AstraZeneca Licenses Potential IPF Treatment RXC006 from Redx for Clinical Development

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by David Melamed, PhD |

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AstraZeneca has acquired a global license for RXC006, an investigational porcupine inhibitor for treating fibrotic diseases, including idiopathic pulmonary fibrosis (IPF), providing $17 million in initial funding to the therapy’s developer Redx Pharma.

AstraZeneca plans to advance RXC006 to a Phase 1 clinical study.

The agreement includes a further $360 million in funding, should RXC006 meet additional development, regulatory, and commercial milestones during the process.

RXC006 is a small molecule designed to block the activity of porcupine, a key enzyme required for the activation of the Wnt signaling pathway, which is a mechanism that regulates cellular growth and development in many types of tissues.

Recent evidence has shown that Wnt activity is central to the scarring (fibrotic) activity observed in patients with IPF.

As the Wnt pathway has known roles in inflammation, cell death, epithelial-mesenchymal transition (a key step in fibrosis development), and fibroblast activation, the blocking of porcupine and Wnt activity by RXC006 is a new approach to limit these events in IPF.

Preclinical studies conducted by Redx showed positive results, demonstrating low levels of Wnt signaling activity in lab-grown lung cells, and, importantly, a reduction of lung scarring in fibrotic mice upon treatment with RXC006.

“We are excited by the potential of porcupine inhibition as a novel approach to tackling fibrotic-associated diseases where there is a real patient need,” Lisa Anson, CEO of Redx, said in a press release.

“This agreement, where AstraZeneca will license this first in class porcupine inhibitor for IPF and progress it into development, highlights, once again, Redx’s ability to generate molecules that have significant potential as novel medicines,” Anson added.

By acquiring the licensing rights to RXC006, AstraZeneca aims to bring the treatment to a clinical trial stage, with the overarching goal of providing a new treatment for IPF patients in need.

“Fibrotic diseases such as idiopathic pulmonary fibrosis have significant impact on patients’ lives and new therapies are urgently needed,” said Mene Pangalos, executive vice president of biopharmaceuticals R&D at AstraZeneca. “We look forward to progressing this porcupine inhibitor into clinical trials as a novel approach to suppress Wnt signalling and potentially modify fibrotic disease processes.”

In addition to work on RXC006, Redx also is actively developing two other small molecule treatments: RXC004, a porcupine inhibitor designed to treat tumors with abnormal Wnt activity, and RXC007, an inhibitor of the protein ROCK2 (Rho Associated Coiled-Coil Containing Protein Kinase 2) designed for treating fibrosis.

RXC004 is being studied in a Phase 1/2 clinical trial (NCT03447470, and still recruiting participants in the U.K.), which is investigating the safety and tolerability of RXC004 in patients with advanced malignancies to determine proper dosage in future studies.

RXC007 is in preclinical development, with studies showing that ROCK2 inhibition reduces fibrosis and lowers pro-fibrotic and pro-inflammatory gene expression in in vivo studies. Redx expects to launch clinical testing of RXC007 in 2021.