LAU-7b is a unique, patent-protected oral formulation of fenretinide, ideally applicable to a once-a-day low dose treatment regimen. Fenretinide, a synthetic retinoid, is a new chemical entity with a well-documented history of safety in clinical studies involving more than 3,000 adult and pediatric patients, in various indication. In preclinical models of CF, fenretinide was shown to address the complex links between fatty acids metabolism and inflammatory signaling, which is distinct from the retinoid class mechanism of action.
Phase 2 APPLAUD study in Cystic Fibrosis
LAU-7b is currently being evaluated in a Phase 2 clinical trial (APPLAUD) in adult patients with CF aiming to demonstrate compound’s ability to treat the exaggerated inflammatory response that leads to irreversible lung damage. APPLAUD is an international (US, Canada and Australia), multicenter, randomized, double-blind, placebo-controlled Phase 2 study of LAU-7b for the treatment of CF through its effect on the CF-linked AA/DHA imbalance. The study aims to enroll approximatively 120 adult patients with CF, for a treatment duration of 6 months. More information about the Phase 1b trial can be found at: www.clinicaltrials.gov (NCT03265288).
APPLAUD is conducted with support from the US Cystic Fibrosis Foundation ($8M Development Award) and its affiliated Therapeutic Development Network.
An earlier Phase 1b clinical data from CF adult patients, with LAU-7b escalating doses of up to 300 mg administrated orally, once-a-day, showed that LAU-7b was safe and well tolerated, and able to maintain the balance between AA and DHA pathways, with a favorable effect on certain biomarkers of inflammation (IL-6, IL-8, IL-10, neutrophils count) at the onset of a pulmonary exacerbation episode, suggestive of a protective effect on the lungs.
The study population involved in the Phase 1b trial was previously characterized in a non-interventional, natural history study, which explored the predictive value for pulmonary exacerbation and response to antibiotic treatment during exacerbations of systemic lipidomic, inflammation and oxidation biomarkers. Data collected from the non-interventional study was used to compare the response to exacerbation antibiotic treatment of these markers to plasma levels obtained in Phase 1b. LAU-7b normalized the plasma levels of DHA and AA, causing a shift towards an anti-inflammatory and pro-resolving pattern, particularly during pulmonary exacerbation.
Phase 2 RESOLUTION clinical study in COVID-19
Laurent Pharmaceuticals is actively enrolling patients in RESOLUTION, a multicentric Phase 2 randomized placebo-controlled trial testing once-a-day oral LAU-7b as a potential treatment against COVID-19 disease. RESOLUTION, which is currently ongoing in Canada, will enroll approximately 200 hospitalized COVID-19 patients who will receive either LAU-7B or a placebo for a treatment duration of 14 days.
RESOLUTION will evaluate the efficacy and safety of early therapy with LAU-7b on prevention of disease progression in hospitalized adults at risk to develop ARDS associated with COVID-19. LAU-7b, which showed potent antiviral effects in-vitro against both SARS-CoV-2 and MERS-CoV coronaviruses, is also being developed for its unique inflammation-controlling properties by acting on the resolution phase of the inflammation process, a natural mechanism that keeps the body’s inflammatory response under control without inducing immune-suppression (a “pro-resolving” effect).
LAU-7b is believed to work by modulating key membrane lipids in conjunction with pro-resolving pathways ERK1/2, NF-kB and cPLA2 that are also needed for coronavirus entry, replication and host defense evasion. The treatment goals are the reduction of COVID-19 disease severity, controlling inflammation in the lungs and prevent the disease progression toward an ARDS. More information about the Phase 1b trial can be found at: www.clinicaltrials.gov (NCT04417257).