Roche Bets Nearly $1 Billion on Chinese Biotech's Preclinical ADC Pipeline

On January 2, 2024, MediLink (Suzhou Yilian Biomedical Co., Ltd.) announced that it had reached a global collaboration and licensing agreement with Roche. The two parties will collaborate to develop YL211, a next-generation antibody-drug conjugate candidate targeting mesenchymal-epithelial transition factor (c-MET) ("c-MET ADC"), for the treatment of solid tumors.

According to the terms of the agreement, Roche will obtain the exclusive rights for the development, manufacturing, and commercialization of MediLink's YL211 project worldwide.MediLink will collaborate with Roche China Innovation Center (CICoR) to advance the YL211 project into Phase I clinical trials, after which Roche will take over further development and commercialization on a global scale.Roche will pay MediLink an upfront payment and near-term milestone payment of 50 million US dollars, with additional potential milestone payments of up to 1 billion US dollars for development, registration, and commercialization, as well as tiered royalties based on global annual net sales in the future.

In the just-passed 2023, MediLink reached a cooperation agreement with BioNTech to license the global rights outside of Greater China for the HER3 (human epidermal growth factor receptor 3) ADC clinical pipeline YL202. The potential total amount of this cooperation exceeds 1 billion US dollars.

Two ADC pipeline successes in a row, with both the commercialization of clinical pipelines and the monetization of early-stage pipelines—how did MediLink, founded in 2020, quickly tap into the BD market? And how did it secure a collaboration with Roche, one of the ADC giants? VCBeat exclusively interviewed Dr. Xiao Liang, co-founder and COO of MediLink, who orchestrated the aforementioned collaborations, hoping to gain more insights from Chinese Biotech experiences in reaching partnerships with multinational corporations (MNCs).

VCBeat: Founded only three years ago, MediLink has already secured two major MNC deals. Is this relatively rare?

Xiao Liang:ADC can be said to be one of the hottest research and development fields at present. Large pharmaceutical companies in the global pharmaceutical industry, including MNCs, have been making moves in the ADC track, with transactions emerging one after another. As a young Biotech company, MediLink is certainly benefiting from the current ADC boom, leveraging the power of this trend.

On the other hand, as an enterprise focusing on innovative R&D in the ADC field, MediLink was founded in Suzhou BioBay, a biopharmaceutical industry park with a strong atmosphere of innovation and entrepreneurship, which provided a foundation for the company's early rapid development. Despite being established for only three years, we have quickly advanced innovation by building upon the shoulders of the first, second, and third generations of ADC technologies, establishing a differentiated technology platform with independent intellectual property rights. These factors have laid the cornerstone for the company to reach cooperation agreements with MNCs.

VCBeat: What Support Contributed to the Success of Two MNC BD Projects Within the Year?

Xiao Liang:The continuous achievement of cross-border transactions is not only attributed to the company's differentiated ADC technology platform, but more crucially, we have a pragmatic team. Under the close collaboration and leadership of the three founders (Tongtong Xue, Jiaqiang Cai, and myself), our business team has efficiently completed comprehensive work ranging from IP innovation, early project initiation, CMC development, preclinical development to clinical development.

At the same time, our investors have provided substantial support in MediLink's external BD collaborations. From resource alignment and BD negotiation strategies to offering valuable advice on IP and legal matters, they have laid a solid foundation for the successful closure of these partnerships.

VCBeat: Why Was MediLink Able to Secure Roche’s First ADC Move, One of the Global ADC’s Three Giants?

Xiao Liang:As one of the MNCs with the earliest presence in the ADC field, Roche has successfully launched ADC products including Kadcyla (T-DM1) and Polivy (CD79 ADC), demonstrating Roche's leading advantage in ADC clinical development and commercialization.In our communication with Roche, we found that they have been paying close attention to the next generation of ADC technology and have a broad understanding of the technology in China's ADC field. Because of this, Roche has extremely high requirements for technology platforms, and only those that are best in class or have such potential can win their favor.

Our collaboration with Roche initially began with an MTA (Material Transfer Agreement), undergoing a lengthy evaluation and validation process. It was only after demonstrating the technology's distinctiveness and product advantages that we eventually gained recognition. This partnership also signifies that MediLink's technology platform has earned Roche's initial trust. We look forward to subsequent clinical successes, laying the groundwork for broader cooperation in the future.

