Financial Performance and Funding - The company has generated no revenues to date and has incurred significant losses since inception, with expectations of continued losses over the next several years[42]. - The company may need to raise substantial additional funding to continue operations, which could lead to dilution of existing shareholders[49]. - The market price of the company's ordinary shares is likely to be highly volatile, and there is no current intention to pay dividends[42]. - Significant shareholders beneficially owned approximately 56.41% of the outstanding ordinary shares as of April 1, 2025[229]. - The company does not currently intend to pay cash dividends on its ordinary shares in the foreseeable future[231]. - An active trading market for the company's ordinary shares may not be sustainable, potentially impairing future capital raising efforts[228]. Product Development and Clinical Trials - The company is heavily dependent on the success of its product candidates, specifically the extended-release and immediate-release formulations of deucrictibant, which are in late-stage development[42]. - Topline data from the RAPIDe-1 study demonstrated efficacy in the Phase 2 clinical trial for treatment of HAE attacks on demand using deucrictibant IR[42]. - The company has established proof-of-concept for deucrictibant in Phase 2 trials for both treatment and prophylaxis of HAE attacks, but future clinical trials may not replicate these results[63]. - The FDA lifted clinical holds on deucrictibant for on-demand and prophylactic treatment of HAE in June 2023 and January 2024, respectively, but future challenges may arise[64]. - The company has completed Phase 2 trials for on-demand and prophylactic settings, providing critical data for late-phase clinical trials[86]. - The company is developing an extended-release formulation for deucrictibant, with plans for multiple dose studies to assess pharmacokinetics and safety[79]. - The company has not yet received regulatory approval for any drugs and may face significant delays in the commercialization of its product candidates[71]. - The company has not submitted any marketing authorization applications for its product candidates, which must include extensive nonclinical and clinical data to establish safety and effectiveness[72]. - The company faces risks in clinical trials, including failure to obtain necessary approvals and potential negative results, which could lead to additional trials or abandonment of product development[73]. - The company may experience setbacks in clinical trials, including delays in commencing or completing trials, which could materially affect its business[42]. Regulatory and Compliance Risks - The company identified material weaknesses in its internal control over financial reporting as of December 31, 2023, which were concluded to be remediated by December 31, 2024[52]. - The company is subject to taxation in multiple jurisdictions, including the Netherlands, Switzerland, and the United States, which may lead to variable effective income tax rates[57]. - The OECD's Global Anti-Base Erosion Model Rules aim to impose a global minimum tax of 15% on multinational enterprises with revenue exceeding €750 million, which could impact the company if revenue thresholds change[60]. - The EU Pillar II Directive, adopted on December 15, 2022, requires member states to implement minimum tax measures starting from fiscal years beginning on or after December 31, 2023[61]. - The company is subject to extensive regulations for clinical trials and marketing, requiring authorization from appropriate regulatory authorities[89]. - Regulatory disruptions at agencies like the FDA and EMA could hinder the approval process for new products[78]. - The company acknowledges that clinical trials may not uncover all possible adverse effects, leading to potential safety concerns post-approval[83]. - The company may face significant delays in obtaining marketing approvals in the United Kingdom due to Brexit, which could restrict revenue generation and profitability[94]. - The company faces challenges in conducting animal testing due to regulatory and public pressures, potentially impacting research and development activities[88]. - The company may experience delays in patient enrollment for clinical trials, which could increase development costs and delay regulatory approvals[81]. Manufacturing and Supply Chain Risks - The company does not own manufacturing facilities and relies on third-party CDMOs, which may affect its ability to supply sufficient product candidates[110]. - The company currently relies on a small number of CDMOs for production, which poses risks to manufacturing operations and could adversely affect business and financial results[111]. - Manufacturing process changes may require repeating trials or conducting additional trials, potentially delaying marketing approval[112]. - Development of in-house manufacturing facilities could enhance control over material supply, but the company lacks experience in this area[113]. - Dependence on third-party manufacturers may adversely affect future profit margins and timely commercialization of products[114]. - Manufacturing challenges may arise during scale-up, leading to increased costs or delays in regulatory approval[115]. - The company