Milan, Italy, 3 February 2022 – Enthera Pharmaceuticals (“Enthera”), a biotech company developing first-in-class biologics for selected autoimmune conditions based on the discovery of a novel apoptosis pathway, together with scientific partners Boston Children’s Hospital of the Harvard Medical School and the University of Milan, today announce a publication in the leading journal Nature Communications, reporting new data reinforcing the ‘IGFBP3/TMEM219’ apoptosis pathway as a key regulator of pancreatic β‐cells and a novel therapeutic target for type 1 diabetes.
The paper demonstrates that a dysregulation of the IGFBP3/TMEM219 (Insulin Like Growth Factor Binding Protein 3/Transmembrane Protein 219) pathway is evident in diabetes and that it associates with beta cell dysfunction/loss which is a central feature of type 1 diabetes.
For several decades, most therapeutic approaches for type 1 diabetes and other autoimmune disorders have mainly focused targeting the autoimmune response. This approach has resulted in a partial clinical efficacy that, at best, has only been able to slow disease progression. In the case of type 1 diabetes, this is attributed to the progressive exhaustion of the β‐cell population. So far, no drug has shown clear efficacy in stopping or reversing the condition.
Silvano Spinelli, Chairman of the Board at Enthera Pharmaceuticals, commented: “The data published today demonstrates that the dysregulation of the IGFBP3/TMEM219 axis is a key element in the development and progression of type 1 diabetes. Our novel approach of targeting the affected tissue in an autoimmune disease and not the immune system itself may represent a disease-modifying treatment not only for type 1 diabetes, but also for multiple other autoimmune conditions, such as inflammatory bowel disease, in which the same pathway is also affected.”
Paolo Fiorina, Professor of Endocrinology at University of Milan and Chief of Endocrinology at Sacco-Melloni Milan Hospitals and Scientific Founder of Enthera Pharmaceuticals, added: ”Beta cell loss is a central feature of type 1 diabetes, yet no therapeutic strategy aimed at preserving it has been approved to date and research is underway. The discovery of the IGFBP3/TMEM219 pathway as a regulator of beta cell homeostasis is highly clinically relevant in the field of diabetes and diabetes research, and it may open a new therapeutic option for patients with type 1 diabetes.”
The TMEM219 receptor is expressed on pancreatic β‐cells and signaling through its ligand IGFBP3 leads to β‐cell loss and dysfunction. In the published study, elevated IGFBP3 levels were observed in patients with established and at-risk for type 1 diabetes and in preclinical models of type 1 diabetes.
The researchers demonstrated that IGFBP3/TMEM219 inhibition in vitro and in vivo preserved the pancreatic β‐cell pool and prevented or delayed diabetes onset, and that long-term IGFBP3/TMEM219 blockade allowed for pancreatic β‐cells mass recovery. It was further demonstrated in several patient cohorts that restoration of appropriate IGFBP3 levels preserved pancreatic β‐cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of β‐cell mass and demonstrated to be disrupted in type 1 diabetes and may therefore serve as a new therapeutic option in type 1 diabetes.
By applying its alternative approach – the targeting of IGFBP3/TMEM219 pathway, which is critically dysregulated in some disease conditions, to prevent tissue damage in pathogenic environments– Enthera is developing first-in-class biologics for the treatment of immune-mediated diseases. Enthera’s lead clinical product Ent001 is currently in development for the treatment of inflammatory bowel disease and type 1 diabetes, with plans to expand the current pipeline with new programs in areas such as fibrotic conditions.
The full published article can be found here: https://www.nature.com/articles/s41467-022-28360-2