Macomics updates data for ENIGMAC drug discovery platform and the role of macrophages in fibrotic disease

Macomics Ltd, a leader in macrophage drug discovery, announces that it has validated its ENIGMAC™ platform in macrophage mediated antifibrotic therapy.

Macomics’ ENIGMAC drug discovery platform is designed to discover therapeutic targets and unlock disease specific target biology. The platform enables identification and validation of novel targets and provides a translationally relevant path to the clinic through the development of more physiologically relevant human models combined with proprietary gene editing technology.

There is clear evidence of causal human genetics in fibrosis and the interplay between macrophages and fibroblasts in fibrotic diseases of the liver, lung and kidney. The identification and functional validation of potential first-in-class targets in this area has been limited by the lack of proper technology and macrophage expertise.

Having already proven its first-in-class target validation potential in oncology, ENIGMAC is a proprietary technology developed to produce gene editable macrophages. The platform can knock in or knock out genes of interest via CRISPRa or CRISPRi expression in iPSC derived cells, unlocking the opportunity for new target discovery informed by human data.

For fibrotic disease-related drug discovery, Macomics has focused on the interplay between macrophages and fibroblasts on the deposition of the extracellular matrix seen in fibrosis with a unique co-culture system. Our goal has been to promote fibrosis regression through macrophage targeting, exploring potential first in class approaches.

Luca Cassetta PhD, co-founder and VP Immunology at Macomics, said:

We have completed and validated gene knock down screenings (pooled and array) in iPS-derived cells in disease relevant models and also demonstrated that gene editing is scalable from single to genome wide.

In its in-house program, Macomics’ therapeutic strategy has utilised the validated in vitro co-culture assay enabling higher throughput arrayed screening for macrophage antibody-dependent cellular phagocytosis (ADCP) fibroblast targets, with validation in human ex vivo precision-cut lung slices (PCLS), as a strategy to identify additional first in class targets.

Simon Dew, CBO of Macomics, said:

We are now using our ENIGMAC platform for new target discovery in fibrotic diseases, as well as other disease areas, both in-house and in drug discovery partnerships.