Source: eMedClub

In the fierce competition of catching up with each other all over the world, domestic stem cells have quickly entered the international first square leading the world in regenerative medicine. According to the CDE website, 12 stem cell products have been submitted for IND approval as of August 2023, compared with 31 in 2021-2022, reflecting the increasing intensity of stem cell product research and development. Mesenchymal stem cell products are the main indications, including liver diseases (such as liver cirrhosis and liver failure), degenerative diseases (such as knee osteoarthritis) and autoimmune diseases (such as lupus nephritis). This also indicates that with the progress of new drug research and development of stem cells and the gradual clarity of the regulatory path, the clinical transformation of stem cells has ushered in a "golden period". The following is a summary of the progress of stem cells in clinical practice of domestic enterprises.

ZhongGuan Biological

On March 25th, 2022, the human umbilical cord mesenchymal stem cell injection (ZGHUM- SC001) developed by ZhongGuan Biological was accepted by IND, and the indication was knee osteoarthritis. As a kind of mesenchymal stem cells derived from human umbilical cord "WHARTON'S JELLY", mesenchymal stem cells have general MSCS characteristics, including self-renewal, multidirectional differentiation, immune regulation, hematopoietic support, secretion of multiple cytokines, antibacterial activity, low immunogenicity, injury repair, no tumorigenicity and so on.

Sncstemcell

On July 21, 2023, according to the official website of CDE, the clinical trial application (IND) for the fifth indication of Sncstemcell stem cell product "ELPIS human umbilical cord mesenchymal stem cell injection" was accepted. This ELPIS product is the fifth indication of Sncstemcell accepted by CDE for moderate and severe active inflammatory bowel disease, which is a common autoimmune disease.

Previously, the four indications declared for this new stem cell drug, namely, moderate and severe chronic plaque psoriasis, severe lupus nephritis, chronic and acute (subacute) liver failure, and moderate and severe uterine adhesion, have been implicitly approved to conduct clinical trials of the new drug.

Q - Stem Biotech

On December 14, 2002, according to the official website of CDE, Quansheng's "Human umbilical Cord Mesenchymal Stem Cell injection" was approved clinically, and the indication was decompensated hepatitis B virus cirrhosis. This is the fourth indication obtained by Quansheng after "mild to moderate acute respiratory distress syndrome (ARDS), ankylosing spondylitis and second degree burn".

Ixcellbio

On February 18, 2022, the application for clinical trial of Ixcellbio "human umbilical cord mesenchymal stem cell injection" was accepted. The indications were ischemic stroke and connective tissue disease-associated interstitial lung disease (CTD-IP), which was obtained after knee osteoarthritis.

Jztmaker

On June 9, 2023, the clinical trial application for human bone marrow mesenchymal stem cell injection (IND) submitted by Jiuzhitangmeiker Institute was implicitly approved by NMPA for autoimmune pulmonary alveolar proteinosis (aPAP). It is a cryopreserved stem cell preparation independently developed by Jiuzhitangmeiker, which is derived from the bone marrow of healthy young adult donors and cultured under hypoxic conditions, simulating the real physiological environment of the human body. This is the first clinical trial application for the treatment of autoimmune pulmonary alveolar proteinosis (aPAP) with stem cells in China.

In addition to the clinical approval of this product, Jiuzhitangmeiker has also ushered in an important development. Recently, the phase I clinical trial of ischemic tolerant human bone marrow mesenchymal stem cells (it-hMSC) in the treatment of ischemic stroke has been completed and showed good safety. The project was evaluated by the Drug Evaluation Center of the State Drug Administration and agreed to enter the phase Ⅱ a clinical trial. This is the first clinical trial in China to use imported stem cells to treat nervous system indications.

Renocell Biotech

On May 30, 2023, according to the official website of CDE, the "RY_SW01 cell injection" declared by Renocell Biotech was accepted by IND and is a stem cell therapy derived from umbilical cord mesenchymal stem cells. Previously, RY_SW01 received clinical implied permission in 2022 for lupus nephritis (LN).

Bopin Biopharma

On June 30th, 2022, according to the official website of CDE, the class I biological product "Human Adipose Mesenchymal Stem Cell injection" IND developed by Bobin Biology was approved, which is mainly used in the treatment of knee osteoarthritis (KOA). The approved stem cell therapy based on human adipose mesenchymal stem cells (ADMSC) has multi-directional differentiation potential, strong proliferation ability and multi-directional differentiation potential, and can differentiate into different tissues under different induction conditions, such as bone tissue, cartilage tissue, adipose tissue and so on.

