Hereditary Angioedema

Industry veteran with late-stage clinical development, medical affairs, and regulatory experience; well-positioned to advance losmapimod towards a potential regulatory submission and approval Interim Chief Medical Officer, Iain Fraser, MBChB, DPhil, will continue to serve on Fulcrum’s executive leadership team as senior vice president (SVP) of early development CAMBRIDGE, Mass., March 18, 2024 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc.® (Fulcrum) (Nasdaq: FULC), a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases, today announced the appointment of Patrick Horn, M.D., Ph.D., as chief medical officer, effective immediately. Dr. Horn is a seasoned executive with over 20 years of end-to-end drug development experience spanning multiple therapeutic areas, with an emphasis on rare diseases, across both large pharmaceutical and biotech companies. Interim chief medical officer, Iain Fraser, MBChB, DPhil, will continue to serve on Fulcrum’s executive leadership team as SVP of early development. Together, Drs. Horn and Fraser will be responsible for leading clinical development and overseeing regulatory strategy and execution. “I am very pleased to enrich our leadership team with Pat, an accomplished industry veteran who has successfully guided multiple therapies—including rare disease programs lacking existing regulatory pathways—through late clinical development, regulatory approval, and commercial launch,” said Alex C. Sapir, Fulcrum’s president and chief executive officer. “This is a key moment for Fulcrum as we continue to advance our Phase 3 REACH trial of losmapimod for patients with facioscapulohumeral muscular dystrophy and reinitiate our Phase 1b PIONEER trial of pociredir in sickle cell disease. We believe both Pat and Iain’s complementary expertise will be invaluable as we near several pivotal milestones for our two key clinical programs and advance our early-stage pipeline.” Dr. Horn added, "Joining Fulcrum is an exciting opportunity to bring potentially transformative therapies to patients especially as we advance towards near-term inflection points for losmapimod, a late-stage clinical program with first-to-market potential, and pociredir, a highly differentiated oral treatment option that may shift the current standard of care. Building on the encouraging clinical data generated to date, I, alongside Iain, look forward to working with the management team to deliver on the promise of Fulcrum’s differentiated pipeline of rare disease programs.” Dr. Patrick Horn is a distinguished professional with over 20 years of experience in the field of rare disease drug development, encompassing all stages from initial research to regulatory approval and commercial launch. His most recent role was as the Chief Medical Officer at HemoShear Therapeutics, specializing in rare metabolic diseases. Previously, he held the position of Chief Medical Officer at Albireo Pharma where he led the team that achieved marketing approvals in the US and Europe for Bylvay™ in progressive familial intrahepatic cholestasis (PFIC). Before his tenure at Albireo, he served as the Senior Vice President of Medical and Clinical Development at Orphan Technologies, directing the advancement of novel treatments for homocystinuria. Prior to this, he was the Chief Medical Officer at Tetraphase Pharmaceuticals, where he oversaw the clinical development of antibiotic candidates, including the program leading to the New Drug Application for eravacycline. Before Tetraphase, Dr. Horn led the clinical program at Dyax Corp. that resulted in the approval of Kalbitor® for the treatment of hereditary angioedema. Dr. Horn received his M.D., and Ph.D., from the University of Chicago and completed his pediatric residency at Boston Children’s Hospital. Prior to transitioning to industry, Dr. Horn was a practicing pediatrician at major academic institutions in Chicago. About Fulcrum Therapeutics Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum’s two lead programs in clinical development are losmapimod, a small molecule in development for the treatment of facioscapulohumeral muscular dystrophy (FSHD), and pociredir (formerly known as FTX-6058), a small molecule designed to increase expression of fetal hemoglobin and in development for the treatment of sickle cell disease (SCD). Fulcrum uses proprietary technology to identify drug targets that can modulate gene expression to treat the known root cause of gene mis-expression. For more information, visit and follow us on Twitter/X (@FulcrumTx) and LinkedIn. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release are forward-looking statements, including express or implied statements regarding advancement of losmapimod towards regulatory submission and approval;; reinitiation of the Phase 1b trial; advancement of Fulcrum’s early-stage pipeline; Fulcrum’s ability to deliver an FDA-approved therapy for FSHD patients; and the potential for pociredir to shift the standard of care;; among others. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Fulcrum’s ability to continue to advance its product candidates in clinical trials; initiating and enrolling clinical trials on the timeline expected or at all; obtaining and maintaining necessary approvals from the FDA and other regulatory authorities; replicating in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of losmapimod, pociredir and any other product candidates; obtaining, maintaining or protecting intellectual property rights related to its product candidates; managing expenses; managing executive and employee turnover, including integrating a new CMO; and raising the substantial additional capital needed to achieve its business objectives, among others. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Fulcrum’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties, and other important factors, in Fulcrum’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Fulcrum’s views as of the date hereof and should not be relied upon as representing Fulcrum’s views as of any date subsequent to the date hereof. Fulcrum anticipates that subsequent events and developments will cause Fulcrum’s views to change. However, while Fulcrum may elect to update these forward-looking statements at some point in the future, Fulcrum specifically disclaims any obligation to do so. Contact: Chris Calabrese LifeSci Advisors, LLC ccalabrese@lifesciadvisors.com 917-680-5608

The company announced the initiation of RAPIDe-3, the Phase 3 clinical trial evaluating the efficacy and safety of deucrictibant immediate-release capsule (PHVS416) for the treatment of HAE attacks ZUG, Switzerland, March 18, 2024 (GLOBE NEWSWIRE) -- Pharvaris (Nasdaq: PHVS), a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to treat and prevent hereditary angioedema (HAE) attacks, presented at two recent congresses: the 3rd National Congress of the Italian Network for Hereditary and Acquired Angioedema (ITACA) and the 2024 HAE International (HAEi) Regional Conference Americas. “We are committed to the continued advancement of our clinical development program of deucrictibant to fulfill unmet needs of current HAE treatment,” said Berndt Modig, Chief Executive Officer of Pharvaris. “In collaboration with regulatory authorities we have designed a robust global study to assess the efficacy and safety of deucrictibant, a molecule which we believe has the potential to be best-in-class for both the prevention and treatment of HAE attacks.” Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris, added, “We hear from the HAE community that rapid onset and complete resolution of angioedema attacks with a single, easy-to-administer oral pill remains a high unmet need. The RAPIDe-3 study is designed to assess the effectiveness of deucrictibant in addressing that unmet need. To our knowledge, Pharvaris has been the first and only company to include and statistically power the novel endpoint ‘End of Progression’ in a pivotal study to show the first point at which medicine stops the worsening of the symptoms of an HAE attack, recognized by people living with HAE and physicians, and which could differentiate deucrictibant from other HAE therapies. We are also presenting quality-of-life data from our prophylaxis study, CHAPTER-1, and a real-world, cross-sectional survey, both of which continue to inform us of the unmet needs in the HAE community and how deucrictibant could potentially address those needs.” The design of the Phase 3 RAPIDe-3 study was showcased for the first time in two posters on Friday. One titled “Design of RAPIDe-3 Phase 3 Trial: Efficacy and Safety of the Oral Bradykinin B2 Receptor Antagonist Deucrictibant Immediate-Release Capsule in Treatment of Hereditary Angioedema Attacks” was presented by Mauro Cancian, M.D., Ph.D., at the ITACA meeting and the second, titled “Efficacy and Safety of the Oral Bradykinin B2 Receptor Antagonist Deucrictibant Immediate-Release Capsule in Treatment of Hereditary Angioedema Attacks: RAPIDe-3 Phase 3 Trial Design” was presented by Anete Grumach, M.D., Ph.D., at the HAEi Americas Congress. RAPIDe-3 is a randomized, double-blind, placebo-controlled, crossover study, which is designed to enroll approximately 120 adolescent and adult participants globally. The primary efficacy endpoint is time to onset of symptom relief, as measured by Patient Global Impression of Change (PGI-C) of at least “a little better” for two consecutive timepoints within 12 hours post-treatment. Other efficacy endpoints include time to End of Progression (EoP) in attack symptoms within 12 hours as measured by PGI-C, and proportion of attacks achieving symptom resolution with one dose of deucrictibant as measured by Patient Global Impression of Severity (PGI-S). In a poster titled “Prophylactic Treatment with Oral Deucrictibant Improves Health-Related Quality of Life of Patients with Hereditary Angioedema” presented by Andrea Zanichelli, M.D., Ph.D., on Friday at the ITACA meeting, two health-related quality of life (HRQoL) outcomes were measured in participants from CHAPTER-1, a double-blinded, placebo-controlled Phase 2 study evaluating the efficacy and safety of deucrictibant for the prevention of HAE attacks. The data illustrates that HRQoL is negatively impacted, including functional and psychological impairment, in people with HAE. Analyses of CHAPTER-1 study data provide evidence that prophylactic