Pharvaris N.v. · NASDAQ:PHVS

Pharvaris — Investor Presentation (July 2022)

31 slides from Pharvaris's investor presentation, Jul 13, 2022

Slide 1: Pioneering science for patient choice
Exhibit 99.1 Pioneering science for patient choice July 2022 © 2022 © 2022
Slide 2: Disclaimer
Disclaimer This Presentation may contain 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 forwar
Slide 3: Fulfilling an unmet need in the treatment of HAE and other bradykinin-mediated diseases
Pharvaris: Fulfilling an unmet need in the treatment of hereditary angioedema (HAE) and other bradykinin-mediated diseases Competitive product profile Large market opportunity Strong fundamentals Convenient, orally available, small Large global HAE market: Novel lead series with strong IP (primary m
Slide 4: Experienced management with deep expertise in development and rare diseases
Experienced management with deep expertise in development and rare diseases Includes the leaders behind Berndt Modig Anne Lesage, Ph.D. Morgan Conn, Ph.D. Wim Souverijns, Ph.D. the discovery, Chief Community Engagement Chief Early Development Officer Chief Business Officer Chief Executive Officer an
Slide 6: HAE is a rare, life-long condition characterized by attacks of swelling
HAE is a rare, life-long condition characterized by attacks of swelling § Rare and potentially life-threatening genetic condition § 1:10,000 to 1:50,000 Individuals affected by HAE globally ‒ At least 6,600 people living with HAE in the U.S. ‒ At least 8,900 people living with HAE in Europe ‒ Global
Slide 7: HAE attacks are unpredictable, debilitating and potentially lethal
HAE attacks are unpredictable, debilitating and potentially lethal Annual attacks (overall) Attacks are unpredictable in frequency, location, timing, and severity 40% Median: 14 attacks/year • Females: 19 (range: 2-165 attacks/y) • Males: 9 (range: 1-42 attacks/y) § Multiple types of triggers 30% §
Slide 8: Swelling of an HAE attack is caused by excess bradykinin
The swelling of an HAE attack is caused by excess levels of bradykinin: PHA121 is designed to block signaling by bradykinin Most genetic causes lead to elevated levels of bradykinin Busse 2020 J Allergy Clin Immunol Pract HMWK: high-molecular-weight kininogen; cHMWK: cleaved high-molecular-weight ki
Slide 9: People living with HAE actively switch products seeking improvement
People living with HAE actively switch products seeking improvement in efficacy, safety/tolerability, and convenience 1 2 3 … but safety & tolerability … while convenience has Efficacy is patients’ are pushing patients to become a key driver for prime concern … explore alternatives … patient prefere
Slide 10: HAE is a valuable, growing market
HAE is a valuable, growing market Kalbitor; $38 ; 1% Ruconest; $199 ; 8% icatibant; $68 ; 3% Firazyr; $255 ; 11% Takhzyro; $854 ; 36% FY2021 § Estimated $2.4B global sales ($M) HAE sales for 2021 Berinert; $334 ; 14% § Estimated 15% CAGR est. 2021-2028 Orladeyo; $123 ; 5% est. Haegarda; $337 ; 14% C
Slide 12: On-demand and prophylaxis: two oral products using the same active ingredient
On-demand and prophylaxis: Developing two oral products utilizing the same active ingredient PHA121 PHVS416 PHVS719 Softgel capsule formulation Extended-release tablet formulation Enabled by Enabled by colonic absorption rapid absorption in the stomach Potential to provide fast, easy, and reliable A
Slide 13: Wholly-owned pipeline focused on bradykinin B2 receptor mechanism
Wholly-owned pipeline focused on bradykinin B2 receptor mechanism Candidate Discovery Preclinical Phase 1 Phase 2 Phase 3 Next Milestone Indication PHA121 Phase 2 topline data PHVS416 in 4Q22 On-demand HAE (RAPIDe-1 trial) Phase 2 topline data PHVS416 in 1Q23 HAE Prophylaxis (CHAPTER-1 trial) (PoC)
Slide 15: Pharvaris compounds are potent, oral competitive inhibitors of the bradykinin B2 receptor
Pharvaris compounds are potent, orally available competitive inhibitors of the bradykinin B2 receptor Competitive antagonism of bradykinin-induced contraction (human umbilical vein preparation) Icatibant PHA121 Increasing antagonist concentration Increasing antagonist concentration pA 8.7 nM pA 0.35
Slide 17: PHA121 was well tolerated in Phase 1 SAD and MAD trials
