deucrictibant immediate-release capsule (PHVS416) / Pharvaris, Royalty - LARVOL DELTA

Pharvaris Announces Orphan Designation Granted to Deucrictibant by the European Commission (GlobeNewswire) - "Pharvaris...announced that the European Commission (EC) has granted orphan designation to its investigational drug, deucrictibant, for the treatment of bradykinin-mediated angioedema."

Orphan drug • Hereditary Angioedema

HAE CHAPTER-1: Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II (clinicaltrials.gov) - P2 | N=34 | Active, not recruiting | Sponsor: Pharvaris Netherlands B.V. | Trial completion date: Dec 2026 ➔ Sep 2025 | Trial primary completion date: Oct 2023 ➔ Jun 2025

Trial completion date • Trial primary completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

RAPIDe-2: Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients with Hereditary Angioedema (clinicaltrials.gov) - P2/3 | N=140 | Enrolling by invitation | Sponsor: Pharvaris Netherlands B.V. | Recruiting ➔ Enrolling by invitation | N=72 ➔ 140 | Trial completion date: Dec 2024 ➔ Jun 2027 | Trial primary completion date: Dec 2024 ➔ Jun 2027

Enrollment change • Enrollment status • Trial completion date • Trial primary completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Efficacy And Safety Of Bradykinin B2 Receptor Antagonism With Oral Deucrictibant In Prophylaxis Of Hereditary Angioedema Attacks: Results Of CHAPTER-1 Phase 2 Trial (AAAAI 2024) - "Deucrictibant (PHA121) is a potent, selective, orally administered antagonist of bradykinin B2 receptor under development for on-demand and prophylactic treatment of HAE attacks... CHAPTER-1 is the first trial evaluating the efficacy and safety of deucrictibant for prophylaxis of HAE attacks. CHAPTER-1 results are anticipated to be presented at the AAAAI conference."

Clinical • P2 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Deucrictibant immediate-release capsule reduces time to end of progression of hereditary angioedema attacks’ manifestations (ACAAI 2023) - P2 | "Within 24 hours after treatment, 78.4%, 89.3%, 93.5% and 29.4% of attacks treated with deucrictibant IR capsule 10, 20, or 30 mg and placebo, respectively, achieved EoP. Conclusion In a post-hoc analysis of placebo-controlled RAPIDe-1 trial, treatment of HAE attacks with deucrictibant IR capsule reduced time to achieve end of progression of attacks' clinical manifestations."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pain

HAE CHAPTER-1: Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II (clinicaltrials.gov) - P2 | N=34 | Active, not recruiting | Sponsor: Pharvaris Netherlands B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

HAE CHAPTER-1: Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Pharvaris Netherlands B.V. | Trial completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

RAPIDe-1: Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (clinicaltrials.gov) - P2 | N=74 | Completed | Sponsor: Pharvaris Netherlands B.V. | Active, not recruiting ➔ Completed | Trial completion date: Sep 2022 ➔ Mar 2023

Trial completion • Trial completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

HAE CHAPTER-1: Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Pharvaris Netherlands B.V. | Trial completion date: Mar 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

RAPIDe-2: Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (clinicaltrials.gov) - P2/3 | N=72 | Recruiting | Sponsor: Pharvaris Netherlands B.V. | Initiation date: Jul 2022 ➔ Dec 2022

Trial initiation date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Efficacy And Safety Of Bradykinin B2 Receptor Inhibition With Oral PHVS416 In Treating Hereditary Angioedema Attacks: Results Of RAPIDe-1 Phase 2 Trial (AAAAI 2023) - "PHA121 is a potent, selective antagonist of bradykinin B2 receptors being investigated for on-demand and prophylactic treatment of HAE attacks...The RAPIDe-1 trial will provide proof-of-concept data of the efficacy and safety of PHVS416 in treating HAE attacks. Topline RAPIDe-1 results are anticipated to be presented at the AAAAI conference."

Clinical • P2 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Pharmacokinetics of PHVS719, extended-release tablet formulation of PHA121, a first-in-class oral human bradykinin B2-receptor antagonist (ACAAI 2022) - "The observed pharmacokinetic of PHVS719 is consistent with the extended-release formulation designed to provide long-term exposure to PHA121. PHVS719 appears to be suitable for once-daily prophylactic dosing in HAE."

PK/PD data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Development of PHVS719: an Oral Extended-Release Bradykinin B2 Receptor Antagonist to Prevent Hereditary Angioedema Attacks (ACAAI 2022) - "Together these data provide evidence that PHVS719 is optimally suited to serve as a once-daily oral pill. Conclusion The active ingredient PHA121 is under clinical investigation in the form of two therapeutic treatment modalities: PHVS416 softgel capsule providing quick absorption for fast symptom relief and PHVS719 once-daily extended-release tablet providing 24 hours coverage to prevent attacks from occurring."

Cardiovascular • Complement-mediated Rare Disorders • Gastrointestinal Disorder • Hereditary Angioedema

HAE CHAPTER-1: Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Pharvaris Netherlands B.V. | Trial completion date: Dec 2022 ➔ Mar 2023

Trial completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

RAPIDe-2: Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (clinicaltrials.gov) - P2/3 | N=72 | Recruiting | Sponsor: Pharvaris Netherlands B.V. | Active, not recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

RAPIDe-2: Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (clinicaltrials.gov) - P2/3 | N=72 | Active, not recruiting | Sponsor: Pharvaris Netherlands B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

RAPIDe-2: Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (clinicaltrials.gov) - P2/3 | N=72 | Recruiting | Sponsor: Pharvaris Netherlands B.V. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

RAPIDe-1: Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (clinicaltrials.gov) - P2 | N=74 | Active, not recruiting | Sponsor: Pharvaris Netherlands B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

An extension phase 2/3 study to test the safety of long term administration of oral PHA-022121 for acute treatment of angioedema attacks in patients with hereditary angioedema Estudio de extensión de fase II/III para probar la seguridad de la administración a largo plazo de PHA-022121 oral para el tratamiento agudo de los ataques de angioedema en pacientes con angioedema hereditario. (clinicaltrialsregister.eu) - P2/3 | N=72 | Ongoing | Sponsor: Pharvaris Netherlands BV

New P2/3 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

RAPIDe-2: Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (clinicaltrials.gov) - P2/3 | N=72 | Not yet recruiting | Sponsor: Pharvaris Netherlands B.V.

New P2/3 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

HAE CHAPTER-1: Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II (clinicaltrials.gov) - P2; N=30; Recruiting; Sponsor: Pharvaris Netherlands B.V.

Clinical • New P2 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema