Rare diseases offer enormous opportunities for drug research simply because there are so many diseases and so few drugs.for more than 7000 rare diseases There are only about 650 FDA-approved therapies that have been identified. Star Therapeutics aims to treat as many of these diseases as possible, which for some reason go unnoticed. The company’s approach may allow it to solve multiple problems at once.
Many drug discovery efforts begin with specific biological targets for specific diseases. CEO Adam Rosenthal said Star took a broader view, identifying multiple rare diseases with shared biological drivers. The goal is to develop a single drug that targets shared biology—one that treats multiple diseases. The South San Francisco-based company, which has been working quietly for the past few years, is now revealing its first disease target and details of the company’s approach and business model, backed by $100 million in financing.
Star is a biotech company, but it’s also a startup, Rosenthal said. The company’s research could uncover new biology, or it could make connections that others weren’t aware of. Star built a team around that biology, then delved into the relationship between multiple diseases. To understand Star’s approach, it may be helpful to look at a recently approved drug for a rare disease. Earlier this month, FDA approves Enjaymo, making it the first treatment for cold agglutinin disease, a blood disorder. Sanofi, which gets monoclonal antibodies, gets a regulatory nod. But the drug’s roots lie in True North Therapeutics, where Rosenthal served as chief commercial officer.
Cold agglutinin disease is an autoimmune disease that causes the destruction of red blood cells. When True North began about a decade ago, Rosenthal recalls, there was little in the scientific literature about the rare disease, which many believed to be a mild form of anemia. Discussions with doctors and patients revealed more serious outcomes, some of them fatal. True North identified biological targets associated with several immune diseases, and the first clinical test of the biotechnology antibody was a basket trial for four different diseases. While cold agglutinin disease eventually became the primary disease target, Rosenthal said the plan is to develop drugs for multiple diseases. Star aims to replicate True North’s approach, but across multiple companies, each focusing on a specific area of biology.
“That’s the motivation for doing this, because it’s through that [True North] Experience has shown that we can really treat a neglected disease,” Rosenthal said.
Star began its work by identifying opportunities from a list of 7,000 rare diseases, prioritizing them based on factors including science, clinical development paths and market opportunities. In a blog post, Rosenthal wrote that the process of finding the biology of common diseases is comparable to the efforts of early astronomers to make connections between groups of stars. Rosenthal said the company’s first focus was hematology and immunology, as it fits with the experience of the Star team, which includes several True North veterans.
The first star disease target was secondary hemophagocytic lymphohistiocytosis (sHLH), an autoimmune disease characterized by an overactive inflammatory response. The disease can be caused by triggers including cancer, immunotherapy and infection. It has no FDA-approved treatments, and it can rapidly lead to multiple organ failure and death.
Star’s first company, Electra Therapeutics, aims to treat sHLH by targeting signaling regulatory proteins (SIRPs), a family of cell surface receptors on various types of immune cells. While these receptors have been targeted by cancer drugs, they also play a role in several autoimmune diseases, said Rosenthal, who is also Electra’s chief executive. The biotech’s lead program, ELA026, is an antibody that targets SIRP and depletes immune cells that deplete bone marrow and T cells, and is designed to act as a brake on an overactive immune system.
Electra’s main asset has entered Phase 1 testing. Studies are underway on experimental drugs for other diseases; Rosenthal declined to identify them, but he did say the company’s approach to SIRP biology has potential applications in immuno-oncology.
Star is backed by a significant amount of cash from a broad consortium of investors. The $100 million behind Star is the total funding the company has raised since its inception in 2018. Funding came from Westlake Village BioPartners, OrbiMed, Redmile Group, Cormorant Asset Management, RA Capital, Cowen Healthcare Investments and New Leaf Venture Partners.
Electra’s initial financial support came from Star. On Wednesday, Electra announced an $84 million Series B round co-led by Westlake Village BioPartners and OrbiMed. The new financing is part of the Star model. The reason for putting the company’s science and technology in different companies, Rosenthal said, is to give each company the ability to focus and the flexibility to seek its own financing. But while the R&D efforts may be separate, spin-off companies will still share many of Star’s resources, and the startups are housed under the same roof, an arrangement that increases efficiency. It also has precedent.
BridgeBio Pharma is one of the companies developing the “hub and spoke model”, forming subsidiaries focused on rare disease assets it acquires or licenses. These subsidiaries share the resources of the parent company. Other companies operating similar models include Roivant Sciences and Cullinan Oncology. One difference between these companies and Star is that Star’s research is homegrown. However, In recent years, Roivant Sciences’ approach has expanded to include in-house drug discovery powered by artificial intelligence and computational technologies. Other new companies adopting the hub-and-spoke model include Centesar Pharmaceuticals and Anji Pharmaceutical.
More startups from Star coming soon. The next focus, Rosenthal said, is rare blood disorders. The company currently has a drug candidate in preclinical studies that can support the submission of an Investigational New Drug Application. Disease targets are also not currently public, but Rosenthal said that, like Electra, the new company already has a list of diseases its drugs can target.
“It’s a menu of options, and it’s up to us to decide what’s the main directive,” Rosenthal said.
Photos by Flickr users NASA Goddard Space Flight Center through Creative Commons license
