ProTrans is NextCell's first drug candidate and the most advanced in its development journey. It is rooted in a patented selection algorithm designed for addressing type 1 diabetes. The therapy dampens destructive autoimmune effects and thereby slows disease progression. The efficacy of ProTrans can be beneficial in a variety of areas where there are currently no suitable options. Other examples encompass conditions like Crohn's disease, multiple sclerosis (MS), and rheumatism.
NextCell has developed a next-generation cell therapy with mesenchymal stromal cells, MSC. There are currently similar drugs that are approved for the treatment of, among other things, children affected by graft against host disease (GVHD) after bone marrow transplantation and treatment of severe Crohn's disease. The potential of MSC-based cell therapy is significantly greater. ProTrans is a further development with a focus on increasing the number of indications and treatment effect.
NextCell’s patented selection algorithm distinguishes ProTrans from other MSC treatments. The algorithm weighs together the results of functional analyses based on the cells’ known mechanism of action for balancing the immune system.
There are large variations between different cells when analyzed in functional analyses. By selecting cells, the variation can be reduced. ProTrans is manufactured from MSCs derived from umbilical cord tissue containing young and viable cells that have not yet been exposed to injury or aging.
MSC treatments have been evaluated since the 1990s and have a strong safety profile, without any serious side effects. Unfortunately, the efficacy of therapy has been varied, therefore to address this limitation, we have developed a robust, reproducible selection process for donor cells utilized in ProTrans manufacture.
Type 1 diabetes is an autoimmune disease where the body's immune system attacks and destroys the insulin-producing beta cells in the pancreas so that the affected individual can no longer produce insulin themselves. It is a life-threatening, incurable disease and at present, the affected person will have to live with the disease for the rest of their life.
ProTrans has been shown to slow the progression of the disease in adult patients newly diagnosed with type 1 diabetes. Although the patients treated continue to need extra insulin, a small residual insulin production may mean better blood sugar control and ultimately counteract complications and consequential disease.
Infection of Sars-CoV-2 (COVID-19) can, in severe cases, lead to hyperinflammation of the lungs, which is a life-threatening condition associated with high mortality.
ProTrans' potential to reverse hyperinflammation in the lungs is now being evaluated in two clinical trials. The aim is to treat patients before their conditions deteriorates to the point they need to be put on a ventilator. Preventing the need for life support treatment can be both life-saving and reduce rehabilitation time.
COVID-19 is an example of a respirator viral infection that can lead to severe complications due to an excessive immune response, impacting primarily the lungs. Sars-CoV-2 is one example of a virus triggering hyperinflammation of the lungs. The broad action of NextCell´s drug candidate, means that systemic treatment with ProTrans could potentially address a broader range of complications stemming from numerous respiratory viruses. To address this, one of NextCell´s studies is designed to also include patients with severe pneumonia associated with influenza A, RS- and HMPV.
In 2018, the first patient was treated with ProTrans at the Karolinska University Hospital's clinical trial unit. Four studies are currently underway, with two actively recruiting patients at university hospitals in Malmö, Uppsala, and Örebro. NextCell has submitted a pediatric development plan to the European Medicines Agency's expert committee for drug development in pediatric patients. The plan outlines the clinical trial program up to commercialization and is a requirement for the upcoming Phase 3 studies.
A phase 1 open-label dose-escalation study concluded in 2019 including nine type 1 diabetes patients. The study demonstrated both a) favorable safety outcomes and b) a dose-dependent effect concerning the preservation of endogenous insulin production one-year post-treatment.
A placebo-controlled Phase 2 study, concluded in 2020, including 15 type 1 diabetes patients, demonstrated a significant treatment effect (p<0.05). ProTrans-treated patients retained 90% of their endogenous insulin production at one-year post-treatment, compared to 53% in the placebo group.
ProTrans-Repeat is an open follow-up study of the patients who participated in ProTrans-1. After the initial treatment, the nine included patients were treated with an additional dose of equal cell number to that they had received one to two years earlier. On October 18, 2022, an interim analysis was presented after the second treatment, which concluded that treatment with the highest dose yields a significantly (p<0.05) superior long-term effect regarding the preservation of endogenous insulin production. On average, the three cohorts – low-dose, mid-dose, and high-dose – retained 41%, 45%, and 81% of their insulin-producing capacity from the initial treatment after approximately 3.5 – 4 years. The long-term effect will be followed up for an additional approximately two years.
A long-term follow-up of 11 patients previously enrolled in ProTrans-2. The study is ongoing for 5 years. Of the 14 patients who completed ProTrans-2, 6 ProTrans-treated and 5 placebo-treated patients accepted to participate in the ProTrans-Obs follow-up study. This follow-up study assesses patients' endogenous insulin production every six months. A 3-year follow-up has been conducted to date. The results from this interim analysis indicate statistically significant maintenance of endogenous insulin production with ProTrans treatment at all analyzed time points (p<0.05).
A Phase 1/2 pediatric study for the treatment of type 1 diabetes, where the first part consists of an open safety study of 6 recently diagnosed children. All patients have been treated, and a safety committee recommended Professor Per-Ola Carlsson to proceed with the second part of the study. The Phase 2 part of this study has been ongoing since late 2022 and is a randomized, placebo-controlled double-blind trial enrolling 30 patients aged 12 to 21 years and 30 patients aged 7 to 11 years.
A Swedish open dose-escalation study (Phase 1) using ProTrans to treat adult patients diagnosed with severe pneumonia due to Sars-CoV-2 infection.
A Canadian randomized, placebo-controlled, double-blind Phase 2 study for the treatment of adult patients diagnosed with severe pneumonia due to Sars-CoV-2 infection. The trial was completed earlier due to lack of patients.
The clinical trials are conducted together with Karolinska University Hospital and Uppsala University and Uppsala University Hospital.
Edvard Smith, MD, PhD, Professor of Molecular Genetics at the Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital.
Per-Ola Carlsson, Professor of Medical Cell Biology with a specific interest in experimental endocrinology at Uppsala University and Uppsala University Hospital.
Dr. Josefin Sundh, Associate Professor and Senior Physician in the Lung Section, Cardiopulmonary Physiology Clinic, University Hospital in Örebro, as well as University Lecturer at the Department of Medical Sciences, Örebro University.
Dr. Inés Colmegna, MD, Associate Professor of Rheumatology in the Department of Medicine at McGill University and The Research Institute of the McGill University Health Centre.
Lindsay Davies, PhD in Biochemistry, with extensive experience in stromal cell biology and the development of cell therapies. In her role as CSO, Davies is responsible for both the existing research portfolio and the development of new clinical treatments.
Sofia Sisay, PhD in Neuroscience, with extensive experience in leading clinical studies and projects within both academia and industry. In her role as Clinical Trial Manager, Sisay is responsible for all ongoing clinical trials and has been project manager since the inception of our first clinical trial.
The drug candidate ProTrans is a stromal cell product derived from umbilical cord tissue. The cells are carefully selected using NextCell's selection algorithm (patent pending).
In a clean room laboratory, a variety of advanced analyses are performed to evaluate the function of the isolated cells, and how they can modulate the immune system. The results are entered into the selection algorithm that calculates the cells' combined ability to attenuate a dysregulated immune response through several mechanisms of action.
The immune system consists of a variety of cell types that are activated or inactivated by a multitude of different signalling molecules. In autoimmune diseases, this delicate balance has been disrupted and the immune system attacks the body´s own cells, resulting in inflammation. This process varies between individuals and can change over time.
ProTrans utilises the body's own way of restoring balance. Mesenchymal stromal cells immediately respond to the pathological inflammatory signalling in the environment and secrete signalling molecules to counteract the inflammation.
Based on experience from the pharmaceutical industry, NextCell has developed ProTrans to reach all the way to the patient. Umbilical cord stromal cells can be grown in large quantities and as they are non-invasively harvested from dispensable material, the supply of raw material is virtually unlimited.
ProTrans therapy is simple and safe and can be provided by your healthcare practitioner. ProTrans is delivered to the clinic as frozen product. The treatment itself is uncomplicated and non-invasive. The bag of cells is thawed and mixed with a standard saline infusion bag. The drug product is then administered by infusion into the arm fold. The treatment is cost-effective as NextCell can produce large scale batches of product, which can be stably stored for extended periods of time.
The classical definition of a stem cell requires that it possess two properties:
Theses properties make stem cells highly suitable for future treatments of:
Hematopoietic stem cells (HSC) give rise to all blood cells. They were discovered in 1961 and the main source of HSC is bone marrow and umbilical cord blood.
Around 50 000 patients receive a stem cell transplantation each year, a therapy given to treat 80 deadly diseases including:
Mesenchymal stromal cells (MSCs) are multipotent, tissue resident cells that can be differentiated into a variety of cell types including osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells). These cells have also been shown to modulate the immune system. MSCs have been used as a treatment in: