01.

Technology

NextCell develops novel stem cell therapies, initially focusing on type- 1 diabetes. The lead candidate ProTrans™, is based on NextCell patent pending Selection Algorithm. Further, NextCell runs Cellaviva, Nordic’s largest private stem cell bank, approved by IVO.
A drug candidate based on mesenchymal stem cells from umbilical cord with regenerative and immunosuppressive activity. Efficiency shown in treating Type 1 diabetes.
Offers parents a service to store stem cells from the umbilical cord, collected at the baby's birth, for future medical needs.

ProTrans

Technology and the Selection Algoritm

NextCell's product portfolio is based on mesenchymal stem cells from Wharton's Jelly (WJMSCs), i.e. the gel found around the blood vessels in the umbilical cord tissue. Mesenchymal stem cells possess immune modulating capabilities, applicable in a multitude of areas with unmet medical needs, such as autoimmune conditions as well as transplant rejection.

Mesenchymal stem cells possess immune modulating capabilities, applicable in a multitude of areas with unmet medical needs, such as autoimmune conditions as well as transplant rejection.

NextCell's mesenchymal products are allogeneic, that is, the patient’s own cells are not used. The basis for NextCell's stem cell therapies is the Company's proprietary selection method  - The Selection Algorithm.

The algorithm consists of an IP protected method for selecting the stem cells with the best efficacy and potency. The method is an overall assessment of multiple functional potency assays for identifying optimal donors and cells for the manufacturing of ProTrans. NextCell's advanced selection approach ensures higher potency and efficacy compared to other applications in stem cell therapy and has the ability to easily scale. It also results in a strong safety profile with few adverse events.

The Selection Algorithm is currently protected by three patent pending families.

Furthermore, NextCell's competitive strength also lies in the use of stem cells from umbilical cord tissue. It serves as a potent cell source, able of rapid expansion and is also a cell source which otherwise would be discarded, making NextCells approach scalable yet with the ability to produce stem cell in great number with consistent high quality.  

NextCell's lead candidate ProTrans™ focusing on treating Type 1 diabetes. ProTrans™ is a Mesenchymal stem cell drug product, derived from umbilical cord tissue. The cells are carefully selected with NextCell’s selec­tion algorithm.
Mechanism of actions

Trial overview

ProTrans™ has, in addition to successful completion of it's safety, shown efficacy in protecting the patient’s own insulin production.

NextCell is running two parallel clinical trials with ProTrans™, ProTrans-1 and ProTrans Repeat.

ProTrans-1 - a two-part phase I/II study

Phase I, the safety part, is completed and show good safety. The phase I was a dose escalation for safety purposes but also showed efficacy, which is efficacy in restoring the patient’s own insulin production, which is partically positive. NextCell has been approved by Swedish Medical Products Agency (Läkemedelsverket) to continue with phase II, the efficacy study. The Phase II, now ongoing, is a double blinded placebo-controlled study with 15 patients. This type of study design gives the highest level of evidence. The study has LPLV in June/July 2020 and data is expected to be published in the third quarter of 2020.

ProTrans Repeat

A phase II study and a direct continuation of ProTrans-1 with the main goal to find out whether repeated treatment can increase or maintain the effect of ProTrans over a long period of time with retained safety. The study includes the nine patients treated in the ProTrans-1 dose escalation segment, as well as a control group of six. Results are expected to be available in the fourth quarter of 2020.

A phase III study

A phase III study is being prepared and NextCell intends to submit an application for ProTrans-3 at the end of 2020. ProTrans-3 will be a larger phase III pivotal trial, which is to be used to form the basis for a conditional market authorization.

ProTransPipeline

Milestones Achieved

2019-12-04
Interim results published with positive effect
2019-09-24
All patients in the dose escalation phase have now completed the trial
2018-10-14
All three patients in the high-dose-cohort treated (nine patients have been treated in total)
2018-01-03
First patient treated
2017-11-28
Initiation meeting at Karolinska Trial Alliance, Huddinge
2017-10-17
Permission granted by the Medicinal Product Agency
2017-07-24
Clinical trial application submitted
2019-06-20
Final patient treated in ProTrans-2
2019-01-30
First two patients have been treated in ProTrans-2
2018-10-25
Approval by the Data and Safety Monitoring board to proceed with the second part of the trial
2019-10-01
All patients have now undergone treatment
2019-09-12
Five out of 18 patients have been included into the trial.
2019-06-19
First patient treated in the ProTrans-Repeat trial
2019-05-17
Initiation meeting was held at Karolinska Trial Alliance, Huddinge
2019-05-09
Permission granted by the Medicinal Product Agency
2018-11-15
Clinical trial application submitted

Study Team

Both clinical trials are conducted together with Karolinska University Hospital and Uppsala University.

Medical Director at NextCell

Edvard Smith, MD, PhD, Professor in Molecular Genetics, Karolinska Institutet and Karolinska University Hospital

Principle Investigator

Per-Ola Carlsson, MD, PhD,  Professor of Medical Cell Biology with specific interest in Experimental Endocrinology at Uppsala University and Uppsala University Hospital

Support & Monitoring

Karolinska Trial Alliance support team, headed by Sofia Sisay, PhD

Clinic

Karolinska Trial Alliance phase I unit, Karolinska University Hospital

Data Safety and Monitoring Board

Ulf Smith MD, PhD, Professor, Chairman. Anders Fasth MD, PhD, Professor. Åke Lernmark PhD, Professor.

