View:
Download DOC
Download PDF
Download XLS
6-K

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

FORM 6-K

 

REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13A-16 OR 15D-16 UNDER
THE SECURITIES EXCHANGE ACT OF 1934

 

For the month of February 2023

Commission File Number: 001-40010

 

Pharvaris N.V.

(Translation of registrant’s name into English)

 

Emmy Noetherweg 2

 

2333 BK Leiden

 

The Netherlands
(Address of principal executive office)

 

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F ☒ Form 40-F ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐

Note: Regulation S-T Rule 101(b)(1) only permits the submission in paper of a Form 6-K if submitted solely to provide an attached annual report to security holders.

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐

Note: Regulation S-T Rule 101(b)(7) only permits the submission in paper of a Form 6-K if submitted to furnish a report or other document that the registrant foreign private issuer must furnish and make public under the laws of the jurisdiction in which the registrant is incorporated, domiciled or legally organized (the registrant’s “home country”), or under the rules of the home country exchange on which the registrant’s securities are traded, as long as the report or other document is not a press release, is not required to be and has not been distributed to the registrant’s security holders, and, if discussing a material event, has already been the subject of a Form 6-K submission or other Commission filing on EDGAR.

 

PHARVARIS N.V.

 

On February 14, 2023 in connection with an investor event, Pharvaris N.V. provided a corporate update included in a corporate presentation on its website in which, among other things, Pharvaris disclosed that it has finalized the protocol for a 26-week rodent toxicology study with the FDA and that the 26-week study will initiate soon. The presentation is attached as Exhibit 99.1 hereto and is incorporated by reference herein.

 

A copy of the corporate presentation is attached hereto as Exhibit 99.1. This Report on Form 6-K (excluding Exhibit 99.1) shall be deemed to be incorporated by reference into the registration statements on Form F-3 (Registration Number 333-263198) and Form S-8 (Registration Number 333-252897). Exhibit 99.1 to this Report on Form 6-K shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended or the Exchange Act.

 

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

 

 

PHARVARIS N.V.

 

 

Date: February 14, 2023

By:

/s/ Berndt Modig

 

Name:

Berndt Modig

 

Title:

Chief Executive Officer

 

 

EXHIBIT INDEX

 

Exhibit

No.

 

Description

99.1

 

Corporate Presentation, dated February 14, 2023

 

 

 

 

 

 

 

 

 

 

 

 

 

Slide 1

Pioneering science for patient choice February 2023 Exhibit 99.1

Slide 2

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 forward-looking statements including, without limitation, statements containing the words “believe,” “anticipate,” “expect,” “estimate,” “may,” “could,” “should,” “would,” “will,” “intend” and similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. Such forward-looking statements involve unknown risks, uncertainties and other factors which may cause our actual results, financial condition, performance or achievements, or industry results, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that might cause such a difference include, but are not limited to, uncertainty in the outcome of our interactions with regulatory authorities, including the FDA with respect to the clinical hold on PHA121 clinical trials in the U.S., the expected timing, progress, or success of our clinical development programs especially for PHVS416 and PHVS719 which are in mid-stage global clinical trials and are currently on hold in the U.S. as a result of the FDA clinical hold, risks arising from epidemic diseases, such as the COVID-19 pandemic which may adversely impact our business, nonclinical studies, and clinical trials, the timing of regulatory approvals, the value of our ordinary shares, the timing, costs and other limitations involved in obtaining regulatory approval for our product candidates PHVS416 and PHVS719, or any other product candidate that we may develop in the future, our ability to establish commercial capabilities or enter into agreements with third parties to market, sell, and distribute our product candidates, our ability to compete in the pharmaceutical industry and with competitive generic products, our ability to market, commercialize and achieve market acceptance for our product candidates, our ability to raise capital when needed and on acceptable terms, regulatory developments in the United States, the European Union and other jurisdictions, our ability to protect our intellectual property and know-how and operate our business without infringing the intellectual property rights or regulatory exclusivity of others, our ability to manage negative consequences from changes in applicable laws and regulations, including tax laws, our ability to successfully remediate the material weakness in our internal control over financial reporting and to maintain an effective system of internal control over financial reporting, changes and uncertainty in general market, political and economic conditions, including as a result of inflation and the current conflict between Russia and Ukraine, and the other factors described under the headings "Cautionary Statement Regarding Forward-Looking Statements" and "Item 3. Key Information--D. Risk Factors" in our Annual Report on Form 20-F and other periodic filings with the Securities and Exchange Commission. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Certain information contained in this Presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this Presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source.

Slide 3

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 Switzerland (headquarters) Strong financial position; cash runway into 4Q24 Experienced management team with successful track record in HAE drug design and development Convenient, orally available, small molecule targeting the validated bradykinin B2 receptor pathway Clinical proof-of-mechanism using surrogate endpoint with higher potency and duration than previously observed for icatibant Positive top-line Phase 2 data from RAPIDe-1 study of PHVS416 for the on-demand treatment of HAE attacks PK/PD profile supports use in both on-demand and prophylactic settings; Phase 2 studies underway* Competitive product profile Strong fundamentals Large market opportunity Large global HAE market: >$2 billion with predicted 9% CAGR over 5 years Potential portfolio expansion into other BK-mediated angioedema and diseases through B2-receptor pathway expertise *The FDA has placed a hold on the clinical trials of PHA121 in the U.S.; see slide 15 for an update on our clinical program

Slide 4

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 Officer Includes the leaders behind the discovery, development, and approval of Firazyr® (icatibant), and a key member of the Takhzyro® (lanadelumab) development team Anna Nijdam Principal Accounting Officer Wim Souverijns, Ph.D. Chief Community Engagement and Commercial Officer Joan Schmidt, J.D. Chief Legal Officer Annick Deschoolmeester Chief Human Resources Officer

Slide 5

Hereditary Angioedema (HAE)

Slide 6

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 least once in their lifetime 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 Globally, under-diagnosed/treated HAE: A rare, life-long genetic condition with significant burden from unpredictable, debilitating, and potentially lethal attacks of swelling Nordenfelt et al, Acta Derm. Venereol 2016: 96: 540-545 Median: 14 attacks/year Females: 19 (range: 2-165 attacks/y) Males: 9 (range: 1-42 attacks/y)

Slide 7

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 2021 Estimated 15% CAGR 2021-2028 SC oral IV est. On-Demand Prophylaxis No new on-demand therapies introduced since 2014 Three new prophylactic products approved since 2017: Haegarda, Takhzyro, and Orladeyo

Slide 8

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 People living with HAE desire HAE therapy that can deliver on ALL fronts Proprietary company research 2022

Slide 9

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: A Delphi initiative. World Allergy Organization Journal (2023);16:1-2; Zuraw et al. NEJM 2008;359:1027-1036; HAEi (haei.org), The State of Management of HAE in Latin America (2015); https://haei.org/potentially-28000-hae-patients-in-china/dj; Ann Allergy Asthma Immunol 2015:114(6), 492-498; Allergol Int. (2020) Nov 6;S1323-8930(20)30135-0 North America Europe Japan South America / Central America Middle East & Africa China / South Korea / Australia & New Zealand APAC 20-30k Plus breakthrough attacks

Slide 10

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 HAE attack is caused by excess levels of bradykinin Busse 2020 J Allergy Clin Immunol Pract; Bork et al 2021 J Allergy Clin Immunol Genetic causes lead to elevated levels of bradykinin HAE HAE due to C1INH deficiency Type I HAE Mutation in SERPING1 (low plasma C1INH antigen) Type II HAE Mutation in SERPING1 (dysfunctional C1INH) HAE with normal C1INH HAE-FXII Mutation in F12 gene HAE-PLG Mutation in PLG gene HAE-HS3ST6 Mutation in HS3ST6 gene HAE-KNG Mutation in KNG1 gene HAE-unknown

Slide 11

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 demonstrate rapid absorption, exposure, and tolerability Dose and exposure threshold predicted from human surrogate endpoint for both on-demand and prophylaxis Bradykinin challenge in healthy volunteers Lesage et al, Frontiers in Pharmacology 2020, doi: 10.3389/fphar.2020.00916; ; Lesage et al, Int. Immunopharmacology 2022, doi.org/10.1016/j.intimp.2022.108523; https://ir.pharvaris.com/static-files/0361cd85-6000-490b-932b-d305e1f3ca1b; https://ir.pharvaris.com/static-files/81a9499d-0769-4b89-8ecd-8ace5ca521d3; https://ir.pharvaris.com/static-files/33217945-6893-4f49-8a93-c80ea6fb2a31; https://doi.org/10.1016/j.jaci.2019.12.094 PHA121 We aspire to develop novel, oral alternatives that improve the standard of care for people living with HAE

Slide 12

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 treatment of hereditary angioedema attacks: 10 years of the icatibant outcome survey (EAACI Poster #1118, June 6-8, 2020): https://clinicaltrials.gov/ct2/show/NCT01034969; https://ir.pharvaris.com/static-files/33217945-6893-4f49-8a93-c80ea6fb2a31; https://doi.org/10.1016/j.jaci.2019.12.094 Bradykinin (BK) BP HR EC85 = 13.8 ng/mL Potency ~4x higher than icatibant (published data) Post- dose (+1h) BK BK Predose Systolic BP Diastolic BP Mean Arterial BP Primate bradykinin challenge Healthy volunteer bradykinin challenge Phase 2 clinical dose selection On-demand (RAPIDe-1) Prophylaxis (CHAPTER-1) RAPIDe-1 on-demand study in people living with HAE On-demand dose confirmation

Slide 13

Product Strategy

Slide 14

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, easy, and reliable symptom relief for all attacks* Enabled by colonic absorption Enabled by early absorption in the stomach and gut *Aspirational; to be confirmed with clinical data

Slide 15

Regulatory update In August 2022, the U.S. Food & Drug Administration (FDA) placed a hold on the 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 Brochure Pharvaris participated in a Type A meeting with the FDA to discuss paths to address the on-demand and prophylactic holds A protocol for a 26-week rodent toxicology study has been finalized with the FDA and the study will initiate soon FDA has agreed to partially lift the clinical hold on on-demand Two remaining U.S. participants in RAPIDe-1 allowed to complete treatment of a final HAE attack per protocol All other clinical studies of PHA121 are currently on hold in the U.S. Outside the U.S., the regulatory status remains unchanged for the CHAPTER-1 study and other studies, including long-term extension RAPIDe-2 study Pharvaris notified country-specific regulatory authorities in Canada, Europe, Israel, and the UK of the U.S. clinical holds All active sites outside of the U.S. continue to recruit participants in the CHAPTER-1 clinical study

Slide 16

Wholly-owned pipeline focused on bradykinin B2 receptor mechanism * The FDA has placed a clinical hold on the 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 Phase 3 Next Milestone PHA121 API* Solution PHA121 Softgel Capsule PHVS416 On-demand HAE Phase 3 initiation PHVS416 HAE Prophylaxis (PoC) Phase 2 top-line data (CHAPTER-1) XR Tablet PHVS719 HAE Prophylaxis Phase 3 readiness PHAxxx undisclosed PHAxxx undisclosed

Slide 17

PHVS416/On-Demand Softgel capsule formulation of PHA121

Slide 18

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 HAE often delay or even avoid therapy against clinical guideline recommendations Proprietary Pharvaris research, 2022 (representative sample of patients, n = 103, and doctors, n = 100)

Slide 19

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 potential to deliver on their hopes Proprietary Pharvaris research, 2022 (representative sample of patients, n = 103, and doctors, n = 100)

Slide 20

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 Randomization Non-attack Attack 1 Attack 2 Attack 3 Part I: Study Site Part II: Home Treatment PHVS416 (10 mg) placebo 10 mg 10 mg placebo 10 mg 10 mg placebo 10 mg 10 mg PHVS416 (20 mg) PHVS416 (30 mg) placebo 20 mg 20 mg placebo 20 mg 20 mg placebo 20 mg 20 mg placebo 30 mg 30 mg placebo 30 mg 30 mg placebo 30 mg 30 mg Primary objective: to evaluate angioedema symptom relief within four hours in acute attacks of patients with HAE type 1 or 2 Study design: Placebo-controlled, three dose levels Part I: patients randomized and received a single dose of PHA121 in clinic for PK and safety assessment Part II: patients treated three attacks with two PHA121 vs. one placebo Before an attack was treated, one of the VAS-3 elements had to be at least hit a score of 30 and it had to be qualified by the clinician 74 HAE patients enrolled from ~30 sites in US, Canada, Europe, Israel, and UK

Slide 21

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 and all key secondary endpoints were met PHVS416 demonstrated rapid onset of action, symptom relief, and resolution of HAE attacks  PHVS416 substantially reduced the use of rescue medications PHVS416 was well tolerated at all dose levels There were no treatment-related SAEs, no treatment-related AEs of severe severity, and no AEs leading to treatment discontinuation This presentation includes data for an investigational product not yet approved by regulatory authorities Consistent outcomes observed across all endpoints and types of measurements

