Hyperammonemia

Patients, providers, and public are invited to help save lives by sharing messages and materialsPASADENA, Calif. and CELEBRATION, Fla., Oct. 09, 2024 (GLOBE NEWSWIRE) -- The National Urea Cycle Disorders Foundation (NUCDF) and Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) are teaming up to launch an awareness campaign during the month of October to improve the diagnosis of urea cycle disorders (UCDs). Their goal is to highlight the critical importance of promptly checking blood ammonia levels and using proper testing techniques. A blood ammonia test is essential to uncover elevated ammonia levels (hyperammonemia), the classic sign of a urea cycle disorder. Resources on recognizing and testing for hyperammonemia are featured on the campaign website, checkammonia.com. Quickly diagnosing UCDs is critical. Toxic ammonia levels can rise rapidly in affected individuals, which if left untreated, can cause coma and death. Newborns with severe UCDs typically become catastrophically ill within 36-48 hours after birth. It is estimated that up to 20% of sudden infant death syndrome (SIDS) cases may be attributed to an undiagnosed inborn error of metabolism such as a UCD. Adults with undiagnosed UCDs may present at emergency rooms with staggering, confusion, combativeness and disorientation that is mistaken for alcohol or drug intoxication, and many die. The campaign’s primary message is that a blood ammonia test, performed promptly and properly, can save lives. Downloadable campaign resources focus on (1) Recognizing the signs of UCDs and promptly ordering a test and (2) Following proper test procedures. About Urea Cycle Disorders A urea cycle disorder is caused by a genetic mutation—a change in a person’s genes—that leads to a deficiency of one of the enzymes needed to metabolize protein. These missing or reduced enzymes make the process less efficient, allowing ammonia to build up in the bloodstream. High ammonia levels are toxic to the brain, causing a range of physical, neurological, and behavioral symptoms. UCDs can strike at any age. Those with more severe UCDs (greater enzyme deficiency) typically become symptomatic very shortly after birth. Those with less severe UCDs (less enzyme deficiency) can develop symptoms at any time later in life. Signs of UCDs The Check Ammonia campaign website highlights the early signs of hyperammonemia in newborns and in infants, children, and adults that should prompt a blood ammonia test. Key warning signs include: Newborns from 1 to 28 days old: poor feeding or vomiting, hypotonia (poor muscle tone or floppiness), lethargy (difficult to wake up), respiratory distress, seizures, or coma.Older infants and children: inconsolable crying, agitation, or hyperactive behavior sometimes accompanied by screaming, self-injurious behavior, and refusal to eat meat or other high-protein foods. Later symptoms may include frequent episodes of vomiting, especially following high-protein meals, lethargy and delirium. Older children may be referred to child psychologists because of their behavior, developmental delays, and eating problems.Adults with high blood ammonia levels: disorientation, confusion, slurred speech, unusual and extreme combativeness or agitation, stroke-like symptoms, lethargy and delirium. Many may be seen by neurologists or psychiatrists because of psychiatric symptoms, including schizophrenia and bipolar disorder. Who should get tested? Routine ammonia checks aren’t necessary for everyone, but the test is crucial for those experiencing symptoms that could be high ammonia. How is high ammonia treated? Once identified, high ammonia levels can be managed and treated in several ways. These treatments may include medications, dietary changes including protein restriction, managing underlying conditions, or hospitalization in more severe cases, especially if neurological symptoms are present. Join the Campaign Patients, providers, and the public are invited to help share the campaign’s messages and materials widely. For electronic copies of campaign materials, visit checkammonia.com. Contact info@nucdf.org with questions or to request hard copies you can deliver to pediatricians, hospitals, emergency rooms, and other healthcare providers in your area. Follow the NUCDF’s social media sites (Facebook, LinkedIn, Instagram and YouTube) to share materials throughout the month. Learn more and hear patient stories: Watch a video on recognizing the signs of urea cycle disorders. Read about Jennings, an infant who passed away three days after he was born due to an undiagnosed UCD. Hear about Zoey, a 19-year-old girl who lost her life suddenly at age 19 from an undiagnosed urea cycle disorder. Read about