Pharvaris N.v. · NASDAQ:PHVS
Pharvaris — Technical Presentation (2021)
9 slides from Pharvaris's technical presentation, 2021
Slide 1: PHA-022121: Efficacy in a Monkey Bradykinin Challenge Model Translated to Human
PHA-022121: Efficacy in a Monkey Bradykinin Challenge Model Translated to Human Anne S.J. Lesage1, Raf Crabbé2, Peng Lu3, Jochen Knolle1, Christoph Gibson4 1Pharvaris GmbH, 2RC Consultancy, 3Pharvaris Inc, 4AnalytiCon Discovery GmbH © 2021
Slide 2: PHA-022121 is a potent and selective oral bradykinin B2 receptor antagonist
PHA-022121 (PHA121) is a potent and selective oral bradykinin B2 receptor antagonist N N N Antagonist potency at the recombinant human bradykinin B2 receptor Kb 150 pM N Highly selective over approx 170 molecular O D O targets, including bradykinin B1 receptor Cl O F N H Activity in primate an
Slide 3: HAE is caused by excess levels of bradykinin
HAE is caused by excess levels of bradykinin PHA121 is designed to block signaling by bradykinin © 2021
Slide 4: Inhibition of bradykinin-induced hemodynamic effects is a validated surrogate efficacy assessment
Inhibition of bradykinin-induced hemodynamic effects is a validated surrogate efficacy assessment Proportion of attacks treated Used to select the dose in the original development program for icatibant, as reviewed by FDA and EMA Clinical dose established with the BK One dose challenge has demon
Slide 5: Pharvaris developed a translational bradykinin challenge monkey model
Pharvaris developed a translational bradykinin challenge monkey model Transient BK effect 110 Mean arterial blood pressure (mmHg) 100 90 PHA121, icatibant, or vehicle 80 70 Bradykinin 60 (BK) BK BK BK BK BK BK BK 50 40 -400 -200 0 200 400 600 800 predose 0 +1 +2 +3 +4 +5 +6 +7 hours Time after BK in
Slide 6: Oral PHA121 inhibits the bradykinin challenge in freely moving monkeys
Oral PHA121 inhibits the bradykinin challenge in freely moving monkeys PHA121/BK Challenge in monkeys Icatibant/BK Challenge in monkeys Vehicle 30 Vehicle PHA-022121, 1 mg/kg BK-induced decrease in MABP PHA-022121, 10 mg/kg Icatibant 0.6 mg/kg BK-induced decrease in MABP 40 25 20 30 (mmHg) (mmHg) 15
Slide 7: Oral pre-treatment with PHA121 blocks the effect of IV bradykinin-induced hemodynamic changes in human studies
Oral pre-treatment with PHA121 blocks the effect of IV bradykinin- induced hemodynamic changes in human studies PHA121 or placebo (po) Bradykinin Human BK (BK) BK BK BK BK BK challenge PHA121 Icatibant EC50 (ng/mL) 2.4 9.5 0 +1 +4 +8 +12 hours EC85 (ng/mL) 13.8 53.8 Predose +24 Phase 1 BK challenge
Slide 8: A single PHA121 dose expected to provide a similar pharmacodynamic effect as two injections of icatibant
A single PHA121 dose expected to provide a similar pharmacodynamic effect as two injections of icatibant Simulation of PK/PD resulting from single vs. double doses of Estimated duration of effect icatibant versus single doses of PHA121 (icatibant versus PHA121) Icatibant PHA121 PHA121 Response 30 mg
Slide 9: Human BK challenge study: A surrogate marker of clinical efficacy
Human BK challenge study: A surrogate marker of clinical efficacy Human BK challenge study has been validated in the icatibant development In the monkey BK challenge study, PHA121 inhibited BK-induced changes with a faster onset and a longer duration of action as compared to icatibant PHA121 t