Therapy Areas: Inflammatory Diseases
Aura Biosciences Presents Updated Phase 1b/2 Clinical Data for AU-011
31 October 2018 - - US-based ocular oncology therapies developer Aura Biosciences has presented updated clinical data from its Phase 1b/2 clinical trial evaluating the safety and efficacy of light-activated AU-011, the company's lead product candidate for the primary treatment of choroidal melanoma, in an oral presentation at the American Academy of Ophthalmology 2018 annual meeting being held October 27-30, 2018, at McCormick Place in Chicago, the company said.

This open-label, multicenter trial is designed to investigate single and multiple ascending doses of light-activated AU-011 in approximately 36 adult subjects with clinically diagnosed primary choroidal melanoma.

The data presented at the meeting show that multiple administrations of light-activated AU-011 are well-tolerated with no related serious adverse events, severe adverse events or dose-limiting toxicities observed.

Drug related adverse events were all expected and included anterior chamber inflammation, posterior chamber inflammation and increase in intraocular pressure, but all were manageable with standard-of-care treatments and resolved without clinical sequelae.

Notably, the posterior inflammation appears to originate within and/or around the tumor which is consistent with AU-011's mechanism of action of acute tumor necrosis.

Treatment with light-activated AU-011 achieved preservation of best corrected visual acuity with a mean change of -1.06 letters at 6 months and a mean change of -0.75 letters at 12 months.

BCVA was preserved even in high risk patients with tumors close to the fovea or the optic disk, a factor that typically correlates with a higher risk of irreversible severe vision loss following radioactive treatments. Importantly, all patients achieved stable disease at the prespecified preliminary efficacy endpoint at 3 months.

Biological activity has been confirmed with long term tumor control in those patients with documented growth before treatment, reduction in tumor thickness and localized inflammation around the tumor. An expansion cohort of the study is currently underway.

The company plans to initiate a pivotal Phase 3 clinical programme following the Phase 1b/2 study.

Choroidal melanoma is a rare and aggressive type of eye cancer. Choroidal melanoma is the most common primary ocular tumor and develops in the uveal tract of the eye.

No targeted therapies are available at present, and current radiotherapy treatments can be associated with severe visual loss and other long-term sequelae such as dry eye, glaucoma, cataracts and radiation retinopathy.

The most common current treatment is plaque radiotherapy, which involves surgical placement of a radiation device on the exterior of the eye over the tumor. The alternative is enucleation, or total surgical removal of the eye.

Choroidal melanoma metastasizes to the liver in about 40-50% of cases in the long term (source: OMF), and only 15% of patients whose melanoma has metastasized survive beyond five years after diagnosis (source: ACS).

Light-Activated AU-011 is a first-in-class targeted therapy in development for the primary treatment of choroidal melanoma.

The therapy consists of proprietary viral-like particle bioconjugates that are activated with an ophthalmic laser. The VPBs bind selectively to unique receptors on cancer cells in the eye and are derived from technology originally pioneered by Dr. John Schiller of the Center for Cancer Research at the National Cancer Institute, recipient of the 2017 Lasker-DeBakey Award.

Upon activation with an ophthalmic laser, the drug rapidly and specifically disrupts the cell membrane of tumor cells while sparing key eye structures, which may allow for the potential of preserving patients' vision and reducing other long-term complications of radiation treatment.

AU-011 can be delivered using equipment commonly found in an ophthalmologist's office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted orphan drug and fast track designations by the US Food and Drug Administration and is currently in clinical development.

Aura Biosciences is developing a new class of therapies to selectively target and destroy cancer cells. Its lead programme, AU-011 in primary choroidal melanoma, is being developed under a CRADA with the National Cancer Institute, part of the National Institutes of Health.
Login
Username:

Password: