EU regulatory approval to administer Adipose-derived mesenchymal Stem Cells (ASCs) in patients with ischemic digital ulcers marks key milestone for partners

欧盟监管部门批准在缺血性数字溃疡患者中使用脂肪来源的间充质干细胞（ASCs）标志着合作伙伴的关键里程碑

Toulouse, France, November 16, 2023 - Cell-Easy, a French Contract Development and Manufacturing Organization (CDMO) focused on advanced cell therapies, and the Toulouse University Hospital, today announce that they have obtained IMPD (Investigational Medicinal Product Dossier) approval for a first-in-human clinical trial.

法国图卢兹，2023年11月16日-Cell Easy，法国合同开发和制造组织（CDMO）专注于先进的细胞疗法，图卢兹大学医院今天宣布他们已获得IMPD（研究性药品档案）批准用于首次人体临床试验。

This trial will use an allogeneic treatment, developed from an autologous process, for patients with ischemic digital ulcers in systemic sclerosis. The CDMO developed the entire manufacturing process from an initially autologous one where the cell donor was the patient himself..

该试验将使用从自体过程开发的同种异体治疗，用于系统性硬化症中缺血性数字溃疡的患者。CDMO从最初的自体细胞开发了整个制造过程，细胞供体本身就是患者。。

The innovative allogeneic approach uses cells from a single donor to produce therapeutic doses for thousands of patients. This is cost-efficient, and therefore it makes the product more accessible for patients.

创新的同种异体方法使用来自单个供体的细胞为数千名患者产生治疗剂量。这具有成本效益，因此它使患者更容易获得产品。

Cell-Easy has conceived and designed a process for the large-scale manufacturing of ASCs in compliance with the GMP (Good Manufacturing Practice) standards required by regulatory agencies. These ASCs will be used in the A-DUSE clinical trial. Prof. Gregory Pugnet, from the Internal Medicine and Clinical Immunology department, Rangueil Hospital, Toulouse, (France) is the main investigator of the trial, which is sponsored by Toulouse University Hospital..

Cell Easy根据监管机构要求的GMP（良好生产规范）标准，构思并设计了大规模生产ASC的流程。这些ASC将用于A-DUSE临床试验。来自法国图卢兹Rangueil医院内科和临床免疫科的Gregory Pugnet教授是该试验的主要研究者，由图卢兹大学医院赞助。。

Gaining ANSM/EMA's approval for the A-DUSE clinical trial is a demonstration of the Cell-Easy team’s ability to carry out a cell therapy development program from end to end. Some highlights from the new large-scale manufacturing process of therapeutic doses of allogeneic ASCs:

获得ANSM/EMA批准A-DUSE临床试验证明了Cell Easy团队从头到尾执行细胞疗法开发计划的能力。新的大规模生产治疗剂量异基因ASCs的一些亮点：

>5,000 doses per tissue donation

>每次组织捐赠5000剂

>4.109 cells per batch

>每批4.109个细胞

x20 cost reduction

x20降低成本

26 parameters analyzed per batch

每批分析26个参数

The Toulouse University Hospital, through its clinical center of investigation in biotherapy (CIC-BT) structure, stands as a pioneering cell therapy player in Europe. It has 20 years' experience in the field of cell therapy based clinical research. In a bid to kickstart the A-DUSE clinical trial safely and efficiently, Prof.

图卢兹大学医院通过其生物治疗临床研究中心（CIC-BT）结构，是欧洲的开拓性细胞治疗参与者。它在基于细胞疗法的临床研究领域拥有20年的经验。为了安全有效地启动a-DUSE临床试验，教授。

G. Pugnet was looking for a robust industrial partner capable of providing high numbers of clinical grade ASC therapeutic doses. The scientific, technical and regulatory expertise of the French CDMO, and its ability to offer an end-to-end service spanning from patient sample procurement through to IMPD writing, convinced the Toulouse study center..

G、 Pugnet正在寻找能够提供大量临床级ASC治疗剂量的强大工业合作伙伴。图卢兹研究中心确信，法国CDMO的科学，技术和监管专业知识及其提供从患者样本采购到IMPD写作的端到端服务的能力。。

“This project represents another remarkable milestone for Cell-Easy, demonstrating our ability to successfully navigate the entire life cycle of Advanced Therapy Medicinal Products (ATMP) development. Our collaborative work with physicians, supply chain partners, regulators and policymakers has enabled us to effectively address the intricacies of these therapies and establish rigorous quality standards,” said Guillaume Costecalde, president at Cell-Easy..

“该项目代表了Cell Easy的另一个显着里程碑，证明了我们成功导航高级治疗药品（ATMP）整个生命周期的能力发展。Cell Easy总裁Guillaume Costecalde说，我们与医生，供应链合作伙伴，监管机构和政策制定者的合作工作使我们能够有效解决这些疗法的复杂性并建立严格的质量标准。。

Beyond conventional GMP manufacturing of ASCs, the A-DUSE clinical trial required the selected partner to provide unfailing support in terms of regulatory and scientific matters, as well as medico-economic understanding of the disease. Close collaboration between Cell-Easy, CIC-BT and Prof. G. Pugnet was instrumental in achieving this objective..

