Connect Biopharma Holdings Limited Ordinary Shares Study result

Good morning, everyone, and thank you for joining us. With me today from Connect are Barry Quart, Chief Executive Officer and Director, and Kimberly Manhart, Executive Vice President, Chief Development Officer. For those of you participating via conference call, the slides are made available via webcast and can be accessed by going to the investor relations page of our website following the conclusion of today's call. Before we begin, I would like to remind you that this call will contain forward-looking statements under applicable securities laws.

These statements involve substantial risks and uncertainties and include statements concerning the top-line results we're announcing today, the timing and content of additional data analysis and future data presentations, our anticipated regulatory strategy, interactions with the FDA and other health authorities, the design, initiation, timing, and results of future clinical trials, our cash runway, and anticipated use of capital, and our future expectations, plans, prospects, corporate strategy, and performance. Actual results may differ materially from those indicated by these forward-looking statements due to various important factors, including those discussed in the Safe Harbor slide, the press release issued by the company today, and our filings with the SEC. Forward-looking statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update these statements.

Now, I'll turn the call over to Barry.

Thank you, David. Welcome, everyone. Thank you for joining us this morning. We are very pleased to have this opportunity to review with you the results of the Seabreeze STAT asthma study. Overall, we achieved our objectives to demonstrate that rademikibart works quickly to improve airway function, and that this improvement results in substantially fewer patients returning to the hospital, emergency department, or clinic for additional care in the months following the asthma attack. Unfortunately, the overall rate of treatment failure in the study was substantially lower than projected. Even with a larger effect size than projected, we still just missed statistical significance. Where the study did achieve statistical significance is in the equally important and more challenging key secondary endpoint of FEV1 improvement on day 7.

We see this endpoint as more challenging because patients are recovering from an acute exacerbation, a population almost never included in clinical trials, and they are receiving aggressive treatment for their acute exacerbation, including systemic steroids and bronchodilators, which result in a sizable increase in the placebo group. We are then asking rademikibart to improve airway function even further, and it does exactly that. The increase in FEV1 at day 7 with rademikibart is more than twice what is obtained with bronchodilators alone. I will also note that benralizumab, which showed significant reduction in treatment failure in the ABRA study, showed no benefit in FEV1 or other measures of respiratory function through 28 days. Improvement in FEV1 has also been used as a primary endpoint for the approval of Ohtuvayre in COPD. It is an established regulatory endpoint.

We believe that demonstration of rapid, significant benefit in FEV1 provides a clear roadmap to phase III, which we intend to confirm with the FDA later this year. Lastly, rademikibart continues to be remarkably well-tolerated. I will not spend a lot of time on the design slide, but I will note that we use the same entry criteria for previous exacerbations in the prior year as the ABRA study. Here is the schematic of patient flow. We screened 323 patients in order to enroll 160 patients. Here is the breakdown of baseline characteristics. Of note, enrollment into the study went quickly in Eastern Europe, resulting in a high proportion of patients coming from Serbia and Georgia.

Although these countries, and more specifically the hospitals we used, follow the same treatment guidelines as we do in the U.S., there may be other aspects of patient care that impacted the unexpectedly low rate of treatment failures observed in the study. Here are the results for the primary endpoint. You may recall that Study 206 was powered based on a 45% placebo treatment failure rate, with approximately a 50% reduction observed for benralizumab in the ABRA study at 28 days. While the 66% reduction seen with rademikibart exceeded the target 50% reduction, there was just not sufficient events to reach statistical significance. In this study, the majority of events resulted in an unscheduled visit to the clinic or emergency department. Fortunately, no deaths or hospitalizations.

Within patients experiencing a treatment failure, there were 5 exacerbations in the placebo group compared to 2 in the active arm for a 60% reduction. Slide 8 clearly shows why treatment failure is not a useful endpoint for demonstrating an acute pharmacologic effect. Within the first week where we demonstrate a significant improvement in FEV1, which you will see on the next slide, there are no treatment failures, probably because patients are covered by steroids for most or all of that week. Conversely, on slide 9, we see that the airway improvement with rademikibart starts quickly and is almost at stat sig by day 3. By day 7, the benefit of a single dose of rademikibart has been fully achieved, and we see a plateau in FEV1 through day 28, providing additional support, I might add, for monthly dosing.

The beneficial effects of a single dose start to wane by 8 weeks, which we see as an ideal scenario for an acute-to-chronic development strategy. The next 2 slides cover safety, which were entirely unremarkable, with fewer AEs and SAEs on drug than placebo. No episodes of hypereosinophilia were noted in the study. Slide 11 just breaks out the individual SAEs, adverse events of special interest, and treatment-emergent adverse events. Conclusions. Clinically meaningful 66% reduction in treatment failure observed through day 28. Rapid, statistically significant, and clinically meaningful increase in post-bronchodilator FEV1 compared to placebo observed at day 7 and maintained through day 28. Day 7 FEV1 improvement was a pre-specified key secondary endpoint based on the FDA's desire to have an endpoint showing rapid benefit for a potential acute indication.

As noted, we plan to propose FEV1 improvement at day 7 to FDA as a phase III endpoint for the acute indication. Based on our prior phase II-B 24-week study showing a 63% decrease in annualized exacerbations in the T2 population, and this study showing substantial benefit in exacerbations as well, we are perfectly situated to also move forward with a chronic maintenance program in asthma. Based on the very low rate of treatment failures in this study, it is reasonable to ask whether there is really a market for treatment of acute exacerbations. Our prior market research was somewhat dated, so we engaged Komodo Health to generate a much more contemporary picture of the market as it was in 2025 based on actual claims. The results are remarkably positive for a product with rademikibart's profile.

With approximately 1.6 million emergency department visits in the U.S. for acute asthma attacks in T2 high patients in 2025. There is essentially zero biologic penetration into this acute market, and there is still very low penetration into the chronic market as well, with a very low 2.26% of all asthma patients that received an asthma biologic in 2025, rising to 3.44% among the type 2 high subset, leaving a very large untapped market. Slide 14 is just a snapshot of the massive Komodo Health database, and slide 15 is the money slide. Approximately 1.6 million ED visits in 2025 with T2 high asthma patients flowing into 3 buckets. The largest is treat and release. These are patients who come in, treated in the ED, and then released.

There's an intermediate group in the middle where patients can be observed to see if they are improving and then discharged or worsening and then admitted. Finally, the patients going directly to a hospital bed from the ED under the admitted bucket. The slides provide the percentage of each bucket who return within 30 days based on actual claims data and the associated costs. From that, we can calculate the total cost for patients returning to the ED or the hospital and how much theoretically can be saved by reducing returns by 66%. Based on this model, giving patients in the middle and right buckets a drug that produces a reduction that we've observed would be highly cost-effective, and certainly a large portion of the treat-and-release patients would also be very cost-effective. With that, we are happy to entertain any questions you have.