2019 年第三季度 生物制药企业许可交易活动纵览 授权交易许可报告 2 1 During the third quarter of 2019, Cortellis Deals Intelligence TM registered 1,377 new deals (excluding mergers 待定 (意向书) 肿瘤/ III期临床临床 肿瘤/ III期临床床 其他 / II期临床 肿瘤/II期临床 感染/ III期临床 肿瘤/临床前 多领域/发现阶段 4 罗氏旗下的基因泰克与Skyhawk签订了价值20亿美元的协议，以扩大其肿瘤和神经科学领域项 目。基因泰克将利用其SkySTAR平台技术发现和开发能对多个靶点调节的RNA选择性剪接的小分 子药物， Skyhawk将获得首付、，里程碑付款和销售提成等。 与此同时，基因泰克还与日本生物医药巨头Sosei集团旗下生物技术公司Sosei Heptares签订了 包括发现和开发基因泰克所选定的，靶向G 蛋白偶联受体（ GPCRs）的新型小分子药物，价值高达 12.6亿美元， Sosei Heptares将获得2600万美元预付和短期投资，和总额可能超过10亿美元的里 程碑付款和销售提成。 默沙东和葛兰素史克引领生物制药交易市场 在这一季度披露的生物制药交易活动中，默沙东和葛兰素史克（ GSK）分别以10笔和9 笔交易位居 前列，紧随其后的是均有8笔交易的勃林格殷格翰、诺华、罗氏和Thermo Fisher （见图 3）。 3 molecules that modulate RNA splicing for multiple targets in exchange for an upfront fee, milestones and royalties. In parallel, the company has also signed a $1.26 billion deal with Sosei Heptares covering Genentech-selected small molecules and/or biologics that modulate G protein coupled receptor (GPCR) targets. The Japanese company will receive $26 million in upfront and near-term fees and milestone payments worth more than $1 billion plus royalties. Merck & Co. and GlaxoSmithKline led the biopharma licensing market Merck & Co and GlaxoSmithKline (GSK) were the big pharma companies that achieved strong licensing activity during this quarter (10 and 9 disclosed deals, respectively), followed by Boehringer Ingelheim, Novartis, Roche and Thermo Fisher (8 disclosed deals each) (see Figure 3). Figure 3: Top commercial licensing players Source: Cortellis Deals Intelligence Merck & Co., as Genentech, has partnered with Skyhawk to discover and develop small molecules for the treatment of neurological diseases and cancers using the SkySTAR technology platform in exchange for $600 million per program. Merck is also expanding its vaccine portfolio with the Themis deal focused on vaccine development using Themiss measles virus vector-based platform in exchange for up to $200 million in milestones plus royalties per products. BARDA has been granted $23 million to produce Mercks V920, a monovalent recombinant vesicular stomatitis virus (rVSV) vaccine for the prevention of Ebola virus disease. Celgene and Relay Therapeutics are collaborating with Merck to develop STING antagonists for an undisclosed indication. Merck has also gained commercialization rights to Samsung Bioepiss SB8, a bevacizumab biosimilar in the pre-registration stage for non-small cell lung cancer. GSKs main licensing activity was focused on its vaccine portfolio. The company outlicensed zanamivir (Relenza), an inhibitor of influenza A and B virus neuraminidase, to Ildong Pharmaceutical. GSK is also collaborating with VBI Vaccines to evaluate VBI-1901, a bivalent vaccine that contains CMV antigens glycoprotein B and pp65, in combination with GSKs AS01B adjuvant system in a phase I/IIa trial for recurrent glioblastoma. Sabin Vaccine Institute has also received rights to GSKs technology and patents to develop prophylactic candidate vaccines against the Ebola Zaire, Ebola Sudan and Marburg viruses. 