Ladarixin

Type 1 diabetes presents a huge unmet need in our society. At Dompé, our research in this area has led us to develop an investigational, small-molecule drug called Ladarixin, which is being studied in Phase 2 and 3 trials.
——————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————

Many people today live with type 1 diabetes. Just in the US, it’s estimated that there are 1.84 million Americans with this autoimmune disease, and the rate of diagnosis is rising each year. It’s a chronic, life-long disease in which the body’s immune system attacks and destroys beta cells, a type of cell found in pancreatic islets that produce insulin.

Current treatment options focus on controlling the body’s blood glucose levels, this implying that patients need regular self-injections of insulin.

At Dompé, we focus our research on delaying disease progression by preserving beta cell function and improving metabolic control. As such, our team have started a program with a molecule called Ladarixin, that is currently used in Phase 2 and Phase 3 clinical trials.

The crucial role cytokines play in diabetes

Our research into Ladarixin stemmed from our work in NETosis and cytokines. Cytokines and cytokine receptors play a crucial role in the body’s immune response to inflammation. Neutrophils, a type of white blood cell, are recruited by cytokines to the site of inflammation, where they secrete various proteins into the extracellular environment, forming a network of trap-like structures known as Neutrophil Extracellular Traps (NETs). This process is known as NETosis.

Under normal circumstances, NETosis is a defense mechanism for the body. Nonetheless, if inflammation becomes dysregulated, it can become detrimental and  can damage healthy tissue. Cytokines are up-regulated in diabetic patients and play a critical role in the inflammatory process of Type 1 diabetes. In particular, the immune system misrecognizes beta cells as external pathogens and so neutrophils are recruited by cytokines to the pancreas to destroy them.

At Dompé, we are researching new compounds that effectively inhibit NETosis by selectively inhibiting the effect of certain cytokines on neutrophils. As patients with type 1 diabetes have higher levels of the cytokine Interleukin 8 (IL-8) compared to normal individuals, our rationale was to create a molecule that preserves beta cell function by antagonising the IL-8 pathway.

What makes IL-8 inhibitors a potential treatment

The result is Ladarixin, an investigational, oral, small molecule that has been synthesized in our labs. It is a non-competitive, dual allosteric inhibitor of CXCL8 (IL-8) receptors, CXCR1 and CXCR2. The hypothesis is that by inhibiting these receptors, inflammation and the destruction of beta cells in pancreatic islets could be prevented. This means that a molecule with this mechanism of action has the potential to inhibit disease progression and the development of severe symptoms.

Most importantly, Ladarixin is available as oral capsules and has displaid a high tolerability with no toxic secondary effects.

Ladarixin is the result of collaborative research and development

We are actively striving to establish partnerships within the scientific community, and to foster the development of this molecule, having already collaborated with numerous research partners and diabetic experts throughout the world.

Ladarixin has undergone Phase 1 and Phase 2 trials, the results of which were presented at the 2020 virtual American Diabetes Association’s Scientific Sessions and published in the June 2020 edition of Diabetes.

Based on those results, a clinical Phase 3, randomized, multicenter, double-blind, placebo-controlled trial was started to study the efficacy and safety of Ladarixin in adolescents and adults with new-onset type 1 diabetes. The trial is ongoing and results will help understanding the effectiveness in preserving beta cell function by inhibiting the biological activity of IL-8.

In another ongoing Phase 2 study, the same molecule is used in a randomized, multicenters, double-blind, placebo-controlled trial as adjunctive therapy to improve glycemic control in overweight insulin-resistant adults with type 1 diabetes.