BAYLX

On May 9, 2023, the new drug product "Human umbilical Cord Mesenchymal Stem Cell injection" of BAYLX was approved by the State Drug Administration (IND). The indication is Alzheimer's disease. Through its powerful anti-inflammatory, immune regulation, amyloid plaque removal, enhanced neurogenesis and other functions, it is expected to become a new method for the treatment of AD. This is also the third indication obtained by Belai after "idiopathic pulmonary fibrosis and rheumatoid arthritis".

Boe Regenerative Medicine

On November 22, 2022, according to the official website of CDE, BOE Regenerative Medicine's "human umbilical cord mesenchymal stem cell membrane" was approved for clinical use in the treatment of coronary artery bypass grafting (CABG) for low ejection fraction coronary heart disease with poor expected results, which is also the first clinically approved stem cell membrane new drug in China.

iwensai

On June 21, 2023, Yi Wensai's new drug clinical trial application (IND) for "Human umbilical cord mesenchymal stem cell Injection" was approved by NMPA for moderate and severe acute respiratory distress syndrome (ARDS). Human umbilical cord mesenchymal stem cell injection was independently developed by Yi Wensai. The active ingredient is human umbilical cord mesenchymal stem cells isolated, screened and expanded from healthy newborn umbilical cord tissue in vitro.

Xirui Life Science

On August 29, 2022, according to the CDE announcement, the application for the clinical trial of "Cytopeutics® umbilical cord mesenchymal stem cells (Neuroncell-EX)" introduced by Xirui Life has been accepted, and the indication is stroke. It is reported that this is a key project from Malaysia's Shide Biological company - mesenchymal stem cell treatment of stroke, and has an international patent, patients in the 90-day golden period to receive stem cell treatment, there is a 90% chance to restore 90% of the state before the onset of disease.

Tianjin Angsai Cell Gene Engineering

On January 17, 2023, the new indication of "mesenchymal stem cells for injection (umbilical cord)" independently developed by Tianjin Angxai was approved IND for the treatment of traumatic spinal cord injury. CDE shows that this "mesenchymal stem cell for injection (umbilical cord)" has been approved for three indications. They were refractory acute graft-versus-host disease (GvHD), chronic acute (subacute) liver failure and acute respiratory distress syndrome.

Vcanbio Cell & Gene Engineering 

On June 2, 2023, according to the official website of CDE, Vcanbio Cell & Gene Engineering's wholly-owned subsidiary Wuhan Optics Valley Zhongyuan Pharmaceutical received two clinical trial implied approval for VUM02 injection, respectively, for patients with chronic plus acute (subacute) liver failure and acute respiratory distress syndrome. The previously approved indications were idiopathic pulmonary fibrosis and decompensated cirrhosis. VUM02 injection (Human umbilical cord derived mesenchymal stem cell injection) is a cryopreserved stem cell preparation independently developed by Zhongyuanxiehe. It is a human umbilical cord derived mesenchymal stem cell (UC-MSC) suspension prepared from healthy newborn umbilical cord tissue after isolation, screening and expansion in vitro.

Boyalife Wsn Ltd.

On February 23, 2023, according to CDE's official website, Boya Life Technology Co., Ltd. Its subsidiary Boyalife Wsn submitted an application for clinical trial of "Watton's gel mesenchymal stem cell injection" to obtain clinical implied approval. Indications: knee osteoarthritis. Umbilical cord mesenchymal stem cells (hUC-MSCs) are a type of mesenchymal stem cell found in Wharton's jelly of the umbilical cord and perivascular tissue.

Shenzhen Yinguan Biological Technology

On December 29, 2022, according to the official website of CDE, Shenzhen Yinguan Biological Technology's IND application for human umbilical cord mesenchymal stem cell injection was accepted. This is the first clinical trial approval of local stem cell drugs in Shenzhen, filling the gap in the field of stem cell therapy for acute ischemic stroke in Shenzhen, and will play a positive role in promoting the clinical transformation application and industrialization of stem cell drugs in Shenzhen and even the whole country.

Guangzhou Saijun Biotechnology

On December 29, 2022, according to the official website of CDE, Guangzhou Saijun BiotechnologyCG-BM1 allogeneic human bone marrow mesenchymal stem cell injection new indication: Chronic and Acute liver failure (ACLF) IND applied for clinical implied approval. It is reported that this is an allogeneic stem cell therapy independently developed by Saijun Biology, which has been approved by clinical implication in 2021 for the treatment of moderate and severe adult acute respiratory distress syndrome (ARDS) caused by infection.

