Executive Summary / Key Takeaways

• Pharvaris N.V. ($PHVS) is a late-stage biopharmaceutical company poised to disrupt the hereditary angioedema (HAE) and acquired angioedema (AAE-C1INH) markets with deucrictibant, an oral bradykinin B2-receptor antagonist designed for both on-demand and prophylactic treatment.
• The company's core technological advantage lies in offering "injectable-like efficacy™ and placebo-like tolerability with the convenience of an oral therapy", a significant differentiator in a market currently dominated by parenteral treatments.
• Key near-term catalysts include topline data from the pivotal Phase 3 RAPIDe-3 study for on-demand HAE treatment, expected in Q4 2025, with a potential New Drug Application (NDA) submission in H1 2026.
• Pharvaris maintains a strong financial position, with cash and cash equivalents of €200 million as of June 30, 2025, and a subsequent $201 million public offering extending its cash runway into the first half of 2027, providing ample liquidity through critical development milestones.
• The global HAE market is projected to grow substantially, reaching USD 12.79 billion by 2030 at a 16.9% CAGR, with oral delivery expanding at a 20.10% CAGR, positioning Pharvaris to capture significant market share if deucrictibant achieves regulatory approval.

A New Dawn for Angioedema Treatment: Pharvaris' Oral Revolution

Pharvaris N.V., incorporated in 2015 and headquartered in Zug, Switzerland, is a late-stage biopharmaceutical company singularly focused on addressing the unmet needs of patients suffering from bradykinin-mediated angioedema, including hereditary angioedema (HAE) and acquired angioedema due to C1-inhibitor deficiency (AAE-C1INH). The company's strategic vision centers on its lead candidate, deucrictibant, an oral small molecule bradykinin B2-receptor antagonist. This innovative approach aims to fundamentally transform the treatment landscape by offering a convenient, non-invasive alternative to the predominantly injectable therapies currently available.

The global hereditary angioedema therapeutics market is a rapidly expanding sector, valued at USD 5.86 billion in 2025 and projected to surge to USD 12.79 billion by 2030, demonstrating a robust compound annual growth rate (CAGR) of 16.9%. This growth is fueled by increasing awareness, improved diagnostics, and the emergence of novel, targeted therapies. Notably, the oral delivery segment within this market is experiencing even faster expansion, with a projected CAGR of 20.10%, expected to exceed USD 4.10 billion by 2030. This trend underscores a clear patient and physician preference for more convenient administration methods, a gap Pharvaris is strategically positioned to fill.

Technological Edge: Deucrictibant's Differentiated Profile

At the heart of Pharvaris' investment thesis is deucrictibant, a novel, potent, and orally bioavailable small-molecule bradykinin B2 receptor antagonist. This core technology is designed to prevent and treat angioedema attacks by inhibiting bradykinin signaling through the B2 receptor, a clinically validated mechanism. The tangible benefits of this oral approach are significant, aiming to provide "injectable-like efficacy™ and placebo-like tolerability with the convenience of an oral therapy".

Pharvaris is developing two distinct formulations of deucrictibant: an immediate-release (IR) capsule for rapid onset in on-demand treatment, and an extended-release (ER) tablet for sustained absorption and efficacy in prophylactic treatment. Early clinical data from Phase 2 trials (RAPIDe-1 and RAPIDe-2) demonstrated that 95–100% of HAE attacks achieved durable symptom relief after a single dose of deucrictibant IR, with a median onset of 1.1 hours. This rapid and sustained relief offers a compelling advantage over existing options. Furthermore, in the CHAPTER-1 Phase 2 study for prophylaxis, 40 mg/day orally administered deucrictibant significantly reduced the mean monthly attack rate by 84.5% compared to placebo, with a 92.3% reduction in moderate and severe attacks. These performance metrics highlight deucrictibant's potential to significantly improve patient outcomes and quality of life.

The company's R&D initiatives are focused on advancing these formulations through pivotal Phase 3 trials. Pharvaris has also secured orphan drug designation for deucrictibant from both the FDA and the European Commission, which provides market exclusivity post-approval. Additionally, the company received clearance to bypass a Thorough QT (TQT) study for both its ER and IR formulations, removing a key regulatory hurdle and suggesting a strong cardiac safety profile. These regulatory advantages streamline the development pathway and enhance deucrictibant's competitive moat.

Competitive Landscape and Strategic Positioning

The HAE treatment market is competitive, featuring established players and emerging therapies. Key competitors include Takeda Pharmaceutical (TAK) (Takhzyro), CSL Behring (CSLLY) (Haegarda, Berinert), BioCryst Pharmaceuticals (BCRX) (Orladeyo), and Ionis Pharmaceuticals (IONS) (donidalorsen).

Current therapies, such as CSL Behring's Berinert, often rely on subcutaneous or intravenous administration, requiring frequent dosing or hospital visits. Takeda's Takhzyro, an injectable monoclonal antibody, is efficacious but still requires parenteral administration. BioCryst's Orladeyo is notable as the first oral drug for HAE prophylaxis approved by the FDA, inhibiting plasma kallikrein. Ionis Pharmaceuticals is also advancing donidalorsen, an RNA-targeted therapy for HAE prophylaxis, which has shown significant attack rate reduction in Phase 3 trials and is preparing for FDA submission.

Pharvaris' deucrictibant, as an oral bradykinin B2-receptor antagonist, offers a differentiated mechanism of action compared to kallikrein inhibitors like Orladeyo and C1-esterase inhibitors. Its dual-use potential for both on-demand and prophylactic treatment in an oral form provides a significant convenience advantage over many existing injectable therapies. This positions Pharvaris to capture market share from injectable therapies, particularly among patients prioritizing ease of use. While BioCryst has an oral prophylaxis option, deucrictibant's potential for both acute and prophylactic oral treatment, coupled with its rapid onset, could offer a qualitatively superior patient experience.

Furthermore, Pharvaris is strategically targeting the acquired angioedema due to C1-inhibitor deficiency (AAE-C1INH) market, a segment estimated at $2 billion with no currently approved therapies. The planned initiation of the CREAATE pivotal Phase 3 study for AAE-C1INH by year-end 2025 positions Pharvaris for a potential first-mover advantage in this underserved niche. The company's strategy also includes building an in-house U.S. sales and marketing team, rather than outsourcing commercialization, aiming to capture a larger share of revenue from deucrictibant. This capital-efficient strategy prioritizes self-commercialization to reduce dilution risks while targeting high-margin oral therapy dominance.

Financial Performance and Liquidity

As a late-stage biopharmaceutical company, Pharvaris' financial performance reflects its significant investment in research and development. For the full year 2024, the company reported research and development expenses of €98.6 million and a net loss of €134.2 million. In the second quarter of 2025, R&D expenses were €29.6 million, contributing to a net loss of €45.5 million (€0.83 per share). These figures underscore the capital-intensive nature of drug development, particularly as deucrictibant progresses through pivotal Phase 3 trials.

Despite these losses, Pharvaris maintains a robust liquidity position. As of June 30, 2025, the company held €200 million in cash and cash equivalents. A significant financial bolstering occurred in July 2025 with the closing of an upsized $201 million public offering, which included ordinary shares and pre-funded warrants. This capital raise extended the company's cash runway into the first half of 2027, providing critical funding for its late-stage clinical programs, the establishment of a U.S. sales and marketing team, and general corporate purposes. This extended runway is crucial, mitigating near-term dilutive fundraising pressure and supporting operations through key data readouts.

The company's current market capitalization stands at approximately $1.55 billion, with a P/B ratio of 7.17 and an EV to EBITDA of -6.79 as of September 29, 2025. These metrics are typical for a pre-revenue, development-stage biotech, where valuation is heavily influenced by pipeline potential and future commercialization prospects rather than current earnings.

Outlook and Key Catalysts

Pharvaris has a clear roadmap with several significant catalysts on the horizon. Topline results for RAPIDe-3, the pivotal Phase 3 study of deucrictibant for the on-demand treatment of HAE attacks, are anticipated in the fourth quarter of 2025. Pending positive data, Pharvaris expects to submit a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) in the first half of 2026.

Further strengthening its pipeline, enrollment continues in CHAPTER-3, a pivotal Phase 3 study of deucrictibant for prophylaxis of HAE attacks, with topline results expected in the second half of 2026. Additionally, startup activities for CREAATE, a pivotal Phase 3 study of deucrictibant for the prophylactic and on-demand treatment of AAE-C1INH attacks, are on track, with the study expected to initiate by year-end 2025.

Management emphasizes 2025 as an "important executional year". Berndt Modig, CEO of Pharvaris, stated the company's commitment to "generating robust clinical data to build a compelling package supporting deucrictibant's efficacy and safety profile" and its focus on "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". Sell-side analysts predict a -2.71 EPS for the current fiscal year and -0.80 USD for the next quarter, reflecting the ongoing investment phase prior to potential revenue generation.

Risks and Challenges

Investing in a late-stage biopharmaceutical company like Pharvaris inherently involves significant risks. The primary risk remains the outcome of the ongoing clinical trials. While prior Phase 2 data has been positive, there is no guarantee that Phase 3 trials will yield similar results or meet regulatory endpoints. Potential off-target effects, unforeseen safety issues, or insufficient efficacy in larger patient populations could impede regulatory approval.

Even with successful clinical development, Pharvaris faces challenges in obtaining regulatory approval, which can be a lengthy and costly process. Post-approval, market acceptance and commercialization efforts, particularly against established competitors with existing sales forces and patient bases, present further hurdles. The company's strategy to build an in-house U.S. sales and marketing team, while potentially maximizing revenue, also entails significant upfront investment and execution risk. Furthermore, the competitive landscape is dynamic, with other companies also developing oral HAE therapies, such as KalVista Pharmaceuticals (KALV) with sebetralstat.

Conclusion

Pharvaris N.V. stands at a pivotal juncture, offering a compelling investment narrative centered on its innovative oral bradykinin B2-receptor antagonist, deucrictibant. The company's strategic focus on providing a convenient, effective oral therapy for both on-demand and prophylactic treatment of HAE and AAE-C1INH positions it to capture a significant share of a rapidly growing market. Deucrictibant's demonstrated rapid onset and durable symptom relief in early trials, coupled with regulatory advantages like orphan drug designation and TQT study waivers, underscore its technological differentiation.

With critical Phase 3 data readouts expected in Q4 2025 and H2 2026, and a robust cash runway extending into the first half of 2027, Pharvaris is well-funded to execute its clinical and pre-commercialization strategies. While substantial clinical and commercialization risks persist, the potential for deucrictibant to disrupt the angioedema treatment paradigm, particularly in the underserved AAE-C1INH market, presents a significant upside for discerning investors. The company's trajectory hinges on successful trial outcomes and effective market penetration, making it a high-potential, high-stakes play in the rare disease biopharma sector.