Fierce 15

Aiming for hard-to-treat, aggressive solid tumors with a tech that’s intended to be self-limited to tumor tissue--and to be personalized to each patient’s tumor

CEO: Mitchell Finer
Based: Cambridge, MA
Founded: 2015
Clinical focus: oncolytic virus

The scoop: This startup is pinpointing next-gen oncolytic viruses, which could offer a less expensive, more efficacious immuno-oncology option than cellular therapy, such as autologous CAR-Ts in development. It’s going straight for the hardest-to-treat solid cancers, including a type of brain cancer, glioblastoma multiforme (GBM).

Oncorus was founded by Mitchell Finer, former CSO of bluebird bio and a managing director at MPM Capital. The approach is expected to be highly specific to tumor tissue, thereby also helping to eliminate some of the risks of immuno-oncology treatments interacting with noncancerous tissue.

“We came on the idea to conditionally control replication by inserting the binding sequence for microRNA into the essential genes of the virus. One has all of the genes intact, inserted in a noncoding region. If the virus infects a neuron and it is not a tumor, that virus is dead; the messenger RNA is destroyed,” Finer told FierceBiotech.

“In a tumor, viral replication ensues with a wild-type virus that retains all the potency. That’s the ‘aha moment’ of the technology,” he continued. This approach is intended to enable the rapid spread of the virus, a problem with earlier attempts, and to keep the virus from engaging with normal cells.

What makes Oncorus Fierce: Use of the latest, most innovative oncology treatments is often confined to the U.S. and European markets given their expense. Oncorus hopes to change that by offering a one-time approach with lasting effects that could prove a way to add immuno-oncology into the mix for a broader mix of patients.

“I see our product as being inexpensive,” said Finer. “It will be able to be shipped globally, potentially for more than 17 months of immuno-therapy. It has improved potency and polyfunctionality as a vaccine, taking the place of cellular therapy. But everything will still go hand-in-hand with surgery, radiation and chemotherapy.”

He added, “It can provide elimination of distant metastases. CAR-T cells don’t stay around; we offer long-lived system immunity and memory.”

Oncorus expects that its virus, by virtue of being a wild-type, not only naturally downregulates the expression of IDO-1, which potentiates T cells, but it also modulates the tumor microenvironment.

Lead candidate ONCR-001 is slated to be injected directly into a tumor, killing its cells and thereby releasing tumor antigens to trigger an immune response that’s personalized to each patient’s tumor.

The startup plans to start out testing in the most severe GBM patients alongside standard of care, which includes chemotherapy and radiation. Within a decade, Finer expects to see a range of oncolytic viruses. “One size won’t fit all, although we will attempt to have as few variants to cover a range of solid tumors,” he said.

Amgen’s T-Vec (talimogene laherparepvec), known as Imlygic, was the first oncolytic virus approved by the FDA last fall to treat melanoma lesions in the skin and lymph nodes. Finer cites it as a precursor for the company.

“How do you make T-Vec better? That’s how you get to Oncorus,” he said. “The virus grows, kills the tumor cells, and that releases antigens. The local injection kills the lesion and surrounding lesions are destroyed presumably by the immune response. It can be used with checkpoint inhibitors.”

Continued Finer, “We are leveraging on the regulatory path of T-Vec in the U.S. and Europe and building a fast follower with a potency advantage and high payload capacity. I can see these products being much more amenable, like a small molecule or an antibody.”

Investors: Celgene ($CELG), MPM Capital, Deerfield Management, Arkin Bio Ventures, Excelyrate Capital and Long March Investment

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