Question-and-Answer SessionSo just to kick things off, could you set the stage by walking us through deucrictibant's value proposition across both acute and prophylactic treatment of hereditary angioedema.Berndt A. ModigCo-Founder, CEO & Executive Director Yes. Thanks, Max, and great to be here again. So deucrictibant being an oral therapy option is -- fulfills a very specific unmet need in this space that we've seen over the years. And so that's a key feature, of course, the oral aspect of it. And you expe ...

Summary of Conference Call on Pharvaris and Deucrictibant Company and Industry Overview - **Company**: Pharvaris - **Industry**: Hereditary Angioedema (HAE) Treatment Key Points and Arguments 1. **Deucrictibant's Value Proposition**: Deucrictibant is an oral therapy that addresses a significant unmet need in HAE treatment, combining oral convenience with high efficacy comparable to injectable therapies [1][2] 2. **Treatment Segments**: The prophylactic treatment segment has grown to approximately 67% of the population and 80% of the market value, while the on-demand segment remains viable due to its flexibility [3][4] 3. **Patient-Centric Approach**: The choice between prophylactic and on-demand treatment is highly individualized, influenced by patient preferences and anxiety levels regarding attacks [5][6] 4. **Mechanism of Action**: Deucrictibant is unique as it is the only therapy with formulations for both prophylactic and on-demand use, acting as a bradykinin B2 receptor antagonist [9][10] 5. **Phase 3 Trials**: The timeline for the RAPIDe-3 Phase 3 trial has been moved up to Q4 2025, with expectations of strong efficacy and safety data based on Phase 2 results [11][17] 6. **Efficacy Metrics**: In Phase 2 trials, deucrictibant showed an 87% reduction in attacks compared to placebo, with 49% of patients experiencing zero attacks [21][22] 7. **Market Opportunity**: There are approximately 150 to 300 new HAE patients diagnosed annually, with a significant portion expressing dissatisfaction with current treatments, indicating a strong market opportunity for deucrictibant [25][26] 8. **Regulatory Milestones**: The FDA has accepted TQT waivers for both formulations of deucrictibant, which will streamline the regulatory process and reduce costs [30][32] 9. **Financial Position**: Pharvaris reported around $200 million in cash, extending its runway to the first half of 2027, with plans for a U.S. sales and marketing infrastructure [40][41] 10. **Future Developments**: Pharvaris plans to initiate trials for acquired angioedema and aims for a broad label for deucrictibant, targeting not just type 1 and 2 angioedema [36][37] Additional Important Insights - **Patient Satisfaction**: A survey indicated that 67% of patients are not satisfied with their current treatment, highlighting the demand for more effective options [25] - **Competitive Landscape**: The company is closely monitoring competitors and the evolving market dynamics, particularly in the context of pricing and payer expectations [28][29] - **AI Utilization**: Pharvaris is exploring the use of AI for data analysis and medical writing, indicating a forward-looking approach to technology integration [43] - **Regulatory Interactions**: Positive interactions with the FDA have been reported, with no major concerns regarding tariffs or regulatory changes impacting the company [45][46]

Group 1 - Pharvaris is developing deucrictibant, a promising molecule for Hereditary Angioedema (HAE) [2] - The presentation features key executives from Pharvaris, including CCO Wim Souverijns and CMO Peng Lu [1] - The session aims to provide insights into the current state of affairs at Pharvaris and engage in a Q&A format [2]

Core Insights - Pharvaris is making significant progress in addressing unmet needs for patients with bradykinin-mediated angioedema, with key clinical trials and financial updates indicating a strong operational focus [2][3][4] Financial Performance - As of June 30, 2025, the company reported cash and cash equivalents of €200 million, a decrease from €281 million at the end of 2024 [11] - The company incurred a loss of €45.5 million for the second quarter of 2025, resulting in a basic and diluted loss per share of €0.83, compared to a loss of €29.7 million or €0.55 per share in the same quarter of 2024 [16] Development Pipeline - Topline results for the pivotal Phase 3 study RAPIDe-3, evaluating deucrictibant for on-demand treatment of HAE attacks, are expected in the fourth quarter of 2025 [3][4] - Enrollment is ongoing for CHAPTER-3, another pivotal Phase 3 study for prophylaxis against HAE attacks, with topline results anticipated in the second half of 2026 [3][4] - The CREAATE study, focusing on prophylactic and on-demand treatment of AAE-C1INH attacks, is on track to initiate by the end of 2025 [3][4] Recent Business Updates - The company successfully closed a public offering raising approximately $201 million in July 2025, which will extend its cash runway into the first half of 2027 [6] - Recent presentations at medical congresses highlighted clinical data supporting deucrictibant's potential to meet the needs of patients with bradykinin-mediated angioedema [5] Corporate Strategy - Pharvaris aims to maintain financial discipline while conducting multiple global Phase 3 studies, which is crucial for the successful development of deucrictibant [2][3] - The company is exploring the potential expansion of treatment applications for bradykinin B2 receptor antagonism, indicating a strategic focus on addressing broader unmet medical needs [3]

Company Overview - Pharvaris N.V. is a late-stage biopharmaceutical company focused on developing novel, oral bradykinin B2 receptor antagonists to address unmet needs in bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) [1][5] - The company aims to provide injectable-like efficacy and placebo-like tolerability with the convenience of oral therapies for the prevention and treatment of bradykinin-mediated angioedema attacks [5] Recent Financial Activity - Pharvaris announced the closing of an upsized underwritten public offering of 9,562,500 ordinary shares, which includes the full exercise of an option by underwriters to purchase an additional 1,312,500 ordinary shares, along with pre-funded warrants to purchase 500,000 ordinary shares [1] - The gross proceeds from this offering amounted to approximately $201.2 million before deducting underwriting discounts, commissions, and other offering expenses [1] Clinical Development - Pharvaris is currently evaluating the efficacy and safety of its drug, deucrictibant, in pivotal Phase 3 studies for both the prevention of HAE attacks (CHAPTER-3) and the on-demand treatment of HAE attacks (RAPIDe-3) [5]

Investment Rating - The report indicates a positive investment outlook for the hereditary angioedema (HAE) treatment sector, particularly following the approval of the first oral on-demand treatment, sebetralstat [14][21]. Core Insights - The report highlights the urgent need for effective HAE treatments due to the high risk of life-threatening episodes, with nearly half of HAE patients facing potential asphyxiation [10][16]. - Sebetralstat, approved by the FDA, is noted for its rapid onset of action, achieving near-complete inhibition of plasma kallikrein within 15 minutes of administration [21]. - The KONFIDENT trial results demonstrate that sebetralstat significantly reduces symptom relief time compared to placebo, with median relief times of 1.61 hours for the 300 mg dose and 1.79 hours for the 600 mg dose [20][21]. Summary by Sections Section 1: HAE Overview - HAE is characterized by recurrent episodes of angioedema without urticaria, with a prevalence of approximately 1.5 per 100,000 individuals [7]. - The disease can lead to severe complications, including laryngeal edema, which has a mortality rate of up to 40% among patients [7][10]. Section 2: Current Treatment Landscape - Existing treatments include long-term preventive therapies (LTP) and on-demand treatments for acute episodes [10][11]. - The global HAE drug market reached $2.9 billion in 2022, with $2 billion attributed to long-term prevention and $900 million to acute on-demand treatments [13]. Section 3: Sebetralstat Approval and Efficacy - Sebetralstat is the first oral on-demand treatment for HAE, approved on July 7, 2025, and is expected to address unmet needs in the treatment landscape [21]. - The KONFIDENT trial, involving 136 patients across 20 countries, confirmed the efficacy and safety of sebetralstat, showing significant improvements in symptom relief and severity reduction compared to placebo [21]. Section 4: Future Developments - Pharvaris is developing deucrictibant, a competitive oral antagonist for HAE, with promising Phase II trial results indicating effective management of HAE attacks [26]. - The report anticipates further advancements in HAE treatments, with ongoing clinical trials expected to yield additional data in the coming years [26].

Core Viewpoint - Pharvaris is advancing its late-stage development of deucrictibant, an oral bradykinin B2 receptor antagonist, targeting unmet needs in bradykinin-mediated diseases, with topline data from the RAPIDe-3 Phase 3 study expected in Q4 2025 and a potential NDA submission in H1 2026 [1][2][4] Group 1: Study and Data - The RAPIDe-3 study has achieved target enrollment, and the topline data announcement is now anticipated in the fourth quarter of 2025 [2] - The study evaluates deucrictibant immediate-release capsules (20 mg) for on-demand treatment of angioedema attacks in approximately 120 participants aged 12 and older, including those with C1 inhibitor deficiency [2][3] - Primary endpoints include time to onset of symptom relief and other measures of symptom resolution and safety [2][3] Group 2: Drug Development - Deucrictibant is being developed in two formulations: an extended-release tablet for prophylactic treatment and an immediate-release capsule for rapid treatment [3][4] - The drug has received orphan drug designation from the FDA and the European Commission for treating bradykinin-mediated angioedema [3] Group 3: Company Overview - Pharvaris aims to provide injectable-like efficacy and placebo-like tolerability through oral therapies for bradykinin-mediated angioedema [4] - The company is conducting multiple pivotal Phase 3 studies, including CHAPTER-3 for prevention and RAPIDe-3 for on-demand treatment of HAE attacks [4]

Core Insights - Pharvaris is advancing its late-stage development of deucrictibant, an oral bradykinin B2 receptor antagonist, aimed at treating bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) [1][14] - The company presented data at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025, highlighting the efficacy and safety of deucrictibant in both prophylactic and on-demand treatment settings [2][5] Prophylaxis - The CHAPTER-1 open-label extension study demonstrated long-term safety and efficacy of oral deucrictibant for prophylaxis in HAE, with participants experiencing sustained attack reduction and improved health-related quality of life (HRQoL) [5][6] - All participants reported clinically meaningful improvements in HRQoL, maintained up to week 62 of the study [5] - The ongoing CHAPTER-3 Phase 3 study is designed to evaluate the efficacy and safety of a once-daily, oral deucrictibant extended-release tablet for HAE prophylaxis [5][4] On-Demand Treatment - The RAPIDe-2 extension study provided evidence of the long-term safety and efficacy of oral deucrictibant for treating HAE attacks, with a median time to onset of symptom relief of 1.1 hours and 97.8% of attacks achieving symptom relief within 12 hours [10][7] - Deucrictibant was well tolerated, with no treatment-related adverse events reported, and 89.2% of attacks that achieved symptom resolution at 24 hours were treated with a single dose [10][8] - The RAPIDe-3 study is the first Phase 3 on-demand study to explore 'end-of-progression' as a new pre-specified endpoint, which is significant for HAE patients [2][5] Expansion Beyond HAE - Pharvaris is exploring the potential of deucrictibant beyond HAE, with ongoing studies validating a novel kinin biomarker assay for characterizing bradykinin-mediated pathologies [9][16] - A real-world survey indicated that patients prescribed long-term prophylaxis (LTP) experienced more mild attacks and better HRQoL compared to those on on-demand treatment (ODT) alone, supporting the importance of both treatment modalities in HAE management [10]

Core Viewpoint - Pharvaris is advancing its late-stage development of deucrictibant, a novel oral bradykinin B2 receptor antagonist, aimed at addressing unmet needs in bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) [1][2] Recent Business Updates - Pharvaris plans to host an R&D-focused update on June 4, 2025, to discuss the pathophysiology of bradykinin-mediated angioedema and the company's approach to addressing unmet needs [3] - The company is currently enrolling participants in two pivotal Phase 3 studies: CHAPTER-3 for prophylaxis against HAE attacks and RAPIDe-3 for on-demand treatment of HAE attacks [5][6] - Pharvaris has received TQT study waivers from the FDA for both the extended-release and immediate-release formulations of deucrictibant, indicating no evident effect on cardiovascular parameters [6] Financials - As of March 31, 2025, the company reported cash and cash equivalents of €236 million, down from €281 million at the end of 2024 [13] - Research and Development (R&D) expenses for Q1 2025 were €30.9 million, compared to €18.5 million in Q1 2024, while General and Administrative (G&A) expenses increased to €11.3 million from €9.8 million [13] - The loss for the first quarter of 2025 was €46.3 million, resulting in a basic and diluted loss per share of €0.85, compared to a loss of €28.0 million or €0.52 per share in Q1 2024 [13] Upcoming Events - Pharvaris will participate in the 46th Annual Goldman Sachs Global Healthcare Conference from June 9-11, 2025, with a fireside chat scheduled for June 11 at 4:00 p.m. ET [7]

Core Insights - Pharvaris is expanding the potential treatment applications of deucrictibant for individuals with bradykinin-mediated angioedema, including hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor deficiency [1][2] - The company will host a virtual R&D call to discuss the pathophysiology, prevalence, current treatment paradigms, unmet needs, and the potential of deucrictibant [2] - Pharvaris aims to provide injectable-like efficacy and placebo-like tolerability through an oral therapy for bradykinin-mediated angioedema attacks [3] Company Overview - Pharvaris is a late-stage biopharmaceutical company focused on developing oral bradykinin B2 receptor antagonists to address various types of bradykinin-mediated angioedema [3] - The company is currently conducting pivotal Phase 3 studies to evaluate the efficacy and safety of deucrictibant for both the prevention and on-demand treatment of HAE attacks [3] Event Details - The virtual event titled "Deucrictibant: Beyond HAE Type 1/2" is scheduled for June 4, 2025, at 8:00 a.m. ET/14:00 CET [1][2] - Registration for the live webcast is available on the company's website, with an archived replay accessible for at least 30 days post-event [2]