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LeadLeo Research Institute, in collaboration with Frost & Sullivan, has released2023Year in ChinaEPCOverview of the Cell Therapeutics Industry
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In December 2023, the 2023 China Stroke Conference was held in Beijing. Stroke is an acute cerebrovascular disease and one of the main causes of disability among Chinese adults. Previously, 14 departments including the National Health Commission jointly formulated and issued the 'Healthy China Action - Implementation Plan for Cardiovascular and Cerebrovascular Disease Prevention and Control (2023-2030)', effectively improving the effectiveness of cardiovascular and cerebrovascular disease prevention and control. The overall requirements propose that by 2030, significant breakthroughs will be made in cardiovascular and cerebrovascular disease prevention and control technologies, with the mortality rate from cardiovascular and cerebrovascular diseases reduced to 190.7 per 100,000 or lower.
Against this backdrop, LeadLeo Research Institute, in collaboration with Frost & Sullivan, has focused on the current situation and pain points of cardiovascular and cerebrovascular diseases in China. They have conducted a comparative analysis of traditional treatments for acute ischemic stroke and cellular drug therapies, and selected those that have achieved significant breakthroughsSpecific research has been carried out on EPC cell drug therapy, exploring the role and therapeutic capabilities of EPC cells in vascular and neural regeneration. The market status quo, industrial chain composition, development environment, and challenges of EPC cell drugs have been analyzed, and based on this, the '2023 China EPC Cell Drug Industry Overview' has been released.
Chengnuo MedicineNew indications for EPC cell-based drugs have been approved for clinical trials, further expanding the therapeutic scope for ischemic diseases.
In November 2023, according to the official website of CDE, Chengnuo Medicine's allogeneic EPC injection (ALF202) has received an implied marketing authorization for clinical trials, intended for the treatment of severe lower limb ischemia. The company's first allogeneic iPSC-derived EPC cell product, ALF201 injection, which is used for the treatment of acute ischemic stroke, is currently in Phase I clinical trials and has demonstrated safety and effectiveness in preclinical studies.
With the increasing prevalence and mortality rates of cardiovascular and cerebrovascular diseases in China, the society's demand for drugs with better therapeutic effects is rising day by day.EPC can promote the regeneration of blood vessels and nerves as well as the repair of injuries, offering broad clinical application prospects. It has particular potential in the research and treatment of ischemic diseases.
The characteristics between batches of EPC sourced from iPSC are stable, and the drug quality is controllable, enabling large-scale production.
EPCs are precursor cells of vascular endothelial cells, originating from peripheral blood, umbilical cord blood, or bone marrow tissue. Under physiological or pathological stimuli, they can be mobilized from bone marrow to peripheral blood. They play a role in restoring vascular integrity and remodeling by repairing damaged vascular endothelium and promoting angiogenesis. They can also promote nerve repair and regeneration by recruiting neural stem/progenitor cells, oligodendrocytes, and immune regulation, improving brain microenvironmental inflammation, and exerting neuroreconstructive and protective effects.
currentThe main preparation methods for EPC include direct extraction and separation from peripheral blood or bone marrow, as well as directed induction differentiation of iPSC. The preparation of EPC derived from iPSC mainly utilizes the strong differentiation potential and unlimited in vitro replication ability of iPSC. Cells from a donor (allogeneic) blood sample are expanded in vitro, and single clone cell lines of iPSC can be obtained using techniques such as plasmid transient transfection and reprogramming systems. These cells are further expanded into an iPSC multi-level cell bank, and EPC is prepared through differentiation batches.
Therefore,The cell sample donors for EPC derived from iPSC are clearly traceable, eliminating the need for repeated sampling. The characteristics of products across batches are relatively stable and their quality is controllable. Compared with autologous bone marrow, EPC derived from iPSC can be easily scaled up for mass production under the premise of meeting the latest requirements of Chinese regulations, providing an adequate supply of cells to meet the dosing needs during the acute phase of related diseases.
iPSCs have significant advantages as starting materials for drug research and development, and can provide patients with an adequate supply of high-quality EPC cells in a timely manner.
currentThe clinical research field of EPC cell therapy involves cardiovascular and cerebrovascular diseases, with a huge unmet demand space. The research and development of generic spot-type EPC cell drugs and their large-scale production are imperative.
