A core focus is the development of our own internal clinical-stage RNAi therapeutics, having developed a broad pipeline of product candidates.
Our technology also serves as an important foundation for several siRNA programs currently in clinical development worldwide. We have partnerships and licensees with pharmaceutical companies around the world, demonstrating the significance of our RNAi platform within the sector.
Quark Pharmaceuticals inc. (‘Quark’) has licensed Silence’s AtuRNAi® for its PF-655 product, which has in turn been licensed to Pfizer. Phase 2 results are awaited in Diabetic Macular Edema.
Novartis has taken an option to license Quark’s QPI 1002, targeting Acute Kidney Injury and Delayed Graft Function in kidney transplant patients. Favourable Phase 2 results were reported in Delayed Graft Function and Quark is reviewing the next stage. Both these Quark drugs use naked siRNA.
Click here for information on our pre-clinical development programmes.
Development of Atu027: An RNAi Therapeutic for Oncology
Atu027 is a drug candidate that uses our AtuPLEX® and AtuRNAi® technologies to target the expression of the protein PKN3 which is known to be a key factor in cancer progression and metastasis.
Atu027 is one of the most thoroughly tested RNAi therapeutics in humans and has an excellent safety record, with over 400 people dosed so far and no immune response observed.
It is composed of AtuRNAi®-type siRNA (targeting PKN3) within a liposomal formulation – our proprietary AtuPLEX® delivery system. This ensures the applicability of Atu027 in the patient’s bloodstream and delivers RNAi of the target gene PKN3 in the vascular endothelium.
In our pre-clinical studies, we examined the utilisation of liposomal siRNA based on AtuPLEX® technology in vivo and its activity in the vascular endothelium of the vasculature. This cellular target structure of all blood vessels often becomes affected at the onset and during progression of many diseases. In cancer, angiogenesis (the growth of new blood vessel) leads to the development of a malformed tumour vasculature which supplies the tumour with oxygen and nutrition, helping cancer cells to further grow and ultimately spread. Beyond the abnormal function of the endothelium in tumour vessels, the cancer patient’s vasculature becomes permeable in order to facilitate cancer cell colonisation at organ sites where metastasis occurs. Atu027 can target the “vascular bed” within the patient’s body in a way that prevents this critical biological process from taking place.
PKN3 in cancer
Our drug discovery research focused on identifying novel target genes critical for carcinogenesis and metastasis. The proprietary PKN3 gene (Protein Kinase N3) was originally identified at Silence Therapeutics as a downstream target of activated PI-3 kinase signalling (Leenders et al. 2004).
The PKN3 target gene is believed to be a key factor for cancer progression and metastasis. Its function in the endothelium is believed to be critical during the different steps of metastasis, since PKN3 integrates incoming signalling cues for coordinated cellular functions, such as cell adhesion and contact formation, cell shape remodelling, cytoskeletal fluidity, and migration.