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A Star is born as new SIRP player aims to Electra-fy rare disease

Star Therapeutics Inc. emerged from stealth mode to tell the world about its approach to drug discovery and development in rare diseases, and to spin out Electra Therapeutics Inc., the first in a projected family of companies. Deploying antibody drug discovery expertise, South San Francisco-based Star aims to generate programs that target multiple diseases with a single therapy. Electra, as part of its coming-out party, disclosed an $84 million series B round that will let the company reach clinical proof of concept in secondary hemophagocytic lymphohistiocytosis (sHLH), an inflammatory disease, with lead candidate ELA-026, while expanding into other indications and advancing two more compounds toward the clinic.

By Randy Osborne

Star Therapeutics Inc. emerged from stealth mode to tell the world about its approach to drug discovery and development in rare diseases, and to spin out Electra Therapeutics Inc., the first in a projected family of companies. Deploying antibody drug discovery expertise, South San Francisco-based Star aims to generate programs that target multiple diseases with a single therapy. Electra, as part of its coming-out party, disclosed an $84 million series B round that will let the company reach clinical proof of concept in secondary hemophagocytic lymphohistiocytosis (sHLH), an inflammatory disease, with lead candidate ELA-026, while expanding into other indications and advancing two more compounds toward the clinic.

Electra was previously backed by parent company Star, which since its inception in 2018 has raised more than $100 million from Westlake Village Biopartners, Orbimed, Redmile Group, Cormorant Asset Management, RA Capital, Cowen Healthcare Investments, and New Leaf Venture Partners. Co-leading the  series B round for Electra are Westlake and Orbimed; Star’s other investors are on board, too.

Work at Electra focuses on antibody therapies that target signal regulatory proteins (SIRP), a family of cell surface receptors on various immune cell types, with an eye to taking SIRP research beyond cancer, where it’s well-recognized. HLH is characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. The secondary form is often triggered by autoimmune diseases, malignancy, or infection.

Adam Rosenthal, CEO of Star and Electra, explained his strategy by citing the influence of time spent at True North Therapeutics Inc., a privately held spinout of Ipierian Inc. that developed sutimlimab for the rare blood disorder cold agglutinin disease (CAD). The drug is designed to selectively target and inhibit C1s in
the classical complement pathway. “We took [sutimlimab] from an idea to clinical proof of concept,” Rosenthal said, at which point the firm was acquired by Bioverativ Inc. in May 2017 for $400 million up front plus assumed cash. In January 2018, Sanofi bought Bioverativ for $11.6 billion. Recently, “through the heroic efforts of all three companies” – more than five years after True North started its work in CAD – sutimlimab was approved in Sanofi’s hands as Enjaymo.

CAD “was a condition that lacked awareness and understanding,” Rosenthal recalled. “Very little was known in the medical literature. The general impression was that it was a mild anemia that often did not require interventional therapies. But when we spoke to treating physicians and directly to patients, we heard stories that revealed a disease with significant morbidity, and the potential to be life threatening. To me, it was eye-opening that all this information was
unknown, and that patients were living in the shadows with the disease. Nothing was being done by our industry.”

Rosenthal’s vision “was to go through all the thousands of [rare diseases with no approved therapies] and figure out which ones mattered, but do it in a systematic way,” he said. When Star was founded, “we started in the areas of immunology and hematology. The idea was to put together constellations of diseases with a common biology in each program. While rare disease was the foundation, we followed the science along the way,” which led to other therapeutic areas as well.

“Everyone else in the CD47/SIRP space has been focused on oncology, using it as an immune checkpoint,” Rosenthal noted. With Electra, researchers settled on sHLH through “the same process [we use] for all our programs, and it’s quite iterative,” starting with the constellation of diseases. “The fun is when it’s
in preclinical development” and priorities must be established among members of the constellation, he said. In that process, sHLH “quickly rose to the top.” Unlike other conditions, such as CAD, “there was more known about the epidemiology. It’s a lifethreatening disease. The immune system is basically out of whack – myeloid and T cells contribute to severe symptoms that can lead to multi-organ failure and death.” A study done by the Mayo Clinic indicated about 10,000 to 15,000 sHLH patients per year in the U.S.

Electra and Star exist independently in some aspects. “We’re all under the same roof, so we have employees who can work across Electra programs and Star programs, but [keeping the firms separate on paper] allows each company to have a different financing or business development strategy,” Rosenthal told
BioWorld. About the two preclinical programs behind ELA-026, Electra is keeping mum for now, saying only that one is focused on immunology and depleting immune cells and the other is in the immuno-oncology space. “We think we have a unique way of utilizing SIRP for a variety of cancers,” he said. “We were well
aware [when Star was established] of what everyone was doing on the oncology side,” but didn’t yet have the understanding of the science to try a different approach, he said. This has changed.

“These are all home-grown ideas,” Rosenthal said, and ELA-026 went from idea to clinic in less than three years. “We’re designing [a phase Ib study] in a way that we’re looking at biomarkers – there are some clinical responses that are very similar to how the disease is diagnosed,” he said, which means “an easy way to look for clinical efficacy.” Star has “other programs that we’re working on,” and another company in the family waits in the wings, focused on rare hematology diseases, he said. A candidate is undergoing IND-enabling studies.