Wuxi Kejin Biotech Advances CG001 for Pyruvate Kinase Deficiency with EMA Orphan Drug Designation and Global Clinical Strategy

Lele (a pseudonym) was admitted to the Neonatal Intensive Care Unit (NICU) on the second day of life for emergency exchange transfusion. Over the subsequent four and a half months, Lele and his family traveled to multiple cities, undergoing several evaluations for the cause of anemia and receiving blood transfusions. After exhausting all known diagnostic tests, which yielded normal results, physicians initially suspected that Lele was suffering from autoimmune hemolytic anemia.

Thereafter, Lele remained trapped in a relentless cycle of anemia and blood transfusions. Transfusion-related allergic reactions led to rashes, while hemolytic anemia resulted in jaundice and hepatosplenomegaly. Following a physician’s recommendation, Lele underwent genetic screening for hematologic disorders and was ultimately diagnosed with Pyruvate Kinase Deficiency (PKD). PKD is a rare disease caused by mutations in the PKLR gene. These mutations lead to pyruvate kinase deficiency, reduced ATP production, impaired erythrocyte maturation, and consequent hemolytic anemia.

According to IQVIA statistics, there are approximately 51 patients with pyruvate kinase deficiency (PKD) per million people globally. Due to the limited prevalence of genetic testing, the actual number of patients is significantly underestimated. Currently, PKD can only be cured through bone marrow transplantation, which is associated with severe side effects and a scarcity of suitable matches. Common treatment options include frequent blood transfusions or splenectomy, which can lead to serious adverse effects such as iron overload and organ damage, imposing substantial economic and lifestyle burdens on patients and their families.

“Lele is now six years old, yet there are still no effective curative drugs for PKD. The longer time goes on, the more uncertainties Lele will face. If we don’t take on this task—developing effective treatments for rare diseases such as PKD—I fear that no one else will step up for a long time,” Dr. Wang Haifeng, Founder and CEO of Wuxi Kejin Biopharma, told VCBeat New Medicine.

“I never intended to start a business; both my work and personal life were quite satisfying before that. However, when our close friend’s child was admitted to the NICU on the second day after birth, it deeply affected us. From then on, I leveraged my business development (BD) experience to search globally for medications for Lele, and eventually, by chance, embarked on an entrepreneurial journey,” recalled Dr. Wang Haifeng.

Prior to founding his company, Dr. Wang Haifeng conducted research and worked at Harvard Medical School, Novartis Institutes for BioMedical Research (Shanghai) Co., Ltd., and WuXi AppTec. With over 17 years of professional experience, Dr. Wang has extensive expertise in the development of cell and gene therapies, and has led multiple production development and clinical trial initiatives across the Asia-Pacific region.

In 2016, Lele was born but diagnosed with pyruvate kinase deficiency, a rare disease lacking effective therapeutic drugs. That same year, Dr. Wang Haifeng joined WuXi AppTec as the Head of Business Development for Cell and Gene Therapy Biologics in the Asia-Pacific region. Since then, Dr. Wang has been searching globally for medications for Lele.

In 2020, Dr. Wang Haifeng learned that a U.S. client was developing a cell therapy for polycystic kidney disease (PKD) and had successfully entered Phase I clinical trials. “At that time, I contacted their CEO to ask whether they planned to enter the Chinese market, and offered to help them conduct clinical trials in China if they were interested. However, the company was not interested in the Chinese market at the time, so after several attempts, I managed to get in touch with Professor Jose Carlos Segovia, the inventor of this technology.”

Professor Jose Carlos Segovia is currently the Co-Founder and Chief Scientific Officer of Wuxi Kejin Biotechnology. He also serves as the Head of the Cell Therapy Center at Spain’s National CIEMAT, a representative for academic exchanges between Spain, EU countries, and the global community, and a Senior Advisor on Advanced Therapies to the European Medicines Agency (EMA). Representing the highest level of technical expertise in Europe in this field, he holds multiple technology patents, has successfully filed applications for five orphan drugs, and possesses over 30 years of professional experience.

Moved by Lele’s story, Professor Jose Carlos Segovia decided to license his next-generation CRISPR/AAV technology. Compared with the first-generation platform, this technology enables precise replacement of mutated genes, aiming to cure patients with polycystic kidney disease (PKD) without carcinogenic risk. After confirming the technological roadmap and CMC feasibility, Dr. Wang Haifeng invited Professor Jose Carlos Segovia to co-found Kejin Biopharma. The company has since recruited dozens of domestic and international experts in cell and gene therapy, virology, oncology, hematology, and senior professionals from the biopharmaceutical industry to oversee its R&D and operations. The core management team hails from Global 500 pharmaceutical companies, with more than 30 years of deep expertise in the cell and gene therapy field, and extensive experience in CMC, clinical development, and regulatory compliance.

Dr. Wang Haifeng said of these entrepreneurial partners, “These partners are highly professional and strongly cohesive. By placing them in the right positions, they can operate independently and take full responsibility. On the platform of Wuxi Kejin Biotechnology, they will unleash their maximum value on their respective stages.”

As a company focused on the research and development of cell therapies for rare diseases, Wuxi Kejin Biopharma has inevitably faced skepticism. In response to challenges related to the market, policies, costs, and payment capabilities for rare disease drugs, Wuxi Kejin Biopharma has provided detailed answers to each concern.

Market concerns that are widely shared by the public are precisely the least of Wuxi Kejin Biotechnology’s worries.There are approximately 7,000 rare diseases worldwide, yet only more than 600 corresponding therapeutic drugs are available, which is far from meeting clinical needs. The global market size for rare disease drugs increased from USD 135.1 billion in 2020 to USD 383.3 billion in 2030, representing a compound annual growth rate (CAGR) of 11.0% from 2020 to 2030. China’s rare disease drug market also surged from USD 1.3 billion in 2020 to USD 25.9 billion in 2030, with a CAGR of 34.5%, significantly higher than the concurrent CAGRs in the United States and other regions worldwide (10.5% and 10.0%, respectively).

Beyond the broad blue-ocean market for rare diseases, Wuxi Kejin Biologics’ specific product pipeline also holds considerable market potential.Taking the flagship project CG001 as an example, CG001 is an ex vivo gene-edited cell therapy for pyruvate kinase deficiency (PKD). During the drug discovery phase, Dr. Wang Haifeng recognized that there were many PKD patients like Lele: approximately 8,000 diagnosed and actively treated patients in Europe and the United States, and around 10,000 in the Asia-Pacific region. According to Agios Pharmaceuticals’ market analysis, the annual market size for PKD treatments is estimated at $500 million. Furthermore, as new cases are identified in newborns each year, this genetic disorder presents a relatively stable market.

In terms of policy, preferential measures are provided globally for rare diseases and other serious conditions that lack effective treatment options.In China, with the release of the first batch of the Rare Disease Catalogue in 2018, attention to this blue-ocean market has been gradually increasing. In May this year, the Center for Drug Evaluation (CDE) released the "Draft for Comments on the Implementation Regulations of the Drug Administration Law of the People's Republic of China (Revised Draft)" (hereinafter referred to as the "Draft for Comments"). The Draft for Comments reflects the state's encouragement of rare disease research and innovation. For newly approved rare disease drugs, a market exclusivity period of up to seven years will be granted, provided that the Marketing Authorization Holder commits to ensuring drug supply; during this period, no other applications for the same variety will be approved. In Europe and the United States, policy incentives and preferential measures are more mature and comprehensive.

In addressing issues of affordability and cost control, Wuxi Kejin Biotech also offers corresponding solutions.Currently, orphan drugs often carry “astronomical” price tags, and China’s national medical insurance system cannot provide substantial coverage in the short term. In response, Wuxi Kejin Biopharma has adopted a product development strategy that prioritizes regulatory submissions in Europe and the United States, with simultaneous follow-up in China. The company first pursues approval and commercialization in Europe and the United States, where patients have greater ability to pay, and then leverages the clinical data generated in these regions to expedite regulatory approval in China. This approach aims to ensure that patients worldwide gain access to affordable therapies within the shortest possible timeframe.

In terms of cost control, since the majority of costs for cell and gene therapies stem from viral vectors, most currently available cell and gene therapy production batches yield sufficient viral vector quantities to treat approximately 30 patients.Wuxi Kejin Biotechnology has achieved a significant reduction in costs through process improvements, enabling the production of a single batch sufficient to meet the viral vector requirements of over a thousand patients. Furthermore, Wuxi Kejin Biotechnology holds a patented technology that enhances cell transplantation efficiency even under conditions of low target cell expression, thereby further reducing production costs.

Dr. Wang Haifeng’s habit and experience of evaluating and addressing these issues prior to founding his venture stemmed from his tenure at WuXi AppTec, where he was responsible for business development. When establishing or introducing a project, he typically assesses its feasibility and comprehensive risks before deciding on the next steps.“From a BD perspective, I have often essentially performed the investors’ due diligence for them. Prior to Wuxi Kejin Biotechnology’s financing round, I had already helped investors pinpoint the market positioning. The strategy of prioritizing regulatory filings in Europe and the United States while pursuing simultaneous development in China was designed to enable investors to achieve returns more rapidly.”

After overcoming the aforementioned challenges, the most critical step is to achieve successful R&D and translation, effectively implementing scientific research outcomes into industrial applications.In addressing challenges in research and development, Wuxi Kejin Biologics has established a CRISPR/AAV platform with proprietary patented technology. This technological platform enjoys global rights protection, breaking down barriers associated with patented technologies.

The CRISPR/AAV technology platform offers three distinct technical advantages.First, leveraging CRISPR/AAV technology, Wuxi Kejin Biotechnology can perform gene knockout and replacement for target sequences of varying lengths, including full-length genes. Second, in terms of editing efficiency, the CRISPR/AAV technology platform achieves an industrial-grade editing efficiency of 70%, with this figure continuing to rise. Third, to address critical challenges such as safety concerns, the CRISPR/AAV platform employs ex vivo editing and screening to mitigate off-target effects and immune storms, while also reducing viral vector dosage to lower costs.

Based on its technology platform, Wuxi Kejin Biotech has currently established six R&D pipelines.Indications cover rare diseases such as pyruvate kinase deficiency, Wiskott-Aldrich syndrome, epidermolysis bullosa, primary hyperoxaluria type 1, congenital pure red cell aplasia, and congenital dyserythropoietic anemia type II, among others. The range of indications for this technology continues to expand. Many international companies have engaged with Wuxi Kejin Biologics to discuss project collaborations, including those involving CAR-T, CAR-NK, and other therapies.

In March this year, Wuxi Kejin Biologics’ cell therapy pipeline CG001 for pyruvate kinase deficiency received Orphan Drug Designation from the European Medicines Agency (EMA). CG001 is an ex vivo edited cell therapy that utilizes CRISPR to target the mutated PKLR gene and employs AAV vectors to deliver a correct PK gene template. This approach enables ex vivo editing of hematopoietic stem cells to correct the mutated pyruvate kinase gene, with the aim of achieving a cure.

This milestone will accelerate Wuxi Kejin Biopharma’s drug R&D progress, with the company planning to launch clinical trials simultaneously in Europe, the United States, and China in the second half of next year. Furthermore, it provides investors with more stable market expectations. Currently, Wuxi Kejin Biopharma has concurrently applied for Orphan Drug Designation from the U.S. FDA, which is expected to expand the company’s market potential.

Looking to the future, Dr. Wang Haifeng stated, “Our most immediate goal is to expedite the market launch of CG001 to benefit more patients and families affected by PKD. Meanwhile, we will maintain a pace of one Investigational New Drug (IND) application per year to steadily advance the rest of our pipeline. Wuxi Kejin Bio remains true to its original mission, continuously developing accessible therapies for patients and helping thousands of families affected by rare diseases.”