Science
We are developing novel therapies targeting macrophage effector functions in diseases where dysregulation of macrophage biology through genetic mutation or micro-environmental sensing is a primary cause of disease pathology.
Approach
Our founders have led the field in understanding the role of macrophages in development, tissue repair, cancer, as well as other diseases. This work, and that of others, has revealed that macrophages are a highly diverse cell type found in every organ in the body, and with key roles in development, tissue homeostasis and repair, as well as in most pathological situations including Alzheimer’s disease, fibrosis of the lung, liver, kidney, inflammation, from the pioneering work of our founders initially in cancer
Our ENIGMAC platform encompasses the Macrophage Atlas, one of the world’s largest collections of patient and normal tissue gene expression across diseases and organs, a proprietary cell based platform, which produces gene editable iPSC cells differentiated into macrophages and microglia, more disease relevant assays. This platform is used for target identification, validation and drug discovery. We can knock genes up as well as down regulate genes of interest using these gene edited macrophages for drug testing potential or for chronic and rechallenge models. Our focus is on first in class drug discovery with the potential to transform patient outcomes.
Pre-clinical portfolio
Macomics has a portfolio of antibody and small molecule programs progressing towards the clinic. Our portfolio is diversified by the mechanism of action and disease with a lead program in IND studies and multiple programs in early discovery. We partnered with ONO Pharma in 2023 to progress an immune-oncology program discovered and validated using our ENIGMAC™ platform.
Macomics will continue to expand its portfolio of validated targets in diseases where macrophages play a central role in aetiology, response to therapy, and patient outcomes.
We have immunology and drug discovery laboratories in Edinburgh and in Cambridge UK.
ENIGMAC™ discovery platform
ENIGMAC™ discovery platform represents a unique tool for gene-to-function studies using human macrophages. Notably, it is disease agnostic and can be integrated with a variety of disease-specific conditions and phenotypic readouts.
The difficulties in performing gene-to-function studies in macrophage field represent a major barrier to entry in order to validate targets and develop new drugs. Macomics has overcome the barriers associated with gene editing macrophages.
ENIGMAC™ incorporates novel assay systems, unique genome editing methods, supported by multi-omics bioinformatics analyses. We use a human Induced Pluripotent Stem Cell (iPSC) line that yields macrophages and microglia phenotypically and functionally very similar to HUMAN monocyte-derived macrophages (MDM). By employing this iPSC system we can produce millions of macrophages per week, which allows multiple high throughput assays to support target validation and drug discovery. In addition, we have developed a suite of technologies to allow fast and reliable gene editing of macrophages. Our proprietary toolbox allows us to perform gene Knock In (KI), Knock Out (KO) and Knock Down (KD) with high efficiency both at iPSC and macrophage and microglia level while maintaining expression/silencing during macrophage differentiation. Knock Down can be performed using a pooled approach that enables screening by flow cytometry-based phenotypes at large scale.
Publications
Further information can be found in selected publications from our Founders and CSO:
- Cassetta, L. et al. Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets. Cancer Cell, 2019. 35(4): 588-602 e10.
- Cassetta, L. and Pollard J.W. Targeting macrophages: therapeutic approaches in cancer. Nat Rev Drug Discov, 2018. 17(12): 887-904.
- Hoves, S. et al. Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity. J Exp Med 2018. 215(3): 859-876.
- Majety, M. et al. A drug development perspective on targeting tumor-associated myeloid cells. FEBS J 2018. 285(4): 763-776.
- Kitamura, T. et al. Immune cell promotion of metastasis. Nat Rev Immunol, 2015. 15(2): 73-86.
- Ries, C.H. et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals novel strategy for cancer therapy. Cancer Cell 2014, 25(6): 846-59, selected for Best of Cancer Cell 2014.
- Wynn, T.A. et al. Macrophage biology in development, homeostasis and disease. Nature, 2013. 496(7446): 445-55.
- Qian, B.Z. et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature, 2011. 475(7355): 222-5.
- Qian, B.Z. and Pollard J.W. Macrophage diversity enhances tumor progression and metastasis. Cell, 2010. 141(1): 39-51.