Angioedema

Anaphylm meets all predefined primary and secondary pharmacokinetic endpoints Anaphylm time to maximum concentration (Tmax) is consistently faster than autoinjectors Anaphylm exposure levels (AUC) are comparable to autoinjectors for 30 minutes after dosing Anaphylm is well-tolerated with no serious adverse events Company receives positive Type C meeting feedback from the U.S. Food and Drug Administration (FDA) regarding the clinical development of Anaphylm Company reaffirms goal of filing NDA before the end of 2024 March 14, 2024 -- Aquestive Therapeutics, Inc. (NASDAQ: AQST), a pharmaceutical company advancing medicines to bring meaningful improvement to patients' lives through innovative science and delivery technologies, today released positive topline clinical data from its Phase 3 pivotal pharmacokinetic (PK) clinical study of Anaphylm™ (epinephrine) Sublingual Film and findings from the FDA Type C meeting. Anaphylm is the Company’s first and only orally administered epinephrine prodrug product candidate under development for the treatment of severe life-threatening allergic reactions, including anaphylaxis. “We are extremely pleased with the pivotal study results as well as our recent FDA interaction,” said Daniel Barber, President and Chief Executive Officer of Aquestive. “When it comes to treating severe allergic reactions including anaphylaxis, we often hear from clinicians that rapid absorption of epinephrine at the first sign of symptoms is critical. Our pivotal study indicates that Anaphylm is comparable to the leading autoinjectors immediately following administration and our time to maximum concentration, or Tmax, is faster than the leading autoinjectors. We believe this performance is unprecedented among the alternate delivery options under development and are excited at the potential of Anaphylm as the only oral medicine for treatment of severe allergies.” “In addition, our recent discussions with the FDA remained consistent with our previous interactions,” continued Mr. Barber. “We believe we have a clear understanding of the remaining clinical development steps necessary for a pre-NDA meeting with the FDA in the second half of the year. Our goal continues to be to file our NDA before the end of 2024 following completion of a positive pre-NDA meeting.” David Golden, M.D., a renowned expert on anaphylaxis and an allergy-immunology consultant at Sinai Hospital of Baltimore and Franklin Square Hospital in Baltimore, stated, “The data from the Anaphylm pivotal study build on the compelling data generated from the prior Anaphylm pilot studies. These latest study results show that the sublingual administration of epinephrine provides rapid and sustained levels of epinephrine similar to approved treatments. Anaphylm is a promising needle-free alternative to the current standard of care, allowing patients to easily carry and administer this life-saving medication.” The two-part, Phase 3, single-center, open-label, randomized study was designed to compare the PK and pharmacodynamics (PD) of single and repeat doses of Anaphylm versus single and repeat doses of the epinephrine intra-muscular (IM) injection and epinephrine autoinjectors (EpiPen® and Auvi-Q®) in healthy adult subjects. The primary endpoint was to compare the PK of epinephrine following the single administration of Anaphylm to the single administration of Adrenalin (epinephrine IM injection) and autoinjectors in healthy adult subjects. The secondary endpoints included evaluating PK sustainability following repeat administration and the safety and tolerability following single and repeat administrations versus epinephrine IM injection and epinephrine autoinjectors. The single dose part of the Phase 3 study was designed as a four-period, four-treatment, four-sequence, comparative PK study with 64 enrolled adult subjects. As outlined in the presentation posted to the Company’s website and filed with the SEC today, key findings from the single dosing part of the study included that Anaphylm: Achieved a geometric mean Cmax of 470 pg/mL bracketed by epinephrine autoinjectors AUVI-Q at 521 pg/mL and EpiPen at 469 pg/mL, Generated partial AUCs between (bracketed) autoinjectors and Adrenalin manual IM injection from 5 to 60 minutes Maintained a median Tmax of 12 minutes compared to 20 minutes for EpiPen, 30 minutes for AUVI-Q, and 50 minutes for Adrenalin, Produced a meaningful change from baseline pharmacodynamic measures of blood pressure and heart rate at the first tracked time point of 2 minutes, and Was consistently well tolerated with no SAEs. The repeat dosing part of the Phase 3 study was designed as a three-period, three-treatment, six sequence, comparative PK study with 36 enrolled adult subjects. As outlined in the presentation posted to the website and filed with the SEC, the key findings from the repeat dosing part of the Study included that Anaphylm: Maintains epinephrine plasma concentrations equal to or greater than existing injection products at all but 1 timepoint out to 2 hours, Demonstrated a median Tmax of 10 minutes after administration of the second dose, Exhibited consistent pharmacodynamics, and Was consistently