Hybrid adenovirus-based product will initially be developed against colorectal cancer and primary hepatic cellular carcinoma.

Ark Therapeutics negotiated a manufacturing partnership with PsiOxus Therapeutics for the latter’s ColoAd1 candidate for the treatment of colorectal cancer. Under terms of the agreement Ark will work with PsiOxus to generate an IV formulation of the adenovirus-based oncolytic product using its suspension-based single-use system (ATOSUS) for toxicological and Phase I/II clinical studies.

ColoAd1 is an Ad3/Ad11p hybrid, designed as a broad-spectrum anticancer therapeutic capable of destroying tumor cells at minute concentrations, but with minimal damage to healthy tissue. The oncolytic virus has been generated using the evolutionary principle of natural selection, to generate a candidate that PsiOxus claims demonstrates anticancer potency at 0.1–10 femtomolar concentration, including activity against drug-resistant cancers. The initial target indications for ColoAd1 will be metastatic colorectal cancer and primary hepatic cellular carcinoma.

The evolutionary approach used to generate ColoAd1 involves generating a chimeric adenovirus library by homologous recombination under atypical conditions of super-infection, PsiOxus explains. Multiple rounds of selection are subsequently carried out to identify strains with a tumor-dependent phenotype that also rapidly killed tumor cells. Candidate oncolytic viruses are then screened on normal cells to select a candidate with optimal therapeutic index.

PsiOxus was established in December 2010 through the merger of Myotec Therapeutics and Hybrid BioSystems. The ColoAd1 candidate originated at Hybrid Biosystems, a firm initially established to exploit viruses as therapeutics. The candidate was developed by Hybrid in collaboration with Bayer Schering. Hybrid Biosystems also developed the PolyStar vaccine vector system, and PolyMap adjuvant/immunotherapeutics platform, both of which PsiOxus inherited when it was formed last year.

PsiOxus’ lead clinical-stage compound, MT-102, is a small-molecule anabolic catabolic transforming agent, which is currently undergoing a placebo-controlled Phase II trial as a treatment for disease-related cachexia. MT-102 was originally developed by Myotec, itself an Imperial College London spin-out established to progress work by university scientists on the underlying mechanisms of cachexia. PsiOxus says promising preclinical results from in vivo studies evaluating MT-102 against age-related sarcopenia will also be followed up through future clinical studies. 

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