#NACFC2018 – Preclinical Study Data Demonstrate Lenabasum’s Potential to Prevent Inflammatory Signals in CF
Treatment with lenabasum can effectively prevent inflammation and induce pro-resolving signals in airway immune cells from patients with cystic fibrosis (CF), results from a preclinical study show.
Lenabasum’s more recent preclinical data was discussed at the 32nd North American Cystic Fibrosis Conference, in a poster presentation titled “Lenabasum Reduces Lps-Induced Inflammation In Airway Macrophages From Human Cystic Fibrosis Lungs.”
Lenabasum, formerly known as anabasum, JBT-101, or resunab, is a synthetic oral small molecule being developed by Corbus Pharmaceuticals to resolve chronic inflammation and prevent tissue scarring. It binds to a specific receptor on activated immune cells, called cannabinoid receptor type 2 (CB2), mimicking the anti-inflammatory effects of natural endocannabinoids without dampening other immune system responses.
Corbus was granted orphan drug status for lenabasum as a potential CF treatment by the U.S. Food and Drug Administration and by the European Medicines Agency. The FDA also placed lenabasum on fast track to speed its development for CF.
In the most recent preclinical study, researchers evaluated the impact of lenabasum in macrophages — immune cells known to contribute to lung inflammation and fibrosis in CF — collected from the airways of CF patients who had undergone lung transplants.
The collected cells were exposed to a compound produced by the bacteria Pseudomonas aeruginosa, known as LPS, that promotes the production of molecular mediators of the inflammatory response in macrophages.
Treatment with lenabasum effectively prevented the production of pro-inflammatory signaling molecules by macrophages, including interleukin-8 and TNF-alpha. At the same time, lenabasum promoted the release of molecules that could help resolve inflammation, such as a natural PPAR-gamma agonist and LXA4 protein.
The drug also decreased levels of sphingosine kinase 1, the rate-limiting enzyme for generation of sphingosine 1-phosphase, known to mediate inflammation.
These positive effects were found to be dependent on the dose of lenabasum used, with greater positive effects on airway macrophages reported with the higher doses.
“We are excited by the positive data from this study and believe that these findings fit with the observed effects of lenabasum in CF airway inflammatory responses,” Mark Tepper, PhD, president and chief scientific officer of Corbus, said in a press release. “We believe the results from this study are significant as they demonstrate for the first time a dramatic reduction in sphingosine kinase 1 (SPHK1), a key regulator of inflammation.”
Corbus is assessing the safety and efficacy of lenabasum in CF patients in a Phase 2b, placebo-controlled study (NCT03451045). Supported by the Cystic Fibrosis Foundation, the trial is expected to enroll about 415 CF patients age 12 and older who have increased risk of pulmonary exacerbations. The trial will include patients from North America, Europe, and Australia.
The study is crecruiting participants, who will be randomly designated to receive a placebo twice daily or lenabasum in 20- or 5-mg doses for 28 weeks.
Researchers will evaluate the impact of the investigational compound by determining the average number of pulmonary exacerbations per subject per time period. They will also evaluate other measures of pulmonary exacerbations, including changes in Cystic Fibrosis Questionnaire-Revised Respiratory domain score, and in forced expiratory volume in 1 second (FEV1).
Corbus expects to announce topline results from the study in 2020.
For more information on the Phase 2 study, click here.