Allakos recently presented preclinical data demonstrating the potential of its Siglec-8 antibodies in inhibiting components involved in fibrosis in rodent models of lung and skin fibrosis. The company believes these antibodies could potentially benefit a wide spectrum of patients with conditions where fibrosis is a major contributor to the disease.
The data were presented at the recent 1st International Conference on Tissue Repair, Regeneration and Fibrosis in Rhodes, Greece.
Siglec-8 is selectively expressed on two types of white blood cells, mast cells and eosinophils. These two immune cell types play an important role in the development and progression of fibrosis, where they mediate many processes that result in tissue damage.
The antibodies developed by Allakos bind to the Siglec-8 receptor, with previous studies showing that Siglec-8 antibodies inhibit the function of mast cells and trigger the programmed death of eosinophils. Some of these antibodies can also kill mast cells and eosinophils by activating a natural process known as antibody-dependent cell-mediated cytotoxicity.
“Our preclinical results demonstrate that a Siglec-8 antibody can reduce key fibrotic processes in multiple animal models,” said Nenad Tomasevic, PhD, vice president of Research at Allakos, in a recent press release. “The action of these Siglec-8 targeting antibodies is highly specific to mast cells and eosinophils, and has the potential to benefit a wide spectrum of patients with severe, often life-threatening, conditions where fibrosis is a major contributor to the disease.”
Allakos is currently evaluating the anti-Siglec-8 antibody, called AK002, in a Phase 1 clinical trial (NCT02859701) to assess its safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers. A clinical trial in patients with fibrosis is planned for the second half of 2017.
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue, in response to injury, in either a reactive benign reparative process or a reactive pathological process. In fibrotic diseases like idiopathic pulmonary fibrosis, excessive fibrosis affects normal organ function and potentially leads to organ failure.