relies on third-party manufacturers who are also subject to environmental and safety regulations, which could impact business operations[221]. Competition and Market Risks - The company faces substantial competition from major pharmaceutical and biotechnology companies, which may hinder its ability to commercialize its product candidates successfully[137]. - The commercial success of the company's product candidates will depend significantly on market acceptance among physicians, patients, and healthcare payors[135]. - Market opportunities for product candidates may be smaller than anticipated, potentially lowering revenue projections[130]. - The company anticipates pricing pressures due to the increasing availability of generic products and cost-containment initiatives by insurers[138]. - The insurance coverage and reimbursement status for newly approved products remains uncertain, which could limit the company's ability to generate revenue[145]. - Governments and pricing authorities, especially in the European Union, impose strict price controls that may adversely affect future profitability[143]. Intellectual Property Risks - The company is exposed to risks related to the enforcement of its intellectual property rights, which could lead to potential litigation and impact its ability to protect its technologies[172]. - The patent protection for the company's products may not be sufficiently broad, which could allow competitors to develop similar products and adversely affect the company's market position[170]. - The company may not be able to secure necessary patent rights or maintain existing patents, which could limit its ability to compete effectively in the market[175]. - The duration of patent protection is limited, with U.S. patents generally expiring 20 years after the effective filing date, which could impact the company's long-term competitive advantage[178]. - The company faces risks related to the expiration of patents for product candidates, which may leave it vulnerable to competition from biosimilars or generics[181]. - Future patents may be challenged in court, potentially leading to loss of exclusivity or invalidation, which could adversely affect the company's competitive position[182]. - The company may not be able to protect its intellectual property rights in all jurisdictions, limiting its ability to prevent third parties from using its inventions[184]. - Changes in patent laws, such as those introduced by the America Invents Act, could weaken the company's ability to obtain and enforce patent protection[189]. - The company may face significant costs and distractions from potential litigation regarding intellectual property rights, which could impact its financial condition[197]. - There is a risk of infringing third-party intellectual property rights, which could result in costly litigation and affect the company's ability to commercialize its product candidates[194]. Operational and Management Risks - The company may encounter ownership disputes related to intellectual property, which could result in litigation and loss of valuable rights[196]. - The company faces challenges in attracting and retaining qualified management and scientific personnel, which is crucial for the successful development and commercialization of its product candidates[162]. - The company may struggle to enter into or maintain strategic alliances necessary for the commercialization of its product candidates, facing competition from other companies and institutions[167]. - The company may face significant product liability claims, which could result in substantial financial liabilities[151]. - The company’s business operations may be subject to significant costs associated with compliance with health care laws, which could lead to penalties and impact financial results[213]. - Rapid technological changes in the pharmaceutical industry could render the company’s product candidates obsolete, adversely affecting financial condition and prospects[215]. - The company’s international operations are subject to various economic, political, and regulatory risks, including differing drug approval requirements and intellectual property protections[216]. - Failure to achieve projected development goals may delay product commercialization, potentially leading to a decline in stock price[219]. Environmental and Legal Risks - The company is subject to extensive environmental, health, and safety laws and regulations, which may lead to significant compliance costs and liabilities[222]. - Misconduct by employees or third parties could result in significant administrative, civil, and criminal fines, adversely affecting the company's reputation and financial condition[224]. - The company may face increased restrictions and compliance costs related to changing legal or regulatory requirements, impacting production and development efforts[222]. - There is no certainty that all employees and collaborators will comply with applicable laws, potentially leading to significant legal and financial repercussions[227]. - The company faces risks related to the handling of sensitive patient data, which is subject to stringent privacy laws[121]. - Non-compliance with GDPR could result in fines up to €20 million or 4% of total worldwide annual turnover, whichever is higher[124].

