Infectious enthusiasm

How oncolytic viruses are coming of age in cancer immunotherapy combinations

After over two decades of scant effectiveness against cancer, oncolytic viruses could be close to finding their place in immuno-oncology combination regimens, where they could both be potentiated by and improve response rates to checkpoint agents. Meanwhile, the next generation of viruses may become more potent on their own by doubling as gene therapy vectors to enable tissue-specific delivery of therapeutic proteins and nucleic acids.

Companies have been studying oncolytic viruses since the 1990s, but only one has been approved in the U.S.

In the first decade of the 2000s, investment was steady but modest. But financings dramatically increased following the 2011 acquisition of BioVex Inc. by Amgen Inc. for $425 million up front and up to $575 in milestones.

The deal gave Amgen Imlygic talimogene laherparepvec (T-Vec), then in Phase III testing (see "The BioVex Effect").

BioVex learned from earlier attempts that may have blunted products' efficacy in an attempt to mitigate safety concerns related to administering a replicating virus. The company deliberately engineered Imlygic for improved potency on multiple fronts. Last year the modified herpes simplex virus type 1 (HSV-1) carrying the gene for GM-CSF became the first oncolytic virus therapy approved in the U.S.

Though a game changer for the field of oncolytic viruses, Imlygic also illustrated how far the therapies still have to go to reach full potential, when patients with more advanced disease fared poorer than expected in its Phase III program.

Adding checkpoint agents to oncolytic viruses could be one way to improve responses in more patients, as it is now understood these agents may synergistically improve each other's efficacy in ways that could better address larger or more distant lesions. Most if not all oncolytic virus players plan to combine their therapies with checkpoint agents, and already a few pharmas have started to test combinations.

Atlas Venture's Jason Rhodes said the VC chose to invest in oncolytic platform play Replimune Ltd. last year in part because of the expectation that the viruses will become

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