Beijing Sanli Heze Biotechnology

On June 7, 2018, according to the official website of CDE, the investigational New drug (IND) application for human dental pulp mesenchymal stem cell injection jointly declared by Beijing Sanli Heze Biotechnology and Capital Medical University was accepted. The indications are: chronic periodontitis, such as periodontal tissue defects caused by chronic periodontitis. The effective component is human dental pulp mesenchymal stem cells, which are derived from the pulp cavity of wisdom teeth or orthodontic teeth extracted from healthy volunteers, and have strong biological and immunological properties such as tissue regeneration and immune regulation.

Beijing Yuge Stem Cell Technology

On March 21, 2023, according to the official website of CDE, the new drug investigational (IND) application for "Human adipose mesenchymal Stem Cell injection" submitted by Beijing Yuge Stem Cell Technology was accepted for the treatment of systemic sclerosis hand lesions.

Xibiman Biotechnology 

On September 25, 2019, CDE official website showed that Xibiman Biotechnology received the clinical implied approval of the second new stem cell drug - autologous human adipose mesenchymal progenitor cell injection (ReJoin®) for the treatment of knee osteoarthritis, after collecting the patient's own adipose tissue, It is grown and prepared using "special media" (serum-free and antibiotic-free) and proprietary formulations from Sibiman Biotechnology Group.

April 3, 2023, Phase III clinical trial of AlloJoin®, Sibiman's alloJOIN ® injection for human adipose mesenchymal progenitor cells. AlloJoin® is the first self-developed innovative stem cell drug in China to enter Phase II clinical directly with the tacit approval of CDE, and is also the first stem cell drug for knee osteoarthritis to enter phase III clinical in China. Previously, AlloJoin's IND application was accepted by the National Drug Administration on November 7, 2018.

Tuohua Biotechnology 

On February 25, 2023, Tuohua Biotechnology's independent research and development of Class I innovative drug "Human umbilical cord mesenchymal stem cell injection" new drug investigational (IND) application was accepted, the indication for the treatment of moderate/severe acute respiratory distress syndrome.

Zehui Biotechnology

On April 18, 2023, according to the official website of CDE, Zehui Biotechnology's human embryonic stem cell product "CAStem cell injection" was approved for clinical use in the treatment of acute graft-versus-host disease (aGVHD) and acute exacerbation of interstitial lung disease. Previously, this CAStem cell injection has been approved to carry out a number of clinical applications, including for acute respiratory distress syndrome, new coronavirus pneumonia related pulmonary fibrosis, meniscus damage and so on.

Beijing Health&Biotech Group

On November 23, 2018, according to the official website of CDE, the human placental mesenchymal stem cell gel developed by Beijing Health&Biotech Group was approved by the implied clinical trial for the treatment of diabetic foot ulcers. This is the second stem cell new drug IND accepted in China, and it is also the first "cell gel" new drug IND accepted.

Bosheng Excellence Biotechnology

On November 7, 2019, it was learned from CDE's official website that Bosheng Excellence Biotechnology stem cell drug human umbilical cord mesenchymal stem cell injection clinical trial application was approved by acquiescence. Indications: For the treatment of hormone-resistant acute graft-versus-host disease, administered intravenously.

SALIAI Stemcell Science and Technology

On September 26, 2021, according to the CDE official website, SALIAI Stemcell Science and Technology developed a national class 1 innovative drug - human umbilical cord mesenchymal stem cell inflammation new drug was approved by CDE clinical trial implied for the treatment of knee joints.

Shengchuang Precision Medical Technology

On March 3, 2021, according to CDE's official website, Shengchuang Precision Medical Technology's declaration of "uterine blood mesenchymal stem cell injection" was clinically accepted, with an indication of idiopathic pulmonary fibrosis. It is worth mentioning that this is the first domestic approved clinical uterine blood derived stem cell therapy candidate, and the second stem cell therapy candidate adapted to "idiopathic pulmonary fibrosis".

Madison Regenerative Medicine

On February 12, 2019, according to CDE's official website, Madison Regenerative Medicine's human primitive mesenchymal stem cells submitted a clinical trial supplement application for the treatment and prevention of acute and chronic graft-versus-host diseases that occur after hematopoietic stem cell transplantation.

Aoke Biological Development

On December 5, 2018, the stem cell innovation drug "Human umbilical cord mesenchymal stem cell injection" declared by Aoke Biological Development was accepted for clinical application for the treatment of moderate and severe ulcerative colitis.

Dekang Biotechnology

On August 31, 2021, Dekang Biotechnology's new Class 1 biologics drug "Allogenic human adipose-derived mesenchymal stem cell Injection" (code DK-001) was clinically accepted for the treatment of "complex perianal fistula in adult patients with inactive/mildly active endovascular Crohn's disease."

