Q&A: First patient dosed in IgGenix ACCELERATE Peanut phase 1 clinical trial

Key takeaways:

• IGNX001 attaches to peanut proteins in order to neutralize them.
• The study targets older adolescents and adults.
• Recruitment for the study is ongoing.

IgGenix announced the first patient dosed with IGNX001, a monoclonal antibody-based therapeutic for peanut allergy.

The ACCELERATE Peanut phase 1 randomized, multi-centered, double-blind, placebo-controlled clinical trial with a single ascending dose evaluates IGNX001 in patients with peanut allergy. It aims to assess the safety, tolerability and proof of mechanism in IGNX001 in patients aged 15 years and older.

Healio spoke with Jessica Grossman, MD, CEO of IgGenix, about IGNX001 and what it means for patients with peanut allergies.

Healio: What is IGNX001?

Grossman: IGNX001 is our antibody therapeutic. We are using a subcutaneous injection. The more specific form of our antibody, without revealing anything confidential, is what’s called an IgG4 antibody, and it uses the same backbone that’s used in multiple other different commercial antibodies such as dupilumab (Dupixent; Regeneron, Sanofi) and Keytruda (pembrolizumab, Merck).

What’s different about our antibody and all antibody therapeutics is what they attach to, what they bind to, what the antigen binding regions also known as CDR’s are for, and IGNX001 binds peanut. The antigen that it is attracted to is peanut. It binds some specific proteins in peanut.

This is our first study in humans. We have a lot of animal data, preclinical data to support it. If a person is allergic to peanut and ingests peanut, the antibody should act like a heat-seeking missile to find that peanut, attach to that peanut and neutralize it so that peanut can’t interact with the allergy cells that are in a peanut-allergic patient’s body.

Healio: What would you say is the main thing that separates it from other immunotherapies?

Grossman: This is the only product that has a mechanism of action that does this. Palforzia (Peanut [Arachis hypogaea] Allergen Powder-dnfp, Stallergenes Greer) is an oral immunotherapy for peanut allergy. It’s actually just giving people minute doses of the allergen, peanuts. So, it’s very different than that. And then there is another antibody therapeutic that is approved for food allergy called Xolair (omalizumab; Genentech, Novartis). It attacks — or binds or attaches to — the IgE antibodies in the bloodstream. It’s more like an anti-immune drug. It neutralizes the allergic antibodies. So, it’s very different. They’re neutralizing antibodies. We’re neutralizing peanut.

Healio: Can you tell us about the trial and what the dosing looks like?

Grossman: This is our first human study in peanut-allergic individuals. It’s a single ascending dose because what we’re trying to see is if it’s safe in humans. We have a very good preclinical safety record. All of our preclinical animal studies showed no safety findings of concern. We’re doing a single dose at three different dose levels: a low dose, a medium dose and a high dose. Starting with the lowest dose, we have a couple patients treated. Then, we’ll mature to the medium dose and then we’ll go to the high dose. I will say in our animal studies we used a dose that was like 48 times our highest dose to look for toxicity or toxicological findings. And we didn’t see any.

Healio: Can you tell us about some of the methods that the trial is using?

Grossman: The primary endpoint is safety and we’re measuring that as adverse events. We’re looking for any abnormalities in labs or clinical signs or symptoms. The secondary endpoint is pharmacokinetics and anti-drug antibodies.

We’re going to measure concentration of antibodies in the blood over time. The study is a 12-week study for that single dose. The patient gets their single dose and then they come in pretty much weekly for the next 12 weeks. And at each time point, we’ll take a blood sample and try to map out how much antibody is in the blood over time.

We’re also looking at anti-drug antibodies over time. The other thing that makes this trial unusual is that we’ve packed in a whole bunch of different pharmacodynamic markers. We packed in a lot of early pharmacodynamic markers because our antibody attaches to peanut. One of the markers that we’re looking at is how patients react to an oral peanut challenge at a 4-week time point.

Healio: Where is the study taking place?

Grossman: It’s in four centers in Australia, and there are several reasons we chose Australia. First of all, I, being a physician myself, have done studies in Australia before and I have just found it to be extremely efficient and cost effective.

A lot of companies take this route. Australia has these mechanisms to get R&D tax incentives. This makes it efficient and super-economical. The other thing that I love about Australia is they have really high-quality, trained physicians. We’re doing our trial at four different hospital sites with hospital-trained immunologists. These are world leading immunologists. So, that was another big benefit of doing it over there.

Healio: Is there a timeline for the study? When can we expect to see some results or any other data?

Grossman: It’s hard to estimate since we’re in very early days and it depends on recruitment, but so far, it’s going well and we think we’ll have some topline data mid-next year, in either June or July 2025.

Healio: Is recruitment still ongoing?

Grossman: Recruitment is still ongoing. If anyone has a peanut allergy and lives in Australia, we would love for them to visit our clinical trial website at: https://www.iggenix.com.au/.

I think the other thing that makes this study unique is there really aren’t a lot of trials in adults. Our trial is for patients aged 15 to 55 years. I think adults aged 18 years and older are often overlooked in allergy trials, and people go straight to pediatrics. We think it’s an important population because a lot of time, that’s actually when they can get the most severe reactions and are also at risk to be at college, be at university, be out of the house, eating out, etc. We think offering a potential solution to that patient age range is important. When we start to really think about getting FDA approval here in the U.S., we want to make sure that we cover those adult patients as well because they really have very few options.

Healio: Is there anything else you would like to add?

Grossman: I think there is an unmet need in a patient population that’s been ignored. People usually say, “Just avoid the allergen” or “Just use your EpiPen (Pfizer),” right? And guess what? Using an adrenaline autoinjector is a traumatic experience, and people are avoiding it.

One of the big challenges with peanut allergy is peanuts are a low-cost source of protein. Peanut flour finds its way into a lot of things. It’s not labeled and finds its way into pizza crust, bread, all sorts of things that you wouldn't think about as they’re using it as a fattening and as a protein flour because it’s quite nutritional.

For people with peanut allergy, they’re avoiding, but there’s also these hidden pockets of peanut allergen out there. We really want to support those patients and make sure they aren’t wrestling with a life-threatening reaction that literally can kill them when they take a bite of food. And the way that we foresee our antibody being used is in a protective way.

The way it would work is you would go to your physician, get your shot of IGNX001, and be protected.

One of the things that we think is a potential advantage about IGNX001 — and we’re studying this in the trial — is we think it should really work immediately, within days. We had a mouse animal study where we injected the mice with our antibody, and what we saw is 2 days after injection, when we fed them peanuts, they have complete protection. So that was super exciting. We’re hoping that holds up in humans as well.

Reference:

• IgGenix announces first patient dosed in phase 1 clinical trial “ACCELERATE Peanut” evaluating IGNX001 in peanut allergy. https://iggenix.com/pressreleases/iggenix-announces-first-patient-dosed-in-phase-1-clinical-trial-accelerate-peanut-evaluating-ignx001-in-peanut-allergy/. Published Oct. 16, 2024. Accessed Nov. 4, 2024.

For more information:

Jessica Grossman can be reached at jgrossman@iggenix.com.