20230722_德邦证券_医药行业ADC药物系列专题报告：由同质化走向多元化联合疗法鸣枪起跑_38页.pdf

0ADC)2023 7 22|S0120521080001 chentl S0120522100005 1 010203ADC ADC ADC CONTENTS0YAZuNmRsRmNoQpMnQrOqRbRdN7NnPpPmOoNfQnNtMfQnPmR9PrQtNxNtOmRxNnMrR2 01ADC 3ADC=1+1 2-ADC 20 Paul Ehrlich 2000 FDA ADC Mylotarg AML ADC ADC ADC 资料来源：Antibody drug conjugate:the“biological missile”for targeted cancer therapy,Zhiwen Fu et al.，Antibodydrug conjugates come of age in oncology.Dumontet,C et al.，辉瑞官网，健康界，德邦研究所 化疗药物：脱靶效应导致严重的副作用 抗体药物：与化疗相比治疗效果不佳，对癌细胞的致死性较差4 资料来源：Antibodydrug conjugates come of age in oncology.Dumontet,C et al.，Strategies and challenges for the next generation of antibodydrug conjugates Alain Beck et al.，德邦研究所 ADC DNA 1 ADC;ADC-;linker ADC 5ADC 4.0 资料来源：医药魔方，德邦研究所 ADC 4.0 ADC ADC ADC 2000:(Mylotarg)2011:(Adcetris)2019:(Polivy)2019:(Enhertu)ADC+payload+linker+DAR ADC+payload+linker+ADC DAR payload ADC DAR 4-8 payload payload linker ADC 6 ADC 15 ADC 7 资料来源：医药魔方，A comprehensive review of key factors affecting the efficacy of antibody drug conjugate.Anupama S.et al,德邦研究所 2023 6 24 ADC 15 ADC 7 8 7 ADC linker Payload DAR Mylotarg US/EU CD33 IgG4 2-3 AML Adcetris CN/US/JP/EU CD30 IgG1 MMAE 4HL PTCL T AITL s/pcALCL Kadcyla CN/US/JP/EU HER2 IgG1 DM1 3.5 HER Besponsa CN/US/JP/EU CD22 IgG4 5-7 ALL Lumoxiti CD22 IgG1 PE38/HCL Polivy CN/US/JP/EU CD79b IgG1 MMAE 3.5 DLBCL B Seagen Padcev US/JP/EU Nectin-4 IgG1 MMAE 3.8 Euhertu CN/US/JP/EU HER2 IgG1 Dxd 7-8 HER2 GC GEJC Trodelvy CN/US/EU TROP2 IgG1 SN38 7.6 HR GSK BlenrepBelantambmafodotionUS/EU BCMA IgG1 MMAF 4 MM()ADCT ZynlontaLoncastuximabtesirineUS/EU CD19 IgG1 PBD 2.3 DLBCL B Rakuten AkaluxCetuximab saratolacanJP EGFR IgG1 lRDye700Dx 1.3-3.8 CN HER2-MMAE 4 Genmab Tivdak Tisotumab vedotin US TFIgG1-Kappa MMAE 4 ImmunoGen ElahereMirvetuximabsoravtansineUS FR IgG1 DM4 3.4 ADC 注：棕色底为获批血液系统肿瘤适应症药物7ADC,PD-1+ADC ADC 资料来源：Antibodydrug conjugates:in search of partners of choice.Jess Fuentes-Antrs.et al,德邦研究所 ADC ADC DNA ADC ADC ADC ADC ADC T T PD-L 1 PD1/PD-L18ADC,PD-1+ADC ADC 资料来源：Antibodydrug conjugates:in search of partners of choice.Jess Fuentes-Antrs.et al,德邦研究所 ADC Anti-PD-1/PD-L1 anti-CTLA-4 ADC ADC ADC Anti-PD-1/PD-L1 anti-CTLA-49ADC,PD-1+ADC 资料来源：Antibodydrug conjugates:in search of partners of choice.Jess Fuentes-Antrs.et al,德邦研究所 ADC ADC Trends in Cancer J.F-16 ADC PFS RFS EFS/OS HR PD-1 ADC 2023 4 3 Seagen FDA Keytruda PD1 Padcev Nectin-4 ADC la/mUC PD1 ADC PD-1+ADC PD-1 ADC10ADC 600 ADC 4.0 资料来源：科伦博泰招股书，弗若斯特沙利文，健康界，德邦研究所 ADC 647 ADC 2017 16 2021 55 2030 ADC 647 30%ADC ADC 2020 ADC Kadcyla ADC 2022-2030 72.8%2030 ADC 662 2 4 82143851592643935316620.00%50.00%100.00%150.00%200.00%0100200300400500600700市场规模（亿元）yoy