Complement Therapeutics: Commercialization Timing Is Right as R&D Enters Land-Grab Phase

In early November, AstraZeneca announced that eculizumab (brand name: Soliris), a complement inhibitor acquired through its $39 billion merger with Alexion, has been officially launched in China. The drug will soon be made available in cities including Suzhou, Qingdao, Beijing, Shanghai, Tianjin, and Hangzhou. Furthermore, a marketing application for new indications was submitted in July of this year and has been accepted for review. This marks the first significant move to enhance market accessibility since the drug’s initial approval in China in 2018, after which it remained largely inactive in the market.

Soliris was approved for market launch in 2007, with current annual sales reaching $4 billion, making it a star product in the complement therapeutics sector. Its recent official launch in China indicates that the time has come for the commercialization of the complement drug market in the country.

With the FDA approval of multiple complement-related drugs since last year, a surge in the development of complement-targeted therapeutics has emerged in both domestic and international markets. To this end,VBInsight interviewed Dr. Han Zhaozhong, who previously participated in the development of Alexion’s complement drugs and founded Linnuo Pharma in Shanghai Zhangjiang Pharma Valley in 2019., to understand the development trends of complement-targeted drugs and the pipeline layout of Linnuo Pharmaceutical.

VBInsight: You previously worked at Alexion, and this year AstraZeneca successfully launched eculizumab in the Chinese market. What are your observations and analyses regarding this development? What were the driving factors behind the drug’s launch?

Dr. Han Zhaozhong:In fact, Alexion has made years of efforts to bring eculizumab to China and other emerging markets, but has not achieved perfect results. The reasons are multifaceted: first, the indications approved for eculizumab are mostly ultra-rare diseases, with few cases and high drug prices,Failed to meet the requirements of China's pharmaceutical payment system at that time; second, awareness of these ultra-rare diseases among the domestic medical community and the general public remains limited, and diagnostic methods are lacking.Unable to locate these patients in a timely manner; Third,At that time, there was a lack of policy guidance and support for the development of the orphan drug market for rare diseases.。Introducing this drug into emerging markets is particularly challenging for mid-sized biopharmaceutical companies like Alexion.

In recent years, there has been a significant improvement in both payment capacity and reforms to the drug regulatory system, particularly in the emphasis placed on orphan drugs for rare diseases. Coupled with the industry resources accumulated through AstraZeneca’s years of deep cultivation and strategic layout in China, the market entry of Alexion’s eculizumab into China can be described as a natural progression, finally providing Chinese patients with access to this life-saving medication.

VBInsight: What major events and significant advancements have occurred in the field of complement-targeted therapies over the past two years? How do you view the prospects of the complement therapeutics market?

Dr. Han Zhaozhong:Since 2021, complement-targeted drugs have entered a period of explosive growth. First, Apellis’s cyclic peptide drug targeting the complement C3 protein was approved for first-line treatment of paroxysmal nocturnal hemoglobinuria (PNH). Shortly thereafter, Chemocentryx’s small-molecule drug targeting another complement protein, C5a, was approved for the treatment of ANCA-associated vasculitis, directly leading to Amgen’s $3.7 billion acquisition of the company. Subsequently, Sanofi’s antibody drug targeting complement C1s was approved for the treatment of cold agglutinin disease. In 2022, clinical trials of a C5-targeting cyclic peptide for dry age-related macular degeneration or geographic atrophy proved successful, drawing significant attention to complement-targeted therapies. Multinational pharmaceutical companies such as AstraZeneca, Sanofi, Roche, and Novartis, along with numerous biopharmaceutical firms, have strategically positioned themselves in the field of complement-targeted drugs. Recognizing the promising future prospects of the complement market, these companies have made substantial investments.

VBInsight: The sector features both multinational corporations (MNCs) and startups. What are their strategic rationales for market entry, and who holds the competitive advantage?

Dr. Han Zhaozhong:The starting point is consistent: potential commercial opportunities. The advantages of multinational corporations (MNCs) lie in their comprehensive disciplinary coverage, abundant talent resources, ample capital, and well-developed industrial support systems, as well as a complete, battle-tested operational framework spanning from drug discovery to commercialization. Their disadvantage is a complex decision-making mechanism, which can sometimes result in missed business opportunities. Startups, on the other hand, benefit from accumulated expertise in specific fields and flexible decision-making processes.Many of the strengths of multinational corporations (MNCs) are precisely the glaring weaknesses of startups. If startups can leverage their own advantages—particularly their accumulated expertise in specific domains—focus on what they do best, allocate resources wisely, and execute the right actions at the right time, they stand a greater chance of achieving successes that MNCs cannot replicate.

