Cyanosis and Hepatic Disease

- Results presented from over a decade of treatment with velmanase alfa in alpha-mannosidosis – - Company also presents immunogenicity and tolerability data from pegunigalsidase alfa clinical trial program in Fabry disease – - Additional presentations provide new insights on prevalence, diagnosis, and progression of these rare lysosomal storage disorders – BOSTON, Feb. 8, 2024 /PRNewswire/ -- Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people living with rare diseases, today announced the presentation of long-term data from up to 12 years of treatment with velmanase alfa in patients with alpha-mannosidosis (AM). The company also announced the presentation of immunogenicity and tolerability data from its pegunigalsidase alfa clinical trial program in Fabry disease, as well as analyses of the prevalence, diagnosis, and progression of these rare lysosomal storage disorders. The data are being presented during the 20th Annual WORLDSymposium™ Research Meeting that is being held February 4-9, 2024, in San Diego, California. "This year's WORLDSymposium marks a significant moment for people living with rare lysosomal storage disorders including alpha-mannosidosis and Fabry disease, and their healthcare teams including clinicians and nurses, who now have access to recently approved treatment options and an important opportunity to understand the impact of these therapies and the barriers that must be addressed to improve diagnosis and disease management," said Giacomo Chiesi, head of Chiesi Global Rare Diseases. "Our company is driven by a commitment to rare disease communities around the world and we are taking full advantage of this conference to share our extensive clinical research in AM, which now spans more than a decade, and in Fabry disease, where we are continuing to evaluate data from our comprehensive development program. We are also emphasizing the importance of the caregiver and patient voice, reporting results from a range of surveys and analyses, hosting symposia, and presenting a special film screening that will help healthcare professionals identify and treat people in these communities in the years ahead." Results from long-term treatment with velmanase alfa in AM In an oral session, Prof. Nathalie Guffon, M.D., Reference Centre of inherited metabolic disease in Femme Mère Enfant Hospital, Hospices Civils of Lyon, France, is presenting results of an analysis that evaluated long‑term efficacy of up to 12 years of treatment with velmanase alfa, which is the first and only enzyme replacement therapy (ERT) available for people with AM. Pooled analyses demonstrate tolerability of pegunigalsidase alfa in Fabry disease and low incidence of de novo anti-drug antibodies Several poster presentations are highlighting immunogenicity and tolerability data from the pegunigalsidase alfa clinical trial program in Fabry disease. John Bernat, M.D., Ph.D., Medical Director of the Iowa Lysosomal Storage Disorders Center, is presenting a poster describing characteristics of anti-drug antibodies (ADAs) reacting with pegunigalsidase alfa, and the patients who develop ADAs, using data from an integrated clinical trial dataset. The analysis includes 108 patients, 27 (25%) of whom were ADA+ before receiving their first dose of pegunigalsidase alfa. There was a low incidence of de novo ADAs (n=17) occurring predominantly in the first year of treatment with pegunigalsidase alfa. Neutralizing antibodies were detected in <25% of patients with de novo ADAs versus in almost all patients who were ADA+ at baseline. In separate poster presentations, Derralynn Hughes, M.D., Professor of Experimental Haematology at the University College London, and Ankit Mehta, M.D., FASN, Baylor University Medical Center, are sharing results from analyses of the tolerability of pegunigalsidase alfa across the clinical program per dosing regimen and prior enzyme replacement therapy (ERT) experience, respectively. Dr. Hughes found that less than a third of patients receiving pegunigalsidase alfa experienced infusion related reactions (IRRs), most of which occurred from the start of the infusion until up to two hours after its end among patients with pre-existing or de novo ADAs. The frequency of IRRs decreased over time and in parallel with a decrease in premedication use among those switching from prior ERT. Dr. Mehta found that IRRs from the start of the infusion until up to two hours after its end occurred in about a quarter of either ERT-naive or ERT-switch patients following treatment with pegunigalsidase alfa. Most of these IRRs were mild to moderate in severity and occurred predominantly in the first year after initiating the therapy. Surveys and epidemiological analyses shed new light on the prevalence, diagnosis, and progression of AM and Fabry disease Chiesi Global Rare Diseases is announcing five additional presentations focused on improving awareness and understanding of the patient experience with rare lysosomal storage disorders including AM and Fabry disease. In an oral presentation, Stuart Gaffney, M.D., Medical Manager, Chiesi Global Rare Diseases, is sharing results from interviews and surveys with Fabry disease patients (n=20), nurses, and clinicians to understand the diagnostic journey and identify unmet medical education needs of UK primary and specialty healthcare professionals. The most common first symptom of Fabry disease was neuropathic pain, and the first severe indication for many patients was chest pain and general heart complaints. Cardiologists were the main specialists identifying Fabry disease, and 55% (11/20) of patients saw a cardiologist who was the first to suspect Fabry disease was the cause of their symptoms. In a poster presentation, Patricia Dorling, Head of Global Health Economics and Outcome Research (GHEOR), Chiesi USA, is reporting results from a study that analyzed data from the Adelphi Fabry Disease Specific Programme™ (DSP), a national representative online survey of physicians treating patients with a confirmed diagnosis of Fabry disease in the United States. Results demonstrate that the burden of complications and use of medical services (HCRU) is substantial with 76% of