Worm-inspired biotech Holoclara has had a busy year. After announcing a $16 million series A round in June, the Pasadena, California, company has now dosed the first patient in a phase 1 trial of its primary asset and planted a flag on its lead indication, the immune disease eosinophilic esophagitis (EoE).
The trial will enroll 64 healthy volunteers, Holoclara CEO and co-founder Andrea Choe, M.D., Ph.D., told Fierce Biotech in an interview. It will be conducted in Australia with the help of global CRO Novotech and Adelaide-based trial operator CMAX Clinical Research.
Results are expected in the second or third quarter of 2025, Choe added.
The drug candidate being tested, HC002, is an oral small molecule that was originally sourced from roundworms (also called nematodes) that live in our guts, but is now synthesized chemically by Holoclara.
“There are no live roundworms being used in this trial,” Choe said.
Preclinical data showed that HC002 has activity across multiple autoimmune and allergic diseases, Choe said; the general idea is that roundworms and other organisms that live inside us evolved mechanisms to modulate our immune systems so that they could lead quiet lives, and our immune systems in turn adapted to them.
Losing these organisms in our hyper-hygienic society, the idea goes, could explain the rise of allergic and autoimmune diseases in the industrialized world.
Choe settled on EoE as the lead indication for HC002 after a patient with the disease reached out to her and spoke about their symptoms. EoE is a chronic immune condition where immune cells called eosinophils build up in the throat in response to foods, allergens or acid reflux. This can lead to food getting stuck in the esophagus, problems with swallowing and chest pain.
Choe realized that the symptoms associated with EoE, like eosinophil proliferation and mucus secretion, were also things that the immune system would do to get rid of a roundworm; so, she said, it made sense that the worms would have evolved molecules to dampen that response, making HC002 a good fit for EoE.
Rates of EoE have spiked in recent years, with cases increasing fivefold since 2009. There are currently two approved treatments for EoE, and Swiss biotech EsoCap published phase 2 data for its EoE candidate on Dec. 17.
HC002 stands out from the crowd by being orally available and intended for long-term use, Choe said, as well as being a molecule that has evolved over time with human biology.
Holoclara plans to expand into other indications in the future, Choe said, with worms also previously showing promise in obesity, arthritis and in boosting stem cells.
“There's a lot of great opportunities out there, and we are turning over every rock,” she said.
To help get HC002 into the clinic, Holoclara appointed Brian Varnum, Ph.D., the former chief development officer and CEO of Armata Pharmaceuticals, to be its head of R&D in August.