A new approach in a challenging disease

A New Approach

Stopping eosinophils before they can cause damage.

Like other blood cells, eosinophils originate as stem cells in the bone marrow. They differentiate and mature into eosinophils through complex molecular signaling and interactions with surrounding tissues, primarily in the bone marrow. Inflammatory signals—from the asthmatic lung, for example—may increase production of mature eosinophils.

This increases eosinophil counts in the blood and ultimately in the lungs, causing tissue remodeling, mucus secretion, airway trapping, and asthma attacks.

Dexpramipexole inhibits the maturation of eosinophils at an early stage, preventing their travel through the blood to the lung, according to evidence from cell cultures and human biopsies.

Not treated.
Large epidemiology studies have shown that eosinophil counts in the bloodstream may predict the risk of asthma exacerbations.

Treated with dexpramipexole.
Across five clinical trials spanning 10 years, dexpramipexole profoundly reduced eosinophils in blood and inflamed tissue and improved lung function in patients with eosinophilic asthma.

How Did We Get Here?

The eosinophil-targeting effects of dexpramipexole were discovered during its earlier clinical development for an unrelated disease. Across five clinical trials, dexpramipexole showed a significant and targeted reduction in eosinophil counts in both the blood and in inflamed organs.

The most recently completed dexpramipexole trial was the EXHALE trial, a Phase 2 study in patients with moderate-to-severe eosinophilic asthma. Treatment with dexpramipexole resulted in a significant, dose-dependent reduction in blood absolute eosinophil count at all doses tested (dexpramipexole doses of 37.5 mg, 75 mg, or 150 mg twice daily) compared to placebo. While the trial was not powered to assess lung function, patients receiving the highest dexpramipexole dose showed large-volume increases in FEV1 (the amount of air a subject can forcibly exhale in one second). Dexpramipexole was well tolerated in the trial, with adverse events balanced across treatment and placebo groups, no serious adverse events, and no adverse events leading to discontinuation.

Areteia was established to advance dexpramipexole through Phase 3 clinical trials and to potential approval in eosinophilic asthma. To our knowledge, dexpramipexole is the only late-stage oral treatment in development for eosinophilic asthma.

Phase 3 Development Program

Phase 3 development is underway.

Following the successful Phase 2 EXHALE trial of dexpramipexole in moderate-to-severe eosinophilic asthma, Areteia is preparing to launch three Phase 3 trials in patients with eosinophilic asthma.

EXHALE 2 and 3

  • Randomized, double-blind, placebo-controlled studies to assess the effects of two different doses of dexpramipexole on exacerbation rates and lung function.
  • Inadequately controlled GINA 4/5 patients
  • 75 mg BID, 150 mg BID and Placebo BID
  • EXHALE 2: North America/EU (N = ~1,260)
  • EXHALE 3: North America/Latin America/Asia Pacific (N = ~840)

EXHALE 4

  • Randomized, double-blind, placebo-controlled study to characterize the effects of dexpramipexole on lung function, as measured by FEV1, in a broader population than in EXHALE 2 and EXHALE 3.
  • Inadequately controlled GINA 3/4/5 patients
  • 75 mg BID, 150 mg BID and Placebo BID
  • Global (N = ~750)

*FEV1: the amount of air a subject can forcibly exhale in one second).

Discovery Programs

We will conduct further translational research on dexpramipexole with the goal of characterizing a molecular mechanism of action and exploring new classes of small molecules for asthma and other immunologic conditions.

We will invest in life cycle management to further enhance dexpramipexole’s product profile, including new formulations, potential for oral corticosteroid sparing, and use in less severe patient populations.