Slide 1: Bradykinin data discussion
Bradykinin data discussion September 2024 1 ©2024
Slide 2: Disclaimer
Disclaimer This Presentation contains certain “forward‐looking statements” within the meaning of the federal securities laws that involve substantial risks and uncertainties. All statements contained in this Presentation that do not relate to matters of historical fact should be considered forward-l
Slide 3: Agenda
Agenda Berndt Modig, CEO Pharvaris Morgan Conn, Ph.D., CBO Pharvaris Peng Lu, M.D., Ph.D., CMO Pharvaris Wim Souverijns, Ph.D., CCO Pharvaris 3 ©2024 This presentation includes data for an investigational product not yet approved by regulatory authorities.
Slide 4: Deucrictibant has the potential to become a preferred therapy for people living with HAE
Deucrictibant has the potential to become a preferred therapy for people living with HAE DEUCRICTIBANT DEUCRICTIBANT extended-release (XR) tablet immediate-release (IR) capsule sustained absorption1 rapid absorption3 Maintains sustained therapeutic exposure over 24 deucrictibant Rapidly reaches ther
Slide 5: With injectable-like efficacy and oral convenience, deucrictibant shows potential to become a preferred therapy
With injectable-like efficacy and oral convenience, deucrictibant shows potential to become a preferred therapy to manage HAE Long-Term Prophylaxis (LTP) On-Demand Treatment (ODT) Efficacy Early-onset attack reduction sustained for over one year in ongoing OLE study 1 Onset of symptom relief wit
Slide 6: Pharvaris: Robust disclosure at 2024 Bradykinin Symposium
Pharvaris: Robust disclosure at 2024 Bradykinin Symposium 1. Bradykinin Challenge Model in Humanized Bradykinin B2 receptor Transgenic Rat; Jolanta Skarbaliene, Ph.D. LTP 2. Prophylactic Treatment With Deucrictibant Improves HAE Disease Control and HRQoL; Markus Magerl, M.D. LTP 3. Long-Term Safety
Slide 7: Bradykinin B2 receptor antagonism is a foundational mechanism to treat and prevent bradykinin-mediated angioedema
Bradykinin B2 receptor antagonism is a foundational mechanism to treat and prevent bradykinin-mediated angioedema attacks1,2 FXIIa Directly blocks the main mediator KNG1 FXII F12 of swelling and inflammation1,3 HMWK Plasma Plasmin Prekallikrein kallikrein Has the potential to prevent or treat C1
Slide 8: Deucrictibant clinical development for LTP and ODT
Deucrictibant clinical development for LTP and ODT Long-Term Prophylaxis (LTP) On-Demand Treatment (ODT) Part 1: randomized controlled primary analysis (complete) Phase 21 Part 2: open-label extension Phase 22 Complete (ongoing) Phase 3 pivotal Start-up Phase 2/3 LTE3 Ongoing Phase 3 OLE Start-up Ph
Slide 9: CHAPTER-1 open-label extension
CHAPTER-1 open-label extension 9 ©2024
Slide 10: CHAPTER-1: Two-part, Phase 2 study of deucrictibant for long-term prophylaxis of HAE attacks
CHAPTER-1: Two-part, Phase 2 study of deucrictibant for long-term prophylaxis of HAE attacks Part 1 (RCT): Double-blind treatment period (12 weeks) Part 2 (OLE): Open-label treatment period Placebo End-of-study Screening R Deucrictibant 20 mg/daya Deucrictibant 40 mg/dayb visit Deucrictibant 40 mg/d
Slide 11: Summary of safety data in LTP ongoing open-label extension
Summary of safety data in LTP ongoing open-label extension Placebo to 20 mg/dayb to 40 mg/daya to Total (N=30) 40 mg/daya (N=9) 40 mg/daya (N=11) 40 mg/daya (N=10) Participants, Events, Participants, Events, Participants, Events, Participants, Events, n (%) n n (%) n n (%) n n (%) n No treatment-r
Slide 12: Continuing deucrictibant treatment sustained the early-onset attack reduction for over one year
Continuing deucrictibant treatment sustained the early-onset attack reduction for over one year RCT OLE 2.50 84.5% reduction; P=0.0008 79.3% reduction; P=0.0009 1.94 2.00 Attack ratea (LS mean) 1.50 In the open-label extension up to 18 months: 1.00 93% attack rate reduction from baseline Median
Slide 13: On average less than one attack per year per participant was treated with rescue medication
