Pharvaris' strategic priorities in 2025

Pharvaris (Nasdaq: PHVS), a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to help address unmet needs of those living with bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema (AAE), today outlined its strategic priorities for 2025.

“This year is paramount to Pharvaris as we continue clinical development of deucrictibant to help address unmet needs for those living with bradykinin-mediated angioedema,” said Berndt Modig, Chief Executive Officer of Pharvaris. “Pharvaris is committed to generating robust clinical data to build a compelling package supporting deucrictibant’s efficacy and safety profile. Our team is focused on the execution of two Phase 3 clinical studies in HAE, the expansion of our pipeline into AAE, and preparations for commercialization of deucrictibant pending regulatory submission and approval; we have significant resources in place to support these strategic investments and provide value for our shareholders.”

2025 Strategic Priorities

Long-term Prophylaxis of HAE Attacks

• Initiated CHAPTER-3 (NCT06669754), a global pivotal Phase 3 study, evaluating deucrictibant for the prophylactic treatment of HAE attacks; topline data anticipated 2H2026. CHAPTER-3 is a randomized, double-blind, placebo-controlled Phase 3 study of orally administered deucrictibant extended-release tablet for the prophylaxis against angioedema attacks in adults and adolescents (12 years and older) with HAE. The study aims to enroll approximately 81 participants with HAE and randomize them in a 2:1 ratio to receive deucrictibant extended-release tablet (40 mg/day), which is currently the intended commercial dosage, or placebo, once daily for 24 weeks. The primary endpoint of the study is to evaluate the efficacy of deucrictibant compared to placebo for prophylaxis against angioedema attacks as measured by the time-normalized number of investigator-confirmed HAE attacks during the 24-week treatment period. Other objectives of the study include evaluating additional clinically relevant outcomes, deucrictibant’s safety and tolerability, pharmacokinetics and its impact on health-related quality of life measures in the prophylactic setting. Pharvaris anticipates announcing topline data of CHAPTER-3 in the second half of 2026.
• Prophylactic open-label extension study CHAPTER-4 (NCT06679881) on track to initiate in 1Q2025. CHAPTER-4 is a long-term, open-label extension study of orally administered deucrictibant extended-release tablet (40 mg/day) for the prophylactic treatment of HAE attacks. Participants in the open-label extension study are 12 years or older, have been diagnosed with HAE, and may either have rolled over from the CHAPTER-3 randomized clinical study, may transition to CHAPTER-4 after participating in the long-term extension study of Phase 2 prophylactic study using the twice-daily deucrictibant immediate-release capsule (CHAPTER-1 Part 2, NCT05047185), or may qualify following an eligibility confirmation via screening period. The intention of the study is to evaluate the tolerability and efficacy of deucrictibant extended-release tablet in the prophylactic treatment of HAE attacks.

On-demand Treatment of HAE Attacks

• Topline data from RAPIDe-3 (NCT06343779), a global Phase 3 study evaluating deucrictibant for the treatment of HAE attacks, anticipated 1Q2026. Advancement of RAPIDe-3, a global pivotal Phase 3 study of deucrictibant immediate-release capsule (20 mg) for the on-demand treatment of HAE attacks in adults and adolescents (12 years and older), is progressing as planned with a target enrollment of approximately 120 participants. The primary efficacy endpoint is time to onset of symptom relief, as measured by Patient Global Impression of Change (PGI-C) rating of at least “a little better” for two consecutive timepoints within 12 hours post-treatment. Other efficacy endpoints include time to End of Progression (EoP) in attack symptoms, substantial symptom relief, complete attack resolution and proportion of attacks achieving symptom resolution with one dose of deucrictibant as measured by Patient Global Impression of Severity (PGI-S) and by Angioedema Symptom Rating Scale (AMRA). Pharvaris anticipates announcing topline data of RAPIDe-3 in the first quarter of 2026.
• Phase 2/3 open-label extension, RAPIDe-2 (NCT05396105), of deucrictibant immediate-release capsule for the treatment of HAE attacks ongoing.All participants from RAPIDe-2 Part A, the dose-blinded open-label extension study of RAPIDe-1 (NCT04618211), as well as participants who have completed RAPIDe-3, have or will be offered to enter Part B, the open-label extension study of deucrictibant immediate-release capsule (20 mg), which is the dose being used in RAPIDe-3 and currently the intended commercial dosage. The intention of the study is to evaluate the tolerability and efficacy of deucrictibant immediate-release capsule in the on-demand treatment of HAE attacks.

Clinical Development of Deucrictibant in AAE-C1 INH

• Clinical development plans of deucrictibant in acquired angioedema due to C1-INH deficiency (AAE-C1INH) underway. Currently, there are no approved therapies to address AAE-C1INH¹. Pharvaris has engaged stakeholders, including the U.S. Food and Drug Administration (FDA), for feedback on a clinical development plan designed to evaluate the potential of deucrictibant to address an unmet medical need for therapies for the treatment of AAE-C1INH; Pharvaris intends to initiate a clinical study in 2025 pending feedback from regulators.

Business Updates

Corporate

• Expansion of Pharvaris team to support deucrictibant launch preparedness, as well as business growth and planning. Chris Wilson joined Pharvaris as the Vice President of Sales & Marketing, North America, bringing a wealth of expertise in HAE product commercialization and executing strategic sales and marketing initiatives. Christa Milley joined Pharvaris as the Vice President, Head of Business Development, bringing an extensive deal sheet that demonstrates her track record of identifying, evaluating, structuring, negotiating, and executing deals to support our corporate development strategy.
• HAE treatment experience and burden of disease data presented at recent medical congresses. Data from the Adelphi Disease Specific Programme™, a real-world cross-sectional survey of physicians and people living with HAE, were presented in two oral presentations at the Spanish Society of Allergology and Clinical Immunology (SEAIC) International Symposium and a poster at the BSI Clinical Immunology Network (BSI-CIPN) Conference. One oral presentation characterized the treatment of HAE airway attacks, detailing the considerable pain, fatigue, and emotional distress experienced; despite the potential consequences, approximately one-third of HAE airway attacks were not treated, underscoring the importance for people with HAE to align with clinical guidelines to carry on-demand therapy, as well as highlighting the need for portable therapies. The second oral presentation investigated the burden of disease in people living with HAE and their caregivers in Europe, concluding that people with HAE who reported a greater need for caregiver support—driven by the support for medication management—experienced significant impairment in activity and a reduced quality of life.The poster presented at BSI-CIPN characterized the experience of people living with HAE in the United Kingdom with current treatments, all of whom were prescribed injectable on-demand medications. The most common unmet need associated with currently prescribed long-term prophylactic and on-demand medications was a desire for a different route of administration. This analysis highlights the unmet need for novel oral options.

About Deucrictibant
Deucrictibant is a novel, potent, oral small-molecule bradykinin B2 receptor antagonist currently in clinical development. By inhibiting bradykinin signaling through the bradykinin B2 receptor, deucrictibant has the potential to prevent the occurrence of HAE attacks and to treat the manifestations of an attack if/when they occur. Based on its chemical properties, Pharvaris is developing two formulations of deucrictibant for oral administration: an extended-release tablet to enable sustained absorption and efficacy in prophylactic treatment, and an immediate-release capsule to enable rapid onset of activity for on-demand treatment.