Biling Biotech: Pioneering Original Nanoparticle Conjugate Drugs Amid the XDC Innovation Surge

As an innovative frontier in the biopharmaceutical sector, the XDC (antibody-drug conjugate and other drug conjugates) track is entering a period of rapid development. Globally, numerous XDC drugs are in clinical trials or awaiting marketing approval. Chinese domestic companies are also active in this field, gradually gaining recognition in the global market through international collaboration and technological innovation.

Among numerous domestic enterprises, Best-link Bioscience is an innovative biotech company that cannot be overlooked.Best-link Bioscience, established in May 2021, specializes in the research and development of innovative nanoconjugate drugs, self-assembling nanodrugs, and precise nanodrug delivery systems. The company has built a nanoconjugate drug platform and a precise drug delivery platform to develop innovative therapeutics for precision oncology and cancer immunotherapy.Best-link Bioscience’s nano-conjugate drugs, developed through the cross-disciplinary integration of conjugation technology and nanotechnology, have emerged as a new drug modality.

What challenges currently need to be addressed in the XDC sector? How does Best-link Bioscience propose to solve them? Recently, VCBeat interviewed Dr. Zhang Fuyao, CEO and General Manager of Best-link Bioscience, and Dr. Jiang Haoyuan, CMO, who shared their unique insights into the XDC landscape, the company’s differentiated positioning, as well as the achievements and progress of its project pipeline.

Dr. Zhang Fuyao, founder of Best-link Bioscience, boasts extensive academic and professional experience. He pursued advanced studies at several prestigious universities and served as a Principal Scientist at the multinational pharmaceutical company Eli Lilly. Upon returning to China, he became a successful serial entrepreneur. Each phase of his career has laid a solid foundation for the establishment of Best-link Bioscience.

Zhang Fuyao pursued advanced studies at four universities. After earning his Ph.D. in Polymer Materials and Engineering from Zhejiang University, he remained on the faculty there. He later expanded his academic horizons internationally, studying at RWTH Aachen University in Germany, The Hong Kong Polytechnic University, and Harvard University in the United States. He obtained a Ph.D. in Organic Chemistry from The Hong Kong Polytechnic University and subsequently joined the laboratory of Professor E. J. Corey, a Nobel Laureate at Harvard University, where he worked and conducted research primarily focused on pharmaceutical synthesis processes.

In Zhang Fuyao’s view, his academic journey across four different universities not only laid a solid foundation for his scholarly pursuits but also cultivated his perseverance and spirit of exploration in venturing into new fields. Furthermore, it provided him with valuable knowledge and experience for his professional development in chemistry and related pharmaceutical sectors.

In 2001, Zhang Fuyao entered the industry by joining Eli Lilly and Company, a multinational pharmaceutical corporation. Serving sequentially as a Scientist, Senior Scientist, and Principal Scientist, he engaged in the research and development of synthetic processes for candidate drugs in Phase I–III clinical trials. His tenure at Eli Lilly deepened his understanding of the biopharmaceutical sector and provided critical experience for his subsequent drug development endeavors and entrepreneurial ventures. Eight years later, Zhang returned to China, where he led and participated in the establishment and development of Yuanli Biotech, a subsidiary of Hengrui Medicine. At Yuanli Biotech, he was comprehensively involved in all aspects of operations, ranging from synthetic process development to new drug R&D. It was during this period that he initiated research and development efforts focused on antibody-drug conjugates (ADCs). By then, Zhang had already led his team to successfully advance multiple projects to market launch in China and globally. In 2016, Zhang embarked on his second entrepreneurial journey, co-founding Shilai Bioscience to explore the fields of nanomaterials and nano-drug delivery systems.

By this point, Zhang Fuyao had accumulated extensive R&D experience in both the antibody-drug conjugate (ADC) and nanomedicine fields. Meanwhile, he also gained keen insights into the bottlenecks and challenges inherent in these two areas of drug development. In his view, leveraging over a decade of entrepreneurial practice, new drug development expertise, and experience in talent team building and management, the time was ripe for him to establish an independent biopharmaceutical company aimed at addressing the current industry’s challenges and bottlenecks in new drug development.

Best-link Bioscience was thus established.

The project operations of Best-link Bioscience since its establishment have benefited significantly from the support of another pharmaceutical industry leader, Dr. Jiang Haoyuan, Chief Medical Officer (CMO). Dr. Jiang provided comprehensive guidance throughout the entire process, from project initiation to clinical development, accelerating the rapid advancement of Best-link’s product pipeline.

