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 Manhard, Executive Vice President and 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 are announcing today, the timing and content of additional data analysis and future data presentations, our anticipated regulatory strategy and 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 releases 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 will gladly turn the call over to Barry.

Thank you, David. Welcome, everyone. Thank you for joining us this morning. I would like to specifically thank Dr. Surya Bhatt for being on the call with us. Dr. Bhatt is director of the University of Alabama at Birmingham, UAB, Center for Lung Analytics and Imaging Research, and the lead author on both dupilumab phase III COPD studies published in the New England Journal of Medicine. We are very excited to have this opportunity to review with you the exciting results of the Seabreeze STAT COPD study. Overall, we achieved our primary objective and several important secondary objectives, demonstrating that rademikibart significantly reduces the number of patients returning to the hospital or emergency department for additional care in the month following an exacerbation. In fact, we achieved an 81% reduction in treatment failures, 85% reduction in new moderate to severe exacerbations, and 100% reduction in ED visits and hospital admissions.

While the study did not achieve the secondary endpoint of day 7 FEV1 improvement, we did see robust improvement in FEV1 at week 4. As observed in the asthma study, rademikibart continues to be remarkably well-tolerated. I will not spend a lot of time on the design study, but I do want to note that we used the same general design and similar entry criteria as the ABRA study out of the U.K., which studied benralizumab in asthma and COPD patients experiencing acute exacerbations. Our study was also powered based on the ABRA study with an expected 45% treatment failure rate on placebo and a 50% reduction on active. Here is the schematic of patient flow. We screened 325 patients in order to enroll 159. 81 patients on placebo, 78 patients randomized to rademikibart. Here is the breakdown of baseline characteristics.

There is a relatively high rate of current smokers, which likely resulted in lower pheno than observed in the asthma trial. Similar to the asthma trial, enrollment in the COPD study went quickly in Eastern Europe, resulting in a high proportion of patients coming from Serbia and Georgia. Different than the asthma trial, we achieved a higher treatment failure rate, more commensurate with the rates we identified in our recent claims database study. Although lower than observed in the ABRA study. Fortunately, our treatment effect size was much larger than we used for powering the study, resulting in a game-changing 81% reduction in the rate of treatment failures with rademikibart compared to placebo, with a p-value of 0.0122. The majority of treatment failures observed with placebo resulted in either a hospital admission or an emergency department visit. The remainder were unscheduled medical visits or intensification of pharmacologic treatment.

With rademikibart treatment, there were zero hospitalizations or emergency department visits for treatment failures, and only two unscheduled medical visits. The seven hospitalizations or ED visits on placebo versus zero on rademikibart is also statistically significant with a P value of 0.0137. Based on 2025 claims data, the reduction in hospital admissions and ED visits would have a huge economic benefit, which we will discuss later in the presentation. A Kaplan-Meier graph of treatment failure shows the separation beginning between the arms in 2 weeks and increasing through 4 weeks. Within the patients experiencing a treatment failure, there were seven exacerbations in the placebo group compared to one in the active arm for an 85% reduction, P = 0.0301.

Just for clarity, treatment failure is a broader category than new exacerbations, as it includes patients whose treatment is intensified, or they may go to an ED or hospital due to worsening of their index exacerbation. Although these latter patients are obviously very important, in this table, we are only looking at the exacerbation endpoint, which would be used in a chronic treatment study to obtain FDA approval for maintenance therapy. Different than asthma patients, we see little difference in post-bronchodilator FEV1 improvement in the first week of treatment. Both groups improve approximately 120 mil. As a reminder, while we normally use pre-bronchodilator FEV1 change to isolate the effect of drug therapy, in the Seabreeze STAT studies, patients immediately get bronchodilator therapy as soon as entering the ED, and it would be unethical to withhold standard of care.

Therefore, by default, we have to use post-bronchodilator assessments, where patients receive the bronchodilator immediately before spirometry, making it more difficult to see a difference between arms. By week 4, however, we do see a clinically meaningful increase in 70 mils in FEV1 with a single dose of rademikibart. Beneficial effects of a single dose is gone by 8 weeks. Of interest, we also evaluated use of rescue inhalers. We see a separation very quickly and a significant reduction with rademikibart in the need for rescue inhalers by week 2, which is maintained through week 7. Exacerbation of Chronic Pulmonary Disease Tool, or EXACT-Pro, is a validated patient-reported outcomes measure designed to assess the frequency and severity of exacerbations in patients with COPD. It consists of 23 items that capture symptoms and impacts on daily life.

EXACT-Pro has been an important secondary endpoint in the phase III programs of numerous approved drugs, including OHTUVAYRE. Rademikibart significantly improves symptom scores by week 1, with important differences observed through week 4. The next two slides cover safety, which are entirely unremarkable, with fewer AEs and SAEs on drug than placebo. Of particular note is the substantially lower rate of SAEs on rademikibart than observed with placebo. Slide 15 breaks out the individual SAEs and adverse events of special interest. The most common SAE in the placebo group was exacerbations, confirming the previously noted significant reduction in exacerbations with rademikibart. There was one unrelated death of a patient randomized to rademikibart after 37 days in the study. Of note, there was also a death in a patient pre-randomization during screening in this population.

We recently engaged Komodo Health to generate a contemporary picture of the COPD market as it was in 2025 based on actual claims data. The results were remarkably positive for a product with rademikibart's profile, with approximately 1.6 million ED visits in the U.S. for acute COPD exacerbations in T2 high patients in 2025. There is essentially zero biologics penetration into this acute market and still very low penetration into chronic COPD market as well, leaving a massive untapped market. Approximately 1.6 million ED visits in 2025 by T2 high COPD patients flows into three buckets. The slides provide the percentage of each bucket who returned within 30 days based on actual claims data and associated costs. From that, we can calculate the total cost for patients returning to the ED or hospital and how much can theoretically be saved by reducing returns.

Different than asthma patients, the largest group of patients are those admitted to the hospital. These patients have the highest rate of returning to the ED or hospital within 30 days from the initial exacerbation and the highest cost of treatment. These patients would have the most benefit from rademikibart treatment. The middle group are patients who are held in an intermediate unit where the patient can be observed to see if they are improving and can be discharged or admitted if they fail to improve sufficiently. They also have a high average cost for post-discharge treatment. The second-largest bucket are patients who are treated and released. Even these patients, the rate of return within 30 days, and the average cost per patient of almost $2,000 for the 30 days post-discharge, making them an important future target for rademikibart treatment.

The total cost of treating all of these patients for the 30 days after the index exacerbation was approximately $6 billion in 2025. We believe a large portion of these costs could be saved by early treatment with rademikibart, based on our trial, with 100% reduction in ED visits and hospital admissions for COPD within 30 days after randomization. We achieved an 81% reduction in treatment failures, 85% reduction in new moderate to severe exacerbations, and 100% reduction in ED visits or hospital admissions. While the study did not achieve the secondary endpoint of FEV1 improvement, we did see robust improvement of FEV1 by week 4. As observed in the asthma study, rademikibart continues to be remarkably well-tolerated.