ADC ADC 4155791141421872383154125286470.0%50.0%100.0%150.0%200.0%0100200300400500600700市场规模（亿美元）yoy11 02ADC 12 GPNMB,CD70,CD56,Trop-2,FR Tissue factor ENPP3 p-cadherin mesothelin STEAP1 CEACAM5 Mucin 1,Nectin 4,SLC44A4,PSMA LIV1,5T4,SC-16,Guanylyl cyclase C HER2,EGFR EDB,ETB,PSMA VEGFR2 ROBO4 Tissue factor Collagen IV,Periostin,Tenascin C CD30,CD22,CD79b,CD19,CD138 CD74 CD37 CD33 CD19 CD98 ADC ADC ADC 资料来源：Antibody drug conjugate:the“biological missile”for targeted cancer therapy.Fu,Z.,Li,S.,Han,S.et al，德邦研究所 ADC ADC-ADC HER2 trop2 nectin4 EGFR CD19 CD22 CD33 CD30 BCMA CD79b ADC/13 ADC IgG1 Antibody ADC ADC G IgG IgG1 IgG2 IgG3 IgG4 IgG1 ADC IgG1 Fc ADCC ADCP CDC IgG2 ADC ADC IgG3 ADC 21 IgG3 7 IgG4 ADCC IgG4 Fab-资料来源：Antibody drug conjugate:the“biological missile”for targeted cancer therapy.Fu,Z.,Li,S.,Han,S.et alA comprehensive review of key factors affecting the efficacy of antibody drug conjugate.Anupama Samantasinghar et al，德邦研究所 ADC IgG C1q CDC ADCCADCP ADC IgG1 21 4+Tisotumab vedotin,Loncastuximab tesirine,Belantamabmafodotin,Sacituzumab govitecan,Trastuzumab deruxtecan,Polatuzumab vedotin,Trastuzumab emtansine,Brentuximab vedotinIgG2 21 6+-IgG3 7 13+-IgG4 21 4a-+Gemtuzumab ozogamicin,Inotuzumab ozogamicin14 Linker ADC ADC linker ADC ADC ADC MDR1 Nature Reviews Drug Discovery Beck.A MDR1 ADC MDR1 ADC 资料来源：Strategies and challenges for the next generation of antibodydrug conjugates.Beck.A.et al.，New Technologies Bloom Together for Bettering Cancer Drug Conjugates.Nicola Ashman et al.，Antibody drug conjugate:the“biological missile”for targeted cancer therapy Zhiwen Fu et al.，德邦研究所15 Linker ADC linker MC-VC-PABC ADC 6 linkerTisotumab vedotin Disitamab vedotin Fe(II)ADC Linker资料来源：Antibody-drug conjugates:Recent advances in linker chemistry.Su Z,et al.德邦研究所 MHH DSDM Sulfo-SPDB MC-VC-PABC SMCC Mal-PEG-NHS GBC-Linker Fe(II)16 Payload ADC 2%ADC IC50 nM pM,ADC payload ADC DNA ADC(Bcl-xl)RNA 资料来源：Antibody drug conjugate:the“biological missile”for targeted cancer therapy.Zhiwen Fu et.al,肿瘤抗体药物偶联物的研发进展和挑战.李博乐等,德邦研究所 ADC 17 DAR ADC ADC DAR(Drug-to-Antibody Ratio DAR)DAR ADC DAR ADC DAR ADC DAR ADC ADC DAR ADC ADC ADC 资料来源：Antibody drug conjugate:the“biological missile”for targeted cancer therapy.Fu,Z.,Li,S.,Han,S.et al，德邦研究所 Lys DAR 0-8 ADC Cys payload18 DAR 2 DAR 4 DAR pClick/DAR ADC 资料来源：Antibody drug conjugate:the“biological missile”for targeted cancer therapy.Fu,Z.et al，Strategies and challenges for the next generation of antibodydrug conjugates.Beck,A.et al.德邦研究所19ADC ADC ADC资料来源：Antibodydrug conjugates:Smart chemotherapy delivery across tumor histologies.Paolo Tarantino.et al,医药魔方.德邦研究所 ADC ADC HER2 HER2 ADC MoAb ADC Bispecific ADCs Dual-payloadADCs ADCs with immune-stimulating payloads Radionuclide ADCs ADC RDC SMDC PDC ISAC FDC ACC VDC AOC ABC ADeC Pro-DC20 03ADC 212415107640 10 20 30HER2TROP2CLDN18.2EGFRB7-H3nectin-4ADC 资料来源：医药魔方，德邦研究所311099870 10 20 30 40HER2EGFRFR B7-H3c-MetTROP2 ADC TOP ADC HER2 ADC HER2 TROP2 CLDN18.2 ADC/ADC ADC/ADC CLD18.2 ADC I/II CMG901 11.88 ADC AZD9592 EGFR/c-Met REGN5093-M114 c-Met22HER2 ADC 3 1 NDA 5 3 HER2 ADC T-DM1 Kadcyla 2013 FDA 2019 T-DXd DS-8201 Enhertu HER2 ADC 2021 RC48 3+1 NDA+5 A166 SYA1501 LCB14-0110 MRG002 A1811 ARX788 5 HER2 ADC DS-8201;HER2;HER2;T-DM1 ImmunoGen;HER2;RC48 Seagen;HER2;HER2;A166;HER2;trastuzumab duocarmazinemedac;Byondis HER2;SYA1501;HER2;III III LCB14-0110 Iksuda;LCB;HER2;HER2 III III MRG002;HER2;HER2 III III SHR-A1811 HER2;HER2 III III ARX788;Ambrx;HER2;HER2 II/III II/III 资料来源：医药魔方，德邦研究所整理。备注：复星医药为本公司关联方，该表所列内容仅为同类型产品的整理与总结，不代表本公司研究所任何投资建议。HER2 ADC 23HER2 ADC HER2 HER2 III HER2 ADC HER2 HER2 HER2 Roche 2020.1 II/III 2013.2 II/III II DS-8201 2023.2 III III 2019.12 II RC48 2021.6 II/III III II II III A166 2023.5 NDA I I I SYA1501 III II II LCB14-0110 III II II MRG002 II II II II III SHR-A1811 III III I/II I/II ARX788 II/III II/III I/II HER2 ADC 资料来源：医药魔方，各公司年报，各公司公告，德邦研究所。备注：复星医药为本公司关联方，该表所列内容仅为同类型产品的整理与总结，不代表本公司研究所任何投资建议。24HER2 ADC DS8201 3 HER2 ADC DS-8201 T-DM1 HER2 ADC 3 T-DM1 DS-8201 RC48 A166 SHR-A1811 DM1 Deruxtecan MMAE MMAF DNA I 2012 NEJM 2022 Lancet 2021 ASCO 2022 ASCO 2023 ASCO Roche EMILIA DESTINY-Breast03 NCT03052634 CTR20181301 SHR-A1811-I-101 HER2 HER2 HER2 HER2 HER2 2 2 39.8%3 4 3 991 524 70 58 108 T-DM1 vs Lap+Cap DS-8201 vs T-DM1 RC48 A166 SHR-A1811ORR 43.6%vs 30.8%79.7%vs 34.2%42.9%2.0 mg/kg 73.91%4.8 mg/kg 81.5%mPFS 9.6 vs 6.4 28.8 vs 6.85.7 2.0 mg/kg 12.3 4.8 mg/kg mOS 30.9 vs 25.112 OS 94.1%vs 85.9%TRAE 41%vs 57%56%vs 52%10%7 AEs 52.4%资料来源：医药魔方，科伦博泰招股书，Trastuzumab emtansine for HER2-positive advanced breast cancer Sunil Verma et al.，Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer Sara A Hurvitz et al.,2021ASCO,Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer Javier Corts etal.，2022ASCO，2023ASCO，德邦研究所整理 HER2 25TROP2 ADC 1 1 TROP2 ADC TROP2 ADC 2020 4 FDA TNBC 2022 6 TNBC SKB264 TROP2 ADC Immunomedics;Seagen;HR;SKB264;Merck&Co.;III III DS-1062;HR III III BIO-106 I/II DB-1305 I/II I/II ESG401;I/II I/II SHR-A1921 I/II I/II BAT8008 I I BL-M02D1 Systimmune;I I DAC-002;I I FDA018 I I FZ-AD004 I I 资料来源：医药魔方，德邦研究所整理 TROP2 ADC 26TROP2 ADC HER2 Trop2 Trop-2 90%HR Gilead;Pfizer 2022.6 III III 2020.4 III I/II SKB264;Merck&Co.III III I/II I/II I/II DS-1062;III III