Slide 22

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 EC85 levels established using bradykinin challenge, a human surrogate endpoint study in healthy volunteers EC85 13.8 mg/L This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 23

†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 one non-missing VAS result post-treatment. VAS-3 = electronically captured, numerically assisted visual analogue scale. Figure is based on descriptive summary of mean and SEM (standard error of the mean). Least-squares mean differences, CIs, and p-values come from a mixed-effects model with repeated measures (MMRM). Data after rescue medication use is not included. The combined PHVS416 result is based on post-hoc analysis using a similar MMRM with all three active doses combined vs placebo Primary endpoint: PHVS416 significantly reduces attack symptoms by VAS-3 at 4h Difference from placebo in change from pre-treatment to 4 h post-treatment, least-squares mean (95% CI) Median time in hours (95% CI) PHVS416 10 mg -16.75 (-21.52, -11.97) p < 0.0001† PHVS416 20 mg -15.02 (-20.22, -9.81) p < 0.0001 PHVS416 30 mg -16.28 (-21.27, -11.29) p < 0.0001 Combined PHVS416 -16.08 (-19.87, -12.29) Median VAS-3 at pre-treatment ranges from 24.33-27.00 across different dose levels This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 24

†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 doses. PHVS416 significantly shortened time to onset of symptom relief (30% reduction in VAS-3) Median time in hours (95% CI) Median time in hours (95% CI) Placebo 8.0 (7.6, 46.9) PHVS416 10 mg 2.1 (1.5, 2.9) p < 0.0001† PHVS416 20 mg 2.7 (1.9, 3.5) p = 0.0021 PHVS416 30 mg 2.5 (1.9, 3.8) p < 0.0001 Combined PHVS416 2.4 (2.0, 2.9) This presentation includes data for an investigational product not yet approved by regulatory authorities VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours

Slide 25

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 before receiving study drug? Internal head/neck Stomach/GI Genital/buttocks External head/neck Cutaneous

Slide 26

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-squares mean differences, CIs, and p-values come from an MMRM. Data after rescue medication use is not included. The combined PHVS416 result is based on post-hoc analysis using a similar MMRM with all three active doses combined vs placebo Difference from placebo in 4 h post-treatment least-squares mean (95% CI) Median time in hours (95% CI) PHVS416 10 mg  64.13 (40.35, 87.91) p < 0.0001† PHVS416 20 mg 62.69 (36.71, 88.67) p < 0.0001 PHVS416 30 mg 71.06 (46.09, 96.03) p < 0.0001 Combined PHVS416 66.05 (47.42, 84.69) Minimally Important Difference (MID) for TOS is 30 This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 27

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 PHVS416 results are based on post-hoc analyses to provide a reference of the result by pooling all three active doses. Median time in hours (95% CI) Median time in hours (95% CI) Placebo 42.0 (22.0, 48.1) PHVS416 10 mg 5.8 (3.6, 7.5) p < 0.0001† PHVS416 20 mg 20.0 (4.5, 20.0) p = 0.0127 PHVS416 30 mg 20.0 (6.0, 20.1) p = 0.0001 Combined PHVS416 7.5 (5.9, 20.0) This presentation includes data for an investigational product not yet approved by regulatory authorities VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours

Slide 28

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 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 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 Part I (Non-Attack) Part II (Attack 1,2,3) Part II (Attack 1,2,3)  10 mg N=23 20 mg N=24 30 mg N=25 Placebo N=53  10 mg N=38 20 mg N=29 30 mg N=36 Subjects (Part I) or Attacks (Part II) with any treatment related AEs  1 (4.3%)  1 (4.2%) -  1 (1.9%)  - -  1 (2.8%) Headache -  1 (4.2%) - - - - - Nausea  1 (4.3%)  -  -  -  -  -  1 (2.8%) Vomiting  -  -  -  -  -  -  1 (2.8%) Fatigue  -  -  -  - -  -  1 (2.8%) Blister  -  -  -  1 (1.9%)  -  -  - This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 30

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 treat MORE attacks Would treat attacks EARLIER Mean /10 7.9 8.1 7.6 7.7 Ratings 8-10 (10=extremely likely) Ratings 6-7 Ratings 4-5 Ratings 1-3 (1=not at all likely) Proprietary Pharvaris research, 2022 (representative sample of patients, n = 103, and doctors, n = 100)

