Executive Summary / Key Takeaways

• Kiniksa Pharmaceuticals is solidifying its leadership in recurrent pericarditis through the commercial success of ARCALYST and a robust pipeline focused on next-generation IL-1 inhibition.
• ARCALYST continues to demonstrate significant commercial momentum, with Q3 2025 net product revenue reaching $180.9 million, representing 61% year-over-year growth, and full-year 2025 guidance raised to $670-$675 million.
• The company's innovative pipeline, particularly KPL-387, an investigational monthly subcutaneous IL-1 receptor antagonist, aims to expand market penetration and enhance patient convenience, with Phase 2 data expected in the second half of 2026.
• Kiniksa maintains a strong financial position, consistently generating positive annual cash flow, which supports ongoing investment in its commercial and clinical development initiatives without reliance on external capital markets.
• Despite strong growth, the company faces competitive pressures from larger pharmaceutical players and risks associated with third-party manufacturing reliance and evolving regulatory landscapes.

The Foundation of Innovation: Targeting Inflammatory Disease

Kiniksa Pharmaceuticals International, plc is a biopharmaceutical company dedicated to developing and commercializing novel therapies for diseases with unmet medical needs, with a primary focus on cardiovascular indications. The company's strategic foundation is built upon a deep understanding of inflammatory pathways, particularly interleukin-1 (IL-1) alpha and beta inhibition, which it leverages to address debilitating conditions like recurrent pericarditis. This targeted approach positions Kiniksa as a specialized challenger in a biopharmaceutical landscape dominated by larger, more diversified players.

The company's journey began with its incorporation in Bermuda in July 2015, evolving through strategic in-licensing and acquisitions to build its initial portfolio. Key historical moves include acquiring rights to vixarelimab from Biogen (BIIB) in September 2016 and, most notably, securing an exclusive worldwide license for ARCALYST from Regeneron Pharmaceuticals, Inc. in September 2017. This latter agreement proved pivotal, leading to the FDA approval of ARCALYST for recurrent pericarditis in March 2021 and establishing Kiniksa's commercial footprint. The company's recent redomiciliation to the United Kingdom in April 2024 and the strategic discontinuation of abiprubart and mavrilimumab programs underscore a sharpened focus on its core IL-1 inhibition franchise.

Kiniksa's core technological differentiation lies in its expertise in IL-1 alpha and beta inhibition. ARCALYST, an interleukin-1α and interleukin-1β cytokine trap, exemplifies this. It is the first and only FDA-approved therapy for recurrent pericarditis, a painful inflammatory cardiovascular disease. Clinical data from the RHAPSODY program demonstrated that continued treatment with ARCALYST without interruption resulted in a 99.5% reduction in event rates compared to pretreatment, setting a high bar for efficacy in the field. This robust efficacy, coupled with its targeted mechanism, has been instrumental in shifting the treatment paradigm towards IL-1 immunomodulation.

Building on this success, Kiniksa is advancing its next-generation assets. KPL-387 is an investigational, independently developed, fully human immunoglobulin G2 monoclonal antibody that binds human interleukin-1 receptor 1 (IL-1R1), thereby inhibiting both IL-1α and IL-1β-mediated signaling. This mechanism is designed to offer a similar comprehensive blockade of the IL-1 pathway as ARCALYST. The key differentiator for KPL-387 is its target profile of a monthly subcutaneous single injection in a liquid formulation, potentially delivered via an auto-injector, offering enhanced patient convenience over ARCALYST's weekly regimen. Phase 1 data for KPL-387 has shown sustained serum concentrations above the target concentration, supporting this monthly dosing paradigm. Market research indicates a strong preference for this profile, with approximately 75% of surveyed recurrent pericarditis patients preferring KPL-387's target profile over existing and investigational therapies, and over 90% of healthcare professionals expressing a high likelihood of prescribing it. Furthermore, healthcare professionals broadly agree that KPL-387's introduction would expand the overall IL-1 alpha and beta inhibition market.

In its preclinical stage, KPL-1161, an Fc-modified immunoglobulin G2 monoclonal antibody, is a modified version of KPL-387 engineered for an increased drug half-life, with the potential to support quarterly subcutaneous dosing. This innovation could open up opportunities in a broader range of chronic, lifelong auto-inflammatory diseases, further expanding Kiniksa's technological moat. The company is currently conducting IND-enabling activities for KPL-1161. These technological advancements are critical for Kiniksa's competitive moat, aiming to provide superior efficacy and convenience, which can translate into sustained market leadership, higher adoption rates, and ultimately, enhanced financial performance.

Commercial Momentum and Financial Strength

Kiniksa's financial performance in 2025 has been characterized by robust growth, primarily driven by the commercial success of ARCALYST. For the three months ended September 30, 2025, net product revenue from ARCALYST reached $180.9 million, marking a significant 61.2% increase compared to the same period in 2024. Year-to-date, for the nine months ended September 30, 2025, ARCALYST net product revenue totaled $475.4 million, representing a 61.4% increase over the prior year. This strong performance led the company to raise its full-year 2025 ARCALYST net sales guidance to between $670 million and $675 million, up from previous guidance ranges.
The growth in ARCALYST sales is a direct result of effective commercial execution. New patient enrollments in Q3 2025 reached their highest level since launch, with over 350 new prescribers contributing to a total of more than 3,825 prescribers to date. The average total duration of therapy for ARCALYST patients has also increased to approximately 32 months, reflecting both patient satisfaction and a growing understanding among healthcare professionals of recurrent pericarditis as a multi-year chronic disease requiring long-term treatment. Approximately 20% of ARCALYST prescriptions are now written for patients following their first recurrence, indicating a trend towards earlier intervention in the disease course.
Profitability has also seen a positive shift. Kiniksa reported a net income of $18.4 million for the third quarter of 2025, a substantial improvement from a net loss of $12.7 million in the same period last year.