Jim Stavas, a fireman who fell into a coma and died after sinus surgery due to an undiagnosed UCD (under “Why we ride”). About the National Urea Cycle Disorders Foundation: NUCDF is a nonprofit organization dedicated to saving and improving the lives of children and adults affected by urea cycle disorders (UCDs) and raising awareness since 1988. Led exclusively by patients and families affected by UCDs, we are the driving force behind critical research to improve the understanding and management of UCDs, find new treatments, and ultimately a cure. NUCDF serves as a lifeline to patients, families, and medical professionals worldwide seeking information, support, and hope. Visit www.nucdf.org or email info@nucdf.org. About Zevra Therapeutics: Zevra Therapeutics, Inc. is a commercial-stage rare disease company combining science, data, and patient needs to create transformational therapies for diseases with limited or no treatment options. Our mission is to bring life-changing therapeutics to people living with rare diseases. With unique, data-driven development and commercialization strategies, the Company is overcoming complex drug development challenges to make new therapies available to the rare disease community. For more information, please visit www.zevra.com or follow us on X (formerly Twitter) and LinkedIn. Caution Concerning Forward-Looking Statements: This press release may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that do not relate solely to historical or current facts, including without limitation statements regarding upcoming events or Zevra’s participation at such events. Forward-looking statements are based on information currently available to Zevra and its current plans or expectations. They are subject to several known and unknown uncertainties, risks, and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. These and other important factors are described in detail in the "Risk Factors" section of Zevra’s Annual Report on Form 10-K for the year ended December 31, 2023, Zevra’s Quarterly Report for the quarter ended June 30, 2024, and Zevra’s other filings with the Securities and Exchange Commission. While we may elect to update such forward-looking3 statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. Although we believe the expectations reflected in such forward-looking statements are reasonable, we cannot assure that such expectations will prove correct. These forward-looking statements should not be relied upon as representing our views as of any date after the date of this press release. NUCDF Contact Jill Williams, 513-288-1509, jwilliams@nucdf.org Zevra Contact Nichol Ochsner, +1 (732) 754-2545, nochsner@zevra.com

Innovative drug treatment developed in collaboration with SciSparc aims to enhance safety and efficacy in mental health and addiction care Vancouver, Canada, Sept. 16, 2024 (GLOBE NEWSWIRE) -- Clearmind Medicine Inc. (Nasdaq: CMND), (FSE: CWY0) (“Clearmind” or the "Company"), a clinical-stage biotech company focused on discovery and development of novel psychedelic-derived therapeutics to solve major under-treated health problems, today announced the publication of an international patent application under the Patent Cooperation Treaty (“PCT”) for its pioneering combination therapy of Ibogaine and N-Acylethanolamines. Ibogaine, a key compound derived from the root of Tabernanthe iboga, a shrub native to West and Central Africa, has shown promise in human clinical trials for treating opioid use disorder (OUD), cocaine use disorder (CUD), and other substance use disorders (SUD). As a result, Ibogaine is considered a potentially effective anti-addiction agent. The patent application follows innovative developments from Clearmind’s successful collaboration with SciSparc Ltd. (Nasdaq: SPRC) (“SciSparc”), a clinical-stage specialty pharmaceutical company focused on treatments for central nervous system disorders. Together, the two companies are researching innovative combination therapies that integrate psychedelic compounds with the N-Acylethanolamines family, including Palmitoylethanolamide (PEA). Dr. Adi Zuloff-Shani, CEO of Clearmind Medicine, commented: “The publication of this patent highlights Clearmind’s commitment to leadership in the psychedelics space through building a diverse patent portfolio, featuring technologies with varying timelines to market. Most importantly, we aim to provide safe and effective solutions for mental health conditions that currently have unmet needs. While treatments with Ibogaine are generally considered safe under proper medical supervision, there have been reports of fatalities or adverse events associated with the ingestion of iboga plant material or Ibogaine. We