New drug targets the fundamental process of inflammation

A new class of anti-inflammatory medication developed in Australia is being prepared for regulatory approval, targeting the fundamental process of inflammation associated with a huge range of diseases.

Using technology he developed at Hudson Institute of Medical Research, Associate Professor Ashley Mansell is working with US-based industry partner Adiso Therapeutics to develop treatments targeted to inflammasomes. Founded in Concord, MA Adiso Therapeutics, with funding from Morningside Ventures, seeks to develop treatments for inflammatory diseases.

Mansell explained that inflammasomes are innate immune sensors that detect disruptions to homeostasis. In other words, they identify when something is wrong and trigger an inflammatory response.

NLRP1 and NLRP3

“Inflammasomes are associated with a wide range of infectious and inflammatory diseases, and the ones we are targeting are NLRP1 and NLRP3, because where there is inflammation, then there’s usually one or both involved,” he said.

“Inflammasome-associated inflammation is associated with nearly every major disease afflicting humankind. This inhibitor may target the fundamental process of inflammation associated with these diseases.

“The drug we have developed through our collaboration with Adiso is called ADS032, the first described dual inflammasome inhibitor and a potential therapeutic to treat both NLRP1 and NLRP3 associated inflammatory diseases.”

The NLRP1 inflammasome can be found predominantly within barrier cells, like skin and bronchial epithelial cells, whereas an NLRP3 inflammasome is found mostly within immune cells such as macrophages and neutrophils, hence the wide applicability of this inhibitor.

Adiso Therapeutics is currently running pre-IND studies for submission of ADS032 to the US Food & Drug Administration in 2024 for potential clinical application in respiratory and dermal inflammation.

Potential for a range of diseases

Inflammasomes as a drug-able target have been undergoing clinical trials for several years.

Compounds that exclusively target NLRP 3 alone are in development for the treatment of neurologic diseases with additional indications also being investigated.

The approach being undertaken by Adiso for ADS032 is fully differentiated, largely due to the dual modulation ability of NLRP 1 & 3 where both of the inflammasome isoforms reside.

Mansell said ADS032 shows great potential in the treatment of a wide range of diseases.

“This publication shares insights that are a significant step forward in the development of a new treatment for inflammation, and I am hopeful ADS032 will progress into clinical trials that will ultimately benefit patients with inflammatory disease.

“The development of ADS032 is a wonderful example of what is possible when academia and industry work together to translate the fundamental research we undertake here at the Hudson Institute to ultimately improve patients’ lives,” Mansell said.

Image credit: L-R: Associate Professor Ashley Mansell and Research Assistant Callum Docherty.