Macomics has released new data supporting the use of its Enigmac drug discovery platform in macrophage-mediated antifibrotic research. The company said the platform has now been validated in disease models focused on the interplay between macrophages and fibroblasts, a relationship that drives fibrotic pathology across organs such as the liver, lung and kidney.

The company said the platform is designed to identify therapeutic targets and define disease-specific biology using human-relevant models. Enigmac enables gene editing using CRISPRa or CRISPRi in induced pluripotent stem cell (iPSC) derived macrophages, allowing knock-in or knock-out studies that support discovery and validation of new targets. According to Macomics, limited technology and a lack of macrophage-specific expertise have historically slowed progress in identifying first-in-class targets for fibrosis.

Macomics has previously applied Enigmac to oncology target validation, and the same approach is now being used to explore the mechanisms that influence extracellular matrix deposition in fibrosis. The company developed a co-culture system to model macrophage–fibroblast interactions, aiming to understand how targeting macrophages could support fibrosis regression.

Luca Cassetta, 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.” He said the platform’s scalability is intended to support both focused and broad discovery programmes.

In its internal programme, the company has used the validated in vitro co-culture system to run higher-throughput arrayed screening. This has included assays measuring macrophage antibody-dependent cellular phagocytosis of fibroblast targets. Findings generated in vitro have been evaluated in human ex vivo precision-cut lung slices, which the company described as a key translational step for selecting additional first-in-class targets.

Simon Dew, chief business officer at 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.” He added that external collaborations are expected to broaden application of the platform across multiple therapeutic areas.

Macomics said the new data reinforce the potential of macrophage-focused approaches in fibrotic disease and support the wider use of human-relevant systems in early discovery. The company plans to continue applying the platform in-house and with partners as it advances additional macrophage-targeted programmes.