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 December 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.

 

 

In connection with an investor event on December 6, 2023, Pharvaris N.V. (the “Company”) provided a corporate update included in a corporate presentation on its website, provided a presentation to be used in their Key Opinion Leader call and issued a press release, which, among other things, provide an update with respect to the Company’s clinical programs, including top-line Phase 2 data from the CHAPTER-1 study of deucrictibant for the prophylactic treatment of HAE attacks and that it has completed the 26-week rodent toxicology study requested by the FDA. A copy of the corporate presentation is attached hereto as Exhibit 99.1. A copy of the presentation from the Key Opinion leader call is attached hereto as Exhibit 99.2. A copy of the press release is attached hereto as Exhibit 99.3.

 

In addition, the Company is filing this Report on Form 6-K for the purpose of updating and supplementing its disclosure regarding the enforceability of judgments against the Company and/or its directors and officers. The updated disclosure, which is attached hereto as Exhibit 99.4 and incorporated herein by reference, updates and supplements the Company’s prior disclosures, including those discussed under the headings “Item 3. Key Information—D. Risk factors.” and “Enforceability of Judgments” in the Company’s Annual Report on Form 20-F for the year ended December 31, 2022 filed with the Securities and Exchange Commission on April 5, 2023.

 

This Report on Form 6-K (excluding Exhibit 99.1, including Exhibit 99.2, Exhibit 99.3 and Exhibit 99.4) shall be deemed to be incorporated by reference into the Company’s Registration Statement on Form F-3 (File No. 333-263198), the Company’s Registration Statement on Form F-3 (File No. 333-273757) and the Company’s Registration Statement on Form S-8 (File No. 333-252897).

 

 

 

 

 

 

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: December 6, 2023

By:

/s/ Berndt Modig

 

Name:

Berndt Modig

 

Title:

Chief Executive Officer

 

EXHIB INDEX

 

Exhibit

No.

 

Description

99.1

 

Corporate Presentation, dated December 6, 2023.

99.2

 

Key Opinion Leader Call Presentation, dated December 6, 2023.

99.3

 

Press Release, dated December 6, 2023.

99.4

 

Enforceability of Judgments and Select Updated Risk Factor.

 


Slide 1

Corporate Presentation December 2023 Pioneering science for patient choice Exhibit 99.1


Slide 2

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-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 deucrictibant 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 clinical trials and are currently on hold in the U.S. as a result of the FDA clinical hold, our ability to replicate the efficacy and safety demonstrated in the CHAPTER-1 Phase 2 study in ongoing and future nonclinical studies and clinical trials, risks associated with 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, including with respect to existing therapies, emerging potentially competitive therapies and with competitive generic products, 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 weaknesses in our internal control over financial reporting and to maintain an effective system of internal control over financial reporting, changes in general market, political and economic conditions, including as a result of the current conflict between Russia and Ukraine, the Israel-Hamas war, 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

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 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 Median: 14 attacks/year Females: 19 (range: 2-165 attacks/y) Males: 9 (range: 1-42 attacks/y)


Slide 4

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; 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 EU 15-20k US 6-9k LATAM 12-16k JP 2-4k ME&A 10-14k APAC 20-30k


Slide 5

Source: Proprietary company research 2022 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 should not have to compromise


Slide 6

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: Haegarda, Takhzyro, and Orladeyo Source: Quarterly filings (NYSE: TAK; NASDAQ: BCRX, PHAR); www.fda.gov; company research


Slide 7

The swelling of an HAE attack is caused by excess levels of bradykinin Source: Busse 2020 J Allergy Clin Immunol Pract; Bork et al 2021 J Allergy Clin Immunol; Notes: 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 Genetic causes lead to elevated levels of bradykinin Hereditary angioedema 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 8

Bradykinin-mediated disease also includes acquired angioedema beyond HAE No products approved for treatment of bradykinin-dependent acquired angioedema Therapies approved broadly for HAE are used for treatment An independent investigator-initiated trial (IIT) in AAE-C1-INH with PHVS416 has been conducted Source: Zanichelli et al 2012 Allergy; Longhurst et al 2016 Clin. Exp. Immunol.; Otani, Banerji 2017 Immunol. Allergy Clin. N. Am.; Bova et al 2018 Int. Arch. Allergy Immunol.; Petersen, “Prophylaxis of angioedema attacks due to acquired C1-Inhibitor deficiency with PHA121, a novel oral bradykinin B2 receptor antagonist” C1-Inhibitor Workshop 2023 (https://2023.haenetworkshop.hu/program/index.php, https://www.linkedin.com/feed/update/urn:li:activity:7060638305842778112/) Acquired angioedema C1INH deficiency (AAE C1-INH) Type I HAE Mutation in SERPING1 (low plasma C1INH antigen) Type II HAE Mutation in SERPING1 (dysfunctional C1INH) Drug Induced ACE Inhibitor Mutation in F12 gene Other Mutation in PLG gene Idiopathic Histamine independent Histamine dependent


Slide 9

Pharvaris has discovered the first orally bioavailable bradykinin B2 receptor antagonist Surce: 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 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 Deucrictibant We aspire to develop novel, oral alternatives that improve the standard of care for people living with HAE and other bradykinin-mediated diseases


