Targeting CD19 on B Cells,for Severe Refractory Systemic Lupus Erythematosus:Preliminary Results 2009 1210 24 6 SLE CABA-201 CABA-201 39 CABA-201 40 CABA-201 SLE I/II Cabaletta Bio Corporate Presentation-November 2023 Fate therapeutics iPSC CAR-T SLE Fate therapeutics iPSC NK T FT819 Fate iPSC CAR-T CD3 CD28 CD19 CAR TRAC CAR TRAC TCR GvHD FT522 iPSC CAR-NK CD19 CD20 Fate B I FT522 FT819 B FT819 CD19 CAR-T 41 FT819 42 FT819 B Fate Therapeutics Corporate Presentation-November 2023 2009 1210 25 FT819 SLE I 2023 7 SLE LN FT819 SLE 43 FT819 SLE I Fate Therapeutics Corporate Presentation-November 2023 CAR-T SLE 44 SLE rapcabtagene autoleucel CD19 CAR-T SLE LN I/II CABA-201 Cabaletta Bio;CD19 CAR-T SLE LN I/II 24H1 CD19 CAR-T CD19 CAR-T SLE I/II CD19 Universal CAR-T CD19 CAR-T SLE I/II Descartes-08 Cartesian Therapeutics BCMA CAR-T SLE I 24H1 2 CD19 CAR-T SLE I 23;CASI Pharmaceuticals CD19 CAR-T SLE I GC012F CD19/BCMA CAR-T SLE I 24H1 IIT BCMA-CD19 cCAR T iCell Gene Therapeutics CD19/BCMA CAR-T SLE I BMS-986353 BMS CD19 CAR-T SLE I 24 BRL-301A CD19 CAR-T SLE I CD19 targeted CAR-T CD19 CAR-T SLE I CD19/BCMA targeted CAR-T CD19/BCMA CAR-T SLE LN I FT819 Fate Therapeutics CD19 CAR-T SLE I KN5501 CD19 CAR-NK SLE I KYV-101 Kyverna Therapeutics CD19 CAR-T LN I 2009 1210 26 autologous T regulatory cells Ain Shams University Treg LN I CD19 CAR-NK CD19 CAR-NK SLE IND AB-101 Artiva Biotherapeutics NK LN IND IMPT-314 ImmPACT Bio CD19/CD20 CAR-T SLE IND NKX019 Nkarta CD19 CAR-NK LN IND SC291 Sana Biotechnology CD19 CAR-T SLE LN IND 2023 Corporate Presentation-November 2023 BMS 2023 R&D Day Cabaletta Bio Corporate Presentation-November 2023 Cartesian Therapeutics Merger Announcement 1.2.3.4.2009 1210 27 2020 2020 2020 2020 2020 2020 2020 2023 2021 2022 2022 2022 2023 2009 1210 28 010-63214682 010-63214682 010-63214682 010-63214682 010-63214682 010-66500808 010-66500821 010-63214682 0755-82828570 0755-83715428 0755-82756804 0755-82871425 0755-82871425 021-20572536 021-20572555 021-20572257-2552 021-20572506 021-20572585 021-20572509 021-20572548 021-20572573 0755-82756805 021-20572559 021-20572559 0755-82756805 021-20572559 玙 021-25072549 2009 1210 29 A 300 500/6 20%6 10%20%6-10%10%6 10%20%3-6 5%3-6-5%5%3-6 5%26 C 3A 1061 A 19 33 12 100033 518034 200120 010-66500801 0755-82027731 021-20572500 010-66500900 0755-82828562 021-20572522