Laifu Medical Technology

On June 16, 2023, the "human umbilical cord mesenchymal stem cell Injection" independently developed by Laifu Medical Technology officially obtained the notification of drug clinical trial approval of CDE. The new indication is mainly used for the treatment of interstitial lung disease, which is another new indication obtained after the approval of the first indication for idiopathic pulmonary fibrosis of the "Human umbilical cord mesenchymal stem cell injection" by lafu Medical in 2021.

Xingrui Biotechnology

On March 24, 2023, according to the CDE official website, Xingrui Biotechnology submitted the "new state stem cell injection" new drug investigational (IND) application was accepted, the indication is knee osteoarthritis, and the repair and regeneration characteristics of stem cells have opened up a new path for the treatment of knee osteoarthritis.

Tuohong Kangheng Pharmaceutical 

On June 12, 2023, according to the CDE official website, Tuohong Kangheng Pharmaceutical's self-developed "Human TH-SCO1 cell injection" new drug investigational application (IND) was granted clinical implied approval for the treatment of chronic radiation proctitis. The human TH-SCO1 cell injection is an injection of human umbilical cord mesenchymal stem cells, developed by Tuohong Kangheng using cell preparation technology with independent intellectual property rights. Previously, the product has been approved for two indications, respectively for the treatment of inactive/mildly active Crohn's disease anal fistula and complex anal fistula.

Wuxi Huatai Rehabilitation

On June 20, 2023, according to the official website of CDE, Wuxi Huatai Rehabilitation's "IHS002 human umbilical cord mesenchymal stem cells" were declared clinical. The product has not yet disclosed more information, medical Mack will continue to follow the report.

Imstem BIOTECH

On January 30, 2022, Imstem BIOTECH filed an IND for IMS001. This is the first time in the world that cells derived from embryonic stem cells have been used in clinical trials for systemic administration of drugs in humans, the first indication being multiple sclerosis。

Beike Bio-Technology 

On June 5, 2020, according to the official website of CDE, Beike Bio-Technology for injection injection human umbilical cord mesenchymal stem cell new drug clinical trial application was accepted. It is reported that the new stem cell drug is the first stem cell product for the treatment of refractory systemic lupus erythematosus in China.

Reforgene Medicine

On August 15, 2022, according to the CDE official website, the clinical trial application for "HBG gene modified autologous CD34+ hematopoietic stem cell injection" declared by Reforgene Medicine has been accepted, and the indication is transfusion-dependent β-thalassemia. RM-001 uses CRISPR/Cas gene editing technology to permanently modify gamma-globin promoter, activate the synthesis of naturally occurring fetal hemoglobin (HbF) in human body, continuously alleviate the symptoms of hemolytic anemia caused by β-globin loss, and achieve the purpose of radical treatment of β-thalassemia with a single administration.

Bioray Laboratories INC.

On August 16, 2022, the official website of CDE showed that Bioray Laboratories INC.BRL-101 autologous hematopoietic stem progenitor cell injection received clinical tacit approval for β-thalassaemia (thalassaemia), based on the self-developed hematopoietic stem cell platform (ModiHSC®).

Saiyao Biotechnology

On February 11, 2022, CDE official website showed that the clinical trial of a Class 1 new drug proposed by Saiyao Biotechnology was officially approved, and the application for human amniotic epithelial stem cell injection for the treatment of hormone-resistant acute graft-versus-host disease after hematopoietic stem cell transplantation was officially approved.

XLotus Therapeutics 

On March 12, 2021, XLotus Therapeutics received an investigational New drug (IND) application for REGEND001 cell autotransfusion for the treatment of early and mid-stage idiopathic pulmonary fibrosis. It is reported that this new stem cell drug is the world's first approved to enter the clinic for respiratory diseases stem cell products, which mainly uses a unique lung tissue regeneration and repair mechanism to play a therapeutic role, using autologous lung base epithelial cells to help rebuild the respiratory system.

Conclusion

With the increasing improvement of national policies and regulatory systems in recent years, as well as the continuous breakthrough of new technologies, the current stem cell therapy in China has made great progress compared with the past decades, and has quite the momentum to catch up with the United States. However, at the same time, due to the large differences in cell source, type, preparation process and other aspects of stem cell-related products, their therapeutic mechanism and in vivo activity are more complex than traditional drugs, so stem cells still face some challenges in patent medicine, including the safety of stem cells, induction efficiency, clinical transformation process exploration, and high research and development costs. Have limited the development of stem cell therapies to some extent. It is believed that with the iteration of new stem cell technology, the future will break through these limitations, become an important main force to solve many clinical needs, and bring trans-era changes to human medical treatment and other industries.