Aura Biosciences, Inc. has released positive phase 2 clinical data evaluating its lead candidate, belzupacap sarotalocan (bel-sar; AU-011), for the treatment of early-stage choroidal melanoma.
First up: Aura.
Headquartered in Boston, Massachusetts, the clinical-stage biotechnology company is developing precision therapies for “high unmet need cancers”—all with the goal of preserving organ function.
- These diseases: Cancers with either no FDA-approved drugs or that are “poorly managed with current available treatments.” In ocular oncology, these include:
- Primary choroidal melanoma
- Choroidal metastasis
- Cancers of the ocular surface
And how is it doing this?
Via a novel oncology technology platform targeting a wide range of solid tumors using virus-like particles (VLPs) derived from the human papillomavirus (HPV) that are designed to be used as oncology therapeutics.
- In turn: These VLPs can be loaded or conjugated with drugs to create a new class of targeted therapies: virus-like drugs conjugates (VDCs).
Talk about these VDCs.
Aura’s novel class of drugs feature a “dual mechanism of action (MOA) that promotes cancer cell death by both the delivery of the cytotoxic payload to generate acute necrosis and by activating a secondary immune mediated response,” according to the company.
Note: “Cytotoxic” refers to a substance that kills cells (ie: cancer cells), while a “payload” is designed to kill target (cancer) cells when internalized and released.
- See the key advantages to using VDCs in these targeted therapeutic areas
Alrighty, now explain bel-sar.
As the company’s lead VDC therapy, bel-sar is designed to be combined with an anti-cancer agent (a novel light-activated cytotoxin) and injected into the eye via suprachoroidal delivery.
How it works: By selectively binding to the cell membrane of choroidal melanoma cells, the therapeutic targets and destroys cancer cells, which—in turn—triggers the immune system to potentially create a long-lasting immunity for tumors.
Okay, now I’m ready for this phase 2 trial.
The open-label, ascending single- and repeat-dose escalation phase 2 trial (NCT04417530) evaluated the safety, tolerability, and preliminary efficacy of up to four dose levels (and repeat dose regimens) of three cycles of bel-sar with one or two laser applications per treatment.
- The participants: 22 patients (aged 18+) diagnosed with early-stage CM (see all criteria)
- The setup: Six cohorts, including
- Cohort 1 (low-dose bel-sar + 1 laser application)
- Cohort 2 (medium-dose bel-sar + 1 laser application)
- Cohort 3 (medium-dose bel-sar + 2 laser applications)
- Cohort 4 (highest-tolerated dose bel-sar + laser applications from Cohorts 1-3)
- Both administered weekly for 2 treatments
- Cohort 5 (bel-sar + laser applications from Cohorts 1-3)
- Administered weekly for 3 treatments
- *Up to 2 cycles for this may be administered, with option for participants to receive a third
- Administered weekly for 3 treatments
- Cohort 6 (high-dose bel-sar + laser applications)
- Both administered weekly for 3 treatments (up to 3 cycles of treatments)
- Study duration: 52 weeks with 12-month follow-up period
And what was measured?
Measured at 52 weeks, the outcomes included:
- Primary
- Visual acuity (VA) preservation, as determined by treatment-related adverse events (TRAEs) and treatment-related serious AEs (SAEs)
- Secondary
- Within-subject difference of historical tumor thickness growth rate
- Post-treatment growth rate
- Time to reach tumor progression
And this data?
Aura reported that bel-sar “achieved an 80% tumor control rate (n = 8/10)” among the phase 3-eligible patients who underwent the therapeutic regimen.
- Also for these patients: Tumor growth completed stopped following treatment
- The numbers: Post-treatment average growth rate was 0.011 mm/yr among responders versus 0.351 mm/yr prior to study entry (p < 0.0001)
Did any patients achieve VA preservation?
Out of those same 10 patients—90%.
And of those patients, 80% had been at a “high risk for vision loss with tumors close to the fovea or optic disc,” Aura reported.
Let’s talk safety profile.
The company noted that bel-sar’s was “highly favorable in all participants regardless of dose,” and that no treatment-related SAEs were reported.
What about other AEs?
Ocular TRAEs were observed as mild, including
- Anterior chamber inflammation (18%)
- Anterior chamber cell (9%)
Both of these were resolved without any aftereffects, with ~70% being self-limited, requiring no treatment, and were resolved within a median of 6 days.
And for those AEs requiring treatment?
Topical steroids administered for (a median of) 6 days successfully resolved any inflammation, while mild eye pain was reported in 9% of patients, according to Aura.
And important to note: There were no reports of treatment-related posterior inflammation events.
What’s significant about this data?
Per Ivana Kim, MD, who presented the end-of-study findings during The Retina Society Annual Meeting in Lisbon, Portugal, these latest findings support the potential for bel-sar “to become the first treatment that achieves the dual goals of treating the tumor while also preserving vision, which could change the treatment paradigm for patients with this disease.”
- Note: Dr. Kim is director of the Ocular Melanoma Center at the Massachusetts (Mass) Eye and Ear and an associate professor of Ophthalmology at Harvard Medical School, in Boston, Massachusetts.
Nice! So what’s next?
The company plans to continue advancement of the bel-sar clinical program with ongoing enrollment for its global phase 3 CoMpass trial (NCT06007690), according to Jill Hopkins, MD, Aura chief medical officer (CMO) and president of Research and Development.
- Note: Patient enrollment (expected to be an estimated 100 participants) commenced in December 2023.
Anything special to know about this trial?
Well ... The FDA has already given Aura a written agreement under a Special Protocol Assessment (SPA) to the study’s design and planned analysis.
Essentially: The trial has been deemed adequate by the federal agency and, if successful, would “address the objectives necessary to support Aura’s planned biologics license application submission,” Aura reported.