Executive Summary / Key Takeaways

• KalVista Pharmaceuticals has transitioned into a commercial-stage company following the landmark FDA approval of EKTERLY (sebetralstat), the first and only oral on-demand therapy for acute hereditary angioedema (HAE) attacks in eligible patients.
• EKTERLY's oral administration and demonstrated rapid symptom relief (median 1.79 hours vs. 6.72 hours for placebo in KONFIDENT) directly address a significant unmet need and treatment burden associated with existing injectable therapies.
• The company is actively building its U.S. commercial infrastructure and pursuing global market access through regulatory submissions in Europe, the UK, Japan, and other regions, complemented by strategic partnerships.
• Fiscal Year 2025 financial results reflect the pre-commercialization investment phase, with a significant increase in General and Administrative expenses ($116.3M vs $54.3M) offsetting a decrease in R&D ($71.7M vs $86.2M), resulting in a net loss of $183.4 million.
• Recent financing activities, including a $100 million royalty financing and equity raises totaling over $60 million, have bolstered liquidity, providing an expected runway of at least 12 months to support the EKTERLY launch and ongoing R&D.

A New Dawn in Hereditary Angioedema Treatment

Hereditary angioedema (HAE) is a rare, debilitating, and potentially life-threatening genetic disorder characterized by unpredictable episodes of severe swelling. These attacks, often triggered by stress, trauma, or medical procedures, can affect various parts of the body, including the limbs, face, gastrointestinal tract, and critically, the airways, posing a risk of asphyxiation. While prophylactic treatments exist to reduce attack frequency, most patients still experience breakthrough attacks, necessitating readily available and effective on-demand therapy.

Historically, on-demand treatment options in the U.S. have exclusively required intravenous or subcutaneous administration. This presents a significant treatment burden for patients, often leading to delayed administration due to the inconvenience, discomfort, or need for assistance, despite clinical evidence strongly supporting the benefits of early treatment. This critical unmet need for a convenient, non-injectable option has long been a priority for patients and healthcare providers alike.

KalVista Pharmaceuticals has positioned itself to address this gap with its lead asset, sebetralstat, now approved by the FDA and marketed as EKTERLY. The company's journey has been marked by a focused effort to develop novel, orally delivered therapies, leveraging its expertise in small molecule protease inhibitors. The recent FDA approval of EKTERLY on July 3, 2025, for the treatment of acute HAE attacks in adults and pediatric patients 12 years and older, represents a pivotal moment, establishing it as the first and only oral on-demand therapy available in the United States.

The Oral Edge: Technology and Performance

At the heart of KalVista's value proposition is its differentiated technology: a novel, orally delivered small molecule plasma kallikrein inhibitor. Plasma kallikrein is a key enzyme in the kinin-kallikrein system, which plays a central role in the inflammatory cascade that drives HAE attacks. By inhibiting plasma kallikrein, EKTERLY aims to prevent the excessive production of bradykinin, a potent mediator of vascular leakage and edema.

The efficacy and safety of EKTERLY were rigorously evaluated in the Phase 3 KONFIDENT clinical trial. The results, published in the New England Journal of Medicine in May 2024, demonstrated statistically significant and clinically meaningful benefits. Specifically, HAE attacks treated with the approved 600 mg dose of EKTERLY achieved the primary endpoint of beginning of symptom relief significantly faster than placebo (median time of 1.79 hours compared to 6.72 hours, p<0.0013). Key secondary endpoints further underscored EKTERLY's rapid action, showing significantly faster time to a reduction in attack severity (p<0.0032) and significantly faster time to complete attack resolution (p<0.0001) compared to placebo. The trial also reported a favorable safety profile, with treatment-related adverse event rates of 2.2% for EKTERLY compared to 4.8% for placebo, and no treatment-related serious adverse events.

This quantifiable advantage in speed and convenience offered by an oral tablet, compared to the intravenous or subcutaneous administration required by previously available on-demand therapies, is EKTERLY's core technological differentiator. It has the potential to fundamentally alter the treatment paradigm by enabling earlier intervention, which is strongly recommended by treatment guidelines and has been shown to reduce attack severity and duration.

Beyond the approved formulation, KalVista is also developing an orally disintegrating tablet (ODT) formulation, specifically for pediatric patients aged 2 to 11 years. The KONFIDENT-KID open-label trial evaluating this formulation recently completed enrollment in March 2025. If approved, the ODT formulation would be the first oral therapy for this younger pediatric population, potentially expanding the addressable market and reinforcing KalVista's leadership in oral HAE treatments. The company is also evaluating the long-term safety of sebetralstat in the KONFIDENT-S extension study, with participants transitioning to the ODT formulation, suggesting a potential future option for adult and adolescent patients as well.

Navigating the Competitive Currents

The HAE treatment landscape is competitive, featuring both established players with injectable therapies and emerging companies developing new modalities. Prior to EKTERLY's approval, the on-demand market in the U.S. was served by injectable options such as Takeda (TAK)'s Firazyr (icatibant, also available generically) and Kalbitor (ecallantide), CSL Behring (CSL)'s Berinert (C1 esterase inhibitor), and Pharming Group (PHAR)'s Ruconest (C1 esterase inhibitor). For prophylaxis, key players include Takeda's Takhzyro (lanadelumab), CSL Behring's Haegarda (C1 esterase inhibitor) and Andembry (approved June 16, 2025), and BioCryst Pharmaceuticals (BCRX)'s Orladeyo (berotralstat), the first oral prophylactic.

KalVista's primary competitive advantage lies in EKTERLY being the first and only oral on-demand therapy. This directly addresses the significant treatment burden and delays associated with injectables, offering a compelling value proposition based on convenience and rapid efficacy demonstrated in KONFIDENT. While competitors like BioCryst have successfully commercialized an oral prophylactic (Orladeyo), their focus is on prevention, not acute attack treatment. Other companies like Pharvaris (PHVS) are developing oral on-demand therapies (deucrictibant), but EKTERLY has achieved the critical first-mover advantage with FDA approval.

Established companies like Takeda and CSL Behring possess significantly greater financial resources, larger commercial infrastructures, and broader product portfolios. Their existing relationships with physicians and payers, coupled with established manufacturing and distribution networks, present a formidable competitive challenge for KalVista as it builds its commercial presence. While precise, directly comparable financial metrics for all niche competitors are not publicly detailed, the financial health and scale of larger players like CSL (FY2024 net margin 20%, $3B operating cash flow) and Takeda (FY2024 net margin 2%, $5B operating cash flow) highlight the resource disparity compared to KalVista's current pre-revenue, cash-burning status (FY2025 net loss $183.4M, operating cash flow -$152.9M). BioCryst, while also currently unprofitable, has established revenue from Orladeyo (Q1 2025 revenue $104M), giving it a different financial footing than KalVista entering the commercial stage.

KalVista's strategic response involves building a focused U.S. commercial team targeting key prescribers (allergists and immunologists) and leveraging partnerships for global reach. The company's ability to effectively execute its launch strategy, secure favorable market access and reimbursement, and differentiate EKTERLY based on its oral convenience and clinical profile will be critical in capturing market share from established injectable therapies and competing with emerging treatments.

Strategic Expansion and Financial Footing

With the foundational U.S. approval secured, KalVista's strategy centers on maximizing EKTERLY's potential and building a sustainable pipeline. The company has moved swiftly to establish its U.S. commercial operations, including sales, marketing, and market access capabilities, initiating active promotion following the July 2025 approval.

Global expansion is a key pillar, with regulatory submissions validated by the EMA (covering 27 EU member states and EEA countries), and submissions made in the UK, Switzerland, Australia, and Singapore via the Access Consortium framework. Decisions on the EMA application and submissions in Germany and the UK are anticipated in the second half of 2025. The company is preparing internal sales and marketing teams for these major European markets. Further expanding its global footprint, KalVista entered into a licensing agreement with Kaken Pharmaceutical (4521.T) for exclusive commercialization rights in Japan, where an NDA decision is expected in early 2026, and with Pendopharm for Canada. These partnerships provide access to key markets while leveraging local expertise.

Financially, the fiscal year ended April 30, 2025, reflects the significant investment required to transition to a commercial-stage company. Operating expenses totaled $188.0 million, a substantial increase from $140.4 million in the prior year. This was primarily driven by a sharp rise in General and Administrative expenses to $116.3 million (from $54.3 million), reflecting the build-out of the commercial and sales organization, as well as increased commercial and medical awareness expenses in anticipation of the EKTERLY launch. Research and development expenses decreased to $71.7 million (from $86.2 million), as the focus shifted towards commercial preparation, though costs associated with the ongoing KONFIDENT-S and KONFIDENT-KID trials and preclinical activities continue. The net loss for the year was $183.4 million, compared to $126.6 million in the prior year.

