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

Sustained Therapeutic Exposure with Once-Daily Oral Deucrictibant Extended-Release Tablet for Prophylaxis of Hereditary Angioedema Attacks (AAAAI 2026) - "Rationale Deucrictibant is an orally administered bradykinin B2 receptor antagonist being developed in two formulations; once-daily extended-release (XR) tablet for long-term prophylaxis and immediate-release (IR) capsule for treatment of bradykinin-mediated angioedema attacks. Mean (SD) plasma concentration for deucrictibant XR at 24 hours post-dose (C24h) was 52 ng/ml (30), which was ∼4-fold higher than the anticipated therapeutic exposure threshold concentration estimated to provide 85% maximal response (EC85; 13.8 ng/mL). PHA022121-C021: Plasma concentrations remained within therapeutic range regardless of fasting or fed Conclusions A single oral dose of deucrictibant XR tablet resulted in sustained exposure for at least 24 hours, with minimal food effect, which was maintained with repeat dosing that reached steady state after two doses, overall supporting once-daily dosing of deucrictibant XR tablet."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Oral Deucrictibant Immediate-Release Capsule in Treatment of Hereditary Angioedema Attacks: Results of the Phase 3 RAPIDe-3 Study (AAAAI 2026) - P3 | "Conclusions RAPIDe-3 evaluates the efficacy and safety of oral deucrictibant IR capsule for treatment of HAE attacks in adolescents and adults. Top-line data are anticipated in 4Q2025 and will be presented."

P3 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Sustained Therapeutic Exposure with Once-Daily Oral Deucrictibant Extended-Release Tablet for Prophylaxis of Hereditary Angioedema Attacks (ACAAI 2025) - "Methods PHA022121-C020 and PHA022121-C017 were phase 1, open-label, studies in healthy volunteers. Daily deucrictibant XR (40 mg) dosing demonstrated sustained exposure, with mean C24h (predose) at concentrations ∼3-fold higher than EC85. Conclusions A single oral deucrictibant XR tablet resulted in sustained exposure for at least 24 hours, which was not altered by repeat dosing, supporting once-daily dosing of deucrictibant XR tablet in phase 3 trials."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Long-term prophylactic treatment with deucrictibant for angioedema due to acquired C1-inhibitor deficiency. (PubMed, J Allergy Clin Immunol) - P2 | "Deucrictibant extended-release tablet effectively prevented angioedema attacks in patients with AAE-C1INH, without safety concerns."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Rare Diseases

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 | Completed | Sponsor: Pharvaris Netherlands B.V. | Active, not recruiting ➔ Completed

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

Pharvaris Updates Timing of Topline Data Announcement for RAPIDe-3 Pivotal Phase 3 Study to the Fourth Quarter of 2025 (GlobeNewswire) - "Pharvaris...updated the guidance for the disclosure of topline data from the ongoing RAPIDe-3 pivotal Phase 3 study evaluating deucrictibant immediate-release (IR) capsule for the on-demand treatment of HAE attacks. Pharvaris anticipates announcing topline data from RAPIDe-3 in the fourth quarter of 2025 and, pending positive data, expects to submit a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) in the first half of 2026. "

FDA filing • P3 data: top line • Hereditary Angioedema

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