Berotralstat Hydrochloride

– Claims data show 40% of patients on long-term prophylaxis have gaps in prescription refills, leading to greater on-demand use and higher rate of LTP discontinuation- -Data from KONFIDENT-S show patients on LTP average 1.7 HAE attacks per month and symptom relief for treated attacks in median 1.3 hours - –Results confirm sebetralstat effective for on-demand treatment of attacks regardless of type of LTP therapy used, including an all-oral regimen– CAMBRIDGE, Mass. & SALISBURY, England--(BUSINESS WIRE)--Feb. 10, 2025-- KalVista Pharmaceuticals, Inc. (NASDAQ: KALV), today announced the presentation of novel data related to long-term prophylaxis and sebetralstat at the Western Society of Allergy, Asthma & Immunology (WSAAI) 2025 Annual Meeting taking place in Waimea, HI from February 9-13, 2025. Raffi Tachdjian, MD, MPH, Associate Clinical Professor of Medicine and Pediatrics in the Division of Allergy and Clinical Immunology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), presented data on the Impact of Long-Term Prophylaxis (LTP) Adherence in Hereditary Angioedema Patients: Results of a Claims Database Analysis. According to a US commercial claims analysis, nearly 40% of HAE patients who initiated LTP had substantial refill gaps in claims over 12 months, with more than half of those discontinuing LTP. For patients with substantial refill gaps, which increase the likelihood of non-adherence, on-demand claims remained unchanged before and after one year of starting LTP. “Despite guidelines emphasizing regular assessment of patients using LTP to confirm efficacy and safety of their therapy, these data suggest many patients experience substantial lapses in refilling their LTP, which may reflect non-adherence,” said Dr. Tachdjian. “We saw no decrease in on-demand claims for patients with LTP refill gaps. These findings are important as most HAE patients in the US now receive LTP, and a greater focus on monitoring appears warranted, as LTP effectiveness is not a given. These data may also help to explain why on-demand treatment volumes in HAE have remained steady despite the advent of several effective subcutaneous and oral LTP options since 2017.” Marc A. Riedl, MD, Professor of Medicine and Clinical Director, US Hereditary Angioedema Association Center at the University of California, San Diego, presented data on the Safety and Effectiveness of Sebetralstat in Patients with Hereditary Angioedema Receiving Long-Term Prophylaxis: Interim Analysis from the KONFIDENT-S Open-Label Study. Participants receiving LTP treated 382 attacks with sebetralstat (mean 1.7 attacks per month), of which more than half involved the abdomen and/or larynx. Sebetralstat enabled early treatment (median 6 minutes) and early symptom relief (median 1.3 hours), and was well-tolerated, regardless of LTP mechanism of action or route of administration. “Treatment guidelines recommend that patients with HAE should consider treating all attacks regardless of LTP use and should treat attacks as early as possible,” noted Dr. Riedl. “These interim results suggest that, if approved, sebetralstat could be a safe and effective oral on-demand treatment for breakthrough attacks, regardless of severity, location, or type of LTP used.” Michael E. Manning, MD, allergist-immunologist at Allergy, Asthma and Immunology Associates, Ltd., Scottsdale, Arizona and Past President of WSAAI, presented Sebetralstat for the Treatment of HAE Attacks in Patients Receiving Berotralstat: Interim Analysis from the KONFIDENT-S Open-Label Study. Participants receiving berotralstat treated 178 attacks with sebetralstat (mean 1.8 attacks per month). Sebetralstat enabled early treatment (median 20 minutes), early symptom relief (median 1.3 hours), and was well-tolerated with no increase in gastrointestinal side effects. “In general, patients prefer oral treatments over injectables, underscoring the strong interest in oral options for HAE,” said Dr. Manning. “These results demonstrate that sebetralstat, when used as an oral on-demand treatment for attacks occurring among patients receiving berotralstat for LTP, enabled rapid treatment and symptom improvement. If approved, sebetralstat could transform the treatment landscape for physicians and patients who prefer to manage HAE without needles.” “Injectable on-demand treatments have side effects and logistical obstacles that hinder adequate disease control and drive an over-reliance on LTP,” said Paul Audhya, MD, MBA, Chief Medical Officer of KalVista. “LTP does not, however, always yield the anticipated reductions in attacks, possibly due to adherence issues in a chronic lifelong setting. Sebetralstat has the potential to enable early treatment of attacks, thereby halting progression at an early stage and reducing morbidity, even among patients on LTP. By overcoming the barriers imposed by current injectable on-demand therapies, sebetralstat could shift the treatment paradigm and become the foundation of HAE management.” Links to all presentations can be found on the KalVista website under Publications. About the KONFIDENT Phase 3 Trial The KONFIDENT phase 3 clinical trial was a randomized, double-blind, 3-way crossover trial evaluating the safety and efficacy of sebetralstat 300 mg and 600 mg versus placebo for the on-demand treatment of HAE in adult and pediatric patients aged 12 years and older. The trial randomized 136 HAE patients from 66 clinical sites across 20 countries, making it the largest clinical trial ever conducted in HAE. In the trial, participants treated each eligible attack with up to two doses of study drug and treated up to three attacks over the course of the study. The trial included Type I and Type II HAE patients who had at least two documented HAE attacks 90 days prior to randomization and also included patients receiving long-term prophylaxis. About the KONFIDENT-S Trial KONFIDENT-S is an open-label extension trial with numerous real-world elements evaluating the long-term safety and efficacy of sebetralstat for the on-demand treatment of HAE attacks in adults and pediatric patients aged 12 years and older with HAE Type I or Type II. KalVista is transitioning ongoing trial participants to a novel oral disintegrating tablet (ODT) formulation to support a planned 2026 sNDA filing. If approved, the ODT formulation would provide people living with HAE with an alternative, novel option for oral, on-demand treatment. About Sebetralstat Sebetralstat is an investigational, novel oral plasma kallikrein inhibitor for the treatment of hereditary angioedema (HAE). We have filed multiple regulatory applications seeking approval of sebetralstat as the first oral, on-demand treatment for HAE in individuals aged 12 and older, with ongoing studies exploring its use in children aged 2 to 11. If approved, sebetralstat has the potential to become the foundational therapy for HAE management worldwide. About Hereditary Angioedema Hereditary angioedema (HAE) is a rare genetic disease resulting in deficiency or dysfunction in the C1 esterase inhibitor (C1INH) protein and subsequent uncontrolled activation of the kallikrein-kinin system. People living with HAE experience painful and debilitating attacks of tissue swelling in various locations of the body that can be life-threatening depending on the area affected. All currently approved on-demand treatment options require either intravenous or subcutaneous administration. About KalVista Pharmaceuticals, Inc. KalVista Pharmaceuticals, Inc., is a global biopharmaceutical company dedicated to developing and delivering life-changing oral therapies for individuals affected by rare diseases with significant unmet needs. Our lead investigational product is sebetralstat, a novel, oral, on-demand treatment for hereditary angioedema (HAE). Sebetralstat is under regulatory review by the U.S. FDA, with a PDUFA goal date of June 17, 2025. In addition, we have completed Marketing Authorization Applications for sebetralstat to the European Medicines Agency and multiple other global regulatory authorities. For more information about KalVista, please visit www.kalvista.com or follow us on social media at @KalVista and LinkedIn. Forward-Looking Statements This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future," "likely," "may," "should," "will" and similar references to future periods. These statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, timing or outcomes of communications with the FDA, our expectations about safety and efficacy of our product candidates and timing of clinical trials and its results, our ability to commence clinical studies or complete ongoing clinical studies, including our KONFIDENT-S and KONFIDENT-KID trials, and to obtain regulatory approvals for sebetralstat and other candidates in development, the success of any efforts to commercialize sebetralstat, the ability of sebetralstat and other candidates in development to treat HAE or other diseases, and the future progress and potential success of our oral Factor XIIa program. Further information on potential risk factors that could affect our business and financial results are detailed in our filings with the Securities and Exchange Commission, including in our annual report on Form 10-K for the year ended April 30, 2024, our quarterly reports on Form 10-Q, and our other reports that we may make from time to time with the Securities and Exchange Commission. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. View source version on businesswire.com: https://www.businesswire.com/news/home/20250210755734/en/ Jenn Snyder Vice President, Corporate Affairs (617) 448-0281 jsnyder@kalvista.com Ryan Baker Head, Investor Relations (617) 771-5001 ryan.baker@kalvista.com Source: KalVista Pharmaceuticals, Inc.

