AZ's R&D chief Barr touts internal 'science success story' after IL-33 antibody's stellar showing in COPD

Biotech AZ's R&D chief Barr touts internal 'science success story' after IL-33 antibody's stellar showing in COPD By Fraiser Kansteiner Sep 8, 2026 10:50am AstraZeneca R&D chief medical officer respiratory diseases With a detailed data drop that AstraZeneca’s R&D chief described as an internal “science success story,” the British Big Pharma has secured an FDA priority review for what it believes could become a flagship biologic in chronic obstructive pulmonary disease (COPD). In detailed results from the late-stage Oberon and Titania trials—first teased in March and detailed in full at the European Respiratory Society Congress in Barcelona this week—the drugmaker laid out the extent of its IL-33 inhibitor’s potential to reduce moderate and severe exacerbations in a wide range of COPD patients still struggling with those “lung attacks,” as AstraZeneca’s Sharon Barr, Ph.D., called them, despite using standard-care inhaled therapy. In the headline results, a 300 mg dose of tozorakimab given once every four weeks curbed those moderate and severe exacerbations in the studies’ primary population of former smokers by 29% in the Oberon study and 34% in Titania.

In the overall population of both current and former smokers, these reductions were 30% and 29%, respectively, versus placebo and inhaled standard of care. The benefits also extended to clinically meaningful exacerbation reductions in all prespecified patient subgroups and specifically turned up promising signals in patients across a range of blood eosinophil counts, with Barr telling Fierce that “it’s the details that make this even more exciting than the high-level results that we’ve already shared.” In fact, during AZ’s tozorakimab poster presentation at the ERS 2026 Congress this past weekend, attendees were so enamored by the data that event organizers had to encourage people to clear the room and look at the other presentations on offer, Barr said in an interview. “I think it really speaks to the fact that there is a lot of buzz around these data because the entire respiratory community has been so desperate for new therapies for these patients,” she explained.

The respiratory disease continues to represent a “staggering unmet medical need,” Barr said, highlighting the COPD exacerbations that the Oberon and Titania studies homed in on, which she added carry a greater mortality risk than a heart attack. “When a patient has a severe exacerbation, only about half of them are still alive within three and a half years,” she pointed out. As for tozorakimab specifically, Barr christened the molecule “an AstraZeneca science success story,” harkening several years back to the point at which researchers began to explore IL-33 as a driver of respiratory disease, and COPD in particular.

At the same time, “there was still so much that wasn’t understood,” she admitted, highlighting the insight that IL-33 signals through both ST2 and EGFR through the RAGE pathway, a discovery Barr attributed to AstraZeneca's own scientists. Understanding the need to tackle both pathways in COPD—and aware of competitor candidates in the hopper, including one that bound ST2—the company ultimately had to make some “courageous decisions,” Barr said. These included taking a prior COPD molecule offline and going back to the drawing board to reinvent its potential IL-33 label “to make sure that we had a molecule that could block signaling through both arms of the pathway, through both the reduced form and the oxidized form, knowing that we wouldn’t be first, but striving to be best.” “When we put [tozorakimab] into the clinic, we firmly believed that we had a differentiated molecule, and we saw the other molecules blocking just ST2 or partially blocking IL-33, unable to deliver two positive pivotal studies in COPD,” Barr explained.

“We kept marching forward because we believed our molecule was differentiated, and now I think we have the clinical validation that supports that.” Ultimately, AstraZeneca finds itself on much better footing these days when it comes to potential biologic rivals to tozorakimab in COPD. Sanofi and Regeneron’s Dupixent, for instance, is approved to treat COPD exacerbations in patients with high eosinophil counts, but not low ones. Meanwhile, the future has become cloudier for other next-gen IL-33 candidates from Sanofi and Regeneron, as well as Roche, which have suffered trial flops in recent years.

One other potential ingredient for AstraZeneca’s success in its duo of studies was that the company was “ambitious in the trial design, willing to look at an all-comers population,” Barr said, “and willing to enroll the most severe patients.” Prior studies for would-be biologics rivals in COPD “avoided enrolling” those patients, she pointed out. She also highlighted the Big Pharma’s painstaking design of exacerbations in its trial, which “gave us a very rigorous readout,” and pointed to “the extra effort and investment” the company put in to understand the effect of mucus plugs in patients. Barr described mucus production as a “key feature in disease diversity,” noting that mucus plugs—obstructing clumps of mucus that block patients’ airways—are associated with worse outcomes in COPD.

In its data announcement, AstraZeneca noted that an integrated analysis of Oberon and Titania found tozorakimab “demonstrated a reduction in patients’ mucus plug score,” with the pharma claiming its biologic is the first to deliver such results in a broad COPD population. “So being able to reduce those mucus plugs, we expect, is an important part of driving benefit for patients who are living with COPD,” Barr said. Again touching on the breadth of the study populations, Barr added that tozorakimab “worked across all eosinophil levels in both current and former smokers across all levels of lung function,” which she suggested “really simplifies decision-making for clinicians, and it allows them to offer therapy to the broadest possible patient population.” In the highest patient eosinophil count group, tozorakimab helped chart a 43% reduction in exacerbation risk, which Barr stressed were “unprecedented data.” In the mid-level group, AZ’s drug delivered a 23% reduction and, in the lowest group, a 34% reduction in eosinophils, which Barr said suggests efficacy “in all patient subgroups.” As for AZ’s recent guidance upgrade on the medicine’s sales opportunity, the lift from a $3 billion to $5 billion range to $5 billion plus was informed by multiple factors, Barr said, including the fact that “in 2024, there were multiple competitors, and there aren’t anymore.” Additionally, “we know that this is a massive unmet medical need, and this is a really incredible set of data that we think will be very convincing to the clinical community,” Barr said.

Looking ahead to a potential evolution of the COPD treatment landscape, Barr noted that most patients start treatment in the community with an option like a triple therapy, and for them, having an option like AstraZeneca’s inhaler Breztri will remain a “really important part” of that journey. But of the patients uncontrolled on triple therapy, which Barr described as “about half of them today,” just a “small fraction” are currently eligible for biologic therapy, which she emphasized AstraZeneca is working to change. Understanding that COPD is not a “one-size-fits-all” disease, AstraZeneca is also looking at its antibody drug Tezspire for patients with T2-driven disease, and the company continues to think about new mechanisms for tackling COPD through both systemic and inhaled drugs, Barr said.

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