PHARMACEUTICALS
Combining small molecules, viruses and polymers to produce novel therapeutics
PsiOxus Therapeutics is a UK development-stage biotechnology company that uses a new approach based on the combination of different elements, including small molecules, viruses, polymers and other macromolecules, to produce novel patent-protected therapeutics to treat serious diseases, with a particular focus on cancer. This article describes the company’s technology and the progress of its new drug candidates.
PsiOxus Therapeutics is a new UK biotechnology company using non-traditional approaches to develop novel therapeutics that address cancer and other clinically unmet diseases. The company’s lead candidate is MT-102, a dual action anabolic-catabolic transforming agent (ACTA) for the treatment of cachexia, a wasting disease that accompanies cancer, heart failure, COPD, renal failure, cirrhosis and rheumatoid arthritis; and for the treatment of sarcopenia, the age- related loss of muscle mass and strength that affects one in five people by the age of 60. Cachexia is associated with significant morbidity and mortality, and PsiOxus initiated its Phase 2 study of MT-102 in March of this year.
“Cachexia is a powerful risk factor for increased morbidity and mortality, so breaking this progressive cycle of weight loss, weakness and fatigue is critical for improving the outcome of many serious diseases, such
as cancer,” says PsiOxus’ CEO Dr John Beadle. “MT-102 is unique in that it reduces muscle breakdown, termed catabolism, as well as increasing muscle build-up, or anabolism. This clinical trial aims to demonstrate this anabolic-catabolic transforming activity in the context of late- stage cancer patients. We look forward to moving MT-102 one step closer to treating these serious diseases.”
Cachexia is a direct cause of as much as 40 per cent of all cancer patient mortalities. The disease causes an anabolic and catabolic imbalance resulting in cell death and tissue wasting. Most research activity to date has focused on pro-anabolic treatment. PsiOxus has chosen to focus its approach on anti- catabolic approaches, and MT-102 operates on both of the fundamental mechanisms using a single agent. PsiOxus is also developing ColoAd1, an oncolytic virus for the systemic treatment of
Adenovirus library created by homologous recombination under non-physiological conditions (non-mutation)
metastatic cancer. ColoAd1 has demonstrated optimal anti-cancer properties in late preclinical development.
The company is also developing treatments based upon the research-phase vaccine platform PolySTAR, which combines recombinant viral vectors with polymers to shield them from the immune system, and the research-phase adjuvant and immunotherapeutic platform PolyMAP, which combines polymers with synthetic adjuvants to significantly enhance the effectiveness of vaccines.
Research and clinical-stage project portfolio
PsiOxus was formed from the merger of two companies, Myotec Therapeutics and Hybrid Biosystems, in 2010. The merger brought together a combined portfolio of clinical-stage and research projects together with an experienced management team and
ColoAd1 has three changes relative to wild-type adenovirus rendering it unable to replicate in normal cells
Directed evolution for development of viral therapeutics
Multiple rounds of selection identifies virus with a tumour- dependent phenotype and that rapidly kills tumour cells
28 sp2 November/December 2011
PsiOxus has used the power of natural selection to generate an entirely novel virus with optimised cancer-lytic properties. Firstly, a chimeric adenovirus library was created by homologous recombination under atypical conditions of super-infection. ColoAd1 is a PsiOxus hybrid of Ad3 and Ad11p. Multiple rounds of selection then identified those chimeric viruses with a tumour dependent phenotype that also rapidly killed tumour cells. ColoAd1 rapidly replicates in cancer cells, causing them to burst. The potent oncolytic viruses were then screened on normal cells to select one with a very high therapeutic index. ColoAd1 has changes rendering it unable to replicate in normal cells.
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