Pharvaris N.V. Ordinary Shares Study result

Maggie, please go ahead. Thank you, and welcome to the topline data announcement of CHAPTER-3, a phase III clinical study of deucrictibant extended release tablet for the prophylactic treatment of hereditary angioedema attacks.

My name is Maggie Beller, Head of Corporate and Investor Communications at Pharvaris. Please note that today's webcast is being recorded, and the slides will be uploaded onto the investor section of our corporate website immediately following the call. Please note that statements of our guests today are their own and not those of Pharvaris, and Pharvaris makes no representation as to the adequacy, fairness, accuracy, or completeness of the information in their comments. In addition, our presentation today will include forward-looking statements, including, but not limited to, statements regarding deucrictibant and its potential, as well as our preclinical and clinical studies, regulatory interactions, and future plans.

Such forward-looking statements are subject to certain risks and uncertainties that could cause actual results to differ materially from those projected. For additional insight regarding the various factors that could cause such differences, please see the section entitled "Risk Factors" in our annual report on Form 20-F and our other filings available on the SEC's website. In addition, any forward-looking statements represent the company's expectation only as of today. While we may elect to update these forward-looking statements, we specifically disclaim any obligation to do so unless required by law. We are joined today by Dr. Marc Riedl, Professor of Medicine at the University of California, San Diego, principal investigator in the CHAPTER-3 study, and a globally recognized expert treating physician who will share his perspective on the CHAPTER-3 data and on their relevance for clinical practice. Thank you, Dr. Riedl, for joining us.

During our call, Pharvaris' Chief Executive Officer, Berndt Modig, will speak to Pharvaris' continued commitment to provide medicines that can further advance the management of bradykinin-mediated angioedema. Pharvaris' President, Dr. Peng Lu, will go through the topline efficacy and safety findings from the CHAPTER-3 study. Additionally, Pharvaris' Chief Commercial Officer, Wim Souverijns, is available for the Q&A portion of the call. I'd now like to hand the call over to Berndt Modig.

Berndt? Thank you, Maggie, and good morning, good afternoon, everybody.

Pharvaris prides itself on being a trusted partner to all stakeholders in the HAE community. I am proud to, once again, speak to you as we execute another key milestone for our company. Starting with the on-demand program, positive phase II data were followed by positive phase III results in December 2025. Most recently, the FDA accepted our NDA submission, bringing us one step closer to making deucrictibant IR available for on-demand treatment of HAE attacks. The next catalyst for the on-demand program is the potential approval in April 2027 of deucrictibant IR, which may represent a new standard of care for on-demand HAE attack treatment. Now turning to long-term prophylaxis, we have similarly built a strong foundation. Positive phase II data were announced in December 2023.

Today, we build on those with positive phase III results, which support deucrictibant XR as a potential long-term prophylactic therapy. Looking forward, we continue to generate additional evidence for deucrictibant in acquired angioedema through the CREAATE phase III study, which results from the prophylactic part of the study anticipated in the first quarter of 2027. We expect to submit our U.S. NDA in prophylaxis during the first half of 2027. When you step back and take a look at the entire timeline, what is exciting is that we have already crossed several major value inflection points, and the upcoming milestones have the potential to transform Pharvaris into a commercial leader in bradykinin-mediated angioedema. I would now like to hand over the call to Pharvaris President, Dr. Peng Lu, to present the CHAPTER-3 data.

Peng? Thanks, Bernd. Before reviewing the data, I would like to take this opportunity to sincerely thank the HAE community, especially study participants, their families, the investigators and the site staff, our study partners, and all Pharvarians for their invaluable contribution to clinical research, especially the CHAPTER-3 study.

CHAPTER-3 was a randomized, double-blind, placebo-controlled phase III study of oral administered deucrictibant extended release tablets, 40 milligrams once daily, for the prophylaxis of hereditary angioedema attacks. Eligible participants were age 12 and older with HAE type 1, type 2, or HAE with normal C1 inhibitor. Participants were randomized in a 2 to 1 ratio, which was stratified by age and baseline attack rate. In total, 85 participants were enrolled, with 55 into the deucrictibant group and 30 with placebo. Baseline demographics and HAE disease characteristics were generally balanced between 2 groups and are consistent with the overall HAE population.

The mean age was about 39 years old, and 4 adolescents were enrolled in each group. Most of the participants had HAE type 1 or 2. A total of 5 participants with HAE normal C1 inhibitor were enrolled. The baseline attack rate was comparable between 2 groups, with a mean rate approximately 3 to 4 attacks per month. After years of dedicated effort, we are proud to announce the CHAPTER-3 study successfully met its primary endpoint, demonstrating a highly statistical significance and clinical meaningful reduction in HAE attack rate. Participants treated with deucrictibant XR experienced substantially fewer HAE attacks during the entire 24-week treatment period, with an estimated attack rate of 0.35 attacks per month with deucrictibant versus 2.06 attacks per month with placebo. This represents an 83% reduction in attack rate with placebo, which was highly statistical significant.

Of note, CHAPTER-3 is the first and only pivotal phase III study to enroll patients across the full spectrum of HAE, including participants with HAE with normal C1 inhibitor. In contrast, all other pivotal HAE studies have exclusively enrolled patients with HAE type 1 or 2. Among the 80 participants with HAE type 1 or 2 in CHAPTER-3, deucrictibant XR achieved 87% reduction in monthly attack rate with placebo. Taken together, these findings demonstrate deucrictibant XR provides injectable-like efficacy with the convenience of oral therapy. This slide highlights one of the most important attributes of deucrictibant XR as a prophylactic therapy, its early onset of protection, combined with durable effects over time. Consistent with its pharmacokinetic profile, deucrictibant XR reaches therapeutic exposure within the first day of dosing and achieves steady state within 2 to 3 days.

Correspondingly, CHAPTER-3 shows that the protection of deucrictibant was maximized within the first week of the treatment and then maintained throughout the study duration. Moving on to some of the key secondary endpoints. Deucrictibant XR demonstrated robust and highly consistent treatment benefits in reducing moderate to severe attacks and attacks treated with on-demand medication. In the responder analysis, all but one participant receiving deucrictibant XR achieved at least 50% attack reduction from the baseline. With the most stringent threshold, almost all and two-thirds of participants achieved at least 70% and 90% reduction, respectively. Nearly half of the participants treated with deucrictibant XR remained attack-free throughout the entire 24-week treatment period. These results demonstrate meaningful attack control and reinforce the robust efficacy of deucrictibant XR across multiple clinical relevance measures. Beyond the reduced attacks, we also observed meaningful improvements in how participants felt and functioned in their daily lives.

As shown in this slide, participants receiving deucrictibant XR experienced substantial improvements across all domains of Angioedema Quality of Life Questionnaire, including functioning, fatigue and mood, fears and shame, and also nutrition. Across every domain, reductions in AE-QoL scores from baseline to week 24 were consistently greater with deucrictibant XR compared to placebo. These results demonstrate the benefits of deucrictibant XR extend beyond attack prevention alone, translating into broader impacts of the treatment on the meaningful improvements on patients' day-to-day quality of life. From the safety side, deucrictibant was well-tolerated, with most events being mild or moderate in severity. The most common adverse events across both groups were upper respiratory tract infection, nasopharyngitis, and headache.