On average less than one attack per year per participant was treated with rescue medication IR, immediate release; LS, least squares; OLE, open-label extension; RCT, randomized controlled trial. N = number of participants randomized in each treatment group in the RCT. N’ = number of participants in
Slide 14: Improvements in disease control and health-related quality of life paralleled attack reduction
Improvements in disease control and health-related quality of life paralleled attack reduction during deucrictibant treatment1,2 The goals of HAE treatment are to achieve complete control of the disease and to normalize people’s lives3 This can currently only be achieved by long-term prophylaxis
Slide 15: Deucrictibant shows greater patient satisfaction versus placebo across effectiveness and side effects
Deucrictibant shows greater patient satisfaction versus placebo across effectiveness and side effects (TSQM instrument) 100 100 98.3 100 Placebo (N′=8) 89.2 90.0 20 mg/daya (N′=10) 90 85.8 86.7 40 mg/dayb (N′=10) 80 Mean score at week 12 70 59.4 60 50.0 50 40 30 20 10 0 Global satisfaction Effective
Slide 16: In non-clinical and clinical studies, deucrictibant has shown no cardiac effects
In non-clinical and clinical studies, deucrictibant has shown no cardiac effects Non-Clinical Studies Clinical Studies Deucrictibant had no evident effects on Deucrictibant showed no evident effects on cardiac electrophysiology, morphology, or cardiac electrophysiology or hemodynamic hemodynamic
Slide 17: Positive Phase 3 data could position deucrictibant to become a preferred LTP
Positive Phase 3 data could position deucrictibant to become a preferred LTP with injectable-like efficacy and the oral convenience of a daily tablet Cinryze® Haegarda® Takhzyro® Orladeyo® garadacimab donidalorsen deucrictibant (pdC1INH) (pdC1INH) (lanadelumab) (berotralstat) Plasma-deriveed Plasma-
Slide 18: RAPIDe-2 long-term extension
RAPIDe-2 long-term extension 18 ©2024
Slide 19: RAPIDe-2 study design and objective
RAPIDe-2 study design and objective1 Objective: To evaluate the long-term safety and efficacy of orally administered deucrictibant immediate-release capsule for the treatment of HAE attacksa Part A: Part B: Double-blind phase Open-label phase deucrictibant IR 10 mg RAPIDe-1 deucrictibant IR particip
Slide 20: Summary of safety profile
Summary of safety profile1 Deucrictibant IR capsule Adverse events (All doses) No treatment-related serious or severe TEAEs Number of patients (safety analysis population) N=19 No treatment-related TEAEs Number of attacks treated N’=337 in laboratory parameters, vital Attacks with any TEAE, n (%
Slide 21: Rapid median onset of symptom relief at ~1.1 hours
Rapid median onset of symptom relief at ~1.1 hours: 98.5% of attacks achieved onset of symptom relief by 12 hours1 Time to onset of symptom relief is defined as PGI-C rating of at least 'a little better' for two consecutive timepoints post-treatmenta Proportion of attacks with symptom relief by PG
Slide 22: Rapid median reduction in attack severity at 2.6 hours
Rapid median reduction in attack severity at 2.6 hours: 97.7% of attacks achieved a reduction in severity by 12 hours1 Reduction in attack severity is defined as achieving ≥1 point reduction in PGI-S from pre- treatment for two consecutive time pointsa Proportion of attacks with reduction in attac
Slide 23: Median attack resolution time 11.5 hours: 85.8% of attacks completely resolved within 24 hours
Median attack resolution time 11.5 hours: 85.8% of attacks completely resolved within 24 hours (90.2% of which with one only dose)1 Time to complete attack resolution is defined as the time to post-treatment PGI-S rating achieving 'none' complete resolution by PGI-S Proportion of attacks with (%)
Slide 24: Mixed-methods study: Non-interventional collection of HAE attack symptoms assessments
Mixed-methods study: Non-interventional collection of HAE attack symptoms assessments following treatment with standard of care PGI-C, PGI-S, and AMRA-3/ AMRA-5 data collected via Qualitative interviews Participants recruited mobile app with a subset of by HAEA At pre-treatment participants Ever
Slide 25: In a propensity-score-matching analysis, deucrictibant showed favorable symptom relief outcomes versus standard of care
