our pipeline
Pharvaris has a platform of novel, potent and selective B2-receptor antagonist small molecules for the treatment of bradykinin-mediated diseases. Pharvaris’ pipeline consists of investigational therapies that are designed to treat all sub-types of hereditary angioedema (HAE).
PHVS416 is a investigational softgel capsule formulation containing PHA121, a highly potent, specific, and orally bioavailable competitive antagonist of the bradykinin B2 receptor. This formulation is designed to provide rapid onset of action and single-dose resolution with oral convenience, through rapid exposure of attack-mitigating medicine in a convenient, small oral dosage form.
PHVS416 is currently in Phase 2 clinical development outside of the U.S for the on-demand and prophylactic treatment of HAE.
Current standard of care for treatment of HAE is via injectable or intravenous administration, which can be painful and burdensome, often requires redosing, and can be associated with a delay in the time to administration and, therefore, time to symptom resolution. PHVS416 is designed to provide rapid, easy, and reliable symptom relief in an oral form for all HAE attacks. Phase 1 studies in healthy volunteers have shown that PHA121, the active ingredient in PHVS416, has a longer half-life than icatibant. In preclinical and human volunteer mechanistic studies, PHA121has demonstrated rapid mitigation of the effects of bradykinin with higher potency and longer duration than icatibant. PHVS416 will be delivered small easy-to-swallow investigational softgel capsule.
* The FDA has placed a clinical hold on the clinical trials of PHA121 in the U.S.
PHVS719 is an extended-release tablet formulation containing PHA121, a highly potent, specific, and orally bioavailable competitive antagonist of the bradykinin B2 receptor. Pharvaris is developing this formulation that is designed to be effective at preventing attacks that is well tolerated in a convenient, small oral tablet. PHVS719 has completed Phase 1 clinical development for the prophylactic treatment of HAE.
Unfortunately, currently available oral prophylactic therapies do not provide the desired tolerability. By utilizing the same mechanism as icatibant, Pharvaris is directly targeting bradykinin, but with a simple, once-daily tablet.
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, oral, 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 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 pharmacological effectiveness 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.
* The FDA has placed a clinical hold on the clinical trials of PHA121 in the U.S.