Slide 10

Product Strategy


Slide 11

Our strategy: Managing HAE with two oral products with 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 Deucrictibant (PHVS416) Immediate-release capsule rapid absorption Deucrictibant (PHVS719) Extended-release tablet sustained absorption Aim to provide sustained exposure of attack-preventing medicine in a convenient, small oral dosage form* Aim to provide rapid and reliable symptom relief, through rapid exposure of attack-mitigating therapy in a convenient, small oral dosage form* Deucrictibant


Slide 12

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 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 26-week rodent toxicology study has been completed using FDA-reviewed protocol Preparing to submit the study results to the FDA by YE23 In June 2023, FDA removed the clinical hold on on-demand trials Eligible participants in the U.S. may join RAPIDe-2, a long-term extension on-demand extension study An end-of-Phase 2 meeting with the agency occurred to align on key elements of RAPIDe-3 global Phase 3 study of PHVS416 for the on-demand treatment of HAE Clinical studies of deucrictibant for the long-term prophylaxis of HAE remain on hold in the U.S. Outside the U.S., CHAPTER-1 and other studies continue, 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


Slide 13

Wholly-owned pipeline focused on bradykinin B2 receptor mechanism * The FDA has placed a hold on clinical trials of deucrictibant for long-term prophylaxis in the U.S.; see slide 12 for an update on our clinical program


Slide 14

On-Demand Deucrictibant immediate-release capsules (PHVS416) [deucrictibant]


Slide 15

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 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


Slide 16

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 medication Side effects Ran out of medication Stockpiling for severe attacks Forgot to take Too painful to inject Physician-reported (n=71) Patient-reported (n=12) Physicians focus on attack severity and lack of a prescription Patients raise logistics and treatment dissatisfaction as key reasons for not treating an attack


Slide 17

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 molecule has the potential to deliver on their hopes Patients want rapid onset of symptom relief … … with single dose durability … … in an oral pill


Slide 18

HAE RAPIDe-1 study: Phase 2 study of on-demand treatment of angioedema attacks in patients with Type I or II HAE 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 Randomization Non-attack Attack 1 Attack 2 Attack 3 Part I: Study Site Part II: Home Treatment Deucrictibant IR (10 mg) placebo 10 mg 10 mg placebo 10 mg 10 mg placebo 10 mg 10 mg Deucrictibant IR (20 mg) Deucrictibant IR (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 deucrictibant in clinic for PK and safety assessment Part II: patients treated three attacks with two deucrictibant 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 19

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 Deucrictibant IR showed rapid onset of action, symptom relief, and resolution of HAE attacks  Deucrictibant IR substantially reduced the use of rescue medications Deucrictibant IR 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 Consistent outcomes observed across all endpoints and types of measurements


Slide 20

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 HAE patients confirmed rapid absorption on oral dosing, consistent with Phase 1 healthy volunteer studies


Slide 21

Primary endpoint: Deucrictibant IR 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 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 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


Slide 22

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 results are based on post-hoc analyses to provide a reference of the result by pooling all three active doses. VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours 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)


Slide 23

In a post-hoc analysis, patients on deucrictibant achieved end of progression by VAS-3 within 25 to 26 min versus 20 h for placebo Source: Maurer et al., ACAAI 2023; https://ir.pharvaris.com/static-files/0bae214b-7ff8-49ec-8340-1bb60a5935b9


Slide 24

At each timepoint, the change in attack symptom from pre-treatment is reported by patient TOS PRO captures change in five symptom complexes of HAE attacks TOS Patient Reported Outcome (PRO) 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 25

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 Minimally Important Difference (MID) for TOS is 30 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)


Slide 26

Deucrictibant IR 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) Deucrictibant IR 10 mg 5.8 (3.6, 7.5) p < 0.0001† Deucrictibant IR 20 mg 20.0 (4.5, 20.0) p = 0.0127 Deucrictibant IR 30 mg 20.0 (6.0, 20.1) p = 0.0001 Combined Deucrictibant IR 7.5 (5.9, 20.0) VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours


Slide 27

Patients treating with deucrictibant IR used substantially less rescue medication N = The number of attacks in the mITT Analysis Set


Slide 28

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 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 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%)  -  -  -


Slide 29

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 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)


Slide 30

Long Term Prophylaxis Deucrictibant extended-release tablets (PHVS719) [deucrictibant]


Slide 31

People living with HAE are seeking highly effective, well-tolerated, and less burdensome prophylactic therapies Source: Proprietary Pharvaris research, 2022 (representative sample of patients, n = 103, and doctors, n = 100) Injectable-like efficacy Easy, painless administration Well-tolerated Effectively targeting the bradykinin receptor with a small molecule has the potential to deliver on their hopes


Slide 32

HAE CHAPTER-1 study has completed: Study design CONFIDENTIAL Double-blind, placebo-controlled Phase 2 study assessing safety and efficacy of deucrictibant in preventing HAE attacks in patients with HAE type 1 or type 2 34 participants enrolled in North America and Europe R = randomization;  *deucrictibant 20 mg/day =  deucrictibant immediate-release capsules (PHVS416) 10 mg twice daily **deucrictibant 40 mg/day = deucrictibant immediate-release capsules (PHVS416) 20 mg twice daily


Slide 33

Positive top-line Phase 2 data from the CHAPTER-1 study of deucrictibant for the prophylactic treatment of HAE attacks


Slide 34

Phase 1 pharmacokinetics offered options to use deucrictibant IR as proof-of-concept in prophylactic development Source: https://ir.pharvaris.com/static-files/0361cd85-6000-490b-932b-d305e1f3ca1b; https://ir.pharvaris.com/static-files/81a9499d-0769-4b89-8ecd-8ace5ca521d3 EC85 Food effect on single dose When dosed BID with food, exposure maintained above target levels, steady state reached within 72 hours Multiple-dose Ctrough (Day 10, BID with food) EC85


Slide 35

Deucrictibant XR single-dose PK study demonstrates QD potential; target for Phase 3 dosage form Deucrictibant IR capsule (2x10mg), fasted Deucrictibant XR tablet (40 mg), fasted EC85 Deucrictibant XR tablet (40 mg), fed Deucrictibant IR and XR well tolerated No SAEs or severe TEAEs Deucrictibant IR rapid exposure confirmed Exceeding EC85 within 15 minutes Deucrictibant XR 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 36

Our strategy: Managing HAE with two oral products with 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 sustained absorption Aim to provide sustained exposure of attack-preventing medicine in a convenient, small oral dosage form* Aim to provide rapid and reliable symptom relief, through rapid exposure of attack-mitigating therapy in a convenient, small oral dosage form* Deucrictibant Based on the results in RAPIDe-1 and CHAPTER-1, deucrictibant has the potential to become the preferred option to treat and prevent HAE attacks


Slide 37

Corporate summary and milestones HAE On-Demand (type 1 and type 2) HAE Prophylaxis (type 1 and type 2) PHVS416 deucrictibant immediate-release capsule RAPIDe-1 Ph2 top-line data meets all primary and key secondary endpoints Phase 3 initiation CHAPTER-1 Ph2 top-line data meets the primary endpoint Phase 3 initiation PHVS719 deucrictibant extended-release tablet -- Ph1 SD PK demonstrates once-daily potential Phase 3 readiness Financially strong: approximately €140M cash as of November 30, 2023


Slide 38

Aspiring to free people from HAE or other bradykinin-mediated diseases


Slide 39

 


Slide 40

The relationship between alternative endpoints to measure symptom relief in an HAE attack was assessed in a mixed-methods study Source: Mendivil et al., UCARE 2023 Overall probability of attacks achieving symptom relief 1.00 0.75 0.50 0.25 0.00 0 2 4 6 8 12 48 24 Hours post-treatment Symptom relief: AMRA-3 20% PGI-C “better” AMRA-3 30% PGI-C “a little better” AMRA-3 50% PGI-S 1-level reduction PRO instrument Number of events Median time to, h (95% CI) PGI-C “a little better” 90 2.147 (1.518, 3.017) AMRA-3 20% reduction from pre-treatment 89 2.191 (1.655, 3.035) AMRA-3 30% reduction from pre-treatment 89 2.990 (2.123, 4.011) PGI-C “better” 92 3.925 (2.969, 5.055) PGI-S 1-level reduction 91 4.012 (3.015, 5.026) AMRA-3 50% reduction from pre-treatment 88 4.354 (3.256, 6.093) Median time to symptom relief using AMRA-3 20% reduction from pre-treatment and PGI-C “a little better” on 2 consecutive timepoints are comparable AMRA-3 50% reduction from pre-treatment, PGI-C “better,” and PGI-S 1-level improvement take longer and are within the same range 30 participants, 98 attacks Kaplan-Meier plot on non-laryngeal attacks achieving symptom relief

Slide 1

December 6, 2023 CHAPTER-1 Phase 2 Top-line Data Exhibit 99.2


Slide 2

Disclaimer This presentation includes data for an investigational product not yet approved by regulatory authorities. 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-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 deucrictibant 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 clinical trials and are currently on hold in the U.S. as a result of the FDA clinical hold, our ability to replicate the efficacy and safety demonstrated in the CHAPTER-1 Phase 2 study in ongoing and future nonclinical studies and clinical trials, risks associated with 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, including with respect to existing therapies, emerging potentially competitive therapies 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 weaknesses in our internal control over financial reporting and to maintain an effective system of internal control over financial reporting, changes in general market, political and economic conditions, including as a result of the current conflict between Russia and Ukraine, the Israel-Hamas war, 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

Agenda This presentation includes data for an investigational product not yet approved by regulatory authorities. Introduction Berndt Modig, CEO Pharvaris Review of CHAPTER-1 top-line Phase 2 data Peng Lu, M.D. PhD, CMO Pharvaris KOL perspective Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego (UCSD), Clinical Service Chief for Allergy/Immunology at UCSD;  principal investigator in the CHAPTER-1 study Closing Remarks, Q&A


Slide 4

Agenda This presentation includes data for an investigational product not yet approved by regulatory authorities. Introduction Berndt Modig, CEO Pharvaris Review of CHAPTER-1 top-line Phase 2 data Peng Lu, M.D. PhD, CMO Pharvaris KOL perspective Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego (UCSD), Clinical Service Chief for Allergy/Immunology at UCSD;  principal investigator in the CHAPTER-1 study Closing Remarks, Q&A


Slide 5

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) This presentation includes data for an investigational product not yet approved by regulatory authorities. An effective oral bradykinin B2 receptor antagonist has the potential to deliver on their hopes Well-tolerated


Slide 6

Agenda This presentation includes data for an investigational product not yet approved by regulatory authorities. Introduction Berndt Modig, CEO Pharvaris Review of CHAPTER-1 top-line Phase 2 data Peng Lu, M.D. PhD, CMO Pharvaris KOL perspective Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego (UCSD), Clinical Service Chief for Allergy/Immunology at UCSD;  principal investigator in the CHAPTER-1 study Closing Remarks, Q&A


Slide 7

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 endpoints  Deucrictibant well-tolerated at both doses  *40 mg/day deucrictibant treatment group; %reduction in monthly attack rate is based on a Poisson regression model Note: all attacks reported herein are investigator-confirmed; attack rate is number of attacks per month of exposure, also referred to as time-normalized number of attacks; all statistical analyses comparing deucrictibant and placebo are made without adjustment for multiplicity. This presentation includes data for an investigational product not yet approved by regulatory authorities. Primary endpoint met: 84.5% (p=0.0008) reduction in monthly attack rate versus placebo*


Slide 8

CHAPTER-1 study design This presentation includes data for an investigational product not yet approved by regulatory authorities. 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 **deucrictibant 40 mg/day = deucrictibant immediate-release capsules (PHVS416) 20 mg twice daily placebo deucrictibant 20 mg/day* deucrictibant 40 mg/day** Part 1: double-blind treatment period (12 weeks) Screening R End-of-Study Visit deucrictibant 40 mg/day** Part 2: open-label treatment period


Slide 9

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.  This presentation includes data for an investigational product not yet approved by regulatory authorities. 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 Treatment Period n=10 Withdrawal of consent n=1 Completed Blinded Treatment Period n=10 Withdrawal of consent n=1 Study Paused by Sponsor/FDA n=1 Completed Blinded Treatment Period n=11


Slide 10

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. This presentation includes data for an investigational product not yet approved by regulatory authorities. Placebo N=11 20 mg/day N=11 40 mg/day N=12 All N=34 Age in years – Mean  41.4  38.4 40.8   40.2 Sex: M/F – n 3/8 6/5 4/8 13/21 Race: White – n (%) 11 (100) 11 (100) 12 (100) 34 (100) BMI (kg/m2) – Mean 26.7 29.5 25.4 27.1 HAE Type – n Type 1 10 9 12 31 Type 2 1 2 0 3 Baseline HAE attack rate per month Mean 1.9 2.1 2.5 2.2 Median (Min, Max) 1.7 (0.7, 3.7) 1.7 (1.0, 5.3) 1.7 (1.0, 6.7) 1.7(0.7, 6.7) Randomized baseline HAE attack rate categories – n (%) 1 to < 2 attacks per 4 weeks 6 (54.5) 7 (63.6) 7 (58.3) 20 (58.8) 2 to < 3 attacks per 4 weeks 3 (27.3) 1 (9.1) 1 (8.3) 5 (14.7) ≥ 3 attacks per 4 weeks 2 (18.2) 3 (27.3) 4 (33.3) 9 (26.5)


Slide 11

Primary endpoint met: deucrictibant significantly reduced attack rate This presentation includes data for an investigational product not yet approved by regulatory authorities. 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 0.33 -1.34 -1.59 % change from baseline 17% -100% -96% Model-based inference  LS mean  1.94  0.40  0.30  % reduction vs placebo 79.3% 84.5% p-value 0.0009 0.0008 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. Model-based inferences are based on a Poisson regression model adjusted for baseline attack rate and  time on treatment. No multiplicity adjustment was applied.


Slide 12

Significant attack reduction and no severe attacks with deucrictibant   This presentation includes data for an investigational product not yet approved by regulatory authorities. 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 13

92.3% reduction in moderate or severe attacks at 40 mg/day dose This presentation includes data for an investigational product not yet approved by regulatory authorities. 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) 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. Monthly attack rates are based on a Poisson regression model adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied.


Slide 14

92.6% reduction in attacks treated with ODT at 40 mg/day dose This presentation includes data for an investigational product not yet approved by regulatory authorities. 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)) 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. Monthly attack rates are based on a Poisson regression model adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied.


Slide 15

Substantial reduction of attack rate from baseline This presentation includes data for an investigational product not yet approved by regulatory authorities. 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 16

Consistent efficacy regardless of baseline attack rate This presentation includes data for an investigational product not yet approved by regulatory authorities. 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 17

All 40 mg/day participants reported an improvement in PGA-Change This presentation includes data for an investigational product not yet approved by regulatory authorities. 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-Change results at Week 12.


Slide 18

AE-QoL: improvement in health-related quality of life This presentation includes data for an investigational product not yet approved by regulatory authorities. 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) 12.5 (10.3, 17.7) 20 mg/day = deucrictibant immediate release (IR) capsules 10 mg twice daily. 40 mg/day = deucrictibant IR capsules 20 mg twice daily. AE-QoL = angioedema quality of life (questionnaire).  N = number of randomized participants. N’ = number of participants with AE-QoL data at Week 12. Nutrition Total Score Functioning Fatigue/ Mood Fear/ Shame Placebo 20 mg/day 40 mg/day Nutrition Total Score Functioning Fatigue/ Mood Fear/ Shame Nutrition Total Score Functioning Fatigue/ Mood Fear/ Shame


Slide 19

Deucrictibant well-tolerated at both doses This presentation includes data for an investigational product not yet approved by regulatory authorities. 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) 2 1 (8.3) 1 Serious TEAEs Serious TEAEs 0 0 0 0 0 0 Treatment related Serious TEAEs Treatment related TEAE 0 0 0 0 0 0 TEAEs leading to study drug discontinuation 0 0 0 0 0 0 TEAEs leading to withdrawal from study 0 0 0 0 0 0 TEAEs leading to death 0 0 0 0 0 0 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 randomized and dosed. n = number of participants having a treatment emergent adverse event. TEAE = treatment-emergent adverse event, defined as adverse events that occur after the first administration of blinded study treatment.  


Slide 20

All treatment-related adverse events were mild This presentation includes data for an investigational product not yet approved by regulatory authorities. 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%) Gamma-glutamyltransferase increased 0 0 1 (8.3%) Nervous system disorders 1 (9.1%) 1 (9.1%) 0 Dizziness postural  0 1 (9.1%) 0 Headache 1 (9.1%) 0 0 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 randomized and dosed. TEAE = treatment-emergent adverse event, defined as adverse events that occur after the first administration of blinded study treatment.  


Slide 21

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 Poisson regressions adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied. Nominal p-value < 0.01 for all secondary endpoints included in this section comparing deucrictibant with placebo. **Participants with <4 weeks of treatment (2 participants on 40 mg/day) were not included in the summaries of proportions achieving threshold reduction of attack rate from baseline. Nominal p-value < 0.05 for all secondary endpoints included in this section comparing deucrictibant with placebo. This presentation includes data for an investigational product not yet approved by regulatory authorities. Placebo N=11 20 mg/day N=11 40 mg/day N=12 Monthly attack rate – LS Mean (95% CI)* All attacks (primary endpoint) 1.94 (1.31, 2.87) 0.40 (0.17, 0.92) 0.30 (0.11, 0.82) % reduction vs placebo, p-value 79.3%, p=0.0009 84.5%, p=0.0008 Moderate or severe attacks 1.50 (0.91, 2.50) 0.26 (0.08, 0.81) 0.12 (0.02, 0.67) Attacks treated with on-demand medication 1.41 (0.88, 2.24) 0.35 (0.14, 0.85) 0.10 (0.02, 0.57) Achieving threshold reduction of attack rate from baseline** >=50% reduction 2/11 (18%) 9/11 (82%) 9/10 (90%) >=70% reduction 2/11 (18%) 8/11 (73%) 8/10 (80%) >=90% reduction 0 6/11 (55%) 6/10 (60%) Attack free during treatment period 0 6 /11(55%) 4/10 (40%)


Slide 22

Agenda This presentation includes data for an investigational product not yet approved by regulatory authorities. Introduction Berndt Modig, CEO Pharvaris Review of CHAPTER-1 top-line Phase 2 data Peng Lu, M.D. PhD, CMO Pharvaris KOL perspective Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego (UCSD), Clinical Service Chief for Allergy/Immunology at UCSD;  principal investigator in the CHAPTER-1 study Closing Remarks, Q&A


Slide 23

Agenda This presentation includes data for an investigational product not yet approved by regulatory authorities. Introduction Berndt Modig, CEO Pharvaris Review of CHAPTER-1 top-line Phase 2 data Peng Lu, M.D. PhD, CMO Pharvaris KOL perspective Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego (UCSD), Clinical Service Chief for Allergy/Immunology at UCSD;  principal investigator in the CHAPTER-1 study Closing Remarks, Q&A


Slide 24

Managing HAE with two oral products utilizing the same active ingredient for on-demand and prophylactic treatment *Aspirational; to be confirmed with clinical data This presentation includes data for an investigational product not yet approved by regulatory authorities. Based on the results in RAPIDe-1 and CHAPTER-1 deucrictibant has the potential to become the preferred option to treat and prevent HAE attacks deucrictibant Immediate release capsule PHVS416 rapid absorption deucrictibant Extended-release tablet PHVS719 sustained absorption Aim to provide sustained exposure of attack-preventing therapy in a convenient, small oral dosage form* Aim to provide rapid and reliable symptom relief, through rapid exposure of attack-mitigating therapy in a convenient, small oral dosage form* deucrictibant


Slide 25

 

Exhibit 99.3

img32735890_0.jpg

Pharvaris Announces Positive Top-line Phase 2 Data from the CHAPTER-1 Study of Deucrictibant for the Prophylactic Treatment of HAE Attacks

 

