NEW YORK – PolTreg, a biotech that spun out of the Medical University of Gdańsk in Poland, is betting an investigational cell therapy could halt progression, or possibly even cure, some patients with type 1 diabetes.
The company is building evidence that its autologous regulatory T-cell (Treg) therapy can treat early-onset and presymptomatic type 1 diabetes. PolTreg is testing the experimental therapeutic candidate PTG-007 in patients with these types of diabetes in two ongoing clinical trials and conducting other studies testing the cell therapy in multiple sclerosis.
Type 1 diabetes is currently treated with insulin, a hormone that in healthy patients is produced in the pancreas and regulates blood sugar. But while daily insulin is effective in keeping the symptoms of diabetes in check, it isn't a cure. Additionally, to treat diabetes, patients must regularly monitor their blood sugar and maintain lifelong lifestyle changes in diet and exercise.
The US Food and Drug Administration two years ago approved the first disease-modifying therapy for type 1 diabetes, Tzield (teplizumab) from Provention Bio, now part of Sanofi. Tzield is a CD3-directed monoclonal antibody designed to delay, on average by two years, the onset of disease in patients who are asymptomatic but progressing toward clinical diabetes. The drug's approval has shone a spotlight on the need to improve screening methods to identify patients likely to develop the disease.
However, PolTreg CEO Piotr Trzonkowski noted that Tzield doesn't cure patients with type 1 diabetes, nor does it prevent disease.
"This is still an unmet medical need," said Trzonkowski, who also serves as head of the medical immunology department at the Medical University of Gdańsk. In 2015, he and two other professors at the university, Natalia Marek-Trzonkowska and Małgorzata Myśliwiec, cofounded PolTreg based on research into Treg-based therapies. Marek-Trzonkowska and Myśliwiec continue to be involved with PolTreg as members of the company's scientific board.
Diabetes is a chronic autoimmune condition, in which the body's immune system attacks insulin-producing beta-cells in the pancreas. Among other problems, diabetics often have insufficient Treg cells, which are the immune cells that are supposed to suppress the immune system and regulate its response. PolTreg's PTG-007 aims to address this by boosting the amount of these Treg cells.
The cell therapy is created by isolating Treg cells from a patient's blood sample and expanding them ex vivo in a laboratory in Gdańsk. These cells are then reinfused back into the patient. The Treg cells are thought to block the autoimmune process and thereby slow or halt development of type 1 diabetes.
It's just one of a growing number of cell therapies being tested as possible treatments for autoimmune disorders.
PolTreg has tested the Treg-cell therapy in combination with Genentech and Biogen's monoclonal antibody Rituxan (rituximab), which is already used as an autoimmune and cancer drug, in children with early-onset disease within a randomized, controlled Phase I/II trial. PolTreg's goal is to treat patients at an early stage of disease, before too many of the pancreatic islets that produce insulin are lost or damaged. Ultimately, the company aims to preserve these islets so that the disease doesn't progress.
So far, data from 54 patients treated within Phase I and Phase II trials of the Treg-cell therapy in patients with early-stage type 1 diabetes suggest that some patients remain in clinical remission, either without a need for insulin injections or only having a low need for insulin, for up to 12 years after treatment. Not all patients experienced as durable of a response in clinical trials, however. Two years posttreatment, about half of patients who received PTG-007 and Rituxan were in clinical remission, but the rest relapsed and continued to need insulin.
PolTreg has said that it plans to publish results from the clinical trials in a peer-reviewed scientific publication.
Patients in the clinical trials received two injections of PTG-007. Patients may need additional doses to sustain the effects, Trzonkowski said, and the company continues to study the number and frequency of doses necessary for the most effective response. Still, an injection every few months could be less burdensome than the standard daily insulin injections, he added.
Next, the company plans to launch a randomized, controlled Phase II trial by year-end to evaluate the same cell therapy in children who are asymptomatic but are likely to develop type 1 diabetes based on their family history and the presence of diabetes-related islet autoantibodies.
In presymptomatic diabetes, PolTreg believes the cell therapy has the potential to go beyond slowing the progression of diabetes and provide a cure by protecting pancreatic islets and preventing symptom onset altogether. "We hope that, with this therapy, [these pediatric patients] will never develop the symptoms of the disease," Trzonkowski said. "That's our hope in this trial."
PolTreg is also preparing to launch a pivotal Phase II/III trial of PTG-007 in early-onset type 1 diabetes and has already sought the European Medicines Agency's feedback on the design of a pivotal trial.
Trzonkowski said the company intends to remain focused on R&D to advance PTG-007 in diabetes and new diseases and develop entirely new cellular therapies. For example, if results from PTG-007's diabetes trials continue to show positive results, PolTreg wants to start testing it in rheumatoid arthritis, inflammatory bowel disease, and other autoimmune conditions, and perhaps even immune-mediated diseases like amyotrophic lateral sclerosis.
But as PTG-007 moves toward a pivotal trial in early-stage type 1 diabetes and the market, PolTreg is seeking external funding and a pharmaceutical partner to handle late-stage registration and potential commercialization activities. "We're a biomed company," Trzonkowski said. "We're not a big pharma with supply chain to reach every hospital."