Single Low Dose of Bel-sar Shows Multiple Complete Responses in NMIBC Phase 1 Trial

Aura Biosciences, Inc. (NASDAQ: AURA) has shared promising early outcomes from its ongoing Phase 1 clinical trial of bel-sar (AU-011) in patients with non-muscle invasive bladder cancer (NMIBC). The trial, which aims to assess the safety and feasibility of bel-sar with and without light activation, currently involves 13 patients. The primary goal is to evaluate the safety and feasibility of local bel-sar administration alone (n=5) and in combination with light activation (n=8). Secondary goals include assessing biological activity and immune-mediated changes within the tumor microenvironment (TME).

Among the 13 participants, 10 had low-grade disease, aligning with the approximate 70% incidence of low-grade disease in NMIBC patients, while the remaining three had high-grade disease. Results indicated that among patients treated with bel-sar and light activation (n=8), four out of five patients with low-grade disease achieved a clinical complete response, meaning no tumor cells were detected upon histopathological analysis. Additionally, two out of three patients with high-grade disease showed visible tumor shrinkage during cystoscopy.

Dr. Sabine Brookman-May, Senior Vice President of Urologic Oncology at Aura Biosciences, expressed optimism regarding the data, highlighting bel-sar’s potential to revolutionize cancer treatment. The trial observed rapid tumor responses and immune effects such as CD8+ T-cell infiltration within days of administering a single low dose. Aura plans to expand the current Phase 1 trial while preparing for a Phase 2 trial to further explore bel-sar’s clinical activity and response durability.

Dr. Neal Shore, Medical Director at Carolina Urologic Research Center, also commented on bel-sar’s potential to redefine NMIBC treatment. The early data suggested that the positive clinical activity and evidence of a bladder urothelial field effect with a single dose could position bel-sar as the first immune ablative treatment for early-stage bladder cancer, administered as an in-office procedure.

Bel-sar is a virus-like drug conjugate designed to induce direct tumor cell necrosis and trigger a durable anti-tumor immune response. The ongoing Phase 1 trial (NCT05483868) is structured in two parts to assess bel-sar’s safety and feasibility as a monotherapy. The treatment is administered 7 to 12 days before a scheduled transurethral resection of bladder tumor (TURBT), a standard care procedure, followed by a 56-day safety monitoring period. The study also evaluates bel-sar’s biological activity through histopathological evaluation of tissue samples collected during TURBT to examine focal necrosis and immune changes within the TME.

Part 1 of the trial, which included five patients treated with a single dose of bel-sar without light activation, has been completed. Part 2, involving 10 patients, is ongoing. Eight patients with confirmed tumors at the time of treatment received either 100ug or 200ug of bel-sar as a single dose. Among these, five had low-grade disease and three had high-grade disease. Most participants had recurrent bladder cancer and had undergone multiple TURBTs and additional treatments before joining the trial.

Safety data as of September 9, 2024, indicated that bel-sar was well-tolerated, with less than 10% of patients reporting Grade 1 drug-related adverse events and no Grade 2 or higher events. No serious adverse events were reported, and there were no significant differences between light-activated and non-light activated groups.

Biological activity data from the eight patients receiving bel-sar with light activation showed clinical activity as early as seven days post-treatment. This was evidenced by clinical complete responses, necrosis, immune activation, or visual tumor shrinkage. Four out of five patients with low-grade disease achieved a clinical complete response, with no tumor cells detected in both treated target and untreated non-target tumors. Additionally, two out of three patients with high-grade disease exhibited visual tumor shrinkage during cystoscopy. Immune activation was observed across all patients in both treated and untreated bladder tumors, indicating a broader immune response within the bladder.

Aura Biosciences will host a Virtual Urologic Oncology Investor Event to discuss these early Phase 1 data.