Primary endpoint met; 40 mg/day orally administered deucrictibant significantly reduced mean monthly attack rate by 84.5% (p=0.0008) compared to placebo
92.3% reduction in occurrence of moderate and severe attacks
92.6% fewer attacks treated with on-demand medication by participants
Deucrictibant well-tolerated
Pharvaris to host a conference call today at 8:00 a.m. EST

 

Zug, Switzerland, December 6, 2023Pharvaris (Nasdaq: PHVS), a clinical-stage company developing novel, oral bradykinin B2 receptor antagonists to treat and prevent hereditary angioedema (HAE) attacks, today announced positive top-line data from the CHAPTER-1 Phase 2 clinical study meeting its primary endpoint, with deucrictibant demonstrating statistically significant and clinically meaningful results of deucrictibant as an oral preventative treatment for people living with HAE. Pharvaris plans to present data from the study at future medical meetings.

 

CHAPTER-1 Clinical Study Design and Results

CHAPTER-1 (NCT05047185) is a double-blind, placebo-controlled Phase 2 study evaluating the efficacy as well as the safety and tolerability of deucrictibant for long-term prophylaxis against angioedema attacks in HAE-1/2. In the study, 34 participants were enrolled globally and randomized to receive one of two doses of deucrictibant (20 mg/day or 40 mg/day) or placebo for 12 weeks of treatment. Deucrictibant immediate-release capsule (PHVS416) was dosed twice-a-day as a proof-of-concept for the once-daily deucrictibant extended-release tablet (PHVS719), which is the intended formulation for the prophylactic treatment of HAE. The open-label portion of the CHAPTER-1 study is ongoing at the 40 mg/day dose.

 

The study’s primary endpoint measured the time-normalized number of investigator-confirmed HAE attacks during the treatment period. The monthly attack rate was reduced by 84.5% (p=0.0008) compared to placebo in participants who received 40 mg/day of deucrictibant.

 


img32735890_1.jpg 

 

Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical Director of the US Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego (UCSD), Clinical Service Chief for Allergy/Immunology at UCSD, and principal investigator in the CHAPTER-1 study, commented, “The HAE community is seeking highly effective, well-tolerated, and less burdensome therapies. The CHAPTER-1 data represent an important step forward in the evolution of HAE treatment. Given these encouraging results, deucrictibant has the potential to significantly improve clinical outcomes for people living with HAE.”

 

Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris, stated, “Deucrictibant is the first HAE treatment with the potential to combine injectable-like efficacy and a favorable safety profile with the convenience of an oral therapy. The study demonstrates, for the first time ever, that antagonism of the bradykinin B2 receptor can provide early and sustained protection from HAE attacks, including substantial reduction of moderate and severe attacks, with clinically meaningful improvement in health-related quality of life. We look forward to advancing the development of deucrictibant for the prevention of HAE attacks.”

 

Berndt Modig, Chief Executive Office of Pharvaris, added, “We sincerely thank the clinical trial participants and their caregivers, the site investigators and staff, the HAE community, and the Pharvaris team for their


contributions to the CHAPTER-1 study. These study results, together with the compelling data from our on-demand program, further strengthens our confidence that deucrictibant can become the preferred option to treat as well as prevent HAE attacks.”

 

In the analysis of the secondary endpoints, deucrictibant demonstrated clinically meaningful improvement in the severity of attacks and a decrease in the number of attacks treated with on-demand medication. Participants on deucrictibant treatment experienced a meaningful improvement in their quality of life. The table below lists additional study findings:

 

Placebo

N=11

20 mg/day

N=11

40 mg/day

N=12

Monthly attack rate – LS Mean (95% CI)*

 

 

 

Moderate or severe attacks

1.50 (0.91, 2.50)

0.26 (0.08, 0.81)

0.12 (0.02, 0.67)

Attacks treated with on-demand medication

1.41 (0.88, 2.24)

0.35 (0.14, 0.85)

0.10 (0.02, 0.57)

Achieving threshold reduction of attack rate from baseline**

 

 

 

>=50% reduction

2/11 (18%)

9/11 (82%)

9/10 (90%)

>=70% reduction

2/11 (18%)

8/11 (73%)

8/10 (80%)

>=90% reduction

0

6/11 (55%)

6/10 (60%)

Attack free during treatment period

0

6 /11(55%)

4/10 (40%)

 

LS = least squares; CI = confidence interval.

*Results of monthly attack rates are based on Poisson regression models adjusted for baseline attack rate and time on treatment. Nominal p-value < 0.01 for all endpoints included in this section comparing deucrictibant with placebo.

**Participants with <4 weeks of treatment (two participants on 40 mg/day) were not included in the summaries of proportions achieving threshold reduction of attack rate from baseline.

Nominal p-value < 0.05 for all endpoints included in this section comparing deucrictibant with placebo.

 

Throughout 12 weeks of treatment in CHAPTER-1, both doses of deucrictibant were well-tolerated. There were no serious adverse events, no severe treatment-emergent adverse events, and no adverse events leading to treatment discontinuation.

