Celldex Therapeutics, Inc Study result

Good morning, and thank you for joining us. We are very excited to start our day discussing positive top-line results from our two phase III studies in chronic spontaneous urticaria, EMBARQ-CSU1 and EMBARQ-CSU2. In addition to being available on the webcast portal, the accompanying slides for this morning's call are also on the investor relations page of our website in the events section. Joining me on the call this morning are Anthony Marucci, co-founder, President, and Chief Executive Officer, Dr. Tibor Keler, co-founder, Executive Vice President, and Chief Scientific Officer, Dr. Diane Young, Senior Vice President and Chief Medical Officer, Teri Lawver, Senior Vice President and Chief Commercial Officer, Dr. Margo Heath-Chiozzi, Senior Vice President of Regulatory Affairs and Quality, and Dr. Diego Alvarado, Vice President of Research.

Before we begin our discussion on this top-line data, I would like to direct your attention to slide 2 with respect to important information regarding the forward-looking statements that today's speakers will be making. We will hold a question and answer period after the presentation of the data. I would also like to note that these are very large studies encompassing almost 2,000 treated patients, and we received results very recently. The team has worked very hard to analyze the key data, and you will find today's discussion fulsome. That said, we are continuing to review data, and there will likely be questions we are unable to answer at this time. We look forward to presenting the full 24-week data set, which we intend to submit for presentation to the American Academy of Allergy, Asthma, and Immunology annual meeting in February.

With that, we will now advance to slide 3, and I will turn the call over to Anthony.

Thank you, Sarah, and good morning, everyone. For decades, we have seen well-controlled disease accepted as an adequate outcome in CSU. Today, we are incredibly pleased to share phase III top-line data that clearly demonstrate that barzolvolimab can do better for patients. Turning to slide 4, the data we are going to share with you this morning deliver on barzolvolimab's potential to be a transformational therapy for patients with CSU. Once again, this time across two studies comprising of nearly 2,000 patients from more than 500 sites in 43 countries, the primary endpoint and all key secondary endpoints have been met at both barzolvolimab dose levels. Across each endpoint, the data are clinically meaningful and demonstrate highly statistical significant decreases in disease activity. We are seeing rapid, profound, and durable efficacy that is best in disease in CSU.

This deep efficacy continues to be clearly demonstrated in patients with the highest level of disease burden, severe disease that is refractory to omalizumab, and CSU that presents with severe angioedema, uniquely positioning and differentiating barzolvolimab. While we are primarily going to show you efficacy at 12 weeks today, we saw in phase II these effects are sustained or deepen from week 12 to week 24 across all primary and key secondary endpoints. Our overall safety profile through the 24 weeks also remains consistent with our phase II experience, now in a much larger, diverse patient population. We have dosed about 2,400 patients with subcutaneous barzolvolimab across our phase II and phase III reported studies, delivering more than 11,000 individual doses of either barzolvolimab 150 or 300 milligrams in our phase III studies alone to date.

Our large phase III experience report reinforces that barzolvolimab has a predictable, consistent, well-tolerated safety profile that we believe results in a favorable benefit to risk profile that will support barzolvolimab's broad use across CSU. We couldn't be more excited about these data and what it means for patients and physicians. To remind you on slide 5, CSU is a miserable disease that affects 1.8 million people in the U.S. alone. These people experience relentless, unpredictable hives, itch, and disfiguring swelling that affects all aspects of their lives, including sleep and mental health. With barzolvolimab, we believe we have developed a highly differentiated medicine of choice for patients with CSU with the unique mechanism of mast cell depletion that directly targets the root cause of CSU. This mechanism is directly tied to the profound clinical benefit patients experience.

We look forward to completing the phase III study while we are actively preparing for a BLA submission in 2027 and potential commercialization. With that, I will ask Diane to talk you through the data.

Diane? Thank you, Anthony. I want to echo Anthony's comments.

These robust data continue to reinforce that barzolvolimab, with its unique mechanism of action, has the potential to redefine the CSU treatment landscape. It's been seven years since barzolvolimab first entered the clinic, and this rapid development would not have been possible without the support of the CSU community, especially patients, investigators, and study coordinators. Their enthusiasm for and dedication to the barzolvolimab program is the reason why we are so excited to share these data with you today. Turning to slide 6, let's review the trial design. The phase III program is designed to establish the efficacy and safety of barzolvolimab in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment. Both phase III trials are randomized, double-blind, placebo-controlled, parallel group global studies.

1,939 patients, 963 in EMBARQ-CSU1 and 976 in EMBARQ-CSU2, were randomized evenly to barzolvolimab 150 milligrams every four weeks following a 300 milligram loading dose, barzolvolimab 300 milligrams every eight weeks following a 450 milligram loading dose, or placebo for 24 weeks, at which point patients on placebo were re-randomized to active treatment across both dosing groups. 1,935 patients were ultimately treated on study and 1,634 or 84% of patients completed the 24-week placebo-controlled treatment period. The total treatment period is 52 weeks. As such, this is an ongoing study and remains blinded until completed. A phase III-B long-term extension study or LTE is ongoing, which patients can enter following completion of the phase III trials. The primary endpoint of the study evaluates the clinical effect of barzolvolimab in reducing urticaria activity, weekly urticaria activity score or UAS7 at week 12.

The study is designed to detect a clinically meaningful difference between each of the active arms versus placebo in the overall population, as well as in the subpopulation of omalizumab-refractory patients. The primary endpoint analysis was performed when all patients completed the placebo-controlled portion of the study at 24 weeks. The study was 90% powered to detect at least a 10-point difference between each of the active arms versus placebo in the overall population, as well as in the subpopulation of omalizumab-refractory patients. The key secondary endpoints are listed on the right-hand side of this slide, and we will review these in more detail shortly. Slide 7 shows the demographic and baseline characteristics of the patients we enrolled into this study. Both studies are very well-balanced across all arms and enrolled a diverse patient population with severe disease.

As seen in our prior studies, roughly two-thirds of our patient population had severe CSU, as demonstrated by a mean UAS7 score greater than or equal to 28 at baseline. They also had very high rates of angioedema. The Dermatology Life Quality Index indicates a severe population with mean scores of 14 to 16. The DLQI is a validated tool that measures the impact of CSU on daily life, indicating that their CSU had a very large impact on their quality of life. Across the two studies, 288 patients were enrolled who were refractory to omalizumab, representing approximately 16% of patients in CSU1 and 13% of patients in CSU2. Turning to slide 8, we are excited to dive into the efficacy results with you now. On slide 9, let's look at the primary endpoint, mean change from baseline in urticaria activity score over seven days at week 12.

UAS7 is a patient-reported outcome tool. Patients record their daily itch and hive severity, which is totaled every week. We observe profound decreases with barzolvolimab treatment in UAS7 at week 12. Both barzolvolimab doses are clearly separated from placebo in both trials. The results are clinically meaningful and highly statistically significant, with mean decreases of about 20 points on barzolvolimab compared to 10 points in the placebo group, with comparisons having p values less than 0.00001. As we saw in phase II, the primary endpoint result is strongly supported by positive data across all key secondary endpoints, shown here on slide 10. For the purposes of today's top-line results, we are going to share the data across the three secondary endpoints we believe are of highest importance to patients and physicians and reflect the greatest unmet needs with current CSU therapies.