believe that combining Ibogaine with Palmitoylethanolamide will further enhance the efficacy and safety of this promising therapy.” About Clearmind Medicine Inc. Clearmind is a clinical-stage psychedelic pharmaceutical biotech company focused on the discovery and development of novel psychedelic-derived therapeutics to solve widespread and underserved health problems, including alcohol use disorder. Its primary objective is to research and develop psychedelic-based compounds and attempt to commercialize them as regulated medicines, foods or supplements. The Company’s intellectual portfolio currently consists of nineteen patent families including 29 granted patents. The Company intends to seek additional patents for its compounds whenever warranted and will remain opportunistic regarding the acquisition of additional intellectual property to build its portfolio. Shares of Clearmind are listed for trading on Nasdaq under the symbol "CMND" and the Frankfurt Stock Exchange under the symbol “CWY0.” About SciSparc Ltd. SciSparc Ltd. (SPRC) is a specialty clinical-stage pharmaceutical company led by an experienced team of senior executives and scientists. SciSparc’s focus is on creating and enhancing a portfolio of technologies and assets based on cannabinoid pharmaceuticals. With this focus, the Company is currently engaged in the following drug development programs based on THC and/or non-psychoactive cannabidiol: SCI-110 for the treatment of Tourette Syndrome, for the treatment of Alzheimer's disease and agitation; and SCI-210 for the treatment of autism and status epilepticus. The Company also owns a controlling interest in a subsidiary whose business focuses on the sale of hemp seeds’ oil-based products on the Amazon.com Marketplace. For further information visit: https://www.clearmindmedicine.com or contact: Investor Relationsinvest@clearmindmedicine.com Telephone: (604) 260-1566US: CMND@crescendo-ir.com General Inquiries Info@Clearmindmedicine.com www.Clearmindmedicine.com Forward-Looking Statements: This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act and other securities laws. Words such as “expects,” “anticipates,” “intends,” “plans,” “believes,” “seeks,” “estimates” and similar expressions or variations of such words are intended to identify forward-looking statements. For example, the Company is using forward-looking statements when it discusses Clearmind’s commitment to be a leader in the psychedelics space by creating a diverse patent portfolio, which contains various technologies with different times to market, but more importantly provides efficacious and safe solutions to various mental health conditions with unmet needs. The Company cannot assure that any patent will issue as a result of a pending patent application or, if issued, whether it will issue in a form that will be advantageous to the Company. Forward-looking statements are not historical facts, and are based upon management’s current expectations, beliefs and projections, many of which, by their nature, are inherently uncertain. Such expectations, beliefs and projections are expressed in good faith. However, there can be no assurance that management’s expectations, beliefs and projections will be achieved, and actual results may differ materially from what is expressed in or indicated by the forward-looking statements. Forward-looking statements are subject to risks and uncertainties that could cause actual performance or results to differ materially from those expressed in the forward-looking statements. For a more detailed description of the risks and uncertainties affecting the Company, reference is made to the Company’s reports filed from time to time with the Securities and Exchange Commission (“SEC”), including, but not limited to, the risks detailed in the Company’s annual report on Form 20-F for the fiscal year ended October 31, 2023 filed with the SEC. Forward-looking statements speak only as of the date the statements are made. The Company assumes no obligation to update forward-looking statements to reflect actual results, subsequent events or circumstances, changes in assumptions or changes in other factors affecting forward-looking information except to the extent required by applicable securities laws. If the Company does update one or more forward-looking statements, no inference should be drawn that the Company will make additional updates with respect thereto or with respect to other forward-looking statements. References and links to websites have been provided as a convenience, and the information contained on such websites is not incorporated by reference into this press release. Clearmind is not responsible for the contents of third-party websites.

New clinical efficacy and safety data for arimoclomol as a possible treatment for Niemann-Pick disease type C, including from long-term and real-world settings, demonstrate clinically meaningful reduction in disease progression Arimoclomol was well tolerated during the Open Label Extension trial and Early Access Program with no safety signals identified PK modeling studies showed that administration of OLPRUVA while fasting vs fed results in higher drug exposure which may allow for lower effective dosages when taken without food CELEBRATION, Fla., Sept. 06, 2024 (GLOBE NEWSWIRE) -- Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) (Zevra, or the Company), a rare disease therapeutics company, today announced the presentation of five posters at the Society for the Study of Inborn Errors of Metabolism (SSIEM) 2024 Annual Symposium. Four posters focused on data from multiple studies showing the efficacy and safety of arimoclomol as a treatment for people living with Niemann-Pick disease type C (NPC), and one poster highlighted data from pharmacokinetic modeling studies of OLPRUVA®, a therapy for the long-term management of certain adult and pediatric patients with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC) or argininosuccinic acid synthetase (AS). “The data collected during the Phase 2/3 study of arimoclomol, including long-term data from Open Label Extension (OLE) and Early Access Program (EAP) participants, add to the large body of evidence that demonstrates arimoclomol’s clinical efficacy and safety as a treatment for people living with NPC,” said Adrian Quartel, M.D., FFPM, Chief Medical Officer of Zevra. “Additionally, we presented PK modeling data from OLPRUVA in both adult and pediatric virtual patients, showing an increase in drug exposure under fasting conditions.” Presentation Details The data for arimoclomol presented at SSIEM is summarized below: Poster Number: 21260 Title:Efficacy Results from a 12-month Double-blind Randomized Trial of Arimoclomol for Treatment of Niemann Pick Disease Type C – presenting an improved 4-Domain NPC Clinical Severity Scale Authors:Marc Patterson, Sven Guenther and Christine i Dali Summary:The treatment effect of arimoclomol was evaluated in a 12-month, double-blind, placebo-controlled clinical trial (NCT02612129) using the original 5-domain Niemann pick type C clinical severity scale (5DNPCCSS) and the modified 4-domain Niemann Pick type C clinical severity scale (4DNPCCSS). A statistically significant treatment effect was shown using the modified 4DNPCCSS and the prespecified 5DNPCCSS primary endpoint in the 12-month clinical trial, representing a clinically meaningful reduction in disease progression with arimoclomol treatment compared to placebo. Poster Number: 21271 Title:Long-term Efficacy and Safety Evaluation of Arimoclomol Treatment in Patients with Niemann Pick Type C – Data from 48 Months Open Label Trial Authors:Marc Patterson, Eugene Mengel, Sven Guenther and Christine i Dali Summary:The long-term safety and efficacy of arimoclomol in the 12-month double-blind, and 48-month open-label extension (OLE) portion of the clinical trial (NCT02612129) were presented using the 4-Domain Niemann Pick Type C Clinical Severity scale (4DNPCCSS) which evaluates ambulation, speech, swallowing and fine motor skills. For those patients transitioning from placebo to arimoclomol at the start of the open-label extension period, the mean annual rate of disease progression reduced from an annual rate of change of 1.9 points during the double-blind phase, to a rate of 0.3 in the first 12 months of treatment, remained numerically smaller for the rest of the trial, and was comparable between the double-blind phase of the trial and the open-label extension phase of the trial. Additionally, arimoclomol was well tolerated with no new safety signals observed. Poster Number: PO-212 Title:Arimoclomol for the Treatment of NPC in a Real-World Setting: Long-term Outcomes from an Expanded Access Program in the USA Authors:Walla Al-Hertani, Elizabeth M. Berry-Kravis, Raymond Wang, Marc Patterson, Can Ficicioglu, Loren Pena, Kristina Julich, Damara Ortiz, Paula Schleifer, Caroline Hastings, Paul Hillman, Ronan O'Reilly, Christine Dali and Daniel Gallo Summary:The long-term safety and efficacy of arimoclomol in a real-world setting were evaluated in a total of 56 adult and pediatric patients in the U.S. arimoclomol expanded access program (EAP) trial (NCT04316637). Data presented included over 3 years of U.S. EAP clinical outcomes and demonstrated that adult and pediatric patients treated with