10 9 8 8 8 8 7 7 6 5 5 5 4 4 4 4 4 4 4 4 4 4 4 0 2 4 6 8 10 12 总共 130 笔交易 和基因泰克一样，默沙东通过与Skyhawk合作，使用其SkySTAR技术平台发现和开发针对神经疾 病和肿瘤的小分子药物，每一个项目Skyhawk将获得6 亿美元的资金。默沙东为了扩大其疫苗产 品组合，与Themis达成了里程碑付款加上市后销售的特许权使用费可高达2 亿美元的合作，将 使用Themis麻疹病毒载体的平台开发候选疫苗。默沙东的单价重组水疱性口炎病毒(rVSV)疫苗 V920，还获得了美国卫生部下属的生物医学高级研究及发展管理局（ BARDA）赞助的2300万美元 生产经费，用于埃博拉病毒预防。新基和Relay Therapeutics正与默沙东合作开发干扰素基因刺激 蛋 白（ STING）拮抗剂，具体适应症未披露。默沙东还获得了三星生物的贝伐单抗生物类似物SB8 的商业权益， SB8用于非小细胞肺癌，目前正处于提交上市申请阶段。 GSK的主要交易活动聚焦于其疫苗产品组合，包括将流感病毒A 和 B神经氨酸酶抑制剂扎那米韦 (Relenza)对外授权给了IIdong制药；同时， GSK还与VBI疫苗合作启动评价含有CMV抗原糖蛋白B 和 pp65的二价疫苗VBI-1901 ，与 GSK开发的AS01B佐剂系統联用，用于复发难治脑胶质瘤I/IIa期临床 试验。 Sabin疫苗研究所获得了GSK开发针对埃博拉- 扎伊尔型、埃博拉- 苏丹型和马尔堡病毒疫苗 的技术和专利授权。 图3. 生物制药交易头部玩家 来源： Cortellis Deals Intelligence交易情报 5 4 Boehringer Ingelheim, together with Novartis, Roche and Thermo Fisher, were also significant deal players in the biopharma market. Boehringer obtained rights for Bridges idiopathic pulmonary fibrosis treatment BBT-877 for $1.3 billion. Yuhan outlicensed the preclinical GLP1R/FGF21R agonist to Boehringer for upfront and near-term fees of $40 million and up to $830 million in milestone payments and royalties. The German-based company also gained rights to Lupins MEK inhibitor LNP3794 to combine with KRAS inhibitor against KRAS-driven cancers, including gastrointestinal and lung cancers, for $20 million in upfront fees and more than $700 million in milestone fees and royalties. Novartis also signed significant deal values, including an $840 million pact with IFM Therapeuticss subsidiary, IFM Due, to develop cGAS-STING programs for inflammatory and autoimmune diseases with the option to acquire the company and a $390 million deal with Recordati to obtain the rights to Novartiss orphan drugs osilodrostat, pasireotide diaspartate and pasireotide pamoate. Roche signed deals covering its oncologic asset atezolizumab with Immunomedics and KAHR Medical. Thermo Fisher continued expanding its diagnostic assets with deals signed with Biodesix, Eli Lilly and Igentify. Respiratory, oncology and infection licensing deals reach $19.4 billion Deals focused on respiratory, oncology and infection therapeutic areas reached a total disclosed value of $19.4 billion, a 52.1% of the total value ($37.2 billion) (see Figure 4). The $6.5 billion pact between Galapagos and Gilead and the $1.3 billion alliance between Boehringer Ingelheim and Bridge Biotherapeutics for idiopathic pulmonary fibrosis, both mentioned earlier, helped to achieve a total disclosed value of $7.8 billion for the respiratory therapeutic area. The oncology market reached $6.5 billion with five deals worth more than 0.5 billion, including the agreement between Immatics and Celgene for the development of T-lymphocyte cell therapies for $1.6 billion, the alliance between Boehringer Ingelheim and Lupin for LNP3794 of $720 million and the letter of intent (LOI) between Talem, a subsidiary of ImmunoPrecise Antibodies, and AgonOx to develop antibodies