Pharvaris N.v. · NASDAQ:PHVS
Pharvaris — Investor Presentation (January 2024)
59 slides from Pharvaris's investor presentation, Jan 22, 2024
Slide 1: Corporate Presentation January 2024
Corporate Presentation January 2024 Pioneering science for patient choice Exhibit 99.2
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: Focused on unmet need in the treatment of HAE and other bradykinin-mediated diseases
Focused on unmet need in the treatment of hereditary angioedema (HAE) and other bradykinin-mediated diseases Deep expertise in bradykinin/B2 receptor biology and chemistry Orally available, small molecule targeting the validated bradykinin B2 receptor pathway Positive top-line Phase 2 data in HAE: R
Slide 4: Deucrictibant: A novel, orally bioavailable bradykinin B2 receptor antagonist
Deucrictibant: A novel, orally bioavailable bradykinin B2 receptor antagonist for bradykinin-mediated angioedema Entering late-stage development for hereditary angioedema Potent inhibition of the bradykinin B2 receptor to compete with bradykinin, the ultimate driver of swelling attacks Results from
Slide 5: Excess levels of bradykinin lead to swelling characteristic of angioedema attacks
Excess levels of bradykinin lead to swelling characteristic of angioedema attacks Hereditary HAE due to C1INH deficiency Type I HAE Type II HAE HAE with normal C1INH HAE-FXII HAE-PLG HAE-HS3ST6 HAE-KNG HAE-unknown HAE-ANGPT HAE-MYOF HAE-HSST HAE-SCLS Acquired C1INH deficiency (AAE C1-INH) Lymphoprol
Slide 6: Clinical dosing guided by validated bradykinin challenge surrogate-marker model
Clinical dosing is guided by prediction from a validated in vivo surrogate-marker model, the bradykinin challenge https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf; Maurer et al 2020: Long-term effectiveness and safety of icatibant for the on-demand treatment of h
Slide 7: Our strategy: Manage HAE with two oral products using the same active ingredient
Our strategy: Manage HAE with two oral products that utilize the same active ingredient for on-demand and prophylactic treatment Deucrictibant has the potential to become the preferred therapy for people living with HAE to manage their condition *Aspirational; to be confirmed with clinical data deuc
Slide 8: Wholly-owned pipeline focused on bradykinin B2 receptor mechanism
Wholly-owned pipeline focused on bradykinin B2 receptor mechanism
Slide 9: Regulatory update
Regulatory update In August 2022, the U.S. Food & Drug Administration (FDA) placed a hold on clinical trials of deucrictibant in the U.S. based on its review of nonclinical data In June 2023, the FDA removed the clinical hold on on-demand trials based on interim results from a 26-week rodent toxicol
Slide 10: HAE: A rare, life-long genetic condition with significant burden
HAE: A rare, life-long genetic condition with significant burden from unpredictable, debilitating, and potentially lethal attacks of swelling Source: Nordenfelt et al, Acta Derm. Venereol 2016: 96: 540-545; Busse 2020 J Allergy Clin Immunol Pract; Bork et al 2021 J Allergy Clin Immunol Unpredictable
Slide 11: Significant global unmet need affecting people living with HAE
Significant global unmet need affecting potentially up to 100,000 people living with HAE Source: Proprietary company research 2022; Maurer et al. Consensus on diagnosis and management of Hereditary Angioedema in the Middle East: A Delphi initiative. World Allergy Organization Journal (2023);16:1-2;
Slide 12: People living with HAE actively switch products
Source: Proprietary company research 2022 People living with HAE actively switch products, seeking improvement in efficacy, safety/tolerability, and convenience Efficacy is a prime concern … … but safety and tolerability drive exploration of alternatives … … while convenience has become a key driver
Slide 13: People living with HAE use approved therapeutics for on-demand or prophylaxis
People living with HAE use approved therapeutics for treatment (‘on demand’) or prevention of attacks (‘prophylaxis’) Estimated $2.7B global HAE sales in 2022 Estimated 15% CAGR 2021-2028 SC oral IV No new on-demand therapies introduced since 2014 Three new prophylactic products approved since 2017:
Slide 14: On-Demand: Deucrictibant immediate-release capsules (PHVS416)
On-Demand Deucrictibant immediate-release capsules (PHVS416)
Slide 15: Only injectable options: Significant unmet need in on-demand treatment of HAE attacks
Only injectable options: Significant unmet need in the on-demand treatment of HAE attacks Source: Proprietary Pharvaris research, 2022 (representative sample of patients, n = 103, and doctors, n = 100) Treatment today means painful injections … … and often one dose does not suffice … … while finding
Slide 16: Not all attacks are treated
Not all attacks are treated: Physicians and patients report reasons for not treating most recent attack Source: Mendivil et al., ACAAI 2023; https://ir.pharvaris.com/static-files/1b7e2270-34fd-411c-8f64-a0da8b2a65ec Attack was mild Not prescribed ODT Too long to resolve attack Not carrying medicatio
Slide 17: People living with HAE are hoping for better on-demand therapies
People living with HAE are hoping for better on-demand therapies that offer rapid symptom relief with one single, oral dose Source: Proprietary Pharvaris research, 2022 (representative sample of patients, n = 103, and doctors, n = 100) Effectively targeting the bradykinin receptor with a small molec
Slide 18: HAE RAPIDe-1 study design
HAE RAPIDe-1 study: Phase 2 study of on-demand treatment of angioedema attacks in patients with HAE-1/2 Source: www.hae-rapide.com; https://clinicaltrials.gov/ct2/show/NCT04618211; https://hae-rapide.us/; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-003445-11 Screening Period R
Slide 19: Positive top-line Phase 2 data from RAPIDe-1
Positive top-line Phase 2 data from RAPIDe-1 study of PHVS416 for the on-demand treatment of HAE attacks A total of 74 patients from 13 countries were enrolled to the study, 62 of them had 147 attacks that were treated with blinded study drug and included in efficacy evaluation The primary endpoint
Slide 20: Rapid absorption with mean plasma levels exceeding EC85 within 30 min
Rapid absorption with mean plasma levels exceeding EC85 (13.8 ng/mL) within 30 min Mean plasma levels maintained >EC85 for approximately 8 h at 10 mg or 20 mg >10 h at 30 mg dose EC85 levels established using bradykinin challenge, a human surrogate endpoint study in healthy volunteers PK analysis in
Slide 21: Primary endpoint: Deucrictibant IR significantly reduced attack symptoms by VAS-3 at 4h
Primary endpoint: Deucrictibant IR significantly reduced attack symptoms by VAS-3 at 4h †Nominal p-value; VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours; N = The number of attacks in the mITT Analysis Set. Attacks in mITT Analysis Set refer to attacks treat
Slide 22: Deucrictibant IR significantly shortened time to onset of symptom relief
Deucrictibant IR significantly shortened time to onset of symptom relief (30% reduction in VAS-3) Nominal p-value; N = The number of attacks in the mITT Analysis Set. Median time based on Kaplan-Meier estimates. p-values based on a marginal Cox proportional hazards model. The combined PHVS416 result
Slide 23: Post-hoc analysis: end of progression within 25 to 26 min
In a post-hoc analysis, patients on deucrictibant achieved end of progression by VAS-3 within 25 to 26 min Source: Riedl et al., ACAAI 2023; https://ir.pharvaris.com/static-files/0bae214b-7ff8-49ec-8340-1bb60a5935b9
Slide 24: Time to almost complete or complete symptom relief
Deucrictibant IR significantly reduced time to almost complete or complete symptom relief (all individual VAS ≤10) †Nominal p-value; N = The number of attacks in the mITT Analysis Set. Median time based on Kaplan-Meier estimates. p-values based on a marginal Cox proportional hazards model. The combi
Slide 25: Patients used substantially less rescue medication
Patients treating with deucrictibant IR used substantially less rescue medication N = The number of attacks in the mITT Analysis Set
Slide 26: Deucrictibant IR was well tolerated at all doses
Deucrictibant IR was well tolerated at all doses N= The number of subjects (Part I) and number of attacks (Part II) in the Safety Analysis Set. The Safety Analysis Set includes all randomized patients who received any dose of study drug. Treatment-related AEs within 48 h post-treatment are included
