Introduction:

Bladder cancer remains a significant global health burden, ranking as the ninth most common cancer globally and the sixth most common in the U.S. Of the newly diagnosed cases, approximately 70-80% are diagnosed as Non-Muscle Invasive Bladder Cancer (NMIBC). Despite the generally favorable survival rates, recurrence and progression after standard of care transurethral resection of bladder tumor (TURBT) and adjuvant intravesical therapy remain high. Frequent recurrences increase the cumulative risk for short- and long-term impairment of bladder function due to repeat TURBT and adjuvant instillation therapies.  Over time, this escalating treatment burden may lead to consideration of radical cystectomy in patients whose disease remains refractory and whose bladder function becomes compromised.  Consequently, there is an urgent need for innovative, effective, function- and organ- preserving therapies in NMIBC, designed to reduce recurrence, progression risk and repeat burdensome treatments. A front-line, focal immunotherapy applied in an ablative or neo-adjuvant approach may obviate the need for TURBT and adjuvant treatments by generating initial tumor necrosis followed by long-lasting specific antitumoral immune memory. Such a meaningful advancement would disrupt the current therapeutic landscape, addressing both oncological outcomes (durable complete response and recurrence-free survival) and quality of life (QoL) in patients with NMIBC.

Belzupacap sarotalocan (AU-011) is a drug-device combination product consisting of a virus-like drug conjugate (VDC) and a laser photoactivation system delivering 689 nm light to activate the drug.  The drug product is a non-replicating virus-like particle (VLP) conjugated to a novel photosensitizer. AU-011 is administered via focal injection at the tumor base using a cystoscopic approach. Tumor specificity of AU-011 is achieved through selective tumor binding of its VLP component to modified glycosaminoglycans (GAGs) on the surface of tumor cells. Following light activation delivered at time of office cystoscopy by a standard laser, the dye component catalyzes the production of reactive oxygen species. This results in a potent and selective acute tumor cell necrosis without harming surrounding healthy cells. Acute cellular necrosis represents a type of immunogenic cell death that involves the release of damage associated molecular patterns (DAMPS) and tumor-specific neoantigens that result in effector immune cell infiltration and activation, promoting subsequent immune-mediated tumor clearance and long-term antitumor immunity.

Such effects have been demonstrated in over 100 cell lines and 15 different animal tumor models. This preclinical data supports the positive Phase 2 end of study results evaluating AU-011 for the first-line treatment of early choroidal melanoma (CM), a vision and life-threatening ocular cancer. The phase 2 results in CM showed that AU-011 achieved 80% tumor control rate (n=8/10) at 12 months, demonstrating durability of response with a highly favorable safety profile and preservation of visual function.

Methods:

Aura is conducting a multi-center, open-label Phase 1b/2 clinical trial AU-011-102 (NCT05483868) in participants with urothelial carcinoma of the bladder to assess the safety and preliminary efficacy of focal administration of AU-011 at time of office-based cystoscopy. A total of 16 participants with both low and high grade NMIBC were previously treated as part of an initial, “window of opportunity” study prior to standard of care therapy TURBT. Seven to 12 (+7) days before planned TURBT, participants received either a single 100 µg AU-011 dose without light activation (n=5) or AU-011 with near-infrared (690 nm) light activation (n=11) across two dose levels (100 µg and 200 µg). Central histopathologic assessment determined tumor response, and safety assessment continued for 56 days after AU-011 treatment.

As previously reported at the EAU 2025 Congress, among 16 safety-evaluable participants (56-day follow-up) receiving a single dose of AU-011 ± light activation, no drug-related grade 2+ AEs, serious AEs, or dose-limiting toxicities were reported.  By design, 5 participants received drug only without light activation and therefore were not evaluated for efficacy. Among 10 efficacy-evaluable participants who received both drug and light activation, 5 had low-grade (LG) and 5 high-grade (HG) disease. Clinical Complete Response (cCR), defined as no tumor cells on TURBT histopathology, was seen in 4/5 participants with LG treated tumors, with 3/5 LG participants also achieving cCR in remote, non-treated tumors. Visual tumor shrinkage was observed in 3/5 HG participants, and 1/5 HG participants demonstrated a cCR in both the treated tumor and a non-treated tumor.  Immune activation was noted in all efficacy-evaluable participants in both target and non-target bladder tumors. Four out of 7 patients with multiple tumors demonstrated a cCR in at least one non-target tumor with infiltration of effector CD8+ and CD4+ T-cells. This data provides evidence of a urothelial field effect. 

Given these encouraging early signs of drug activity, Aura is evaluating in the Phase 1b/2 trial multiple dosing schedules across two dose levels (200-400 µg), and two distinct treatment paradigms—immune-ablative and neoadjuvant—in participants with NMIBC. Approximately 26 participants across intermediate- and high-risk NMIBC will receive two cycles of focally administered AU-011 followed by laser activation approximately 24-hour post injection. In the immune-ablative cohorts, TURBT is not mandated, allowing for assessment of AU-011’s potential to achieve complete tumor ablation and generate systemic immune memory. In the neoadjuvant cohorts, participants receive two cycles of AU-011 prior to a TURBT approximately four weeks after treatment. For both approaches, patients will be monitored for response assessments and recurrence at 3, 6, 9, and 12 months.  Endpoints of this trial include multiple efficacy assessments, such as complete response rate at 3 months and durability of response up to 12 months in the immune ablative cohorts and recurrence-free survival in the neoadjuvant cohorts. Patients will also be monitored for safety.

The trial is actively enrolling at multiple sites, with participants to be distributed across immune-ablative and neoadjuvant treatment cohorts.

Results:

Conclusion:

Funding: Aura Biosciences