2020年第二季度行业纵览与解析：交易引领生物制药行业发展.pdf

交易引领生物制药行业发展 2020年第二季度行业纵览与解析 交易并购报告 1 目录 前言 . 2 交易并购引领行业发展 . 3 诺和诺德和Alexion分别通过收购Corvidia和Portola进入心脏和Xa因子抑制剂市场 . 3 中枢神经系统（CNS）药物产品组合和处于晚期研发阶段的资产获得买家青睐 . 4 亚太地区的并购交易 . 6 日本在“安静”的亚洲市场引领并购交易 . 6 涉及COVID-19治疗药物的并购交易 . 8 许可授权交易引领制药行业发展 . 10 Genmab和艾伯维高居榜首 . 10 其他价值30亿美元的交易 - 大型制药企业与专注于目标产品的公司达成合作伙伴关系 . 11 亚太地区的许可交易 . 12 亚太地区交易额位居前十的交易量占全球前十项交易的55% . 12 本季度亚太地区交易额排名前三的交易 . 13 涉及COVID-19疗法的许可交易 . 14 2020年第三季度展望 . 16 2 前言 2020年第二季度，尽管新冠病毒大流行仍在肆虐，制药公司却并未停止建立合作伙伴关系，前十大 许可交易的总金额达到270亿美元，其中前五项的每笔交易金额均超过30亿美元。相比2020年第一 季 度（ 205亿美元）增加了24% ，但 比 2019年第二季度（ 335亿美元）减少了19% 。 生物制药市场的并购交易（ M Menarini agreed to pay $12.50 per share to Stemlines shareholders, consisting of $11.50 up-front in cash and a non-tradeable CVR; Orifarm acquired Takedas assets for $505 million upfront, $70 million in non-contingent cash and up to $95 million in milestone fees; PTC acquired Censa for an upfront fee of $53 million (including $10.4 million in cash and up to 850,000 shares valued up to $42.9 million), $326.5 million in development/regulatory milestones and commercial milestones of up to $160 million plus royalties; Shionogi acquired Tetra Therapeutics for up to $500 million, including milestone fees; 1 诺和诺德/Corvidia Alexion/Portola 2 Menarini/Stemline 3 *Orifarm/Fakeda的某些资产（欧洲） 4 PTC Therapeutics/Censa Chr Hansen/UAS Laboratories Supemus/US WorldMeds的CNS资产 5 Shionogi/Tetra 6 Dual/OncoQuest的免疫肿瘤资产 UCB/Engage Therapeutics 心血管/II期 血液/已上市 癌症/已上市 多领域/已上市 内分泌和代谢/II期 多领域/已上市 神经病和精神病/已上市 神经病和精神病/II期 $- $500 $1,000 $1,500 $2,000 $2,500 癌症/III期 神经病和精神病/II期 首付款+前期股权（百万美元） 里程碑付款（百万美元） 余款/杂项费用（百万美元） 3 M Menarini agreed to pay $12.50 per share to Stemlines shareholders, consisting of $11.50 up-front in cash and a non-tradeable CVR; Orifarm acquired Takedas assets for $505 million upfront, $70 million in non-contingent cash and up to $95 million in milestone fees; PTC acquired Censa for an upfront fee of $53 million (including $10.4 million in cash and up to 850,000 shares valued up to $42.9 million), $326.5 million in development/regulatory milestones and commercial milestones of up to $160 million plus royalties; Shionogi acquired Tetra Therapeutics for up to $500 million, including milestone fees; 4 中枢神经系统（CNS）药物产品组合和处于晚期研发阶段的资产获得买家青睐 在本季度，数家生物制药公司改变了他们的策略，以加强其神经/ 精神病产品组合，并收购了处 于晚期研发阶段的在研药物或已上市药物。在神经病药物市场， Supernus以 3亿美元的首付款和 高达 2.3亿美元的里程碑付款收购了美国WorldMeds 的 CNS产品组合，将其当前的药物资产扩展 到三种已上市药物，包括用于治疗晚期帕金森病（ PD）相关的运动功能受限“关期现象”的盐酸 阿扑吗啡（ Apokyn）、用于治疗宫颈肌张力障碍的B 型肉毒毒素（ Myobloc）以及作为左旋多巴/ 卡 比多巴的每日辅助治疗药物用于治疗PD患者“关期现象”的沙芬酰胺（ Xadago）。该项交易涉及 的产品还包括用于治疗PD的阿扑吗啡输液泵，该产品计划在2020年下半年提交NDA 和 2021年下 半年可能上市。 日本Shionogi 公司以高达 5亿美元的金额（包括里程碑付款）收购了 Tetra Therapeutics及其磷酸二 酯 酶（ PDE） 4D/B项目。交易完成后， Shionogi获得了BPN-14770的完全控制权； BPN-14770是 PDE4D 的一种变构抑制剂，用于治疗阿尔茨海默病和脆性X 染色体综合征相关的认知障碍。 Shionogi曾 在 2018年以1.6亿美元获得了该化合物在日本、韩国和台湾的开发权。比利时UCB公司以1.25亿 美元现金和高达1.45亿美元的或有费用收购了Engage Therapeutics及其产品阿普唑仑吸入制剂， 该制剂使用了Staccato递送技术。该药物于2017年从Alexza获得Engage的许可，目前正在进行适 应症为活动性癫痫发作的II期试验。 癌症仍然是交易金额最高的并购交易。