First,The iPSC technology platform uses iPSCs as the starting material for EPC drug research and development. iPSCs possess ESC-like characteristics in terms of morphology, properties, and functions, and have strong self-renewal and differentiation capabilities. Theoretically, they can differentiate into almost all functional cells and tissue types in the human body, making them widely applicable. This has enhanced the platform's innovation capabilities and provided a foundation for developing various new cell therapies.
Secondly,iPSCs possess the ability to replicate infinitely under suitable in vitro conditions, with an unlimited number of cell lines and high consistency. They can meet the latest regulatory requirements for site-specific gene editing and single-cell screening, significantly improving the efficiency and functionality of tumor immune cells and regenerative medicine-related cells derived from iPSC differentiation.
Third,The cell samples used in the iPSC development platform come from adult cells from carefully screened fixed donors, with clear and traceable sources. Moreover, due to the strong proliferation and differentiation potential of iPSCs, there is no need for repeated sampling. The characteristics of endothelial progenitor cell products produced between batches are relatively stable, effectively ensuring that the quality of drugs developed by the platform is controllable and avoiding inconsistent clinical efficacy.
In addition,iPSCs are prepared from adult cells, eliminating the need for embryonic extraction. They are readily available and pose no ethical or moral risks. Coupled with their personalized characteristics, they greatly enhance the commercialization potential of drugs after they are launched on the market, with enormous market application potential.
EPC can promote the regeneration of blood vessels and nerves as well as the repair of injuries, holding great potential in the research and treatment of ischemic diseases.
EPC can act on both blood vessels and nerves, helping to repair damaged blood vessels, nerves, and myelin sheaths, promoting the regeneration of blood vessels and nerves, and inhibiting brain inflammation. In the future, endothelial progenitor cells derived from iPSC are expected to develop into an ideal first-choice drug for ischemic diseases, especially irreversible acute conditions.
First,EPCs are involved in the self-healing vascular regeneration after stroke. When the body is damaged or stimulated, they can be mobilized through the bloodstream to that site, forming new blood vessels. They restore vascular integrity and tissue reperfusion by repairing damaged vascular endothelium and promoting angiogenesis. Secondly, EPCs promote nerve and myelin repair by recruiting neural stem/progenitor cells, oligodendrocytes, and immune regulation, assist in nerve regeneration, improve inflammation in the brain microenvironment, and play a role in neural reconstruction and protection.
In addition,EPC has specific differentiation potential and can further differentiate into mature endothelial cells. It also possesses strong autocrine and paracrine abilities and can participate in the treatment of a range of cardiovascular and cerebrovascular diseases. Relevant studies have shown that EPC plays an important role in cardiovascular and cerebrovascular diseases, peripheral vascular diseases, and wound healing.
ALF201 injection has strong large-scale production capabilities and commercial potential
ALF201 injection is the world's first iPSC-derived allogeneic EPC cell therapy product independently developed by NuonMed. It is currently in the clinical Phase I trial stage and has strong large-scale production capabilities and commercial potential. It can rapidly provide sufficient and more effective treatment options for patients with acute ischemic stroke (AIS).
In terms of drug sources and preparation,ALF201 is an iPSCs technology platform independently developed by Chengnuo Medicine. It collects peripheral blood monocytes from healthy donors, reprograms them into iPSCs, and after establishing a library, it can be used to differentiate EPC cells in batches in a targeted manner. Its advantages include compliant and traceable sample sources, strong cell proliferation capacity and differentiation potential. While achieving mass production, it ensures relatively stable characteristics between batches and guarantees drug efficacy.
In terms of clinical application and indications,The clinical study of ALF201 injection for acute ischemic stroke has entered Phase I clinical trials, and ALF202 for severe lower limb ischemia has obtained an implied marketing authorization from the clinical trial authority. As iEPCs are further explored in the clinical research of ischemic diseases, the scope of indications will be further expanded in the future, such as atherosclerosis, pulmonary hypertension, coronary heart disease, cerebral microvascular disease, male erectile dysfunction, etc.
In terms of treatment targets and mechanisms,EPC cell therapy acts on both blood vessels and nerves, effectively avoiding the risks of disability, paralysis, and nerve damage caused by AIS to patients.
Large-scale production isKey elements for EPC pharmaceutical R&D companies to improve R&D efficiency and the commercialization process after future drug launches
chinaThe competitive barriers in the EPC cell drug industry mainly include preparation technology, large-scale production, and the first-mover advantage of leading enterprises. Among them, large-scale production is the core barrier and a key element for EPC drug R&D enterprises to improve R&D efficiency and the commercialization process after the drug is launched in the future.