 

In August 2022, the U.S. Food & Drug Administration (FDA) placed clinical studies of deucrictibant, including CHAPTER-1, on hold. Pharvaris notified country-specific regulatory authorities in Canada, Europe, Israel, and the UK regarding the clinical holds in the U.S., and the regulatory status of deucrictibant outside the U.S. has not been affected. In June 2023, Pharvaris announced the removal of the clinical hold of deucrictibant for the on-demand treatment of HAE in the U.S. Pharvaris has completed the 26-week rodent toxicology study requested by the FDA, which we believe met its objective. Pharvaris is preparing to submit the study results to the FDA by the end of the year. However, neither the nature nor timing of the response from FDA is certain.

 

Conference Call
Pharvaris will host a live conference call and webcast to discuss the CHAPTER-1 study topline data in greater


detail at 8:00 a.m. EST today via a live webcast; presentation slides may be accessed on the “Events and Presentations” page of the Pharvaris investor relations website. Participants interested in asking a verbal question during the Q&A may do so in the live conference call. An archived replay will also be available on the website for 90 days following the event.

 

About Deucrictibant

Deucrictibant is a potent, selective, and orally available antagonist of the bradykinin B2 receptor. By inhibiting bradykinin signaling through the bradykinin B2 receptor, deucrictibant has the potential to treat the clinical signs of an HAE attack and to prevent the occurrence of attacks. Based on its chemical properties, Pharvaris is developing two formulations of deucrictibant for oral administration; a capsule to enable rapid onset of activity for acute treatment, and an extended-release tablet to enable sustained absorption and efficacy in prophylactic treatment.

 

About Pharvaris

Building on its deep-seated roots in HAE, Pharvaris is a clinical-stage company developing novel, oral bradykinin B2 receptor antagonists to treat and prevent HAE attacks. By directly pursuing this clinically proven therapeutic target with novel small molecules, the Pharvaris team aspires to offer people with all sub-types of HAE efficacious, safe, and easy-to-administer alternatives to treat attacks, both on-demand and prophylactically. The company brings together the best talent in the industry with deep expertise in rare diseases and HAE. For more information, visit https://pharvaris.com/.

 

Forward-Looking Statements

This press release contains certain forward-looking statements that involve substantial risks and uncertainties. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements relating to our future plans, studies and trials, and any statements containing the words “believe,” “anticipate,” “expect,” “estimate,” “may,” “could,” “should,” “would,” “will,” “intend” and similar expressions. These forward-looking statements are based on management’s current expectations, are neither promises nor guarantees, and involve known and unknown risks, uncertainties and other important factors that may cause Pharvaris’ actual results, performance or achievements to be materially different from its expectations expressed or implied by the forward-looking statements. Such risks include but are not limited to the following: uncertainty in the outcome of our interactions with regulatory authorities, including the FDA with respect to the clinical hold on prophylactic deucrictibant in the U.S.; the expected timing, progress, or success of our clinical development programs, especially for PHVS416 (immediate-release deucrictibant capsules) and PHVS719 (extended-release deucrictibant tablets), which are in mid-stage


global clinical trials; risks arising from epidemic diseases, such as the COVID-19 pandemic, which may adversely impact our business, nonclinical studies, and clinical trials; the expected timing and results of the rodent toxicology study and our ability to resolve any issues to the satisfaction of the FDA or any regulatory agency in a timely manner; 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, including with respect to existing therapies, emerging potentially competitive therapies 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 weaknesses 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 Hamas attack against Israel and the ensuing war; 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 U.S. Securities and Exchange Commission. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. While Pharvaris may elect to update such forward-looking statements at some point in the future, Pharvaris disclaims any obligation to do so, even if subsequent events cause its views to change. These forward-looking statements should not be relied upon as representing Pharvaris’ views as of any date subsequent to the date of this press release.

 

Contact
Maggie Beller

Executive Director, Head of External and Internal Communications

maggie.beller@pharvaris.com


Exhibit 99.4

ENFORCEABILITY OF JUDGMENTS

 

We are organized and existing under the laws of the Netherlands. As such, under Dutch private international law, the rights and obligations of our shareholders vis-à-vis the company originating from Dutch corporate law and our Articles of Association, as well as the civil liability of our officers (functionarissen) (including our directors and executive officers) are governed in certain respects by the laws of the Netherlands.

We are not a resident of the United States and our officers may also not all be residents of the United States. As a result, depending on the subject matter of the action brought against us and/or our officers, United States courts may not have jurisdiction. If a Dutch court has jurisdiction with respect to such action, that court will apply Dutch procedural law and Dutch private international law to determine the law applicable to that action. Depending on the subject matter of the relevant action, a competent Dutch court may apply another law than the laws of the United States.

Also, service of process against non-residents of the United States can in principle (absent, for example, a valid choice of domicile) not be effected in the United States.

