Slide 1: Pioneering science for patient choice
Pioneering science for patient choice March 2023 Exhibit 99.1
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: Pharvaris: Focused on unmet need in HAE and other bradykinin-mediated diseases
Pharvaris: Focused on unmet need in the treatment of hereditary angioedema (HAE) and other bradykinin-mediated diseases Novel lead series with strong IP (primary CoM granted in multiple territories; initial term to 2038); FDA orphan drug designation World-wide operations: the Netherlands, USA, and S
Slide 4: Experienced management with deep expertise in development and rare diseases
Morgan Conn, Ph.D. Chief Business Officer Anne Lesage, Ph.D. Chief Early Development Officer Experienced management with deep expertise in development and rare diseases Berndt Modig Chief Executive Officer Jochen Knolle, Ph.D. Chief Scientific and Operating Officer Peng Lu, M.D., Ph.D. Chief Medical
Slide 5: Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE)
Slide 6: HAE: a rare, life-long genetic condition with significant burden
Unpredictable frequency, location, timing, and severity Multiple types of triggers If untreated, attacks last multiple days Attacks are commonly painful, leading to hospitalization or multiple sick days Half of people living with HAE experience a potentially life-threatening laryngeal attack at leas
Slide 7: 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’) CONFIDENTIAL - board materials est. est. Source: Quarterly filings (NYSE: TAK; NASDAQ: BCRX, PHAR); EvaluatePharma; www.fda.gov; company research Estimated $2.4B global HAE sales for
Slide 8: People living with HAE actively switch products
People living with HAE actively switch products, seeking improvement in efficacy, safety/tolerability, and convenience Efficacy is patients’ prime concern … … but safety & tolerability are pushing patients to explore alternatives … … while convenience has become a key driver for patient preference P
Slide 9: Significant global unmet need: up to 100,000 people living with HAE
Significant global unmet need: Potentially up to 100,000 people living with HAE CONFIDENTIAL EU 15-20k US 6-9k LATAM 12-16k JP 2-4k Plus breakthrough attacks ME&A 10-14k Proprietary company research 2022; Maurer et al. Consensus on diagnosis and management of Hereditary Angioedema in the Middle East
Slide 10: The swelling of an HAE attack is caused by excess bradykinin
HMWK: high-molecular-weight kininogen; cHMWK: cleaved high-molecular-weight kininogen; FXII(a): Factor XII(a); ACE(i): angiotensin-converting enzyme (inhibitor); tPA: tissue plasminogen activator; KNG1: gene encoding HMWK; PLG: gene encoding plasminogen; F12: gene encoding FXII The swelling of an HA
Slide 11: First orally bioavailable bradykinin B2 receptor antagonist
Pharvaris has discovered the first orally bioavailable bradykinin B2 receptor antagonist New molecular entity, orally administered Potent inhibition of the bradykinin B2 receptor to compete with bradykinin, the ultimate driver of swelling attacks Results from Phase 1 healthy volunteer studies demons
Slide 12: Predictive value of the BK challenge surrogate-marker model
Predictive value of our unique in vivo surrogate-marker model, the BK challenge, allows for derisking of our clinical studies 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 tr
Slide 13: Product Strategy
Product Strategy
Slide 14: Two oral products utilizing the same active ingredient
On-demand and prophylaxis: Developing two oral products utilizing the same active ingredient PHA121 PHVS719 Extended-release tablet formulation Aim to maintain compound exposure to prevent attacks, for convenient and effective control* PHVS416 Softgel capsule formulation Potential to provide rapid,
Slide 15: Regulatory update
Regulatory update In August 2022, the U.S. Food & Drug Administration (FDA) placed a hold on clinical trials of PHA121 in the U.S. based on its review of nonclinical data The agency requested that Pharvaris conduct an additional long-term rodent toxicology study and update the Investigator’s Brochur
Slide 16: Wholly-owned pipeline focused on bradykinin B2 receptor mechanism
Wholly-owned pipeline focused on bradykinin B2 receptor mechanism * The FDA has placed a hold on clinical trials of PHA121 in the U.S.; timeline based on studies ongoing outside the U.S.; see slide 15 for an update on our clinical program Candidate Indication Discovery Preclinical Phase 1 Phase 2 Ph
Slide 17: PHVS416/On-Demand
PHVS416/On-Demand Softgel capsule formulation of PHA121
Slide 18: On-demand treatment of HAE attacks: significant unmet need
On-demand treatment of HAE attacks: No new approvals beyond injectable options have left a significant unmet need Treatment today means painful injections … … and often one dose does not suffice … … while finding a place to administer the drug causes an extra burden As a result, people living with H
Slide 19: Patients hope for better on-demand therapies: rapid, single, oral dose
People living with HAE are hoping for better on-demand therapies that offer rapid symptom relief with one single, oral dose Patients want rapid onset of symptom relief … … with single dose durability … … in an oral pill Effectively targeting the bradykinin receptor with a small molecule has the pote
Slide 20: RAPIDe-1 study design
