Our scientific approach:
targeting the bradykinin B2 receptor
Hereditary angioedema (HAE) most commonly occurs as a result of insufficient levels or function of a protein called C1 inhibitor (C1-INH), a naturally occurring inhibitor of the plasma kallikrein enzyme. C1-INH deficiency results in uncontrolled plasma kallikrein activity which leads to elevated levels of bradykinin and painful swelling affecting different body areas.
Antagonism of the bradykinin B2 receptor mediation is a well-tolerated, well-established, clinically proven mechanism of action in HAE.1,2,3 In 2017, based on detailed insights into the three-dimensional structure of the B2 receptor, Pharvaris was able to design a small molecule that fits in the pocket of the B2 receptor, where bradykinin naturally binds.4
By inhibiting bradykinin signaling through the bradykinin B2 receptor, we have the potential to treat the clinical signs of an HAE attack and also to prevent the occurrence of attacks. Based on its chemical properties, we are developing therapies that can be orally administered either by a capsule to enable rapid onset of activity for acute treatment, or through an extended-release tablet to enable sustained efficacy in prophylactic treatment. With these two formulations, we aspire to provide people living with HAE treatment options with robust efficacy, a well-tolerated profile & low-burden administration which can be taken anywhere, anytime.
Pharmacological profile of PHA121 published in International Pharmacology
In Vitro Pharmacological Profile of a New Small Molecule Bradykinin B2 Receptor Antagonist
Posters and Presentations
1 Cicardi M et al. N Engl J Med 2010;363:532-41
2 Lumry WR et al. Ann Allergy Asthma Immunol 2011;107:529-37
3 Maurer M et al. Clin Exp Allergy 2022;52:1048-58
4 Lesage A, et al. In Vitro Pharmacological Profile of a New Small Molecule Bradykinin B2 Receptor Antagonist. Front Pharmacol 2020;11:916.