Can YiLian Bio, a Rising ADC Innovator Focused on Solid Tumors, Achieve Late-Mover Advantage?

Following the PD-1 wave, antibody-drug conjugates (ADCs) have emerged as another hot trend in R&D. By combining the dual advantages of small-molecule drugs and antibody-based therapeutics, ADCs can precisely deliver toxins to tumor cells to exert cytotoxic effects, earning them the nickname “biological missiles.”

Compared with small-molecule drug therapy, ADCs offer greater specificity and fewer side effects; compared with antibody drugs, ADCs demonstrate stronger tumor-killing efficacy and a bystander effect.Since the launch of the first ADC drug in 2000, 14 ADC drugs have been approved on the global market. Among them, DS-8201, launched by Daiichi Sankyo Co., Ltd., has garnered the most significant attention. Following the approval of DS-8201, R&D enthusiasm for ADC drugs surged rapidly, marking a peak period in their development.

According to Nature’s projections, the total sales of the 10 ADC products launched before 2020 will exceed $16.4 billion by 2026. The domestic ADC market in China gradually gained momentum in 2020 and is expected to reach RMB 7.4 billion in 2024 and RMB 29.2 billion in 2030, with a compound annual growth rate (CAGR) of 25.8% from 2024 to 2030.

Such a promising market outlook is attracting another wave of companies to delve deeply into this field. However, the public is quietly concerned about another issue: Will ADCs repeat the pitfalls seen in PD-1 development? Could it be that future ADCs will also become so numerous that industry insiders jokingly remark there are “enough to take a bath in”?

From small-molecule innovative drugs to large-molecule conjugate therapeutics, Dr. Cai Jiaqiang, with nearly 30 years of experience in innovative R&D within the biopharmaceutical sector, is undoubtedly well-positioned to answer this question. His response: no.

“Unlike PD-1, which represents a drug targeting a single molecule, ADCs represent a broad class of drug molecules.”ADC drugs consist of three components: an antibody, a small-molecule toxin, and a linker. The antibody determines which types of diseases are targeted, the toxin dictates the mechanism of action, and the linker controls when and where the toxin is released from the antibody to exert its therapeutic effect.“The combinations of these three components are highly diverse. Variations in antibodies, linkers, and small molecules can lead to differentiated clinical outcomes. Such combination effects cannot be determined through simple prediction; in-depth research is required.”

Dr. Cai stated that, unlike antibody drugs, which achieve therapeutic effects solely by targeting receptors, the emergence of antibody-drug conjugates (ADCs) has created more opportunities to “turn waste into treasure” for many small-molecule drugs that were previously undruggable or exhibited poor efficacy, thereby providing scientists with greater scope for innovation.

“Although the development of small-molecule drugs has a history spanning over a century, why does the drug success rate remain so low to this day? One reason is that while many diseases appear ‘feasible’ at the molecular and cellular levels, or in terms of pathogenic mechanisms, numerous small-molecule drug candidates encounter obstacles in becoming viable medicines due to various factors such as pharmacokinetics and toxicity.”

In a sense, ADC drugs have addressed these issues to some extent.“ADCs are akin to targeted prodrugs, greatly expanding the potential for developing drugs from small molecules that were previously considered undruggable. It can be said that for every small molecule capable of becoming a drug, an ADC can be developed—and potentially even more, since each candidate small molecule can be paired with different types of antibodies.”

This means that ADCs have a longer journey ahead and a broader scope for exploration. This is also why Dr. Jiaqiang Cai, together with the other two founders, Dr. Tongtong Xue and Dr. Liang Xiao, established MediLink to dedicate themselves to the development of next-generation ADC products and R&D platforms. The vast potential for growth in ADC drug development has bolstered their confidence in embarking on this entrepreneurial path.

In March this year, MediLink completed a Series A financing round totaling RMB 350 million, with participation from several prominent investment firms including Xingze Capital, Zhengxingu Innovation Capital, and Qiming Venture Partners. One of the key reasons for the strong investor interest is the three founders’ extensive R&D experience in antibody-drug conjugate (ADC) therapeutics and their impressive industry track records.

Xue Tongtong, Xiao Liang, and Cai Jiaqiang, three industry scientists, were personally involved in the first wave of ADC drug development in China. At that time, Daiichi Sankyo’s DS-8201 had not yet been launched, and ADCs were not as prominent as they are today.

As early as 2014, Dr. Xue led the acquisition of toxin-linker technology for the first innovative ADC project through external collaboration, thereby initiating ADC innovation and development efforts. By that time, Drs. Xue Tongtong and Xiao Liang had already commenced R&D on third-generation site-specific, quantitatively controlled antibody-drug conjugates (ADCs). After becoming colleagues with Dr. Cai Jiaqiang in late 2015, Drs. Xue Tongtong, Xiao Liang, and Cai Jiaqiang jointly embarked on the independent R&D of ADC toxin-linker technologies. Their years of seamless collaboration laid the foundation for their subsequent reunion to co-found a startup.

Dr. Cai Jiaqiang told VCBeat, “We are fully aware of each individual’s strengths and capabilities. We have a clear understanding of how to efficiently formulate and execute plans to achieve our goals, what issues should be addressed at specific milestones, and what roles each person should assume.”“We often say that the field of new drug development is advancing so rapidly that it cannot be driven simply by a group of capable, long-time colleagues coming together. Instead, one must partner with ‘friends from yesterday’—those who have recently worked alongside you—to ensure synchronized domain expertise and seamless professional collaboration.”

It was ADC that brought three industry scientists together as colleagues; likewise, it was ADC that transformed them from work partners into comrades on their entrepreneurial journey.

Just as an antibody-drug conjugate (ADC) is composed of three distinct components—an antibody, a linker, and a small-molecule toxin—it follows that no team specializing in only one of these areas can successfully develop ADCs. This, however, is precisely the strength of MediLink. The “perfect” combination of the diverse research backgrounds and industry experiences of Dr. Xue, Dr. Xiao, and Dr. Cai has enabled MediLink to achieve its rapid growth today.

Since entering the field of new drug research in 1991, Dr. Cai Jiaqiang has been dedicated to the biomedical industry for nearly three decades.From serving as a Senior R&D Team Leader and Project Manager at the multinational pharmaceutical company Merck & Co., to holding the position of Senior Director at WuXi AppTec, a leading domestic CRO, and later leading innovative R&D efforts at two listed pharmaceutical companies, Dr. Cai has amassed extensive experience in small-molecule innovative drug discovery and conjugate technology development. He has led and overseen the R&D of over 100 new drug projects, published nearly 200 articles and patents, nominated 30 preclinical candidate compounds, and currently has 25 innovative compounds at various stages of clinical or preclinical development.

“Since earning his Ph.D. in 2009, Dr. Xue Tongtong has been dedicated to the field of innovative drug research. He possesses not only extensive experience in the development of large-molecule drugs and antibody-drug conjugates (ADCs), but also, more notably, exceptional operational management capabilities. Pharmaceutical management differs significantly from general management; it involves highly complex and specialized elements that require a strong sense of foresight,” stated Dr. Cai.“Dr. Xue previously served as General Manager of a large innovation R&D team at a publicly listed company, where he was responsible for the R&D management of both small and large molecules, as well as external collaborations and commercialization. Leading a team of over 1,000 people, he has amassed extensive experience in R&D management and is an outstanding executive.”

“Dr. Xiao Liang returned to China in 2013 after earning his Ph.D. from the University of California. Over the following seven to eight years, he engaged in research and development, gaining profound insights into antibody-based therapeutics and demonstrating exceptional technical expertise in antibody CMC (Chemistry, Manufacturing, and Controls) processes.

Thus,MediLink’s founding team includes experts specializing in the R&D of small-molecule toxin-linkers, specialists in antibody-based macromolecular drugs and CMC processes, as well as professional managerial talent with comprehensive experience in both R&D and management.By consolidating ADC R&D projects into a portfolio, we have formed a seamlessly coordinated team"Iron Triangle"Team. Dr. Cai smiled sheepishly, “To be honest, it’s indeed hard to find a team with such a combination.”

This is a key reason why capital has shown particular favor toward the MediLink team, and it also underpins the team’s confidence in its determination to become the next industry benchmark, despite being a “latecomer.” Although the company is a “newcomer,” its team is undoubtedly composed of “veterans.”

As mentioned at the beginning of this article, although 14 ADC drugs have already been approved and launched globally, there is still significant room for growth and a long road ahead in the development of ADCs. “Even the latest generation of ADC drugs still faces numerous challenges, such as drug resistance, toxicity, and side effects.”"Addressing these challenges by making improvements and innovations in targets, antibodies, toxins, linkers, and other aspects to launch drugs with superior clinical benefits is the endeavor MediLink is striving for."

Dr. Cai revealed that solid tumors are the key focus area for MediLink. “This is primarily due to the excellent efficacy of ADC drugs in tumor treatment and the clinical needs of patients. Given the heterogeneity of tumors, the same drug can have varying effects on different patients. Most patients with solid tumors still lack effective treatment options. Taking breast cancer as an example, among the currently marketed ADC drugs, even DS-8201, which has received strong positive feedback, only benefits slightly more than half of the patients. For the remaining patients, this drug may have limited or no efficacy. Therefore, we must seek additional treatment solutions to address this issue.”

Currently, MediLink has established a pipeline of more than 10 product candidates targeting solid tumors. “In terms of our technology platform, we are not only striving to outperform the latest generation of ADC products but are also actively developing next-generation ADC technologies, with a focus on how tomorrow’s ADCs can surpass today’s.”“Our aim is to continually ‘reinvent ourselves’ by developing outstanding ADC drugs that deliver tangible benefits to patients.”