FDA Grants Fast Track Designation to Belzupacap Sarotalocan for Non–Muscle Invasive Bladder Cancer

The FDA has granted a fast track designation to belzupacap sarotalocan (AU-011) for the treatment of patients with non–muscle invasive bladder cancer (NMIBC), representing the first virus-like drug conjugate (VDC) candidate therapy from Aura Biosciences, Inc., the drug developer.¹

The planned phase 1 clinical trial of belzupacap sarotalocan will assess the safety and early proof of mechanism, distribution, local necrosis, and evidence of immune activation in this population. The company plans to launch the trial in the second half of 2022, with preliminary data expected in 2023.

“We are pleased that belzupacap sarotalocan has been granted fast track designation,” Mark De Rosch, PhD, FRAPS, chief operating officer and head of Regulatory Affairs at Aura Biosciences, Inc., stated in a press release. “We believe that, given that NMIBC presents such a high unmet medical need, the opportunity for more frequent interactions with Division of Oncology at FDA and the potential for priority review will be valuable as we advance further into clinical development in patients with NMIBC.”

AU-011 is a first-in-class VDC therapy in which the virus-like component of the agent selectively binds unique heparin sulphate proteoglycans (HSPGs), which are modified and overexpressed on the tumor cell surface of malignant cells in the choroid so that a potent cytotoxic drug that is activated with infrared light can be delivered.²

Following activation with an ophthalmic laser, the cytotoxic drug rapidly and specifically disrupts the cell membrane of malignant cells with a pro-immunogenic cell death that can activate the immune system producing sustained antitumor immunity. The unique specificity of tumor binding by the VDC enables the preservation of key eye structures, which may facilitate preserved patient vision and reduce other chronic complications of radiation treatment.

Notably, AU-011 can be administered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, providing a potentially less invasive, more convenient therapeutic option for patients and physicians.

Belzupacap sarotalocan previously received fast track and orphan drug designations from the FDA for the treatment of patients with choroidal melanoma and is currently under evaluation in a phase 2 trial (NCT04417530) in this population.

Data demonstrating the agent’s preclinical activity were presented during the 2022 Genitourinary Cancers Symposium.³ In a panel of human bladder cancer cell lines that comprised different stages of disease, AU-011 demonstrated consistent tumor cell binding and cytotoxicity in vitro, suggesting that the agent’s targeting of bladder cancer cells through HSPGs is tumor grade agnostic.

Moreover, tumor binding and distribution of AU-011 was seen in both ex vivo human bladder cancer tissues and in an in vivo murine bladder cancer model, suggesting that further evaluation of AU-011 in patients with urothelial neoplasia is warranted.

“NMIBC has no approved targeted therapies, and patients experience high levels of recurrence and progression, ultimately leading to cystectomy or the removal of the entire bladder,” Cadmus Rich, MD, chief medical officer and head of R&D of Aura, stated in the press release. “This milestone supports our goal to advance the development of belzupacap sarotalocan for patients with NMIBC in need of better and earlier targeted treatment options with the potential to help preserve the bladder.”

References

1. Aura Biosciences receives FDA fast track designation for belzupacap sarotalocan (AU-011) for the treatment of non-muscle invasive bladder cancer. News release. Aura Biosciences, Inc. June 30, 2022. Accessed July 6, 2022. https://bwnews.pr/3Pd1x2R
2. Aura Biosciences to present preclinical data demonstrating applicability of AU-011 in bladder cancer at the 2022 ASCO Genitourinary Cancer Symposium. News release. Aura Biosciences, Inc. February 14, 2022. Accessed July 6, 2022. https://bwnews.pr/3RfSWhx
3. Aura Biosciences presents final phase 1b/2 data for its first virus-like drug conjugate, AU-011, in patients with choroidal melanoma at the American Academy of Ophthalmology 2021 Annual Meeting. News release. Aura Biosciences, Inc. November 15, 2021. Accessed July 6, 2021. https://bwnews.pr/3NNrRzo