Slide 27: Doctors and patients consider oral acute therapy would increase treated attacks
Both doctors and patients consider an oral acute therapy would increase likelihood that patients would treat more attacks, earlier Source: Proprietary Pharvaris research, 2022 (representative sample of patients, n = 103, and doctors, n = 100) Doctors (n=100) Patients (n=103) Anticipated impact of OR
Slide 28: Renamed VAS to AMRA, reflecting electronic attack assessment
We have renamed VAS to AMRA, reflecting its evolution from a paper-based to electronic attack assessment 2008–2011 Jerini-Shire Why do we need change? Addressing user experience to leverage technology and accuracy of data collection1 HAE ODT trials require frequent assessments to be recorded by part
Slide 29: Real-world study: similar median time to symptom relief for AMRA-3 and PGI-C
In a real-world study using standard-of-care therapy, similar median time to symptom relief for AMRA-3 ≥20% and PGI-C ‘a little better’ Source: Mendivil et al., UCARE 2023 (ir.pharvaris.com/static-files/f2d3d4ea-2526-4885-9951-a90015add462) PRO instrument Events (n) Median time to, h (95% CI) PGI-C
Slide 30: HAE RAPIDe-3 global Phase 3 study
HAE RAPIDe-3 study: A global Phase 3 study of on-demand treatment of angioedema attacks in patients with HAE-1/2 Endpoints Onset of symptom relief Patient Global Impression of Change (PGI-C) rating of at least “a little better” for two consecutive timepoints within 12 hours post-treatment Secondary
Slide 31: Long Term Prophylaxis: Deucrictibant extended-release tablets (PHVS719)
Long Term Prophylaxis Deucrictibant extended-release tablets (PHVS719)
Slide 32: People seeking effective, well-tolerated, less burdensome prophylactic therapies
Injectable-like efficacy Easy, painless administration People living with HAE are seeking highly effective, well-tolerated and less burdensome prophylactic therapies Proprietary Pharvaris research, 2022 (representative sample of patients, n = 103, and doctors, n = 100) An effective oral bradykinin B
Slide 33: CHAPTER-1 Phase 2 prophylactic study of deucrictibant in HAE
CHAPTER-1, a Phase 2 prophylactic study of deucrictibant in HAE 92.3% reduction in occurrence of moderate and severe attacks* 92.6% reduction in occurrence of attacks treated with on-demand medication* Clinically meaningful results across primary, secondary, and health-related quality of life endpoi
Slide 34: CHAPTER-1 study design
CHAPTER-1 study design Double-blind, placebo-controlled Phase 2 study evaluating deucrictibant for long-term prophylaxis in HAE-1/2 34 participants enrolled in North America and Europe R = randomization; *deucrictibant 20 mg/day = deucrictibant immediate-release capsules (PHVS416) 10 mg twice daily
Slide 35: Participant disposition
Participant disposition 20 mg/day = deucrictibant immediate release (IR) capsules 10 mg twice daily; 40 mg/day = deucrictibant IR capsules 20 mg twice daily; n = number of participants. All Screened n=44 Randomized n=34 Screen Failed n=10 Placebo n=11 20 mg/day n=11 40 mg/day n=12 Completed Blinded
Slide 36: Balanced demographics and baseline characteristics
Balanced demographics and baseline characteristics 20 mg/day = deucrictibant immediate release (IR) capsules 10 mg twice daily. 40 mg/day = deucrictibant IR capsules 20 mg twice daily. N = number of randomized participants. Placebo N=11 20 mg/day N=11 40 mg/day N=12 All N=34 Age in years – Mean 41.4
Slide 37: Primary endpoint met: deucrictibant significantly reduced attack rate
Primary endpoint met: deucrictibant significantly reduced attack rate Monthly attack rate measured as time-normalized number of investigator confirmed HAE attacks Placebo N=11 20 mg/day N=11 40 mg/day N=12 Monthly attack rate – Median Baseline 1.67 1.67 1.74 On study 2.15 0 0.15 Change from baseline
Slide 38: Significant attack reduction and no severe attacks with deucrictibant
Significant attack reduction and no severe attacks with deucrictibant Participants grouped by treatment Time (week) 20 mg/day = deucrictibant immediate release (IR) capsules 10 mg twice daily. 40 mg/day = deucrictibant IR capsules 20 mg twice daily.