VBInsight: Compared to the complement therapeutics sector abroad, what stage has development reached in China? Is the upstream and downstream service ecosystem for complement drug developers well-established?

Dr. Han Zhaozhong:In fact, both domestic and international sectors are in a relatively early stage of “land grabbing” in the field of complement drug development. Due to factors such as the ongoing establishment of a pharmaceutical innovation ecosystem, a shortage of new drug R&D personnel, and an immature industrial support system, China lags behind foreign countries by several years in this area.Compared with the development speed of other industries in recent years, I believe that in the coming years, domestic new drug R&D enterprises and related upstream and downstream service ecosystem chain enterprises should be able to seize opportunities, leverage late-mover advantages, rapidly develop products with international competitiveness, and enter the global market.

VCBeat: Amid the Complement Drug Boom, What Strategic Moves Has Linnuo Made?

Dr. Han Zhaozhong:Currently, we are preparing an Investigational New Drug (IND) application for a complement-targeting nanobody, intended for the treatment of immune-mediated kidney diseases, particularly IgA nephropathy. Another candidate, a bispecific antibody targeting both angiogenesis and complement activation, is nearing completion of preclinical proof-of-concept studies and is planned for the treatment of age-related degenerative macular degeneration. In the discovery or molecular optimization phase, we are also developing a complement-targeting therapeutic capable of crossing the blood-brain barrier to target the central nervous system, intended for the treatment of complement-mediated central nervous system disorders. TheseProgressive, Iterative Product Development PlanWe believe this will position Linnuo (Shanghai) Pharmaceutical Technology Co., Ltd. in a relatively favorable competitive position within the industry.

VBInsight: What observations and analyses of the industrial landscape, clinical needs, and current status of drug development for complement therapies informed these strategic moves?

Dr. Han Zhaozhong:After more than two decades of exploration, the development of complement-targeted therapeutics has finally entered a period of rapid growth. Targets have expanded from C5 to include C3, C5a, C1s, CFB, MASP-2, CFD, and even C6, among others. The types of drug molecules have also diversified, extending from monoclonal antibodies to cyclic peptides, small molecules, nucleic acid drugs, and even vector-mediated gene therapies. Indications are likewise broadening from rare diseases to major and chronic conditions. In-depth research into complement biology, particularly its physiological functions and pathological mechanisms, has made it possible to develop safer and more effective drugs to address the clinical needs of complement-mediated immune diseases. This is the fundamental reason why pharmaceutical companies both in China and abroad have shifted from a wait-and-see approach to making substantial investments in the R&D of complement-targeted drugs. From the perspective of complement biology, the complement system performs normal biological functions in the human body, including anti-infection defense, immune system regulation, clearance of necrotic tissue, and maintenance of homeostasis. Complete inhibition carries certain clinical risks; therefore, selective inhibition of the complement system is critically important.

VCBeat: Based on these analyses, what strategic thinking has shaped your pipeline layout, and what drug development plan have you formulated?

Dr. Han Zhaozhong:Linnuo Pharmaceutical’s approach to technology development and pipeline layout is grounded in biomedical innovation that balances scientific rationality, technical feasibility, commercial prospects, and clinical needs. Based on these considerations, we initially selected indications with large patient populations, including immune-mediated kidney diseases, age-related macular degeneration, and central nervous system disorders. From a target perspective, the chosen targets must demonstrate a strong association with the diseases, supported by robust preclinical and clinical data, while also accounting for safety risks. In terms of drug molecules, we adopt nanobody structures characterized by high specificity, potent biological activity, relatively low development risk, extended dosing intervals, and convenience for subcutaneous administration. Furthermore, taking into account market dynamics, resources, and risks, we implement a phased, iterative development strategy and pathway.

Arterial New Medicine: Why Did Linnuo Choose to Prioritize the Development of Its IgA Nephropathy Project? What Are the Differentiated Advantages of This Product?

