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 enables uncontrolled plasma kallikrein activity which leads to elevated levels of bradykinin resulting in swelling and pain affecting different body areas.
By inhibiting bradykinin signaling through the bradykinin B2 receptor, we have the potential to treat all clinical signs of an HAE attack and also to prevent the occurrence of attacks.
on-demand & prophylactic treatment
HAE patients, together with their treating physicians, may opt for treatment of attacks (on-demand treatment) or may prefer to prevent attacks (prophylactic treatment) based on clinical assessment and personal choice.
Pharvaris aims to bring the promise of both of these new options to people living with HAE.
On-Demand
PHVS416- Rapid onset
- Effective Symptom Mitigation
- Single Oral Capsule
Prophylaxis
PHVS719- Sustained Attack Suppression
- Daily Oral Tablet
why do we believe PHVS416 & PHVS719 can work?
Deucrictibant
- Deucrictibant demonstrated highly potent and selective competitive antagonism of the B2 receptor (preclinical)
- Deucrictibant has shown rapid and potent activity at multiple oral doses in a validated bradykinin-mediated challenge model (clinical)
- Deucrictibant has been observed to be safe and well-tolerated at the doses studied to date (clinical)
Why do we believe PHVS416& PHVS719 can work?
HAE is a bradykinin-mediated disease. Blocking bradykinin shuts down the swelling attack, as shown by over a decade of patient experience with icatibant, an injectable therapy.
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 excess bradykinin signaling through its B2-receptor will inhibit all aberrant bradykinin activity in all circumstances.
We believe PHVS416, our on-demand rapid exposure product candidate, has the potential to treat and prevent HAE attacks, and PHVS719, our small daily dose extended-release product candidate, has the potential to prevent or reduce HAE attacks in a prophylactic setting.