Chiba University

– US subgroup in the phase 3 KONFIDENT trial demonstrates median time to treatment of 38 minutes and time to beginning of symptom relief 1.3 hours – – Despite growing use of long-term prophylaxis therapies in the US on-demand treatment prescription volumes stay stable and non-prescription healthcare costs for management of HAE remain substantial – CAMBRIDGE, Mass. & SALISBURY, England--(BUSINESS WIRE)-- KalVista Pharmaceuticals, Inc. (NASDAQ: KALV), today announced that it presented the US subgroup analysis from the sebetralstat phase 3 KONFIDENT trial and real-world claims and patient survey data at the Eastern Allergy Conference (EAC) 2024, as well as the Japanese subgroup from KONFIDENT at the 123rd Annual Meeting of the Japanese Dermatological Association (JDA) 2024. KONFIDENT is the first pivotal phase 3 trial to include Japanese sites in an HAE development program. The following presentations occurred at EAC 2024: Sebetralstat for On-demand Treatment of Hereditary Angioedema Attacks: US Subgroup Analysis from the Double-blind, Placebo-controlled Phase 3 KONFIDENT Trial: Daniel Soteres, Asthma & Allergy Associates P.C., Colorado Springs, Colorado, United States. (Poster presentation) Median time from attack onset to administration was 38 minutes (IQR 5-124) for the US subgroup (78 attacks), which compares favorably to the median time to treatment of 41 minutes (IQR 6-140) in the overall trial population Median time to beginning of symptom relief for 300 mg in the US subgroup was 1.28 hours (IQR 0.77-3.12), which also compares favorably to the 300 mg median time to beginning of symptom relief of 1.61 hours (IQR 0.78-7.04) for the overall trial population Trends in volume of on-demand hereditary angioedema treatments in the US: A retrospective analysis of a large multi-payer claims database: Daniel Soteres, Asthma & Allergy Associates P.C., Colorado Springs, Colorado, United States. (Poster presentation) Despite the advent of multiple non-androgen LTPs since 2017, the overall trend in the total number of claims reimbursed and quantity dispensed for on-demand treatments has remained stable in the US Average year-over-year variability in the total number of on-demand syringes and vials dispensed per quarter has remained within 3% and 10%, respectively, of baseline from Q3 2018 – Q3 2023 Healthcare Costs Among Commercially Insured Patients with Hereditary Angioedema Managed with Long-term Prophylaxis: a Retrospective US Claims Database Analysis: Daniel Soteres, Asthma & Allergy Associates P.C., Colorado Springs, Colorado, United States. (Poster presentation) Claims database analysis revealed that HAE-related non-pharmacy resource utilization costs among patients receiving non-androgen LTP were substantial, averaging >$641,000 in HAE healthcare costs per patient per year Approximately one-third of patients receiving non-androgen LTP had ≥1 HAE-related ER visits during follow-up (33%), and nearly one-quarter (22%) had ≥1 HAE-related home health visit Real-World Impact of Treated Hereditary Angioedema Attacks on Patients’ Quality of Life: Maeve O’Connor, Allergy, Asthma, & Immunology Relief of Charlotte, Charlotte, NC, United States. (Poster presentation) Attacks occurring among patients receiving non-androgen LTP and those receiving on-demand treatment only similarly impact physical and social quality of life (QoL) Attacks treated in <1 hour were associated with a lower impact on QoL Real-world Impact of Treated Hereditary Angioedema Attacks on Patients’ Employment and Work Productivity: Maeve O’Connor, Allergy, Asthma, & Immunology Relief of Charlotte, Charlotte, NC, United States. (Poster presentation) HAE attacks among patients receiving non-androgen LTP and those receiving on-demand treatment only similarly impacted the work lives of employed patients resulting in impairments in their ability to work, substantial absenteeism, reduced productivity, and presenteeism among those who were able to work Burden of the Untreated Attacks and its Impact on Social, Mental and Physical Health: Maeve O’Connor, Allergy, Asthma, & Immunology Relief of Charlotte, Charlotte, NC, United States. (Poster presentation) Patients, including those taking LTP, reported that untreated HAE attacks often progressed in severity, migrated to other locations, and were associated with social isolation and impact on physical/mental health 70% of patients indicated that their last untreated attack had an impact on their energy levels; 55% and 22% of LTP and on-demand only patients, respectively, felt reluctant to go out in public The following presentation occurred at the Annual Meeting of the JDA 2024: Sebetralstat KONFIDENT Is the First Phase 3 On-demand HAE Trial to Include Japanese Sites: Daisuke Honda, Chiba University Graduate School of Medicine, Chiba, Japan. (Poster presentation) Despite the relatively small number of attacks that were treated in the subgroup of Japanese KONFIDENT participants, primary endpoint results were consistent with those observed in the overall trial population Among Japanese participants, sebetralstat was well tolerated with no treatment-related TEAEs, no serious or severe TEAEs, and no TEAEs leading to study discontinuation “We have observed exceptional consistency of results across subgroups in