4:06 AM
Sep 08, 2017
 |  BioCentury  |  Product Development

Maximizing neoantigens

How Replimune optimized its oncolytic virus platform to combine with anti-PD-1s

In conjunction with raising $55 million in a series B round on Friday, Replimune Group Inc. unveiled details of its Immulytic oncolytic virus platform, including next-generation constructs that underpin the company’s strategy for creating multimodal partners for checkpoint inhibitors.

President and CEO Robert Coffin said Replimune launched in 2015 to create an oncolytic virus platform that maximized the ability to provoke an immune response to tumor neoantigens so they can be combined with PD-1 and PD-L1 inhibitors.

The company reunited veterans from BioVex Inc. (now part of Amgen Inc.), which created the first oncolytic virus approved in the U.S., Imlygic talimogene laherparepvec, also known as T-Vec.

“T-Vec, which we previously developed at BioVex, is the beginning of what you can do with this technology -- but not the best you can do,” Coffin told BioCentury.

Oncolytic viruses attack tumor cells both directly by killing cells they replicate within, and indirectly as neoantigens freed from the dead cells provoke an immune response.

“It greatly increases the number of cells which end up dying, and also the mode of death is very immunogenic.”

Robert Coffin, Replimune

Neoantigens and the T cells that recognize them are considered central to checkpoint inhibitors’ ability to unleash a tumor-specific immune response. While many modalities can be used to produce neoantigens, using a virus to liberate them from tumors circumvents the challenge of selecting the right neoantigens and delivering them immunogenically.

Coffin said Replimune wanted its neoantigen-generating viruses “to kill as much tumor as possible in the first place, to release as much antigen as possible in the first place, and to make that death and antigen release as immunogenic as you can.”

A fusogenic...

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