Slide 39: 92.3% reduction in moderate or severe attacks at 40 mg/day
92.3% reduction in moderate or severe attacks at 40 mg/day dose Placebo N=11 20 mg/day N=11 40 mg/day N=12 Monthly attack rate of moderate or severe attacks LS mean 1.50 0.26 0.12 % reduction vs placebo 82.8% 92.3% Nominal p-value 0.0066 0.0067 20 mg/day = deucrictibant immediate release (IR) capsul
Slide 40: 92.6% reduction in attacks treated with ODT at 40 mg/day
92.6% reduction in attacks treated with ODT at 40 mg/day dose Placebo N=11 20 mg/day N=11 40 mg/day N=12 Monthly attack rate of attacks treated with ODT LS mean 1.41 0.35 0.10 % reduction vs placebo 75.1% 92.6% Nominal p-value 0.0074 0.0040 ODT = on-demand treatment (icatibant, C1-inhibitor (C1-INH)
Slide 41: Substantial reduction of attack rate from baseline
Substantial reduction of attack rate from baseline 20 mg/day = deucrictibant immediate release (IR) capsules 10 mg twice daily. 40 mg/day = deucrictibant IR capsules 20 mg twice daily. N = number of randomized participants. Results based on participants with at least 4 weeks of treatment.
Slide 42: Consistent efficacy regardless of baseline attack rate
Consistent efficacy regardless of baseline attack rate 20 mg/day = deucrictibant immediate release (IR) capsules 10 mg twice daily. 40 mg/day = deucrictibant IR capsules 20 mg twice daily. N = number of randomized participants.
Slide 43: All 40 mg/day participants reported an improvement in PGA-Change
All 40 mg/day participants reported an improvement in PGA-Change 20 mg/day = deucrictibant immediate release (IR) capsules 10 mg twice daily. 40 mg/day = deucrictibant IR capsules 20 mg twice daily. PGA-Change = patient global assessment of change (question). N = number of participants with PGA-Chan
Slide 44: AE-QoL: improvement in health-related quality of life
AE-QoL: improvement in health-related quality of life AE-QoL Total Score Placebo 20 mg/day 40 mg/day Baseline N 11 10 12 Mean 45.3 39.1 41.1 Median (Q1, Q3) 42.6 (29.4, 57.4) 37.5 (16.2, 55.9) 40.4 (31.6, 49.3) Week 12 N’ 8 10 10 Mean 35.7 20.2 13.2 Median (Q1, Q3) 37.5 (19.1, 49.3) 18.4 (7.4, 33.8)
Slide 45: Deucrictibant well-tolerated at both doses
Deucrictibant well-tolerated at both doses Placebo (N=11) 20 mg/day (N=11) 40 mg/day (N=12) Subjects n (%) Number of events Subjects n (%) Number of events Subjects n (%) Number of events TEAEs TEAE 7 (63.6) 16 6 (54.5) 11 7 (58.3) 12 Treatment related TEAEs Treatment related TEAE 1 (9.1) 1 2 (18.2)
Slide 46: All treatment-related adverse events were mild
All treatment-related adverse events were mild System Organ Class Preferred Term Placebo (N=11) 20 mg/day (N=11) 40 mg/day (N=12) Participants with at least one treatment-related TEAE 1 (9.1%) 2 (18.2%) 1 (8.3%) Gastrointestinal disorders 0 1 (9.1%) 0 Nausea 0 1 (9.1%) 0 Investigations 0 0 1 (8.3%)
Slide 47: Main efficacy results
Main efficacy results 20 mg/day = deucrictibant immediate release (IR) capsules 10 mg twice daily; 40 mg/day = deucrictibant IR capsules 20 mg twice daily. N = number of randomized participants. LS mean = least squares mean. CI = confidence interval. *Results of monthly attack rates are based on Poi
Slide 48: Deucrictibant XR demonstrates QD potential: Phase 3 dosage form
As seen in a single-dose Phase 1 PK study, deucrictibant XR demonstrates QD potential: Phase 3 dosage form Source: Company data Deucrictibant IR and XR well tolerated No SAEs or severe TEAEs Deucrictibant XR extended-release maintained exposure above EC85 for >24h with and without food Similar AUC24
