11:52 AM
Jul 12, 2018
 |  BC Innovations  |  Product R&D

All-in-one viruses

How PsiOxus is building a gene therapy cancer platform on its oncolytic virus

Having taken its lead oncolytic virus into the clinic, PsiOxus Therapeutics Ltd. is building an immuno-oncology platform that uses engineered versions of the vector to selectively target multiple genes at a time to tumor cells wherever they reside.

The idea behind the company’s T-SIGn platform is that by delivering to tumor cells genes that interplay with immuno-oncology pathways, the company can either weaponize the cells to modify the tumor microenvironment or alter their properties to make them more vulnerable to immune attack.

PsiOxus’ lead compound, enadenotucirev, is an oncolytic Ad11p/Ad3 chimeric group B adenovirus in Phase I/II testing for platinum-resistant ovarian cancer and Phase I testing for advanced solid tumors. Data for the two trials are expected in 1H19 and 2H19, respectively.

Rather than using the virus primarily for its oncolytic activity, PsiOxus is using it as a delivery vehicle. The company has created “armed” versions of enadenotucirev that travel through the circulation and carry up to four exogenous genes to tumor cells, including metastases.

PsiOxus has one T-SIGn program in the clinic and four disclosed preclinical programs, three of which it expects to enter the clinic by next year.

The T-SIGn candidates are designed to genetically modify tumor cells to express combination therapies, and cover a range of payloads that include intratumoral therapeutic antibodies, cytokines and membrane-bound ligands.

“While we think the oncolytic activity is really interesting, if you can deliver genes to tumors there is so much more you can do.”

John Beadle, PsiOxus

“While we think the oncolytic activity is really interesting, if you can deliver genes to tumors there is so much more you can do,” said CEO John Beadle.

Beadle said enadenotucirev was generated by directed evolution to allow it to be delivered IV rather than intratumorally, yet to be only active in tumor cells. In contrast, other oncolytic virus platforms require intratumoral delivery.

Last year, the company published Phase I data in the Journal for ImmunoTherapy of Cancer supporting the mechanism behind its platform. A comparison of IV vs. intratumoral enadenotucirev showed the virus is lytic in tumor cells, and does not replicate...

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