Turning Worm-Derived Molecules into Life-Changing Therapies

For those battling chronic inflammatory diseases, effective and sustainable treatments remain elusive. Now, scientists are exploring symbiont chemistry as an unconventional but promising source of therapeutics for autoimmune conditions.

Human health has evolved in tandem with symbiotic organisms. In this Innovation Spotlight, Andrea Choe, the co-founder and chief executive officer of Holoclara, discusses how she was inspired to take advantage of this long history and develop a new type of therapeutic, leading to the recent announcement of a Phase 1 clinical trial assessing the effectiveness of a worm-derived molecule for treating eosinophilic esophagitis (EoE).

What is the link between worms and the immune system?

Humans have spent the last five million years evolving alongside symbiotic organisms—microbes and multicellular guests that quietly shaped our immune defenses, inflammation, metabolism, and aging. Despite decades of compelling preclinical data, these evolutionary insights have yet to translate into real-world therapies. At Holoclara, we’re changing that by focusing first on gut worm-derived molecules. Building on my doctoral research with co-founders Paul Sternberg from the California Institute of Technology and Frank Schroeder from the Boyce Thompson Institute at Cornell University, we’re harnessing nature’s own immunomodulators to create the medicines that patients desperately need.

Before starting your company, what did scientists know about the effects of worms and their excretory and secretory products on the immune system?

Decades of preclinical research have demonstrated the therapeutic potential of worms across a wide range of diseases, including inflammation and metabolism.¹ Yet, despite this scientific evidence showing that worms have the potential to treat disease, most of these incredible connections and discoveries seemed to stop there—in the lab. No treatments have made it into the clinic, where the patients who needed them most could access them.

At Holoclara, we’ve built a platform for first-in-class drug discovery, starting with identifying molecules derived from gut-dwelling worm species. Studies have shown that worms impart a therapeutic effect on the mammalian immune system.^2,3 Through comprehensive mapping of these effects, we are pioneering safe, orally available worm-derived therapies for allergic and autoimmune disorders. By mining one of nature’s many symbiotic species, we are creating therapies for chronic inflammatory conditions that work with the immune system rather than against it.

What led you to found Holoclara and what is the company’s main goal?

Bringing cures to patients has been my mission from day one. As a medical student, I treated countless patients with Crohn’s disease, multiple sclerosis, asthma, rheumatoid arthritis, and other debilitating diseases. Witnessing firsthand their ongoing challenges in the healthcare system lit a fire under me to find real solutions. My dual MD and PhD program enabled me to dig deeper into the underlying science behind these chronic, debilitating diseases, and when I discovered the connection between our health and worms, the foundational pieces of Holoclara began to fall into place.

In a nutshell, Holoclara is harnessing worms to turn potential cures into reality. We have developed a next-generation technology that leverages the power of nature’s symbionts to bring these patients the safe and effective solutions they’ve been waiting for.

What is the current Phase 1 clinical trial trying to determine?

The Phase 1 clinical trial for our worm-derived compound HC002 will evaluate its safety, tolerability, and pharmacokinetics in healthy adults. With HC002, we’re introducing a completely new type of medicine—one that harnesses molecules from worms, our natural symbiotic partners who have co-evolved with humans and protected us from disease over millennia. This first-in-human study could potentially lead to further medicines that would benefit millions of patients suffering from chronic inflammatory diseases, and we hope to share initial results later this year.

What is EoE and why did you choose this disorder as the lead indication for HC002?

EoE is a chronic inflammatory disorder characterized by elevated levels of eosinophil, a type of white blood cell, in the esophagus. It can be considered an invisible disease because eosinophils can build up in reaction to an allergen, damaging the esophageal tissue and potentially causing difficulty swallowing, chest and abdominal pain, vomiting, and loss of appetite. With recent studies now indicating that the actual prevalence of this condition is much higher than previously thought,⁴ we at Holoclara have selected EoE as a lead indication for HC002 with the goal of treating this severely under-addressed disease.

What benefits could a treatment like HC002 provide above and beyond what is already available?

Currently, only two FDA-approved therapies exist for EoE despite it being an increasingly prevalent condition worldwide. There is no FDA-approved oral therapy for kids right now, meaning they would need to get an injection every week. There is a critical need for effective and well-tolerated solutions like HC002 in this area that prioritize patients and long-term disease management. Our therapy is an orally available small-molecule drug designed for long-term use, while existing treatments are typically either injectable biologics or steroids which are not intended for long-term use.

HC002 was born out of our commitment at Holoclara to pioneering breakthrough science into solutions for underserved patient communities. This first program to address eosinophilic esophagitis is only the beginning of our crucial work to explore other applicable indications and pave a new path for worm-derived therapeutics for allergic and autoimmune disorders alike.

What excites you about the future of symbiont-derived molecules?

Our worm-derived medicines follow in the footsteps of other remarkable innovations resulting from relationships between human systems and other organisms, such as CRISPR, which is derived from the bacterial immune system, and Ozempic, with origins from the Gila monster.

Now that we are taking the world’s first worm-derived medicines through clinical trials, it’s becoming increasingly clear that a wide array of symbiotic microbes and other life forms likely also harbor untapped therapeutic potential. I believe that the emerging field of metabolomics will take precision medicine even further as we study the small molecules that drive biological processes and uncover new therapeutic targets instead of just improving existing ones. This shift will open the door to more personalized, effective treatments that better align with the complexity of human biology and our environment.