意大利Menarini公司以高达6.77亿美元（每股12.50美元） 的价格收购了Stemline ，其中包括每股11.50美元的现金首付款和不可交易的或有价值权（ CVR）， 获得欧洲药品管理局（ EMA）批准后，在任何EU5国家首次上市Elzonris后，每名股东可额外获得 每股1.00美元的现金。这项交易使得Menarini加强了其肿瘤产品组合。 2019年 1月， Stemline推出 了靶向白细胞介素 -3（ IL-3）受 体 -（ CD123）的药物 tagraxofusp（ Elzonris）。 Menarini还为 Stemline 提供了一些临床项目，包括处于 II期试验阶段、用于治疗某些恶性肿瘤（包括脑癌）的 SL-701和 处于I 期试验阶段、用于治疗实体瘤和血液肿瘤的SL-801 ，该药物为一种可逆性核输出蛋白-1 （ XPO1）抑制剂。 OncoQuest将其临床和临床前免疫药物资产出售给了韩国 Dual Industrial，换取了总价值达3 亿美 元的Dual普通股和可转换债券，以及7,500万美元的研究资金。韩国Dual获得了oregovomab （抗 CA-125抗体），该药物目前处于II期试验阶段，适应症为卵巢癌。该项交易涉及的产品还包括 OncoQuest拥有的处于I 期试验阶段、用于治疗乳腺癌的抗MUC1抗体，该项目由OncoQuest与其 在中国境内拥有控制权的合资企业OncoVent共同开发。 5 在代谢领域， PTC Therapeutics收购了 Censa Pharmaceuticals，因此获得了合成药sepiapterin （ CNSA-001）的口服制剂。该药物目前处于I/II期试验阶段，适应症为因原发性四氢生物蝶呤 （ BH4）缺乏引起的高苯丙氨酸血症（ PKU）。 PTC向 Censa的股东支付了约5,300万美元的首付款 （包括 1,040万美元的现金和高达850,000股的股票，价值高达4290万美元）和2.175亿美元的里程 碑付款以获得两个处于最晚期研发阶段项目，并收到了优先审评凭证，包括完成适应症为PKU 的 CNSA-001 III期试验受试者入组所需支付的3,000万美元；每增加一个适应症的里程碑付款为 1.09亿美元，商业化里程碑付款高达1.6亿美元，外加特许专利使用费。 武田在多个治疗领域中，继上一期宣布战略并执行后，与Orifarm签署了另一项资产剥离协议， 出售其非处方药（ OTC）和处方药，包括约110种药物和膳食补充剂，如Pamol 、 Kodimagnyl和 Zymelin，以及丹麦和波兰的两个制药厂，首付款达5.05亿美元，还将在4 年内支付7,000万美元的 非或有现金以及高达9,500万美元的里程碑付款。该项交易预计将在武田2020财政年度（ 2021年 3 月）前完成。 此外，武田对其拥有的某些非处方药和处方药产品（包括Nesina和 Edarbi）进行剥离，以2.66亿美 元的首付款和高达1,200万美元的可能里程碑付款，全部出售给Celltrion 。总部位于丹麦的Chr Hansen以5.3亿美元收购了益生菌供应商UAS Laboratories ，以强化Chr Hansen的微生物平台。 6 在日本， Astellas收购了英国生物技术公司Nanna Therapeutics ，后者专注于年龄相关适应症，包括 线粒体相关疾病。 Nanna拥有一个具有新型DNA编码化学文库（ DEL）技术的筛选平台，武田计划 将 Nanna的资产用于早期项目的开发。 Nanna的股东获得了1,200万英镑（约1,500万美元）的首付 款，并有资格获得高达5,750万英镑（约7,100万美元）的里程碑付款。 亚太地区的并购交易 日本在“安静”的亚洲市场引领并购交易 本季度，亚太地区的并购交易规模与第一季度并购交易规模相近。在第一季度中，日本武田制药 （ Takeda）达成的交易额高居榜首。如前所述，武田与丹麦Orifarm和韩国Celltrion就其在欧洲和 亚洲的非处方药和处方药分别签署了两项平行交易，总金额为9.48亿美元。日本公司Shionogi以 高达5亿美元的价格收购了总部位于美国的Tetra Therapeutics公司，韩国Dual以3.75亿美元的价格 接管了加拿大OncoQuest的免疫肿瘤药物资产。所有这些交易均为本季度APAC 地区签署的金 额最高的并购交易（图2 ）。 图 2. 2020年第二季度亚太地区交易额排名前七的交易并购案 来源： Cortellis。数据截取日期为2020年7月31日。 1 Astellas以 1,200万英镑（约1,500万美元）的首付款和高达5750万英镑（约7,100万美元）的里程碑付款收购了Nanna； 2 Mycenax/Gedeon的交易金额高达1,650万美元。 Mycenax获得了200万美元的独家谈判权，并有资格获得300万 美元的签约费。 *交易尚未完成。 6 M The Mycenax/Gedeon transaction was at valued up to $16.5 million. Mycenax received $2 million for exclusive negotiation rights and was eligible to receive a $3 million signing fee. *Deals not completed. In Japan, Astellas acquired U.K. biotech firm Nanna Therapeutics, which is focused on age-related indications, including mitochondria-related diseases. Nanna owns a screening platform with novel DNA-encoded chemical library (DEL) technology, and Takeda planned to apply Nannas assets to the development of early-stage programs. Nannas shareholders received an upfront fee of GBP 12 million (approximately $15 million) and were eligible to receive milestone fees of up to GBP 57.5 (approximately $71 million). *Orifarm/武田的某些资产（欧洲） Shionogi/Tetra Dual/OncoQuest的免疫肿瘤资产 *Celltrion/Takeda的资产（亚洲） 1 Astellas/Nanna Bard1/Sienna癌症诊断 2 *Gedeon Richter/Mycenax 生物类似药tocilizumab 多领域/已上市 神经和精神病/II期 癌症/III期 多领域/已上市 多领域/发现 癌症/诊断 免疫/I期 $- $100 $200 $300$400 $500 $600 $700 $800 首付款+前期股权（百万美元） 里程碑付款（百万美元） 余款/杂项费用（百万美元） 6 M The Mycenax/Gedeon transaction was at valued up to $16.5 million. Mycenax received $2 million for exclusive negotiation rights and was eligible to receive a $3 million signing fee. *Deals not completed. In Japan, Astellas acquired U.K. biotech firm Nanna Therapeutics, which is focused on age-related indications, including mitochondria-related diseases. Nanna owns a screening platform with novel DNA-encoded chemical library (DEL) technology, and Takeda planned to apply Nannas assets to the development of early-stage programs. Nannas shareholders received an upfront fee of GBP 12 million (approximately $15 million) and were eligible to receive milestone fees of up to GBP 57.5 (approximately $71 million). 6 M The Mycenax/Gedeon transaction was at valued up to $16.5 million. Mycenax received $2 million for exclusive negotiation rights and was eligible to receive a $3 million signing fee. *Deals not completed. In Japan, Astellas acquired U.K. biotech firm Nanna Therapeutics, which is focused on age-related indications, including mitochondria-related diseases. Nanna owns a screening platform with novel DNA-encod d chemical library (DEL) technology, and Takeda planned to apply Nannas assets to the development of early-stage programs. Nannas shareholders received an upfront fee of GBP 12 million (approximately $15 million) and were eligible to receive milestone fees of up to GBP 57.5 (approximately $71 million). 6 M The Mycenax/Gedeon transaction was at valued up to $16.5 million. Mycenax received $2 million for exclusive negotiation rights and was eligible to receive a $3 million signing fee. *Deals not completed. In Japan, Astellas acquired U.K. biotech firm Nanna Therapeutics, which is focused on age-related indications, including mitochondria-related diseases. Nanna owns a screening platform with novel DNA-encoded chemical library (DEL) technology, and Takeda planned to apply Nannas assets to the development of early-stage programs. Nannas shareholders received an upfront fee of GBP 12 million (approximately $15 million) and were eligible to receive milestone fees of up to GBP 57.5 (approximately $71 million). 6 M The Mycenax/Gedeon transaction was at valued up to $16.5 million. Mycenax received $2 million for exclusive negotiation rights and was eligible to receive a $3 million signing fee. *Deals not completed. In Japan, Astellas acquired U.K. biotech firm Nanna Therapeutics, which is focused on age-related indications, including mitochondria-related diseases. Nanna owns a screening platform with novel DNA-encoded chemical library (DEL) technology, and Takeda planned to apply Nannas assets to the development of early-stage programs. Nannas shareholders received an upfront fee of GBP 12 million (approximately $15 million) and were eligible to receive milestone fees of up to GBP 57.5 (approximately $71 million). 7 总部位于澳大利亚的公司Bard1 以 2,370万美元的价格对Sienna Cancer Diagnostics 进行了并购。 