除了传统的ASC GMP制造之外，使用临床试验还要求所选合作伙伴在监管和科学事项以及对该疾病的医学经济理解方面提供不忠实的支持。Cell Easy，CIC-BT和G.Pugnet教授之间的密切合作有助于实现这一目标。。

In less than 20 months, Cell-Easy developed a new production process in ASC along with all the associated analytical tests for robust batch qualification.

在不到20个月的时间里，Cell Easy在ASC开发了一个新的生产流程以及所有相关的分析测试，以获得可靠的批次认证。

Within the framework of this partnership, the resources made available by the CDMO have resulted in:

在这种伙伴关系的框架内，CDMO提供的资源导致：

Establishment of partnerships with local healthcare centers capable of selecting donors based on medical-biological criteria, of supplying human adipose tissue and of qualifying donations at GMP level, as required by EU/US regulatory agencies

根据欧盟/美国监管机构的要求，与当地医疗中心建立伙伴关系，这些中心能够根据医学生物学标准选择捐赠者，提供人体脂肪组织和GMP级合格捐赠

Conducting toxicity and tumorogenicity studies in mice, and

在小鼠中进行毒性和致瘤性研究，以及

Co-authoring the IMPD for submission to the local French agency, the ANSM

共同编写IMPD提交给当地法国机构ANSM

Injection of allogeneic ASC, a promising opportunity for healing digital ulcers

注射同种异体ASC，治疗数字溃疡的有希望的机会

Systemic sclerosis is an orphan disease characterized by the development of microangiopathies and progressive fibrosis. Digital Ulcers (DUs) are common in the course of the disease and are an expression of its severity. Not only do DUs cause intense pain and hand disability, but more critically they can lead to infections that can result in gangrene and eventual amputation.

系统性硬化症是一种孤儿疾病，其特征在于微血管病和进行性纤维化的发展。数字溃疡（DU）在疾病过程中很常见，并且是其严重程度的表现。DUs不仅会引起剧烈疼痛和手部残疾，而且更重要的是它们会导致感染，导致坏疽和最终截肢。

With optimal standard of care only 60% of DUs are healed after three months and 46.2% experience recurrence during this period, with 11.2% having a chronic course. To date, no medication has demonstrated a positive effect on the healing of refractory DUs. In this clinical context with no therapeutic alternative, the partnership between Toulouse University Hospital, represented by Prof.

采用最佳护理标准，三个月后只有60%的DU愈合，46.2%在此期间复发，11.2%患有慢性病程。迄今为止，没有药物对难治性DUs的愈合有积极作用。在没有治疗选择的临床背景下，图卢兹大学医院之间的合作伙伴关系由教授代表。

G. Pugnet, the CIC-BT, and Cell-Easy, through the A-DUSE Clinical Trial (digital injection of allogeneic ASC), represents a promising opportunity for many patients in the healing of refractory ischemic DUs..

G、 Pugnet，CIC-BT和Cell-Easy，通过A-DUSE临床试验（数字注射同种异体ASC），为许多患者治疗难治性缺血性DUs提供了一个很有希望的机会。。

Since 2021, French players in biotherapy have been working hard to convert a promising MSC-based therapy concept into reality for patients living with ischemic digital ulcers due to systemic sclerosis.

自2021年以来，法国生物治疗领域的参与者一直在努力将一种有前途的基于MSC的治疗概念转变为现实，用于因系统性硬化症而患有缺血性数字溃疡的患者。

About Grégory Pugnet, coordinating investigator

关于协调调查员Grégory Pugnet

Grégory Pugnet, M.D., PhD., coordinating investigator of the multicentric randomized control clinical trial (ADUSE, NCT04356755, EU CT Number 2023-508432-53-00), is among the few specialists in systemic autoimmune disease; in which he is leading important clinical research activity. He worked for 18 months at the French Reference Center for Systemic Sclerosis in Cochin Hospital (Paris, France).

Grégory-Pugnet博士。，多中心随机对照临床试验（ADUSE，NCT04356755，EU CT编号2023-508432-53-00）的协调研究者是为数不多的系统性自身免疫性疾病专家之一；他正在领导重要的临床研究活动。他在法国科钦医院（法国巴黎）的法国系统性硬化症参考中心工作了18个月。

Pugnet is an active member of the GFRS (Groupe Francophone de Recherche sur la Sclérodermie), and a member of the scientific committee of the French Reference Center for Cell Therapy in Autoimmune Diseases (MATHEC network), with the FAI2R network, labeled by the French Ministry of Health in 2017. Grégory also actively participates in CIC-BT, coordinated by Louis Buscail, and has secured funding for three ASC-based cell therapy projects in scleroderma (A-DUSE, A-MUSE) and neuroinflammatory muscular diseases (A-NEMIS) in collaboration with CIC-BT and Cell-Easy..

