Lingke Pharmaceuticals Secures RMB 200 Million Series C1 Financing and Files for Hong Kong IPO, Says Founder Dr. Wan Zhaokui

VCBeat News learned at the earliest opportunity that,Lingke Pharmaceutical (Hangzhou) Co., Ltd. (“Lingke Pharmaceutical”), an innovative drug R&D company, announced today that it has successfully completed its C1 round of financing amounting to RMB 200 million.This round of financing was jointly participated in by Shengshi Investment, Tailong Investment, and Liandong Investment. It is reported that the funds will be primarily used to accelerate the clinical development of Lingke Pharmaceutical's core products.

Lingke Pharmaceutical was established in 2018 and co-founded by senior drug R&D experts and executives from Pfizer, Merck, and Johnson & Johnson. The company focuses on the research and development of first-in-class (FIC) and best-in-class (BIC) small-molecule drugs for oncology and autoimmune diseases.Centered on the development of second-generation highly selective and third-generation tissue-specific JAK inhibitors, the company has four indications in Phase II clinical trials.

Autoimmune diseases represent a vast area of unmet medical needs, with several blockbuster drugs already emerging. Due to their proven efficacy and druggability, as well as significant therapeutic advantages over biologics in multiple aspects, JAK inhibitors are gradually becoming the preferred treatment choice for clinicians and patients worldwide. According to Frost & Sullivan, the market size for JAK1 inhibitors alone is projected to reach $30.5 billion by 2030, indicating substantial future growth potential. However, the industry must also address challenges such as high technical barriers, safety concerns, and the risk of market saturation due to intense competition.

How Should We View the Dual Nature of JAK Inhibitors? How Is Lingke Pharmaceutical Differentiating Its JAK Pipeline? And How Can Chinese Innovative Drug Companies Propel JAK Inhibitors to Become Blockbuster Drugs? Recently, VCBeat’s New Medicine interviewed Dr. Wan Zhaokui, Founder of Lingke Pharmaceutical.

Lingke Pharmaceutical’s core team possesses an average of over 20 years of experience in new drug R&D or the pharmaceutical industry, with deep expertise in medicinal chemistry, biology, and clinical and commercial development. Founder Dr. Wan Zhaokui graduated with a master’s degree from the University of Science and Technology of China in 1994 before pursuing further studies in the United States. He earned his Ph.D. from Boston University in 1999 and subsequently conducted postdoctoral research at Harvard University until 2001. Dr. Wan began his industry career at Wyeth. After Pfizer acquired Wyeth in 2009, he remained with the company as a Senior Principal Scientist until 2013. At that time, many multinational corporations (MNCs) were establishing new drug R&D centers in China; among the numerous opportunities extended by these MNCs, Dr. Wan chose to join Johnson & Johnson.

“Johnson & Johnson advocates a decentralized management approach, granting significant autonomy. At that time, J&J’s drug R&D in China was just getting started, presenting a valuable opportunity,” said Wan Zhaokui.

Dr. Wan Zhaokui joined the company as one of the key leaders of the Asia-Pacific R&D Center. Leveraging his extensive experience accumulated over many years in new drug development, Dr. Wan oversaw the medicinal chemistry department at Johnson & Johnson and indirectly managed several other cross-disciplinary scientific departments. This broad exposure equipped him with comprehensive expertise, which became one of his key advantages when he considered launching his own venture in late 2017. During his career at multinational corporations (MNCs), Dr. Wan led or participated in the development of multiple drug candidates, including HSD-016, HSD-621, Brepocitinib (currently in Phase III clinical trials), and Halaven™.

Dr. Wan Zhaokui, Founder of Lingke Pharmaceutical. Source: Photo provided by the interviewee

Several founding members of Lingke Pharmaceutical have long-standing connections. Dr. Jun Wang, Co-founder and Chief Scientific Officer, met Zhaokui Wan in 2008. Dr. Wang brings over 30 years of experience in new drug development across academia and industry, including a lengthy tenure at Merck & Co. Prior to co-founding Lingke, he served as Vice President at Medicilon. Dr. Michael Vazquez, Co-founder, Executive Vice President, and Head of Chemistry, was Mr. Wan’s colleague during their time at Pfizer. After nearly 30 years at Pfizer, Dr. Vazquez took early retirement and joined this Chinese biotech company based on his trust in Mr. Wan. The company’s other young co-founder is Yan Chen, who serves as Chief Operating Officer and brings 11 years of experience in pharmaceutical marketing management and investment financing.

“Our team has been together for five years. It is very stable, and we collaborate well with one another,” introduced Wan Zhaokui. “In fact, I play a ‘supporting role,’ focusing on providing service to everyone by creating a good platform and environment so that they can work freely and confidently.”

Lingke Pharmaceutical focuses on the research and development of innovative drugs for autoimmune diseases and cancer. Since its official establishment in 2018, the company has launched 10 R&D projects, with the majority focused on immunology. Wan Zhaokui believes that the immune disease market is the second-largest pharmaceutical market. Entering the field of chronic autoimmune diseases presents higher barriers to entry. The company’s team possesses extensive experience in the autoimmune sector, giving it a significant competitive advantage.

For a long time, biologics have been one of the important treatments for autoimmune diseases. Although they have improved the quality of life for many patients, several major issues with biologics cannot be ignored: inconvenience in production, transportation, and management; high costs; more importantly, their slow onset of action, often suboptimal efficacy, and the development of drug resistance. Small-molecule immunosuppressants, particularly JAK inhibitors, are characterized by strong efficacy and rapid onset, attracting successive entries from multinational corporations (MNCs). Wan Zhaokui and his team, who have worked in foreign pharmaceutical companies for many years, believe this is a rare opportunity.

“There are relatively few small-molecule drugs in the autoimmune field, so differentiated small-molecule immunosuppressants will have significant room for growth. We identified this opportunity.”

In terms of its specific pipeline strategy in the autoimmune field, Lingke Pharmaceutical has adopted a dual-track approach. According to Wan Zhaokui, the first tier of the company’s product portfolio focuses on addressing unmet needs through differentiation at relatively stable and validated targets. This strategic rationale underpins the company’s focus on JAK inhibitors, with a decision to initiate development with second-generation JAK inhibitors.

First-generation JAK inhibitors have demonstrated promising efficacy, validating the effectiveness of their targets and pathways; however, there remains room for improvement in their safety profiles. Since its inception, Lingke Pharmaceutical has focused on developing second-generation JAK inhibitors with higher selectivity, aiming to create drugs with improved safety.

Second-generation JAK inhibitors can selectively inhibit members of the JAK family while minimizing inhibition of JAK2, thereby suppressing disease-specific signaling pathways without compromising JAK2 function. First-generation non-selective JAK inhibitors may cause adverse effects such as anemia and thrombocytopenia. Consequently, the development of second-generation inhibitors has garnered high expectations, becoming a highly competitive arena for numerous pharmaceutical companies and biotech firms. Recently, several second-generation JAK inhibitors have been approved internationally, including AbbVie’s upadacitinib (Rinvoq, a JAK1 inhibitor), Pfizer’s abrocitinib (Cibinqo, a JAK1 inhibitor), and BMS’s deucravacitinib (Sotyktu, a TYK2 inhibitor).

Among domestic companies developing second-generation JAK inhibitors, Lingke Pharmaceutical’s LNK01001 is at the forefront. Preclinical data show that in head-to-head comparisons with upadacitinib and abrocitinib, LNK01001 demonstrates substantially higher selectivity for JAK2 across kinase assays, cellular assays, and whole-blood experiments. In terms of molecular design, LNK01001 avoids certain potential safety risks, and GLP toxicology studies have shown favorable results on key safety parameters. LNK01001 has completed Phase II clinical trials for rheumatoid arthritis, with encouraging results: the trial demonstrated statistically significant differences versus placebo on both the primary and key secondary efficacy endpoints, along with good safety and tolerability. Moreover, after 24 weeks of treatment, the ACR20 response rates exceeded 90% in both the high- and low-dose groups. Phase II clinical trials of LNK01001 for ankylosing spondylitis and atopic dermatitis are nearing completion.