VCBeat: Where is the window period for laying out the next generation of ADCs? Are ADCs with non-overheated targets, sufficient potential, and unconquered targets becoming a prominent advantage for ADC Biotechs?

Xiao Liang:Reviewing the development process of the ADC field over the past few decades, it can be seen that the first significant success came from the application of tubulin inhibitors, such as toxins like MMAE and DM1. This success gave rise to the widely used vc-MMAE technology platform. The second major success came from the application of topoisomerase inhibitors, such as toxins like SN38 and DXd, forming the currently well-known GGFG-DXd platform.This also makes it possible for ADC targets that previously failed with older toxins, such as the TROP2 target.

For the next generation of ADC technology, we expectThe window of opportunity in the future will appear inA new generation toxin linker platform with better safety and the ability to address drug resistance issues will help overcome the limitations of existing technology platforms.Of course, for ADC Biotech, there are also certain opportunities in exploring various targets and combinations based on existing technology platforms, coupled with efficient and rapid preclinical/clinical development capabilities.

VCBeat: In terms of BD, what are the key milestones in ADC new drug development projects? What BD potential does the early-stage project have?

Xiao Liang:Technical features, target selection, clinical strategies, etc., are all crucial.Early-stage projects, compared to Phase II/III projects, have less clinical data or are still in the preclinical stage, posing greater future risks but also offering potentially higher rewards.But whether the project value can be truly realized needs to be measured by: 1) the differentiated advantages of its own technology; 2) the capability and efficiency of subsequent development.Cooperating at an early stage is actually a balance of risks and benefits for both parties. Leveraging the partner's capabilities in later-stage development to accelerate the rapid market entry of the product could be a truly complementary advantage and a powerful collaboration for both sides.

VCBeat: What are the differences in evaluation and transaction for ADC pipelines at different stages of licensing out?

Xiao Liang:Products in the early stage will place more emphasis on differentiated advantages in technology and targets, while products in the later stage will be more reflected in clinical data, which essentially represents different risks. In terms of transactions, the overall framework will also adopt different models to achieve balance.For example, for products in the early stage or products in the late stage with relatively fierce target competition, partners often propose an option model to balance risks. This means allowing the Licensor to first bear or jointly bear a certain percentage of the development costs, and then decide whether to exercise the option-in based on clinical results.Some recent transactions in China have adopted a similar model.

VCBeat: As the transferor, how to choose the BD transferee? What are the criteria?

Xiao Liang:Cooperation is a two-way selection process. For MediLink, our ultimate goal is to benefit cancer patients worldwide with our products as early as possible. Therefore, our considerations are not limited to financial figures but focus more on how to accelerate the rapid development of the projects. Currently, our product pipeline is focused on solid tumors, soWhen selecting partners, they tend to favor companies with strong clinical development resources and experience in the corresponding solid tumor indications, as well as a successful track record in recent years.

Another key point is whether there is a deep understanding of the cooperative project itself and whether it can contribute to the development of future products. For instance, in the YL211 project, which is a collaboration with Roche and targets cMet, Roche has previously developed antibodies targeting cMet, possessing profound understanding and development experience with this target. Additionally, Roche has a mature companion diagnostic platform, Ventana, which can provide significant assistance during the clinical development phase of the project.

At the same time, Roche's familiarity with the Chinese market and its continuous investment are also important reasons for us to include the Chinese region in the authorized cooperation scope. In 2022, Roche China Innovation Center (CICoR) was officially upgraded and established. The efficiency and professionalism demonstrated by the CICoR R&D team and the China BD team during the due diligence cooperation process left a deep impression on us. The resonance in cooperation philosophy between the two teams has created conditions for establishing a good partnership.

VCBeat: Based on your observation, what are the current tendencies of MNCs and Pharma in ADC development? Do MNCs have specific standards and requirements for projects?

Xiao Liang:Based on our observations, virtually all multinational corporations (MNCs) and pharmaceutical companies that have ventured into the oncology pipeline have adopted various strategies to develop or acquire ADC (antibody-drug conjugate) products or technologies. Examples include Pfizer and Seagen’s merger and collaboration, the platform-type partnership between Kelun-Biotech and MSD, as well as several project-based licensing collaborations reached by Chinese pharmaceutical companies such as RemeGen and Hansoh Pharma with overseas firms in the past two years.In terms of project standards, we generally feel that it needs to reach the top three globally, or have a relatively eye-catching differentiated advantage in targets or technology, with the potential to surpass the former.

VCBeat: ADC was one of the hottest fields for domestic innovative drug licensing out in 2023. What role do you think China's ADC innovative drug development plays in the global landscape?

Xiao Liang:Globally, ADC licensing deals have entered a mature phase, and in the past two years, China has also gradually entered a window period. However, there are still very few companies in China that have achieved large-scale deals.ReasonOn the one hand, China's Biotech companies need to accumulate more reputation in the global market, and on the other hand, overseas companies show certain distinctions in their requirements for data from Chinese Biotech companies, necessitating sufficient clinical data POC.

Based on our observations, the number of ADC innovative drug developments in China should rank first. However, most of them are still in a follower position in terms of target or technology layout. There is also a portion of true innovation, but it is currently still in the early development stage and has the potential to demonstrate significant promise in the future. The domestic companies that have achieved large transaction amounts so far have been cultivating the ADC field for many years. As a rising star, MediLink has also made some achievements in the past two years, including upfront payments totaling nearly 200 million US dollars from deals based on our ADC technology platform, with cumulative total deal amounts exceeding 5 billion US dollars. Nevertheless, continuous efforts and steady progress are still required to achieve the next phase of goals.

VCBeat: Has the ADC industry chain in China entered a mature and thriving period?

Xiao Liang:ADC consists of three components, including the antibody, linker, and toxin. Relatively speaking, contract research organization (CRO) services that provide standalone antibody development and toxin-linker development have become fairly mature in China. However, contract development and manufacturing organization (CDMO) services for ADC as a whole are still in a phase of rapid growth. For example, WuXi XDC has recently completed its IPO and achieved solid performance in the capital markets. It is expected that within the next two to three years, China’s ADC industry chain will gradually mature.

VCBeat: For Biotech founders who want to engage in BD work, what experiences can you share?

Xiao Liang:BD cooperation is one of the ways for a company to achieve its strategic goals, before launching the cooperation.The first step is to determine the company's current development strategy, understand the competitive landscape, and anticipate potential future scenarios to establish the most appropriate strategy for the present.At the same time, BD cooperation is a long-term process, and its success or failure involves various factors, soMaintaining a positive mindset, reasonable expectations, and collaborating with the team while making good use of external resources will all contribute to the successful completion of the transaction.

YL211 is a next-generation antibody-drug conjugate (ADC) that specifically targets the mesenchymal-epithelial transition factor (c-MET). c-MET, a member of the receptor tyrosine kinase (RTK) family, is closely associated with tumor formation, invasive growth, and metastasis, making it a key target for treating epithelial-mesenchymal transition. Although various c-MET-targeted therapies, including ADCs, have demonstrated efficacy in patients with solid tumors, there remains an opportunity globally to provide better treatment options to address significant unmet medical needs. YL211, currently in the clinical application stage, utilizes MediLink's next-generation TMALIN® ADC platform technology along with a highly specific c-MET antibody. YL211 has shown promising efficacy and safety in multiple preclinical tumor models and safety evaluation experiments.

Tumor Microenvironment Activable LINker-payload (TMALIN^®) The novel antibody-drug conjugate (ADC) platform technology, independently developed by MediLink, is a new type of ADC platform with dual cleavage mechanisms that can be activated both extracellularly and intracellularly through the tumor microenvironment and lysosomes. It features high water solubility, high uniformity, excellent in vivo and in vitro stability, as well as tumor tissue enrichment properties. Compared to existing ADC technologies, this platform has demonstrated a wider therapeutic window in multiple in vivo efficacy models and safety evaluation experiments. Currently, several ADC products based on this platform have entered the clinical trial stage.

MediLink, founded in 2020, is a clinical-stage biopharmaceutical company focused on developing innovative conjugated drugs. It has developed the latest generation of proprietary Tumor Microenvironment Activable LINker-payload (TMALIN®) new antibody-drug conjugate platform technology, which achieves high DAR value uniformity and stable conjugation while further increasing the therapeutic window of ADC drugs, enhancing their efficacy in treating solid tumors. The goal is to provide better treatment options for cancer patients worldwide. Headquartered in Suzhou, China, with research and development branches established in Shanghai, China, and Boston, USA.