A San Francisco-based biotech company is developing an anti-IgE therapy that prevents allergic reactions by directly disarming the immune system cells that trigger them.
The company, Excellergy, says its next-generation treatment would go beyond existing anti-IgE medicines such as Xolair by targeting not only free-floating IgE, but IgE already attached to immune cells.
Xolair primarily neutralizes “free” IgE antibodies in the bloodstream. Excellergy has developed a monoclonal antibody that additionally would remove IgE bound to mast cells and basophils, the immune cells which drive allergic reactions. According to the company, this distinction could translate into faster-acting and longer-lasting protection.
“We are downregulating those cells, shutting them off and disarming them,” Excellergy CEO Todd Zavodnick tells Allergic Living. If proven safe and effective in clinical trials, the therapy could offer “complete allergic control for a patient immediately,” he says.
A small Phase 1 trial is planned for the first quarter of 2026.
How IgE Triggers Allergic Reactions
People with allergies produce IgE antibodies that recognize specific allergens, such as foods, medications, or insect venom. Some IgE floats freely in the bloodstream. Other IgE binds to mast cells, found in tissues like the skin and gut, as well as basophils, found in the blood.
When an allergen binds to IgE on the surface of these cells, it triggers the release histamine and other inflammatory chemicals. This causes the symptoms of an allergic reaction, including itching, hives, swelling, breathing difficulty and, in severe cases, anaphylaxis.
In February 2024, the Food and Drug Administration approved Xolair (omalizumab) as the first anti-IgE biologic medication for reducing allergic reactions due to accidental exposure to foods, medications or insect stings. The drug is approved for use in adults and children ages 1 and older. Xolair is also used to treat asthma and chronic urticaria.
Xolair works by gradually lowering levels of free IgE in the blood. Over time, this reduces how much IgE is available to attach to mast cells and basophils, explains Dr. Alexander Eggel. He’s a co-founder of Excellergy and an associate professor in the Department of BioMedical Research at University of Bern in Switzerland.
In the Phase 3 OUtMATCH trial, Xolair increased tolerance to multiple food allergens after 16 to 20 weeks of treatment. “Xolair is doing that very well, and doing it for a lot of indications,” Eggel says. “But there are some limitations associated with that treatment.”
Targeting Already-Bound IgE
One limitation, Eggel says, is that Xolair has little immediate effect on mast cells and basophils that are already densely coated with IgE. These cells have “high-affinity” receptors for IgE, meaning the attachment is very strong.
As a result, those cells can remain primed to react to allergens until they natural degrade at the end of their lifespan. Basophils typically live for only about five to six days, but mast cells can persist for months to years, he says. “That’s where the problem lies. They carry IgE on their surface for their entire lifespan,” he says. “Those cells remain sensitized for quite a long time.”
Excellergy’s approach builds on research by Eggel and colleagues. They designed what they describe as a “trifunctional” antibody. In laboratory and mouse studies, the molecule binds to free IgE 20 to 30 times more potently than Xolair, Zavodnick says.
The antibody also removes IgE already attached to mast cells and basophils. It does this without triggering an allergic reaction. (Mast cells and basophils are also called “effector” cells.)
The therapy is part of a new class of drugs the company calls “allergic effector cell response inhibitors.” Eggel says his team saw the potential to create a better anti-IgE approach with these inhibitors.
“They not only block free IgE like omalizumab does,” Eggel says. “It also very efficiently removes the IgE from those basophils and mast cells, very rapidly, within hours of treatment.”
Tests in peanut-allergic mice found their immune cells were desensitized within 36 hours of receiving the experimental therapy. The mice also didn’t react when exposed to peanut allergen.
What’s Next for Excellergy’s Inhibitors?
Eggel notes that Xolair can remove some IgE from immune cells at very high concentrations, but those levels are well above current dosing. Excellergy’s molecule does this more efficiently and at lower doses, he says. “This renders the allergic cells inert and no longer reacting,” he says.
It’s still early days for Excellergy’s effector cell response inhibitor approach. The upcoming Phase 1 clinical trial will assess the antibody in healthy volunteers. They will receive different doses of the antibody to evaluate safety and how it behaves in the body. Results are expected toward the end of 2026. Like Xolair and other monoclonal antibodies, the treatment would be administered by injection.
Later trials will test clinical effectiveness. Excellergy recently announced $70 million in funding to support development, with a Phase 2 trial planned for 2027, Zavodnick says. The CEO previously held the same role at Dermavent Sciences, which developed the steroid-free psoriasis and eczema cream Vtama.
“Our product doesn’t just bind free IgE,” he says. “We’re removing it from effector cells, and shutting those cells off…. It’s the logical next step from where Xolair has built the market.”
Related Reading:
After Stopping Xolair, Kids Could Eat Some Allergenic Foods
What to Know About the First Xolair Biosimilar
