Pharvaris (PHVS) Status Update summary

Unmet needs and disease landscape

• Bradykinin-mediated angioedema includes hereditary and acquired forms, with significant unmet needs in diagnosis and treatment, especially for types beyond HAE type 1 and 2.

• Accurate classification and tailored management are critical due to the heterogeneity of disease mechanisms and presentations.

• There is a lack of controlled clinical trial data and approved therapies for acquired and normal C1 inhibitor forms, leading to reliance on off-label treatments with limited efficacy.

• Improved education and access to diagnostics and therapies are needed, particularly for rare subtypes and non-specialist physicians.

Clinical development and strategy

• Deucrictibant is being evaluated in two pivotal phase III studies (RAPIDe-3 and CHAPTER-3) for both prophylactic and on-demand treatment, including patients with HAE with normal C1 inhibitor.

• The development strategy is informed by regulatory guidance and includes expansion into acquired angioedema due to C1 inhibitor deficiency.

• A new randomized, placebo-controlled phase III CREAATE study will assess deucrictibant in acquired C1 inhibitor deficiency, with endpoints focused on attack frequency and symptom relief.

• Data from investigator-initiated studies (POP-AID and ONCE-AID) show promising efficacy and safety for deucrictibant in reducing attack rates and severity.

Biomarker innovation

• A novel cold activation biomarker assay has been developed to identify bradykinin-mediated angioedema by quantifying bradykinin and its breakdown peptides in plasma.

• The assay distinguishes between healthy individuals and those with bradykinin-mediated angioedema, including rare subtypes with normal C1 inhibitor.

• This tool is intended for research and patient identification, not as a formal diagnostic, and supports clinical trial enrollment and disease understanding.