treatment with oral deucrictibant for 12 weeks improved HRQoL for people living with HAE, in addition to significant reduction of attacks. In a poster titled “Need for Caregiver Support for People Living with Hereditary Angioedema in European Countries,” also presented by Andrea Zanichelli, M.D., Ph.D., on Friday at the ITACA meeting, the Adelphi HAE Disease Specific Programme™ (DSP™) examined caregiver support requirements among people living with HAE in some European countries, as well as the impact of their condition on their HRQoL and ability to work. About Deucrictibant Deucrictibant is a potent, selective, and orally available antagonist of the bradykinin B2 receptor. By inhibiting bradykinin signaling through the bradykinin B2 receptor, deucrictibant has the potential to treat the clinical signs of an HAE attack and to prevent the occurrence of attacks. Based on its chemical properties, Pharvaris is developing two formulations of deucrictibant for oral administration; a capsule to enable rapid onset of activity for acute treatment, and an extended-release tablet to enable sustained absorption and efficacy in prophylactic treatment. About Pharvaris Building on its deep-seated roots in HAE, Pharvaris is a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to treat and prevent HAE attacks. By directly pursuing this clinically proven therapeutic target with novel small molecules, the Pharvaris team aspires to offer people with all sub-types of HAE efficacious, safe, and easy-to-administer alternatives to treat attacks, both on-demand and prophylactically. The company brings together the best talent in the industry with deep expertise in rare diseases and HAE. For more information, visit . Forward-Looking Statements This press release contains certain forward-looking statements that involve substantial risks and uncertainties. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements relating to our future plans, studies and trials, and any statements containing the words “believe,” “anticipate,” “expect,” “estimate,” “may,” “could,” “should,” “would,” “will,” “intend” and similar expressions. These forward-looking statements are based on management’s current expectations, are neither promises nor guarantees, and involve known and unknown risks, uncertainties and other important factors that may cause Pharvaris’ actual results, performance or achievements to be materially different from its expectations expressed or implied by the forward-looking statements. Such risks include but are not limited to the following: uncertainty in the outcome of our interactions with regulatory authorities, including the FDA; the expected timing, progress, or success of our clinical development programs, especially for deucrictibant immediate-release capsules (PHVS416) and deucrictibant extended-release tablets (PHVS719), which are in late-stage global clinical trials; risks arising from epidemic diseases, such as the COVID-19 pandemic, which may adversely impact our business, nonclinical studies, and clinical trials; the outcome and timing of regulatory approvals; the value of our ordinary shares; the timing, costs and other limitations involved in obtaining regulatory approval for our product candidates, or any other product candidate that we may develop in the future; our ability to establish commercial capabilities or enter into agreements with third parties to market, sell, and distribute our product candidates; our ability to compete in the pharmaceutical industry, including with respect to existing therapies, emerging potentially competitive therapies and with competitive generic products; our ability to market, commercialize and achieve market acceptance for our product candidates; our ability to raise capital when needed and on acceptable terms; regulatory developments in the United States, the European Union and other jurisdictions; our ability to protect our intellectual property and know-how and operate our business without infringing the intellectual property rights or regulatory exclusivity of others; our ability to manage negative consequences from changes in applicable laws and regulations, including tax laws, our ability to successfully remediate the material weaknesses in our internal control over financial reporting and to maintain an effective system of internal control over financial reporting; changes and uncertainty in general market, political and economic conditions, including as a result of inflation and the current conflict between Russia and Ukraine and the Hamas attack against Israel and the ensuing war; and the other factors described under the headings “Cautionary Statement Regarding Forward-Looking Statements” and “Item 3. Key Information—D. Risk Factors” in our Annual Report on Form 20-F and other periodic filings with the U.S. Securities and Exchange Commission. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. While Pharvaris may elect to update such forward-looking statements at some point in the future, Pharvaris disclaims any obligation to do so, even if subsequent events cause its views to change. These forward-looking statements should not be relied upon as representing Pharvaris’ views as of any date subsequent to the date of this press release. Contact Maggie Beller Executive Director, Head of External and Internal Communications maggie.beller@pharvaris.com

Delays in treating attacks lead to increased anxiety, quality of life issues, higher frequency of returning attacks, and suboptimal clinical outcomes in both on-demand and prophylaxis patients CAMBRIDGE, Mass. & SALISBURY, England--(BUSINESS WIRE)-- KalVista Pharmaceuticals, Inc. (NASDAQ: KALV), a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of oral, small molecule protease inhibitors, today announced that it presented multiple analyses of the relationship between the time to attack treatment and the effects delays in treatment have on clinical outcomes of people living with hereditary angioedema (HAE) at the 2024 HAEi Regional Conference Americas that took place in Panama City, Panama. “These data show once again that people living with HAE still face challenges in following established guidelines for treating their attacks,” said Ben Palleiko, Chief Executive Officer of KalVista. “Even short treatment delays can lead to worse clinical outcomes, and despite efficacious on-demand treatments, the fact that they need to be injected results in barriers which lead to significant underuse and resultant overuse of long-term prophylaxis. If approved, sebetralstat should enable improved compliance with these guidelines, which has the potential to help people with HAE to better control their disease with a lower overall burden of treatment.“ The following presentations occurred at the 2024 HAEi Regional Conference Americas: Relationship Between Time to ​On-demand Treatment and Quality of Life During Hereditary Angioedema Attacks: Sandra Christiansen, University of California San Diego, La Jolla, CA, United States (Oral Presentation) Treatment delays are associated with lower QoL and poorer general health during HAE attack, emphasizing the benefits of compliance with HAE guidelines and greater awareness of the impact of delayed treatment on QoL Characterizing the Negative Impact of Delayed On-Demand Treatment of HAE Attacks: Ricardo Zwiener, Servicio de Alergia e Inmunología Clínica, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina (Poster Presentation) The time to feeling in control of an HAE attack and time to feeling fully recovered were shorter for patients treating HAE attacks in <1 hour versus those who waited ≥1 hour Anxiety Associated with Refilling On-demand Therapy for HAE Attacks Contributes to Treatment Delay and Non-Treatment: Anete S. Grumach, Clinical Immunology, Faculdade de Medicina, Centro Universitario FMABC, Santo Andre, Brazil (Poster Presentation) Anxiety associated with not being able to refill on-demand treatment impacted treatment decisions, which contributed to treatment delay or resulted in non-treatment of HAE attacks Treatment Patterns of Patients Requiring Redosing of an On-demand Treatment After the Return of an HAE Attack: William Lumry, Allergy and Asthma Research Associates, Dallas, Texas, United States. (Poster Presentation) HAE attacks initially treated within 1 hour returned less frequently compared with attacks treated at 1 hour or longer Anxiety Associated with On-Demand Treatment for Hereditary Angioedema (HAE) Attacks: Maeve O’Connor, Allergy, Asthma, & Immunology Relief of Charlotte, Charlotte, NC, United States (Poster Presentation) Both adults and adolescents with HAE reported moderate to extreme anxiety when anticipating use of parenteral on-demand treatment, irrespective of use of on-demand only or on-demand plus LTP Characteristics of Hereditary Angioedema Attacks Among Long-Term Prophylaxis Users: Maeve O’Connor, Allergy, Asthma, & Immunology Relief of Charlotte, Charlotte, NC, United States (Poster Presentation) Among HAE patients who had treated a recent attack, the location and duration of the most recent attacks were similar between long-term prophylaxis (LTP) and on-demand only users Links to all posters and presentations can be found on the KalVista website under “Publications”. About KalVista Pharmaceuticals, Inc. KalVista Pharmaceuticals, Inc. is a pharmaceutical company focused on the discovery, development, and commercialization of oral, small molecule protease inhibitors 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. FDA for sebetralstat in the first half of 2024 and expects to approval in Europe and Japan later in 2024. In addition, KalVista’s oral Factor XIIa inhibitor program represents a new generation of therapies that may further improve the treatment for people living with HAE and other diseases. 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, our expectations about safety and efficacy of our product candidates and timing of clinical trials and their results, our ability 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, 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. View source version on businesswire.com: Contacts KalVista Pharmaceuticals, Inc. Jarrod Aldom Vice President, Corporate Communications (201) 705-0254 jarrod.aldom@kalvista.com Ryan Baker Head, Investor Relations (617) 771-5001 ryan.baker@kalvista.com Source: KalVista Pharmaceuticals, Inc. View this news release online at: