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 January 2025
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 January 13, 2025, Pharvaris N.V. (the “Company”) issued a press release. The press release is attached as Exhibit 99.1 hereto and is incorporated by reference herein. Also on January 13, 2025, the Company made available an investor presentation on its website. A copy of the investor presentation is attached hereto as Exhibit 99.2.
Exhibit 99.1 to this Report on Form 6-K shall be deemed to be incorporated by reference into the registration statements on Form F-3 (Registration Number 333-273757, 333-277705 and 333-278650) and Form S-8 (Registration Number 333-252897). Exhibit 99.2 to this Report on Form 6-K shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (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.
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PHARVARIS N.V. |
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Date: January 13, 2025 |
By: |
/s/ Berndt Modig |
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Name: |
Berndt Modig |
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Title: |
Chief Executive Officer |
EXHIBIT INDEX
Exhibit No. |
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Description |
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Exhibit 99.1
Pharvaris Outlines 2025 Strategic Priorities
ZUG, Switzerland, January 13, 2025 – Pharvaris (Nasdaq: PHVS), a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to help address unmet needs of those living with bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema (AAE), today outlined its strategic priorities for 2025.
“This year is paramount to Pharvaris as we continue clinical development of deucrictibant to help address unmet needs for those living with bradykinin-mediated angioedema,” said Berndt Modig, Chief Executive Officer of Pharvaris. “Pharvaris is committed to generating robust clinical data to build a compelling package supporting deucrictibant’s efficacy and safety profile. Our team is focused on the execution of two Phase 3 clinical studies in HAE, the expansion of our pipeline into AAE, and preparations for commercialization of deucrictibant pending regulatory submission and approval; we have significant resources in place to support these strategic investments and provide value for our shareholders.”
2025 Strategic Priorities
Long-term Prophylaxis of HAE Attacks
On-demand Treatment of HAE Attacks
Clinical Development of Deucrictibant in AAE-C1 INH
Business Updates
Corporate
1 Petersen et al. J Allergy Clin Immunol July 2024.
The poster presented at BSI-CIPN characterized the experience of people living with HAE in the United Kingdom with current treatments, all of whom were prescribed injectable on-demand medications. The most common unmet need associated with currently prescribed long-term prophylactic and on-demand medications was a desire for a different route of administration. This analysis highlights the unmet need for novel oral options.
Upcoming Participation at Investor Conferences
Presenter: Berndt Modig, CEO
Date, time: Wednesday, January 15, 2025, 5:15-5:55 p.m. PST (8:15-8:55 p.m. EST)
Presenters: Berndt Modig, CEO; Wim Souverijns, Ph.D., CCO; Peng Lu, M.D., Ph.D., CMO
Date, time: Wednesday, February 12, 2025, 9:20-9:50 a.m. EST
Live audio webcasts of the J.P. Morgan and Oppenheimer presentations will be available on the Investors section of the Pharvaris website at: https://ir.pharvaris.com/news-events/events-presentations. The audio replays will be available on Pharvaris’ website for 30 days following the presentation.
Upcoming Presentations at Medical Congresses
Date, time: Sunday, March 2, 2025, 9:45-10:45 a.m. PST (12:45-1:45 p.m. EST)
Presenter: John Anderson, M.D.
Date, time: Sunday, March 2, 2025, 9:45-10:45 a.m. PST (12:45-1:45 p.m. EST)
Presenter: Michael E. Manning, M.D.
Date, time: Sunday, March 2, 2025, 9:45-10:45 a.m. PST (12:45-1:45 p.m. EST)
The posters will be available on the Investors section of the Pharvaris website at: https://ir.pharvaris.com/news-events/events-presentations.
About Deucrictibant
Deucrictibant is a novel, potent, oral small-molecule bradykinin B2 receptor antagonist currently in clinical development. By inhibiting bradykinin signaling through the bradykinin B2 receptor, deucrictibant has the potential to prevent the occurrence of HAE attacks and to treat the manifestations of an attack if/when they occur. Based on its chemical properties, Pharvaris is developing two formulations of deucrictibant for oral administration: an extended-release tablet to enable sustained absorption and efficacy in prophylactic treatment, and an immediate-release capsule to enable rapid onset of activity for on-demand treatment.
About Pharvaris
Pharvaris is a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to potentially address all types of bradykinin-mediated angioedema. Pharvaris has the ambition to provide injectable-like efficacy and placebo-like tolerability with the convenience of an oral therapy to prevent and treat HAE attacks. With positive data in both Phase 2 prophylaxis and on-demand studies in HAE, Pharvaris is currently evaluating the efficacy and tolerability of deucrictibant in a pivotal Phase 3 study for the prevention of HAE attacks (CHAPTER-3) and a pivotal Phase 3 study for the on-demand treatment of HAE attacks (RAPIDe-3). 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; the expected timing, progress, or success of our clinical development programs, especially for deucrictibant immediate-release capsules and deucrictibant extended-release tablets, which are in late-stage global clinical trials; our ability to replicate the efficacy and safety demonstrated in the RAPIDe-1, RAPIDe-2, and CHAPTER-1 Phase 2 studies in ongoing and future nonclinical studies and clinical trials; risks arising from epidemic diseases, such as the COVID-19 pandemic, which may adversely impact our business, nonclinical studies, and clinical trials; our ability to potentially use deucrictibant for alternative purposes, for example to treat C1-INH deficiency (AAE-C1INH); the outcome and 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, 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 produce sufficient amounts of drug product candidates for commercialization; 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 (including the Biosecure Act), 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 Corporate and Investor Communications
maggie.beller@pharvaris.com
Pioneering science for patient choice Corporate Presentation January 2025 Exhibit 99.2
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 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. 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 are neither promises nor guarantees, and involve known and unknown risks, uncertainties and other important 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, the expected timing, progress, or success of our clinical development programs, especially for deucrictibant immediate-release capsules and deucrictibant extended-release tablets, which are in late-stage global clinical trials, our ability to replicate the efficacy and safety demonstrated in the RAPIDe-1, RAPIDe-2, and CHAPTER-1 Phase 2 studies in ongoing and future nonclinical studies and clinical trials, risks arising from epidemic diseases such as the COVID-19 pandemic, which may adversely impact our business, nonclinical studies, and clinical trials, our ability to potentially use deucrictibant for alternative purposes, for example to treat C1-INH deficiency (AAE-C1INH), the outcome and 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, 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 produce sufficient amounts of drug product candidates for commercialization, 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 (including the Biosecure Act), 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, 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 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. This presentation includes data for an investigational product not yet approved by regulatory authorities. 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.
FDA orphan drug designation1 Robust IP on CoM (granted in multiple territories, initial term to 2038) and formulations2,3 DEUCRICTIBANT Pioneering science for patient choice for hereditary angioedema (HAE) Source: 1U.S. FDA OOPD listing. 2World Intellectual Property Organization. 3European Patent Office. 4Lesage et al. Int. Immunopharmacology. 2022. 5Riedl MA et al. AAAAI 2024. 6Maurer M et al. AAAAI 2023. 7Riedl MA et al. BKS 2024. 8Maurer M et al. BKS 2024. 9Riedl MA at al. BKS 2024. 10IQVIA predictions. 11Evaluate Pharma Uptake Curves 2008-2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. TWO LATE-STAGE PROGRAMS LARGE GLOBAL HAE MARKET STRONG FUNDAMENTALS Deucrictibant is an orally available small molecule targeting the validated bradykinin B2 receptor4 Results from randomized Phase 2 trials 5,6 and their ongoing extensions7,8 demonstrate a differentiated profile for both preventing and treating HAE attacks with injectable-like efficacy, rapid onset of action, a favorable tolerability profile, and oral convenience over current standard of care9 for people living with HAE Predicted $5.2B market in 203610 While people living with HAE appear satisfied with their treatment, history has shown that the availability of a more efficacious, better-tolerated and/or more convenient alternative drives a dynamic switch to the better product11 Internationally, the long-term prevention market is likely to grow significantly10 Two pivotal Phase 3 studies designed to differentiate current standard of care in both prophylaxis and on-demand treatments Accomplished team with track record in HAE drug development and commercialization Approximately €305M cash and cash equivalents as of September 30, 2024
Median: 14 attacks/year Females: 19 (range: 2-165 attacks/y) Males: 9 (range: 1-42 attacks/y) HAE: A rare, life-long genetic condition with significant burden HAE: hereditary angioedema Source: 1Betschel SD, et al. J Allergy Clin Immunol Pract. 2023. 2Christiansen SC, et al. Ann Allergy Asthma Immunol. 2023. 3Bork K et al. Allergy Asthma Clin Immunol. 2021. 4Lumry WR Front. Med. 2018. 5Nordenfelt P et al. Acta Derm. Venereol 2016. This presentation includes data for an investigational product not yet approved by regulatory authorities. Painful and debilitating Rare Unpredictable attacks Frequency, location, severity1 Often, unknown triggers1,2 If untreated, attacks may last up to 5 days3 Leading to hospitalization1 Potentially life-threatening due to asphyxiation1 1:30,000 to 1:80,000 individuals globally4 United States4 ~7,000 individuals Europe4 ~15,000 individuals
The HAE market is dynamic, with people actively seeking a better* product HAE: hereditary angioedema. *Treatment selection is driven by physicians and patient preference. Source: 1Evaluate Pharma uptake curves 2008-2023 2SEC filings (BioCryst, CSL Behring, Pharming, Takeda). 3U.S. Chart Audit 2023-2024, ADIVO. This presentation includes data for an investigational product not yet approved by regulatory authorities. U.S. HAE switches, gains and losses 3 33.6% Evolution of HAE product sales1,2 People living with HAE actively switch therapies1,2: first-to-market is no guarantee for long-term market leadership ODT LTP
In the U.S., significant growth in the long-term prophylaxis (LTP) and on-demand therapy (ODT) market is expected over the next decade1 Source: 1IQVIA market evolution and company data. 2Evaluate Pharma uptake curves 2008-2023. 3SEC filings (BioCryst, CSL Behring, Pharming, Takeda). This presentation includes data for an investigational product not yet approved by regulatory authorities. Growth expected to be driven by: New options Increased convenience Increased treatment rate Value of on-demand1-3 $850m >$1,200m >2% CAGR 22% 38% 24% ~40% share by person Growth expected to be driven by: New options Increased convenience Continued paradigm shift from ODT to LTP Value of prophylaxis1-3 $1,869m $4,000m 6% CAGR 58% 21% ~50% share by person LTP to further grow as the dominant treatment paradigm in the U.S. market through to 20361 2022 LTP 69% ODT 31% 2036 LTP 77% ODT 23% HAE market growth will be driven by increased efficacy and convenience of new therapies
People living with HAE are seeking a life not defined by their condition nor burdened by its management1 Source: 1Lumry WR et al. Allergy Asthma Proc. 2020. 2Geba et al, J Drug Access.2021. 3U.S. Chart Audit 2023-2024, ADIVO. This presentation includes data for an investigational product not yet approved by regulatory authorities. People living with HAE actively switch between products3, seeking improvement in efficacy, safety/tolerability, and convenience Efficacy is a prime driver… but safety and tolerability cause exploration of alternatives… …while convenience is a key driver for overall preference2
Bradykinin B2 receptor antagonism is a foundational mechanism to treat and prevent bradykinin-mediated angioedema attacks1,2 Source: 1Maurer M, et al. Allergy. 2022. 2Zuraw BL World Allergy Orphan J. 2010. 3Lumry WR et al. Allergy Asthma Proc. 2020. 4Riedl MA et al. AAAAI 2024. 5Maurer M et al. AAAAI 2023. 6Petersen RS et al. J Allergy Clin Immunol. 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. cHMWK Inactive fragments HMWK ACEi + Prekallikrein FXII Plasminogen Plasmin FXIIa tPA Kininase II /ACE Plasma kallikrein KNG1 F12 PLG C1-INH Bradykinin B2 receptor Deucrictibant Bradykinin Angioedema Has potential to prevent or treat bradykinin-mediated angioedema irrespective of source of bradykinin4-6 Directly blocks the main mediator of swelling and inflammation1,3 Deucrictibant is a bradykinin B2 receptor antagonist in development for prevention and treatment of HAE attacks
Deucrictibant has the potential to address unmet needs of people living with HAE HAE: hereditary angioedema. *To be confirmed with clinical data from Phase 3 studies Source: 1Company data: single-dose cross-over PK study in healthy volunteers (n=14) under fasting conditions. 2Lesage A et al. IDDST 2024. 3Crabbe et al. AAAAI 2021. 4Maurer M et al. AAAAI 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. Rapidly reaches therapeutic exposure within 15-30 minutes4, making it optimal for on-demand oral treatment of HAE attacks* DEUCRICTIBANT immediate-release (IR) capsule rapid absorption3 deucrictibant Maintains sustained therapeutic exposure over 24 hours2 from day one, allowing for once-daily oral treatment to prevent HAE attacks* DEUCRICTIBANT extended-release (XR) tablet sustained absorption1 Two oral products with the same active ingredient for the prevention and treatment of HAE attacks
Deucrictibant differentiated profile for LTP and ODT LTP: long-term prophylaxis. ODT: on-demand therapy. XR: extended-release tablet formulation of deucrictibant. IR: immediate-release capsule formulation of deucrictibant. Sources: 1Company research. 2Leasge et al. IDDST 2024. 3Groen K et al. ACAAI 2022. 4Li H et al. EAC 2024. 5Maurer M et al. HAEi Workshop, 2022. 6Maurer M et al. AAAAI 2023. 7Riedl et al. WSAAI 2024. 8Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Rapid Absorption Within 15-30 minutes6, deucrictibant IR reaches therapeutic exposure resulting in the halt of attack progression within 30 minutes7 Longer Effective Exposure A longer effective exposure can potentially result in a high rate of single-dose attack resolution8 Single Oral Pill Specific formulations allow for once-daily dosing3 (XR for LTP) or rapid, single-dose resolution4 of HAE attacks (IR for ODT) Oral ODT or LTP Formulations Deucrictibant is the only HAE therapy1 in development that allows for oral administration in both prophylaxis and on-demand2 Rapid to Steady State Deucrictibant XR has the potential to achieve steady state within 2-3 days5, providing protection against HAE attacks on the initial day3 of LTP initiation LTP ODT
Wholly-owned pipeline focused on bradykinin B2 receptor mechanism HAE: hereditary angioedema. AAE: acquired angioedema. OLE: open-label extension This presentation includes data for an investigational product not yet approved by regulatory authorities. MOLECULE INDICATION deucrictibant HAE On-Demand HAE Prophylaxis Complete Enrollment PHAXXX AAE PRE-IND PHASE 1 PHASE 2 PHASE 3 REGISTRATIONAL NEXT MILESTONE OLE Complete Enrollment Initiation OLE Undisclosed
On-Demand Treatment (ODT) Long-Term Prophylaxis (LTP) Deucrictibant clinical development program OLE: open-label extension. LTE: long-term extension. Source: 1NCT05047185. 2NCT06669754. 3NCT06679881. 4NCT04618211. 5NCT05396105. 6NCT06343779. Phase 24 Complete Phase 2/3 LTE5 Ongoing Phase 3 pivotal6 Ongoing Phase 21 Part 1: randomized controlled primary analysis (complete) Part 2: open-label extension (ongoing) Phase 3 pivotal2 Ongoing Phase 3 OLE3 Start-up This presentation includes data for an investigational product not yet approved by regulatory authorities.
Deucrictibant shows the potential to address unmet needs of people living with HAE HAE: hereditary angioedema. OLE: open-label extension. LTE: long-term extension. PGI-C: patient global impression of change. PGI-S: patient global impression of severity. Source: 1Riedl MA et al. BKS 2024. 2Valerieva A et al. EAACI 2024. 3Magerl M et al. BKS 2024. 4Riedl MA et al. AAAAI 2024. 5Maurer M et al. BKS 2024. 6Maurer M et al. AAAAI 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. Efficacy Safety & Tolerability On-Demand Treatment (ODT) Onset of symptom relief with median PGI-C “a little better” ~ 1.1 hour Symptom resolution with PGI-S “none” ~ 11.5 hours in ongoing LTE study5 85.8% of attacks achieved complete symptom resolution within 24 hours in ongoing LTE; 90.2% of which with single dose5 Phase 2 safety and tolerability profile confirmed in ongoing LTE study5,6 Potential preferred option for ODT Long-Term Prophylaxis (LTP) Efficacy Quality of Life Safety & Tolerability Formulation Early-onset attack reduction sustained for over one year in ongoing OLE study1 Improvement in disease control and health-related quality of life paralleled attack reduction in Phase 22,3 Phase 2 safety and tolerability profile confirmed in ongoing OLE study1,4 Intended commercial formulation for once-daily dosing ready for Phase 3 Potential preferred option for LTP
Long-Term Prophylaxis Deucrictibant extended-release tablets
On-Demand Treatment (ODT) Long-Term Prophylaxis (LTP) Deucrictibant clinical development for LTP and ODT OLE: open-label extension. LTE: long-term extension. Source: 1NCT05047185. 2NCT06669754. 3NCT06679881. 4NCT04618211. 5NCT05396105. 6NCT06343779. Phase 24 Complete Phase 2/3 LTE5 Ongoing Phase 3 pivotal6 Ongoing Phase 21 Part 1: randomized controlled primary analysis (complete) Part 2: open-label extension (ongoing) Phase 3 pivotal2 Ongoing Phase 3 OLE3 Start-up This presentation includes data for an investigational product not yet approved by regulatory authorities.
Positive topline data from CHAPTER-1, a Phase 2 study of deucrictibant the for prophylaxis of HAE attacks *40 mg/day deucrictibant treatment group; %reduction in monthly attack rate is based on a Poisson regression model. 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. HAE: hereditary angioedema. Source: Aygören-Pürsün E et al. EAACI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. 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 Primary endpoint met: 84.5% reduction in monthly attack rate versus placebo at week 12 (p=0.0008)*
Continuing deucrictibant treatment sustained the early-onset attack reduction for over one year IR, immediate release; OLE, open label extension; RCT, randomized controlled trial. N = number of participants randomized in each treatment group in Part 1 of the study. N’ = number of participants in the OLE. a1 month = 4 weeks. bDeucrictibant IR capsule, 10 mg twice daily. cDeucrictibant IR capsule, 20 mg twice daily. Source: Riedl MA et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. In the open-label extension up to 18 months: 93% attack rate reduction from baseline Median attack rate = 0 for every month 99% of days symptom free RCT OLE Time (months) Attack ratea (mean ± SEM) Baseline 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 0 1 2 3 4 RCT OLE Placebo (n=11) 20 mg/day† (n=11) 40 mg/day‡ (n=12) 1.94 0.40 0.30 Attack rate* (LS mean) 79.3% reduction P=0.0009 0.15 40 mg/day‡ (n=30) 0.0 0.5 1.0 1.5 2.0 2.5 84.5% 93% reduction from baseline 40 mg/dayc OLE 40 mg/dayc RCT 20 mg/dayb RCT Placebo RCT reduction P=0.0008
Deucrictibant efficacy and tolerability profile could address unmet needs in the prophylactic setting, with the convenience of a daily tablet § Crossover, 12 weeks/treatment. §§ Crossover, 16 weeks/treatment (results reported for weeks 3-16 for each treatment arm). † Parallel-arms, 26 weeks. †† Parallel-arms, 24 weeks. ¶ Parallel-arms, 25 weeks. ‡ Parallel-arms, 12 weeks. # vs. placebo. ¶¶ Weeks 5-25. ¤ vs. RCT Part 1 baseline. Source: 1Cinryze® US PI, Feb 2023. 2Longhurst H et al. N Engl J Med. 2017. 3Haegarda® US PI, Jan 2022. 4Takhzyro® US PI, Feb 2023. 5Banerji A et al. JAMA. 2018. 6Zuraw B et al. J Allergy Clin Immunol. 2021. 7Orladeyo® US PI, Nov 2023. 8Craig TJ et al. Lancet. 2023. 9Riedl MA et al. N Engl J Med. 2024. 10Aygören-Pürsün E et al. EAACI 2024. 11Aygören-Pürsün E et al. BKS 2024. 12Riedl MA et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Mean monthly attack reduction vs. placebo ≥50% attack reduction ≥70% attack reduction Cinryze® (pdC1INH) Haegarda® (pdC1INH) Takhzyro® (lanadelumab) Orladeyo® (berotralstat) garadacimab 89%8 95% vs. 33%8 92% vs. 17%8 74% vs. 8%8 62% vs. 0%8 71-85%1 - - - - 84%2 90%#2,3 83%#2,3 58%#2,3 40% vs. 0%2,3 73-87%4 100-100% vs. 32%4,5 76-89% vs. 10%4,5 55-67% vs. 5%4,5 31-44% vs. 2%4,5 44%6,7 58% vs. 25%6,7 50% vs. 15%6,7 23% vs. 8%6,7 10% vs. 2.5%6 ≥90% attack reduction % patients attack-free vs. placebo Anti-FXIIa mAb Plasma kallikrein inhibitor Anti-plasma kallikrein mAb Plasma-derived C1INH Plasma-derived C1NH Mechanism of Action donidalorsen 55-81%9 83-93% vs. 27%¶¶9 65-92% vs. 18%¶¶9 48-62% vs. 9%¶¶9 35-53% vs. 9%¶¶9 Plasma kallikrein inhibitor deucrictibant Ph 3† Ph 3†† (150mg daily) Ph 3† (300mg q2w / q4w) Ph 3§§ (60 IU/Kg) Ph 3§ (500 U, 1,000 U) Clinical Trial(s) Ph 3¶ (80 mg q4w, q8w) Ph 2‡ (40mg/day) Ph 2/3 OLE Bradykinin B2 receptor antagonist 85%10,11 90% vs. 18%11 80% vs. 18%11 60% vs. 0%11 40% vs. 0%11 93%¤12 pending publication pending publication pending publication pending publication Mean reduction in use of ODT vs. placebo 88%8 - 89%2 74-87%4 54%7 67-92%¶¶9 93%10,11 pending publication
Commercial XR formulation maintains exposure above therapeutic level for at least 24 hours Extended-release matrix controls release and absorption of compound in small intestine as well as in colon Supports once-daily dosing while maintaining exposure more consistently versus twice-daily IR (used in proof-of-concept Phase 2 CHAPTER-1 study) Formulation patent applications filed with broad coverage of worldwide pharmaceutical markets XR: extended-release tablet formulation of deucrictibant. IR: immediate-release capsule formulation of deucrictibant. Source: Company data: single-dose cross-over PK study in healthy volunteers (n=14) under fasting conditions This presentation includes data for an investigational product not yet approved by regulatory authorities.
CHAPTER-3 RCT and CHAPTER-4 OLE RCT: randomized clinical trial. OLE: open-label extension. HAE: hereditary angioedema. XR: extended-release tablet. This presentation includes data for an investigational product not yet approved by regulatory authorities. Two-part, global Phase 3 study of deucrictibant for prophylaxis of HAE attacks Enrollment Target enrollment of approximately 81 adolescents and adults living with HAE Top-line data anticipated in the second half of 2026 Objectives Evaluation and characterization of investigator-confirmed HAE attacks during 24-week treatment period Incidence of treatment-emergent adverse events Evaluation of deucrictibant XR pharmacokinetics Measure of change in participant-reported quality of life R Deucrictibant XR tablet 40 mg/day Deucrictibant XR tablet 40 mg/day End-of-study visit Screening Double-blind treatment period (24 weeks) Open-label treatment period Placebo
On-Demand Deucrictibant immediate-release capsules
On-Demand Treatment (ODT) Long-Term Prophylaxis (LTP) Deucrictibant clinical development for LTP and ODT OLE: open-label extension. LTE: long-term extension. Source: 1NCT05047185. 2NCT06669754. 3NCT06679881. 4NCT04618211. 5NCT05396105. 6NCT06343779. Phase 24 Complete Phase 2/3 LTE5 Ongoing Phase 3 pivotal6 Ongoing Phase 21 Part 1: randomized controlled primary analysis (complete) Part 2: open-label extension (ongoing) Phase 3 pivotal2 Ongoing Phase 3 OLE3 Start-up This presentation includes data for an investigational product not yet approved by regulatory authorities.
RAPIDe-1, a Phase 2 on-demand study of deucrictibant in HAE HAE: hereditary angioedema. IR: immediate-release. AMRA, Angioedema Symptom Rating Scale. *pooled 10, 20, 30 mg deucrictibant treatment group †based on post-hoc analysis. Source: 1Maurer M et al. AAAAI 2023. 2 Riedl MA et al. ACAAI 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. Deucrictibant IR showed rapid onset of action, symptom relief, and resolution of HAE attacks End of symptom progression in 25-26 minutes* (based on AMRA-3)†2 Onset of symptom relief achieved in 2.4 hours* (≥30% reduction in AMRA-3)1 5-fold reduction in use of rescue medication*1 Deucrictibant IR substantially reduced the use of rescue medications1 Deucrictibant IR well-tolerated at all doses1 Primary endpoint met: deucrictibant IR significantly reduced attack symptoms versus placebo*1
RAPIDe-2*, a long-term extension of RAPIDe-1 *A total of 265 attacks from 17 participants were included in the modified intention-to-treat efficacy analysis set (data cutoff: 1 March 2024); a total of 337 attacks from 19 participants were included in the safety analysis set (data cutoff: 10 June 2024). HAE: hereditary angioedema. IR: immediate-release capsule formulation of deucrictibant. PGI-C: Patient Global Impression of Change. PGI-S: Patient Global Impression of Severity. Source: Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. In the current analysis of the ongoing RAPIDe-2 Phase 2/3 extension study, deucrictibant IR capsule was well-tolerated for all studied doses with no new safety signals observed Results from the ongoing RAPIDe-2 extension are consistent with the Phase 2 RAPIDe-1 study and provide evidence on the long-term safety and efficacy of deucrictibant IR capsule for repeat treatment of HAE attacks 1.1 hours median time to onset of symptom relief by PGI-C 98.5% of attacks by 12 hours 97.7% of attacks by 12 hours 11.5 hours median time to complete attack resolution by PGI-S1 85.8% of attacks within 24 hours 86.0% of attacks were treated with a single dose of deucrictibant IR capsule 2.6 hours median time to reduction in attack severity by PGI-S Efficacy analysis showed:
Plasma-derived C1NH (23%) - Icatibant (60%) – Recombinant hC1INH (9%) - Other (9%) Deucrictibant’s rapid-onset and complete symptom resolution may address unmet medical need in HAE with a single oral capsule References on following slide This presentation includes data for an investigational product not yet approved by regulatory authorities. Time to onset of symptom relief (median) Standard of Care Berinert® (pdC1INH), Firazyr® (icatibant), Ruconest® (rhC1INH) - - 2.4 h8 - 4.0 h8 - - 13.5 h8 - PSM Analysis of Mixed Methods Study9 Clinical Trial(s) Time to ≥50% VAS reduction (median) Time to reduction in attack severity (median)d Time to symptom resolution (median) % attacks resolved within 24 h with 1 dose - % attacks treated with 1 dose of study drug (no additional doses of study drug and/or rescue med.) VAS/AMRAa TOSb PGI-Cc VAS/AMRAe TOSf PGI-Sg Mechanism of Action sebetralstat tablet deucrictibant IR capsule 2.4 vs. 8.0 h3 - 2.0 vs. 7.6 h4,5 - - 1.1 h7 3.9 vs. 22.8 h3 - - 2.6 h7 7.5 vs. 42.0 h3 - 5.2 vs. 23.3 h4,5 - - 11.5 h7 75.0% vs. 15.7†6 81.7% vs. 22.4%‖6 90.2%7 - - 1.6-1.8 vs. 6.7 h1 Not reported yet2 7.7-9.3 vs. > 12 h1 - - ≥24.0 vs. >24 h1 42.5-49.5% vs. 27.4%#1 Ph 2 (10mg, 20mg, 30 mg pooled) Ph 2/3 Ext.* (10mg, 20mg, 30mg pooled) Ph 3* (300mg, 600mg) pending publication 86.0%§7 ≤60.2-≤60.9 vs. ≤44.0%1 Bradykinin B2 receptor antagonist Plasma kallikrein inhibitor - - 1.1 h8 - 2.1 h8 - - 12.3 h8 - Ph 2/3 Ext. PSM Analysis (10mg, 20mg, 30mg pooled) -
ODT comparison data references * Non-laryngeal and laryngeal attacks included for treatment with study drug. # Symptom resolution assessed by PGI-S. † Symptom resolution assessed by VAS/AMRA. ‖ Symptom resolution assessed by TOS. a. Time to onset of symptom relief by VAS/AMRA defined as ‘VAS-3 ≥30% reduction from pre-treatment score’ in 3. b. Time to onset of symptom relief by TOS defined as ‘The time point when TOS PRO first reaches at least “A little better” for all symptom complexes affected at baseline, ’and no new symptom in any other symptom complex is reported. Relief is confirmed if the improvement is sustained at 2 consecutive time points’ in 4,5. c. Time to beginning (or onset) of symptom relief by PGI-C defined as ‘beginning of symptom relief as assessed in a time-to-event analysis. The beginning of symptom relief was defined as a rating of “a little better” on the 7-point Patient Global Impression of Change (PGI-C) scale (ratings range from “much better” to “much worse”) at two or more consecutive time points within 12 hours after the first administration of the trial agent’ in 1 and as ‘Patient Global Impression of Change (PGI-C) rating of at least “a little better” for 2 consecutive timepoints by 12 hours post-treatment’ in 7,8. d. Time to reduction in attack severity defined as ‘reduction in the severity of the attack, defined as an improved rating on the 5-point Patient Global Impression of Severity (PGI-S) scale (ratings range from “none” to “very severe”) at two or more consecutive time points within 12 hours after the first administration’ in 1 and ‘achieving ≥1 point reduction in the Patient Global Impression of Severity (PGI-S) from pretreatment for 2 consecutive timepoints by 12 hours post-treatment’ in 7,8. e. Time to symptom resolution by VAS/AMRA defined as ‘all 3 individual VAS items ≤10’ in 3. f. Time to symptom resolution by TOS defined as ‘The time point when TOS PRO first reaches “A lot better or resolved” for all symptom complexes affected at baseline, and no new symptom in any other symptom complex is reported’ in.4,5 g. Time to symptom resolution by PGI-S defined as ‘achieving PGI-S rating of “none” at 24 hours post-treatment’ in 1 and as ‘achieving PGI-S rating of “none” at 24 hours post-treatment’ in 7,8 . 1Riedl MA et al. N Engl J Med. 2024. 2EudraCT: 2021-001226-21. 3Maurer M et al. AAAAI 2023. 4Riedl MA et al. C1-INH Workshop 2023. 5RAPIDe-1 Phase 2 Top-line data presentation. 6Li HH et al. EAC 2024. 7Maurer M et al. BKS 2024. 8Riedl MA et al. BKS 2024. 9Mendivil et al. GA2LEN UCARE 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities.
RAPIDe-31 RCT RCT: randomized clinical trial. *Adolescent patients receive a non-attack dose for PK sampling prior to randomization. Source: 1Maurer M et al. EAACI 2024. 20 mg capsule This presentation includes data for an investigational product not yet approved by regulatory authorities. Global Phase 3 study of deucrictibant for on-demand treatment of HAE attacks Enrollment Target enrollment of approximately 120 adolescents and adults living with HAE Top line data anticipated in 1Q2026 Secondary Endpoints Time to end of progression of attack symptoms, substantial symptom relief, and symptom resolution PGI-C, Patient Global Impression of Severity (PGI-S), Angioedema syMptom Rating scAle (AMRA) Use of rescue medication Incidence of treatment-emergent adverse events Primary Endpoints Onset of symptom relief Patient Global Impression of Change (PGI-C) rating of at least “a little better” for two consecutive timepoints within 12 hours post-treatment Rollover to open-label extension Screening and PRO training R Day 1 Visit Placebo Deucrictibant 20 mg/day Deucrictibant 20 mg/day Placebo End-of Study Visit* after second HAE attack treated with study drug Post-Attack-Visit after first attack treated with study drug Double-blind crossover treatment with 2 qualifying attack treatment periods
Symptom evolution towards relief and resolution Symptom progression Clinical trial endpoints span the entire attack timecourse AMRA, Angioedema Symptom Rating Scale; EoP, end of progression; HAE, hereditary angioedema; IR, immediate release; PGI-C, Patient Global Impression of Change; PGI-S, Patient Global Impression of Severity. Source: 1NCT04618211. 2Riedl et al. ACAAI 2023. 3Medivil et al. GA2LEN UCARE 2023. 4NCT05396105. 5NCT06343779. 6Maurer et al. EAACI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Time (not to scale) Clinical manifestations Treatment with deucrictibant IR End of progression Onset of symptom relief Complete symptom resolution RAPIDe-11,2,3 RAPIDe-35,6 AMRA all 3 items ≤10 PGI-S “none”; AMRA all 3 items ≤10 Time to EoP by PGI-C Onset of HAE attack AMRA-3 ≥30% reduction Primary endpoint PGI-C “a little better” Substantial symptom relief AMRA-3 ≥50% reduction RAPIDe-24 PGI-S “none”; AMRA all 3 items ≤10 PGI-C “a little better” AMRA ≥30% reduction; PGI-C “better”; PGI-S ≥1 point reduction; AMRA ≥50% reduction PGI-C “better”; PGI-S ≥1 point reduction; AMRA ≥50% reduction Time to EoP by AMRA Post-hoc
Patient-reported outcomes (PRO) assessments Source: Riedl MA et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. PGI-C PGI-S AMRA Much worse Worse A little worse Same A little better Better Much better Very severe Severe Moderate Mild None Worst symptoms 100 No symptoms 0 Patient Global Impression of Change1 Patient Global Impression of Severity2 Angioedema syMptom Rating scAle3
Acquired Angioedema
Bradykinin B2 receptor inhibition broadly applicable across angioedema Notes: bold = known or potential role for bradykinin involvement in disease. †also designated as Normal C1INH Angioedema (HAE-nC1INH) 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; FXII: gene encoding FXII; ANGPT: gene encoding angiopoietin; MYOF: gene encoding myoferlin; HSST: gene encoding heparan sulfate sulfotransferase; SCLS: systemic capillary leak syndrome. Source: Busse 2020 J Allergy Clin Immunol Pract; Bork et al 2021 J Allergy Clin Immunol; Zanichelli et al 2012 Allergy; Longhurst et al 2017 Clin. Exp. Immunol.; Otani, Banerji 2017 Immunol. Allergy Clin. N. Am.; Bova et al 2018 Int. Arch. Allergy Immunol.; Petersen et al 2024 J Allergy Clin Immunol This presentation includes data for an investigational product not yet approved by regulatory authorities. AE-URT AE-ANA HAE-C1INH (Type 1, 2) AAE-C1INH HAE-FXII†, HAE-PLG†, HAE-KNG† HAE-ANGPT†, HAE-MYOF †, HAE-HSST†, SCLS AE-ACEI, AE-tPA, AE-DPPIV, AE-NSAID, etc. AE-UNK, HAE-UNK †, EAE Mast cell degranulation Hereditary C1INH deficiency Acquired C1INH deficiency KKS pathway mutations Intrinsic vascular endothelium dysfunction Drug adverse reactions (various mechanisms) Unknown aetiology or mechanism AE-MC Mast-cell mediated AE-BK Bradykinin mediated AE-VE Vascular endothelium AE-DI Drug induced AE-UNK Unknown Name/ Acronym Mechanism Types of angioedema Italic = genetic cause *Aspirational Angioedema Bradykinin B2 receptor Angioedema BK BK BK BK BK Deucrictibant Deucrictibant* Deucrictibant* Deucrictibant* Deucrictibant* Plasmin Plasmin Plasmin FXIIa Carboxypeptidase N BK metabolites FXII Plasminogen prePK HMWK cHMWK HMWK C1-INH (SERPING1) C1-INH (SERPING1) HS3ST6 PLG Plasma kallikrein HMWK LMWK Kallidin VEGFR2 VEGF Tie2 Myoferlin ANGPT1 CPN KNG1 HMWK LMWK Kallidin PR3 cHMWK
Deucrictibant proof-of-concept in acquired angioedema due to C1-INH deficiency (AAE-C1INH)1,2 Source: 1Petersen RS et al. J Allergy Clin Immunol. 2024. 2Petersen RS et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. POP-AID ONCE-AID Part 1: On-demand treatment Part 2: Prophylactic treatment Long-term extension (XR tablet) Investigator-initiated trial (IIT) by the Amsterdam UMC Estimated prevalence of 1:100,000 to 1:500,000 or ~10% of HAE type 1/2 Currently, no therapies approved for AAE
Deucrictibant XR tablet for the prevention of acquired angioedema (AAE-C1INH) attacks1,2 Attacks before and during deucrictibant XR treatment Notes: the baseline attack rate covers 90 days prior to randomization for prophylactic treatment in the randomized controlled trial for Patients 1,2, and 3, and 90 days prior to enrollment in the open-label portion for Patient 4. *Patient 4 reported five angioedema attacks in the two months prior to enrollment, but did not recall the exact dates on which these attacks occurred. Graph A: Angioedema Control Test (AECT) score during prophylactic treatment with deucrictibant XR tablet. Graph B: Angioedema Quality of Life (AE-QoL) score during prophylactic treatment with deucrictibant XR tablet. Source: 1Petersen RS et al. J Allergy Clin Immunol. 2Petersen RS et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Attacks per month Patient 1 Patient 2 Patient 3 Patient 4 Baseline 1.2 1.2 0.9 2.2 Placebo 2.0 0.6 1.0 N/A Deucrictibant 0 0 0 0.1
Our aspiration is to become a market leader in HAE Notes: Aspirational, to be confirmed with Phase 3 clinical data This presentation includes data for an investigational product not yet approved by regulatory authorities. 1 2 4 3 Win the oral LTP market Become preferred LTP Leverage portfolio with B2R antagonist MoA Become standard of care in ODT LTP ODT Both Rooted in a deep commitment to engage with the HAE community
www.pharvaris.com NASDAQ: PHVS
Appendix
Deucrictibant: Only compound today1 with the potential to deliver injection-like efficacy orally across both LTP and ODT *To be confirmed with clinical data from Phase 3 studies. **Patient preference varies. Source: 1Company research. 2Company data: target threshold exceeded on first day in single-dose cross-over PK study in healthy volunteers (n=14) under fasting conditions. 3Lesage A et al, IDDST 2024. 4Riedl MA et al. AAAAI 2024. 5Riedl MA et al. BKS 2024. 6Maurer M et al. HAEi Workshop, 2022. 7Lesage et al. Int. Immunopharmacology. 2022. 8Crabbe et al. AAAAI 2021. 9Maurer M et al, AAAAI 2023. 10Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Deucrictibant XR Extended-release tablet Sustained absorption2 Maintains sustained therapeutic exposure over 24 hours3 from initial dose, allowing for once-daily oral treatment to prevent HAE attacks* Highly effective at preventing attacks*,4,5 Rapid protection2 and elimination6 Well-tolerated4,5 Ease of oral administration**,7 Deucrictibant IR Immediate-release capsule Rapid absorption6 Rapidly reaches therapeutic exposure within 15-30 minutes8, making it optimal for on-demand oral treatment of HAE attacks* Rapid onset of action9,10 Single dose resolution10 Ease of oral administration**,7
People living with HAE are seeking: Source: 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. Highly effective, well-tolerated and less burdensome prophylactic therapies 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 Injectable-like efficacy Well-tolerated Easy, painless administration Effectively targeting the bradykinin receptor with a small molecule has the potential to deliver on their hopes
Pharvaris has the ambition to realize the potential of deucrictibant to become a preferred option for bradykinin-mediated conditions Source: 1Riedl MA et al. BKS 2024. 2Maurer M et al. BKS 2024. 3Company research. 4Petersen RS et al. J Allergy Clin Immunol. 2024. 5Lesage et al. Int. Immunopharmacology, 2022. This presentation includes data for an investigational product not yet approved by regulatory authorities. HAE Long-term extension data1,2 reinforces our belief that deucrictibant has the potential to become a preferred option for the management of HAE AAE Based on the community’s interest3 and the initial intriguing data4, Pharvaris plans to pursue development of deucrictibant in AAE nC1 Leveraging B2-receptor mechanism5, potential for application to normal C1-INH hereditary angioedema
Rare allergy & immunology conditions (commercial) BK-mediated diseases (R&D) BK-mediated angioedema: nC1, AAE Pharvaris aspires to leverage its foundational B2R expertise to develop therapies for conditions beyond HAE HAE Type 1/2 This presentation includes data for an investigational product not yet approved by regulatory authorities.