Core Insights - Pharvaris has received orphan designation from the European Commission for its investigational drug, deucrictibant, aimed at treating bradykinin-mediated angioedema [1][3] - The U.S. FDA had previously granted orphan drug designation to deucrictibant in March 2022 [2] - The company is currently executing a Phase 3 development program to evaluate the efficacy and safety of deucrictibant in hereditary angioedema (HAE) [3][5] Company Overview - Pharvaris is a late-stage biopharmaceutical company focused on developing oral bradykinin B2 receptor antagonists to address bradykinin-mediated diseases [1][5] - The company aims to provide injectable-like efficacy with the convenience of oral therapy for preventing and treating angioedema attacks [5] - Deucrictibant is being developed in two formulations: an extended-release tablet for sustained absorption and an immediate-release capsule for rapid onset of action [4] Clinical Development - Pharvaris is conducting pivotal Phase 3 studies for both the prevention of HAE attacks (CHAPTER-3) and the on-demand treatment of HAE attacks (RAPIDe-3) [5] - The company is also in discussions with regulators regarding a pivotal trial for acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) [3]

Core Insights - Pharvaris is advancing its late-stage development of deucrictibant, an oral bradykinin B2 receptor antagonist aimed at treating hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) [1][10] - Recent presentations at the AAAAI/WAO Joint Congress highlighted positive safety and efficacy data from pivotal Phase 3 studies, indicating a median of zero days with attack symptoms per month for participants on long-term prophylactic treatment [2][4] Prophylactic Program - The CHAPTER-1 Open-Label Extension study involved 30 participants receiving deucrictibant 40 mg/day for an average of 12.8 months, with a maximum exposure of 20.8 months [3] - Participants in the OLE experienced sustained protection from HAE attacks, with a median proportion of days with symptoms being zero each month [4][6] - Health-related quality of life (HRQoL) measures showed significant improvements, particularly in "functioning" and "fear/shame" domains [5][6] On-Demand Program - The RAPIDe-2 extension study evaluated the long-term safety and efficacy of deucrictibant for on-demand treatment of HAE attacks, with data from 337 attacks, including seven upper airway attacks [7] - The median time to onset of symptom relief was 0.9 hours for upper airway attacks, consistent with 1.1 hours for non-airway attacks [7][6] - Deucrictibant was well-tolerated in both extension studies, with no safety signals observed [6][7] Product Overview - Deucrictibant is being developed in two formulations: an extended-release tablet for prophylactic treatment and an immediate-release capsule for on-demand treatment [9][10] - The company aims to provide injectable-like efficacy with the convenience of an oral therapy for HAE attacks [10]

Company Overview - Pharvaris 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) [2] - The company aims to provide injectable-like efficacy and placebo-like tolerability with the convenience of an oral therapy for the prevention and treatment of HAE attacks [2] Clinical Development - Pharvaris is currently evaluating the efficacy and safety of its drug, deucrictibant, in pivotal Phase 3 studies: one for the prevention of HAE attacks (CHAPTER-3) and another for the on-demand treatment of HAE attacks (RAPIDe-3) [2] Upcoming Events - Pharvaris management will participate in the Leerink Partners Global Healthcare Conference 2025, scheduled for March 10-12, 2025, in Miami, FL [1] - CEO Berndt Modig will be featured in a fireside chat on March 10 at 9:20 a.m. ET, with a live audio webcast available on the company's website [1]

Financial Data and Key Metrics Changes - The company reported having €5 million in cash as of September 24, which is expected to provide a cash runway into the third quarter of 2026, beyond the readout of the on-demand phase three study [43]. Business Line Data and Key Metrics Changes - The company is developing ducriptaban, a novel oral bradykinin B2 receptor antagonist, for both on-demand and prophylactic treatment of hereditary angioedema (HAE) [2][4]. - Phase two data showed that ducriptaban achieved an 85% reduction in attacks compared to placebo, with over 90% reduction in moderate to severe attacks requiring rescue medication [27][30]. Market Data and Key Metrics Changes - In the U.S. market, approximately 65% of HAE patients are currently on prophylaxis, with expectations that this could increase to 70-80% with the introduction of an oral option [32]. - The European market is slower in adopting prophylactic therapies, but countries like Germany and France are expected to catch up soon [10][11]. Company Strategy and Development Direction - The company aims to provide innovative oral therapies for both on-demand and prophylactic treatment, addressing the need for convenience and efficacy in HAE management [7][14]. - The strategy includes capturing a broader patient base globally, beyond just the U.S. and Western Europe, by offering oral therapies [11]. Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming oral therapies penetrating the market, highlighting the significant unmet need in the HAE community [13][14]. - The company anticipates growth in both prophylactic and on-demand markets, driven by the ease of administration and efficacy of their oral product [33]. Other Important Information - The company is also exploring opportunities in acquired angioedema, which is a different patient population but shares similar physiological responses to HAE [48][49]. - The company plans to release more data regarding efficacy, safety, and quality of life from ongoing studies in 2025 [45]. Q&A Session Summary Question: What is the opportunity in acquired angioedema? - The acquired angioedema population is estimated to be about 10% on top of type one and type two HAE, with a high unmet medical need and potential for commercial opportunity [48][49]. Question: How does the company plan to manage recruitment for the acquired angioedema study? - The company is optimistic about recruitment, noting a strong desire among patients to join clinical trials due to the lack of available treatments [58].