PHA121 was well tolerated in Phase 1 SAD and MAD trials 1 mg PHA-022121 fasted 1000 PHA121 (oral solution) 2 mg PHA-022121 fasted 4.5 mg PHA-022121 fasted 100 12 mg PHA-022121 fasted § No clinically significant changes were 22 mg PHA-022121 fasted 10 observed for physical exams, vitals, ECG, and 40
Slide 18: Phase 1 pharmacokinetics offer options for development
Phase 1 pharmacokinetics offer options for development Multiple-dose C trough (Day 10, BID with food) 250 Food effect on single dose 250 45 40 22 mg PHA121 35 200 200 (fasted) 30 22 mg PHA121 25 (HCHF meal) 150 150 20 22 mg PHA121 (standard meal) 15 EC85 10 100 100 5 0 12 mg 22 mg 33 mg 50 50 BID BI
Slide 19: Inhibition of bradykinin-induced hemodynamic effects is a validated surrogate assessment
Inhibition of bradykinin-induced hemodynamic effects is a validated surrogate assessment § In healthy volunteers, pre-dosing a bradykinin-B2-receptor antagonist blocks the Bradykinin (BK) hemodynamic effects of bradykinin • Bradykinin effects restored as single-dose eliminated BP HR § Used to select
Slide 20: Preclinical: oral PHA121 inhibits bradykinin challenge with longer duration than icatibant
In preclinical in vivo studies, oral PHA121 inhibits challenge by bradykinin with longer duration and faster onset than SC icatibant https://education.aaaai.org/sites/default/files/L37%20Lesage_1.pdf © 2022 20
Slide 21: Oral PHA121 blocks bradykinin-induced hemodynamic changes in healthy volunteers
In healthy volunteers, oral pre-treatment with PHA121 blocks the effect of bradykinin-induced hemodynamic changes PHA121 or placebo (po) Potency ~4x higher EC (ng/mL) 2.4 50 than icatibant Bradykinin EC (ng/mL) 13.8 BK BK BK BK BK (BK) 85 (published data) +12 0 +1 +4 +8 hours +24 Predose A single PH
Slide 23: HAE RAPIDe-1 study: treating acute attacks on-demand
HAE RAPIDe-1 study: Treating patients on-demand for acute attacks in Type 1 or 2 HAE § Primary objective: to evaluate angioedema Study Site Home Treatment Non-attack Attack 1 Attack 2 Attack 3 symptom relief within four hours in acute attacks of patients with HAE type 1 or 2 PHVS416 PHVS416 placebo
Slide 24: On-Demand: PHVS416 aims to provide clear differentiation
On-Demand: PHVS416 aims to provide clear differentiation for efficacy and convenience Clinical data PHVS416 icatibant sebetralstat berotralstat BERINERT® RUCONEST® KALBITOR® FDA Approval (Phase 2) 2011 (Phase 3) (EOP2, dropped) 2009 2014 2009 Mechanism B2R B2R pKi pKi C1INH C1INH pKi Dose ≤30 mg 30
Slide 26: Data from prophylactic proof-of-concept study and PHVS719 tablet PK to enable Phase 3
Data from prophylactic proof-of-concept study (PHVS416) and PHVS719 tablet PK to enable Phase 3 development Candidate Phase 1 Phase 2 Phase 3 Indication PHVS416 Utilizing the food effect observed in Phase 1, PK/PD modeling Data 1Q23 Prophylaxis HAE suggests that twice-daily dosing of PHVS416 can mai
Slide 27: HAE CHAPTER-1 study enrolling: prevention of attacks in HAE
HAE CHAPTER-1 study enrolling: Prevention of attacks in HAE (proof of concept with PHVS416 softgel capsule) § Primary objective: assessing safety and efficacy of 12 WEEKS PHA121 in preventing HAE attacks in patients with HAE type 1 or type 2 Placebo BID: 2 placebo capsules • Placebo-controlled, 3 pa
Slide 28: PHVS719 single-dose PK study demonstrates QD potential
PHVS719 single-dose PK study demonstrates QD potential Mean plasma concentration time profile § PHVS416 and PHVS719 well tolerated 200§ No SAEs or severe TEAEs PHVS416 capsule (2x10mg), fasted § PHVS416 rapid exposure confirmed § Exceeding EC85 within 15 minutes PHVS719 tablet (40 mg), fed§ PHVS719
Slide 29: Prophylaxis: PHVS719 aims to combine efficacy and convenience
Prophylaxis: PHVS719 aims to combine efficacy and convenience compared to approved therapies and oral pipeline PHVS719 KVD824 ORLADEYO® TAKHZYRO® HAEGARDA® CINRYZE® FDA Approval (Phase 1/2) (Phase 2) 2020 2018 2017 2008 Mechanism B2R pKi pKi pK mAb C1INH C1INH Dose 40 mg (est.) 1-3x300 mg 150 mg, 11
Slide 30: Pharvaris poised for multiple milestones
Pharvaris poised for multiple milestones HAE On-Demand HAE Prophylaxis (type 1 and type 2) (type 1 and type 2) RAPIDe-1 Ph2 topline data CHAPTER-1 Ph2 topline data PHVS416 soft capsule (anticipated 4Q22) (anticipated 1Q23) ü Ph1 SD PK demonstrates PHVS719 XR tablet -- once-daily potential Financiall