To fund these operations and the commercial launch, KalVista has actively strengthened its balance sheet. As of April 30, 2025, the company held $220.6 million in cash, cash equivalents, and marketable securities.

Key financing activities during FY2025 included net proceeds of $55.9 million from a public offering and $4.7 million from a private placement in November 2024. Critically, the company also secured $100 million in upfront funding from a royalty financing agreement with DRI Healthcare Acquisitions LP in November 2024, exchanging tiered royalty payments on future worldwide net sales of sebetralstat for immediate capital. This agreement is accounted for as a deferred royalty obligation ($105.9 million carrying amount as of April 30, 2025, including an embedded derivative liability), incurring $5.7 million in interest expense during the year.

Post-fiscal year end, in July 2025, KalVista elected to receive an additional $22 million payment under this agreement, further boosting liquidity. The $11 million upfront payment from the Kaken licensing agreement was received in June 2025, recorded as deferred revenue as of April 30, 2025. Management anticipates that existing capital resources, combined with expected sales of EKTERLY, will provide sufficient funding for at least the next 12 months. An at-the-market (ATM) offering program for up to $100 million also remains available as a potential source of future funding.

Looking ahead, the company anticipates General and Administrative expenses will continue to increase as commercialization efforts for EKTERLY ramp up. Research and development expenses are expected to remain at or slightly below current levels as ongoing trials continue and the preclinical oral Factor XIIa inhibitor program progresses. This Factor XIIa program is currently under strategic review to evaluate future development pathways, including potential partnerships, representing a key element of KalVista's strategy to build a sustainable pipeline beyond sebetralstat. The change in fiscal year end to December 31, effective for FY2026, will alter future reporting periods, with a transition report planned for the eight months ending December 31, 2025.

Risks and Considerations

While the FDA approval of EKTERLY marks a significant de-risking event, substantial challenges remain. The company is heavily dependent on the successful commercialization of EKTERLY, and its lack of prior commercial experience introduces execution risk. Achieving sufficient market acceptance among physicians, patients, and crucially, third-party payors, is not guaranteed, particularly in a market with established competitors. The ability to secure adequate coverage and reimbursement levels will be paramount to commercial success.

Competition is intense, not only from existing approved therapies but also from pipeline candidates being developed by companies with greater resources. The potential for generic versions of existing drugs and the impact of healthcare reform measures, such as the Inflation Reduction Act (IRA) which could affect pricing and reimbursement, pose ongoing risks. While EKTERLY's orphan drug designation provides certain benefits, it does not guarantee market exclusivity against clinically superior products or prevent the approval of different drugs for the same indication.

Operational risks include reliance on third-party manufacturers for commercial supply, potential delays or issues in international regulatory reviews, and the inherent uncertainties and costs associated with ongoing clinical trials (KONFIDENT-S, KONFIDENT-KID) and preclinical development (Factor XIIa program). The company's cash burn rate, while currently manageable with recent financings, will need to be carefully balanced against revenue growth from EKTERLY sales to ensure long-term financial stability.

Conclusion

KalVista Pharmaceuticals stands at a transformative juncture, having achieved the pivotal FDA approval for EKTERLY, the first oral on-demand therapy for HAE. This milestone, underpinned by compelling clinical data demonstrating rapid symptom relief and a favorable safety profile, positions the company to address a critical unmet need in the HAE market and potentially disrupt the dominance of injectable therapies. The company's strategic focus on building a U.S. commercial presence and expanding globally through regulatory submissions and partnerships lays the groundwork for future revenue generation.

While the transition to commercialization brings increased operating expenses and the challenge of competing with larger, established players, KalVista's recent financing activities have provided the necessary capital runway for the initial launch phase. The success of EKTERLY's commercial uptake, the outcomes of international regulatory reviews, and the strategic advancement of its pipeline, particularly the Factor XIIa program, will be key determinants of the company's long-term trajectory. For investors, the story of KalVista is now centered on the execution of its commercial strategy and the realization of the significant market opportunity presented by EKTERLY's unique oral advantage in the competitive HAE landscape.