ARCALYST collaboration profit, which drives collaboration expenses, grew by 118% year-over-year to $126.6 million in Q3 2025, as commercial and manufacturing costs remained steady against rising sales. This indicates strong operating leverage as the product scales. Operating expenses for Q3 2025 were $156.8 million, an increase of 29% year-over-year, primarily due to higher collaboration expenses tied to ARCALYST revenue growth and increased personnel-related costs in selling, general, and administrative functions. Research and development expenses, however, decreased due to the close-out of the abiprubart Phase 2b clinical trial.

Kiniksa maintains a robust financial position, with cash, cash equivalents, and short-term investments totaling $352.1 million as of September 30, 2025.

The company consistently generates positive annual cash flow from operations, providing the flexibility to fund its current operating plan and capital expenditure requirements for at least the next twelve months without needing to access additional capital markets.

This financial discipline is a critical enabler of its innovation strategy, allowing for continued investment in the IL-1 inhibition franchise.

Strategic Outlook and Pipeline Advancement

Kiniksa's strategic outlook is firmly anchored in maximizing the ARCALYST opportunity while aggressively advancing its next-generation IL-1 inhibitors. The upward revision of ARCALYST's 2025 net sales guidance reflects management's confidence in sustained commercial momentum, driven by continued prescriber growth, increased duration of therapy, and earlier patient initiation. The company's commercial teams are leveraging digital marketing and AI to optimize physician targeting and education, further expanding the breadth and depth of ARCALYST prescribing.

The pipeline is set to deliver future value, with KPL-387 at the forefront. The Phase 2/Phase 3 clinical trial for KPL-387 in recurrent pericarditis was initiated in mid-2025, with data from the Phase 2 dose-focusing portion anticipated in the second half of 2026. The goal is to make KPL-387 available to patients by the 2028-2029 timeframe. This development is critical for Kiniksa to maintain its leadership in recurrent pericarditis by offering a potentially more convenient monthly subcutaneous dosing option, which is expected to expand the overall IL-1 alpha and beta inhibition market. The recent Orphan Drug Designation for KPL-387 for pericarditis further supports its strategic positioning. Beyond KPL-387, the preclinical KPL-1161, with its potential for quarterly dosing, represents a long-term growth driver, with IND-enabling activities currently underway.

Competitive Landscape and Risks

Kiniksa operates in a highly competitive biopharmaceutical industry, facing both direct and indirect competition. Direct competitors include large pharmaceutical companies like AbbVie (ABBV), Novartis (NVS), Johnson & Johnson (JNJ), and Pfizer (PFE), all of whom have significant resources and established immunology portfolios. While these larger players possess greater financial resources, extensive R&D capabilities, and global market presence, Kiniksa differentiates itself through a specialized focus on underserved inflammatory diseases and targeted IL-1 inhibition. Kiniksa's agility and innovation speed in niche areas provide a unique value proposition, potentially leading to superior efficacy in specific disease mechanisms. However, its smaller scale results in higher operational costs and generally lower profitability margins compared to its larger rivals, who benefit from diversified revenue streams and greater operational efficiency.

The company's reliance on third-party manufacturers for its commercial supply of ARCALYST and clinical supply of product candidates presents a notable operational risk. Regeneron (REGN) is currently the sole manufacturer of ARCALYST drug substance, with a technology transfer underway to Samsung Biologics in South Korea. This transfer is subject to significant risks, including regulatory approval, demonstrating comparability between the drug substances produced by different manufacturers, and potential delays. Any disruption in this supply chain could materially impact Kiniksa's ability to meet patient demand and generate revenue.

Furthermore, the regulatory and reimbursement landscape poses ongoing challenges. While ARCALYST benefits from Orphan Drug exclusivity for recurrent pericarditis, the 12-year exclusivity period for CAPS has lapsed, and the approval for recurrent pericarditis via an sBLA does not automatically confer a new 12-year exclusivity, potentially opening the door to biosimilar competition. Third-party payors continue to exert pressure on drug pricing and reimbursement, which could limit market access or reduce the profitability of ARCALYST and future approved products. The evolving healthcare legislation and administrative actions in the U.S., including potential changes from the current presidential administration, introduce further uncertainty regarding regulatory approvals, drug pricing, and market access. Intellectual property protection is also a continuous battle, with the potential for challenges to patents and the need to defend against infringement claims.

Conclusion

Kiniksa Pharmaceuticals stands at a pivotal juncture, having successfully commercialized ARCALYST as the market leader in recurrent pericarditis and strategically streamlined its pipeline to focus on its core IL-1 inhibition franchise. The consistent, robust revenue growth of ARCALYST, coupled with a strong balance sheet and positive cash flow, provides a solid foundation for future investment. The development of KPL-387 and KPL-1161 represents a clear technological roadmap to expand its market dominance by offering enhanced convenience and potentially addressing a broader spectrum of auto-inflammatory diseases.

While the company faces inherent risks associated with competitive pressures, manufacturing dependencies, and regulatory complexities, its focused strategy, proven commercial execution, and innovative pipeline position it for continued value creation. The ability to deliver differentiated therapies that meet significant unmet medical needs, supported by a disciplined financial approach, underpins the compelling investment thesis for Kiniksa Pharmaceuticals. Investors will closely monitor the progress of KPL-387's clinical trials and the successful completion of the ARCALYST manufacturing technology transfer as key indicators of the company's long-term trajectory.