Aura Biosciences, Inc. (NASDAQ:AURA) is a clinical-stage biotechnology company developing precision immunotherapies to treat solid tumors. The company's proprietary platform is designed to enable the targeting of a broad range of solid tumors using Virus-Like Particles (VLPs) that can be conjugated with drugs or loaded with nucleic acids to create Virus-Like Drug Conjugates (VDCs). Aura's lead VDC candidate, bel-sar, is currently being evaluated in multiple oncology indications, including small choroidal melanoma, choroidal metastases, and bladder cancer.
Business Overview
Aura's initial focus is in ocular and urologic oncology, areas of high unmet medical need where local targeted therapies may enable early intervention. The company's lead candidate, bel-sar, is a novel biologic for which the intended use in ocular oncology requires delivery to the suprachoroidal space and activation by a laser. Bel-sar consists of a human papilloma virus (HPV)-derived VLP conjugated to hundreds of infrared laser-activated molecules. The VDC is designed in a way that prevents the conjugation from interfering with tumor binding, enabling its selectivity to tumor cells but not to normal cells. Laser activation of bel-sar is designed to result in precise tumor cell killing with minimal damage to surrounding healthy tissues.
Aura is currently evaluating the safety and efficacy of bel-sar as a potential vision-sparing therapy in an ongoing global Phase 3 CoMpass trial for the first-line treatment of adult patients with small choroidal melanoma and indeterminate lesions. Bel-sar is also being explored for choroidal metastases and cancers of the ocular surface, and is in Phase 1 clinical development in bladder cancer.
Financials
Aura has funded its operations primarily through the sale of convertible preferred stock, common stock, and warrants. As of March 31, 2023, the company had cash and cash equivalents and marketable securities of $202.9 million, which management believes will enable it to fund its operating expenses and capital expenditure requirements into the second half of 2026.
For the three months ended March 31, 2023, Aura reported a net loss of $19.7 million, compared to a net loss of $17.5 million for the same period in 2022. The company's research and development expenses increased to $17.1 million for the three months ended March 31, 2023, from $14.4 million for the same period in 2022, primarily due to ongoing clinical costs related to the progression of the Phase 2 study of bel-sar in early-stage choroidal melanoma and CRO costs associated with the advancement of the Phase 3 trial of bel-sar in the same indication, as well as higher personnel expenses related to the company's growth.
Aura's general and administrative expenses increased to $5.3 million for the three months ended March 31, 2023, from $5.0 million for the same period in 2022, primarily driven by personnel expenses and increases in general corporate expenses related to the company's growth.
For the full year 2022, Aura reported an annual net loss of $76.4 million, with no revenue generated. The company's annual operating cash flow was -$63.8 million, and its annual free cash flow was -$64.6 million.
Regulatory and Clinical Developments
Aura has received Orphan Drug Designation for bel-sar for the treatment of uveal melanoma from the FDA and EMA, as well as Fast Track designation from the FDA for the treatment of choroidal melanoma and bladder cancer. The company has also obtained written agreement from the FDA under a Special Protocol Assessment (SPA) for the design and planned analysis of the global Phase 3 CoMpass trial evaluating bel-sar in early-stage choroidal melanoma.
The ongoing Phase 3 CoMpass trial is a global, randomized, multi-center, masked study designed to enroll approximately 100 patients with small choroidal melanoma and indeterminate lesions. The trial is comparing bel-sar versus sham delivered via suprachoroidal injection followed by laser light activation, with the primary endpoint being time to tumor progression.
Interim 12-month results from a Phase 2 trial evaluating bel-sar in small choroidal melanoma and indeterminate lesions demonstrated that patients who received three cycles of bel-sar therapy showed a local complete response with a tumor control rate of 80% and a visual acuity preservation rate of 90%. The majority of patients were at high-risk for vision loss with tumors close to the fovea or optic disk. The overall tolerability profile of bel-sar was favorable, with no dose-limiting toxicities, treatment-related serious adverse events or significant adverse events reported as of August 3, 2023.
Aura is also evaluating bel-sar in a Phase 1 multi-center, open-label clinical trial for the treatment of Non-Muscle Invasive Bladder Cancer (NMIBC) and Muscle Invasive Bladder Cancer (MIBC). The trial has completed enrollment of the bel-sar only cohort, and preliminary data from the first patient in the light activated cohort demonstrated a clinical complete response with evidence of extensive necrosis and immune activation.
Competitive Landscape and Growth Opportunities
Aura's bel-sar is currently the only product candidate in development for the first-line treatment of early-stage choroidal melanoma, a rare and serious form of eye cancer. There are no FDA-approved therapies for this indication, with current standard of care treatments including plaque brachytherapy, proton beam irradiation, and enucleation, all of which are associated with significant vision loss.
Beyond choroidal melanoma, Aura sees significant growth opportunities for bel-sar in other ocular oncology indications, such as choroidal metastases and cancers of the ocular surface, as well as in bladder cancer. The company believes bel-sar's dual mechanism of action, which promotes cancer cell death through both the delivery of a cytotoxic payload and activation of a secondary immune response, could provide benefits across a range of solid tumor types.
Risks and Challenges
Aura faces several risks and challenges common to clinical-stage biotechnology companies, including the need to successfully complete ongoing and future clinical trials, obtain regulatory approvals, and establish commercial manufacturing and sales capabilities. The company's reliance on third-party contract development and manufacturing organizations (CDMOs) and contract research organizations (CROs) also introduces risks related to supply chain disruptions and the ability of these partners to meet Aura's requirements.
Additionally, as a biologic-device combination product, bel-sar faces additional regulatory complexities that could impact the timing and likelihood of approval. The company also operates in highly competitive therapeutic areas, and may face challenges in differentiating its product candidate and achieving broad market acceptance.
Aura's financial position is also a key consideration, as the company will require substantial additional capital to fund its ongoing operations and future growth. While the company's current cash and cash equivalents are expected to fund its activities into the second half of 2026, Aura may need to raise additional funds through equity or debt financing, or strategic partnerships, to support the continued development and potential commercialization of bel-sar.
Outlook
Aura Biosciences is a promising clinical-stage biotechnology company with a unique precision immunotherapy platform and a lead candidate, bel-sar, that has demonstrated encouraging results in early-stage clinical trials. The company's focus on underserved areas of ocular and urologic oncology, where bel-sar's dual mechanism of action may provide significant benefits, positions Aura for potential long-term growth.
The successful completion of the ongoing global Phase 3 trial of bel-sar in small choroidal melanoma and indeterminate lesions, as well as the continued advancement of the product candidate in other indications, will be key milestones to watch for Aura. Additionally, the company's ability to secure the necessary funding to support its development and commercialization efforts will be crucial in determining its future trajectory.
Conclusion
Overall, Aura Biosciences presents an intriguing investment opportunity for those interested in the promising field of precision immunotherapies for solid tumors. The company's innovative approach, robust clinical pipeline, and experienced management team suggest it is well-positioned to potentially make a meaningful impact in the treatment of difficult-to-treat cancers.