Sienna正在将一种用于膀胱癌早期诊断的体外诊断试剂进行商业化。 台湾公司Mycenax同意以 1,650万美元的价格将其LusiNex资产出售给匈牙利Gedeon Ritcher公 司，该药物资产为 Actemra/RoActemra的生物类似药，包括细胞库、 CMC技术、知识产权和临床 试验数据。 Mycenax获得了200万美元的独家谈判权，并有资格额外获得300万美元的签约费。 Lusinex目前处于I期研发阶段，两家公司预计将很快进入III期研发阶段。 8 涉及COVID-19治疗药物的并购交易 本季度达成了多项并购交易，包括拥有与SARS-CoV-2感染相关（ COVID-19；图 3）治疗药物资产的 目标公司。 Novavax以约1.67亿美元的金额收购了Praha Vaccines （ Cyrus Poonawalla Group的子公司，也包括 印度血清研究所）及其生产设施。该项交易完成后， Novavax从 2021年开始确保其处于I/II期研发 阶段的COVID-19候选疫苗NVX-CoV2373的抗原年产量超过10亿支，该疫苗的成分包括提取自 SARS-CoV-2 棘突蛋白（ S）的抗原和皂苷提取物佐剂Matrix-M 。 Kalythera签署了一份具有约束力的投资条款清单，以3,700万美元的价格收购了Salzman集团。 Salzman集团拥有R-107产 品，为 COVID-19候选治疗药物，计划于2020年第三季度进行该药物的I 期试验。同时， Kalythera获得了该化合物的进一步开发权，两家公司尚未达成最终协议，但正在努 力共同开发该化合物。 BetterLife制药公司宣布以3,600万美元收购了Altum 。该公司获得了Altum公司药物AP-003在中国 大陆、日本和东盟国家以外市场的专有权。 AP-003是一种干扰素-2b （ IFNa2b）吸入制剂，用于治 疗早期COVID-19 ，目前处于II期研发阶段。 Noachis Terra公司正在开发的TerraCoV2 （用于预防COVID-19的疫苗）目前处于临床前研究阶段。 该候选疫苗已获得美国国家过敏症和传染病研究所（ NIAID）的许可，被Oragenics以 200万美元的 价格收购。计划在2020年晚些时候对TerraCoV2疫苗开展试验。 默克公司收购了Themis公司，后者正在开发一种基于麻疹病毒载体平台的SARS-CoV-2候选疫 苗，目前处于临床前研究阶段，计划于2020年开始临床研究。 Curative收购了KorvaLabs拥有的经CLIA认证和DEA许可的分析实验室，未披露价格。此前，两家 公司已达成协议，以生产和加工Curative拥有的COVID-19口服液体型诊断试剂。 9 图 3. 涉及具有开发SARS-CoV-2感染（COVID-19）疗法的潜在目标公司的并购交易 来源： Cortellis。数据截取日期为2020年7月31日。 1 Kalythera签署了一份具有约束力的投资条款清单，收购了Salzman集团。 *交易尚未完成。 9 Figure 3. M GSK will pay IDEAYA $100 million in upfront and $20 million as an equity purchase, 10 Licenses shaping the industry Genmab and AbbVie topped the charts This quarter, from the five deals valued over $3 billion, the top deal was AbbVie agreeing to jointly develop and commercialize Genmabs bispecific antibodies, including epcoritamab (DuoBody- CD3xCD20), DuoHexaBody-CD37 and DuoBody-CD3x5T4, as potential cancer treatments. In the $3.9 billion deal (Figure 4), AbbVie paid $750 million upfront to gain access to the programs, and Genmab is also eligible to receive up to $1.15 billion in development, regulatory and sales milestone payments. Up to $2 billion is reserved for an option exercise and milestones related to four antibodies that could emerge from a discovery research collaboration combining Genmabs DuoBody technology and AbbVies ADC technology. For epcoritamab, Genmab will book net sales in t e United States and Japan, with AbbVie responsible for global commercialization. AbbVie will also remunerate Genmab tiered royalties of between 22% to 26% on net sales of the drug outsi e the United States and Japan. For DuoHexaBody-CD37, DuoBody-CD3x5T4 and the antibodies to be discovered, the companies will share development and commercialization in the United States and Japan, with Genmab retaining the right to co-commercialize these products outside of the two territories. Pre-tax profits from product sales will be shared on a 50:50 basis. Figure 4. The top 10 licensing deals signed in Q2 2020 by value Source: Cortellis. Data collected on July 31, 2020. From AbbVie, Genmab received $750 million upfront and was eligible to receive up to $1.15 billion in contingent fees and up to $2 billion for an option exercise and milestones related to four antibodies. BMS is paying Repare an upfront payment of $65 million (including $15 million in equity) and up to $3 billion, including $301 million in total milestones per program, $176 million for certain specified research and $125 million for certain specified commercial milestones; GSK will pay IDEAYA $100 million in upfront and $20 million as an equity purchase, 1 Genmab/艾伯维 Alteogen/未披露 Fate/杨森 2 Repare/BMS 3 IDEAYA/葛兰 4 Roche/信达 uniQure/CSL 武田/Neurocrine 5 Arcus/吉利德 6 Alnylam/Blackstone 癌症/II期 不详/不详 癌症/发现 癌症/发现 癌症/临床前 癌症/发现 血液/III期 神经/II期 癌症/注册前 内分泌/注册前 首付款+前期股权（百万美元） 里程碑付款（百万美元） 余款/杂项费用（百万美元） $- $500 $1,000 $2,000$1,500 $2,500 $3,000 $3,500 $4,000 $4,500 10 Licenses shaping the industry Genmab and AbbVie topped the charts This quarter, from the five deals valued over $3 billion, the top deal was AbbVie agreeing to jointly develop and commercialize Genmabs bispecific antibodies, including epcoritamab (DuoBody- CD3xCD20), DuoHexaBody-CD37 and DuoBody-CD3x5T4, as potential cancer treatments. In the $3.9 billion deal (Figure 4), AbbVie paid $750 million upfront to gain access to the programs, and Genmab is also eligible to receive up to $1.15 billion in development, regulatory and sales milestone payments. Up to $2 billion is reserved for an option exercise and milestones related to four antibodies that could emerge from a discovery research collaboration combining Genmabs DuoBody technology and AbbVies ADC technology. For epcoritamab, Genmab will book net sales in the United States and Japan, with AbbVie responsible for global commercialization. AbbVie will also remunerate Genmab tiered royalties of between 22% to 26% on net sales of the drug outside the United States and Japan. For DuoHexaBody-CD37, DuoBody-CD3x5T4 and the antibodies to be discovered, the companies will share development and commercialization in the United States and Japan, with Genmab retaining the right to co-commercialize these products outside of the two territories. Pre-tax profits from product sales will be shared on a 50:50 basis. Figure 4. The top 10 licensing deals signed in Q2 2020 by value Source: Cortellis. Data collected on July 31, 2020. From AbbVie, Genmab received $750 million upfront and was eligible to receive up to $1.15 billion in contingent fees and up to $2 billion for an option exercise and milestones related to four antibodies. BMS is paying Repare an upfront payment of $65 million (including $15 million in equity) and up to $3 billion, including $301 million in total milestones per program, $176 million for certain specified research and $125 million for certain specified commercial milestones; GSK will pay IDEAYA $100 million in upfront and $20 million as an equity purchase, 10 Licenses shaping the industry Genmab and AbbVie topped the charts This quarter, from the five deals valued over $3 billion, the top deal was AbbVie agreeing to jointly develop and commercialize Genmab