Firstly, the industry has significant first-mover advantages, and there are currently no listed ones globally.EPC cell drugs are all in the drug research and development phase. The fastest-progressing drug with an enterprise as the R&D entity is Northern, a Canadian cell and gene therapy company. The eNOS-transfected autologous EPCs from Therapeutics are currently in Phase II/III for the treatment of idiopathic pulmonary arterial hypertension; in terms of therapies for acute ischemic stroke, only ALF201 from NuoMed has entered clinical trials globally. If clinical research progresses smoothly, the product's launch will rapidly penetrate the terminal market, giving it an opportunity to enter the downstream tertiary hospital channels first, thereby quickly occupying more advantageous resources and establishing a higher market position.
Secondly, becauseThe research, development, and production of EPC cell drugs have extremely high environmental requirements. To achieve large-scale production, EPC drug R&D companies need to have a strictly controlled process flow and a high level of automation. Based on the characteristics of stem cells and the compliance of related therapies, most EPC cell drugs currently under research mainly use autologous EPC for development, which requires repeated sampling from donors multiple times, affecting the continuity of treatment and the efficiency of drug preparation and reinfusion. Therefore, stable and healthy donor sources, efficient in vitro expansion and differentiation techniques are key to enhancing large-scale production capacity. The development of generic off-the-shelf drugs is one of the main trends in the future research field of EPC cell drugs.
Midstream enterprises further achieve cost reduction and efficiency improvement, and promoteEPC Drug Clinical Outcome Translation
The upstream of the EPC cell drug industry includes suppliers of cell storage services, equipment, reagents, and consumables. The midstream consists of EPC cell drug research, development, and manufacturing enterprises. The downstream is the terminal market for EPC drug applications.
Midstream of the industryEPC cell drug R&D and production enterprise, mastering independent R&D technology for EPC cell drugs and maintaining close cooperation with upstream and downstream partners. Firstly, midstream enterprises can enter the upstream market by building their own clinical-grade cell banks, which can improve cell access efficiency, control over process flow and cell quality, thereby ensuring drug R&D efficiency and achieving large-scale production. Secondly, by cooperating with local advanced upstream enterprises, midstream enterprises can ensure a stable supply of high-quality raw materials. Through customization or joint development of upstream equipment and reagents, they are expected to further optimize R&D production processes, improve drug R&D and large-scale production efficiency, or reduce the pricing range of future marketed drugs, thereby promoting penetration into downstream markets. In addition, midstream enterprises cooperate closely with downstream hospital sectors, where top medical institutions can provide high-quality medical resources. By participating in clinical trials and research with authoritative experts and directors, they can promote the clinical transformation of EPC drugs.
Insights: The FutureEPC derived from iPSC is expected to develop into an ideal first-choice drug for ischemic diseases, especially irreversible acute conditions.
In China and even globally, heart disease and cerebrovascular diseases are high-incidence diseases. The massive patient base determinesEPC cell therapies have a vast potential and accessible market, with overall market demand continuing to rise as the prevalence and mortality rates of heart disease and cerebrovascular diseases increase.
Based on current clinical research findings,EPC cell therapy can act on both blood vessels and nerves, helping to repair damaged blood vessels, nerves, and myelin sheaths, promoting the regeneration of blood vessels and nerves, and reducing brain inflammation. It has significant advantages in the field of cardiovascular and cerebrovascular disease treatment, providing an optimal treatment method for more patients with heart and cerebrovascular diseases. Especially for patients with acute ischemic stroke (AIS), which is a condition that often leads to disability and death in the acute phase, there is currently a lack of drugs in clinical practice that can simultaneously address both vascular and nerve repair and protection. From the perspective of the treatment window, the only therapy currently used in the acute phase of AIS is EPC, and clinical studies have shown that EPC can effectively extend the dosing window to 96 hours. The ongoing Phase I clinical study of ALF201 for stroke treatment has a patient treatment window of within 7 days after stroke onset. Compared to traditional intravenous thrombolysis, mechanical thrombectomy, and drug therapy for treating AIS, the EPC drug has a longer dosing window and can effectively reduce disability and mortality rates as well as recurrence rates. With the successful progress of the ALF201 clinical trial, the advantages of EPC drugs will become even more apparent. In the future, after EPC drugs are approved for marketing and enter large-scale commercial production, they may become an ideal first-choice drug.
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"TheOverview of China's EPC Cell Therapy Industry in 2023
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