the KONFIDENT trial including attack severity, location, treatment paradigm (with or without long-term prophylaxis) and geography,” said Ben Palleiko, CEO of KalVista Pharmaceuticals. “This data further highlights that patients on LTP generally continue to have attacks, and that those attacks have similar impact as on-demand only users, showing the continued unmet need although it is not generally recognized. In parallel, claims data also highlight that on-demand prescription volumes have remained stable despite the introduction of subcutaneous and oral long-term prophylaxis options. Sebetralstat has the potential to transform the management of HAE.” Links to all posters and presentations can be found on the KalVista website under “Publications”. About KalVista Pharmaceuticals, Inc. KalVista Pharmaceuticals, Inc. is a global pharmaceutical company focused on the development and delivery of oral medicines for diseases with significant unmet need. KalVista disclosed positive phase 3 data for the KONFIDENT trial for its oral, on-demand therapy sebetralstat in February 2024. The Company anticipates submitting a new drug application to the U.S. Food and Drug Administration (FDA) for sebetralstat in June 2024 and expects to approval in the UK, Europe and Japan later in 2024. For more information about KalVista, please visit . 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 or other international regulatory agencies, our expectations about safety and efficacy of our product candidates, our ability to obtain regulatory approvals for sebetralstat and other candidates in development within our expected timelines or at all, our success in engaging with potential commercial partners, the success of any efforts to commercialize sebetralstat, the ability of sebetralstat and other candidates in development to treat HAE or other diseases, our ability to commence pediatric trials of sebetralstat and develop an ODT formulation, the future progress and potential success of our oral Factor XIIa program, our ability to reduce spending on discovery and preclinical activities, and our expectation to become cash flow positive. 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, 2023, 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.

Although drug eruptions are often linked to the human leukocyte antigen (HLA), the mechanism of its involvement in presenting symptoms of the skin remains unclear. In a recent study, researchers used genetically engineered mice to demonstrate the role of HLA in mediating intracellular reactions in keratinocytes, leading to drug eruptions in the skin. Their findings could lead to improved preventive and treatment measures for drug eruptions. Although medications can often help patients find a cure or respite from their condition, millions of people worldwide suffer from unpredictable drug toxicities every year. In particular, drug eruptions which manifest through symptoms such as redness, blisters, and itching on the skin, are quite common. Severe drug eruptions can become life-threatening and can have long-lasting consequences. Thus, understanding how and why drug eruptions occur is an important area of research in medical science. To this end, previous studies have identified specific variants of certain genes as potential causal agents of drug eruptions. Scientists believe that the genes encoding the human leukocyte antigen (HLA), a protein expressed on the surface of leucocytes known to play an important role in the immune system, are involved in the onset of drug eruption. However, current theories cannot explain why HLA-related drug eruptions typically manifest on the skin rather than in multiple organs throughout the body. To address this knowledge gap, a research team including Lecturer Shigeki Aoki, Kousei Ito, and Akira Kazaoka from the Graduate School of Medical and Pharmaceutical Sciences, Chiba University, conducted an in-depth study on the link between HLA and drug eruptions. Their findings were published in PNAS Nexus on April 2, 2024. The researchers first conducted a series of experiments on keratinocytes from mice, which are the primary type of cells found in the skin. These keratinocytes were engineered to express a specific variant of the HLA gene called HLA-B*57:01, which specifically bind to the antiviral drug abacavir. Then, they validated these findings in genetically modified mice expressing HLA-B*57:01, that were exposed to abacavir. The researchers found that HLA-B*57:01 expressing keratinocytes that were exposed to abacavir exhibited endoplasmic reticulum (ER) stress responses, such as immediate release of calcium into the cytosol and elevated expression of heat shock protein 70 (HSP70). They also observed an increased production of cytokines and immune cell migration. Abacavir exposure triggered HLA misfolding in the ER, leading to ER stress. Moreover, the researchers observed that the ER stress could be reduced by using 4-phenylbutyrate (4-PB). By alleviating this stress, they managed to suppress the onset of severe drug eruption symptoms. This newfound knowledge could form the basis for innovative treatment options for management of drug eruptions. But how does this new information contrast with what was already known about HLA? "HLA molecules are an integral component of our immune system, that typically present foreign antigens to white blood cells, which judge these antigens as self or non-self. In this established role, HLAs are usually secondary players," explains Dr. Aoki. "However, our research highlights a novel function of the HLA molecule within skin cells. We revealed that a specific HLA genotype in keratinocytes can recognize certain drugs as foreign, triggering an endoplasmic reticulum stress response." Taken together, the findings of this study uncover a new role of HLA proteins in sensing and responding to potential threats in skin cells. Thus, their functions may extend well beyond mere antigen presentation for the immune system. Moreover, considering that the variant of HLA possessed by an individual can be determined through genetic testing, this study could help develop preventive measures and diagnostics against severe adverse drug reactions. According to Dr. Aoki, this is in line with current research directions and trends in medical science. "In 10 years, we anticipate entering the 'whole genome era,' where personalized medicine based on individual genomes will become a standard practice," he comments. He further adds, "Building on the findings of this study, we believe that a comprehensive understanding of the mechanism underlying HLA-dependent adverse drug reactions will enable the delivery of safe medical care, allowing patients to avoid unnecessary suffering due to side effects." Overall, future investigations in this research area might minimize the occurrence of drug eruptions and save people from potentially fatal adverse drug reactions. About Dr. Shigeki Aoki Dr. Shigeki Aoki is a lecturer at the Graduate School of Pharmaceutical Sciences, Chiba University, Japan. His research focuses mainly on cancer metabolism and drug toxicity. He has authored multiple papers published in reputed journals. Dr. Aoki is a member of various professional bodies in Japan. He has also received several awards for his research, including the Award for Young Scientists conferred by The Pharmaceutical Society of Japan.

WASHINGTON, May 7, 2024 /PRNewswire/ -- Santa J. Ono, president of the University of Michigan, has joined the United States-Japan Foundation Board of Trustees. Ono, an accomplished medical researcher and leader in higher education across North America, is a second-generation Japanese American who maintains strong ties to family in Japan. His grandfather, Akira Ono, was governor of Chiba Prefecture. In addition to leading one of the largest, most-respected university systems in the U.S., Ono serves at a number of public service and advocacy organizations, including the Council on Competitiveness, the Michigan Economic Development Corporation, and the University Climate Change Coalition, which he chairs. He is an outspoken promoter of greater mental health treatment for young adults and at-risk youth. Ono has received an honorary doctorate from Chiba University and was also elected to the American Academy of Arts & Sciences. "We are thrilled to be able to add somebody with Santa Ono's demonstrated leadership, and deep ties to Japan, to our board," said Lawrence K. Fish, USJF board chair. "We look forward to working with him, and tapping into his knowledge, his network, and his creativity, as we elevate our impact in both countries." "I am so proud, so honored to join the USJF Board of Trustees," said Ono, "We have a fantastic opportunity to deepen our understanding and strengthen our engagement between the United States and Japan. So I look forward to us drawing closer together as friends, partners, and allies in order to address the great challenges of our time." Before moving to Ann Arbor as Michigan's 15th president in October 2022, Ono was president of the University of British Columbia, and the University of Cincinnati. As a faculty member at Johns Hopkins, Harvard, University College London, and Emory, Ono drew widespread recognition for his groundbreaking research on ophthalmology and immunology, in particular for his work on macular degeneration and deteriorating eyesight. In addition to his presidential duties, Ono is professor of ophthalmology and visual sciences, and microbiology and immunology, at Michigan's medical school. Ono's parents -- Takashi and Sachiko Ono -- moved to the U.S. in 1959. His father, a mathematician, had been invited to Princeton's Institute for Advanced Study by then-director Robert Oppenheimer. Ono was born in Vancouver, where his father was teaching at the time. He currently serves as the chair of the U-M Health Board, the chair of Fulbright Canada, and is the honorary chairperson of the Japan American Society of Michigan and Southwestern Ontario. In addition to Chair Fish, Ono joins on the USJF board: Vice Chair Tak Niinami, Wendy Cutler, Richard E. Dyck, Arfiya Eri, Colleen Hanabusa, James M. Kondo, Craig M. Mullaney, Richard J. Samuels, Keiko Tashiro, Donna Tanoue, and Takeshi Ueshima. The United States-Japan Foundation was started in 1980 with a mission of improving relations between the two countries. It has since given out more than $100 million in grants and oversees the US-Japan Leadership Program with a network of 500 fellows from the two countries. Contact: [email protected] SOURCE United States-Japan Foundation