This week’s “2017 NEVYs Nominee Spotlight” is on Oncorus, a nominee for Hottest Early Stage Startup — Therapeutics. Today we’ll delve into why their work is so impactful to this region, and patients everywhere.

Germinating an idea
The approval in 2015 of Amgen’s IMLYGIC® (talimogene herparvovec), or T-VEC, established a clear regulatory path for the development of oncolytic virus immunotherapy. But how do you make T-VEC better?

Enter Oncorus.

Co-founded by industry veteran Mitchell Finer, Ph.D., former CSO of bluebird bio and a managing director at MPM Capital, Oncorus uses a next-generation oncolytic herpes simplex virus (oHSV) immunotherapy platform to improve upon first generation oncolytic viruses. Oncorus’s oHSV platform is based upon the work of renowned scientists Joseph Glorioso III, Ph.D., and Paola Grandi, Ph.D., both from the University of Pittsburgh and who serve on Oncorus’s Scientific Advisory Board. In addition to licensing certain patent rights from the University of Pittsburgh, the company has a number of other filed and licensed patents that make up its intellectual property portfolio.

Similar to T-VEC, Oncorus’s immunotherapy platform is designed to act both locally at the site of injection through oncolysis and systemically by stimulating the immune response against the patient’s tumor burden distributed across the body. The Oncorus approach improves upon first generation oncolytic viruses by preserving important replication genes, thereby dramatically improving potency. This provides greater killing of tumor cells, as has been demonstrated in animal models.

Located in Kendall Square, Cambridge, Oncorus launched in July 2016 with a $57 million Series A financing; in December, the company announced additional financing support from Astellas Venture Management LLC (AVM), increasing its Series A proceeds to $61 million. AVM joined a team of investors led by MPM Capital (with equal contributions from MPM BV2014 and the Oncology Impact Fund), and included Deerfield Management, Arkin Bio Ventures, Celgene, Inc., Excelyrate Capital, Long March Investment Fund and MPM’s SunStates Fund.

Oncorus’s oHSV immunotherapy platform

To specifically target cancer cells, Oncorus utilizes differences in genetic control sequences between normal cells and cancer cells, which restricts viral replication to tumor cells and leaves normal cells intact. Oncorus’s oncolytic viruses retain all viral genes required for robust viral replication in a tumor-specific fashion while simultaneously enhancing safety by prohibiting replication in normal cells. This approach also leads to a virus that can modulate the tumor microenvironment, facilitating a systemic anti-tumor T-cell immune response. The virus is designed to replicate at maximum productivity, enabling robust and scalable manufacturing. Delivery by local injection further enables this therapy to be easily integrated into current medical practice.

In order to prevent replication in normal (non-tumor) cells, oHSV replication is under the control of micro-RNAs (or miRs), which are fundamentally different in normal cells versus cancer cells. miRs are short non-coding RNAs that regulate the ability of classical messenger RNAs (mRNAs) to be translated into protein or to promote the degradation of classical mRNAs. By engineering miR binding sites into essential viral genes, upon virus entry into normal cells, replication is blocked and viral activity is rendered dead.

Capitalizing on Cambridge

According to Finer and his team, four key ingredients were critical in selecting Cambridge as home:

  • People: “There’s a deep and broad skill set of highly-trained and experienced professionals across all functional areas needed to build a successful biotech company.”
  • Science: “Both the quality and quantity of academic institutions and the research being conducted are unparalleled, which contributes to the talent pool, and leads to the creation of highly innovate and defensible intellectual property, which is important for attracting investors.”
  • Capital: “The strong presence of Tier-A venture capital firms, and potential strategic partners in the area has fueled the translational innovation underway at Oncorus, while creating the opportunities for strategic collaboration, non-dilutive funding, and eventual liquidity for investors.”
  • Concentration: “The close proximity of these core ingredients allows for frequent interactions and rapid progress on our plans.”

Looking to the future

The differential expression of miRs between tumor cells and normal adjacent has been observed in almost every tumor type, so Finer and his team believe that this could be a promising approach for many types of cancer. Currently, the company’s lead candidate — ONCR-001 — is in preclinical development for glioblastoma multiforme (GBM), a highly malignant and aggressive cancer.

“We chose GBM as a lead indication because patients have few treatment options, and the cancer often recurs within one-to-two years. With our powerful combination of experience and expertise, joined by such a terrific group of investors, it’s an exciting time at Oncorus. We look forward to advancing cancer therapies that will make a meaningful difference in peoples’ lives,” concluded Finer.

A leader in corporate philanthropy, Oncorus has taken a pledge to donate a portion of product sales revenue to fund promising cancer research and to support cancer care in the developing world.

This was a guest post by the Oncorus team. Come meet them at the NEVYs this Wednesday, as they cheer on their own nomination and congratulate other nominees.

New England Venture Capital Association (NEVCA) members support entrepreneurs winning. Great VCs depend on great entrepreneurs.