At the presentation of the company’s financial results for the fourth quarter and year ended 31 December 2021, Pharvaris CEO Berndt Modig says: “The time since our initial public offering in February 2021 has been transformational for Pharvaris, enabling us to reach clinical development milestones. We look forward to our next milestones and will continue to execute our strategy efficiently in 2022 supporting our mission to provide individual choice for managing HAE through potent and convenient oral on-demand and prophylactic therapies.”

Pipeline

  • Top-line Phase 1 data demonstrate extended-release PHVS719 suitable for once-daily dosing. The Phase 1 pharmacokinetics (PK) study of PHVS719 included 8 healthy volunteers dosed in an open-label randomized five-period crossover single-dose study to assess bioavailability of two different extended-release formulations with and without food, in comparison to a single dose of PHVS416 without food. The pharmacokinetics of a single dose of PHVS719 (40 mg) under fasted conditions yielded exposure above 13.8 ng/mL (the EC85 determined in a Phase 1 bradykinin challenge in healthy volunteers) by the two-hour timepoint and maintained this exposure for at least an additional 28 hours. The overall exposure was not affected by food. The 24-hour area-under-the-curve (AUC24h) exposure of PHA121 using PHVS719 (40 mg) is similar to that observed in Phase 1 studies with PHVS416 softgel capsules dosed 20 mg twice a day with food (one of the doses used in the CHAPTER-1 prophylactic proof-of-concept study). The study showed that PHVS416 and PHVS719 were well tolerated. During the study, there were no severe adverse events (SAEs) or severe treatment-emergent adverse events (TEAEs) reported.

    “We are thrilled to have achieved with the PHVS719 extended-release formulation for the first time the possibility of a once-daily oral bradykinin receptor antagonist for prevention of HAE attacks,” says Jochen Knolle, CSO of Pharvaris. “The versatile properties of PHA121, in this case the ability to be absorbed through the colon, combined with the appropriate slow-release technologies, has enabled a release profile well-suited to all-day exposure of compound. This single-dose study showed that PHVS719 (40 mg) maintained PHA121 exposure for a full day above the levels that prevented the effects of a surge of bradykinin as shown in our mechanistic study in healthy volunteers. We look forward to confirming these results in an upcoming multi-dose PK study, to support use of PHVS719 in a future pivotal clinical study when combined with the anticipated results of our CHAPTER-1 proof-of-concept study.”

  • Orphan Drug Designation granted by FDA. On 18 March 2022, the FDA granted orphan drug designation to PHA121, the active ingredient in our PHVS416 and PHVS719 product candidates, for treatment of bradykinin-mediated angioedema.
  • Phase 2 on-demand study (RAPIDe-1) of PHVS416 ongoing. RAPIDe-1, a Phase 2 clinical study of PHVS416 for the on-demand treatment of HAE attacks, continues enrollment and attack surveillance across 33 clinical sites in Canada, Europe, Israel, the UK and the U.S. Top-line data from the study is anticipated to be available in the fourth quarter of 2022.
  • Phase 2 prophylactic study (HAE CHAPTER-1) of PHVS416 enrollment ongoing. CHAPTER-1, a Phase 2 clinical trial of PHVS416 for the prophylactic treatment of HAE attacks, is enrolling patients across clinical sites in Canada, Europe, Israel, the UK and the U.S. Top-line data from the study is anticipated to be available in the fourth quarter of 2022.
  • RAPIDe-2 expected to initiate in 2022. RAPIDe-2, an open-label extension study evaluating PHVS416 for the on-demand treatment of people with HAE, is expected to initiate in the second half of 2022.
  • Preclinical data of PHA121 published in International Immunopharmacology. In March 2022, Pharvaris announced the publication of preclinical data in International Immunopharmacology demonstrating the specificity and potency of PHA121, the active ingredient in our PHVS416 and PHVS719 product candidates.
    (Source: Pharvaris)