The biotech industry has traditionally focused on common diseases with large patient groups, partly due to the financial incentives matching broader marketplace demand. But in recent years, there has been increased interest in creating treatments for rare and orphan diseases. These illnesses afflict fewer than 200,000 individuals in the United States, as defined by the U.S. Food and Drug Administration.
These conditions are frequently without satisfying solutions, leaving patients and families little to turn to. The arrival on the scene of precision technologies like mRNA platforms has started to shift the paradigm. By facilitating more bespoke strategies, these technologies provide new hope for the treatment of long-term and genetically based disorders previously deemed too trivial in nature to be commercially viable.
One of the firms where innovation and unmet medical need intersect is Arcturus Therapeutics, with its San Diego, California, headquarters. With co-founder Joseph E. Payne at the helm, Arcturus has taken its RNA-centric research into the realm of orphan genetic diseases. Although the company received widespread attention during the COVID-19 pandemic due to its development of the self-amplifying mRNA vaccine KOSTAIVE, it has also been working towards therapeutic applications of its platform technologies, particularly in respect of disorders that include cystic fibrosis (CF) and ornithine transcarbamylase (OTC) deficiency. These have been the long-standing challenges for the clinical community that would require innovative approaches combining biological sophistication and regulatory foresight.
Payne’s training in synthetic organic chemistry and career in drug discovery at companies like Merck Research Laboratories and Bristol-Myers Squibb enabled him to understand the applications of mRNA beyond vaccines. As Arcturus matured from a lean biotech company into a publicly traded company, its pipeline grew from infectious disease uses to cover genetically driven chronic diseases. Cystic fibrosis, for example, is caused by CFTR gene mutations and affects around 100,000 individuals worldwide. Even with advances in therapy in the last decade, there remains a subset of patients who are resistant to existing small-molecule treatments. Arcturus seeks to meet this unmet need with mRNA delivered via their technology, LUNAR, for delivering functional mRNA encoding for the CFTR protein.
The company’s strategy with respect to OTC deficiency is similarly rational. OTC deficiency is a genetic urea cycle disorder that disrupts the body’s ability to break down nitrogen waste products. Patients can suffer life-threatening metabolic crises, and existing treatments are based on severe dietary restrictions and liver transplantation in advanced cases. Arcturus has recognized OTC as a target for mRNA therapy that can restore enzymatic activity through endogenous protein production. These programs represent more than scientific ambitions. They also represent a commitment to dealing with the complexity of regulatory processes.
Rare disease trials typically use patients in smaller populations, which often requires more direct working contact with regulatory authorities such as the FDA and the European Medicines Agency.
By early 2025, Arcturus had reported that its rare disease programs were in Phase 2 clinical trial development. The company stated it had more than 500 patents and patent applications for its RNA delivery and expression platforms in various jurisdictions, such as the United States, Europe, Japan, and China. An intellectual property position such as this allows the company the legal framework to pursue various indications while still protecting its innovations from a competitive overlap. It also highlights a more systemic trend in the biotech industry to generate IP portfolios that are both scientifically validated and strategically defensible.
Payne’s involvement in driving these efforts around rare diseases extends beyond his executive responsibilities. He has remained an active voice in determining the company’s technical course, especially as it relates to disease targeting and platform design. While numerous founder-CEOs in the biotech industry have stepped aside to more symbolic positions over the years, Payne has continued to participate in scientific decision-making and external communication. His capacity to communicate with both scientific teams and industry constituencies has been pivotal to Arcturus’s growth from a vaccine company to one that is moving into chronic disease treatment with long-term consequences.
Strategically, addressing rare diseases resonates with many strengths. Regulatory bodies usually offer such incentives as orphan drug status, fast-track review procedures, and market exclusivity durations. These initiatives aim to de-risk development and get companies to invest in neglected medical fields. Arcturus’s continued partnership with the Japanese pharma company Meiji Seika Pharma, under its ARCALIS joint venture, demonstrates its desire to take its saRNA treatments beyond Western markets. Japan’s regulatory scheme has increasingly emphasized innovation in the treatment of rare diseases, and therefore, it is fertile ground for early uptake.
Concurrently, these endeavors entail inherent risks. Rare disease studies need to weigh strict safety controls against the logistical challenges of restricted patient access. In addition, mRNA-based treatment is still untested in the chronic disease context, with careful trial design and extended outcome measurement imperative. Investors and analysts alike are keeping a close eye on Arcturus’s progress as it gears up for pivotal trial phases and potential licensing deals.
As of 2025, the biotech space is still saturated with companies trying to apply nucleic acid technologies to various indications. Arcturus’s emphasis on rare diseases, nonetheless, makes it stand out from peers focusing mainly on infectious disease or oncology indications. Entering the space of rare disease is in line with the pattern of Payne going after high-impact spaces where technical breakthroughs and unmet opportunities intersect. It also indicates long-term dedication, since the process from preclinical discovery to regulatory approval in such instances typically takes several years.
Joseph E. Payne’s vision for Arcturus’s growth exemplifies a particular type of vision, one rooted both in science and general knowledge of therapeutic need. His efforts with the company’s foray into rare and orphan diseases provide a model for how RNA technology can be leveraged to address complicated, high-stakes medical problems that may otherwise fall short of the attention of larger pharmaceutical companies.
