With its lead candidate in a phase 3 trial for a rare eye cancer, Aura Biosciences is looking to expand the drug into a more common disease: bladder cancer.
In a phase 1 trial in patients with non-muscle invasive bladder cancer, Aura’s viruslike drug conjugate (VDC) bel-sar—along with infrared light activation—completely eradicated the tumors of four out of five patients with low-grade disease, the company said in an Oct. 17 release.
The trial so far includes 13 patients, with five receiving bel-sar alone and eight receiving bel-sar with light activation. The four patients who saw their tumors completely eliminated had low-grade disease and were in the light activation group.
The treatment also activated patients’ immune systems, with effector CD8+ and CD4+ T cells successfully infiltrating tumors, according to the biotech.
“Bel-sar is ideally suited for the treatment of early-stage local cancers,” Elisabet de los Pinos, Ph.D., founding CEO of Aura, said in an interview with Fierce Biotech. “If we can treat early-stage disease with something that's extremely potent yet very safe, that preserves the function of the organ and stimulates the immune system, we have something that's so much better than the surgery.”
There were no grade 2 or higher adverse events, the company said, and fewer than 10% of patients experienced grade 1 adverse events.
Bladder cancer is often detected early, with about 70% to 80% of new cases being early-stage disease. It is the fourth most common cancer seen in men, and it makes up about 4% of all cancer cases in the U.S.
Aura’s VDCs are modified human papillomavirus particles that have no DNA and therefore can’t replicate inside the body. They bind to a type of glycosaminoglycan commonly expressed by cancer cells but not by healthy cells. This makes them well suited for delivering toxic payloads to tumors while leaving normal tissue alone.
With bel-sar, the cancer-killing chemicals used are photosensitizers. Exposing these chemicals to a certain wavelength of infrared light activates them, and they then begin to produce toxic reactive oxygen species that break down the membranes of cancer cells.
Tumors normally hide from the immune system, de los Pinos said, but now “suddenly, by a big bang,” the VDCs are “exposing new antigens to the immune system.”
In this way, bel-sar activates the immune system against cancer cells throughout the bladder, even in tumors not near the injection site, the company said in the release.
Bel-sar can be injected and light-activated using tools already common in a urologist’s office, Sabine Brookman-May, M.D., Aura’s new senior vice president and therapeutic area head of urologic oncology, said in a joint interview with de los Pinos. Brookman-May joined Aura two weeks ago, she said, after a 12-year stint at Johnson & Johnson, where she most recently served as vice president of bladder cancer development.
The treatment process includes an "endoscopic procedure, doing the injection, but also the laser activation,” Brookman-May explained. “It would be as easy as it can be done [on] a surface of an eye, also within the bladder.”
The portion of the trial where patients didn't receive light activation is complete, while the second part—where eight patients received either 100 micrograms or 200 micrograms of a single bel-sar dose with light activation—is still ongoing. All of the patients received a transurethral resection of bladder tumor surgery seven to 12 days after treatment, even though some of the patients no longer had their tumors, so no one was put at risk.
“In clinical practice, when this drug is approved, it will be immune ablative,” de los Pinos said. “You will use the drug and the immune system to do what currently the surgery is doing.”
With bel-sar, Aura hopes to avoid bladder cancer recurrence, which is common when patients have their tumors removed surgically. This creates a big treatment burden for patients, Brookman-May said, and also increases the chance that the cancer will progress.
Aura is now looking to expand the phase 1 trial to include a few more patients, Brookman-May said, in order to optimize the injection method, treatment schedule and dose. The company is also preparing for a phase 2 study, which it hopes to initiate as quickly as possible.
Because bel-sar’s mechanism of action is not specific to any one disease, de los Pinos said, Aura is also exploring its potential in other indications. These include esophageal, colon and lung cancers.
“There's just so much opportunity in early-stage disease that is local, and it's amenable to our treatment,” de los Pinos said. “The reality is that you don't change that much from a local administration in the eye to a local administration in the bladder or potentially in the lung. You're talking about the same order of magnitude. So, we envision being able to go very quickly.”