REGENXBIO Inc. (NASDAQ:RGNX) is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO has developed a broad pipeline of gene therapy product candidates using its proprietary adeno-associated virus (AAV) gene delivery platform, the NAV® Technology Platform, as a one-time treatment to address an array of diseases.
Business Description
REGENXBIO's investigational gene therapies are designed to deliver functional genes to address genetic defects in cells, enabling the production of therapeutic proteins or antibodies that are intended to impact disease. Through a single administration, gene therapy could potentially alter the course of disease significantly and deliver improved patient outcomes with long-lasting effects. The company's lead programs and product candidates include ABBV-RGX-314 for the treatment of wet age-related macular degeneration (wet AMD) and diabetic retinopathy (DR), RGX-202 for the treatment of Duchenne muscular dystrophy (Duchenne), and RGX-121 for the treatment of Mucopolysaccharidosis Type II (MPS II).
In addition to its internal product development efforts, REGENXBIO also selectively licenses the NAV Technology Platform to other leading biotechnology and pharmaceutical companies, which the company refers to as NAV Technology Licensees. As of March 31, 2024, the NAV Technology Platform was being applied in one commercial product, Zolgensma®, and the preclinical and clinical development of a number of other licensed products.
Financials
For the full year ended December 31, 2023, REGENXBIO reported annual revenue of $90.2 million and a net loss of $263.5 million. The company's annual operating cash flow was -$218.4 million, and its annual free cash flow was -$228.4 million.
In the first quarter of 2024, the company generated $15.6 million in license and royalty revenue, a decrease from $19.1 million in the prior year period. The decrease was primarily attributable to non-recurring development milestone revenue recognized in the first quarter of 2023 and a slight decrease in Zolgensma royalty revenues.
Research and development expenses decreased to $54.8 million in the first quarter of 2024, compared to $58.5 million in the prior year period. The decrease was primarily due to lower manufacturing and clinical supply costs for the company's lead product candidates, as well as a reduction in personnel-related costs, partially offset by an increase in clinical trial expenses.
General and administrative expenses also decreased to $18.3 million in the first quarter of 2024, down from $22.6 million in the prior year period. The decrease was driven by lower professional services and consulting fees, as well as a reduction in personnel-related costs.
Liquidity
As of March 31, 2024, REGENXBIO had cash, cash equivalents, and marketable securities of $380.5 million, which the company believes is sufficient to fund its operations for at least the next 12 months based on its current business plan.
Pipeline Updates and Milestones
REGENXBIO has made significant progress across its pipeline in 2024, advancing each of its programs toward pivotal stage clinical trials and commercialization.
ABBV-RGX-314 for Wet AMD and Diabetic Retinopathy
ABBV-RGX-314, which is being developed in collaboration with AbbVie, is a potential one-time treatment for wet AMD, DR, and other chronic retinal conditions. The company is evaluating ABBV-RGX-314 in multiple ongoing clinical trials, including two pivotal trials (ATMOSPHERE and ASCENT) for the treatment of wet AMD using subretinal delivery, as well as two Phase II trials (AAVIATE and ALTITUDE) evaluating the therapy using in-office suprachoroidal delivery for the treatment of wet AMD and DR, respectively.
In the AAVIATE trial evaluating suprachoroidal delivery of ABBV-RGX-314 for wet AMD, the company reported positive interim results in January 2024, demonstrating that patients treated with the therapy continued to show stable vision and retinal anatomy, while experiencing a meaningful reduction in anti-VEGF treatment burden. The highest reduction was seen in the highest dose level, with 50% of patients remaining injection-free.
Based on positive interim results from the ALTITUDE trial evaluating suprachoroidal delivery of ABBV-RGX-314 for DR, REGENXBIO and AbbVie are now designing and evaluating two pivotal trials, with plans to initiate the first pivotal trial in the first half of 2025. The companies expect to hold an end-of-Phase II meeting with the FDA in the first quarter of 2025 to support the pivotal trial design.
RGX-202 for Duchenne Muscular Dystrophy
REGENXBIO is developing RGX-202 as a potential one-time AAV therapeutic for the treatment of Duchenne. The company's AFFINITY DUCHENNE trial is evaluating the safety, tolerability, and clinical efficacy of RGX-202 in patients with Duchenne.
In March 2024, REGENXBIO reported additional positive interim data from the AFFINITY DUCHENNE trial, including robust microdystrophin expression and reductions in serum creatine kinase (CK) levels in older boys aged 8 to under 12 years old. Based on these results, the company has selected the dose level 2 (3e14 vg/kg) as the pivotal dose and has already begun enrolling patients in an accelerated dose level 2 expansion cohort. REGENXBIO plans to enroll up to a total of seven patients at the pivotal dose and expects to hold an end-of-Phase II meeting with the FDA in early Q3 2024 to support the final pivotal trial design. The company intends to use microdystrophin expression as a surrogate endpoint to support a Biologics License Application (BLA) filing for RGX-202 under the accelerated approval pathway.
RGX-121 for Mucopolysaccharidosis Type II (MPS II)
REGENXBIO is developing RGX-121 as a potential one-time AAV therapeutic for the treatment of MPS II, also known as Hunter syndrome. The company's CAMPSIITE trial has achieved its primary endpoint of reduction of natural substrate in the cerebrospinal fluid. REGENXBIO plans to use these data to support a BLA submission for RGX-121 in 2024, and believes the therapy is likely to be eligible for priority review, potentially resulting in the receipt of a Rare Pediatric Disease Priority Review Voucher in 2025.
Outlook
REGENXBIO believes it is well-positioned for success in 2024 and beyond, with a pipeline filled with programs that are initiating pivotal stage trials, fully enrolled at pivotal stage, or under a filed BLA. The company's recent $131.1 million public offering in March 2024 has strengthened its balance sheet and extended its operating runway into 2026 to support the acceleration of its product candidates through multiple value-generating milestones.
The company expects to initiate the pivotal trial for RGX-202 in Duchenne in late Q3 or early Q4 2024, and to initiate the first pivotal trial for the suprachoroidal delivery of ABBV-RGX-314 in diabetic retinopathy in the first half of 2025. Additionally, REGENXBIO plans to file a BLA for RGX-121 in MPS II in 2024, potentially receiving a Rare Pediatric Disease Priority Review Voucher.
Risks and Challenges
REGENXBIO faces several risks and challenges common to the biotechnology industry, including the inherent uncertainties of drug development, the need for regulatory approvals, and the ability to successfully commercialize its product candidates if approved. The company also relies on the success of its NAV Technology Licensees, including the commercialization of Zolgensma by Novartis Gene Therapies, to generate royalty and milestone revenue.
Additionally, REGENXBIO's transition to recurring profitability is dependent upon achieving a level of revenues adequate to support its cost structure, which depends heavily on the successful development, approval, and commercialization of its product candidates. The company may never achieve recurring profitability and will continue to need to raise additional capital to fund its operations.
Conclusion
REGENXBIO is well-positioned for significant value generation in 2024 and beyond, with a robust pipeline of gene therapy product candidates addressing large commercial opportunities. The company's recent progress, including the selection of the pivotal dose for RGX-202 in Duchenne, the advancement of ABBV-RGX-314 in wet AMD and diabetic retinopathy, and the planned BLA submission for RGX-121 in MPS II, demonstrate the company's ability to execute on its strategic priorities and deliver meaningful value for shareholders. With a strengthened balance sheet and a clear path forward for its lead programs, REGENXBIO is poised to continue its momentum and capitalize on the significant potential of its gene therapy platform.