—ORLADEYO net revenue expected to be between $515-$535 million in 2025— —Total revenue (including RAPIVAB®) expected to be between $540-$560 million in 2025— —Company achieved operating profit in 2024 (not including stock-based compensation) and expects to approach quarterly EPS profitability/positive cash flow in 2H 2025— —New drug application planned in 2025 for ORLADEYO granules in children up to age 12; will address significant unmet need— —Pipeline advancing into patients with Netherton syndrome (BCX17725) and diabetic macular edema (avoralstat) in 2025— RESEARCH TRIANGLE PARK, N.C., Jan. 10, 2025 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced preliminary, unaudited ORLADEYO® (berotralstat) net revenue and total revenue for the fourth quarter and full year 2024. The company also provided guidance for full year 2025 ORLADEYO net revenue and total revenue, full year 2025 operating expenses, and its expectation that the company will approach quarterly earnings per share (EPS) profitability in the second half of 2025. “2024 was a year of outstanding execution for the company on multiple fronts and it is exciting to carry this momentum into 2025. We had another year of exceptional ORLADEYO revenue growth moving us significantly closer to peak sales of $1 billion, and we did this while driving the company toward profitability in the near-term. We are excited that this year we expect to submit a new drug application to expand the ORLADEYO label to children under age 12 and to be in patient studies in two new clinical programs (BCX17725 and avoralstat),” said Jon Stonehouse, president and chief executive officer of BioCryst. Preliminary Fourth Quarter and Full Year 2024 ORLADEYO Revenue and Total Revenue, and 2025 ORLADEYO and Total Revenue OutlookPreliminary, unaudited ORLADEYO net revenue in the fourth quarter of 2024 was $123.5 million (+36 percent y-o-y). Preliminary, unaudited ORLADEYO net revenue for full year 2024 was $437 million (+34 percent y-o-y). The company expects full year 2025 global net ORLADEYO revenue will be between $515 million and $535 million. “ORLADEYO revenue accelerated in 2024, with 34 percent annual growth in the fourth year on the market, compared to 30 percent in 2023. Over 1,200 U.S. physicians have prescribed ORLADEYO, and thousands of patients have benefitted in over 30 countries worldwide as physicians and patients continue to gain confidence in the exceptional efficacy and convenience that are possible with ORLADEYO. As we head into 2025, oral, preventative therapy with ORLADEYO is the new benchmark for HAE, and we are excited to soon bring this new option to children under age 12,” said Charlie Gayer, chief commercial officer of BioCryst. Preliminary, unaudited total revenue in the fourth quarter of 2024 was $130.8 million (+40 percent y-o-y). Preliminary, unaudited total revenue for full year 2024 was $450 million (+36 percent y-o-y). The company expects full year 2025 total revenue (including RAPIVAB® (peramivir injection)) will be between $540 million and $560 million. Operating Expense OutlookThe company expects full year 2025 GAAP operating expenses to be between $485 million and $495 million. This includes an estimated $60 million related to stock-based compensation, therefore operating expenses not including stock-based compensation are forecasted at between $425 million and $435 million for the year. This operating expense outlook includes additional commercial investment to support the launch of the company’s pediatric product in HAE, ongoing work on the transition study (APeX-T), and continued generation of real-world evidence to support and enhance the company’s global commercial activities. For R&D, the additional investments include support for clinical activities for both BCX17725 and avoralstat. Profitability OutlookIn 2024, revenue growth significantly exceeded operating expense growth. The company expects this pattern to continue, and over the next three years the company expects an annual CAGR for revenue of around 20 percent, compared to a projected annual operating expense CAGR of closer to five percent over the same period. Building on its significant operating profit in 2024 (not including stock-based compensation), the company expects to approach quarterly positive EPS and positive cash flow in the second half of 2025, and to be profitable on an EPS basis, with positive cash flow, for full year 2026. Presentation Tuesday at 43rd Annual J.P. Morgan Healthcare ConferenceOn Tuesday, January 14, 2025 at 6:00 p.m. ET, the company will present at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco. Links to a live audio webcast and replay of the presentation may be accessed in the Investors section of BioCryst’s website at www.biocryst.com. About BioCryst Pharmaceuticals BioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with hereditary angioedema and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat diseases. BioCryst has commercialized ORLADEYO® (berotralstat), the first oral, once-daily plasma kallikrein inhibitor, and is advancing a pipeline of small-molecule and protein therapies. For more information, please visit www.biocryst.com or follow us on LinkedIn. Non-GAAP Financial Measures The information furnished in this release includes non-GAAP financial measures that differ from measures calculated in accordance with generally accepted accounting principles in the United States of America (GAAP). In particular, we provide the non-GAAP financial measure of expected full year 2025 GAAP operating expense, adjusted to show the expected results without including our estimated stock-based compensation expense. We believe providing this non-GAAP measure, which shows our expectations with this item adjusted, is valuable and useful since it allows management and investors to better understand the company’s expected financial performance in the absence of certain non-cash items, such as stock-based compensation, and allows investors to more accurately understand our expectations and compare them to future results. This non-GAAP measure also corresponds with the way we expect Wall Street analysts to compare our results. Non-GAAP measures should be considered only as supplements to, and not as substitutes for or in isolation from, our other measures of financial information prepared in accordance with GAAP, such as GAAP revenue, operating income, net income and earnings per share. Forward-Looking StatementsThis press release contains forward-looking statements, including statements regarding preliminary, unaudited revenue results and future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause BioCryst’s actual results, performance or achievements to be materially different from any preliminary, unaudited revenue results and future results, performance or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: BioCryst’s completion of its customary closing, review and audit procedures for the fourth quarter and full year 2024, which may cause actual revenue results for these periods to differ materially from the preliminary, unaudited revenue results; BioCryst’s ability to successfully implement or maintain its commercialization plans for ORLADEYO; BioCryst’s ability to successfully progress its pipeline development plans as described herein; the results of BioCryst’s partnerships with third parties may not meet BioCryst’s current expectations; risks related to government actions, including that decisions and other actions, including as they relate to pricing, may not be taken when expected or at all, or that the outcomes of such decisions and other actions may not be in line with BioCryst’s current expectations; the commercial viability of ORLADEYO, including its ability to achieve sustained market acceptance and demand; ongoing and future preclinical and clinical development of product candidates may take longer than expected and may not have positive results; BioCryst may not be able to enroll the required number of subjects in planned clinical trials of product candidates; BioCryst may not advance human clinical trials with product candidates as expected; the FDA or other applicable regulatory agency may require additional studies beyond the studies planned for products and product candidates, may not provide regulatory clearances which may result in delay of planned clinical trials, may impose certain restrictions, warnings, or other requirements on products and product candidates, may impose a clinical hold with respect to product candidates, or may withhold, delay or withdraw market approval for products and product candidates; product candidates, if approved, may not achieve market acceptance; BioCryst’s ability to successfully commercialize its products and product candidates; BioCryst’s ability to successfully manage its growth and compete effectively; risks related to the international expansion of BioCryst’s business; timing for achieving and sustainability of profitability and positive cash flow may not meet management’s expectations; statements and projections regarding financial guidance and goals and the attainment of such goals may differ from actual results based on market factors and BioCryst’s ability to execute its operational and budget plans; and actual financial results may not be consistent with expectations, including that revenue, operating expenses and cash usage may not be within management’s expected ranges. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst’s most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, which identify important factors that could cause actual results to differ materially from those contained in BioCryst’s projections and forward-looking statements. BCRXW Contact:John Bluth+1 919 859 7910jbluth@biocryst.com