to target T-cell mediated anti-tumor activity for $720 million. Deals with an infection target reached a total disclosed value of $5.1 billion, including the alliance between Emergent and the US Department of Health and Human Services for the supply of the smallpox vaccine ACAM2000 for $2 billion and the $604 million deal between Mundipharma and Cidara for rezafungin, a beta-1,3-glucan synthase inhibitor against fungal infections. Respiratory, cancer and infection therapy areas concentrated the total deal value in Q3 2019 总计 372亿美元 2019年第3季度总交易价值集中在呼吸、肿瘤和感染治疗领域 勃林格殷格翰，诺华，罗氏和Thermo Fisher也是生物制药交易市场的主要玩家。勃林格殷格翰 以 13亿美元获得Bridge开发的特发性肺纤维化药物BBT-877的权益。 Yuhan将其处于临床前的 GLP1R/FGF21R双激动剂对外授权给勃林格殷格翰，基于合作条款将获得 千万美元的预付和近 期付款，以及高达8.3亿美元的里程碑付款和上市后销售提成。勃林格殷格翰的KRAS抑制剂还达 成了与Lupin的 MEK抑制剂LNP3794联合开发的协议，将用于包括KRAS突变驱动的胃肠道肿瘤和 肺癌等治疗。 Lupin将获得2 千万首付款和超过7 亿美元的里程碑和上市后销售提成。诺华也开展 了几笔高价值的交易，包括与IFM治疗的子公司IFM Due达成总价值为8.4亿美元的合作协议，主 要用于对cGAS-STING 通路候选药物用于自身免疫疾病的开发支持，和对 IMF Due的收购选择权。 诺华还将其三个孤儿药osilodrostat, pasireotide diaspartate和 pasireotide pamoate以 3.9亿美元出 售给 Recordati。罗氏签订的交易涵盖了其肿瘤资产atezolizumab分别与Immunomedics和 KAHR Medical的合作开发协议。 Thermo Fisher为了持续扩大其诊断资产，与Biodesix, Eli Lilly 和 Igentify 都分别达成了合作协议。 呼吸，肿瘤和感染领域交易额达194亿美元 呼吸，肿瘤和感染治疗领域的总披露交易额达194亿美元，占总交易额（ 372亿美元）的52.1% （见 图 4）。前文提及的两笔高额交易，吉利德与Galapagos价值65亿美元合作，勃林格殷格翰与Bridge Biotherapeutics就治疗特发性肺纤维化药物达成的13亿美元合作协议，促使呼吸治疗领域总披 露交易金额达到78亿美元。肿瘤治疗市场5 笔交易均超过5 千万美元，使得总交易额达到65亿 美元，包括新基与Immatics达成16亿美元开发T 淋巴细胞疗法的协议；勃林格殷格翰与Lupin就 LNP3794达成的7.2亿美元合作开发协议； ImmunoPrecise 的子公司Talem与 AgonOx签订的以靶 向 T细胞调控抗肿瘤活性抗体的开发战略合作意向书，交易金额达7.2亿美元。涉及感染疾病领 域的总披露交易金额为51亿美元，包括Emergent与美国卫生与公共服务部签订的供应天花疫苗 ACAM2000的合作，价值 20亿美元；萌帝制药与 Cidara就用于真菌感染的 -1,3-葡聚糖合酶抑制剂 rezafungin达成的6.04亿美元的合作开发协议。 图4. 各治疗领域披露的最大交易额（百万美元） 来源： Cortellis Deals Intelligence交易情报 毒性/ 中毒, $140 未披露, $4,806 肿瘤, $6,501 多领域, $3,605 免疫, $3,181 感染, $5,078 呼吸, $7,825 其他,$628 眼科, $312 不适用, $9 神经科学/ 精神类, $874 肌肉与骨骼, $1,192 炎症, $0 泌尿生殖/ 性功能, $182 血液, $56 胃肠道, $2,145 内分泌/ 代谢, $538 皮肤, $40 心血管, $40 6 图5. APAC 地区公司在过去5年内的第三季度里披露的交易量和交易额 来源： Cortellis Deals Intelligence交易情报 亚太地区公司交易活动势头强劲，交易额达121亿美元 2019年第三季度期间， Cortellis Deals Intelligence交易情报共收录了259笔亚太地区（ APAC）公司的 交易（并购和拆分转让除外），较 2018年第三季度增长 26.3%（见图 5）。总披露交易额也从去年同 期的51亿增长至121亿美元，增幅高达137.3% 。 交易额在过去5年同期中达到最高 5 Asia Pacific-based organizations show strong licensing size and activity worth $12.1 billion In the third quarter of 2019, Cortellis Deals Intelligence recorded 259 new deals (excluding mergers & acquisitions and divestments) involving Asia Pacific (APAC)-based organizations, an increase of 26.3% from 205 in Q3 2018 (see Figure 5). The total disclosed deal value increased by 137.3% to $12.1 billion from $5.1 billion in the same quarter last year. Figure 5: Deal volume and total disclosed deal value involving APAC-based organizations for the last five third- quarter periods Source: Cortellis Deals Intelligence $0.8 $0.9 $1.4 $1.3 $1.5 $3.5 $2.1 $4.5 $3.8 $10.6 0 50 100 150 200 250 300 $- $2.0 $4.0 $6.0 $8.0 $10.0 $12.0 $14.0 Q3-15 Q3-16 Q3-17 Q3-18 Q3-19 Licensing deals reach the highest value in the last five years 最高交易额 ( 十亿美元) 总交易额 ( 十亿美元) 披露的交易数量 交易数量 7 图6. APAC 地区的公司交易额. 来源： Cortellis Deals Intelligence交易情报 APAC地区公司有17笔均超过1亿美元的交易 2019年第三季度APAC 地区有17笔高额交易，总额超过1 亿美元（见图6 ），其 中 10笔均超过5 千万美 元。 52.9%的合作协议集中在早期资产，从交易围绕的治疗领域看， 41.4%的交易涵盖肿瘤项目。 前3大APAC地区公司的交易横跨多个治疗领域 中国豪森药业与总部位于美国的公司Atomwise达成合作协议，基于Atomwise的 AI技术药物设计 平台，开发针对多个治疗领域的11个靶标的候选药物， 这将为Atomwise带来15亿美元的收益，包 括技术使用权，期权费，授权许可和上市后销售的特许权使用费。 6 Seventeen APAC-based licenses, each worth over $100 million, were formed We tracked 17 high-value new APAC-based licensing deals worth in excess of $0.1 billion during the third quarter of 2019 (see Figure 6), including 10 deals worth in excess of $0.5 billion. 52.9% of these agreements were focused on early-stage assets, and 41.1% covered oncology assets. Figure 6: Deal value for APAC-based organizations. Source: Cortellis Deals Intelligence Top three APAC license deals span multiple therapeutic areas United States based company Atomwise and the Chinese company Hansoh Pharmaceutical agreed to develop candidates for up to 11 target proteins for multiple therapeutic areas and using Atomwises artificial intelligence technology in exchange for $1.5 billion, including technology access, option fees, income from sublicenses and royalties. $51 $26 $15 $26 $40 $20 $10 $80 $18 $3 $5 $5 $15 $1 $16 $1,236 $1,020 $1,000 $830 $850 $700 $672 $545 $429 $245 $180 $135 $104 $1,500 $1,200 $115 $310 $142 $0 $200 $400 $600 $800 $1,000 $1,200 $1,400 $1,600 Hansoh/Atomwise Boehringer Ingelheim/Bridge Biotherapeutics Takeda/Sosei Heptares Grnenthal/Mesoblast Genentech/Sosei Heptares Boehringer Ingelheim/Yuhan Takeda/Evotec Boehringer Ingelheim/Lupin PT Kalbe Genexine/Henlius Biotech Astellas/Frequency Therapeutics Exelixis/Aurigene Adaptimmune/Noile-Immune Asieris/PhotoCure Symbio/Chimerix I-Mab/MacroGenics Biotheus/Alligator Ono Pharma/Forty Seven Upfront + equity ($M) Milestones ($M) Remainder ($M), includes other fees such as option fees and R&D funding as well as mixed payments 6 Seventeen APAC-based licenses, each worth over $100 million, were formed We tracked 17 high-value new APAC-based licensing deals worth in excess of $0.1 billion during the third nulluarter of null1nullnullsee nulligure 6nullnull including 10 deals worth in excess of $0.nullbillion. null.nullnullof these agreenullents were focused on earlnull-stage assetsnull and null1.1null covered oncolognull assets. Figure 6: nullal value for APAC- based organinullations. Source: Cortellis nulleals nullntelligence nullonull three APAC license deals snullan multinullle theranulleutic areas nullited nulltates based conullnullannull Atonullwise and the Chinese conullnullannull nullansoh Pharnullaceutical agreed to develonull candidates for unull to 11 target nullroteins for nullultinullle theranulleutic areas and using Atonullwisenulls artificial intelligence technolognull in exchange for $1.null billionnull including technolognull accessnull onulltion feesnull inconulle fronull sublicenses and ronullalties. $null $null $1null $null $null $null $10 $null $1null $null $null $null $1null $1 $16 $1,nullnull6 $1,0null0 $1,000 $null0 $null0 $null0 $6null $nullnull $nullnull $nullnull $1null $1null $10null $1,null00 $1,null00 $11null $null0 $1null $0 $null00 $null00 $600 $null00 $1null000 $1nullnull00 $1nullnull00 $1null600 nullnsohnullAtonullwise nulloehringer nullngelheinullnullridge nulliotheranullutics nullakedanullnullosei nullenulltares null nenthalnullnullesoblast nullnentechnullnullosei nullenulltares nulloehringer nullngelheinullnullnulluhan nullakedanullnullvotec nulloehringer nullngelheinullnullunulln Pnull nullalbe nullnexinenullnullenlius nulliotech Astellasnullrenullencnull nullheranulleutics nullxelixisnullurigene Adanulltinullnullunenulloile-nullnullnullune AsierisnullhotoCure nullnullnullbionullhinullerix null abnullnullacronullnics nulliotheusnullAlligator nullno Pharnullanullnullortnull even nullnullront null enullitnull null$nullnull nulllestones nullnull nullenullainder null$nullnullnull includes other fees such as onullion fees and nullnullnull funding as well as nullixed null nullents Gastrointestinal/Discovery Musculoskeletal/Phase III Undisclosed/Discovery OtherMiscellaneous/Phase II Cancer/Discovery Respiratory/Phase I Undisclosed/Discovery Cancer/Phase III Diversified/Discovery Gastrointestinal/Precllinical Cancer/Phase III Cancer/Discovery Infection/Preclinical Cancer/Phase II Undisclosed/Discovery Cancer/Phase II Cancer/Phase III 首付款 + 股权 (百万美元) 里程碑付款 (百万美元) 尾款(百万美元), 包括期权费、研发费用和混合付款 未披露/发现阶段 呼吸/I期临床 胃肠道/发现阶段 肌肉与骨骼/ III期临床 未披露/发现阶段 胃肠道/临床前 多领域/发现阶段 Cancer/ III期临床 肿瘤/ III期临床 其他/ II期临床 肿瘤/发现阶段 肿瘤/发现阶段 肿瘤/ III期临床 感染/临床前 肿瘤/ II期临床 未披露/发现阶段 肿瘤/ II期临床 8 总部位于韩国的Bridge Biotherapeutics将自分泌运动因子（ autotaxin）抑制剂BBT-877对外 授权给勃林格殷格翰，包括了 5,050万美元首付，以及高达11亿美元的近期付款，里程碑和 上市后销售提成。 BBT-877目前处于特发性肺纤维化I期临床阶段，计划开展II期临床。 日本公司武田制药与Sosei Heptares签订了发现和开发G 蛋白偶联受体（ GPCR）靶点的新 型小分子药物和生物制剂的协议，目前将重心放在胃肠道疾病开发上，也包括扩展至其 他治疗领域的可能性。 Sosei Heptares将获得 2,600万美元的首付和近期付款，以及超过 12 亿美元的研发资助、里程碑和上市后销售提成。 里程碑付款集中在感染和肿瘤领域的交易 感染和肿瘤疾病领域的交易额主要集中在里程碑付款（总披露额分别为3,500万和3,300 美元），多数是因临床开发资产达到阶段性付款节点（见图7 ）。杨森支付Arrowhead2,500万 美元以启动JNJ-3989 (ARO-HBV)和 JNJ-6379,两个治疗乙肝候选药物的IIb期临床试验。 MorphoSys获得GSK支付的2,500万美元，将用于otilimab类风湿性关节炎III期临床试验的 启动资助。 Agenus收到吉利德支付的1,500万美元用于肿瘤药物AGEN1223 和 AGEN2373在 美国的新药临床申请（ IND）。 Jazz向 Pfenex支付 1,100万美元用于其处于临床前阶段急性淋 巴白血病治疗候选药物PF-745的开发。艾伯维再支付CytomX 1,000万美元，用来选择第二 个靶标。美国FDA 接受Neurocrine公司的 opicapone上市申请NDA ，因 此 Neurocrine需要支 付 BIAL 1,000万美元。在三菱田边顺利向日本当局递交vadadustat用于慢性肾病引起贫血 的上市申请后， Akebia获得了1,000万美元的付款。 Denali与赛诺菲合作启动DNL758临床I 期试验项目并从中获得 1,000万美元付款。吉利德向 DURECT支付 1,000万美元，基于使用其 SABER技术开发HIV 长效可注射液的进展。还有， daratumumab用于多发骨髓瘤一线治疗 在日本获批， Genmab作为其授权方获得了杨森700万美元的付款。 7 Korea-based Bridge Biotherapeutics licensed its autotaxin inhibitor, BBT-877, to Boehringer Ingelheim for approximately $50.5 million in upfront and near-term fees and milestones of up to $1.1 billion plus royalties. BBT-877 is currently in a phase I tri