pipeline & platform

Pharvaris has a platform of novel, potent and selective B2-receptor antagonist small molecules for the treatment of B2-receptor-mediated diseases. PHA121, the company’s most advanced program, is designed to treat all sub-types of hereditary angioedema (HAE).

B2-receptor-mediated diseases

We have identified and are developing an orally bioavailable small-molecule bradykinin B2 receptor antagonist with high therapeutic potential.

Bradykinin has a high affinity and high agonist potency at the bradykinin B2 receptor, but a near 1000-fold lower affinity and potency at the bradykinin B1 receptor, making it a selective B2 agonist. Bradykinin activates the bradykinin B2 receptor, resulting in increased permeability of blood vessels, release of fluid into surrounding tissue and edema (swelling). Multiple pathological conditions can result in the overabundance of bradykinin. Blocking bradykinin signaling through its B2-receptor will inhibit all bradykinin biological activities in all circumstances.

PHA121 (PHA-022121) is a highly potent, specific, and orally bioavailable competitive antagonist of the bradykinin B2 receptor that has completed Phase 1 clinical development for the treatment of HAE. PHA121 utilizes the same mechanism as icatibant, the leading therapy for on-demand treatment of HAE. Pharvaris is developing this novel small molecule for on-demand and prophylactic treatment of HAE and other bradykinin-mediated diseases through formulations optimized for each setting. Data from single- and multiple-ascending-dose Phase 1 studies in healthy volunteers demonstrate rapid exposure and predictable linear pharmacokinetics at doses up to 50 mg. In a bradykinin-challenge study in healthy volunteers, PHA121 showed significant inhibition of bradykinin-induced hemodynamic changes with an average composite EC50 of 2.4 ng/mL and EC85 of 13.8 ng/mL, approximately four-fold more potent than historical data for icatibant. Quantitative modeling indicates that single oral doses of PHA121 will maintain pharmacologically active drug levels for a substantially longer time than 30 mg of subcutaneous icatibant. PHA121 has been observed to be well-tolerated at all doses studied to date.

PHVS416 is a softgel capsule formulation containing PHA121. Pharvaris is developing this formulation to provide rapid exposure of attack-mitigating medicine in a convenient, small oral dosage form. PHVS416 is currently in Phase 2 clinical development for the on-demand treatment of HAE.

PHVS719 is a tablet formulation containing PHA121. Pharvaris is developing this formulation to provide prolonged preventive treatment in a convenient, small oral dosage form.