Considerations For Allergic Rhinitis Trials Are Nothing To Sneeze At

A conversation with CEO Inimmune David Burkhart, Ph.D., and Clinical Leader Executive Editor Abby Proch

The closure of GSK’s Hamilton, Montana, R&D site is now 10 years in the past. And in the decade since, a team of its former innate immune experts have been developing next-generation, disease-modifying immunotherapies. They’re focusing on a several classes of toll-receptor agonists, targeting a common but still largely unsolved condition for millions around the world: seasonal allergies.

In this Q&A, CEO David Burkhart discusses how their collective career hiccup has evolved into a robust clinical pipeline and highlights the company’s lead allergy candidate, INI‑2004, now in a Phase 2 allergic rhinitis chamber trial.

Burkhart explains how INI‑2004’s mechanism of action reprograms the immune system to address the underlying cause of allergy rather than just its symptoms, setting it apart from conventional antihistamines and corticosteroids, and shares insights related to site selection, trial design (including the use of allergy chambers), and seasonal timing to support more precise, efficient studies.

When we talk about where you are now with INI-2004 and your Phase 2 trial, what brought you to this point? Have you had other successful candidates?

It's not our first candidate. We have developed several classes of toll-receptor agonists, including one focused around TLR7/8, with a lead compound called INI-4001. From all of our history and the work in the literature, we knew that these innate immune agonists had tremendous potential across several disease-modifying immunotherapy applications.

So, we advanced both an allergy program and an oncology program individually to have two shots on goal as a biotech company. In parallel, INI-4001 is moving forward into oncology to treat patients with solid tumors. INI-2004 was advanced in the allergy program as an intranasal spray to treat allergic rhinitis. This provides an opportunity to establish proof of concept in allergic disease, and then we plan to expand into other allergy indications from there.

We’ve now been a company for 10 years, and we've just recently began enrollment for a new Phase 2 INI-2004 allergic rhinitis chamber trial, which will be complete by June 2026. INI-4001 is still in a Phase 1 oncology trial in Australia.

For allergic rhinitis, there is a standard of care and a sea of companies treating the condition. What about the condition and the landscape made you want to move forward with your candidate?

A lot of people think that allergy is already a disease that's been dealt with. To some extent, it has. But that's primarily true for patients with mild to moderate disease. There's over-the-counter treatments that help about 20% of patients substantially solve their problem. But for the vast majority of allergy sufferers, those over-the-counter treatments often provide only partial relief, if any, especially for severe disease sufferers. And then those patients often move to prescription oral corticosteroids, which again provide efficacy for only 20%-25% of patients. Those corticosteroids come with pretty serious side effect profiles, which are trade-offs for their quality of life.

At Inimmune, we wanted to develop a disease-modifying allergy immunotherapy that had a very clean safety profile. All of those over-the-counter treatments, antihistamines, and corticosteroids, primarily treat the symptoms. They don't actually treat the underlying problem of the disease. INI-2004 is targeted to do just that and has a durable response — it works by reprogramming the immune system so it no longer reacts to that ragweed or tree pollen as an allergen.

With this class of drug, are there competitors to be mindful of, say when you're choosing a site or working with your KOLs and your potential PIs?

There are a few other companies exploring different classes of molecules for allergy immunotherapy, but not in the same way as ours. Currently, disease-modifying immunotherapies exist for allergy sufferers, such as SCIT (subcutaneous) and SLIT (sublingual) immunotherapies. However, those require repeated weekly or monthly injections or tablets and take years to show full benefit. Whereas with our immunotherapy, we're able to achieve that same level of efficacy in just four to six weeks.

Is this something that you lead with when prospecting sites, and how do you identify sites that you'd like to work with?

Allergic rhinitis presents some unique challenges. If you're allergic to red cedar, for example, or a specific tree pollen, and that hasn't come out yet because of the timing of the season, you won’t begin reprogramming the immune response. If you use the nasal spray, as long as you get exposed to that allergen within a one-week window, it will desensitize you. Then you would stay on INI-2004 to get the full reprogramming of the immune response and the disease-modifying therapy.

For site selection, it's critical to understand the timing of the allergy season for those allergic rhinitis sufferers. For example, we need to understand the pollen seasons and regional patterns so we're not starting patients too early or too late on the immunotherapy.

That's another layer to the site selection process that other therapeutic areas don't have to consider. Did you rely on in-house expertise or consultants to get the timing right?

Each geography is unique. Fortunately, many of the trial sites understand their local season because they have to. In Australia, for example, there's actually two allergy seasons. That's both a challenge and an opportunity. But also, fortunately, because of the prevalence and growth of allergy as a disease, a lot of local and state governments and other agencies are tracking the pollen levels at different times of the year.

When do you opt for a chamber trial design instead of a field study? And how is it used?

The real advantage of these allergy chamber studies is that you can challenge your placebo patients and treated patients at the same time with the same dose of allergen in a very controlled environment. There's basically a large room with specific seating areas. All of the patients go in at the same time, and they all get challenged with a very controlled amount of a specific allergen. It really helps you more precisely assess the efficacy of the drug and improves the signal-to-noise ratio and variability of the trial.

Are these chambers found anywhere, or are they built specifically for a trial?

There are a handful of sites around the world that are already set up to do allergy chamber trials. The one we chose in Kingston, Ontario, is one of the largest and most experienced. They were one of the best fits for us because we wanted to test approximately 80 to 90 patients at a time. And those clinical trial sites also have databases of patients that they know have a specific degree or severity of allergy in response to ragweed, for example. So, they can call upon that database of patients and get your patients enrolled fairly quickly.

Do you find that patients who enrolled in Phase 1 are rejoining for Phase 2, or do you have more recruitment efforts to find additional patients?

We would if we were using the same site, but we're not. Our Phase 1 trial started with healthy volunteers in Australia and then moved to seasonal allergic rhinitis sufferers in Minnesota, and we’re doing the Phase 2 trial in Kingston because that's where that specialty chamber site is. Our Phase 2b field trial will probably be in the U.S., but we haven't selected sites for that yet.

Finally, what have you learned from Phase 1 that helped you inform the Phase 2 and what from Phase 2 will be useful to Phase 3?

From Phase 1, we learned that patients needed to get exposed to a certain amount of allergen to get a good response from INI-2004. Some of the patients who got the lowest dose of allergen in the Phase 1 nasal challenge study — in which you put the allergen in a mask, you put the mask on, and you breathe it in — were all getting different levels of allergen based upon their allergy severity. So, the patients in the Phase 1 trial who received the lowest allergen dose showed the weakest response to the treatment. In many ways, it behaved like an allergy vaccine. They were getting too little of the allergen to reprogram the response effectively. And the patients who were getting higher doses of the allergen had the most robust efficacy response. That's something which we'll further evaluate in the Phase 2 data.

For the Phase 2 field trial and then a Phase 3, we want to focus on patients with severe allergic rhinitis because they're one of the largest groups of patients with the greatest unmet medical need. In it, we want to know how quickly it takes effect. In part, that's important because we’re also going into food allergy, and we want to make sure we get patients' immune responses reprogrammed quickly because those patients face a risk of anaphylaxis.

About The Expert:

David Burkhart, Ph.D., is CEO and cofounder of Inimmune. A passionate and results-oriented leader, he focuses on building high-performing teams and advancing innovative immunotherapies that address significant unmet medical needs. He also loves cats.

Dr. Burkhart brings nearly 20 years of experience across the biotechnology and pharmaceutical industries, with expertise spanning project management, business development, licensing, medicinal and analytical chemistry, formulation, and drug delivery. Prior to founding Inimmune, he led the formulation R&D team at GlaxoSmithKline, where he focused on targeted drug delivery strategies, including nanoparticle formulations for vaccines and immunotherapeutics.

Earlier in his career, he served as a senior scientist at Hollister-Stier Laboratories, gaining experience in cGMP analytical and manufacturing operations. Dr. Burkhart earned his Ph.D. in organic chemistry from the University of Idaho and completed postdoctoral research in oncology at the University of Colorado Boulder.