Clinical dosing is guided by prediction from a validated in vivo surrogate-marker model, the bradykinin challenge Notes: BK: bradykinin; NHP: non-human primates; SQ: sub-cutaneous; EC85: effective concentration achieving 85% inhibition of bradykinin effect Source: 1FDA Clinical Pharmacology and Biology Review: icatibant. 2Maurer M et al. Clin Exp Allergy. 2022. 3FIRAZYR® Patient Registry. 4Lesage et al. Int. Immunopharmacology. 2022. 5Derendorf H et al. ACAAI 2020. 6Riedl MA et al. AAAAI 2024. 7Maurer M et al. AAAAI 2023. clinical Icatibant development program (shared mechanism) As assessed by FDA, exposure of icatibant above EC85 for 6 hours correlates with clinical activity1,2,3 nonclinical Non-human primate study Oral deucrictibant suppresses BK effect in NHP faster than SQ icatibant; target exposures for Phase 14 clinical Phase 1 healthy volunteer study EC85 assessed in humans at 13.8 ng/mL; target exposure for studies in people living with HAE5 clinical RAPIDe-1 Phase 2 on-demand Clinical efficacy correlates with exposure exceeding and remaining above EC856 clinical CHAPTER-1 Phase 2 prophylaxis Clinical efficacy demonstrated based on dose prediction targeting exposure above EC857 Bradykinin, injected IV in healthy volunteers, induces a transient, limited change in cardiac parameters (heart rate , blood pressure) which can be blocked by pre-injection of a bradykinin B2 receptor antagonist (e.g., icatibant or deucrictibant) Post- dose (+1h) BK BK Predose Systolic BP Diastolic BP Mean Arterial BP This presentation includes data for an investigational product not yet approved by regulatory authorities.
CHAPTER-1 Randomized Clinical Trial (RCT) Topline Data Long-term Prophylaxis Data
CHAPTER-1 HAE, hereditary angioedema; IR, immediate release; R, randomization. *Deucrictibant IR capsule, 10 mg twice daily; †Deucrictibant IR capsule, 20 mg twice daily; c1 month = 4 weeks. CHAPTER-1 is a Pharvaris-sponsored clinical trial. Source: NCT05047185 This presentation includes data for an investigational product not yet approved by regulatory authorities. Primary endpoint Time-normalized number of investigator-confirmed HAE attacks (monthlyc HAE attack rate) Secondary endpoints Time-normalized number of moderate and severe HAE attacks Time-normalized number of HAE attacks treated with on-demand medication Two-part, Phase 2 study of deucrictibant for long-term prophylaxis of HAE attacks R Placebo Deucrictibant 20 mg/day* Deucrictibant 40 mg/day† Deucrictibant 40 mg/dayb End-of-study visit Screening Part 1: Double-blind treatment period (12 weeks) Part 2: Open-label treatment period
CHAPTER-1 (RCT): Participant disposition aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. Source: Aygoren-Pursun E et al. EAACI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. All screened (n=44) Randomized (n=34) Placebo (n=11) 20 mg/daya (n=11) 40 mg/dayb (n=12) Completed blinded treatment period (n=10) Completed blinded treatment period (n=10) Completed blinded treatment period (n=11) Screen failed (n=10) Withdrawal of consent (n=1) Study paused by sponsor/FDA (n=1) Withdrawal of consent (n=1)
Balanced demographics and baseline characteristics BMI, body mass index; HAE, hereditary angioedema; IR, immediate-release; N = number of randomized participants. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. c1 month = 4 weeks. Source: Aygoren-Pursun E et al. EAACI 2024. 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 monthc 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 ratec 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) 40 mg/dayb n=12 20 mg/daya n=11 Placebo n=11 All N=34
Primary endpoint met: deucrictibant significantly reduced attack rate BL, baseline; IR, immediate-release; LS, least squares. N = number of randomized participants. Model-based inferences are based on a Poisson regression model adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied. aBased on time normalized number of attacks per 4 weeks. bDeucrictibant IR capsule, 10 mg twice daily. cDeucrictibant IR capsule, 20 mg twice daily. Source: Aygoren-Pursun E et al. EAACI 2024. 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 – 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 0.0 0.5 1.0 1.5 2.0 Placebo (n=11) 20 mg/day (n=11) 40 mg/day (n=12) 1.94 0.40 0.30 Monthly Attack Ratea (LS Mean) 79.3% reduction P=0.0009 84.5% reduction P=0.0008 40 mg/day † n=12 20 mg/day* n=11 Placebo n=11
Significant attack reduction and no severe attacks with deucrictibant *20 mg/day = deucrictibant immediate release (IR) capsules 10 mg twice daily; †40 mg/day = deucrictibant IR capsules 20 mg twice daily. Source: CHAPTER-1 Topline Data Presentation. December 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. 0 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 1 2 3 4 5 6 7 8 9 10 11 Participants grouped by treatment Placebo 20 mg/day † 40 mg/day* Time (weeks) Mild attack Moderate attack Severe attack Acute treatment used
Primary endpoint met: deucrictibant significantly reduced attack rate BL, baseline; IR, immediate-release; LS, least squares. N = number of randomized participants. Model-based inferences are based on a Poisson regression model adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied. aBased on time normalized number of attacks per 4 weeks. bDeucrictibant immediate-release (IR) capsule, 10 mg twice daily. cDeucrictibant IR capsule, 20 mg twice daily. Source: Aygoren-Pursun E et al. EAACI 2024. 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 0.0 0.5 1.0 1.5 2.0 1.94 0.40 0.30 Monthlya Attack Rate (LS Mean) 92.3% reduction P=0.0067 1.50 0.26 0.12 0.45 0 0 All Attacks Moderate or Severe Attacks Severe Attacks 40 mg/dayc n=12 20 mg/dayb n=11 Placebo n=11
Primary endpoint met: deucrictibant significantly reduced attack rate BL, baseline; IR, immediate-release; LS, least squares. N = number of randomized participants. Model-based inferences are based on a Poisson regression model adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied. aBased on time normalized number of attacks per 4 weeks. bDeucrictibant immediate-release (IR) capsule, 10 mg twice daily. cDeucrictibant IR capsule, 20 mg twice daily. Source: Aygoren-Pursun E et al. EAACI 2024. 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 0.0 0.5 1.0 1.5 2.0 1.94 0.40 0.30 Monthly Attack Ratea (LS Mean) 92.6% reduction P=0.0040 All Attacks Attacks Treated with ODT 1.41 0.35 0.10 40 mg/dayc n=12 20 mg/dayb n=11 Placebo n=11
Deucrictibant substantially reduced attack rate from baseline IR, immediate release. N = Participants with ≥4 weeks of treatment. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. Source: Wedner HJ et al. ACAAI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. 18% (2/11) 82% (9/11) 90% (9/10) 18% (2/11) 73% (8/11) 80% (8/10) 0 55% (6/11) 60% (6/10) 0 55% (6/11) 40% (4/10) ≥ 50% Reduction from Baseline ≥ 70% Reduction from Baseline ≥ 90% Reduction from Baseline Attack Free 0 25% 50% 75% 100% Percentage of Participants Placebo (n=11) 20 mg/daya (n=11) 40 mg/dayb (n=10)
Deucrictibant reduced the proportion of days with symptoms, and the monthly attack rate, regardless of baseline attack rate IR, immediate-release. N = number of randomized participants with ≥4 weeks of treatment. aBased on time normalized number of attacks per 4 weeks. bDeucrictibant IR capsule, 10 mg twice daily. cDeucrictibant IR capsule, 20 mg twice daily. Source: Aygoren-Pursun E et al. EAACI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. ≥ 1 and < 2 Attacks per Month at Baseline ≥ 2 Attacks per Month at Baseline 1.79 0.24 0.28 Placebo (n=11) 20 mg/dayb (n=11) 40 mg/dayc (n=12) 2.20 0.65 0.20 Monthly Attack Rate (Mean) Monthly Attack Rate (Mean) 0.0 0.5 1.0 1.5 2.0 2.5 2.5 2.0 1.5 1.0 0.5
Unmet need for additional HAE therapies that improve disease control and HRQoL Source: 1Maurer M et al. Allergy. 2022. 2Bork K, et al. Allergy Asthma Clin Immunol. 2021. 3Bygum A, et al. Front Med. 2017. 4Mendivil J, et al. Orphanet J Rare Dis. 2021. 5Chong-Neto HJ. World Allergy Organ J. 2023. 6Lumry WR, et al. Allergy Asthma Proc. 2010. 7Grumach A, et al. J Allergy Clin Immunol. 2024. 8Bouillet L, et al. Allergy Asthma Proc. 2022. 9Betschel SD, et al. J Allergy Clin Immunol Pract. 2023. 10Center for Biologics Evaluation and Research. The voice of the patient – hereditary angioedema. US Food and Drug Administration; May 2018. 11Covella B, et al. Future Pharmacol. 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. International hereditary angioedema (HAE) guidelines recommend that the goals of treatment are to achieve total disease control and normalize patients' lives.1 HAE negatively impacts functional and psychological domains of health-related quality of life (HRQoL).2-6 Patients with well-controlled disease report lower disease burden, lower burden on daily activities, and greater HRQoL than patients with poorly-controlled disease.7 Despite the availability of approved therapies for HAE, an unmet need remains for additional prophylactic treatments combining injectable-like efficacy, a well-tolerated profile, and ease of administration.8-11
Measuring disease control, HRQoL, and treatment satisfaction HAE, hereditary angioedema; HRQoL, health-related quality of life. Source: 1Weller K, et al. Allergy. 2020. 2Weller K, et al. J Allergy Clin Immunol Pract. 2020. 3Weller K, et al. Allergy. 2012. 4Weller K, et al. Allergy. 2016. 5Vanya M, et al. J Patient Rep Outcomes. 2023. 6Atkinson MJ, et al. Value Health. 2005. This presentation includes data for an investigational product not yet approved by regulatory authorities. Never Very often Rarely Sometimes Often Angioedema Control Test (AECT)1,2 : a four-item questionnaire with a five-point response scale developed and validated to retrospectively quantify disease control and to aid treatment decisions in patients with recurrent angioedema (AECT-4Wk – four-week recall used) Angioedema Quality of Life Questionnaire (AE-QoL)3-5: A tool validated for HAE and comprising a 17-item questionnaire across four domains, ‘functioning’, ‘fatigue/mood', 'fear/shame’, and ‘nutrition,’ on a five-point response scale Treatment Satisfaction Questionnaire for Medication (TSQM) Version II6: An 11-item questionnaire to gauge patients’ satisfaction with “effectiveness”, “side effects”, “convenience”, and “global satisfaction” of a medication Extremely dissatisfied Extremely satisfied Somewhat satisfied 0 4 1 2 3 How often have you had angioedema in the last four weeks? How much has your quality of life been affected? How much has the unpredictability bothered you? How well has your angioedema been controlled by therapy?
