Business Overview and History
Avidity Biosciences, Inc. is a clinical-stage biopharmaceutical company at the forefront of developing a novel class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs). The company's proprietary AOC platform aims to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to tackle the root causes of diseases previously untreatable with such approaches.
Avidity Biosciences was founded in 2012 as a limited liability company under the name Avidity NanoMedicines LLC. In 2016, the company changed its name to Avidity Biosciences LLC and then converted to a Delaware corporation named Avidity Biosciences, Inc. in 2019.
Since its inception, Avidity has been focused on developing its innovative AOC platform to address previously untreatable diseases. In its early years, the company concentrated on organizing and staffing, conducting business planning, raising capital, developing its AOC platform, identifying potential product candidates, and establishing its intellectual property portfolio. Avidity also conducted extensive research and preclinical studies to advance its clinical programs.
As a company with a limited operating history, Avidity has faced challenges common to the biopharmaceutical industry, including incurring significant operating losses since inception and the need to secure substantial additional financing to achieve its goals. To address these challenges, the company has relied on various means of raising capital over the years, including public offerings, sales agreements, the sale and issuance of convertible preferred stock, funding under collaboration agreements, and a private placement of common stock.
Product Pipeline
Avidity's lead clinical-stage programs target rare neuromuscular disorders, including myotonic dystrophy type 1 (DM1), facioscapulohumeral muscular dystrophy (FSHD), and Duchenne muscular dystrophy (DMD).
Avidity's most advanced product candidate, delpacibart etedesiran (del-desiran), formerly known as AOC 1001, is designed to treat DM1 by reducing levels of the disease-causing DMPK mRNA. Del-desiran is currently in a global Phase 3 HARBOR trial, having received Breakthrough Therapy designation from the FDA for the treatment of DM1. Del-desiran consists of a proprietary monoclonal antibody (mAb) that binds to the transferrin receptor 1 (TfR1) conjugated with a small interfering RNA (siRNA) targeting the DMPK mRNA. In the company's Phase 2 MARINA trial, del-desiran demonstrated reversal of disease progression in people living with DM1 across multiple endpoints including myotonia, muscle strength, and activities of daily living compared to natural history data. The FDA has also granted del-desiran Orphan Drug and Fast Track designations.
The company's second clinical-stage program, delpacibart braxlosiran (del-brax), formerly AOC 1020, is the first investigational therapy designed to directly target the DUX4 gene in FSHD. Del-brax is currently in a Phase 1/2 FORTITUDE trial. Del-brax utilizes Avidity's proprietary mAb targeting TfR1 to deliver an siRNA against the DUX4 mRNA. In the Phase 1/2 FORTITUDE trial, del-brax demonstrated remarkable and consistent reductions of greater than 50% in DUX4 regulated genes, trends of functional improvement, and favorable safety and tolerability in people living with FSHD. Avidity has received Orphan Drug and Fast Track designations from the FDA and Orphan Designation from the European Medicines Agency (EMA) for del-brax.
Avidity's third clinical candidate, delpacibart zotadirsen (del-zota), formerly AOC 1044, is being developed for the treatment of Duchenne muscular dystrophy (DMD) with mutations amenable to exon 44 skipping (DMD44). Del-zota is currently in a Phase 2 EXPLORE44 open-label extension study. In the Phase 1/2 EXPLORE44 trial, del-zota demonstrated consistent delivery of the phosphorodiamidate morpholino oligomer (PMO) to skeletal muscle, a 25% increase in near full-length dystrophin production, and a profound reduction in creatine kinase levels in people living with DMD44. The FDA has granted Orphan Drug, Rare Pediatric Disease, and Fast Track designations for del-zota.
In addition to its rare neuromuscular disease pipeline, Avidity has expanded its focus to precision cardiology, advancing two wholly-owned candidates targeting rare genetic cardiomyopathies – AOC 1086 for PLN cardiomyopathy and AOC 1072 for PRKAG2 syndrome. These new programs leverage the company's AOC platform to address unmet needs in the cardiovascular disease space.
Financials
Avidity Biosciences reported total revenue of $10.90 million for the year ended December 31, 2024, up from $9.56 million in the prior year. This revenue was primarily generated from the company's collaboration agreements with Eli Lilly and Company and Bristol Myers Squibb. For the most recent quarter, revenue was $2.97 million, representing a year-over-year growth of 29.26% compared to the prior year quarter.
The company's net loss for the year ended December 31, 2024, was $322.30 million, compared to a net loss of $212.22 million in 2023. For the most recent quarter, the net loss was $102.26 million. Avidity's research and development expenses totaled $303.59 million in 2024, up from $190.97 million in the previous year, reflecting the advancement of its clinical programs and continued investment in its proprietary AOC platform. This increase was due to higher costs associated with the progression of clinical trials and preclinical studies, including higher manufacturing costs related to monoclonal antibodies used across programs, as well as higher personnel costs.
General and administrative expenses were $86.24 million in 2024, up from $54.19 million in 2023, primarily due to higher personnel costs and professional fees to support the company's expanded operations and commercial readiness initiatives.
For the most recent fiscal year, Avidity reported an annual operating cash flow of -$300.87 million and an annual free cash flow of -$307.94 million.
Liquidity
As of December 31, 2024, Avidity had $1.50 billion in cash, cash equivalents, and marketable securities, providing the company with a strong financial position to advance its pipeline and prepare for potential commercialization of its product candidates. The company believes this will be sufficient to fund its operations for at least the next 12 months.
Avidity's cash and cash equivalents stood at $219.87 million. The company's debt-to-equity ratio is 0.0048, indicating a low level of debt relative to equity. Avidity's current ratio and quick ratio are both 15.73, suggesting a strong ability to meet short-term obligations.
Key Milestones and Upcoming Catalysts
In 2024, Avidity achieved several important milestones across its rare disease pipeline:
- Initiated the global Phase 3 HARBOR trial for del-desiran in DM1, with enrollment on track. - Reported positive long-term data from the Phase 1/2 MARINA-OLE study of del-desiran, showing reversal of disease progression in DM1 patients. - Began enrollment of the biomarker cohort in the Phase 1/2 FORTITUDE trial for del-brax in FSHD. - Presented positive initial data from the Phase 1/2 EXPLORE44 trial of del-zota in DMD44 patients, demonstrating significant increases in dystrophin production and reductions in creatine kinase levels.
Looking ahead, Avidity expects to achieve several key milestones in 2025:
- Complete enrollment in the del-desiran Phase 3 HARBOR trial and the del-brax Phase 1/2 FORTITUDE biomarker cohort. - Initiate a global, potentially registrational trial for del-brax in FSHD. - Present topline data from the del-zota EXPLORE44 trial and the ongoing EXPLORE44-OLE study. - Submit a Biologics License Application (BLA) for del-zota in DMD44 by the end of 2025. - Advance its precision cardiology candidates, AOC 1086 and AOC 1072, into clinical development.
Risks and Challenges
As a clinical-stage biopharmaceutical company, Avidity Biosciences faces several risks and challenges common to the industry:
- Uncertainty around the successful completion of clinical trials and regulatory approvals for its product candidates. - Potential delays or setbacks in the development and commercialization of its therapies. - Competition from other companies developing treatments for rare diseases, including those with more established platforms or resources. - Ability to manufacture its product candidates at scale and maintain a reliable supply chain. - Potential inability to obtain adequate coverage and reimbursement for its therapies, if approved. - Reliance on collaborations and partnerships to advance certain programs, which could be terminated or fail to deliver expected results. - Potential inability to protect its intellectual property or successfully defend against patent challenges.
Despite these risks, Avidity's focus on its innovative AOC platform and its progress in advancing a diverse pipeline of rare disease programs position the company as a promising player in the rapidly evolving field of RNA therapeutics.
Industry Trends
The RNA interference (RNAi) field has gained significant momentum in recent years, with six RNAi-based medicines receiving regulatory approval since 2018 to treat a variety of rare diseases and high cholesterol. The compound annual growth rate (CAGR) for the global RNAi therapeutics market is estimated to be around 24.5% from 2022 to 2030. This growth trend underscores the increasing importance and potential of RNA-based therapies in addressing previously untreatable diseases.
Geographic Markets and Performance
Avidity Biosciences is currently a small-cap company that sells its products exclusively in the United States. As the company advances its pipeline and potentially gains regulatory approvals, it may expand its geographical reach in the future.
Corporate Governance and Reputation
There are no reported scandals, short seller reports, or CEO departures for Avidity Biosciences, indicating stability in its corporate governance and leadership. This clean record contributes to the company's reputation as it continues to develop its innovative AOC platform and advance its clinical programs.
Conclusion
Avidity Biosciences is at the forefront of developing a new class of RNA therapeutics with the potential to address the root causes of various rare and devastating diseases. The company's lead clinical candidates in DM1, FSHD, and DMD have demonstrated promising early results, and its expansion into precision cardiology further showcases the versatility of its AOC platform.
With a strong financial position, a robust pipeline, and multiple upcoming milestones, Avidity Biosciences is well-positioned to continue its pioneering efforts in the field of RNA-based therapeutics and potentially deliver transformative treatments to patients in need. The company's focus on rare diseases and its innovative approach to RNA therapeutics set it apart in the biopharmaceutical industry, making it a company to watch as it progresses through late-stage clinical trials and potential regulatory approvals.