Aura Biosciences, which is developing a new class of virus-like drug conjugates for the treatment of cancer, has gone public by an initial public offering (IPO) on the NASDAQ.
Aura’s technology platform relies on recombinant virus-like particles (VLPs) derived from human papillomavirus (HPV) that can be loaded (conjugated) with therapeutic agents, ultimately forming a new class of targeted drugs.
Heparan sulfate proteoglycans (HSPGs) are a large family of molecules in the extracellular matrix (ECM) and on cell membranes. Tumors modify HSPGs through key sulfate modifications that provide high specificity of binding to a number of ligands. Tumor-modified HSPGs regulate many aspects of tumor progression, including proliferation, invasion, angiogenesis, and metastasis. Aura’s VLPs selectively bind to tumor-modified HSPGs, bypassing normal cells.
Virus-like drug conjugates (VDCs) are a new class of drugs with a dual mechanism of action that promotes the death of malignant cells both by delivering a cytotoxic payload that causes acute necrosis and by creating a highly immunogenic environment that activates a secondary immune-mediated anti-tumor response. In fact, VDCs are analogous to the well-known monoclonal antibody conjugates (ADCs), which have a very limited ability to carry a drug load.
A single VDC is capable of delivering hundreds of cytotoxic molecules conjugated to its capsid proteins. Because of VLP’s ability to selectively recognize specifically modified and overexpressed HSPG present on many tumor types, VDCs have the potential to be used in the therapy of a wide range of cancers without binding to normal cells, which helps limit off-target toxicity. Because VDCs have a large number of HSPG binding sites, this multivalency ensures strong and selective binding to tumor cells.
Aura’s main drug candidate is AU-011, or belzupacap sarotalocan, for the first-line treatment of primary choroidal melanoma, the most common intraocular cancer in adults. Choroidal melanoma accounts for approximately 90% of all cases of uveal melanoma, which includes melanomas in the choroid (vascular layer), ciliary body, and iris; collectively, they form the uveal tract. In the vast majority of cases, the disease is diagnosed at an early stage without clinical signs of metastasis. Despite modern methods of treating choroidal melanoma with radiation, the long-term prognosis is poor; more than half of patients die.
AU-011, injected intravitreally, selectively binds to the surface of choroidal melanoma cells. VDCs then deliver a potent cytotoxic photosensitizer (phthalocyanine dye IRDye 700DX) into the cells, which is then activated by a near-infrared laser. Because of the targeting binding of VDCs to the tumor cells, the generation of singlet oxygen in close proximity to the cell membrane causes its physical destruction, leading to acute cellular necrosis. The process also triggers natural anti-tumor immunity, which attracts the patient’s innate immune system, which detects and destroys neighboring cancer cells.
AU-011 successfully completed the NCT03052127 phase 1b/2 clinical trial, demonstrating statistically significant reduction in tumor growth rates and high levels of tumor suppression with preservation of visual acuity in patients with small primary choroidal melanoma whose tumors were characterized by active growth.
Now Aura is conducting the NCT04417530 phase 2 clinical trial, which is testing first-line suprachoroidal administration of AU-011 in patients diagnosed with a primary indeterminate lesions and small choroidal melanoma.
Aura plans to launch a pivotal clinical trial of AU-011 in the second half of 2022. AU-011 is also being studied in the treatment of choroidal metastases. Intentions have been expressed regarding the applicability of AU-011 in the therapy of non-invasive bladder cancer.