First indication: Type-1 Diabetes

Type 1 diabetes is an chronic autoimmune condition in which the immune system is attacking the insulin producing cells in the pancreas. The causes of this autoimmune reaction is not known and is not linked to modifiable lifestyle factors. Today, there is no cure and it cannot be prevented and the disease is usually diagnosed in children and young adults. Between 20-40 million are living with type 1 diabetes worldwide.

ProTrans will be given to patients directly after diagnosis. It is the immunomodulating effect of the stem cells in ProTrans is given in an attempt to protect the insulin producing cells and to modulate the immune system. The effect might be transient, resulting in a longer honeymoon phase or reduced need of insulin, but the goal is to reprogram the immune system to accept the body’s own insulin producing cells. ProTrans reduces the immune systems attack, and thus the insulin production is protected (other wording preferred). By restoring the patient’s innate insulin ability, the need for insulin treatment is reduced.

ProTrans™ – Carefully selected stem cells

The drug candidate ProTrans is a stem cell product from umbilical cord cells. The cells are carefully selected with NextCell’s selec­tion algorithm (patent pending).

In a clean room laboratory, a variety of advanced analyses are performed to evaluate the function of cells and how they affect the immune system. The results are entered into the selection algorithm that calculates the cells’ combined ability to attenuate an overactive immune system through several mechanisms of action.

ProTrans™ – Biological intelligence

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 progression varies between individuals and can change over time.

ProTrans utilizes the body’s own way of restoring balance. Mesenchymal stem cells immediately respond to the pathological inflammatory signalling in the environment and secrete signalling molecules to counteract the inflammation.

ProTrans™ – Industrially designed cell therapy

Based on experience from the pharmaceutical industry, Next­Cell has developed ProTrans to reach all the way to the patient. Umbilical cord stem cells can be grown in large quantities and as they are non-invasively harvested from dispensable material, the supply of raw materials is virtually unlimited.

ProTrans therapy is simple and safe and can be done at the health center (vårdcentralen). ProTrans is delivered as frozen cells in a small bag. ProTrans is thawed, and the bag of cells is then paired with a standard infusion bag. The stem cells are gently mixed with a saline solution before being given as an infusion into the arm fold. The treatment is cost-effective as NextCell can produce large production batches, can stably store frozen ProTrans for extended periods, and treatment is uncomplicated and non-invasive.

Cellaviva

Cellaviva is Sweden’s first private stem biobank for storing stem cells from umbilical cord.

Cellaviva offers prospective parents to save their new born child stem cells for fututre medical needs. After expansion to Denmark, and with a customer base throughout Scandinavia, the business has grown to become a market leader in stem cell banking throughout the Nordic Countries, and the only stem cell bank with permission from the Swedish Inspection for Health and Care (IVO).

Cellaviva launched its product, banking of stem cells from the umbilical cord, in September 2015 and today the Swedish market still can be regarded as relatively immature. However, family stem cell banking and cord blood banking is a proven business model. Expectant parents all over the world have been offered to store stem cells from their new born children for more than two decades. Globally, today, a 150 thousand of different companies have stem cells from over 4 million children stored. In 1988, the first stem cell transplant with umbilical cord blood cells was performed. Previously, the only stem cell source was bone marrow. Collecting stem cells from bone marrow is an extensive and invasive procedure and must be done close to the time that the transplant will be performed.

Birth is a unique opportunity to collect stem cells from the umbilical cord, otherwise discarded by using a non-invasive procedure. In addition, the stem cells are both unaffected by environmental factors and most powerful at birth.

Today, stem cells are used to treat a variety of severe diseases, such as blood cancers and immune system disorders. If needed, banked stem cells from the newborn baby can make treatment of severe illnesses easier, and shorten the waiting times for therapy, because matching stem cells are already available. In some cases, family members can also be treated with the stem cells from the newborn baby.

Read more on Cellaviva's webpage

What do they mean?

Unlimited Applications

The classical definition of a stem cell requires that it possess two properties:

  1. Self-renewal: The ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
  2. Potency: The capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent—to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells.

Theses properties make stem cells highly suitable for future treatments of:

  • Regenerative Medicine
  • Gene Therapy
  • Inflammation
  • Autoimmune diseases
  • Cancer

Hematopoietic Stem Cells

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:

  • Leukemia
  • Lymphoma
  • Metabolic diseases
  • Immune system diseases

Mesenchymal Stem Cells

Mesenchymal Stem Cells (MSC) are multipotent stromal cells that can differentiate into a variety of cell types, including: osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells) and adipocytes (fat cells). These cells have also shown to be able to influence the immune system by activation, suppression and modulation. Experimental treatment in:

  • Regenerative Medicine, restoring damaged tissue
  • Immune activation, for cancer treatment
  • Immune suppression, for treatment of graft-vs-host disease and transplant rejection
  • Immune modulation, for treatment of autoimmune diseases