Novel anti-cancer gene editing action

In 2021 the Company entered into a collaboration with Professor Steve Wilton’s group at Murdoch University, Perth, Western Australia to design and test a novel series of gene silencing reagents, antisense oligonucleotides, targeting Midkine (“MDK”). These oligonucleotide drugs interfere with processing of the Midkine mRNA ultimately leading to reduced active Midkine protein produced in diseased tissues and tumours. Prof. Wilton is a pioneer in this gene silencing technology, having contributed to one of the FDA approvals for RNA therapeutic drugs of this style.

During 2022 the collaboration with Professor Steve Wilton’s group was completed, with the Company’s proprietary oligonucleotides successfully reducing high MDK levels in cancer cells by generating a truncated form of the MDK protein. The switch to the truncated MDK is consistent with >90% efficacy at the mRNA level. These positive results demonstrate the pre-clinical proof of principle in cancer for the antisense oligonucleotide drug development program and underpin the Company’s ability to progress to in vivo studies and clinical trials in due course targeting MDK in cancer. These results underpin the potential for first-in-class medicines targeting the “hard to treat” cancers that express Midkine.

It is important to reduce MDK because high MDK levels are prevalent in many solid tumours and are associated with metastasis, poor response to treatment and poor patient prognosis.

On 11 October 2022 the results of our anti-cancer RNA pre-clinical study were presented at the 29th European Society of Gene & Cell Therapy in Edinburgh. The results demonstrated for the first time that a splice switching RNA medicine can impair Midkine action by inducing a change in the Midkine mRNA, that not only reduces full length Midkine but also generates a non-functional shortened Midkine. Production of truncated Midkine has been shown to reduce the size of cancers in vivo and underpins the potential for anti-Midkine RNA medicines to treat cancer in patients.

In addition, the Midkine RNA program was presented on 3 December 2022 at the European Society of Medical Oncology Asia conference in Singapore. The presentation reported that the lead oligonucleotide program showed >90% efficacy in human cancer cells (at the mRNA level), reduced functional Midkine and is ready for efficacy testing as a novel anticancer medicine.