Pharvaris — Investor Presentation (July 2022) on 6ix

Pharvaris — Investor Presentation (July 2022)

Slide 1: Pioneering science for patient choice

Slide 2: Disclaimer

Slide 3: Fulfilling an unmet need in the treatment of HAE and other bradykinin-mediated diseases

Slide 4: Experienced management with deep expertise in development and rare diseases

Slide 5: Hereditary Angioedema (HAE)

Slide 6: HAE is a rare, life-long condition characterized by attacks of swelling

Slide 7: HAE attacks are unpredictable, debilitating and potentially lethal

Slide 8: Swelling of an HAE attack is caused by excess bradykinin

Slide 9: People living with HAE actively switch products seeking improvement

Slide 10: HAE is a valuable, growing market

Slide 11: Product Strategy

Slide 12: On-demand and prophylaxis: two oral products using the same active ingredient

Slide 13: Wholly-owned pipeline focused on bradykinin B2 receptor mechanism

Slide 14: Programs

Slide 15: Pharvaris compounds are potent, oral competitive inhibitors of the bradykinin B2 receptor

Slide 16: PHA121 PK/PD in humans

Slide 17: PHA121 was well tolerated in Phase 1 SAD and MAD trials

Slide 18: Phase 1 pharmacokinetics offer options for development

Slide 19: Inhibition of bradykinin-induced hemodynamic effects is a validated surrogate assessment

Slide 20: Preclinical: oral PHA121 inhibits bradykinin challenge with longer duration than icatibant

Slide 21: Oral PHA121 blocks bradykinin-induced hemodynamic changes in healthy volunteers

Slide 22: PHVS416/On-Demand

Slide 23: HAE RAPIDe-1 study: treating acute attacks on-demand

Slide 24: On-Demand: PHVS416 aims to provide clear differentiation

Slide 25: PHVS719/Prophylaxis

Slide 26: Data from prophylactic proof-of-concept study and PHVS719 tablet PK to enable Phase 3

Slide 27: HAE CHAPTER-1 study enrolling: prevention of attacks in HAE

Slide 28: PHVS719 single-dose PK study demonstrates QD potential

Slide 29: Prophylaxis: PHVS719 aims to combine efficacy and convenience

Slide 30: Pharvaris poised for multiple milestones

Slide 31: © 2022 © 2022