We specialize in the development of therapeutics that are aimed at slowing the degenerative processes associated with aging and improving functional outcomes for patients suffering from age-related diseases, including severe respiratory failure in patients with COVID-19. Our small molecules are aimed at stimulating biological resilience and are developed through a drug discovery platform based on a reverse pharmacology approach.
BIOLOGICAL RESILIENCE
As we age, our physical, visual and cognitive performances gradually decline due, in part, to the accumulation of multiple biological, physiological and environmental stresses to which we are exposed during our lifetime. The functional decline can be much faster in some individuals as a consequence of, among other things, the degenerative processes affecting specific cells, tissues and organs.
Through evolution, cells, tissues and organisms have developed natural means or pathways to counteract and balance the effects of the many stresses they face. This natural ability to compensate for stress and remain functional, called biological resilience, degrades over time. The decline in biological resilience contributes to the acceleration of these degenerative processes and the impairment of functional performance, which, in turn, can lead to severe disability, reduced healthspan and ultimately death.
Our therapeutic approach is aimed at targeting and activating key biological resilience pathways that can protect against and counteract the effects of the multiple biological and environmental stresses, including inflammatory, oxidative and metabolic stresses that lead to age-related diseases.
PLANT SECONDARY METABOLITES
We have developed our drug candidates through a drug discovery platform in collaboration with Sorbonne University and its leading institutes in Paris, France based on work with medicinal plants. Plants are major sources of small molecules, called secondary metabolites, which are produced as a defence mechanism to various environmental stresses, including attack from predatory and pathogenic species (e.g., insects, bacteria and fungi). Plant secondary metabolites are already the basis for many therapeutics, including drugs used for the treatment of metabolic and inflammatory diseases.
REVERSE PHARMACOLOGY
We utilize a reverse pharmacology approach by testing a collection of bioactive secondary metabolites along with chemical analogs that we have synthesized in phenotypic screens of various age-related diseases.
We discovered Ruvembri by screening a collection of phytoecdysteroids that had been gathered for over 30 years by scientists from Sorbonne University, along with synthesized analogs for their ability to stimulate protein synthesis in muscle cells. We discovered in experimental settings that Ruvembri improves muscle function in various pathological contexts including sarcopenia (aging) and neuromuscular diseases. It also demonstrated a significant improvement of the respiratory function in dystrophic animals. Because of its specific mode of action and preclinical observations it is currently tested clinically for the treatment of COVID-19 related acute respiratory failure.
Utilizing our expertise in functional screens and assays, we expanded our drug discovery efforts to other age-related diseases, with a focus on retinopathies. Using cellular models developed with the Institute of Vision at Sorbonne University, we discovered Macuneos (BIO201) by screening a variety of carotenoids and flavonoids for their ability to protect retinal pigment epithelium (RPE) cells against the photo-oxidative stress induced by blue light in the presence of A2E (a phototoxic byproduct of the visual pigment cycle).
SCIENTIFIC COLLABORATIONS