well tolerated with no SAEs. The Company also successfully completed a Type C meeting with the FDA that addressed open items from the November 2022 End-of-Phase 2 meeting including addressing (1) the impact of any product hold time, (2) the potential for emesis (vomiting), and (3) the impact of potential mouth conditions such as angioedema (swelling). In response to these questions, the FDA indicated that the Company has “adequately addressed” the FDA’s previous concerns by removing product hold time from the administration instructions and provided additional information on how to characterize emesis in the Company’s NDA submission. Regarding mouth conditions, the FDA recommended administering Anaphylm after oral exposure to a known allergen and assessing PK performance thereunder. The Company will execute this study in the second quarter of 2024. This study will replace the Company’s previously planned angioedema study. The FDA noted that substantial progress had been made in the Anaphylm clinical development program and did not outline any new clinical development requirements. As expected, the FDA reiterated that, as with other epinephrine programs under development, concentrations of epinephrine above known EpiPen levels must be justified from a safety perspective, and PK sustainability remains a focus. Furthermore, the FDA recommended that Aquestive begin its pediatric study after completion of the remaining adult studies. The Company is aligned with this recommendation from the FDA. The FDA reserved judgement on the sufficiency of the Anaphylm clinical development program until completion of ongoing and planned studies, the results of which are expected to be presented at the pre-NDA meeting. Table 1 provides an updated view on the expected clinical study dates. Table 1: Anaphylm Clinical Study Timeline Status The next anticipated meeting with the FDA is the pre-NDA meeting targeted for the second half of 2024. Aquestive’s goal is to file the NDA with the FDA before year end 2024. A presentation containing additional information about this topline data and the Company’s recent FDA Type C meeting is available on the Events and Presentations page within the Investor page of the Aquestive website. Anaphylaxis is a serious systemic hypersensitivity reaction with that is rapid in onset and potentially fatal. As many as 49 million people in the United States are at chronic risk for anaphylaxis. Lifetime prevalence is at least 5%, or more than 16 million people in the United States. Direct costs of anaphylaxis have been estimated at $1.2 billion per year, with direct expenditures of $294 million for epinephrine, and indirect costs of $609 million. The frequency of hospital admissions for anaphylaxis has increased 500–700% in the last 10–15 years. Of patients who previously experienced anaphylaxis, 52% had never received an epinephrine auto-injector prescription, and 60% did not have an auto-injector currently available. The most common causes of anaphylaxis are foods (such as peanuts), venom from insect stings, and medications. Epinephrine injection is the current standard of treatment intended to reverse the severe manifestation of anaphylaxis, which may include skin rash, throat swelling, respiratory difficulty, gastrointestinal distress, and loss of consciousness. Anaphylm is a polymer matrix-based epinephrine prodrug candidate product. The product is similar in size to a postage stamp, weighs less than an ounce, and begins to dissolve on contact. No water or swallowing is required for administration. The packaging for Anaphylm is thinner and smaller than an average credit card, can be carried in a pocket, and is designed to withstand weather excursions such as exposure to rain and/or sunlight. The tradename for AQST-109, “Anaphylm” has been conditionally approved by the United States Food and Drug Administration (FDA). Final approval of the Anaphylm proprietary name is conditioned on FDA approval of the product candidate. Aquestive is a pharmaceutical company advancing medicines to bring meaningful improvement to patients' lives through innovative science and delivery technologies. We are developing orally administered products to deliver complex molecules, providing novel alternatives to invasive and inconvenient standard of care therapies. Aquestive has five commercialized products marketed by its licensees in the U.S. and around the world, and is the exclusive manufacturer of these licensed products. The Company also collaborates with pharmaceutical companies to bring new molecules to market using proprietary, best-in-class technologies, like PharmFilm®, and has proven drug development and commercialization capabilities. Aquestive is advancing a late-stage proprietary product pipeline focused on treating diseases of the central nervous system and an earlier stage pipeline for the treatment of severe allergic reactions, including anaphylaxis. For more information, visit Aquestive.com and follow us on LinkedIn. The content above comes from the network. if any infringement, please contact us to modify.

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

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: