DUBLIN – The pioneering team behind Amgen Inc.'s oncolytic viral therapy talimogene laherparepvec (T-vec) has re-surfaced in a new venture, Replimune Ltd., which closed a $30 million series A round to take forward a new generation of the technology.

Replimune's founders are executive chairman Philip Astley-Sparke and CEO Robert Coffin, the former CEO and chief scientific officer, respectively, of University College London spinout Biovex Ltd., which Amgen, of Thousand Oaks, Calif., acquired in a deal worth up to $1 billion, $475 million of which came up front. (See BioWorld Today, Jan. 26, 2011.)

Biovex raised upward of $150 million in private equity funding before that profitable exit. Two of its backers, Forbion Capital Partners, of Naarden, the Netherlands, and Omega Fund Management LLC, of Boston, have come back for more. Each participated in Replimune's seed round and in the series A round, which was led by the influential Cambridge, Mass.-based firm Atlas Venture.

Replimune is not yet divulging any details around its scientific strategy. "We are still somewhat in stealth mode," Coffin told BioWorld Today. The company is developing its technology in-house – it does not come from an academic lab – and it plans to pursue development of its novel therapy as a single agent and in combination with immune checkpoint blockers, an increasingly prominent theme in oncolytic virotherapy.

Although oncolytic viral agents such as T-vec have demonstrated activity when administered as a monotherapy, they tend not to be as potent as antibody-based immune checkpoint inhibitors. Conversely, the absence of a pre-existing immune response within the tumor microenvironment is one of the main obstacles to successful checkpoint inhibitor blockade. Preliminary data indicate that combinations of the two are highly synergistic – with the added benefit that such combinations have a more benign safety profile than combinations of two checkpoint blockers.

Which agents Replimune would deploy in a combination with oncolytic viral therapy "is certainly not set in stone as yet," Coffin said, given the rapid evolution of the field. Replimune aims to be in the clinic by the end of 2016. "This funding sees us through to a significant amount of clinical data," he said.

T-vec is based on a modified version of herpes simplex virus 1, which grows selectively in transformed cells and which expresses the immunostimulatory cytokine granulocyte macrophage colony-stimulating factor. It is administered intratumorally, a delivery strategy that Replimune will emulate.

"We are of the view that systemic administration of oncolytic viruses has been and will remain a very significant challenge," Coffin said. Rapid viral clearance from the circulation makes it difficult to achieve a therapeutic effect. However, the company will also explore intrapleural and intraperitoneal delivery, where the same issue does not arise.

Replimune is headquartered in Oxford, UK, where its main R&D activity is located. It will also establish an office in the Boston-Cambridge area, which will be responsible for clinical operations. Jason Rhodes of Atlas, Sander Slootweg of Forbion and Otello Stampacchia of Omega Funds have all joined its board on foot of the funding round.

The company has emerged just ahead of T-vec's imminent approval in melanoma – it has an Oct. 27 PDUFA date, following a 22-1 vote recommending approval from an FDA advisory panel in April. (See BioWorld Today, April 30, 2015.)

Given the leading role Coffin and Astley-Sparke have played in developing oncolytic viral therapy, their new venture will be followed by the wider field with interest. The progress of T-vec has helped several other firms raise cash this year, including Viratherapeutics GmbH, of Innsbruck, Austria; Psioxus Therapeutics Ltd., of Abingdon, UK; and Western Oncolytics Ltd., of Cleveland.

The field suffered a serious setback over the summer when a trial at the Mayo Clinic in Scottsdale, Ariz., was put on clinical hold following the death of a patient who had received a vesicular stomatitis virus strain engineered to express human interferon-beta. The Medimmune unit of London-based Astrazeneca plc had in-licensed the program from Rochester, Minn.-based Omnis Pharma Inc. (See BioWorld Today, July 7, 2015.)