Express | 89% tumor growth control rate! Announcement of clinical trial results of innovative virus-like drug conjugates

▎WuXi AppTec Content Team Editor

Aura Biosciences today announced results of an interim analysis of a Phase 2 clinical trial of its innovative viroid drug conjugate (VDC) therapy belzupacap sarotalocan (AU‑011). The data support the potential of this therapy as first-line therapy for patients with early-stage choroidal melanoma. Detailed trial data will also be announced at the 2022 American Academy of Ophthalmology (AAO) annual meeting.

Choroidal melanoma is a cancer that arises from melanocytes within the choroidal stroma. The choroid is a sponge-like membrane located at the back of the eye, between the sclera (the white part of the eye) and the retina. The retina is responsible for transmitting visual information to the brain, and the choroid, which is rich in blood vessels, is responsible for supplying nutrients to the retina. When choroidal melanoma tumors expand, they can cause retinal detachment, which can lead to blindness. Such tumors may also metastasize to other parts of the body, such as the liver, causing death. It is worth mentioning that 80% of patients with choroidal melanoma are diagnosed at the early stage of the disease, but to date there are no approved treatments available.

▲Aura tumor targeting platform (Image source: Reference [3])

Aura’s tumor targeting platform is a technology developed to couple Virus-Like Particles to cytotoxic drugs. Virus-like drug conjugates can target various types of solid tumor cells by identifying tumor-associated heparan sulfate proteoglycan (HSPG) on the cell surface, and have the flexibility to replace different poisoning drugs. Belzupacap sarotalocan is an innovative virus-like drug-drug conjugate. Its single virus-like particle can bind to about 200 phthalocyanine dye molecules. When the drug is connected to the tumor through the HSPG on the cell surface, 689 nm light can stimulate the production of singlet oxygen, damage the cell membrane and various organelles, and then cause tumor cell necrosis. Meanwhile, the damaged tumor cells will release damage-associated molecular pattern (DAMP) molecules to activate antigen-presenting cells (APCs), thereby triggering subsequent immune-mediated tumor cell killing responses.

▲Clinical trial design (Image source: Reference [3])

This phase 2 trial was designed to examine the safety and preliminary efficacy of multiple ascending doses of belzupacap sarotalocan. The drug is injected through the choroid for up to 3 cycles in patients with early-stage choroidal melanoma (indeterminate and small choroidal melanoma, IL/CM). A total of 20 patients were enrolled and assigned to 6 different cohorts.

Data results show that patients in cohorts 5 and 6 who received 3 cycles of treatment had a statistically significant tumor growth rate compared to the information recorded at the time of enrollment. significantly improved (-0.296 mm/yr, p = 0.0007). In addition, most of these patients have tumors close to the center of vision and are at high risk of blindness.In an average follow-up period of 6 months, the tumor growth of the patients was controlled, and the patients’ vision preservation rate reached 88.9 % (8/9).

▲Clinical trial design (Image source: Reference [3])

Belzupacap sarotalocan has a favorable safety profile, with no dose-limiting toxicities or serious treatment-related adverse reactions observed.

▲Clinical trial results (Image source: Reference [3])

“Preliminary analysis of data from this Phase 2 clinical trial via choroidal injections showed tolerability of up to 3 cycles of therapy, as well as dose-related antitumor responses. These results further provide Clinical evidence supports belzupacap sarotalocan as a potential innovative target therapy for this disease to treat early stage patients via choroidal injection,” said Cadmus Rich, PhD, Head of R&D and Chief Medical Officer at Aura.

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