Core Insights - Pharvaris is focused on advancing the clinical development of deucrictibant, a novel oral bradykinin B2 receptor antagonist, to address unmet needs in bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema (AAE) [1][11] Strategic Priorities for 2025 - The company aims to execute two pivotal Phase 3 clinical studies for HAE, specifically RAPIDe-3 for on-demand treatment and CHAPTER-3 for prophylaxis, with topline data expected in 1Q2026 and 2H2026 respectively [2][4] - Pharvaris plans to expand its pipeline into AAE, with the initiation of a clinical study for acquired angioedema due to C1-INH deficiency anticipated in 2025 [3][6] - The company is operating from a strong financial position, with an estimated cash runway extending into 3Q2026 [3] Clinical Development Updates - RAPIDe-3 is a global Phase 3 study evaluating deucrictibant for the on-demand treatment of HAE attacks, targeting approximately 120 participants, with primary efficacy endpoints focused on symptom relief [2][5] - CHAPTER-3 is a randomized, double-blind, placebo-controlled Phase 3 study for prophylaxis against HAE attacks, aiming to enroll about 81 participants and evaluate the efficacy of deucrictibant compared to placebo [4] - An open-label extension study, CHAPTER-4, is set to initiate in 1Q2025 to further evaluate the long-term efficacy and tolerability of deucrictibant [4] Business Updates - The company has expanded its team to support the launch of deucrictibant, with new appointments in sales, marketing, and business development [8] - Pharvaris presented data on HAE treatment experiences and unmet needs at recent medical congresses, highlighting the demand for novel oral therapies [8] - Upcoming presentations at investor conferences and medical congresses are scheduled, including participation in the J.P. Morgan Healthcare Conference [9][13]

Core Insights - Pharvaris is advancing the clinical development of deucrictibant, a novel oral bradykinin B2 receptor antagonist, for the prevention and treatment of hereditary angioedema (HAE) attacks [1][9] - The company plans to initiate the pivotal Phase 3 study, CHAPTER-3, for prophylactic treatment of HAE by the end of 2024 [1][3] - Recent presentations at medical congresses highlighted positive long-term extension data for deucrictibant, reinforcing its differentiated profile and potential efficacy [2][3] Clinical Development Updates - CHAPTER-3 is a randomized, double-blind, placebo-controlled Phase 3 study aimed at enrolling approximately 81 participants aged 12 years and older, with a primary endpoint focused on the efficacy of deucrictibant compared to placebo [3] - Enrollment in the RAPIDe-3 study, a global pivotal Phase 3 study for on-demand treatment of HAE, is progressing as planned with a target of approximately 120 participants [3] - Long-term prophylaxis data from the CHAPTER-1 OLE study showed a 93% reduction in attacks compared to baseline, while the RAPIDe-2 OLE study indicated a median onset of symptom relief in approximately 1.1 hours [3][4] Financial Position - As of September 30, 2024, the company reported cash and cash equivalents of €305 million, down from €391 million at the end of 2023 [6] - Research and Development expenses for Q3 2024 were €25.8 million, an increase from €18.5 million in Q3 2023, while General and Administrative expenses rose to €12.1 million from €7.7 million in the same period [6] - The company reported a loss of €41.7 million for Q3 2024, with a basic and diluted loss per share of €0.77, compared to a loss of €23.6 million and a loss per share of €0.58 in Q3 2023 [6] Future Plans - The company intends to expand the clinical development of deucrictibant into acquired angioedema due to C1-INH deficiency (AAE-C1INH) following promising data from an investigator-initiated trial [4] - Upcoming investor events include participation in the Evercore ISI's 7th Annual HealthCONx Conference and the Oppenheimer Movers in Rare Disease Summit [5]

