Executive Summary / Key Takeaways

• KalVista Pharmaceuticals has launched EKTERLY, the first and only oral on-demand therapy for hereditary angioedema (HAE), fundamentally shifting the treatment paradigm by offering a convenient and effective alternative to injectables.
• Early U.S. launch metrics are robust, with 937 patient start forms in under four months, representing over 10% of the HAE community, driven by strong demand from high-burden patients and broad prescriber adoption.
• The company's financial position is strengthened by recent convertible note financing, providing sufficient capital to fund operations through profitability into 2027, supporting aggressive global commercialization and pipeline expansion.
• Technological differentiation, particularly EKTERLY's oral administration and favorable safety/efficacy profile, provides a significant competitive moat against established injectable and biologic therapies, with ongoing R&D for pediatric formulations and a Factor XIIa inhibitor.
• While initial refill rates are high due to early adoption by high-burden patients, and Q4 2025 demand may see seasonal disruption, the long-term outlook is positive, with formal payer access expected in early 2026 and international launches underway.

The Dawn of Oral On-Demand: Reshaping HAE Treatment

KalVista Pharmaceuticals, Inc. is a global biopharmaceutical company dedicated to addressing significant unmet needs in rare diseases, with a primary focus on hereditary angioedema (HAE). The company's core strategy revolves around developing and commercializing life-changing oral therapies, a mission that culminated in the recent launch of EKTERLY (sebetralstat). This novel, orally delivered, small molecule plasma kallikrein inhibitor represents a pivotal advancement, positioning KalVista as a challenger poised to redefine the standard of care in HAE management. Historically, the HAE treatment landscape has been dominated by intravenous or subcutaneous injectable therapies, which impose a substantial burden on patients. KalVista's journey, marked by years of research and development, has been strategically funded through various capital raises, including equity, convertible debt, and royalty financing, laying the groundwork for its commercialization phase.

The broader pharmaceutical industry is witnessing a growing emphasis on patient-centric solutions and the integration of advanced technologies like AI in drug discovery, which can accelerate R&D. KalVista's focused approach on small molecule inhibitors aligns with this trend, offering the potential for more precise targeting and convenient administration. The company's strategic initiatives, including global partnerships and pipeline expansion, are designed to capitalize on the universal need for more accessible HAE treatments.

Technological Edge: EKTERLY's Differentiated Profile

KalVista's competitive advantage is fundamentally rooted in its proprietary technology: the development of small molecule plasma kallikrein inhibitors. EKTERLY, as the first and only oral on-demand treatment for acute HAE attacks, offers distinct and tangible benefits over existing injectable alternatives. Clinical data from the Phase 3 KONFIDENT trial, published in the New England Journal of Medicine, demonstrated that EKTERLY achieved symptom relief significantly faster than placebo, with a median time of 1.79 hours compared to 6.72 hours. This efficacy is comparable to injectable therapies, but with the added convenience of oral administration and a pristine safety profile.

Further technological differentiation is evident in the ongoing R&D initiatives. The KONFIDENT-KID trial, the largest ever conducted in pediatric HAE, has shown promising interim results for an orally disintegrating tablet (ODT) formulation for children aged 2 to 11. In this trial, the median time to symptom relief was a rapid 1.5 hours, with no treatment-related adverse events or difficulty swallowing reported. This ODT formulation is a unique feature, enabling children to self-treat attacks, a critical advantage over injectables. Data from the KONFIDENT-S open-label extension trial further highlights EKTERLY's reliability; the proportion of patients requiring a second dose within 12 hours decreased from 22.5% at the first attack to 13.5% by the 30th attack, while the use of conventional injectable therapy dropped from 8% to 0% over the same period. Patient satisfaction scores are notably high, with 84% of attacks treated with sebetralstat rated as satisfied to extremely satisfied. These technological advancements and their quantifiable benefits directly contribute to KalVista's competitive moat, enabling superior patient outcomes, fostering strong customer loyalty, and supporting a long-term growth strategy by addressing a critical unmet need. The company is also advancing an oral Factor XIIa inhibitor program in preclinical research, aiming to further expand its pipeline of innovative HAE therapies.

Commercial Momentum and Financial Performance

The commercial launch of EKTERLY in the U.S. in July 2025 marked a significant turning point for KalVista, transitioning the company into a revenue-generating entity. For the three months ended September 30, 2025, KalVista reported product revenue, net, of $13.70 million. This initial revenue, which includes $1.4 million from the launch period through July 31, 2025, primarily stemmed from stocking orders by specialty pharmacies and the commercial distribution network. The rapid uptake has been driven by strong early demand, particularly from high-burden HAE patients who self-report two or more attacks per month. These patients are refilling prescriptions frequently, often every three to four weeks, and with multiple cartons per shipment, significantly higher than the average three to four refills per year seen with most injectable on-demand therapies.