Improvements in disease control and health-related quality of life paralleled attack reduction during deucrictibant treatment1,2 AE-QoL, Angioedema Quality of Life Questionnaire; 4-week AECT, Angioedema Control Test (4-week recall period); IR, immediate-release; RCT, randomized controlled trial. N = number of participants with AECT and AE-QoL data at week 12. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. Source: 1Magerl M et al. 2024 BKS. 2Zanichelli A et al. ITACA 2024. 3Maurer M et al. Allergy. 2022. The goals of HAE treatment are to achieve complete control of the disease and to normalize people’s lives3 This can currently only be achieved by long-term prophylaxis (LTP) AECT score1 AE-QoL score1 This presentation includes data for an investigational product not yet approved by regulatory authorities. 90% well-controlled participants in both deucrictibant groups vs. 37.5% in placebo group at week 12 ‘Functioning’ and ‘fear and shame’ domains showed greatest improvements at Week 12
Deucrictibant shows greater patient satisfaction versus placebo across effectiveness and global satisfaction (TSQM instrument) IR, immediate release; TSQM, Treatment Satisfaction Questionnaire for Medication. N′ = number of participants with TSQM results at week 12. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. Source: Magerl M et al. 2024 BKS. This presentation includes data for an investigational product not yet approved by regulatory authorities. Placebo (N′=8) 20 mg/daya (N′=10) 40 mg/dayb (N′=10)
AE-QoL: HRQoL improved across all domains AE-QoL, Angioedema Quality of Life Questionnaire; IR, immediate-release; HRQoL, health-related quality of life. N = number of randomized participants with AE-QoL data at baseline. N′ = number of participants with AE-QoL data at week 12. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. Source: Valerieva A et al. EAACI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Deucrictibant AE-QoL Total Score Placebo 20 mg/daya 40 mg/dayb Baseline N=11 N=10 N=12 Mean (SD) 45.3 (18.5) 39.1 (22.0) 41.1 (15.5) 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 N′=10 N′=10 Mean (SD) 35.7 (19.6) 20.2 (15.6) 13.2 (6.9) Median (Q1, Q3) 37.5 (19.1, 49.3) 18.4 (7.4, 33.8) 12.5 (10.3, 17.7) Placebo 20 mg/daya 40 mg/dayb Nutrition Total Score Functioning Fatigue/Mood Fear/Shame Nutrition Total Score Functioning Fatigue/Mood Fear/Shame Nutrition Total Score Functioning Fatigue/Mood Fear/Shame 60 40 20 0 60 40 20 0 60 40 20 0 (N=11) (N’=8) Week 12 Baseline (N=10) (N’=10) Week 12 Baseline (N=12) (N’=10) Week 12 Baseline
AE-QoL: Total score improved from baseline by week 4 and throughout treatment AE-QoL, Angioedema Quality of Life Questionnaire; IR, immediate-release. N = number of participants with AE-QoL data at week 12. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. Source: Valerieva A et al. EAACI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Placebo (N=8) 20 mg/daya (N=10) 40 mg/dayb (N=10) Mean AE-QoL total score improvement from baseline Week 4 Week 12 Week 8 Baseline
TSQM: Greater patient satisfaction with effectiveness vs placebo IR, immediate-release; TSQM, Treatment Satisfaction Questionnaire for Medication; XR, extended release. N = number of participants with TSQM results at week 12. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. *Dose frequency was twice daily using IR capsule; once-daily XR tablet is the intended formulation for the Phase 3 trial. Source: Valerieva A et al. EAACI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Placebo (N=8) 20 mg/daya (N=10) 40 mg/dayb (N=10) +40.0 +36.7
TSQM: Greater overall patient satisfaction vs placebo IR, immediate-release; TSQM, Treatment Satisfaction Questionnaire for Medication. N = number of participants with TSQM results at week 12. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. Source: Valerieva A et al. EAACI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Placebo (N=8) 20 mg/daya (N=10) 40 mg/dayb (N=10) +29.8 +26.4
Deucrictibant was well tolerated at both doses GGT, gamma-glutamyltransferase; IR, immediate-release; TEAE, treatment-emergent adverse event. N = number of participants who received at least one dose of blinded study treatment. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. Source: Wedner HJ et al. ACAAI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Deucrictibant was well tolerated at both doses, and all reported treatment-related treatment-emergent adverse events (TEAEs) were mild in severity. No serious TEAEs, no severe TEAEs, and no TEAEs leading to treatment discontinuation, study withdrawal, or death were reported. Deucrictibant Adverse events Placebo (N=11) 20 mg/daya (N=11) 40 mg/dayb (N=12) Events Participants, n (%) Events, n Participants, n (%) Events, n Participants, n (%) Events, n TEAEs 7 (63.6) 16 6 (54.5) 11 7 (58.3) 12 Treatment-related TEAEs 1 (9.1) 1 2 (18.2) 2 1 (8.3) 1 Nausea 0 0 1 (9.1) 1 0 0 Increased GGT 0 0 0 0 1 (8.3) 1 Dizziness postural 0 0 1 (9.1) 1 0 0 Headache 1 (9.1) 1 0 0 0 0 Serious TEAEs 0 0 0 0 0 0 Treatment-related serious TEAEs 0 0 0 0 0 0 TEAEs leading to study drug discontinuation, study withdrawal, or death 0 0 0 0 0 0
CHAPTER-1 Part 2: open-label extension Long-term Prophylaxis Data
CHAPTER-1: Two-part, Phase 2 study of deucrictibant for long-term prophylaxis of HAE attacks HAE, hereditary angioedema; OLE, open-label extension; IR, immediate-release; R, randomization; RCT, randomized controlled trial. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. CHAPTER-1 is a Pharvaris-sponsored clinical trial. Source: NCT05047185 This presentation includes data for an investigational product not yet approved by regulatory authorities. Placebo Deucrictibant 20 mg/daya Deucrictibant 40 mg/dayb Part 1 (RCT): Double-blind treatment period (12 weeks) Screening R End-of-study visit Deucrictibant 40 mg/dayb Part 2 (OLE): Open-label treatment period Open-Label Extension (OLE) Evaluate safety (primary objective) and efficacy of deucrictibant administered for long-term prophylaxis against HAE attacks 100% of CHAPTER-1 completers continued in OLE Data from RCT and OLE also presented for RCT completers for direct comparison
CHAPTER-1: All participants who completed the RCT entered the OLE FDA, Food and Drug Administration; IR, immediate-release; OLE, open label extension; RCT, randomized controlled trial. n = number of participants. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. This presentation includes data for an investigational product not yet approved by regulatory authorities. All screened (n=44) Randomized (n=34) Placebo (n=11) 20 mg/daya (n=11) 40 mg/dayb (n=12) Screen failed (n=10) Entered OLE (n=9) Entered OLE (n=10) Entered OLE (n=11) Data cutoff: 10 June 2024 Withdrawal of consent (n=1) Study pause (n=1) Withdrawal of consent (n=1) Lost to follow-up (n=1) Completed blinded treatment period (n=9) Completed blinded treatment period (n=10) Completed blinded treatment period (n=11)
Balanced demographics and baseline characteristics BMI, body mass index; HAE, hereditary angioedema; IR, immediate-release. N = number of randomized participants; RCT, randomized controlled trial. aDeucrictibant IR capsule, 10 mg twice daily. bDeucrictibant IR capsule, 20 mg twice daily. c1 month = 4 weeks. This presentation includes data for an investigational product not yet approved by regulatory authorities. 30 participants in the OLE received deucrictibant 40 mg/day with a mean (SD) treatment duration of 12.83 (5.03) months Age (years), mean (SD) 41.4 38.4 40.8 39.1 (14.5) Sex: Male/Female, n (%) 3/8 6/5 4/8 12 (40.0) / 18 (60.0) Race: White, n (%) 11 (100) 11 (100) 12 (100) 30 (100) BMI (kg/m2), mean 26.7 29.5 25.4 27.4 HAE type, n Type 1 10 9 12 27 Type 2 1 2 0 3 Baseline monthly‡ HAE attack rate 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 monthlyc HAE attack rates, n (%) 1 to <2 attacks 6 (54.5) 7 (63.6) 7 (58.3) 18 (60.0) 2 to <3 attacks 3 (27.3) 1 (9.1) 1 (8.3) 3 (10.0) ≥3 attacks 2 (18.2) 3 (27.3) 4 (33.3) 9 (30.0) 40 mg/dayb n=12 20 mg/daya n=11 Placebo n=11 40 mg/dayb n=30 OLE RCT
Deucrictibant was well-tolerated with no new safety signals Includes participants who received at least one dose of blinded study treatment in the OLE by the cutoff date of 10 June 2024. aDeucrictibant IR capsule, 20 mg twice daily. bDeucrictibant IR capsule, 10 mg twice daily. ECG: electrocardiogram. IR: immediate-release capsule formulation of deucrictibant. OLE: open-label extension. TEAE: treatment emergent adverse event. Source: Anderson J, et al. ACAAI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Data snapshot (cutoff: 10 June 2024) included 30 participants in the OLE who received deucrictibant 40 mg/day with a mean (SD) treatment duration of 12.83 (5.03) months in the OLE Deucrictibant was well-tolerated, with one treatment-related treatment-emergent adverse event (TEAE) of tooth discoloration. No treatment-related serious or severe TEAEs and no treatment-related TEAEs in laboratory parameters, vital signs, or ECG findings No TEAEs leading to treatment discontinuation, study withdrawal, or death Adverse events Participants, n (%) Events, n Participants, n (%) Events, n Participants, n (%) Events, n Participants, n (%) Events, n TEAEs 5 (55.6) 25 7 (63.6) 31 6 (60.0) 16 18 (60.0) 72 Treatment-related TEAEs 1 (11.1) 1 0 0 0 0 1 (3.3) 1 Tooth discoloration 1 (11.1) 1 0 0 0 0 1 (3.3) 1 Serious TEAEs Tendon injury Hip arthroplasty (arthritis) 0 0 0 0 0 0 1 (9.1) 0 1 (9.1) 1 0 1 1 (10.0) 1 (10.0) 0 1 1 0 2 (6.7) 1 (3.3) 1 (3.3) 2 1 1 Treatment-related serious TEAEs 0 0 0 0 0 0 0 0 TEAEs leading to study drug discontinuation, study withdrawal, or death 0 0 0 0 0 0 0 0 40 mg/daya to 40 mg/daya (n=10) 20 mg/dayb to 40 mg/daya (n=11) Placebo to 40 mg/daya (n=9) Total (N=30)
Reduced attack rate in the RCT remained low in the OLE IR, immediate release; OLE, open-label extension; RCT, randomized controlled trial; SEM, standard error of the mean. (n) = number of patients analyzed at each timepoint. LS mean estimates of attack rate are based on Poisson regression models adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied. aBased on time normalized number of attacks per 4 weeks. b1 month = 4 weeks. cDeucrictibant IR capsule, 10 mg twice daily. dDeucrictibant IR capsule, 20 mg twice daily. Source: Anderson J, et al. ACAAI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Following early-onset reduction in attack rate with deucrictibant in the first month of the RCT, attack rate remained low during long-term (up to >1.5 years) deucrictibant 40 mg/day treatment in the OLE RCT OLE Time (monthsb) Attack ratea (mean ± SEM) Baseline 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 0 1 2 3 4 11 11 11 11 30 29 28 28 28 28 28 28 28 28 21 19 16 11 11 10 9 7 11 11 11 11 12 10 10 12 40 mg/dayd OLE (n) 40 mg/dayd RCT (n) 20 mg/dayc RCT (n) Placebo RCT (n) 40 mg/dayd OLE 40 mg/dayd RCT 20 mg/dayc RCT Placebo RCT
Continuing deucrictibant treatment sustained the early-onset attack reduction for over one year IR, immediate release; OLE, open-label extension; RCT, randomized controlled trial; SEM, standard error of the mean. (n) = number of patients analyzed at each timepoint. LS mean estimates of attack rate are based on Poisson regression models adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied. aBased on time normalized number of attacks per 4 weeks. b1 month = 4 weeks. cDeucrictibant IR capsule, 10 mg twice daily. dDeucrictibant IR capsule, 20 mg twice daily. Source: Anderson J, et al. ACAAI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. In the open-label extension up to 18 months: 93% attack rate reduction from baseline Median attack rate = 0 for every month 99% of days symptom free RCT OLE Time (months) Attack ratea (mean ± SEM) Baseline 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 0 1 2 3 4 RCT OLE Placebo (n=11) 20 mg/dayc (n=11) 40 mg/dayd (n=12) 1.94 0.40 0.30 Attack ratea (LS mean) 79.3% reduction P=0.0009 0.15 40 mg/dayd (n=30) 0.0 0.5 1.0 1.5 2.0 2.5 84.5% 93% reduction from baseline 40 mg/dayc OLE 40 mg/dayc RCT 20 mg/dayb RCT Placebo RCT reduction P=0.0008
Occurrence of moderate and severe attacks remained low in the OLE treatment period IR, immediate release; LS, least squares; OLE, open-label extension; RCT, randomized controlled trial. N = number of participants randomized in each treatment group in the RCT. N’ = number of participants in the OLE. LS mean estimates of attack rate are based on Poisson regression models adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied. The P-values in this figure are nominal. aBased on time-normalized number of attacks per 4 weeks. bDeucrictibant IR capsule, 10 mg twice daily. cDeucrictibant IR capsule, 20 mg twice daily. Source: Riedl MA et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities.
On average less than one attack per year per participant was treated with rescue medication IR, immediate release; LS, least squares; OLE, open-label extension; RCT, randomized controlled trial. N = number of participants randomized in each treatment group in the RCT. N’ = number of participants in the OLE. LS mean estimates of attack rate are based on Poisson regression models adjusted for baseline attack rate and time on treatment. No multiplicity adjustment was applied. The P-values in this figure are nominal. aBased on time normalized number of attacks per 4 weeks. bDeucrictibant IR capsule, 10 mg twice daily. cDeucrictibant IR capsule, 20 mg twice daily. Source: Riedl MA et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities.
On-Demand Program
We have renamed VAS to AMRA, reflecting its evolution from a paper-based to electronic attack assessment1 What is a Visual Analogue Scale (VAS)? Simple, reproducible, paper-based tool to allow patient self-assessment of symptom severity Analog scale with an ‘X’ hand-marked to reflect severity of attack Source: 1 CDER. Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for Purpose Clinical Outcome Assessments. FDA. June 2022. 2008–2011 Jerini-Shire Why do we need change? Addressing user experience to leverage technology and accuracy of data collection1 HAE ODT trials require frequent assessments to be recorded by participants; a digital tool is an accessible method for timely data input 2023 Pharvaris How has Pharvaris evolved the VAS to a contemporary electronic standard? Electronic Clinical Outcome Assessment (eCOA) Presents the numeric scale vertically (e.g. from ‘Worst possible’ = 100 to ‘No symptom’ = 0) Participants can see in real time the exact score (between 0 and 100) selected Performed at home Angioedema symptom Rating scAle (AMRA) A numeric rating scale requires a self- explanatory name This presentation includes data for an investigational product not yet approved by regulatory authorities.
In a real-world study using standard-of-care therapy, median time to symptom relief for PGI-C “a little better” is 0.8 h faster than AMRA-3 ≥30% reduction Source: Mendivil et al., UCARE 2023. PRO instrument Events (n) Median time to, h (95% CI) PGI-C “a little better” 90 2.147 (1.518, 3.017) AMRA-3 30% reduction from pre-treatment 89 2.990 (2.123, 4.011) Onset of symptom relief (AMRA-3 ≥30%) for deucrictibant (20mg) in RAPIDe-1 was 2.7 hours (p=0.0021) 0.843 hours This presentation includes data for an investigational product not yet approved by regulatory authorities.
RAPIDe-1 Randomized Clinical Trial (RCT) Topline Data On-demand Data
RAPIDe-1 HAE: hereditary angioedema; IR, immediate-release capsule formulation of deucrictibant. VAS: visual analog scale. Source: NCT04618211. This presentation includes data for an investigational product not yet approved by regulatory authorities. Phase 2 study of on-demand treatment of attacks in patients with HAE-C1INH-Type 1/2 R Deucrictibant IR (10 mg) Deucrictibant IR (20 mg) Deucrictibant IR (30 mg) Screening 10 mg 10 mg placebo placebo 10 mg 10 mg placebo 10 mg 10 mg PART I: STUDY SITE PART II: HOME TREATMENT 20 mg 20 mg placebo placebo 20 mg 20 mg placebo 20 mg 20 mg 30 mg 30 mg placebo placebo 30 mg 30 mg placebo 20 mg 30 mg Attack 1 Attack 2 Attack 3 Non-attack 74 HAE patients enrolled from ~30 sites in US, Canada, Europe, Israel, and UK Primary objective To evaluate angioedema symptom relief within four hours in acute attacks of patients with HAE-C1INH-Type 1/2 Study design Placebo-controlled, with three dose levels Before an attack was treated, one of the VAS-3 elements had to hit a score of ≥30 and be qualified by the clinician
Baseline characteristics BMI, body mass index; HAE, hereditary angioedema; IR, immediate release; mITT, modified intent-to-treat; VAS, visual analog scale. Source: Misra L, et al. Indian J Anaesth. 2016. This presentation includes data for an investigational product not yet approved by regulatory authorities. 10 mg (n=22) 20 mg (n=18) 30 mg (n=22) Total (n=62) Age (years), mean 42.5 44.5 41.9 42.9 Sex, n (%) Male Female 7 (31.8) 15 (68.2) 5 (27.8) 13 (72.2) 8 (36.4) 14 (63.6) 20 (32.3) 42 (67.7) Race, n (%) White Other 20 (90.9) 2 (9.1) 18 (100) 0 22 (100) 0 60 (96.8) 2 (3.2) BMI (kg/m2), mean 27.5 27.6 27.9 27.7 Time since HAE diagnosis (years), mean 21.11 21.64 23.98 22.28 HAE type, n (%) HAE-1 HAE-2 HAE-1 or HAE-2 18 4 0 15 2 1 22 0 0 55 6 1 Demographics and baseline characteristics were generally balanced between the different dose groups mITT analysis set: 62 patients with 147 attacks Safety analysis set: 73 patients with 156 attacks Deucrictibant IR dose group 10 mg (n=22) 20 mg (n=18) 30 mg (n=22) Total (N=62)
PK analysis in HAE patients confirmed rapid absorption on oral dosing, consistent with Phase 1 healthy volunteer studies HAE, hereditary angioedema; PK, pharmacokinetic. Source: Jacobs JS, et al. WSAAI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. 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
Primary endpoint: deucrictibant IR significantly reduced attack symptoms by VAS-3 at 4h *VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours; †Nominal p-value. Note: 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. 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 MMRM. Data after rescue medication use is not included. Combined deucrictibant result is based on post-hoc analysis using a similar MMRM with all three active doses combined vs placebo. IR; immediate release; LS, least squares; MRMM, mixed-effects model with repeated measures; VAS, visual analog scale. Source: Jacobs JS, et al. WSAAI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Difference from placebo in change from pre-treatment to 4 h post-treatment, LS mean (95% CI) Median time in hours (95% CI) Deucrictibant 10 mg -16.75 (-21.52, -11.97) P<0.0001† Deucrictibant 20 mg -15.02 (-20.22, -9.81) P<0.0001 Deucrictibant 30 mg -16.28 (-21.27, -11.29) P<0.0001 Combined deucrictibant -16.08 (-19.87, -12.29) Median VAS-3 at pre-treatment ranges from 24.33-27.00 across different dose levels
Deucrictibant IR significantly shortened time to onset of symptom relief (30% reduction in VAS-3) *VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours; †Nominal p-value. Note: 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 deucrictibant results are based on post-hoc analyses to provide a reference of the result by pooling all three active doses. CI, confidence interval; IR; immediate release; VAS, visual analog scale. Source: Maurer M, et al. APAAACI 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. Median time in hours (95% CI) Median time in hours (95% CI) Placebo 8.0 (7.6, 46.9) Deucrictibant 10 mg 2.1 (1.5, 2.9) P<0.0001† Deucrictibant 20 mg 2.7 (1.9, 3.5) P=0.0021 Deucrictibant 30 mg 2.5 (1.9, 3.8) P<0.0001 Combined deucrictibant 2.4 (2.0, 2.9)
Deucrictibant IR significantly reduced time to 50% reduction in VAS-3 *VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours; †Nominal p-value. Note: 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 deucrictibant results are based on post-hoc analyses to provide a reference of the result by pooling all three active doses. CI, confidence interval; IR; immediate release; VAS, visual analog scale. This presentation includes data for an investigational product not yet approved by regulatory authorities. Median time in hours (95% CI) Median time in hours (95% CI) Placebo 22.8 (20.0, 24.1) Deucrictibant 10 mg 3.3 (2.4, 3.9) P<0.0001† Deucrictibant 20 mg 4.0 (2.9, 6.0) P=0.0003 Deucrictibant 30 mg 4.0 (3.3, 5.8) P<0.0001 Combined deucrictibant 3.9 (3.0, 4.8)
In a post-hoc analysis, patients on deucrictibant achieved end of progression by VAS-3 within 25 to 26 minutes EoP: end of progression. HAE: hereditary angioedema. VAS: visual analog scale. Source: Riedl MA, et al. ACAAI 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities.
Deucrictibant IR significantly reduced time to almost complete or complete symptom relief (all individual VAS ≤10) *VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours; †Nominal p-value. Note: 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. CI, confidence interval; IR; immediate release; VAS, visual analog scale. Source: Maurer M, et al. APAAACI 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. Median time in hours (95% CI) Median time in hours (95% CI) Placebo 42.0 (22.0, 48.1) Deucrictibant 10 mg 5.8 (3.6, 7.5) P<0.0001† Deucrictibant 20 mg 20.0 (4.5, 20.0) P=0.0127 Deucrictibant 30 mg 20.0 (6.0, 20.1) P=0.0001 Combined Deucrictibant IR 7.5 (5.9, 20.0)
Patients treating with deucrictibant IR used substantially less rescue medication Note: n = The number of attacks in the mITT Analysis Set. CI, confidence interval; IR; immediate release; VAS, visual analog scale. Source: Jacobs JS, et al. WSAAI 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities.