Core Insights - Pharvaris is a late-stage biopharmaceutical company focused on developing oral bradykinin B2 receptor antagonists for the prevention and treatment of hereditary angioedema (HAE) attacks [2] Group 1: Company Overview - Pharvaris aims to provide effective, well-tolerated, and easy-to-administer treatment alternatives for HAE patients, both on-demand and prophylactically [2] - The company is currently enrolling a pivotal Phase 3 study for the on-demand treatment of HAE attacks and plans to initiate another pivotal Phase 3 study for prevention by the end of 2024 [2] Group 2: Upcoming Events - Pharvaris management will participate in the Inaugural Guggenheim Securities Healthcare Innovation Conference from November 11-13, 2024, with a fireside chat scheduled for November 13 at 9:30 a.m. ET [1] - A live audio webcast of the event will be available on the Investors section of the Pharvaris website, with a replay accessible for 30 days post-presentation [1]

Core Insights - Pharvaris is hosting a virtual investor event on October 23, 2024, to discuss the unmet needs in hereditary angioedema (HAE) treatment and the potential of its drug, deucrictibant [1] - The event will feature presentations from key medical and executive personnel, followed by a live Q&A session [2] - Pharvaris is a late-stage biopharmaceutical company focused on developing oral bradykinin B2 receptor antagonists for HAE, with ongoing Phase 3 studies for both on-demand and prophylactic treatments [3] Company Overview - Pharvaris is developing novel, oral bradykinin B2 receptor antagonists aimed at preventing and treating HAE attacks [3] - The company aims to provide effective and well-tolerated treatment alternatives for bradykinin-mediated angioedema [3] - Positive data from Phase 2 studies has encouraged Pharvaris to advance deucrictibant, with pivotal Phase 3 studies currently enrolling [3]

Core Insights - Pharvaris is set to initiate the pivotal Phase 3 clinical study, CHAPTER-3, for deucrictibant, aimed at the prophylactic treatment of hereditary angioedema (HAE) by the end of 2024 [1][2] - The company plans to expand the clinical development of deucrictibant to include acquired angioedema due to C1-inhibitor deficiency (AAE-C1INH) as a new indication [1][3] - The CEO of Pharvaris expressed confidence in deucrictibant's potential to become a preferred therapy for HAE management, supported by new long-term extension study data [2] Clinical Development - CHAPTER-3 will evaluate the efficacy and safety of once-daily dosing of deucrictibant extended-release tablets, designed to maintain therapeutic plasma levels for over 24 hours [2][3] - The study is on track to begin by the end of 2024, with startup activities progressing as planned [2] - Data from ongoing studies indicate that deucrictibant can provide injectable-like efficacy with favorable tolerability and convenience of oral administration [3] Research Findings - A recent investigator-initiated trial at Amsterdam UMC demonstrated that deucrictibant significantly reduced mean monthly attack rates in patients with AAE-C1INH, with no severe adverse events reported [3][4] - The results from this trial support the hypothesis that deucrictibant can effectively prevent and treat AAE-C1INH, addressing an unmet medical need [4] Upcoming Events - Pharvaris will present findings at the CIIC Fall 2024 Conference, including long-term efficacy and safety data from the RAPIDe-2 and CHAPTER-1 extension studies [6] - A live conference call will be held to discuss updates and data in detail, with presentation materials available on the company's investor relations website [7] Product Overview - Deucrictibant is a novel oral bradykinin B2 receptor antagonist, developed in both extended-release and immediate-release formulations for prophylactic and on-demand treatment of HAE [8][9] - The company aims to provide effective, well-tolerated, and easy-to-administer alternatives for patients with bradykinin-mediated angioedema [9]