Porcupine is a novel drug target that aims to address the issue of high unmet need in fibrosis.
Porcupine is a key enzyme in the Wnt signalling pathway. Aberrant Wnt signalling is involved in fibrogenesis, and inhibition of Wnt signalling is likely to prevent several mechanisms important for fibrotic disease progression.
Current treatments for fibrosis provide limited benefit and there is an urgent need to develop new therapies to treat fibrotic conditions.
Recent publications have shown that Porcupine (PORCN) inhibitors are effective in preclinical models and could be beneficial in the treatment of fibrotic indications, including renal, heart, lung and skin conditions.
Our scientists have demonstrated that RXC006 potently inhibits PORCN resulting in striking anti-fibrotic effects in animal models of kidney, liver and lung fibrosis. RXC006 has been nominated as a candidate for development in Idiopathic Pulmonary Fibrosis and IND-enabling studies have been initiated. RXC006 is from a different chemical series to our lead oncology asset RXC004 and is protected by a separate composition of matter patent.
By targeting Porcupine, we aim to prevent progression or reverse fibrosis in patients with these devastating diseases.
Porcupine inhibitor, RXC006 suppresses fibrosis in a bleomycin-induced mouse model of IPF
Image representative of group mean Ashcroft scores. Scale bar indicates 1.2 mm. Small region of dense collagenous connective tissue (fibrosis; black arrows demarcate) and lymphocyte infiltrates/aggregates (*) are present. A bronchiole (Br) and blood vessels (BV) are indicated.
Out Licensing Agreement with AstraZeneca
In August 2020, Redx Pharma signed a significant out licensing agreement for its porcupine inhibitor, RXC006, with AstraZeneca. AstraZeneca will take RXC006 forward into clinical development, targeting fibrotic diseases including idiopathic pulmonary fibrosis (IPF). Under the terms of the exclusive global agreement, AstraZeneca will pay Redx several early milestones that amount to $17 million, by the time of successful commencement of a phase 1 study. In addition, Redx is eligible to receive up to a further $360 million from AstraZeneca in development, regulatory and commercial milestone payments throughout the course of the programme should it successfully reach these milestones. Redx is also eligible for tiered royalties of mid-single digit percentages, based on any future net sales.