Chengnuo Medicine Secures China's First IND Approval for iPSC-Derived Cell Therapy ALF201 in Acute Ischemic Stroke

In April 2022, ALF201 Injection (Application No.: CXSL2200090), an iPSC-derived cell therapy product developed by Chengnuo Medicine for the treatment of acute ischemic stroke, received implicit approval for clinical trials from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration.

ALF201 is an allogeneic endothelial progenitor cell (EPC) injection derived from iPSC-directed differentiation, and it is the first candidate product globally approved for clinical trials in the treatment of acute ischemic stroke.As a result, Chengnuo Medicine has become the first domestic iPSC stem cell pharmaceutical company to file an Investigational New Drug (IND) application for a First-In-Class therapy. The approval of ALF201 also marks a significant milestone in China’s iPSC field.

Professor Gu Yuchun, who leads the development of Chengnuo Medicine, has been significantly influenced by three key events over his more than two-decade-long career, reinforcing his commitment to deepening his expertise in regenerative medicine. Meanwhile, during the process of submitting Investigational New Drug (IND) applications for Chengnuo Medicine’s iPSC-derived cell therapies, three critical factors decisively impacted the company, ultimately enabling Chengnuo Medicine to successfully obtain IND approval.

20 Years AgoAt that time, Professor Gu Yuchun was affiliated with the Department of Anatomy and Physiology at the University of Cambridge, serving as a research fellow in Professor Roger Hardie’s laboratory. During this period, Gu collaborated on projects with the Clinical Research Center of GlaxoSmithKline (GSK), a renowned British pharmaceutical company. Through this industry-academia partnership, Gu recognized the fundamental differences between industrial development and scientific research: “Pharmaceutical development and scientific research are essentially opposite processes. Drug development involves validating a predefined pathway, whereas scientific research entails formulating and then testing hypotheses. Pharmaceutical development is a comprehensive endeavor requiring extensive support in terms of funding, personnel, and equipment, while scientific research is comparatively more straightforward.” It was precisely this collaborative experience with GSK that shaped Gu Yuchun’s understanding of pharmaceutical company operations.

Two years later, Gu Yuchun rose from a researcher to an Assistant Professor/Professor (tenured position) at the College of Medicine, University of Birmingham, UK. He had expected to spend his career teaching and conducting research at the university, but an unexpected event altered the course of his life. “2007, my mother was diagnosed with melanoma. To others, given my background in clinical medicine and the advanced healthcare system in the UK, one would assume I had access to more treatment options and strategies; yet I felt utterly powerless against my mother’s illness.”

At that time, Professor Gu Yuchun reviewed extensive literature and learned that Peking University Cancer Hospital was conducting research on tumor immunotherapy cells and had made certain progress. “Melanoma remains one of the most dangerous malignant tumors. When I unexpectedly came across literature on cell therapy, it felt as if a ray of light had appeared in my mind. As the fundamental unit for understanding human biology in medicine, cells play diverse roles across various organs throughout the body. When cells perform similar functions both in animal models and in the human body, we can leverage this congruence to develop related therapies,” recalled Professor Gu Yuchun.

2010, Professor Gu Yuchun, who was invited to teach at Peking University, resolutely resigned from his faculty position at the University of Birmingham and established his own molecular pharmacology laboratory at the Institute of Molecular Medicine.

At that time, the global cell therapy industry was still in its early stages. When Professor Gu Yuchun’s team conducted related research, they encountered their first major challenge: preparing target cells required collecting peripheral blood from cancer patients, but many patients were too ill to endure long-distance travel. For instance, Professor Gu’s mother was in Nanjing while his laboratory was in Beijing. Transporting peripheral blood samples collected in Nanjing to Beijing for experimentation was not feasible due to regulatory restrictions and time-sensitive constraints.

This predicament inspired Professor Gu Yuchun to conceive an idea: Could there be a platform capable of generating various cell types without relying on patients’ peripheral blood? “Thus, I began exploring induced pluripotent stem cell (iPSC) technology and attempting to develop iPSC-derived cell therapies. After years of development, we have been able to create therapies for tumors, degenerative diseases, cardiovascular conditions, ophthalmic disorders, and other diseases using iPSC-derived cells.”

As time went on, cohorts of doctoral students graduated from Professor Gu Yuchun’s laboratory, and the initial R&D team for Chengnuo Medicine’s iPS technology began to take shape among these students.

In 2017, Professor Gu Yuchun led his team to co-found Regenocell Therapeutics in collaboration with scientists from China and the United Kingdom.

Chengnuo Medicine focuses on induced pluripotent stem cell (iPSC) technology and downstream cell therapy drug development, and currently holds dozens of international and domestic invention patents in related fields.