Deucrictibant IR was well tolerated at all doses Note: 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. AE, adverse event; SAE, serious adverse event. Source: Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. No treatment-related SAEs or AEs of severe severity No AEs leading to treatment discontinuation Few treatment-related AEs reported within 48 h after administration of study drug 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%) - - - Part I (Non-Attack) Part II (Attack 1,2,3) 10 mg n=23 20 mg n=24 30 mg n=25 10 mg n=23 20 mg n=24 30 mg n=25 Placebo n=53
Greater improvement in MSCS and TOS with deucrictibant than placebo *Nominal p-value; Note: LS 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 deucrictibant result is based on post-hoc analysis using similar MMRM with all three active doses combined vs placebo. CI, confidence interval; LS mean, least-squares mean; LSMD, least-squares mean difference; MSCS, mean symptom complex severity; TOS, treatment outcome score. Source: Manning ME, et al. CIIC 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. Placebo N=51 PHVS416 10 mg N=37 PHVS416 20 mg N=28 PHVS416 30 mg N=31 Combined PHVS416* N=96 Change in MSCS score at 4 hours n 40 32 26 27 85 LS 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 (Deucrictibant – Placebo) P value -0.79 P<0.0001* -0.61 P=0.0008 -0.39 P=0.0291 -0.61 TOS at 4 hours n 40 32 25 28 85 LS 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 (Deucrictibant – Placebo) P value 64.13 P<0.0001* 62.69 P<0.0001 71.06 P<0.0001 66.05 Placebo Deucrictibant 10 mg Deucrictibant 20 mg Deucrictibant 30 mg Combined deucrictibant*
Time to symptom relief by TOS PRO demonstrated consistent efficacy at all doses *Within 48-hour assessments. KM, Kaplan-Meier; NE, not estimable; PRO, patient reported outcome; SC, symptom complex; TOS, treatment outcome score. Source: Manning ME, et al. CIIC 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. Placebo N=51 PHVS416 10 mg N=37 PHVS416 20 mg N=28 PHVS416 30 mg N=31 Combined PHVS416* N=96 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) Placebo Deucrictibant 10 mg Deucrictibant 20 mg Deucrictibant 30 mg Combined Deucrictibant*
RAPIDe-2 long-term extension data On-demand Data
RAPIDe-2 IR, immediate-release. aIncluding laryngeal attacks (without breathing difficulties). *RAPIDEe-2 is an extension of RAPIDe1, a phase 2 study of on-demand treatment of attacks in patients with HAE-C1INH-Type 1/2; †≥1 symptom with VAS score ≥30. HAE, hereditary angioedema; IR, immediate-release; VAS, visual analog scale. Source: Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Phase 2/3 LTE study of ODT of attacks in patients with HAE-C1INH-Type 1/2* Objective: To evaluate the long-term safety and efficacy of orally administered deucrictibant immediate-release capsule for the treatment of HAE attacks RAPIDe-3 participants Deucrictibant 20 mg Placebo Placebo Deucrictibant 20 mg RAPIDe-1 participants Deucrictibant 10 mg Deucrictibant 20 mg Deucrictibant 30 mg Deucrictibant 20 mg PART B: OPEN-LABEL PHASE PART A: DOUBLE-BLIND PHASE Part A enrolls adult (≥18 years) participants who completed RAPIDe-1 Participants continue self-administering the same double-blinded dose of deucrictibant IR capsule (10 mg, 20 mg, or 30 mg) received in RAPIDe-1 to treat qualifying non-laryngeal attacks†, and laryngeal attacks presenting without breathing difficulties
Study endpoints ECG, electrocardiogram; PGI-C, Patient Global Impression of Change; PGI-S, Patient Global Impression of Severity; PRO, patient-reported outcome; TEAE, treatment-emergent adverse event. Source: 1Guy W (ed). ECDEU Assessment Manual for Psychopharmacology.1976. 2Cohn DM, et al. Clin Transl Allergy. 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. Key efficacy endpoints Primary endpoint: Safety, including TEAEs, clinical laboratory tests, vital signs, and ECG findings Efficacy: Assessed using PRO tools Patient Global Impression of Change1 Patient Global Impression of Severity2 PGI-C PGI-S Much worse Worse A little worse Same A little better Better Much better Very severe Severe Moderate Mild None Onset of symptom relief PGI-C rating of at least “a little better” for 2 consecutive timepoints by 12 hours post-treatment Time to reduction in attack severity ≥1 level reduction in PGI-S from pre-treatment for 2 consecutive timepoints by 12 hours post-treatment Proportion of attacks achieving complete attack resolution PGI-S rating of “none” at 24 hours post-treatment Efficacy (PRO) assessment scales
Baseline characteristics *All participants who had ≥1 attack treated with deucrictibant and non-missing PGI-C results from ≥1 post-treatment timepoint. †All participants who received any dose of deucrictibant in the study. ‡Number by the cutoff date of 10 June 2024. BMI, body mass index; HAE, hereditary angioedema; IR, immediate-release; SD, standard deviation. aNumber by the cutoff date of 10 June 2024. Source: Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. 265 attacks from 17 participants included in the mITT efficacy analysis set (data cutoff: 01 March 2024)* Baseline characteristics consistent with the RAPIDe-1 Phase 2 trial 337 attacks from 19 participants included in the safety analysis set (data cutoff: 10 June 2024)† 7 of 337 attacks were laryngeal Number of attacks treated‡ 337 Number of participants‡ 19 Age in years, mean (SD) 42.7 (17.6) Sex: Male/female, n (%) 7 (36.8) / 12 (63.2) Race: White/other 18 / 1 BMI, mean (SD) 27.0 (3.8) Years since HAE diagnosis, mean (SD) 21.7 (15.2) HAE type, n (%) HAE-1 17 (89.5) HAE-2 2 (10.5) Deucrictibant IR capsule (All doses)
Deucrictibant was well-tolerated across all doses *Number in the safety analysis set (data cutoff: 10 June 2024). †Tooth caries unrelated to treatment.ECG, electrocardiogram; IR, immediate-release; TEAE, treatment-emergent adverse event (defined as adverse event occurring during time window from first study drug administration). Source: Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Number of attacks treated* 337 Number of participants* 19 Attacks with any TEAE, n (%) 13 (3.9) Treatment-related TEAEs, n 0 Serious TEAEs, n 1† Treatment-related serious TEAEs, n 0 TEAEs leading to study drug discontinuation, study withdrawal, or death, n 0 Deucrictibant IR capsule (All doses) TEAEs within 5 days after administration of study drug No treatment-related TEAEs No treatment-related serious or severe TEAEs, no treatment-related TEAEs in laboratory parameters, vital signs, or ECG findings No TEAEs leading to treatment discontinuation, study withdrawal, or death
PGI-C “a little better” is the RAPIDe-3 primary endpoint CI, confidence interval; IR, immediate-release; PGI-C, Patient Global Impression of Change. *Includes 10 mg, 20 mg, and 30 mg dose groups. †PGI-C rating of at least “a little better” for 2 consecutive timepoints by 12 hours post-treatment. Source: Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. 1.1 hours (95% CI, 1.0, 1.2) median time to onset of symptom relief by PGI-C† Kaplan-Meier plot of time to onset of symptom relief Proportion of attacks achieving onset of symptom relief Time (hours) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 1 2 3 4 5 6 8 12 24 48 160 49 23 16 13 9 7 4 1 0 Number at risk: 98.5% (261/265) of attacks achieved onset of symptom relief using PGI-C† by 12 hours Deucrictibant IR capsule combined dose group* Deucrictibant IR capsule combined dose group*
Rapid median reduction in attack severity at 2.6 hours: 97.7% of attacks achieved a reduction in severity by 12 hours *≥1 point reduction in PGI-S from pre-treatment for 2 consecutive timepoints by 12 hours post-treatment; †261 attacks have non-missing pre-treatment PGI-S. PGI-S, Patient Global Impression of Severity. Source: Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. 2.6 hours (95% CI, 2.0, 2.9) median time to reduction in attack severity by PGI-S* 97.7% (255/261†) of attacks achieved reduction in attack severity using PGI-S* by 12 hours
Median attack resolution time 11.5 hours: 85.8% of attacks completely resolved within 24 hours (90.2% of which with one only dose)1 *PGI-S rating of “none” at 24 hours post-treatment. †261 attacks have non-missing pre-treatment PGI-S. ‡Percentage of 224 attacks achieving complete attack resolution using PGI-S within 24 hours. IR, immediate-release; PGI-S, Patient Global Impression of Severity. Source: 1Maurer M et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. 11.5 hours (95% CI, 11.0, 13.0) median time to complete attack resolution by PGI-S1* 85.8% (224/261†) of attacks achieved complete attack resolution using PGI-S* within 24 hours1 90.2% (202/224) of attacks achieved complete attack resolution with a single dose of deucrictibant IR capsule2 Attacks treated with 1 or 2 doses of deucrictibant prior to achieving complete attack resolution2 1 dose of deucrictibant IR capsule, n (%) 2 doses of deucrictibant IR capsule, n (%) 90.2%‡ (202/224) 9.8%‡ (22/224)
Mixed-methods study: Non-interventional collection of HAE attack symptoms assessments following treatment with standard of care Note: Standard of care was icatibant or plasma derived/recombinant C1-Inhibitor. AMRA, angioedema Symptom Rating Scale; HAEA, US Hereditary Angioedema Association; PGI-C, Patient Global Impression of Change; PGI-S, Patient Global Impression of Severity. Source: Riedl MA, et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Participants recruited by HAEA PGI-C, PGI-S, and AMRA-3/ AMRA-5 data collected via mobile app At pre-treatment Every hour up to 4 hours following treatment administration Then at 8, 12, 24, and 48 hours Qualitative interviews with a subset of participants
In a propensity-score-matching analysis, deucrictibant showed favorable symptom relief outcomes versus standard of care AMRA, Angioedema syMptom Rating scAle; CI, confidence interval; IR, immediate-release; PGI-C, Patient Global Impression of Change; PGI-S, Patient Global Impression of Severity. N=73 for both cohorts. Parameters: The first 10 consecutive attacks were selected for each participant; Greedy Nearest Neighbor 1:1 matching was used with Caliper = 0.5; participants were matched for sex, age, baseline attack severity (defined by AMRA score), and exact attack primary location. Source: Riedl MA, et al. BKS 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. A PGI-C: “A little better” 1.07 (0.98, 1.89) 2.38 (1.68, 3.10) B PGI-S: ≥1 point reduction 2.14 (1.93, 2.94) 4.02 (3.15, 5.19) C PGI-C: “Better” 2.66 (1.98, 3.55) 4.49 (3.09, 6.18) RAPIDe-2 cohort (deucrictibant; N=73) Mixed-methods cohort (SOC; N=73) Time to symptom relief in hours, median (95% CI) A. Time to symptom relief defined as PGI-C "A little better" Time (hours) Proportion of attacks (%) 0 1 2 3 4 5 6 8 12 0 20 40 60 80 100 C. Time to symptom relief defined as PGI-C "Better" Time (hours) Proportion of attacks (%) 0 1 2 3 4 5 6 8 12 0 20 40 60 80 100 RAPIDe-2 study cohort (deucrictibant IR capsule) KM estimate: 2.66 (1.98, 3.55) Mixed-methods study cohort (SOC) KM estimate: 4.49 (3.09, 6.18) B. Time to reduction in attack severity defined as PGI-S ≥1 point reduction Time (hours) Proportion of attacks (%) 0 1 2 3 4 5 6 8 12 0 20 40 60 80 100 RAPIDe-2 study cohort (deucrictibant IR capsule) KM estimate: 1.07 (0.98, 1.89) Mixed-methods study cohort (SOC) KM estimate: 2.38 (1.68, 3.10) RAPIDe-2 study cohort (deucrictibant IR capsule) KM estimate: 2.14 (1.93, 2.94) Mixed-methods study cohort (SOC) KM estimate: 4.02 (3.15, 5.19)
Introduction to HAE
Locations of HAE attacks HAE: hereditary angioedema. Source: 1Zuraw BL. N Engl J Med. 2008. 2Nzeako UC, et al. Arch Intern Med. 2001. 3Lumry WR. Am J Manag Care. 2013. 4Farkas H. Allergy Asthma Clin Immunol. 2010. 5Nygren A, et al. Acta Paediatr. 2016. 6Lumry WR. Am J Manag Care. 2013. 7Agostoni A, et al. J Allergy Clin Immunol. 2004. This presentation includes data for an investigational product not yet approved by regulatory authorities. HAE Type 1 and 2 are indistinguishable in their clinical presentation,1 having identical symptoms characterized by edema of one or several organ systems2 Angioedema attacks vary in location, frequency, duration, and severity3,4 50% of patients will have ≥1 laryngeal attack in their lifetime6,7 Death may result due to airway obstruction and asphyxiation3,6,7 Asphyxia may ensue more rapidly in children than adults6 Most common attack locations3-6 FACE ABDOMEN GENITALS EXTREMITIES LARYNX Less common attack location3
Characteristics of HAE attacks *In Chinese patients, the percentage of abdominal attacks is lower (approximately 34%).6 CT: computed tomography. GI: gastrointestinal. HAE: hereditary angioedema. Source: 1Agostoni A, et al. J Allergy Clin Immunol. 2004. 2Frank MM. eMedicine. September 2010. 3Frank MM. Immunol Allergy Clin North Am. 2006. 4Bork K, et al. Am J Gastroenterol. 2006. 5Koruth JS, et al. Gastrointest Endosc. 2005. 6Liu S, et al. Eur J Dermatol. 2019. 7Bork K, et al. Am J Med. 2006. 8Lumry WR, et al. Allergy Asthma Proc. 2010. 9MacGinnitie AJ. Pediatr Allergy Immunol. 2014. 10Zuraw BL. N Engl J Med. 2008. This presentation includes data for an investigational product not yet approved by regulatory authorities. Abdominal attacks are often accompanied by vomiting and/or diarrhea4 Patients report needing 24-50 hours of bed rest per attack4 Abdominal attacks may necessitate hospitalization4 Abdominal pain is caused by edema of the mucosa at any portion of the GI tract2; it can be severe and may lead to onerous surgeries2,3 Abdominal films, CT scans, ultrasonography, or endoscopy may be useful in identifying edema of the intestinal wall1,2,5 Some patients have an erythematous, nonpruritic, non-raised rash, known as erythema marginatum2,3,9-10 Patients may first notice a sensation of tingling prior to the start of skin swelling2,39-10 Angioedema develops over several hours10 Swelling can interfere with daily functioning (e.g., inability to dress or wear shoes)11 Facial swelling may be associated with obstruction of the upper airway7 Attacks are disfiguring and disabling and may result in serious loss of function (e.g., lips too swollen to eat, swollen throat resulting in difficulty breathing)8
Triggers of HAE attacks *Medications include estrogen-containing oral contraceptives, hormone replacement therapies, ACE inhibitors.1,2 ACE, angiotensin-converting enzyme; HAE, hereditary angioedema. Source: 1Lumry WR. Am J Manag Care. 2013. 2Farkas H, et al. Allergy. 2017. 3Steiner UC, et al. Orphanet J Rare Dis. 2018. 4Caballero T, et al. J Invest Allergol Clin Immunol. 2016. This presentation includes data for an investigational product not yet approved by regulatory authorities. A number of possible attack triggers have been proposed for HAE1 Many attacks, particularly among children, occur without a clear trigger1,2 Common triggers include mechanical trauma, mental stress, and airway infection2 Dental eruption is not a common trigger but can provoke an attack in some children2 Menstruation and ovulation are common triggers in adolescent girls2 The same trigger may not always provoke an attack1 Possible triggers for HAE attacks1-4 MINOR TRAUMA EMOTIONAL STRESS HORMONAL INFLUENCES SURGERY OR DENTAL PROCEDURE EXPOSURE TO COLD CERTAIN FOODS OR MEDICATIONS* AIRWAY INFECTION HAE ATTACK
A timely and accurate diagnosis is key HAE, hereditary angioedema. Source: 1Zanichelli A, et al. Ann Allergy Asthma Immunol. 2016. 2Greve J, et al. Allergo J Int. 2022. 3Farkas H, et al. Allergy. 2017. 4Christiansen SC, et al. Clin Pediatr. 2016. 5Banerji A, et al. Allergy Asthma Proc. 2018. 6Schöffl C, et al. J Dtsch Dermatol Ges. 2019. 7Zanichelli A, et al. Clin Trans Allergy. 2018. This presentation includes data for an investigational product not yet approved by regulatory authorities. Many patients experience a delay of over 10 years from onset of symptoms to correct diagnosis1,5,6 Due its rarity and overlap of symptoms with other conditions, HAE is frequently under-recognized and misdiagnosed1,2 It often takes several years to acheive an accurate diagnosis of HAE3-5 The most common misdiagnoses are allergic angioedema and appendicitis1 Misdiagnosis is more likely to occur in patients without a family history of HAE1 Misdiagnosis or delayed diagnosis of HAE can result in mismanagement and incorrect treatment, which can have serious implications for the patient1,2 Patients without a family history of HAE may experience longer delays in diagnosis than patients with a family history6,7 Earlier onset of symptoms has been shown to be correlated with longer delays in diagnosis4 Diagnostic delays vary considerably between countries6 and according to decade of birth6,7
HAE treatment goals EAACI, European Academy of Allergy and Clinical Immunology; HAE, hereditary angioedema; LTP, long-term prophylaxis; ODT, on-demand treatment; QoL, quality of life; WAO, World Allergy Organization. Source: 1Maurer M, et al. Allergy. 2022. 2Betschel S, et al. Allergy Asthma Clin Immunol. 2019. This presentation includes data for an investigational product not yet approved by regulatory authorities. The goals of HAE treatment are to achieve complete control of the disease and to normalize patients’ lives. This can currently only be achieved by LTP. The aim of treating an attack on demand is to reduce the duration and severity of an attack, to minimize the impact of an attack on the functional ability of the patient, and reduce morbidity and potential mortality. The aim of LTP is to reduce the frequency and/or severity of attacks and minimize the impact of HAE on QoL, thereby enabling patients to live normal lives. WAO/EAACI Guidelines1 The International/ Canadian HAE Guidelines2
Not all HAE attacks are treated: physicians and patients report reasons for not treating most recent attack HAE, hereditary angioedema; ODT, on-demand therapy. Source: Mendivil J et al. ACAAI 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. 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
Current treatments vary in efficacy, leading to the need for additional healthcare resources to fully treat attacks HAE, hereditary angioedema; INH, inhibitor; pd, plasma-derived; rh, recombinant humanized. Source: 1Banerji A, et al. Allergy Asthma Proc. 2018. 2Bernstein JA, et al. J Manag Care Spec Pharm. 2020. This presentation includes data for an investigational product not yet approved by regulatory authorities. Characteristics of HAE patients utilizing on-demand treatments in 20182 Need for urgent medical care among patients with HAE-C1-INH having an attack1 89% of these patients had on-demand medication for HAE attacks Redosing rates and time to attack resolution for current on-demand treatments are sub-optimal Variable = Value, Reference (Range) rhC1-INH Icatibant Ecallantide pdC1-INH Distribution unit 2,100 U 3 mL 10 mg/mL 1 mL 10 mg/mL 500 U Distribution unit wholesale cost, $ 5,965 (5,070-6,263) 11,148 (9,475-11,705) 4,923 (4,184-5,169) 2,955 (2,512-3,103) Dosing 50 U/kg 30 mg 30 mg 20 U/kg Redosing rate, % 3 (2-10) 29 (7-44) 12 (6-18) 19 (8-30) Self-administration rate, % 95 (80-98) 100 0 95 (85-98) Time to resolution, hour 4.4 (4.0-15.0) 6.0 (2.2-24.3) 3.1 (2.8-3.8) 8.4 (6.2-21.5) Ecallantide Icatibant rhC1-INH pdC1-INH Some patients with on-demand treatment still require emergency care for HAE attacks P=0.09
Current on-demand treatments for HAE approved in the U.S. ADR, adverse drug reaction; HAE, hereditary angioedema; INH, inhibitor; ODT, on-demand treatment; pd, plasma-derived; rh, recombinant humanized. Source: 1Maurer M, et al. World Allergy Organ J. 2022. 2Riedl MA, et al. Ann Allergy Asthma Immunol. 2021. 3Tachdjian R, et al. Allergy Asthma Proc. 2024. This presentation includes data for an investigational product not yet approved by regulatory authorities. Potential injection-associated ADRs include3: Pain Bruising Extravasation Rash Vesicles Urticaria Erythema Hemorrhage Infection Incorrect route of administration Poor venous access On-demand treatment Firazyr, icatibant Berinert, pdC1-INH Ruconest, rhC1-INH Kalbitor, ecallantide Mechanism of action Bradykinin B2R antagonist C1-INH replacement C1-INH replacement Kallikrein inhibitor Administration Subcutaneous Intravenous Intravenous Subcutaneous Plasma half-life 1-2 hours >30 hours ~3 hours 2 hours RUCONEST (rhC1-INH) BERINERT (pdC1-INH) FIRAYZR (icatibant) KALBITOR (ecallantide) All recommended first-line ODTs are injectables1,2
Patients are not fully satisfied with current treatment options Source: 1Mendivil J, et al. ACAAI 2023. 2Tachdjian R, et al. Allergy Asthma Proc. 2024. 3Kelbel T. Ann Allergy Asthma Immunol. 2022. This presentation includes data for an investigational product not yet approved by regulatory authorities. … reported not being satisfied/completely satisfied with discreetness of administration, route of administration, ease of portability, and time to resolve attacks Patients also express a dislike for injections in general, while some with severe needle phobia could benefit from other therapies2,3 Patient-reported treatment satisfaction (N=48)
Self-administration and people’s ability to always carry their on-demand medication outside their home remain important unmet needs HAE, hereditary angioedema; ODT, on-demand treatment. Source: 1Radojicic C, et al. AAAAI 2023. 2Geng B, et al. ACAAI 2023. This presentation includes data for an investigational product not yet approved by regulatory authorities. 90% of patients (n=32) believe it is important or very important to recover quickly from an HAE attack Despite that, only 50% of patients carry their rescue medication with them when they leave their home1 No patients ≤24yrs (n=14) carry ODT all the time 29% of patients <40yrs (n=56) 45% of patients ≥40yrs (n=51) Patients carrying ODT all the time2
Current ODTs for HAE present a substantial burden for patients due to their difficult routes of administration *Patients used this treatment as prophylaxis and ODT; †Six percent of respondents (n=2) reported that they did not know or that the question did not apply to them. HAE, hereditary angioedema; ODT: on-demand therapy. Source: Riedl MA, et al. Ann Allergy Asthma Immunol. 2017. This presentation includes data for an investigational product not yet approved by regulatory authorities. 30% of HAE patients receiving intravenous C1 esterase inhibitor infusions via a peripheral vein voice some level of dissatisfaction* Reasons patient for dissatisfaction include time to prepare and administer Peripheral Vein Users (n=34) Patients’ impressions about intravenous C1 esterase inhibitor use (n=34) Agree, % Equally agree and disagree, % Disagree, % I can take it and feel confident I’ve administered it correctly† 79 12 3 When I take it I know I’ve infused all the medication 88 9 3 I worry about the long-term damage I’m doing to my veins 59 35 6 The length of time it takes often causes me to put off other more enjoyable things in my life 32 21 47 I often spend too much time trying to get the infusion to work while my symptoms worsen 21 21 59
Patients express a desire for alternative routes of administration, reflecting a general desire to move away from injectables Source: Radojicic C, et al. Allergy Asthma Proc. 2021. This presentation includes data for an investigational product not yet approved by regulatory authorities. Survey of patients with HAE: Satisfaction and unmet needs (N=75) 86% Patients who reported being satisfied with their prophylactic treatment but are interested in a medication that is easier to administer 61% Patients who wished they could treat their HAE more discreetly
Both doctors and patients consider an oral acute therapy would increase likelihood that patients would treat more attacks, earlier Note: Percentages may not sum to 100 due to rounding. Source: 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.
For both patients on prophylaxis or on-demand therapy, switching treatment is moderately easy for HCPs1 *Based on HCPs experience, considering all the barriers there may be from an access/coverage and clinical perspective. Source: 1Company Research (October 2024). Switching barriers Base: Total U.S. HCPs (N=88)1. LTP ODT Ease of switching Tx* (% selected; 1=not easy at all to 10=very easy) Mean /10 Change in brand of ACUTE therapy Change in brand of PROPHY therapy 6.2 6.1 HCPs would feel comfortable switching therapy after at least 6 months on current treatment This presentation includes data for an investigational product not yet approved by regulatory authorities.
Efficacy is prime for HCPs, but patient preference drives choice for oral administration1 Source: 1Company Research (October 2024). This presentation includes data for an investigational product not yet approved by regulatory authorities. HCPs top reasons for selecting a therapy (current users, n = 216) Efficacy 44% Convenience of dosing frequency 30% Convenience of administration 28% Insurance coverage/cost 27% Patient’s preference 27% Patient preference or request for prophylactic route of administration based on HCPs experience (current users, n = 216) Oral (preferred over injection) 38% Subcutaneous injection (preferred over oral) 18% No preference/request 46% Efficacy remains the first driver for HCP preference Dosing frequency and route of administration play less of decisive role in HCP preference and are at par with patients’ preference Nearly 40% of patients actively request or prefer an oral LTP Less than 20% would prefer or request an injection
I prefer the CONVENIENCE of an ORAL ON-DEMAND therapy, even if EFFICACY IS LOWER than injectable routes of administration (IV or subcutaneous) I prefer the MOST EFFECTIVE ON-DEMAND therapy available, even if the route of administration is an INJECTABLE I prefer the CONVENIENCE of an ORAL PROPHYLACTIC therapy, even if EFFICACY IS LOWER than injectable routes of administration (IV or subcutaneous) I prefer the MOST EFFECTIVE PROPHYLACTIC therapy available, even if the route of administration is an INJECTABLE Efficacy vs. Convenience trade-off Base: Total U.S. Patients (N=94); excluding those not on prophylaxis and unlikely to start (N=87)1. But people living with HAE are not willing to trade off efficacy for the convenience of an oral therapy1 LTP ODT Notes: ODT: on-demand therapy. LTP: long-term prophylaxis. Source: 1Company Research (October 2024). An oral therapy with injectable-like efficacy has the potential to become the preferred option for patients This presentation includes data for an investigational product not yet approved by regulatory authorities.
Despite high compliance on novel therapies, including Orladeyo®, breakthrough attacks are still common with nearly 3 attacks per year1 Total TAKHZYRO® CINRYZE® ORLADEYO® HAEGARDA® DANOCRINE® Base: current users 216 83 22 55 46 *10 Compliance High 65% 64% 50% 71% 70% 60% Medium 33% 35% 50% 27% 28% 30% Low 2% 1% 0% 2% 2% 10% Number of attacks in the past 6 months Average # attacks (total treated or not) 1.4 1.6 1.6 1.7 1.4 0.9 % pts with 1+ attack (total treated or not) 66% 64% 77% 79% 59% 60% Average # attacks resulting in ER visit 0.4 0.4 0.8 0.3 0.7 0.3 % pts with 1+ attack resulting in ER visit 34% 27% 59% 26% 58% 33% Base: Total U.S. HCPs (N=88)1. Notes: *small base size for DANOCRINE. Source: 1Company Research (October 2024). This presentation includes data for an investigational product not yet approved by regulatory authorities.