Pugnet是GFRS（Groupe Francophone de Recherche surlaSclérodermie）的积极成员，也是法国自身免疫性疾病细胞治疗参考中心（MATHEC network）科学委员会的成员，FAI2R网络，由法国卫生部于2017年。Grégory还积极参与由Louis Buscail协调的CIC-BT，并与之合作，为硬皮病（A-DUSE，A-MUSE）和神经炎症性肌肉疾病（A-NEMIS）三个基于ASC的细胞治疗项目提供资金。CIC-BT和cell Easy。。

About CIC-BT

关于CIC-BT

The Clinical Center of Investigation in BioTherapy (CIC-BT 1436) is an academic organization under the supervision of Toulouse University Hospital (CHUT)/INSERM/University. It was established at the end of 2005 to support researchers and companies developing cell, gene and molecular therapy ATMPs, from the preclinical phases through to the coordination and conduct of phase 1-3 clinical trials.

生物治疗研究临床中心（CIC-BT 1436）是图卢兹大学医院（CHUT）/INSERM/大学监督下的学术组织。它成立于2005年底，以支持研究人员和公司开发细胞，基因和分子治疗ATMPs，从临床前阶段到协调和进行1-3期临床试验。

Its structure draws on the expertise of CHUT's research and innovation department for regulatory aspects when CHUT is the study sponsor..

当CHUT是研究发起人时，其结构借鉴了CHUT研究和创新部门在监管方面的专业知识。。

Coordinated by Prof. Louis Buscail, CIC-BT has been responsible for numerous projects, funded by a total of six million euros ($6.4M) (CHU promoter), including five national clinical research hospital programs – Programme Hospitalier de Recherche Clinique (PHRC) (2010, 2013, 2014, 2017 and 2022), three inter-regional PHRCs (2013, 2019 and 2022), one Horizon 2020 program, one SudOE program and two associations.

CIC-BT由Louis Buscail教授协调，负责多个项目，共资助600万欧元（640万美元）（CHU发起人），其中包括五个国家临床研究医院计划-Recherche Clinique计划医院（PHRC）（2010年，2013年，2014年，2017年和2022年），三个区域间PHRC（2013年，2019年和2022年），一个Horizo​​n 2020计划，一个SudOE计划和两个协会。

CIC-BT also carries out extensive research in cardiovascular and digestive pathologies, in geriatrics and pediatrics, as well as translational research in collaboration with teams involved in regenerative medicine (RESTORE), neurodegenerative diseases (INFINITY), cardiovascular diseases (I2MC) and oncology (CRCT)..

CIC-BT还与参与再生医学（RESTORE），神经退行性疾病（INFINITY），心血管疾病（I2MC）和肿瘤学的团队合作，开展心血管和消化病理学，老年医学和儿科以及转化研究。（CRCT）。。

www.chu-toulouse.fr

www.chu-toulouse.fr

About Cell-Easy

关于细胞容易

Cell-Easy is a rapidly growing French Contract Development and Manufacturing Organization (CDMO) with a dedicated focus on advanced cell therapies. Established in 2017, Cell-Easy's commitment extends beyond development and manufacturing; it also places a strong emphasis on regulatory and CMC aspects..

Cell Easy是一家快速发展的法国合同开发和制造组织（CDMO），专注于先进的细胞疗法。Cell Easy成立于2017年，其承诺超越开发和制造；它还强调监管和CMC方面。。

Cell-Easy offers a comprehensive range of services, from process development and process scale-up through to cGMP manufacturing of next-generation advanced cell therapies. This also includes the development of analytical tests to qualify cell therapies such as ASCs, CAR-T or CAR-NK cells, iPSCs and macrophages.

Cell Easy提供全面的服务，从流程开发和流程扩展到下一代先进细胞疗法的cGMP制造。这还包括开发分析测试以鉴定细胞疗法，例如ASC，CAR-T或CAR-NK细胞，iPSC和巨噬细胞。

Cell-Easy has demonstrated its ability to support biotech/pharmaceutical companies in advancing their programs up until phase 2, and to partner with top 30 international pharmaceutical multinationals. Thanks to its flexibility and tailored CDMO solutions, Cell-Easy facilitates patient access to these innovative therapies..

Cell Easy已经证明了其支持生物技术/制药公司推进其计划直至第二阶段的能力，并与前30名国际制药跨国公司合作。由于其灵活性和量身定制的CDMO解决方案，Cell Easy便于患者获得这些创新疗法。。

www.cell-easy.com

www.cell-easy.com

Media and analysts contact

媒体和分析师联系

Andrew Lloyd & Associates

安德鲁·劳埃德及其同事

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Saffiyah Khalique-Emilie Chouinard

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saffiyah@ala.associates / emilie@ala.associates

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