The Next Generation Of Food Allergy Therapies May Be Coming Soon

Growing up with a severe peanut allergy, Grace Guthrie has always been acutely aware that any accidental exposure could land her in the emergency room.

“It makes you hyper vigilant about food,” says Guthrie, 28. “The last time I had a reaction was in a restaurant, and the soup had unannounced peanuts in it. Within a few minutes I started feeling symptoms – I started to feel a lot of chest tightness and my voice got very hoarse to the point where it was hard to talk. I ended the night in the hospital where they gave me intravenous epinephrine, and a steroid to stabilize my immune system.”

Such experiences are still all too common. The Centers for Disease Control & Prevention (CDC) estimate that almost 6% of U.S. adults and children have a food allergy, the most common of which are shellfish, peanut, milk, and tree nut. Each year, 200,000 Americans require emergency medical care for life-threatening allergic reactions to food, known as anaphylaxis.

Economically, food allergies and sensitivities costs approximately 25 billion dollars every year in the U.S. alone, placing considerable strain on not only patients and families, but also the healthcare system.

Why Allergies Happen

Food allergies occur when the immune system overreacts to particular proteins within a food and produces Immunoglobulin E (IgE) antibodies. These bind to basophils and mast cells within your skin, airways, and gastrointestinal tract, triggering the release of a chemical called histamine. Because histamine plays a key role in the body’s inflammatory response, and regulates numerous bodily functions, this release can have severe consequences.

Standard allergy medications such as Benadryl or the EpiPen work by suppressing histamine, but this merely tackles the symptoms, rather than preventing it in the first place. For more than a decade, allergy clinics have pursued a prophylactic treatment approach known as oral immunotherapy to try to increase patients’ tolerance slowly and steadily to small doses of their allergen trigger. The idea is that over time, this will train their immune system to produce Immunoglobulin G (IgG) antibodies, which are thought to inhibit the function of the harmful IgE antibodies.

The American Academy of Allergy, Asthma and Immunology has reported that for peanut, egg and milk allergies, oral immunotherapy works to desensitize approximately 60-80% of patients, but it is no panacea.

“It does not cure food allergies, so patients still need to avoid those foods and carry their epinephrine autoinjector,” says Michele Pham, assistant professor of medicine and director of the adult food allergy program at the University of California, San Francisco. “It may help patients better tolerate low exposures and cross-contact, but success rates vary by food, and it is not successful for everyone.”

Current Treatments Fall Short

In 2020, the Food & Drug Administration granted regulatory approval to an oral immunotherapy for children with peanut allergies called Palforzia, developed by California-based Aimmune Therapeutics. The company was subsequently bought by Nestlé for $2.6 billion.

However, the product failed commercially, and last November, Nestlé announced that it was stopping further development of the drug, according to the food giant’s 2022 annual report.

One of the major problems with oral immunotherapy is that the treatment process is arduous for patients and their families. It requires regular visits to a clinic for up to four hours, so the patient can be monitored in case of adverse effects, and in some cases, it can even induce anaphylactic shock, a traumatic experience. In the phase 3 trial of Aimmune’s oral immunotherapy, known as the PALISADE trial, nearly 14% of participants in the treatment arm experienced anaphylaxis and 10% had to withdraw from the trial altogether due to the severity of their reactions.

These challenges are a particular problem because food allergies are becoming progressively more common, for reasons no one fully understands. The non-profit Food Allergy Research & Education (FARE) organization reported that private insurance claims with diagnoses of anaphylactic food reactions increased by 377 percent between 2007 and 2016.

It is painfully clear that patients and physicians need a new paradigm.

The Next Generation of Therapies in Development

Anat Binur, co-founder and CEO of Ukko, an Israeli company looking to develop the next generation of allergy therapeutics, describes the current treatments as being trapped in a deadlock. “Food allergy immunotherapy has saved lives,” she says. “But because approaches use the allergen itself as the therapeutic compound, you have this trade-off between safety and efficacy. You have to go with small doses, and you can’t go with the most efficacious route which may be injection, because it’s too risky to inject the patient with a toxic protein.”

Ukko’s aim is to revamp the entire oral immunotherapy process through a clever combination of artificial intelligence (AI) and advanced protein engineering. The company has developed a computational design platform that allows them to tweak the sequence of a protein within a peanut or a shellfish, for example, and edit out the elements which induce an allergic response.

This requires a multi-stage process involving screening hundreds of blood samples from people with allergies from all over the world, identifying the sites on a protein within certain foods that trigger allergic reactions, and then using AI to predict how best to alter that protein sequence. Finally, the edited version is tested on patient immune cells in vivo, to ensure that it will still modulate the immune system in a therapeutic manner, but without causing harm. Ukko is planning to test its product on patients for the first time through a Phase I/IIa clinical trial next year.

“We want to get rid of the bad parts of the protein and keep the good parts, the ones which are actually training your immune system, such that you won’t react,” says Binur. “With oral immunotherapy you need a build-up phase because not everyone can tolerate ingesting the allergen that they’re allergic to. Whereas we’ll be completely the opposite. No build-up, it’ll work immediately.”

Another company, Stanford spin-off IgGenix, is synthetically creating the IgG antibodies which the body needs to stop the IgE-mediated allergic response. Through cutting-edge single-cell genomics, they take blood samples from individuals who are highly allergic, isolate the B cells which are producing the IgE antibodies in response to different stimuli – which can range from peanuts to their pet cat – before extracting their underlying genetic sequences and manipulating them to create corresponding IgG antibodies.

Their aim is to create what is effectively an allergy blocker, initially just for peanuts, which patients can receive as an injection every two months. Right now, they are conducting preclinical studies and they hope to initiate a Phase I trial in the later part of next year.

“We’ve tested now dozens and dozens of serum samples and plasma samples, and we’re able to inhibit the peanut allergen interacting with the cells in 80% of them,” says Jessica Grossman, CEO of IgGenix. “The advantage is its very specific. It’s only binding to peanut, so it shouldn’t bind any human proteins and the effect will be immediate. With oral immunotherapy, the body naturally makes these IgG blockers, but it takes six months.”

According to a 2023 study, about 40 percent of children with food allergies have multiple food allergies, and the ultimate dream of Ukko and IgGenix is to create either a single one-shot therapeutic which could provide protection against all common allergies at the same time, or even a personalized vaccine.

“If I fast forward 10-20 years from now, the vision could potentially be that you could make a customized therapy for someone, let’s say who’s allergic to peanut and shellfish, and they would get a cocktail of those antibodies,” says Grossman.

However, even if all goes to plan, both Ukko and IgGenix are still years from potential regulatory approval. In the meantime, the next advance for the field could potentially be a drug being developed by California-based biotech Alladapt Immunotherapeutics.

Their version of oral immunotherapy combines tiny protein fragments from 15 different commonly allergic foods. These fall into nine different food groups, namely eggs, fish, milk, peanuts, sesame, shellfish, soy, tree nuts, and wheat, with the idea of being able to offer a broader range of protection at the same time.

Ashley Dombkowski, CEO and co-founder of Alladapt Immunotherapeutics is optimistic that the added convenience of being able to work against multiple allergies simultaneously could be able to help the product succeed where Palforzia failed.

“Most peanut-allergic patients seeking treatment are poly-sensitized,” she says. “Tackling only peanut allergies makes it even more challenging for physicians to find enough patients to implement the procedure in their offices at scale. Next-generation approaches will need to address these kinds of issues to support patient needs and clinician workflow.”

For patients like Guthrie, the idea of better and more tolerable therapies would be life-changing, greatly reducing anxiety for her and her family.

“Oral immunotherapy can be grueling, costly and I don’t know how available it is beyond major cities,” Guthrie says. “New treatments are hugely important because they [could] help kids and adults live their fullest life without constantly worrying about what they’re eating.”

Such a leap for allergy sufferers would indeed be one to savour.

Thank you to David Cox for additional research and reporting on this article. I’m the head of Leaps by Bayer, the impact investment arm of Bayer AG. We invest in potentially breakthrough technologies to overcome ten of humanity’s greatest challenges, which we call “Leaps,” including to reverse autoimmune diseases and chronic inflammation. Ukko is one of the 55+ companies in our portfolio.

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