Oncorus has raised $79.5 million to advance oncolytic viruses. The series B round equips Oncorus to move its lead prospect into the clinic and nominate an intravenously administered viral candidate early next year.

That second, intravenous candidate will move the oncolytic virus sector into unchartered territory by unshackling it from the constraints of intratumoral delivery. But in the nearer term, Oncorus’ fate is tied to a lead asset, ONCR-177, that superficially looks more familiar. ONCR-177, like Amgen’s Imlygic, the only approved oncolytic virus, it is built on a herpes simplex virus and is delivered intratumorally.

Yet, in many other regards, the candidate is distinct from Imlygic and other experimental oncolytic viruses in large part because of Oncorus’ attempts to overcome issues that have held the modality back to date. 

Whereas some oncolytic viruses feature diminished replication capacity to improve safety, Oncorus has freed ONCR-177 to go full throttle when within tumors while using microRNA attenuation to keep it under control in healthy tissues. To further enhance efficacy, Oncorus has loaded ONCR-177 with an alphabet soup of transgenes: IL-12, CCL4, FLT3L and CTLA-4 and PD-1 antagonists.

Oncorus has preclinical data suggesting the transgenes dial up the anti-tumor response. Some of the data come from animals with bilateral tumors. After injecting ONCR-177 into one of the animal’s tumors, Oncorus sees strong activity in the other, untreated tumor, suggesting the drug is priming the immune system to attack cancer cells. Other rechallenge studies of the response of cured animals to the reintroduction of a tumor months later add further weight to that conclusion. 

“In each case, the animal rapidly rejects the reimplantation, suggesting very strongly that what we’ve done is establish robust, durable anti-tumor immunity,” Oncorus CEO Ted Ashburn said.

Buoyed by the preclinical data set, which features positive survival data in models where Imlygic has struggled, Oncorus plans to take ONCR-177 into human testing early next year. The clinical program will explore the use of ONCR-177 as a single agent in tumors that “aren’t necessarily candidates for checkpoint inhibitor therapy,” Ashburn said, and in combination with PD-1/L1 drugs to broaden the efficacy of those cornerstones of immuno-oncology.

In parallel, Oncorus is working on a synthetic oncolytic virus platform it thinks could facilitate systemic delivery, thereby enabling treatment of lung cancer using the modality. Systemic delivery has been closed off to the field as the immune system wipes out oncolytic viruses in the bloodstream. Oncorus has a plan to bypass those defenses.

“We’re taking polynucleotides that encode for an oncolytic virus and encapsulating them within a lipid nanoparticle. There are no proteins involved, no actual viral particles, just polynucleotides in a lipid nanoparticle,” Ashburn said.

When injected, Oncorus thinks the immune system will ignore these nanoparticles, enabling them to pass unmolested to the tumor. Once inside the tumor, the polynucleotides instruct the metabolic machinery to start making viral proteins, which then self-assemble into oncolytic viral particles. The particles can replicate, express transgenes and cause cell lysis. 

Ashburn said Oncorus has data showing the idea works in two different preclinical models. Biopsies of the animals showed viruses encoded for by the polynucleotides had infected tumors, giving Oncorus the confidence to push ahead with plans to nominate a clinical candidate by early next year. 

The potential of the two platforms enabled Oncorus to bring Cowen Healthcare Investments and Perceptive Advisors on board as co-leads of the series B. Organizations that participated in the series A, including Celgene and Astellas Venture Management, also contributed to the latest financing.