LAU-7b

first-in-class pro-resolving drug candidate.

LAU-7b is a proprietary oral drug candidate based on fenretinide, an atypical retinoid with a well-documented safety profile established in more than 3,000 patients. Existing data suggest that low-dose fenretinide has the potential to modulate certain membrane lipids and exerts inflammatory-controlling, antifibrotic and antiviral properties in a variety of in vitro and ex vivo systems, and animal models of acute and chronic inflammation, cystic fibrosis (CF), and non-CF pulmonary fibrosis.

Membrane lipids

a balancing act.

Lipids are fundamental cell components responsible for cell membrane structure, fluidity, and function. Membrane lipids play multiple biological roles ranging from first-line host defense against pathogens, to inflammation signaling and protein trafficking. Their potential as therapeutic targets remain largely untapped.

Low-dose LAU-7b focuses on certain phospholipids and sphingolipids that play central roles in the activation/resolution of the inflammation process, as well as in the host defense against pathogens.

Proposed mode of action for LAU-7b lipid modulation

Although not fully established, LAU-7b’s lipid-modulating mechanism appears to follow a multitarget pharmacology involving desaturases (delta-4 and delta-9) and ceramide synthase (CerS5), all of which playing important roles in fatty acid metabolism. LAU-7b activity is also associated with the modulation of cPLA2, ERK 1/2 and NF-κB inflammation signaling pathways.

Resolution

the inflammation “off switch”.

LAU-7b was shown to increase phospholipids linked to docosahexaenoic acid (DHA) involved in the resolution phase of inflammation, and indirectly having a downregulating effect on the arachidonic acid (AA) pathway responsible for the inflammation activation process. The balancing effect on DHA/AA mimics body’s own inflammation-controlling process (a “pro-resolving” effect). 

References:

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
Youssef M. et al, 2021. Lung. https://doi.org/10.1007/s00408-020-00353-2
Poliakov E. et al, 2017. PLoS ONE. https://doi.org/10.1371/journal.pone.0176487
Rodriguez-Cuenca S. et al, 2016. PLoS ONE. https://doi.org/10.1371/journal.pone.0162047
Rodriguez-Cuenca S. et al, 2015. Biochimica et Biophysica Acta. http://dx.doi.org/10.1016/j.bbalip.2014.09.021