arimoclomol, including those with and without miglustat as a component of their routine clinical care, experienced relatively stable disease as measured by the 5DNPCCSS and 4DNPCCSS and show that arimoclomol was well tolerated. Poster Number: 20950 Title:Arimoclomol safety profile in the treatment of NPC in a Real-World setting: Long-term data from an Expanded Access program in the USA Authors:Can Ficicioglu, Elizabeth M. Berry-Kravis, Walla Al-Hertani, Raymond Wang, Marc Patterson, Loren Pena, Kristina Julich, Damara Ortiz, Paula Schleifer, Paul Hillman, Caroline Hastings, Ronan O'Reilly, Christine Dali and Daniel Gallo Summary:Safety data from 94 adult and pediatric participants in the arimoclomol US EAP were presented. Safety outcomes reported from exposure periods spanning as much as 46 months of treatment, demonstrated a safety profile consistent with the published clinical trial experience of arimoclomol in NPC. The data for OLPRUVA presented at SSIEM is summarized below: Poster Number: PO-609 Title:Modeling the Pharmacokinetics of Phenylbutyrate in Fed and Fasted States Authors:Steiner, Rebecca Baillie, Tongli Zhang, Christina Friedrich, Meredith Hart, Mike Reed Summary:Pharmacokinetic modeling evaluating whether sodium phenylbutyrate (NaPBA) could be safely and effectively administered while fasting showed greater absorption and bioavailability with increased drug exposure in fasted administration of NaPBA compared to fed administration of NaPBA and glycerol phenylbutyrate (GPB) in both adult and child virtual patients, which is predicted to increase efficacy in proportion to increased drug exposure, theoretically allowing for a 30% dose decrease compared to fed conditions. About the SSIEM 2024 Annual Symposium The Society for the Study of Inborn Errors of Metabolism (SSIEM) 2024 Annual Symposium took place September 3-6, 2024, in Porto, Portugal. The annual symposium is intended to foster the study of inherited metabolic disorders and promote the exchange of ideas between professionals in different disciplines who are researching inborn errors of metabolism (IEM). About Niemann-Pick Disease Type C (NPC) Niemann-Pick disease type C (NPC) is an ultra-rare, progressive, and neurodegenerative lysosomal storage disorder characterized by an inability of the body to transport cholesterol and other lipids within the cell, leading to an accumulation of these substances in various tissue areas, including brain tissue. The disease is caused by mutations in the NPC1 or NPC2 genes, which are responsible for making lysosomal proteins. Both children and adults can be affected by NPC with varying clinical presentations. Those living with NPC lose independence due to physical and cognitive limitations, with key neurological impairments presenting in speech, cognition, swallowing, ambulation, and fine motor skills. Disease progression is irreversible and can be fatal within months or take years to be diagnosed and advance in severity. About Arimoclomol Arimoclomol, Zevra’s orally-delivered, investigational drug product candidate for the treatment of NPC, has been granted Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, and Rare Pediatric Disease designation by the FDA, and Orphan Medicinal Product designation for the treatment of NPC by the European Medicines Agency (EMA). The FDA has accepted the resubmission of the NDA for arimoclomol and has set a user fee action date (PDUFA date) of September 21, 2024. About Urea Cycle Disorders UCDs are a group of rare, genetic disorders that can cause harmful ammonia to build up in the blood, potentially resulting in brain damage and neurocognitive impairments if ammonia levels are not controlled. Any increase in ammonia over time is serious. Therefore, it is important to adhere to any dietary protein restrictions and have alternative medication options to help control ammonia levels. About OLPRUVA® OLPRUVA (sodium phenylbutyrate) was approved for the treatment of certain UCDs in December 2022 and has recently been marketed under the brand name, OLPRUVA®. OLPRUVA (sodium phenylbutyrate) for oral suspension is a prescription medicine used along with certain therapies, including changes in diet, for the long-term management of adults and children weighing 44 pounds (20 kg) or greater and with a body surface area (BSA) of 1.2 m2 or greater, with UCDs, involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). OLPRUVA is not used to treat rapid increase of ammonia in the blood (acute hyperammonemia), which can be life-threatening and requires emergency medical treatment. For more information, please visit www.OLPRUVA.com. Important Safety Information Certain medicines may increase the level of ammonia in your blood or cause serious side effects when taken during treatment with OLPRUVA. Tell your doctor about all the medicines you or your child take, especially if you or your child take corticosteroids, valproic acid, haloperidol, and/or probenecid. OLPRUVA can cause serious side effects, including: 1) nervous system problems (neurotoxicity). Symptoms include sleepiness, tiredness, lightheadedness, vomiting, nausea, headache, confusion, 2) low potassium levels in your blood (hypokalemia) and 3) conditions related to swelling (edema). OLPRUVA contains salt (sodium), which can cause swelling from salt and water retention. Tell your doctor right away if you or your child get any of these symptoms. Your doctor may do certain blood tests to check for side effects during treatment with OLPRUVA. If you have certain medical conditions such as heart, liver or kidney problems, are pregnant/planning to get pregnant or breast-feeding, your doctor will decide if OLPRUVA is right for you. The most common side effects of OLPRUVA include absent or irregular menstrual periods, decreased appetite, body odor, bad taste or avoiding foods you ate prior to getting sick (taste aversion). These are not all of the possible side effects of OLPRUVA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. About Zevra Therapeutics, Inc. Zevra Therapeutics, Inc. is a rare disease company combining science, data, and patient needs to create transformational therapies for diseases with limited or no treatment options. Our mission is to bring life-changing therapeutics to people living with rare diseases. With unique, data-driven development and commercialization strategies, the Company is overcoming complex drug development challenges to make new therapies available to the rare disease community. Expanded access programs are made available by Zevra and its affiliates and are subject to the Company's Expanded Access Program (EAP) policy as published on its website at www.zevra.com. Participation in these programs is subject to the laws and regulations of each jurisdiction under which each respective program is operated. Eligibility for participation in any such program is at the treating physician's discretion. For more information, please visit www.zevra.com or follow us on X (formerly Twitter) and LinkedIn. Cautionary Note Concerning Forward-Looking Statements This press release may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that do not relate solely to historical or current facts, including without limitation statements regarding the promise and zpotential impact of our preclinical or clinical trial data; the initiation, timing and results of any clinical trials or readouts, the content, information used for, timing or results of any NDA submissions or resubmissions for arimoclomol or any other product candidates for any specific disease indication or at any dosage; the potential benefits of any of our products or product candidates for any specific disease or at any dosage; our strategic and product development objectives, including with respect to becoming a leading, commercially focused rare disease company; potential revenues from our arimoclomol expanded access program; the potential for royalty and milestone contributions, the presentation of data at conferences; and the timing of any of the foregoing. Forward-looking statements are based on information currently available to Zevra and its current plans or expectations. They are subject to several known and unknown uncertainties, risks, and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. These and other important factors are described in detail in the “Risk Factors” section of Zevra’s Annual Report on Form 10-K for the year ended December 31, 2023, Zevra’s Quarterly Report on Form 10-Q for the three months ended June 30, 2024, and Zevra’s other filings with the Securities and Exchange Commission. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. Although we believe the expectations reflected in such forward-looking statements are reasonable, we cannot assure that such expectations will prove correct. These forward-looking statements should not be relied upon as representing our views as of any date after the date of this press release. Zevra Contact Nichol Ochsner+1 (732) 754-2545nochsner@zevra.com Russo Partners Contacts Adanna G. Alexander, Ph.D.+1 (646) 942-5603adanna.alexander@russopartnersllc.com Ignacio Guerrero-Ros, Ph.D.+1 (646) 942-5604ignacio.guerrero-ros@russopartnersllc.com