LNK01001 has attracted external collaborations due to its superior performance. In March 2022, the Company entered into a commercialization cooperation agreement with Simcere Pharmaceutical, granting the latter exclusive commercialization rights in China for LNK01001, a highly selective JAK1 inhibitor, across two indicated indications.

Wan Zhaokui stated that Lingke Pharmaceutical is already engaged in the development of third-generation JAK inhibitors. “Whether first- or second-generation, oral administration delivers the drug systemically to all organs and tissues throughout the patient’s body. Similar to biologics, this results in systemic immunosuppression, leading to safety profiles that remain less than ideal. The third generation aims to deliver drugs specifically to diseased tissues and organs, thereby reducing systemic immunosuppression and significantly improving safety. Currently, companies such as Pfizer, Johnson & Johnson, AstraZeneca, Roche, and Novartis have all made strategic investments in third-generation products, with Lingke’s candidate ranking among the forefront.”

LNK01003 is one of the third-generation JAK inhibitors. This orally administered, gut-restricted small-molecule JAK inhibitor was independently developed by Lingke Pharmaceutical and is intended for the treatment of ulcerative colitis and other related conditions. By restricting drug exposure to the gastrointestinal tract and combining this with high systemic clearance, it can significantly reduce potential side effects associated with systemic immunosuppression. Furthermore, due to its enrichment in gastrointestinal tissues, LNK01003 can more effectively inhibit multiple signaling pathways of inflammatory cytokines associated with IBD. Therefore, LNK01003 has the potential to enhance therapeutic efficacy while improving safety.

In April this year, the company announced that LNK01003 demonstrated favorable results in Phase I clinical trials involving healthy volunteers, exhibiting good pharmacokinetic (PK) properties and tolerability in both single-ascending-dose and multiple-ascending-dose studies. The company is currently conducting proof-of-concept (POC) clinical studies in patients.

LNK01004 is another tissue-restricted third-generation JAK inhibitor independently developed by Lingke Pharmaceutical, representing a novel therapeutic agent for cutaneous immune-mediated diseases. Preclinical studies have demonstrated that the drug primarily accumulates in the epidermal and dermal tissues, exhibiting excellent safety and efficacy in animal models. LNK01004 has completed Phase I clinical trials in healthy volunteers. Recently, safety and pharmacokinetic (PK) studies have been initiated in patients with psoriasis, along with an preliminary exploration of the initial efficacy of LNK01004 following multiple topical administrations in subjects with mild-to-moderate plaque psoriasis.

“We hold a leading position in the development of both second- and third-generation JAK inhibitors, which reinforces my belief that our initial choice of therapeutic area for startup was correct. These products have already demonstrated Best-in-Class and First-in-Class potential. Drawing on our first-hand experience in successfully developing JAK inhibitors over a decade ago, combined with our current team’s highly effective drug screening capabilities and outstanding creativity, we have been granted a second opportunity in this field. Therefore, I often joke with Michael that we may have surpassed our past selves,” remarked Wan Zhaokui, reflecting on Lingke Pharmaceutical’s JAK inhibitors, which feature significant differentiation.

The broad range of indications addressable by JAK inhibitors, their substantial market size, and the continuous expansion of China’s autoimmune disease market have attracted a large number of Chinese pharmaceutical companies to invest in the research and development of JAK inhibitors. According to a research report published by Industrial Securities, the overall size of China’s autoimmune disease market is projected to grow from USD 2.4 billion in 2019 to USD 24.1 billion in 2030, with a growth rate significantly higher than the global average. Based on corporate announcements and relevant clinical trial registration data, there are currently more than 20 JAK inhibitors under development led by domestic companies.

Some analysts believe that JAK inhibitors will experience intense market saturation, similar to PD-1 inhibitors. However, Wan Zhaokui argues, “Even today, high-quality JAK inhibitors remain scarce. Given the broad range of indications for JAK inhibitors, a product with superior performance will undoubtedly deliver substantial commercial and clinical value once developed. Furthermore, the industry has certainly learned from the PD-1 landscape about the consequences of low-quality, homogeneous competition. Prudent companies and investors will prioritize quality, making timely decisions on whether to enter or exit the market.”

