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Targeting the underlying drivers of fibrosis

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Fibrosis is a common underlying mechanism driving disease progression across a range of chronic conditions, including chronic kidney disease and systemic sclerosis.

Certa Therapeutics is developing asengeprast to address fibrosis at an upstream control point, modulating multiple biological pathways that contribute to inflammation, tissue remodelling and organ dysfunction.

Our approach is focused on generating clinically meaningful disease modification by broadly impacting the underlying processes that drive fibrosis, rather than targeting individual downstream pathways.

Diabetic retinopathyWet age-related macular degenerationDiabetic macular edemaEYESclerodermaSystemic sclerosisSKINSystemic sclerosisInterstitial lung disease (ILD)Interstitial pulmonary fibrosis (IPF)LUNGDiabetic CardiomyopathyMyocardial InfarctionHEARTHepatic encephalopathyLIVERChronic kidney disease (CKD)Diabetic kidney disease (DKD)Focal Segmental GlomerulosclerosisLupus nephritisKIDNEY

Fibrosis is triggered by inflammation​

Chronic inflammation leads to tissue scarring​

Fibrosis causes tissue remodeling ​

This limits organ function and leads to organ failure

No approved drugs

To inhibit fibrosis progression

The role of fibrosis in disease progression

Fibrosis is a pathophysiological process characterised by excessive deposition of connective tissue, leading to structural changes and progressive loss of organ function.

This process is central to the progression of many serious and life-limiting conditions, including chronic kidney disease and systemic sclerosis.

Despite advances in standard of care therapies, fibrosis continues to drive disease progression in these conditions, contributing to organ damage and long-term morbidity.

A targeted approach to modulating fibrosis

Certa’s lead asset, asengeprast (FT011) broadly modulates fibrotic and inflammatory processes.

Evidence across preclinical & clinical studies

The activity of asengeprast has been evaluated across a range of experimental and clinical settings.

Clinical Trials
Preclinical models

Demonstrated anti-fibrotic effects and improvements in organ function across multiple models of kidney disease and fibrosis.

STNx

STNx + Asengeprast

Figure: Representative images of kidney tissue from a rodent model of kidney disease (STNx model). The blue stain highlights fibrosis in this model. There is limited fibrosis with Asengeprast treatment.  From Gilbert et al. 2012 A Purpose-Synthesised Anti Fibrotic Agent Attenuates Experimental Kidney Diseases in the Rat. PLoSONE7(10):e47160.doi:10.1371/journal.pone.0047160

Biological evidence of a treatment effect and clinical relevance

  • Molecular and transcriptomic analyses of tissues from animal models of chronic kidney disease (CKD model) shows a dysregulation of genes associated with fibrosis and inflammation.
  • Thousands of genes that are dysregulated in the CKD model are reversed following asengeprast treatment.
  • Asengeprast reverses the disease gene profile back towards a healthy baseline.
  • The Asengeprast Gene Signature is made up of the top 500 most significantly differentially expressed genes that are modified in the CKD model and reversed by asengeprast treatment. The Asengeprast Gene Signature Score is single score that reflects the changes in activity of these genes.
  • Treating the CKD model with asengeprast:
    • reduces the Asengeprast Gene Signature Score
    • reduces kidney fibrosis
    • improves renal function (as measured by glomerular filtration rate and proteinuria).


In the CKD model, the Asengeprast Gene Signature Score significantly correlates with kidney fibrosis and reduced renal function.

The molecular pathways modulated by asengeprast are clinically relevant and are dysregulated in clinical tissues.

CKD biopsies:

  • The Asengeprast Gene Signature Score correlates with renal fibrosis and markers of kidney injury in biopsies from patients with Focal Segmental Glomerulosclerosis, Membranous Nephropathy and Immunoglobulin A nephropathy.

Systemic Sclerosis:  

  • Certa conducted a Phase 2a clinical trial in patients with diffuse systemic sclerosis.
  • In skin biopsies from participants that received oral asengeprast treatment, the Asengeprast Gene Signature Score was reduced from baseline to 12 weeks.
  • The gene signature score also correlated with disease severity in these patients as measured by ACR-CRISS.

The findings support the potential for a broad anti-fibrotic effect that translates from preclinical models to human disease.