Furthermore, substantially all of our assets are located outside the United States. As of the date of this filing, (i) there is no treaty in force between the United States and the Netherlands for the reciprocal recognition and enforcement of judgments, other than arbitration awards, in civil and commercial matters and (ii) both the Hague Convention on Choice of Court Agreements (2005) and the Hague Judgments Convention (2019) have entered into force for the Netherlands, but have not entered into force for the United States. Consequently, a judgment rendered by a court in the United States will not automatically be recognized and enforced by the competent Dutch courts. However, if a person has obtained a judgment rendered by a court in the United States that is enforceable under the laws of the United States and files a claim with the competent Dutch court, the Dutch court will in principle give binding effect to that United States judgment if (i) the jurisdiction of the United States court was based on a ground of jurisdiction that is generally acceptable according to international standards, (ii) the judgment by the United States court was rendered in legal proceedings that comply with the Dutch standards of proper administration of justice including sufficient safeguards (behoorlijke rechtspleging), (iii) binding effect of such United States judgment is not contrary to Dutch public order (openbare orde) and (iv) the judgment by the United States court is not incompatible with a decision rendered between the same parties by a Dutch court, or with a previous decision rendered between the same parties by a foreign court in a dispute that concerns the same subject and is based on the same cause, provided that the previous decision qualifies for recognition in the Netherlands. Even if such a United States judgment is given binding effect, a claim based thereon may, however, still be rejected if the United States judgment is not or no longer formally enforceable. Moreover, if the United States judgment is not final (for instance when appeal is possible or pending) a competent Dutch court may postpone recognition until the United States judgment will have become final, refuse recognition under the understanding that recognition can be asked again once the United States judgment will have become final, or impose as a condition for recognition that security is posted.

A competent Dutch court may deny the recognition and enforcement of punitive damages or other awards. Moreover, a competent Dutch court may reduce the amount of damages granted by a United States court and recognize damages only to the extent that they are necessary to compensate actual losses or damages. Thus, United States investors may not be able, or experience difficulty, to enforce a judgment obtained in a United States court against us or our officers.

 

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RISK FACTORS

The following risk factors should be read in conjunction with, and amend and supplement, those included in the Annual Report on Form 20-F filed by Pharvaris N.V. (“we”, “our”, “us” or the “Company”) on April 5, 2023 (the “Form 20-F or the “Annual Report”). Investing in the Company’s ordinary shares involves a high degree of risk. You should carefully consider the risks described below, and all other information contained in or incorporated by reference in the Form 20-F, before making an investment decision regarding the Company’s securities. Defined terms used, but not defined, in these “Risk Factors” have the meaning ascribed to them in the Form 20-F.

Risks Related to Our Ordinary Shares and Our Status as a Public Company

 

Investors may have difficulty enforcing civil liabilities against us or our directors and/or other officers.

We are organized and existing under the laws of the Netherlands. As such, under Dutch private international law, the rights and obligations of our shareholders vis-à-vis the company originating from Dutch corporate law and our Articles of Association, as well as the civil liability of our officers (functionarissen) (including our directors and executive officers) are governed in certain respects by the laws of the Netherlands.

We are not a resident of the United States and our officers may also not all be residents of the United States. As a result, depending on the subject matter of the action brought against us and/or our officers, United States courts may not have jurisdiction. If a Dutch court has jurisdiction with respect to such action, that court will apply Dutch procedural law and Dutch private international law to determine the law applicable to that action. Depending on the subject matter of the relevant action, a competent Dutch court may apply another law than the laws of the United States.

Also, service of process against non-residents of the United States can in principle (absent, for example, a valid choice of domicile) not be effected in the United States.

Furthermore, substantially all of our assets are located outside the United States. On the date of this filing, (i) there is no treaty in force between the United States and the Netherlands for the reciprocal recognition and enforcement of judgments, other than arbitration awards, in civil and commercial matters and (ii) both the Hague Convention on Choice of Court Agreements (2005) and the Hague Judgments Convention (2019) have entered into force for the Netherlands, but have not entered into force for the United States. Consequently, a judgment rendered by a court in the United States will not automatically be recognized and enforced by the competent Dutch courts. However, if a person has obtained a judgment rendered by a court in the United States that is enforceable under the laws of the United States and files a claim with the competent Dutch court, the Dutch court will in principle give binding effect to that United States judgment if (i) the jurisdiction of the United States court was based on a ground of jurisdiction that is generally acceptable according to international standards, (ii) the judgment by the United States court was rendered in legal proceedings that comply with the Dutch standards of proper administration of justice including sufficient safeguards (behoorlijke rechtspleging), (iii) binding effect of such United States judgment is not contrary to Dutch public order (openbare orde) and (iv) the judgment by the United States court is not incompatible with a decision rendered between the same parties by a Dutch court, or with a previous decision rendered between the same parties by a foreign court in a dispute that concerns the same subject and is based on the same cause, provided that the previous decision qualifies for recognition in the Netherlands. Even if such a United States judgment is given binding effect, a claim based thereon may, however, still be rejected if the United States judgment is not or no longer formally enforceable. Moreover, if the United States judgment is not final (for instance when appeal is possible or pending) a competent Dutch court may postpone recognition until the United States judgment will have become final, refuse recognition under the understanding that recognition can be asked again once the United States judgment will have become final, or impose as a condition for recognition that security is posted.

A competent Dutch court may deny the recognition and enforcement of punitive damages or other awards. Moreover, a competent Dutch court may reduce the amount of damages granted by a United States court and recognize damages only to the extent that they are necessary to compensate actual losses or damages. Thus, United

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States investors may not be able, or experience difficulty, to enforce a judgment obtained in a United States court against us or our officers.

 

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