Charles Elson, M.D., is co-founder and chief scientific officer of ImmPrev Bio, Inc., a company founded to explore the potential of a groundbreaking new treatment concept for Crohn's disease.
Charles Elson, M.D., has spent his career investigating the immune factors behind inflammatory bowel disease, which affects approximately 1.6 million Americans. The two major forms of inflammatory bowel disease are Crohn’s disease, which affects approximately 800,000 Americans, and ulcerative colitis, which affects most of the rest. (There are some comparatively rare forms of disease that also fall within IBD.)
For the past several decades, Elson, a professor in the UAB Division of Gastroenterology and Hepatology, has consulted with pharmaceutical companies on their treatments numerous times. He never figured he would one day run a company of his own, until he became so convinced of the potential for a groundbreaking new treatment concept for Crohn’s disease that he was willing to give the startup world a shot. This year, with funding from Birmingham-based First Avenue Ventures, Elson co-founded ImmPrev Bio, Inc., and became the company’s chief scientific officer.
Although the exact causes of Crohn’s are still unclear, it occurs when some combination of genetic predisposition and environmental factors triggers an immune response. This is no mild reaction: Patients suffer from pain, scarring, ulcers and abscesses. The treatments that are currently available dampen this immune reaction to prevent damage.
“When I was training, we had three drugs; now there are several billion-dollar drugs — Stelara, Humira, Remicade, Entyvio,” said Elson, who retired from clinical care this year. Most of the drugs began as treatments for rheumatoid arthritis “because there is much more of it,” Elson said. He noted that Humira “has become the most successful drug by earnings in history.”
Elson’s lab discovered that about half of patients with Crohn’s disease share an interesting antibody response. In their bloodstreams, these patients have antibodies to a dozen or so proteins expressed by the gut bacteria Lachnospiraceae.
These drugs can be extremely effective. “If patients follow the regimen, you can keep them without a flare for years — 20 years, easily,” Elson said. But “these are all treating a late stage, and it doesn’t change the natural history of the disease,” he added. “If you are on Remicade and doing well and you stop it, the disease will flare back up.”
Elson’s lab has uncovered an alternative treatment path. With ImmPrev Bio, he aims to take this discovery and see if it has a future as a product: a kind of antivaccine to remove mistaken memories from the immune system. “Vaccines create memory cells to protect you,” Elson said. “In an immunologic disease, however, the memory cells are the bad guys.”
Flagellins and antiflagellins
Studying samples from patients treated in UAB clinics and elsewhere, The proteins are all flagellins, which come together in massive numbers (30,000 to 50,000 at a time) to form a flagellum, the whip-like appendage that many bacteria use to move around. (“They can propel bacteria at the equivalent of 50 miles per hour in a fluid,” Elson said.)
Elson and his team have developed an immunological test to identify this reactivity to Lachnospiraceae flagellins. And, consistently, patients who are reactive have significantly increased memory T cells specific to flagellin in their circulations.
In a paper posted to BioRXiv in August 2023, Elson and co-authors reported that they had identified a key epitope (the specific region of a protein that an antibody targets) in a critical part of Lachnospiraceae bacteria flagellins called the hinge region.
ImmPrev Bio is creating a patient-ready diagnostic test, which it will use to identify potential patients for a first-in-human clinical trial of its second product: a therapy that targets flagellin-specific memory T cells for eradication.
Looking at samples from pediatric patients with Crohn’s disease, the researchers found that the magnitude of reactivity to this epitope “predicted the development of a complicated disease course in pediatric Crohn’s disease patients two to three years in advance,” they wrote. In an analysis of sera from infants without IBD, the antibody response to the same “Crohn’s” epitope peaked at 1 year of age, indicating that the elevated reactivity “to Lachnospiraceae flagellins in Crohn’s disease patients may result from an aberrant immune recall response of sensitization that occurred in early life.”
Research shows that people in the antiflagellin-positive group “have a higher risk of complications, including fistulas and strictures,” Elson said. “That’s true in adults and children who are tested at the time of diagnosis and followed for years. We have spent 30 years investigating this, and the more we know, this looks to be fundamental to at least a subset of Crohn’s disease.”
A diagnostic test and a targeted treatment
ImmPrev Bio is synthesizing this epitope to create a patient-ready diagnostic test. “That is a way to identify easily and quickly patients who are more likely to benefit from this therapy,” Elson said. “Everybody will have some low-level antibodies — infants in three different continents have high response to these flagellin antibodies in our studies, although their mothers do not. It’s one of the first things you respond to in the gut bacteria. But in some people, it comes back.”
ImmPrev Bio plans to use its diagnostic test to identify potential patients for a first-in-human clinical trial of its second product: a therapy that targets flagellin-specific memory T cells for eradication. The technique has already worked in cell cultures and in animal models, killing about half of the targeted memory cells and weakening the rest. “Will that actually work in a person?” Elson said. “We don’t know yet. That’s where the company comes in.”
Before he thought about starting his own company, Elson approached several pharmaceutical firms about his project; but it was still at such an early stage that none were interested. “This was not my first choice,” Elson said. “But it became the only possible way to find out if this will work in humans. It may not; it is a high-risk, high-reward situation.”
Getting approval from the Food and Drug Administration for a human clinical trial requires numerous tests and lots of paperwork, all of which cost money. The funding ImmPrev Bio has received from First Avenue Ventures “has been critical,” Elson said. For his part, Mike Goodrich, principal of the First Avenue Ventures fund, said, “We are thrilled to be working with Dr. Elson on this innovative diagnostic and therapy for Crohn’s disease.”