Slide 31

PHVS719/Prophylaxis Extended-release tablet formulation of PHA121

Slide 32

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 open-label extension Primary endpoint: Number of investigator-confirmed HAE attacks Secondary endpoints include moderate or severe HAE attacks, HAE attacks requiring acute treatment Target enrolment of 30 HAE patients globally Regulators in Canada, Europe, Israel, and the UK have been notified of U.S. clinical hold; the regulatory status of the CHAPTER-1 study outside the U.S. remains unchanged Screening Period Randomization BID dosing after meals PHA121 40 mg/day (20 mg BID) BID: 2 PHVS416 capsules PHA121 20 mg/day (10 mg BID) BID: 1 PHVS416 capsule, 1 placebo capsule Placebo BID: 2 placebo capsules 12 WEEKS https://clinicaltrials.gov/ct2/show/NCT05047185, https://haechapter-1.com/

Slide 33

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 food) EC85 Food effect on single dose When dosed BID with food, exposure maintained above target levels, steady state reached within 72 hours

Slide 34

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 minutes PHVS719 extended release demonstrated: maintained exposure above EC85 for >24h with and without food Similar AUC24h as 20 mg BID PHVS416 with food (one of CHAPTER-1 doses)

Slide 35

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 demonstrates once-daily potential Phase 3 readiness Financially strong: Cash runway into 4Q24

Slide 36

Nasdaq: PHVS

Slide 37

Appendix Additional RAPIDe-1 top-line clinical data

Slide 38

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-treatment score  Time to almost complete and complete symptom relief (VAS; all 3 items ≤10) Change of MSCS (mean symptom complex severity) score from pre-treatment to 4h post-treatment TOS (treatment outcome score) at 4h post-treatment Other Endpoints Included in the top-line Outputs Proportion of study-drug-treated attacks requiring the use of HAE rescue medication Time to the first use of HAE rescue medication Safety and PK assessments CONFIDENTIAL This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 39

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 p-value    <0.0001†  <0.0001  <0.0001   †nominal p-value; N = The number of attacks included in the mITT Analysis Set p-values for PHVS416 20mg and PHVS416 30mg are based on statistical tests in the pre-specified multiple comparison procedure, other p-values are nominal least-squares = Least squares. The least-squares mean differences and p-values are based on mixed-effects model for repeated measures *The combined PHVS416 results are based on post-hoc analyses to provide a reference of the result by pooling all three active doses This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 40

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 FDA compendium of clinical outcome assessments (2021) as listed by Division of Pulmonology, Allergy and Critical Care Electronically captured patient-reported assessment of three symptoms Skin pain, skin swelling, abdominal pain Patient indicates the severity of symptom on a sliding scale, from 0-100 Once an attack qualifies and is treated, VAS-3 assessed every ~30 min until 4 hours post-treatment and then at 5, 6, 8, 24, 48 hours post-treatment Firazyr is a registered trademark of Shire, and marketed by Takeda; Ruconest is a registered trademark of and marketed by Pharming; FDA 2021 COA compendium: https://www.fda.gov/drugs/development-resources/clinical-outcome-assessment-compendium 64 Please tap on the scale to indicate your skin pain now 100: worst possible 0: no symptom

Slide 41

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, 2.9) Hazard ratio 3.81 3.08 3.61 p-value   <0.0001† 0.0021 <0.0001   Time to VAS-3 50% reductiona           Median time in hours (95% CI) 22.8 (20.0, 24.1)  3.3 (2.4, 3.9)  4.0 (2.9, 6.0)  4.0 (3.3, 5.8) 3.9 (3.0, 4.8) Hazard ratio 4.55 3.65 3.87 p-value   <0.0001† 0.0003 <0.0001   Time to almost complete or complete symptom relief by VASa           Median time in hours (95% CI) 42 (22.0, 48.1) 5.8 (3.6, 7.5) 20 (4.5, 20.0) 20 (6.0, 20.1) 7.5 (5.9, 20.0) Hazard ratio 5.09 2.25 2.65 p-value   <0.0001† 0.0127 0.0001   Change in MSCS score at 4 hoursb           least-squares mean difference: PHVS416 - Placebo   -0.79 -0.61 -0.39 -0.61 p-value   <0.0001†  0.0008 0.0291   TOS at 4 hoursb           least-squares mean difference: PHVS416 - Placebo   64.13 62.69 71.06 66.05 p-value   <0.0001† <0.0001 <0.0001 †nominal p-value; N = The number of attacks included in the mITT Analysis Set p-values for PHVS416 20mg and PHVS416 30mg are based on statistical tests in the pre-specified multiple comparison procedure, other p-values are nominal aHazard ratios and p-values are based on marginal Cox proportional hazards models bp-values are based on mixed-effects models for repeated measures *The combined PHVS416 results are based on post-hoc analyses to provide a reference of the result by pooling all three active doses This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 42

