Macomics has validated its ENIGMAC macrophage discovery platform in antifibrotic biology, completing pooled and arrayed CRISPR-based gene modulation screens in iPSC-derived macrophages and demonstrating scalability to genome-wide interrogation. The company confirms functional readouts using a macrophage–fibroblast co-culture assay focused on extracellular matrix dynamics and reports ex vivo confirmation in human precision-cut lung slices, alongside a higher-throughput assay to identify antibody-dependent cellular phagocytosis targets on fibroblasts.
The core development is an expansion of a macrophage-centric discovery engine previously applied in oncology into fibrotic disease, with an emphasis on human-relevant models that bridge from in vitro screening to human tissue validation. ENIGMAC uses CRISPRa/i to knock in or knock down genes in gene-editable macrophages derived from iPSCs, enabling systematic target discovery and functional validation. Operationally, the platform points to a translational path anchored in human biology rather than reliance on preclinical models that have been unreliable in fibrosis. Macomics is now running both internal programs and partnered discovery efforts off this base.
Strategically, this is a diversification move aimed at an antifibrotic field that has struggled to translate animal signals into clinical benefit. By centering macrophage–fibroblast interactions and deploying ex vivo human tissue, the company is addressing a known failure mode in fibrosis discovery: targets that modulate matrix deposition in rodents but stall at first-in-human. The focus on macrophage-mediated clearance mechanisms, including ADCP against fibroblast-expressed targets, also indicates a willingness to test nontraditional antifibrotic hypotheses beyond integrins and TGF-β signaling. The tension is clear: macrophage programs face safety and specificity questions, and a fibroblast-directed clearance strategy must navigate the line between resolving scarring and disrupting essential tissue repair.
If the platform performs as advertised, the immediate impact will be upstream. Sponsors evaluating antifibrotic bets may use ENIGMAC-derived targets to refresh pipelines that have been whittled by negative readouts, and CROs could see an uptick in discovery-stage collaborations tied to genome-scale screens and complex co-culture assays. Research sites should expect early clinical protocols built around human tissue–anchored biomarkers, including phagocytic activity, matrix turnover signals, and spatial tissue analyses, potentially requiring access to lung biopsies or banked explant material in IPF and other interstitial lung diseases. For regulators, the use of human ex vivo validation aligns with an emerging preference for mechanistic, human-based evidence to support first-in-class INDs, though it won’t replace the need for convincing in vivo pharmacology and safety.
The next proof points are straightforward: disclosure of lead targets, modality choices, and the biomarker strategy that will carry into Phase 1b in organ-specific fibroses. Watch for whether initial assets prioritize lung, where PCLS data are readily leveraged, or branch quickly to liver and kidney, where human tissue access and readouts differ. Also monitor how the company mitigates on-target risk when engaging macrophage effector functions against fibroblasts, particularly in organs with active remodeling. Partnering cadence will be a signal of platform credibility, as will movement toward IND-enabling packages with translational biomarkers tied directly to the co-culture and PCLS assays. The broader question is whether human-first macrophage discovery can finally bend the antifibrosis attrition curve; the answer will hinge on demonstrating that ex vivo signals translate into durable clinical improvements in matrix burden without compromising tissue integrity.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