Professor Gu Yuchun’s rigorous and pragmatic approach to academic research, coupled with his original aspiration to develop “cell therapies affordable for the general public,” has attracted a large cohort of highly skilled professionals from Peking University, the Chinese Academy of Sciences, and overseas universities.

Through the team’s unremitting efforts, Chengnuo Medicine has secured China’s first implicit clinical trial approval for an iPSC-derived cell therapy drug.

As the first company in China to obtain clinical trial approval in the iPSC field, Arterial Medicine has summarized three main reasons for Chengnuo Medicine’s recognition by the CDE.

One, all of Chengnuo Medicine’s drugs are developed with a patient-centric approach. “Everyone knows that cell therapies are effective, but the prohibitive treatment costs deter many patients.”The applicant is willing to be an enterprise that makes bold attempts and conducts careful verification before there is a precedent for the approval of iPSC drugs.“As long as there is demand from patients, we remain committed to being a company that provides affordable cell therapies for the general public. Furthermore, as an innovator and practitioner in this field, we hope that Chengnuo Medicine’s Investigational New Drug (IND) application approval will inspire and bring hope to more of our industry colleagues,” said Professor Gu Yuchun.

Secondly, Chengnuo Medicine made all the preparations within its scope of understanding. At the time of project application, the state had not yet issued relevant quality standards, so Chengnuo Medicine established its own quality standards. In 2019, the National Institutes for Food and Drug Control (NIFDC) promulgated standards for embryonic stem cell products. The internal standards established by the company showed a 90% similarity to the national standards, indicating that the preparations previously made by Chengnuo Medicine were largely effective, which also shortened the cycle for document submission.

Nevertheless, while maintaining an open stance toward iPSC-derived cell therapies that have never been approved before, the Center for Drug Evaluation (CDE) has imposed even more stringent requirements.From its application in 2020 to approval in 2022, Chengnuo Medicine spent two years refining the details.Regulatory authorities place particular emphasis on drug safety issues. “In the absence of clear industry standards, we addressed inquiries from regulatory bodies by referencing global perspectives on iPSC-derived cell therapies from the United States, Europe, Japan, and other regions. Throughout this process, we remained fully confident, knowing that products capable of withstanding comprehensive scrutiny are precisely what Chengnuo aims to deliver.”

Third, For an emerging industry and enterprise, funding is also particularly crucial. Since its establishment, Regenocell Medicine has completed a multi-pipeline product layout. The company is currently actively pursuing its next round of financing to support subsequent clinical research on its core project ALF201, IND filings for three additional drug candidates, and the exploration and scale-up of large-scale manufacturing processes. Furthermore, Regenocell Medicine has established stable collaborative partnerships with hospitals and academic institutions such as Beijing Tiantan Hospital, Beijing Tongren Hospital, the University of Cambridge, and Aston University, thereby accelerating project advancement.

Based on the aforementioned advantages,Chengnuo MedicineHas established a presence in three major sectors.

First,Stem Cell Therapy Field, Chengnuo Medicine leverages the intrinsic functions of stem cells to restore physiological functions through cell supplementation, and utilizes its iPSC technology platform to achieve low-cost, large-scale production; furthermore,Field of Tumor Immunotherapy, Chengnuo Medicine utilizes genetically modified iPSC-derived immune cells to enhance targeting, overcome the tumor microenvironment, and revolutionize cancer therapy; alsoIn Vivo Reprogramming and Gene Therapy, Chengnuo Medicine achieves cellular rejuvenation through in vivo reprogramming technology and utilizes cells as safe vehicles for delivering regulatory factors and gene-based therapeutics.

Currently, Chengnuo Medicine can differentiate iPSCs into somatic cells such as endothelial progenitor cells, pancreatic islet cells, immune cells, and retinal pigment epithelial cells. By integrating scalable automated cell manufacturing technologies with 3D printing technology, the company provides cellular materials required for clinical applications in disease treatment and lays the foundation for in vitro tissue and organ regeneration.

In terms of pipeline R&D, Chengnuo Medicine currently has four pipelines under development.

The most advanced product currently is the approved ALF201 injection, indicated for acute ischemic stroke. According to the Report on Stroke Prevention and Treatment in China, there were 12.42 million stroke patients in China in 2019, with 2.5 million new cases annually; ischemic stroke accounts for 75%–90% of all stroke cases. Existing treatments fail to rapidly restore blood supply, making it difficult to effectively control neuronal damage and local inflammation. The approval of ALF201 reflects national recognition of iPSC-derived cell therapies, demonstrates increased attention to major refractory diseases, and has bolstered confidence in the development of the CGT industry.