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 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 doses. Median time in hours (95% CI) Median time in hours (95% CI) Placebo 22.8 (20.0, 24.1) PHVS416 10 mg 3.3 (2.4, 3.9) p < 0.0001† PHVS416 20 mg 4.0 (2.9, 6.0) p = 0.0003 PHVS416 30 mg 4.0 (3.3, 5.8) p < 0.0001 Combined PHVS416 3.9 (3.0, 4.8) This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 43

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 scale (0 = normal, 1 = mild, 2 = moderate, 3 = severe) Calculated as average score from all affected anatomic sites of attack (symptom complexes or SC) pre-treatment  Decrease in MSCS score reflects improvement in symptom severity TOS (Treatment Outcome Score) is a measure of symptom response to treatment:  Patient assessment of response for each affected SC recorded on categorical scale (significant improvement [100], improvement [50], same [0], worsening [-50], significant worsening [-100]) Calculated as weighted average of the response at all SC using pre-treatment severity as the weight  TOS value >0 reflects improvement in symptoms from pre-treatment 

Slide 44

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  (-1.06, -0.75) Difference (PHVS416 – Placebo, LSMD) p-value -0.79  <0.0001† -0.61   0.0008 -0.39 0.0291 -0.61  TOS at 4 hours n 40 32 25 28 85 least-squares mean  (95% CI) -3.62  (-19.68, 12.45) 60.52  (41.74, 79.29) 59.08  (37.58, 80.57) 67.44  (47.15, 87.74) 62.57  (50.95, 74.19) Difference (PHVS416 – Placebo, LSMD)  p-value 64.13 <0.0001† 62.69 <0.0001 71.06 <0.0001 66.05  †Nominal p-value; MSCS = Mean Symptom Complex Severity, TOS = Treatment Outcome Score, CI = confidence interval, LSMD = least-squares mean difference; least-squares mean, LSMD, CIs, and p-values for MSCS change from pre-treatment/TOS come from mixed-effect models with repeated measures (MMRM). Data after rescue medication use is not included. The combined PHVS416 result is based on post-hoc analysis using similar MMRM with all three active doses combined vs placebo This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 45

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, NE) 1.89 (0.97, 3.97) 2.15 (1.75, 4.00) 1.98 (1.80, 3.87) 1.98 (1.88, 3.87) Attacks achieving “a lot better or resolved” for all SCs at any time point – n (%)* 13 (26.5%) 30 (83.3%) 23 (82.1%) 25 (86.2%) 78 (83.9%) Median (95% CI) time by KM estimate (hours) 23.28 (5.78, 47.17) 4.02 (3.93, 5.77) 5.93 (3.90, 8.58) 4.12 (3.92, 7.22) 5.23 (3.98, 5.78) Time to symptom relief by TOS PRO demonstrated consistent efficacy at all doses TOS = Treatment Outcome Score. PRO = Patient Reported Outcome. SC = Symptom Complex. KM = Kaplan-Meier. NE = Not Estimable * Within 48 hours assessments This presentation includes data for an investigational product not yet approved by regulatory authorities

Slide 46

Bradykinin B2 Receptor Angioedema bradykinin HMWK inactive fragments PHA121 ACEi prekallikrein kininase II / ACE KNG1 cHMWK tPA FXIIa FXII plasminogen plasmin plasma kallikrein C1-INH  © 2023 Pharvaris F12 PLG

Slide 47

HMWK: high-molecular-weight kininogen; cHMWK: cleaved high-molecular-weight kininogen The swelling of an HAE attack is caused by excess levels of bradykinin Busse 2020 J Allergy Clin Immunol Pract; Bork et al 2021 J Allergy Clin Immunol Genetic causes lead to elevated levels of bradykinin HAE HAE due to C1INH deficiency Type I HAE Mutation in SERPING1 (low plasma C1INH antigen) Type II HAE Mutation in SERPING1 (dysfunctional C1INH) HAE with normal C1INH HAE-FXII Mutation in F12 gene HAE-PLG Mutation in PLG gene HAE-HS3ST6 Mutation in HS3ST6 gene HAE-KNG Mutation in KNG1 gene HAE-unknown