Jiang Haoyuan graduated from the Medical School of Soochow University and holds a Ph.D. in Biology from The Hong Kong Polytechnic University. With years of experience as a clinician at the Affiliated Hospital of Zhejiang University, she furthered her studies at Boston University, Indiana University, and the University of Florida in the United States. She subsequently joined Hengrui Medicine, where she served as the Head of Clinical Development, establishing a clinical R&D team encompassing project management, operations, and data management departments. During her tenure, she simultaneously oversaw the clinical research and operations for more than ten Class 1 innovative drugs. At Hengrui Medicine, she engaged with top-tier talent across various specialized fields, significantly broadening her professional horizons. To further accumulate expertise in clinical operations, she joined WuXi PRA, a joint venture between WuXi AppTec and PRA Health Sciences, serving as Vice President of Clinical Operations for Greater China. In this role, she was responsible for the management and operations of international clinical trials, marking another significant milestone in her career.

From Jiang Haoyuan’s perspective, every step in her career has been a valuable accumulation of experience, with each platform offering her unique life experiences and opportunities for growth. After leaving Kindstar Global, she served as Chief Marketing Officer (CMO) at Qingfeng Pharmaceutical and Yangshengtang Group, respectively, where she oversaw the entire process of her companies’ product pipelines—from project initiation and clinical enrollment to regulatory submission.

For both Zhang Fuyao and Jiang Haoyuan, talent development and team building are particularly critical in early-stage biotech startups. The core founding team of Best-link Bioscience consists of “veteran employees” who were willing to join Zhang Fuyao in his new entrepreneurial venture, with many having worked alongside him for over eight years.

“The recognition and support from my team members have been the driving force behind my continuous progress. In fact, I feel fortunate to have met so many outstanding young professionals, with whom we share mutual appreciation and help each other succeed. This spirit of teamwork and the atmosphere of shared growth have enabled our team to be built faster and with higher quality than I had anticipated,” said Zhang Fuyao.

At the time of Best-link Bioscience’s establishment, the antibody-drug conjugate (ADC) sector, after decades of development, had already become one of the most successful fields in oncology therapeutics. R&D activities in China were highly vigorous, leading to the emergence of intense competition and market saturation. Drawing on his professional expertise accumulated at Yuanli Biotech and Shilai Biotech, Zhang Fuyao gained profound insights into the difficulties and bottlenecks associated with ADC drugs that could not be effectively addressed at the time. Meanwhile, he recognized the development potential of nanomedicines. He believed that integrating these two approaches could offer a highly innovative pathway for new drug development. This strategic thinking paved the way for Best-link’s differentiated positioning, with its forward-looking innovative nano-conjugate drugs serving as the key factor enabling the company to stand out in a crowded market. “Pharmaceutical innovation requires at least five years of foresight. This was one of the most important lessons I learned while working with Mr. Sun from Hengrui Medicine,” noted Zhang Fuyao.

Although the field of conjugated drugs, represented by ADCs, was highly competitive in China at that time, there remained room for innovation and improvement.Zhang Fuyao pointed out that the primary challenges lie in poor and inefficient delivery, as well as insufficient penetration of drugs into the deep tumor tissue. These drug molecules face a dilemma during the delivery process: difficulty in extravasation from blood vessels and difficulty in cellular uptake.

This is primarily because drugs face multiple barriers during their journey to tumor tissue. XDC drugs must sequentially overcome the blood barrier, tumor vascular barrier, tumor stromal barrier, and cellular barrier to exert their therapeutic effects. The delivery of XDCs from the bloodstream to tumor tissue is a passive targeting process. During this process, factors such as the nanoscale size, charge, and aggregation state of the drug molecules affect their physical stability, posing a risk of the drug being trapped at various barriers and thereby reducing delivery efficiency.

Meanwhile, ensuring effective drug delivery into tumor cells remains a major challenge for XDC drugs. Zhang Fuyao explained that traditional ADC drugs bind to antigens on the surface of tumor cells via antibodies and enter the cells through endocytosis. However, while this approach addresses cellular entry, it hinders deep penetration into the tumor mass. The high-affinity binding between antibodies and antigens leads to a target occupancy effect, causing ADC molecules to accumulate primarily at the tumor periphery and making it difficult for them to penetrate deeply into the tumor interior.

To address these issues,Best-link Bioscience has constructed a unique nano-conjugate drug technology platform by integrating multidisciplinary technologies. Through strategic design and synthesis, the team comprehensively optimized key parameters—including drug stability, nanoparticle size, surface charge, conjugation methods, selection of tumor microenvironment-responsive linkers, and hydrophilic-lipophilic balance—thereby enhancing drug delivery efficiency and deep tumor penetration.

Best-link Bioscience has proposed a more innovative drug delivery strategy.“First, through rational design of the conjugate’s stability, nanoscale dimensions, charge characteristics, conjugation chemistry, and hydrophilic-lipophilic balance, we address the challenge of drug extravasation across tumor microenvironment vascular walls, thereby enhancing delivery efficiency from systemic circulation to tumor tissue and achieving high accumulation of the drug within the tumor. Subsequently, by rationally designing tumor microenvironment-responsive linkers, the active small-molecule payload is effectively released from the accumulated conjugates within the tumor microenvironment. Leveraging the bystander effect concept known from antibody-drug conjugates (ADCs), the payload diffuses into tumor cells, thus resolving the issue of cellular uptake. Since cellular internalization is no longer target-dependent and free from target occupancy effects, the payload can continuously penetrate deep into the tumor, sustaining cytotoxic activity against tumor cells in the tumor core, thereby overcoming the limited deep-tumor penetration observed with existing therapies.”As our nano-conjugate drugs are target-independent, they can be used to treat pan-tumor indications. Preclinical evaluation results demonstrate that the same nano-conjugate drug exhibits superior inhibitory effects against pancreatic cancer, small cell lung cancer, colorectal cancer, soft tissue sarcoma, triple-negative breast cancer, endometrial cancer, and liver cancer, thereby demonstrating true broad-spectrum activity.“mentioned Zhang Fuyao.

Leveraging its independently developed platforms for nanoconjugate drugs and nanoself-assembly, Best-link Bioscience has enhanced drug delivery efficiency and tumor tissue penetration through innovative design and self-assembly methods for nanoconjugate drugs, thereby providing new paradigms and directions for drug development.

Based on proprietary nanoconjugate drugs and nanoself-assembly technology platforms,Best-link Bioscience has currently established five product pipelines, with two candidates in Phase I clinical trials and a third candidate undergoing simultaneous IND submissions in both China and the United States.

Zhang Fuyao introduced,BL0020 is a nano-conjugate drug developed based on the company’s innovative technology platform, designed to address challenges encountered in the clinical application of existing conjugate drugs, including their low permeability and low delivery efficiency.“In designing BL0020, we first avoided the target occupancy effect caused by dependence on cell-surface targets of tumor cells, thereby addressing the issue of poor deep-tumor penetration. More importantly, by rationally optimizing factors such as molecular weight, nanoscale dimensions, and surface charge, we achieved appropriate nanoparticle size and surface characteristics. This approach overcomes the renal and hepatic clearance issues associated with ADCs, PDCs, and conventional nanomedicines, prolongs the drug’s half-life in systemic circulation, increases plasma drug concentration, and resolves the challenge of BL0020, a nano-conjugated drug, in extravasating from tumor vasculature, thereby significantly enhancing drug delivery efficiency.”

According to reports, BL0020 has demonstrated significant potential in the treatment of various refractory malignant tumors in preclinical studies, including pancreatic cancer, small cell lung cancer, liver cancer, breast cancer, endometrial cancer, colorectal cancer, and soft tissue sarcoma.BL0020 is currently undergoing clinical trials in China and Australia, and has also received clinical trial authorization from the U.S. FDA.The clinical trial of this drug is progressing smoothly, with dose escalation having reached the therapeutic level. Preliminary clinical data indicate that BL0020 demonstrates favorable tolerability and safety profiles, along with encouraging efficacy results. The degree of tumor shrinkage was positively correlated with dosage. Disease in patients with gastric cancer and breast cancer was effectively controlled over multiple cycles, and partial response (PR) was observed in several patients with small cell lung cancer.

Since its establishment in 2021, Best-link Bioscience has advanced multiple product pipelines to the clinical stage and achieved positive data within just three years, a testament to the power of collaboration within the Best-link Bioscience team.

First, Best-link Bioscience boasts a team of outstanding researchers and clinical professionals capable of independently handling all tasks from drug design to CMC process development and IND filing, thereby significantly reducing reliance on external resources.

Secondly, Best-link Bioscience established a clear timeline and objectives during the project planning phase. This end-in-mind strategy helped the team focus its efforts while maintaining proactive communication with regulatory authorities to ensure the timely completion of key milestones.

Furthermore, Best-link Bioscience anticipated potential difficulties and challenges during the project planning phase and addressed them through proactive preparation and strategic planning. This forward-looking approach helped minimize project delays and avoid unforeseen issues, ensuring the rapid progress of clinical trials.

Taking BL0020 as an example, the clinical team leveraged the variations in clinical approval processes and timelines across different countries. By aligning with the regulatory submission requirements of each country, they strategically planned key milestones and prepared for multi-country simultaneous clinical trial applications in accordance with the submission schedule. This parallel approach to multi-country clinical submissions effectively shortened the overall project timeline.

Over the three years since its establishment, Best-link Bioscience has maintained a harmonious relationship of mutual support and trust with its shareholder team, earning full recognition and strong backing from existing shareholders. “I believe that entrepreneurs must embrace an altruistic spirit. Only by delivering effective new therapies to patients, driving the company’s sound development, generating returns for investors, and fostering growth for the corporate team can we achieve a win-win outcome,” said Zhang Fuyao.

The story of Best-link Bioscience is set to continue, with a promising future ahead.