Committed to developing treatments
for severe inflammatory and
fibrotic lung diseases.
A rare genetic disease with unaddressed lung inflammation.
Cystic fibrosis (CF) is the most common fatal hereditary disease among Caucasians, affecting an estimated 83,000 people worldwide. Mutant cystic fibrosis transmembrane regulator (CFTR) results in impaired mucocilliary clearance in the airways, exaggerated AA-mediated inflammation and inadequate pro-resolving DHA response, leading to chronic infection, exaggerated lung inflammation and local lung tissue destruction over time.
Existing data suggest that LAU-7b has a therapeutic approach that appears to be complementary to CFTR modulators. LAU-7b pro-resolving effect has the potential to correct the DHA/AA imbalance and control inflammation without interfering with the natural defenses. LAU-7b was also shown to rebalance certain long-chain sphingolipids (ceramides) involved in the CFTR protein recruitment, aggregation and confinement inside the membrane lipid rafts, in response to cellular stress during inflammation.
Youssef M. et al, 2021. Lung. https://doi.org/10.1007/s00408-020-00353-2
Garic D. et al, 2020. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-020-03530-x
Garic D. et al, 2020. Journal of Molecular Medicine. https://doi.org/10.1007/s00109-017-1564-y
Abu-Arish A. et al, 2018. Poster NACFC2018.
APPLAUD Phase 2 study in adult patients with cystic fibrosis
APPLAUD is a placebo-controlled phase 2 clinical study of the efficacy and safety of LAU-7b in the treatment of cystic fibrosis in adults, aiming to evaluate LAU-7b’s effect on the resolution of inflammation and preservation of lung function. A total of 166 patients were enrolled at hospital sites across Canada, the US and Australia, for a treatment duration of 6 months. The study measures the lung function at 24 weeks, pulmonary exacerbations, quality of life, Pseudomonas aeruginosa infection level, systemic inflammatory and lipidomic biomarkers.
More details about the study can be found on www.clinicaltrials.gov (#NCT03265288).
A global health crisis requiring effective treatments.
COVID-19 is an acute respiratory disease borne from infection with SARS-CoV-2 coronavirus and rapidly qualified as a pandemic. While most patients are thought to have a favorable prognosis, certain patients may have worse outcomes with hyperinflammation in the lungs that may require mechanical ventilation. With viral mutations increasing uncertainty around coronavirus persistence and seasonality, there is an urgent need to develop efficacious COVID-19 treatments.
Proposed mode of action for LAU-7b in CF
LAU-7b: potential for dual antiviral and inflammation-controlling mechanism in COVID-19
Membrane lipids play a central role in coronavirus infection, and are needed for virus fusion to the plasma membrane when they enter or are released from the cell. Viruses also attack the lipid synthesis (lipogenesis) and signal the host cells to produce lipids for their envelopes and also to hide from the immune system.
LAU-7b is believed to work by decreasing cell membrane fluidity required for virus entry and release, as well as reducing de-novo ceramides synthesis required for pathogen proliferation. LAU-7b may also have inflammation-controlling properties by acting on DHA pro-resolving cascade and may also involve secondary pathways ERK1/2, NF-kB and cPLA2 all of which known to have a role in virus immune evasion.
RESOLUTION Phase 2 study with LAU-7b in hospitalized COVID-19 patients
RESOLUTION is a placebo-controlled phase 2 clinical study with LAU-7b as a potential treatment against COVID-19 disease. The aim of the study was to demonstrate that LAU-7b is a safe and effective treatment option for hospitalized COVID-19 patients that are at risk of lung complications because of their age, underlying conditions or both. A total of 240 patients were enrolled in hospitals across the United States and Canada, for a treatment duration of 14 days. In the RESOLUTION trial, which follows the FDA and WHO recommendations, the disease progression was measured on a 7-point ordinal scale to inform the primary and secondary endpoints of the study. The study also evaluated the duration of hospitalization and improvement in quality of life.
More details about the study can be found on www.clinicaltrials.gov (#NCT04417257).