Strategic agreement to help fix the body's leaky pipes

Danish biotechnology company Mirrx Therapeutics and Sydney’s Centenary Institute of Cancer Medicine and Cell Biology have executed a strategic collaboration and commercialisation agreement. The agreement formalises the two bodies’ long-standing collaboration to discover and develop therapeutic oligonucleotide drug candidates targeting vascular endothelial cadherin (VE-cadherin).

VE-cadherin is a key cell-cell junctional protein in the endothelial lining of the blood vessels that regulates junctional structure and downstream signalling events, including regulation of vascular permeability and promotion of normal angiogenesis. Pharmacological modulation of VE-cadherin expression has the potential to treat a broad range of diseases for which regulation of vascular permeability and angiogenesis are important, including ischemic conditions, inflammation, oedema and solid tumours.

Mirrx and the Centenary Institute have discovered that VE-cadherin expression is regulated, in part, by the microRNA miR-27a. This negative regulator is itself down-regulated during angiogenic processes, leading to increased expression of VE-cadherin and reduced vascular permeability and stimulation of angiogenesis. The collaborators’ drug candidate CD5-2, a potent, 15-mer oligonucleotide drug, leverages Mirrx’s Blockmir technology to selectively inhibit miR-27a VE-cadherin regulation without affecting miR-27a regulation of its other targets.

In vivo investigation of CD5-2 in a variety of animal models has demonstrated that the drug potently inhibits vascular permeability and promotes angiogenesis, leading to increased blood flow, decreased oedema and faster recovery; for example, in the industry-standard hind limb ischemia mouse model. The collaborators have published the discovery and characterisation of CD5-2 in the journal Blood.

Professor Mathew Vadas, executive director of the Centenary Institute, said, “Leaky blood vessels, as manifest by tissue swelling that can ultimately obstruct blood supply, is a very important clinical problem from the emergency room all the way to rehabilitation. The potential of a useful drug preventing vascular leak is very exciting and we look forward to its clinical development in collaboration with Mirrx.”

Mirrx CEO Dr Thorleif Møller said, “We are very pleased to have entered into this partnership with the Centenary Institute, which to the best of our knowledge has provided the first therapeutic in vivo proof of concept for blocking microRNA binding sites in messenger RNA. Moreover, the partnership has validated our second-generation Blockmir design with improved specificity and potency.”

The agreement includes cross-licensing of patents, collaborative research and joint commercialisation activities. It was facilitated by Bio-Link Australia, which has been engaged by the collaborators to facilitate licensing of CD5-2 to a biopharmaceutical company interested to pursue its further development and commercialisation.