Operating expenses for the three months ended September 30, 2025, totaled $59.7 million, comprising $12.0 million in research and development (R&D) expenses and $46.5 million in selling, general, and administrative (SG&A) expenses. While R&D expenses decreased by $6.7 million compared to the prior year, SG&A expenses saw a substantial increase of $21.7 million, reflecting the significant investment in EKTERLY's global commercialization. This resulted in an operating loss of $46.1 million and a net loss of $49.5 million for the quarter. Despite these losses, the company's liquidity is robust. As of September 30, 2025, KalVista held $309.2 million in cash, cash equivalents, and marketable securities.

The recent issuance of $143.8 million in convertible senior notes in September 2025, yielding net proceeds of $139 million, further solidified its financial position.

Management projects that existing capital resources, combined with forecasted EKTERLY revenue, will fund operations through profitability into 2027.

Competitive Landscape and Strategic Positioning

KalVista operates in a competitive landscape dominated by established players offering injectable and biologic therapies for HAE, such as BioCryst Pharmaceuticals (BCRX), Pharming Group (PHAR), and Takeda Pharmaceutical (TAK). Prior to EKTERLY, all on-demand HAE treatments required intravenous or subcutaneous administration, creating a significant treatment burden. KalVista's EKTERLY directly addresses this unmet need by offering the first and only oral on-demand option, providing a distinct competitive advantage.

Compared to BioCryst Pharmaceuticals, which also focuses on oral HAE therapies, KalVista's EKTERLY offers a differentiated on-demand profile, while BioCryst's lead product is an oral kallikrein inhibitor. Against Pharming Group, which primarily offers biologics, EKTERLY's oral convenience presents a significant patient-friendly alternative. Takeda, a large pharmaceutical company with a broad HAE portfolio, possesses extensive resources and global reach, but KalVista's specialized focus on small molecule inhibitors allows for innovation agility and targeted R&D. EKTERLY's ability to provide rapid symptom relief with a favorable safety profile, coupled with its oral administration, is a key differentiator that positions it to capture market share from existing injectable options like Firazyr and icatibant, which account for a significant portion of patient switches. The company's strategic focus on expanding its pediatric indication and developing an oral Factor XIIa inhibitor further strengthens its long-term competitive standing by addressing broader patient populations and potential new mechanisms of action.

Outlook and Risks

KalVista's outlook is characterized by aggressive global expansion and continued investment in EKTERLY's commercialization. Management anticipates that SG&A expenses will remain consistent or increase as the company scales its U.S. launch and initiates international rollouts. A staged launch in Europe is planned over the next 12 to 18 months, commencing with Germany, which saw initial commercial sales in October 2025. The U.K. commercial launch is anticipated in the first half of 2026, pending pricing and reimbursement discussions with NICE. In Japan, approval is expected by year-end, with a launch through partner Kaken Pharmaceutical (4521.T) in early 2026. The company also plans to submit an NDA for the pediatric formulation of EKTERLY in Q3 2026.

While the early U.S. launch has exceeded expectations, with 937 patient start forms representing over 10% of the HAE community in under four months, management acknowledges potential seasonal disruptions to demand in the remainder of 2025 due to the holiday period. Payer access is progressing as anticipated, with medical exceptions being successfully leveraged and formal coverage policies from major payers and PBMs expected in early 2026. The gross-to-net discount is projected to average in the upper teens to low twenties, consistent with other specialty medicines.

Key risks include the inherent uncertainties of pharmaceutical commercialization, such as unforeseen expenses and delays. The company expects to incur operating losses for the foreseeable future as it invests in global expansion and pipeline development. While EKTERLY's oral convenience is a strong differentiator, some payers may initially require a step-through generic icatibant, though patients with prior experience on icatibant can navigate this quickly. The long-term trajectory of refill rates and carton quantities will normalize as adoption expands beyond the initial high-burden patient population, which could impact revenue growth rates. Furthermore, the competitive landscape remains dynamic, with other companies advancing their own HAE therapies.

Conclusion

KalVista Pharmaceuticals stands at a pivotal juncture, having successfully launched EKTERLY, an oral on-demand therapy that promises to revolutionize the treatment of hereditary angioedema. The company's strategic focus on addressing the significant unmet need for convenient, effective, and safe HAE treatments has been validated by strong early commercial uptake in the U.S. and initial international launches. EKTERLY's technological differentiation, offering oral administration with comparable efficacy and a superior safety profile to injectables, establishes a robust competitive moat.

With a fortified balance sheet, providing funding through profitability into 2027, KalVista is well-positioned to execute its aggressive global commercialization strategy and advance its pipeline, including a pediatric formulation and a Factor XIIa inhibitor. While the path to sustained profitability will involve navigating evolving payer dynamics and normalizing patient usage patterns, the fundamental shift towards oral therapies in HAE, driven by EKTERLY's compelling profile, underpins a strong long-term investment thesis. The company's commitment to patient satisfaction and its leadership in oral HAE treatment position it for continued growth and market leadership.