HAE RAPIDe-1 study: Phase 2 study of on-demand treatment of angioedema attacks in patients with Type I or II HAE 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
Slide 21: 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 22: PK profile in HAE patients
PK profile in HAE patients: Rapid absorption confirmed on oral dosing, consistent with Phase 1 healthy volunteer studies 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
Slide 23: Primary endpoint: PHVS416 significantly reduces 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 treated with blinded study drug that had non-missing VAS result at pre-treatment and at least
Slide 24: PHVS416 significantly shortened time to onset of symptom relief
†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 results are based on post-hoc analyses to provide a reference of the result by pooling all three active
Slide 25: TOS Patient Reported Outcome
TOS Patient Reported Outcome (PRO) TOS PRO captures change in five symptom complexes of HAE attacks At each timepoint, the change in attack symptom from pre-treatment is reported by patient A lot better or resolved A little better Same A little worse A lot worse PRO – how do you feel now compared to
Slide 26: TOS endpoint shows early response to treatment
TOS endpoint shows early response to treatment: Significant at 4h Source: Vernon M, Rentz AM, Wyrwich KW, et al. Qual Life Res.2009; †Nominal p-value; N = The number of attacks in the mITT Analysis Set. TOS = Treatment Outcome Score. Figure is based on descriptive summary of mean and SEM. The least-
Slide 27: Reduced time to almost complete or complete symptom relief
PHVS416 significantly reduces 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 combined PHVS
Slide 28: Patients used substantially less rescue medication
Patients treating with PHVS416 used substantially less rescue medication N = The number of attacks in the mITT Analysis Set This presentation includes data for an investigational product not yet approved by regulatory authorities
Slide 29: PHVS416 was well tolerated at all doses
PHVS416 was well tolerated at all doses No treatment-related SAEs or AEs of severe severity No AEs leading to treatment discontinuation No treatment-related AEs of laboratory parameters, vital signs, or ECG parameters Few treatment-related AEs reported within 48 h after administration of study drug
Slide 30: Doctors and patients on impact of an oral acute therapy
Both doctors and patients consider an oral acute therapy would increase likelihood that patients would treat more attacks, earlier CONFIDENTIAL Doctors (n=100) Patients (n=103) Anticipated impact of ORAL acute therapy on attacks treated Would treat MORE attacks Would treat attacks EARLIER Would trea
Slide 31: PHVS719/Prophylaxis
PHVS719/Prophylaxis Extended-release tablet formulation of PHA121
Slide 32: CHAPTER-1 study ongoing outside U.S.
HAE CHAPTER-1 study ongoing outside U.S.: Prevention of attacks in HAE (proof of concept with PHVS416 softgel capsule) Primary objective: assessing safety and efficacy of PHA121 in preventing HAE attacks in patients with HAE type 1 or type 2 Placebo-controlled, 3 parallel arms, two doses Includes op
Slide 33: Phase 1 pharmacokinetics support softgel proof-of-concept in prophylaxis
Phase 1 pharmacokinetics offer options to use softgel capsule as proof-of-concept in prophylactic development https://ir.pharvaris.com/static-files/0361cd85-6000-490b-932b-d305e1f3ca1b; https://ir.pharvaris.com/static-files/81a9499d-0769-4b89-8ecd-8ace5ca521d3 Multiple-dose Ctrough (Day 10, BID with
Slide 34: PHVS719 single-dose PK demonstrates QD potential
PHVS719 single-dose PK study demonstrates QD potential; target for Phase 3 dosage form PHVS416 capsule (2x10mg), fasted PHVS719 tablet (40 mg), fasted EC85 PHVS719 tablet (40 mg), fed PHVS416 and PHVS719 well tolerated No SAEs or severe TEAEs PHVS416 rapid exposure confirmed Exceeding EC85 within 15
Slide 35: Corporate summary and milestones
Corporate summary and milestones HAE On-Demand (type 1 and type 2) HAE Prophylaxis (type 1 and type 2) PHVS416 softgel capsule RAPIDe-1 Ph2 top-line data meets all primary and key secondary endpoints Phase 3 initiation CHAPTER-1 Ph2 top-line data (expected 2H23) PHVS719 XR tablet -- Ph1 SD PK demons
Slide 36: PHARVARiS
PHARVARiS Nasdaq: PHVS
Slide 37: Appendix: Additional RAPIDe-1 top-line clinical data
Appendix Additional RAPIDe-1 top-line clinical data
Slide 38: 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 39: 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 40: VAS-3 is a measure of HAE attack severity
VAS-3 is a measure of HAE attack severity, based electronically captured numerically assisted visual scale Used in approval of two most recently approved on-demand therapies FIRAZYR® icatibant and RUCONEST® C1 esterase inhibitor [recombinant] VAS, MSCS, TOS are only endpoints listed for attacks in F
Slide 41: 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 42: PHVS416 significantly reduces time to 50% reduction in VAS-3
PHVS416 significantly reduces 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 43: 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 44: 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 45: Time to symptom relief by TOS PRO demonstrated consistent efficacy
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