JAK kinases participate in the JAK/STAT signaling pathway across multiple cell types, with regulation occurring at various functional levels. The high number of variables and significant development challenges create substantial barriers to entry. Furthermore, safety concerns have long elicited mixed feelings among patients regarding JAK inhibitors.The duality of JAK inhibitors is equally evident to developers: while their prospects inspire great optimism, they have also led to setbacks for many participants, with the FDA’s black box warning continuing to “loom” over this field.

Gilead acquired the leading JAK1 inhibitor filgotinib with an upfront payment of $300 million and milestone payments totaling $1.3 billion. However, due to its inferior safety and efficacy compared to other leading JAK1 inhibitors, it has only been approved for one indication in Europe. In contrast, Upadacitinib, developed by AbbVie, was the first globally approved JAK1 inhibitor. Its first indication for rheumatoid arthritis (RA) received U.S. approval in September 2019, achieving sales of $700 million in that year. With several additional indications approved over the past year and a half, its sales reached nearly $2.6 billion in 2022, demonstrating strong market acceptance. Recent real-world data indicate that the safety profile of Upadacitinib is comparable to that of biologics.^[1]Upadacitinib’s sales are projected to reach $8 billion in 2025; its sales volume for the rheumatoid arthritis (RA) indication is expected to exceed four times the combined total of the first-generation JAK inhibitors tofacitinib and baricitinib in 2026. Moreover, its peak sales, anticipated around 2030, will surpass $10 billion, cementing its status as a mega-blockbuster drug. Nevertheless, upadacitinib carries a boxed warning, similar to another blockbuster drug, Humira.

In this regard, Wan Zhaokui stated, “These warnings are intended to alert physicians and patients to the primary risks of the medication and how to manage and mitigate them; however, recognition of JAK inhibitors is growing, and their utilization rate in the treatment of patients with rheumatoid arthritis has been rising year by year.”We have seen a report based on real-world data indicating that both patients and physicians report significantly higher satisfaction with JAK inhibitor (JAKi) therapy than with biologics.^[2]. Another real-world data study of patients in Australia found^[3]: The preferred usage rate of JAK inhibitor cycling and switching in patients with rheumatoid arthritis reached 30%.Meanwhile, the second-generation JAK inhibitor upadacitinib has replaced tofacitinib and baricitinib, the first-generation JAK inhibitors that were rapidly supplanting earlier therapies. Specifically, approximately 70% of patients previously treated with tofacitinib and around 90% of those on baricitinib have switched to upadacitinib.”

“This observation from overseas highlights that JAK inhibitors, with their favorable efficacy and rapid onset of action, are truly favored by both physicians and patients; in fact, experts and patients in China have provided similar feedback.”

Lingke Pharmaceutical is committed to delivering differentiated innovative therapies to patients worldwide, leveraging its extensive experience and proprietary technologies to drive the development of products with superior efficacy, safety, and cost-effectiveness, while continuing to seek strong domestic and international partners.Let the Two-Faced God JAK Reveal Its Angelic Side to More Patients。

References:

1. Burr NE, Gracie DJ, Black CJ, et al Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta-analysis. Gut 2022;71:1976-1987.

2. Taylor PC, Fautrel B, Piette Y, et alPOS0680 PHYSICIANS’ REASONS FOR PRESCRIBING JANUS KINASE INHIBITORS (JAKi) IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA), AND ASSOCIATED ALIGNMENT BETWEEN PHYSICIANS AND PATIENTS IN A REAL-WORLD CLINICAL SETTING. Annals of the Rheumatic Diseases 2022;81:616-617.

3. Ciciriello S, Smith T, Osullivan C, et al POS0223 PATTERNS OF JANUS KINASE INHIBITOR CYCLING FOR THE MANAGEMENT OF RHEUMATOID ARTHRITIS IN REAL-WORLD CLINICAL PRACTICE: AN ANALYSIS OF THE OPAL DATASET. Annals of the Rheumatic Diseases 2021;80:330-33