Onchilles Pharma is harnessing a new cancer-killing pathway to tackle solid tumors.
The San Diego-based biotech has shown that when N17350 is injected directly into the tumor, the vaccine-like therapeutic is even able to clear cancer lesions that are distant from the injected tumor.
N17350 is a therapeutic elastase, a type of serine protease, which targets the ELANE pathway in cancer cells. This pathway was first identified in the lab of Onchilles co-founder Lev Becker, Ph.D., where he saw that neutrophils release ELANE to kill cancer cells. Healthy cells are spared because the elevated levels of histone H1 are only seen in cancer cells.
“It's novel in the sense that cancer hasn't seen this molecule before,” Onchilles CEO Court Turner explained to Fierce.
When N17350 enters the cancer cell, it releases the CD95 death domain, which is in charge of triggering programmed cell death, called apoptosis. Once the CD95 is free, it binds to histone H1 to trigger cell death. The cells then release antigens specific to the patient’s tumor that recruit the immune system, resulting in a vaccine-like killing effect.
“I wouldn't describe N17350 as a vaccine,” Turner pointed out. “I would say that the systemic immune response is a result of the action of our drug.”
Onchilles is already putting its theory to the test in a phase 1/2 open-label, dose-finding and expansion study in patients with advanced solid tumors. The biotech dosed its first patient in June and is currently enrolling participants across nine sites in Australia and the U.S.
The initial data, which was reported at the annual meeting of the Society for Immunotherapy of Cancer on Saturday, is from the initial dose-finding portion of the study and includes three patients. There were no dose-limiting toxicities seen when these patients received 1 mg/mL of N17350, Onchilles noted.
“There is no direct cancer cytotoxic medicine out there that doesn't also kill nearby immune cells or normal cells,” Turner said. “We’re able to treat them without any dose-limiting toxicities and without any adverse events associated with drugs. Because the drug appears to be safe and effective, we can move to earlier and earlier lines of therapy.”
One patient with Merkel cell carcinoma, a rare and aggressive skin cancer, received a single injection of N17350 into one of the six lesions on their body. Eight weeks later, all five non-injected lesions were also undetectable, based on the response evaluation criteria in solid tumors, a test used to measure how well a solid tumor responds to treatment.
The second, dose-escalation portion of the study includes a total of six patients so far, including the Merkel cell carcinoma patient alongside participants with angiosarcoma, leiomyosarcoma, breast cancer and two melanoma patients. All of these tumor types are superficial lesions that can be easily injected with N17350.
Onchilles aims to take the therapy to visceral tumor types—a term for a tumor that develops in an internal organ—once the study moves to the next dose level. The plan is to eventually dose around 70 patients, Turner told Fierce.
“Once we get through about 70 patients, we would go into a phase 2 dose-expansion study of five specific tumor types, including things like lung cancer, head and neck cancer and a few others,” the CEO said.
Turner foresees this study occurring towards the third quarter of next year, he added.
Onchilles spun out of the University of Chicago back in 2017 and raised a $25 million series A1 financing last year to advance N17350 proof-of-concept studies.