In a propensity-score-matching analysis, deucrictibant showed favorable symptom relief outcomes versus standard of care1 A. Time to symptom relief defined as PGI-C "A little better" B. Time to reduction in attack severity defined as PGI-S ≥1 point reduction 100 100 Proportion of attacks (%) Proporti
Slide 26: Positive Phase 3 data could position deucrictibant to become a preferred ODT
Positive Phase 3 data could position deucrictibant to become a preferred ODT with rapid-onset and complete symptom resolution with a single oral capsule sebetralstat tablet deucrictibant IR capsule Standard of Care Berinert® (pdC1INH), Firazyr® (icatibant), Ruconest® (rhC1INH) Plasma kallikrein Plas
Slide 27: Commercial vision
Commercial vision PHARVARiS. ons
Slide 28: In the U.S., significant growth in the LTP and ODT market is expected over the next decade
In the U.S., significant growth in the long-term prophylaxis (LTP) and on-demand therapy (ODT) market is expected over the next decade1 Value of prophylaxis1-3 Value of on-demand1-3 $4,000m ODT ODT 6% CAGR Icatibant Gx >$1,200m 23% >2% CAGR 31% Orladeyo Ruconest $850m Cinryze $1,869m Kalbitor ~40% s
Slide 29: Despite treatment satisfaction, the U.S. HAE market is dynamic
Despite treatment satisfaction, the U.S. HAE market is dynamic, with people actively seeking a better1 product People actively switch therapies2,3: first-to-market is Across ~7,000 people with HAE, there were over no guarantee for long-term market leadership >1,500 unique counts of treatment initiat
Slide 30: Deucrictibant: Only compound today with the potential to deliver injection-like efficacy orally across both LTP and ODT
Deucrictibant: Only compound today1 with the potential to deliver injection-like efficacy orally across both LTP and ODT Deucrictibant XR Deucrictibant IR Extended-release tablet Immediate-release capsule Sustained absorption2 Rapid absorption6 Maintains sustained therapeutic exposure over Rapidly r
Slide 31: Our strategy is to become a market leader in HAE
Our strategy is to become a market leader in HAE Rooted in a deep commitment to Leverage engage with the HAE community portfolio with B2R antagonist MoA Become 4 preferred LTP LTP Become standard Win the oral LTP 3 market ODT of care in ODT 2 1 Both Notes: Aspirational, to be confirmed with Phase 3
Slide 32: Going Beyond HAE
Going Beyond HAE 32 ©2024
Slide 33: Bradykinin B2 receptor inhibition is broadly applicable across angioedema
Bradykinin B2 receptor inhibition is broadly applicable across angioedema Type/Endotype Mechanism Name/Acronym AE-MC AE-URT Mast-cell Mast cell degranulation mediated AE-ANA Hereditary C1INH HAE-C1INH (Type 1, 2) AE-BK deficiency Bradykinin Acquired C1INH deficiency AAE-C1INH mediated KKS pathway mu
Slide 34: Deucrictibant proof-of-concept in angioedema due to acquired C1-INH deficiency (AAE)
Deucrictibant proof-of-concept in angioedema due to acquired C1- INH deficiency (AAE)1 Estimated prevalence of 1:100,000 to 1:500,000 or ~ 10% of HAE type 1/2 Currently, no therapies approved for AAE Investigator-initiated trial (IIT) by the Amsterdam UMC Source: 1Petersen RS et al. J Allergy
Slide 35: POP-AID investigator-initiated study: Deucrictibant prevention and treatment of acquired angioedema
POP-AID investigator-initiated study: Deucrictibant prevention and treatment of acquired angioedema Attacks per month Patient 1 Patient 2 Patient 3 Baseline 1.2 1.2 0.9 Placebo 2.0 0.6 1.0 Deucrictibant 0 0 0 Antagonism of the bradykinin B2 receptor with deucrictibant has the potential to effectivel
Slide 36: PHVS has the ambition to realize the potential of deucrictibant to become the preferred option
PHVS has the ambition to realize the potential of deucrictibant to become the preferred option for bradykinin-mediated conditions Long-term extension data1,2 reinforces our belief that deucrictibant has HAE the potential to become the preferred option for the management of HAE Based on the community
Slide 37: www.pharvaris.com
www.pharvaris.com NASDAQ: PHVS 37 ©2024 This presentation includes data for an investigational product not yet approved by regulatory authorities.