2024年第一季度，中国多家创新药企与全球制药巨头进行了一系列跨境交易。法律专家表示，对外授权许可交易的增加体现了国际社会对中国药企研发实力日益认可，这既带来了市场信心，也带来了更多战略合作。
对2024年第一季度仍显冷清的交易市场来说，创新药行业构成了一股“清流”。
过去三个月，从并购交易，到对外授权许可（license-out），中国创新药企业频频与阿斯利康、诺华等海外医药巨头“交手”，展现出国际市场对于中国创新药研发水平的认可，也以产业板块之力，提振了当下市场信心。
锦天城律师事务所高级合伙人虞正春律师对此颇有感触。“1至2月，中国创新药企业与海外药企完成了超过30起以上的跨境交易，包括并购、股权融资、权益合作等多种类型，其中以license-out交易为主。”他说。
这延续了2023年的势头——实际上，过去一年中国license-out合作项目超过百起，交易金额及首付款比例都创下历史新高。
虞律师解释道，中外药企的交易形式主要包括两类：一类是并购交易，主要包括股权并购、资产并购；一类是权益合作，主要包括完全权益转让或者部分权益合作。
“无论哪种方式，都是合作方利用各自不同的优势共同推进创新药的研发及商业化，从而极大提升该过程的成功率及效率。”而基于创新药高风险、高投入的特点，license-out合作成为了创新药研发的新趋势，中国部分创新药管线也得到了跨国药企的认可。
放大镜下的out-licensing交易
据环球律师事务所生命科学及医疗业务牵头人周磊律师的行业经验，实际上，中国创新药企业对于license-out许可交易的热情要来的更早一些。
2017年，环球曾代表百济神州与新基公司完成license-out和股权交易，近14亿美元的交易金额创下彼时令行业惊讶的突破，也开始为中国创新药企的研发能力的国际评价提供了证明。周律师认为，在这一里程碑式的案例后，更多中国药企开始通过license-out的方式“出海”。
尽管此后还有很多比如传奇生物和强生等具有行业影响力的license-out项目，但在2021年以前，跨境许可交易还是呈现license-in比license-out火热的一边倒趋势。而到了2022年，“随着自主研发能力持续提升，以及国内和香港资本市场降温、行业政策影响等因素，创新药行业进入调整期，创新药企的诉求更加向‘卖出’倾斜，license-out交易数量快速增长，并大幅超过了license-in交易的数量”，周律师说。
虞正春律师也坦言，在目前中国创新药企业股权融资难度较大的环境下，“通过license-out拿到高额的首付款，也是破局的重要渠道”。
不过他表示，被跨国药企看中的，主要还是具有“首创新药模式”（First-in-class）潜力的管线，这就把大多数的中国创新药企业排除在外。
此外，近年还出现了某些管线“扎堆出海”的情况，例如“2023年，我们观察到license-out合作的管线主要布局在ADC、单/双抗药物、CGT药物、GLP-1药物等赛道——其中GLP-1药物尤其火爆。2024年也没有太大差异”，虞律师说。
当然，能够实现“出海”，“本质上是因为中国本土药企力量加强，做出了很好的药”，环球律师事务所合伙人黄旭春律师说，“跨国药企看到了中国的研发能力，从而希望通过合作将药品尽早引入到境外市场，作为对自身产品管线的补充”。
实际上，license-out合作能够实现“各取所需”：一方面，创新药企业通过获得高额首付款，补偿融资困难，推进管线研发、降低研发风险，吸纳海外临床开发经验及商业化能力，未来进一步取得高额的里程碑付款以及海外市场销售分成；
另一方面，对于引进方，购买“授权”也能够分摊研发风险和成本、丰富产品管线，如市场潜力大的管线顺利上市，也能够快速抢占市场，获得丰厚回报。
更需“长期主义精神”
虽然license-out交易逻辑相对清晰，但伴随热度加增，周磊律师观察到license-out交易过程正变得日趋复杂。
“一是license-out交易往往会与股权交易捆绑，混合交易变得更加普遍，例如我们团队处理的几个项目中还包含着并购和投资交易；二是license-out交易可能需要讨论双方共同完成早期开发临床研发、生产和CMO、商业化运营等全流程，双方要进行一揽子谈判和合作；三是部分涉及更深入的项目并不只针对单一产品，而是基于整个产品线的全面合作。”他介绍道。
正是因为这样的复杂性，市场热度越高，有时候反而要把交易做得越“扎实”一些，要秉持相对冷静的“长期主义精神”，这对服务于此类交易的律师提出了许多新要求。
一是“看得全”。“要把交易相关问题放到整个市场里去考虑。律师技能要丰富，在监管、合规、交易、知识产权等多方面帮助客户安排好整个项目。服务好一笔license-out交易往往需要全能、一站式的团队。”周律师说。
二是有国际化视野。周律师坦言，部分国内创新药企对国际交易、商业惯例、估值模型等还不熟悉，这就需要交易律师承担部分商业职能，“帮助客户厘清商业诉求、完成项目落地”。
三是突出的协调能力。黄旭春律师说，license-out交易往往涉及创新药企业内部的运营、财务、供应链等诸多职能部门，“律师需要具备很强的协调能力，深度接触各个部门、听懂他们的顾虑和需求，最终协调好各方利益，并体现到法律文本中。服务license-out交易中最难的就是这些增值内容 ”。
此外，在如火如荼的市场环境下，周磊律师已经处理了很多license-out交易出现“退货”甚至争议的情况，例如产品在研发、审批、销售等里程碑节点上没有达成预定目标，无法触发里程碑付款或者由于重大行业环境变化、政策调整和交易一方的控制权变化等重大情势变更。
实际上，周律师提醒道：“创新药研发成功率整体并不高，交易完成后的长期合作过程中常面临争议。律师在交易前写下的合同条款能否在此后难免发生的争议中保护好客户利益，这不是靠抄写模板就能达成的。”
“经历了签约官宣时的‘繁花盛景’，还要经历可能‘丑陋’的诉讼仲裁争议，才能成为一名好的许可交易律师。”他说。
“从我的经验来说，交易律师特别需要在准备协议时，尽量预测未来磨合过程中可能出现的困难，并在协议里预留下解决问题的方案，随后帮助双方企业搭建好沟通机制。未来即使发生争议，企业也可以迅速根据机制，找到有效方案。”黄旭春律师说。
其他关键问题：IP和数据
实际上，一款创新药是否有“价值”，除了其本身的创新性，也取决于创新药企业是否对其展开了充足、有效的知识产权保护。
“律师在服务license-out交易时，会着重关注企业对产品是否有专利保护，该专利保护能否确保产品在市场上处于优势地位、其他产品无法轻易越过屏障去构成竞争；还会从商业秘密、专有技术和不竞争的角度出发，确保产品有市场竞争力。”黄旭春律师说。
虞正春律师也指出，“客户很关注合作中所涉及知识产权的剩余保护期限、是否涉及所属国药品专利期限补偿制度、目前已有专利能否完整保护药品技术方案以及是否存在侵权风险等问题，对开展不同国家的全面专利自由实施分析（FTO）的需求也越来越多”。
此外，虞律师说，交易文件中也要特别约定好知识产权归属和许可权限问题。“知识产权还有涉税问题——根据合作方所属国家的不同税收政策以及签署的双边协定，不同交易架构可能会产生不同税率，必须纳入考量。”最后，双方也要约定好知识产权争议解决机制，一旦产生纠纷，可以实现有效维权。
医药类跨境合作还要特别注意敏感个人信息及人类遗传资源信息的跨境传输问题。“在license-out项目中可能涉及临床试验数据、药品不良反应信息跨境传输等情形，涉及受试者的个人健康数据、包含人类生物学组学数据的人类遗传资源信息等。中国创新药企业应提前关注各国的相关监管制度，及早部署，合规开展跨境合作。”虞律师提醒道。
FROM CHINA TO THE WORLD
The first quarter of 2024 saw a flurry of cross-border transactions involving Chinese companies and global pharmaceutical giants like AstraZeneca and Novartis in the space of innovative drugs. Legal experts say the industry's focus on out-licensing transactions signals a growing international recognition of China's R&D prowess in innovative drugs, promising both market confidence and strategic partnerships.
In the still sluggish deal-making market of the first quarter of 2024, the innovative drugs industry stands out as an exception. Over the past three months, Chinese innovative drug companies have engaged in multiple deals with overseas pharmaceutical giants such as AstraZeneca and Novartis, from mergers and acquisitions to out-licensing transactions. This activity demonstrates the international market's recognition of China's research and development prowess in innovative drugs, boosting market confidence amidst the current climate in the medicine sector.
Yu Zhengchun, senior partner at Allbright Law Offices, has valuable insights to share. "Between January and February, Chinese innovative drug companies completed over 30 cross-border deals with overseas pharmaceutical firms, including M&A, equity financing, and equity cooperation, with out-licensing deals being predominant."
This momentum follows that of 2023, which saw over a hundred out-licensing deals in China alone, reaching historic highs in both deal value and down payment ratios.
According to Yu, deals between Chinese and foreign pharmaceutical companies typically take two forms: M&A, including equity and asset acquisitions, and equity cooperation, encompassing full equity transfers or partial equity partnerships. "Regardless of the form, cooperation partners leverage their respective strengths to jointly advance the R&D and commercialization of innovative drugs, significantly improving the success rate and efficiency of the entire process."
Given the high-risk, high-investment nature of innovative drugs, out-licensing has become the new trend in R&D, with some innovative drug pipelines in China gaining recognition from multinational pharmaceutical companies.
OUT-LICENSING UNDER SCRUTINY
Alan Zhou, leader of the life science and healthcare practice at Global Law Office, observes that Chinese innovative drug companies have long shown enthusiasm for out-licensing transactions. In 2017, Global Law Office represented BeiGene in completing out-licensing and equity transactions with Celgene Corporation, with a deal value of nearly USD 1.4 billion. This breakthrough surprised the industry and served as early proof of the international recognition of the R&D capabilities of Chinese innovative drug companies. Zhou believes that after this landmark deal, more Chinese pharmaceutical companies began to "go global" through the out-licensing model.
While there have been many influential out-licensing projects since then, such as Legend Biotech and Johnson & Johnson, license-in transactions were decisively more popular than out-licensing before 2021. However, in 2022, "with continuous improvement of indigenous R&D capabilities, as well as factors such as the cooling of domestic and Hong Kong capital markets and the impact of industry policies, the innovative drugs industry entered a period of adjustment," says Zhou. "The demands of innovative drugs companies shifted more towards 'selling,' resulting in a rapid growth of the number of out-licensing deals, which exceeded the number of license-in transactions by a large margin."
Yu also acknowledges that in the current climate, where equity financing remains quite difficult for Chinese innovative drug companies, "getting a higher down payment through out-licensing is also an important way out." However, he notes that multinational pharmaceutical companies are mainly interested in pipelines with the potential for "first-in-class" drugs, which excludes most Chinese innovative drug companies.
Furthermore, there have been cases of pipelines going global "in clusters" in recent years. For example, "in 2023, the pipelines for out-licensing were mainly in ADC, mono/dual antibody drugs, CGT drugs, and GLP-1 drugs, with GLP-1 drugs being particularly popular. This year is not expected to be very different," says Yu.
Certainly, the ability to "go global" is essentially attributed to the growing strength of Chinese pharmaceutical companies, which has led to the production of excellent drugs. According to Charlene Huang, partner at Global Law Office, "multinational pharmaceutical companies have recognized China's R&D capabilities and hope to introduce drugs to overseas markets as soon as possible through cooperation as supplements to their own product pipelines."
In fact, everyone can benefit from out-licensing. On one hand, with high down payments, innovative drug companies can compensate for financing difficulties, promote pipeline R&D, lower R&D risks, and learn from overseas clinical development experience and commercialization capabilities, thus obtaining high milestone payments and shares from overseas market sales in the future. On the other hand, for licensees, purchasing "licenses" can also amortize R&D risks and costs and enrich product pipelines. If pipelines with great market potential successfully go to market, they can also quickly grab market share and earn handsome returns.
"LONG-TERMISM" NEEDED
Although the logic of out-licensing deals is relatively straightforward, Zhou notices that the out-licensing process is becoming more complex as it continues to grow in popularity.
"First, out-licensing deals are often bundled with equity deals, making mixed transactions more common. For example, several projects handled by our team also include M&A and investment. Second, an out-licensing deal may require both parties to discuss how they will jointly complete the entire process of clinical R&D for early-stage development, production and CMO, commercial operations, etc. Both sides need to engage in a slew of negotiations and cooperation. Third, some more in-depth projects do not target only one product but are based on comprehensive cooperation across the entire product line."
It is precisely because of such complexity that despite the hot market, sometimes it is necessary to make deals more "solid" and uphold a relatively calm "long-term" spirit, which puts forward many new requirements on lawyers advising such deals.
First is to have a "panoramic view". "We need to consider deal-related issues against the entire market. Lawyers must have a rich skillset to help clients arrange the entire project in various aspects such as regulation, compliance, deal-making, intellectual property, etc. Advising an out-licensing deal well often requires an all-around and one-stop team," says Zhou.
Second is to have an international perspective. Zhou admits that some domestic innovative drugs companies are not yet familiar with international deal-making, business practices, valuation models, etc., which requires transactional lawyers to undertake some commercial functions to "help clients clarify business demands and complete project implementation".
Third is to have outstanding coordination ability. According to Huang, out-licensing often involves many functional departments within an innovative drugs company, such as operations, finance, and supply chain. "Lawyers need to have strong coordination skills, have in-depth contact with various departments, understand their concerns and needs, and ultimately coordinate the interests of all parties and reflect those interests in legal texts. The most challenging part of advising out-licensing deals is these value-added services."
In addition, despite the bustling market environment, Zhou has already dealt with many cases of "product return" or even disputes in out-licensing deals, such as the failure to achieve predetermined targets in product milestones such as R&D, examination and approval, and sales making it impossible to trigger milestone payments, or significant changes in industry environment, policy adjustments, or controlling power of one side to the transaction.
As a matter of fact, "the overall success rate of innovative drugs R&D is not high, and there are often disputes over long-term cooperation after a deal is completed. Whether the contract terms written by lawyers before the transaction can protect the interests of clients in the disputes that may inevitably arise later cannot be achieved simply by copying contract templates," reminds Zhou.
"To become a top transactional lawyer for out-licensing, one must go through not only the 'beautiful moments' of official deal announcement but also the potentially 'ugly' moments of litigation and arbitration."
"In my experience, transactional lawyers need to predict as much as possible the difficulties that may arise in future integration when preparing agreements, and include solutions in the agreements and help both sides establish a proper communication mechanism. This way, even if disputes occur in the future, companies can quickly find effective solutions based on that mechanism," says Huang.
OTHER ISSUES: IP AND DATA
In fact, the "value" of an innovative drug depends not only on its novelty but also on whether the company behind it has provided sufficient and effective IP protection.
"When advising on out-licensing deals, lawyers focus on whether the enterprise has patent protection for the product and if this protection can ensure a competitive edge in the market, preventing other products from easily entering the competition. They also ensure the product's competitiveness in terms of trade secrets, proprietary technology, non-compete clauses, etc.," says Huang.
Yu also points out that clients are very concerned about the remaining protection period of IP involved in cooperation, whether it includes the compensation system for the patent period of drugs in their respective countries, whether existing patents can fully protect drug technology solutions, and whether there is any risk of infringement. There is also a growing demand for comprehensive patent free-to-operate (FTO) analysis in different countries.
Additionally, Yu states that issues of IP ownership and licensing rights should be specifically agreed upon in transaction documents. "IP also involves tax issues. Depending on the different tax policies of the cooperating parties' countries and the bilateral treaties signed, different deal structures may result in different tax rates, which must be considered." Finally, parties should agree on a mechanism for resolving IP disputes so that if a dispute arises, the parties can effectively safeguard their rights.
Special attention must also be paid to the cross-border transfer of sensitive personal information and human genetic resources information in cross-border pharmaceutical cooperation. "An out-licensing project may involve the cross-border transfer of clinical trial data and adverse drug reaction information, as well as the personal health data of subjects and human genetic resources information containing human biometrics data. Chinese innovative drug companies should pay attention to relevant regulatory systems in various countries in advance, make early preparations, and carry out cross-border cooperation in compliance with regulations," cautions Yu.