III I/II III III III II TROP2 ADC 资料来源：医药魔方，Biotech前瞻，德邦研究所整理27TROP2 ADC Trop2 ADC TNBC DS-1062 SKB-264 Trop2 ADC TNBC TNBC ADC SKB264 DS-1062 Immunomedics;Seagen;Merck&Co.;2-CL2A SN38 Datopotamab Deruxteen 2021 NEJM 2022 SABCS 2022 SABCS ASCENT NCT04152499 TROPION-PanTumor01 3 88%4 468 55 44 vs SKB264 DS-1062ORR 35%vs 5%40%32%mPFS 5.6 vs 1.7 5.7 4.4mOS 12.1 vs 6.7 14.6 13.5 TRAE 51%vs 33%57.6%9 Aes 20.5%资料来源：科伦博泰招股书，2022 SABCS，Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer Aditya Bardia et al.，德邦研究所整理28nectin-4 ADC 1 Seagen;Agensys III II 9MW2821;I/II I/II I/II I/II BAT8007 I ISHR-A2102 I I SYS6002;Corbus I I 资料来源：医药魔方，德邦研究所整理 nectin-4 ADC 1 nectin-4 ADC 2019 12 2023 3 PD-1/PD-L1 Nectin-4 Nectin-4 P13K/Akt Nectin-4 29nectin-4 ADC nectin-4 ADC Nectin-4 nectin-4 ADC 9MW2821 10 II RP2D 12 ORR 50%DCR 100%资料来源：医药魔方，Powles,Thomas et al.Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma，迈威生物公告，德邦研究所整理 9MW2821 Seagen;Agensys;Payload/2021 NEJM 2023 EV-301 NCT05216965 608 12 vs ORR 40.6%vs 17.9%50%mPFS 5.55 vs 3.71mOS 12.88 vs 8.97 TRAE 51.4%vs 49.8%30HER3 ADC 4 HER3 HER HER3 NSCLC 80%30%50%4 HER3 ADC U3-1042 EGFR/HER3 ADC BL-B01D1 DB-1310 SHR-A2009 U3-1042 HER3 ADC III III HER2 II II BL-B01D1 EGFR/HER3 ADC II II II II I I DB-1310 HER3 ADC I/II I/II SHR-A2009 HER3 ADC I I 资料来源：医药魔方，德邦研究所整理 HER3 ADC 31HER3 ADC HER3 ADC EGFR/HER3 ADC EGFR-Mutated NSCLC ORR(63.2%)U3-1042(41.0%)HER3 ADC BL-B01D1 EGFR HER3 资料来源：医药魔方，ASCO官网，BUSINESS WIRE，CPHI制药在线，德邦研究所整理 U3-1042 BL-B01D1 Payload I DX-8951 I Ed-04 JSMO 2023 2023 ASCO U31402-A-U102 NCT05194982 EGFR-Mutated NSCLC EGFR-Mutated NSCLC EGFR TKI EGFR TKI 78 38 U3-1042 BL-B01D1 ORR 41.0%63.2%mPFS 6.4mOS 16.2 TRAE 56.9%G3 30%32CLDN18.2 ADC CLDN18.2 ADC 2023 6 14 CLDN18.2 ADC CLDN18.2 70%50%30%CLDN18.2 资料来源：医药魔方，免疫时间微信公众号，德邦研究所整理 CLDN18.2 ADC LM-302 Turning Point;II IIRC118 I/II I/II SHR-A1904 I/II I SO-N102 Sotio;I/II XNW27011 I/II IATG-022 I I CMG901;AstraZeneca;I IIBI343 I IJS107;I IPR301 I ISKB315;Merck&Co.I ISYSA1801;Elevation Oncology;I ITORL-2-307 TORL Biotherapeutics;I TQB2103 I I33CLDN18.2 ADC CLDN18.2 ADC 2023 6 CLDN18.2 ADC SYSA1801 CMG901 CMG901 ORR DCR CLDN18.2 ADC 资料来源：医药魔方，ASCO官网，CISION，德邦研究所整理 zolbetuximab CMG901 SYSA1801 Astellas payload/MMAE MMAE 2023 ASCO GI 2023 ASCO 2023 ASCO GLOW III KYM901 I SYSA1801-CSP-001 I CLDN18.2 HER2 CLDN18.2-positive CLDN18.2-positive 507 8 17 Z+vs+CMG901 SYSA1801 ORR 53.8%vs 48.8%75%47.1%DCR 100%64.7%mPFS 8.21 VS 6.80 mOS 14.39 VS 12.16 TRAE 72.8%VS 69.9%11%24.2%34 ADC ADC GLP-1 35 2019 2018 2017 2016 2015 1.6 6 20%5%20%-5%+5%5%2.A 500 10%-10%10%10%36 37 600 N1 9+86 21 68761616+86 21 68767880400-8888-128