About FibrosIX

FibrosIX is a pre-clinical stage biotechnology start-up, founded in 2016. It is developing proprietary first-in-class small-molecule therapeutics that inhibit fibrotic disease. These drugs modulate a critical signaling pathway that plays a central role in the pathogenesis of fibrotic disease.

The lead drug candidate, FBX081, is being developed for the prevention of lung fibrosis in cancer patients induced by chemotherapy (bleomycin) and/or radiation therapy.

Target Indication

Over 300,000 cancer patients in the US each year are at risk for developing pulmonary fibrosis due to cancer treatment.

Pulmonary fibrosis is a progressive, potentially fatal, disease that is characterized by poor lung function and shortness of breath. Once it develops, lung fibrosis is a life-long disability with high follow-on healthcare costs. It can be brought on by many different mechanisms, or as the result of cancer treatments, such as chemotherapy and radiotherapy.

Over 300,000 cancer patients in the US each year are at risk for developing pulmonary fibrosis due to cancer treatment.

For cancer patients, lung fibrosis is a treatment-limiting side effect. Not only do they experience difficulty breathing, but their cancer treatment is put on hold until symptoms are managed, another cancer treatment can be found, or in some cases treatment ceases altogether, putting them at greater risk of recurring cancer. In 2-5% of cases the lung fibrosis is fatal.

With no therapies clinically approved to treat this indication, there is a significant unmet clinical need for new drugs in this underserved patient population. Oncologists currently have no way of predicting exactly who will develop lung fibrosis during cancer treatment. Therefore, FBX081 is envisioned to be incorporated into the standard of care at the start of all chemotherapy and radiotherapy.

FibrosIX therapeutics are technologically unique

What differentiates FibrosIX compounds is that they were developed to inhibit a critical pathway common in the majority of fibrotic diseases: Myocardin-Related Transcription Factor and Serum Response Factor (MRTF/SRF) signaling. The activation of this genetic switch (MRTF/SRF driven transcription) is responsible for the transition of healthy fibroblasts to an aberrant phenotype of myofibroblast. Once myofibroblasts form, they begin the process of out-of-control wound healing characteristic of fibrosis, leading to the reduced function of healthy tissue. In the case of lung fibrosis, this translates to difficulty breathing that worsens over time, and is potentially fatal.

There are many ways that fibrosis can be triggered within the body. In some disease states, multiple redundant pathways are activated. However, all must proceed through the critical step of myofibroblast activation. The majority of current anti-fibrotic technologies target only one of the activation signals and have limited efficacy.

In contrast, FibrosIX small-molecules target the critical myofibroblast activation pathway, through the molecular target pirin, to stop fibrotic scar tissue from forming. This has led to demonstrated efficacy in pre-clinical treatment models of lung, skin, intestine, and conjunctiva fibrosis. In all cases, FibrosIX compounds were shown to halt the progression of fibrotic disease.

Future directions in the anti-fibrotic area include idiopathic pulmonary fibrosis and scleroderma. In addition, FibrosIX is investigating new indications, including hyper-inflammation.

Selected References

Sisson, T. H. et al. Inhibition of Myocardin-Related Transcription Factor/Serum Response Factor Signaling Decreases Lung Fibrosis and Promotes Mesenchymal Cell Apoptosis. The American Journal of Pathology 185, 969–986 (2015). PMCID: PMC4380846. doi: 10.1016/j.ajpath.2014.12.005

Hutchings, K. M. et al. Pharmacokinetic optimization of CCG-203971: Novel inhibitors of the Rho/MRTF/SRF transcriptional pathway as potential antifibrotic therapeutics for systemic scleroderma. Bioorg. Med. Chem. Lett. 27, 1744–1749 (2017). PMCID: PMC5395305. doi: 10.1016/j.bmcl.2017.02.070

Lisabeth, E. M. et al. Identification of Pirin as a Molecular Target of the CCG-1423/CCG-203971 Series of Anti-Fibrotic and Anti-Metastatic Compounds. ACS Pharmacol & Trans Science 2, 92-100 (2019). PMCID: PMC7006939. doi: 10.1021/acsptsci.8b00048