A Swiss biotech company has launched the first clinical trial of a combination antibody that blocks allergic reactions to peanut. The biologic therapy aims to neutralize peanut proteins before they can trigger an immune response.
The company, Mabylon, says its treatment could protect from peanut allergy reactions with just two to four injections a year.
People with peanut allergy have IgE antibodies attached to, or bound to, immune system cells called mast cells and basophils. This state is known as sensitization.
Allergic reactions occur when peanut protein binds to these IgE antibodies on the cell surface. This triggers the release of histamines and other inflammatory chemicals. Symptoms such as itching, hives, swelling, breathing difficulty and potentially life-threatening anaphylaxis can follow.
Mabylon’s experimental therapy combines three, lab-engineered antibodies into a single, “tri-specific” molecule. The molecule binds to the exact sites on peanut proteins that IgE would attach to. By occupying those sites, their combined antibody neutralizes the allergen before it interacts with IgE on mast cells and basophils. This prevents immune cell activation.
Dr. Niccolò Pengo, Mabylon’s chief scientific officer, says a single injection could provide protection for three to six months.
“We will be able to neutralize the major peanut allergens, Ara h 2, Ara h 3, and Ara h 6,” Pengo says. This “will block the allergic cascade and protect the patient from the allergic reaction when they encounter peanut.”
Previous studies have shown that Ara 2, 3 and 6 are most strongly linked to severe allergic reactions to peanut.
“This clinical trial is an important milestone and a significant advancement of our efforts to address the unmet needs in peanut allergy management through innovative antibody engineering,” says Dr. Alcide Barberis, Mabylon’s CEO.
Phase 1 Trial Begins
The Phase 1 trial consists of two parts. Part A will enroll up to 32 adults without peanut allergy. Participants will receive one or two doses of the antibody therapy, known as MY006, at a low, middle or high dose level, or a placebo. This phase is to assess safety and measures such as absorption and how long the antibodies stay in the body.
Part B of the trial will include up to 16 peanut-allergic adults and adolescents ages 12 to 55. This phase will continue to assess safety, as well as MY006’s protective effects against reactions to peanut protein and how long they last. Participants will receive a single dose, then undergo a food challenge to peanut several weeks after the injection.
To develop the antibody therapy, researchers mapped the “hot spots,” or epitopes, on peanut proteins where IgE antibodies bind. They then screened antibodies derived from the memory B cells of peanut-allergic individuals to identify antibodies that target those hotspots.
In the lab, the team engineered a single molecule containing three antibodies that together block these epitopes. The resulting therapy is considered an IgG4 antibody. IgG4 antibodies are known as blocking antibodies because they can bind to allergens and compete with IgE without activating mast cells.
“If you block these hotspots, you are able to control the allergic reaction,” Pengo says.
He says that combining multiple antibodies into one molecule produces a more potent allergen neutralization effect than administering each of the three antibodies separately. This increases the chances the therapy will fully block an allergic response. “We expect higher efficacy because of how we engineered this molecule,” he says.
Early research suggests that nearly all patients should be able to tolerate at least 1,000 milligrams of peanut (3 to 4 peanuts), within days of starting therapy.
The antibodies are engineered to be long-lasting, allowing injections to be given only a few times a year. This could offer an advantage over the existing biologic anti-IgE therapy, omalizumab (or Xolair).
A Different Approach
The U.S. Food and Drug Administration approved Xolair in February 2024 to help prevent allergic reactions from accidental exposures to food allergens in adults and children. Xolair is administered by injection every two or four weeks. It works by binding to free-floating IgE in the bloodstream. By gradually reducing the amount of free-floating IgE, Xolair reduces the amount of IgE available to attach to mast cells and basophils.
The Mabylon approach differs in that it targets the allergen instead of IgE. This could neutralize the peanut protein before it ever engages with IgE and activates immune cells. “The approach we’re taking really differentiates us,” Pengo says.
The treatment would likely need to continue indefinitely to maintain protection. Mabylon is also exploring monoclonal antibody injections for birch and grass pollen allergy.
Related Reading:
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