Dr. Han Zhaozhong:Clinical and preclinical studies in recent years have demonstrated that excessive complement activation plays a critical role in the pathogenesis and progression of IgA nephropathy. Novartis’s small-molecule inhibitor of complement factor B (CFB) has shown excellent performance in Phase II clinical trials, while complement-targeted therapies from AstraZeneca and other pharmaceutical companies have gradually completed proof-of-concept and entered pivotal confirmatory clinical stages. The candidate drug molecule developed by Linnuo Pharma targets a novel site that offers a better balance between efficacy and safety. In terms of molecular structure, it adopts a nanobody fusion protein format administered via subcutaneous self-injection, which features higher specificity, greater biological activity, more stable plasma concentrations, and a longer half-life compared to small molecules. Regarding its mechanism of action, the candidate not only directly inhibits the target but also clears it from the bloodstream. In animal models, our candidate molecule has exhibited these desired pharmacological properties along with favorable safety profiles. Furthermore, ongoing chemistry, manufacturing, and controls (CMC) development results indicate that Linnuo’s candidate molecule demonstrates superior characteristics in yield, purity, and stability, effectively supporting the planned product development roadmap. Additionally, Linnuo’s patent filing strategy ensures long-term exclusivity in this field.

VCBeat New Medicine: When developing complement inhibitors, Alexion used paroxysmal nocturnal hemoglobinuria (PNH), an ultra-rare disease, to validate the safety and efficacy of its drugs. It subsequently expanded into relatively more prevalent rare diseases such as atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), and neuromyelitis optica (NMO), and is now further expanding into broader indications such as kidney diseases. What insights do these product development strategies offer to today’s biopharmaceutical companies?

Dr. Han Zhaozhong:Just as with individuals, there are countless paths to growth for enterprises, yet one path is always more suitable.When Alexion pioneered clinical trials for complement therapeutics, it was a startup with limited resources. With its target entirely unproven in clinical settings, the company strategically initiated product development by focusing on paroxysmal nocturnal hemoglobinuria (PNH), an ultra-rare disease with a well-defined pathogenic mechanism. This approach allowed Alexion to first establish its market position and secure the resources necessary for subsequent product development, before gradually expanding into indications with significant unmet clinical needs, substantial market value, and clear competitive advantages at appropriate times. This proved to be an effective strategy for Alexion at that stage. Subsequently, the company successfully integrated diverse resources across science, technology, medicine, regulation, and marketing—particularly human capital—achieving annual sales of nearly $5 billion and ultimately being acquired by AstraZeneca for $39 billion.For Chinese innovative drug companies today, the key to emerging as the ultimate winners in a shifting capital market remains rooted in their projects—specifically, the scientific or technological innovation and market competitiveness of these projects. At the core of every project lies talent, and the essence of talent is doing the right things at the right time. What follows is a test of judgment and execution capabilities.。

VBInsight: New drug development is a process that requires long-term investment. Under the current market conditions, how does Linnuo Pharmaceutical address its funding challenges?

Dr. Han Zhaozhong:Over the past three years, Linnuo Pharmaceutical has completed two rounds of financing, receiving strong support from Zhangke Lingyi and Zhejiang Puhua Capital. As a result, we have achieved stable and rapid development in platform technology development, therapeutic product development, team building, and R&D infrastructure: we have filed nearly 10 international invention patents covering platform technologies and product development with cross-disciplinary scope; two First-in-Class (FIC) innovative drug projects have entered the preparatory stage for Investigational New Drug (IND) application submissions; we operate a laboratory of nearly 1,000 square meters in Shanghai Zhangjiang Pharma Valley, capable of fully executing processes from molecular discovery to preclinical proof-of-concept; and our team’s expertise and project experience span preclinical development, Chemistry, Manufacturing, and Controls (CMC), regulatory filings, and clinical trials. Building on the refinement of our platform technologies and project progress, we are actively pursuing business collaborations, exploring technical and product partnership opportunities with pharmaceutical and biotechnology companies both domestically and internationally to optimize resource utilization. Meanwhile, we are engaging in active communications with investment institutions and plan to officially launch our next round of financing around the upcoming Lunar New Year. I believe that regardless of fluctuations in the international political and economic landscape or the duration of the “capital winter,” market demand for innovative drugs will always persist.As long as we do the right things and do them at the right time, we will surely break through the so-called “capital winter.”