Slide 49: Our strategy: Manage HAE with two oral products using the same active ingredient
Our strategy: Manage HAE with two oral products that utilize the same active ingredient for on-demand and prophylactic treatment *Aspirational; to be confirmed with clinical data deucrictibant (PHVS416) Immediate-release capsule rapid absorption deucrictibant (PHVS719) Extended-release tablet sustai
Slide 50: Focused on unmet need in the treatment of HAE and other bradykinin-mediated diseases
Focused on unmet need in the treatment of hereditary angioedema (HAE) and other bradykinin-mediated diseases Deep expertise in bradykinin/B2 receptor biology and chemistry Orally available, small molecule targeting the validated bradykinin B2 receptor pathway Positive top-line Phase 2 data in HAE: R
Slide 51: www.pharvaris.com
www.pharvaris.com NASDAQ: PHVS Aspiring to free people from HAE or other bradykinin-mediated diseases
Slide 52: Additional RAPIDe-1 top-line clinical data Appendix
Additional RAPIDe-1 top-line clinical data Appendix
Slide 53: RAPIDe-1: Primary, key secondary and other endpoints
RAPIDe-1: Primary, key secondary and other endpoints Primary Endpoint Change in VAS-3 score from pre-treatment to 4h post-treatment Key Secondary Endpoints Time to onset of symptom relief (VAS-3; ≥30% reduction from the pre-treatment score) Time to a ≥50% reduction in VAS-3 score from the pre-treatm
Slide 54: Results summary of primary efficacy endpoint
Results summary of primary efficacy endpoint Placebo N=51 PHVS416 10 mg N=37 PHVS416 20 mg N=28 PHVS416 30 mg N=31 Combined PHVS416* N=96 Mean VAS-3 at pre-treatment 27.76 26.16 25.46 29.73 27.11 Change in VAS-3 at 4 hours least-squares mean difference: PHVS416 - Placebo -16.75 -15.02 -16.28 -16.08
Slide 55: Results summary of key secondary efficacy endpoints
Results summary of key secondary efficacy endpoints Placebo N=51 PHVS416 10 mg N=37 PHVS416 20 mg N=28 PHVS416 30 mg N=31 Combined PHVS416* N=96 Time to onset of symptom relief by VAS-3 30% reductiona Median time in hours (95% CI) 8.0 (7.6, 46.9) 2.1 (1.5, 2.9) 2.7 (1.9, 3.5) 2.5 (1.9, 3.8) 2.4 (2.0
Slide 56: PHVS416 significantly reduced time to 50% reduction in VAS-3
PHVS416 significantly reduced time to 50% reduction in VAS-3 †Nominal p-value; VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours; N = The number of attacks in the mITT Analysis Set. Median time based on Kaplan-Meier estimates. p-values based on a marginal Cox
Slide 57: MSCS and TOS: definitions
MSCS and TOS: definitions Validated patient-reported outcome measures to comprehensively capture symptom severity and change of HAE attacks MSCS (Mean Symptom Complex Severity) score is a point-in-time measure of symptom severity: Patients rated the severity of each affected symptom on a categorical
Slide 58: Greater improvement in MSCS and TOS with PHVS416 than placebo
Greater improvement in MSCS and TOS with PHVS416 than placebo Placebo PHVS416 10 mg PHVS416 20 mg PHVS416 30 mg Combined PHVS416 Change in MSCS score at 4 hours n 40 32 26 27 85 least-squares mean (95% CI) -0.29 (-0.51, -0.08) -1.08 (-1.33, -0.83) -0.91 (-1.19, -0.62) -0.68 (-0.95, -0.40) -0.90 (-1.
Slide 59: Time to symptom relief by TOS
Placebo PHVS416 10 mg PHVS416 20 mg PHVS416 30 mg Combined PHVS416 Number of attacks 49 36 28 29 93 Attacks achieving “a little better” for all SCs at two consecutive time points - n (%)* 18 (36.7%) 32 (88.9%) 25 (89.3%) 27 (93.1%) 84 (90.3%) Median (95% CI) time by KM estimate (hours) 7.62 (3.95, N