Idiopathic Pulmonary Fibrosis (IPF)
The lead clinical indication for the exploration of C21 is Idiopathic Pulmonary Fibrosis (IPF). Preclinical data shows that C21 consistently reduces, and in some experimental models, even reverses the established fibrosis typical for IPF.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease of unknown cause. It is characterized by fibrosis of the alveoli and the supporting framework (interstitium) of the lungs. The disease is typically found in people between the ages of 40 and 80 (mean age is 66) and affects more men than women. It is a serious disease with a prognosis worse than many forms of cancer; median survival is around 2-3 years and 5-year mortality rate is 50-70%.
The unmet need for patients with IPF is very high since there is no real effective treatment available for these patients at the moment. Current treatment is typically palliative and includes supplemental oxygen and pulmonary rehabilitation. The only two drugs approved for IPF are Esbriet and Ofev; both slow down the progression of the disease but none of them has this far demonstrated significant improvement in terms of survival.
Frequency: IPF is currently rising with the disease today affecting about 15-20/100 000 individuals. The IPF market is estimated to reach $1 billion in 2020.
Preclinical data shows that C21 consistently reduces, and in some experimental models, even reverses the established fibrosis typical for IPF. The properties of C21 are favourable for treatment of fibrotic diseases as the concept allow to address the condition from a number of different angles, e.g. below;
- AT2 Receptor is upregulated in IPF lungs ( the target of C21)
- Anti-apoptotic effect (prevent apoptosis of alveolar endothelial cells (initiating factor))
- Anti-inflammatory effect (important in early phases)
- Anti-proliferative effect (reduces cancer like proliferation of fibroblasts/myofibroblasts)
- Improvement of vascular remodeling (reduces secondary pulmonary hypertension)
- Anti-cytokine effect (strong effect on e.g. IL-6 of importance for recruitment fibroblasts, differentiation into myofibroblasts and potent local anti-TGFß effect)
- Anti-fibrotic effect (as demonstrated in the lung, heart, kidney, small and large vessels and skin)
- Anti-fibrotic effect (lung: prevents and reverses pulmonary and vascular fibrosis, reverses collagen deposition and ECM accumulation)
Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension (PAH) is a rare, often fatal, cardiopulmonary disease with an annual mortality rate of about 15% of diagnosed cases.
C21 has demonstrated potent effects on pulmonary arterial hypertension in an animal model where PAH was induced by pre-treatment with monocrotaline, a chemotherapeutic drug with PAH as a typical side effect. C21 demonstrated to reverse the increased blood pressure in the pulmonary system, largely by alleviating the fibrosis in the blood vessels.
PAH has an estimated total patient population in the US, EU5 and Japan ranging between 42 000 – 74 000 diagnosed prevalent patients. The market value of PAH in 2014 based on sales of drugs has been estimated to be between $2.5b to $3.3b.