patients undergoing routine clinical examinations over two years and 19% of patients being hospitalized due to Fabry disease over one year. In a poster presentation, Khashayar Azimpour, M.D., Ph.D., Director, Global Health Economics and Outcome Research (GHEOR), Chiesi USA, is reporting results from a study aimed to estimate diagnosed Fabry disease prevalence and treatment rates in the U.S. via a retrospective cohort analysis. The 2021 diagnosed prevalence was 5,462 people, and 3,747 of those people with Fabry disease had received treatment. The findings highlight potentially higher gender disparities in treatment than previous estimates, signifying greater need for treatment in females. In a poster presentation, Nicole Muschol, M.D., International Center for Lysosomal Disorders (ICLD) at the University Medical Center Hamburg-Eppendorf in Germany, is reporting results from a Delphi study that generated 60 internationally applicable best practice recommendations for the initial assessment of newly diagnosed AM patients and their routine follow-up and integrated care coordination. In a poster presentation, Prof. Guffon is highlighting results from an international caregiver and patient survey designed to assess the impact of AM on patients' functional ability and quality of life. Results confirm that an important treatment goal is stabilizing and slowing disease progression. Untreated patients reported deterioration at a functional, pain and quality of life level, while patients treated with ERT or allogeneic haematopoietic stem cell transplantation reported less decline in walking ability and improved ability to self-care. Chiesi Global Rare Diseases is sponsoring three satellite symposia during WORLDSymposium to review perspectives on the management of Fabry disease and AM including insights from clinicians, caregivers, and patients. The company is also presenting a special screening of "Rare Land," a film focused on AM, with an expert panel featuring Robert Hopkin, M.D., Clinical Geneticist at Cincinnati Children's Hospital Medical Center and Martin Magner, M.D., Ph.D., Department of Paediatrics and Hereditary Metabolic Disorders of the General University Hospital of Prague. In addition, the company is presenting during the Industry Expert Theater session and is participating in the Patient Voice and Preference meeting. Indication and Important Safety Information for Elfabrio® (pegunigalsidase alfa-iwxj) Indication Elfabrio® (pegunigalsidase alfa-iwxj) is indicated for the treatment of adults with confirmed Fabry disease. Important Safety Information Prior to Elfabrio administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Inform patients and caregivers of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions (IARs), and instruct them to seek medical care immediately if such symptoms occur. If a severe hypersensitivity reaction (including anaphylaxis) or severe IAR occurs, immediately discontinue Elfabrio administration and initiate appropriate medical treatment. If a mild to moderate hypersensitivity reaction or IAR occurs, consider slowing the infusion rate or temporarily withholding the dose. In clinical trials, 20 (14%) Elfabrio-treated patients experienced hypersensitivity reactions. Four Elfabrio-treated patients (3%) experienced anaphylaxis reactions that occurred within 5 to 40 minutes of the start of the initial infusion. The signs and symptoms of hypersensitivity reactions and anaphylaxis included headache, nausea, vomiting, throat tightness, facial and oral edema, truncal rash, tachycardia, hypotension, rigors, urticaria, intense pruritus, moderate upper airway obstructions, macroglossia, and mild lip edema. In clinical trials, 41 (29%) Elfabrio-treated patients experienced one or more infusion-associated reactions, including hypersensitivity, nausea, chills, pruritus, rash, chest pain, dizziness, vomiting, asthenia, pain, sneezing, dyspnea, nasal congestion, throat irritation, abdominal pain, erythema, diarrhea, burning sensation, neuralgia, headache, paresthesia, tremor, agitation, increased body temperature, flushing, bradycardia, myalgia, hypertension, and hypotension. A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitor serum creatinine and urinary protein-to-creatinine ratio. If glomerulonephritis is suspected, discontinue treatment until a diagnostic evaluation can be conducted. When switching to Elfabrio from a prior enzyme replacement therapy, the risk of hypersensitivity reactions and infusion-associated reactions may be increased in certain patients with pre-existing anti-drug antibodies (ADAs). Consider monitoring IgG and IgE ADAs and clinical or pharmacodynamic response (eg, plasma lyso-Gb3 levels). The most common adverse reactions (≥15%) were infusion-associated reactions, nasopharyngitis, headache, diarrhea, fatigue, nausea, back pain, pain in extremity, and sinusitis. Please see Full Prescribing Information for Elfabrio. Indication and Important Safety Information for Lamzede® (velmanase alfa-tycv) Indication Lamzede® (velmanase alfa-tycv) is indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients. Important Safety Information Considerations Due to Hypersensitivity Reactions and/or Infusion-Associated Reactions (IARs) Prior to Lamzede administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Inform patients and caregivers of the signs and symptoms of hypersensitivity reactions and IARs and instruct them to seek medical care immediately if such symptoms occur. If a severe hypersensitivity reaction (including anaphylaxis) or severe IAR occurs, immediately discontinue Lamzede administration and initiate appropriate medical treatment. In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, consider temporarily holding the infusion for 15 to 30 minutes, slowing the infusion rate to 25% to 50% of the recommended rate, and initiating appropriate medical treatment. Hypersensitivity Reactions Including Anaphylaxis Anaphylaxis and severe hypersensitivity signs and symptoms included cyanosis, hypotension, emesis, urticaria, erythema, facial swelling, pyrexia, and tremor. Infusion-Associated Reactions (IARs) The most frequent symptoms of IARs that occurred in >10% of the population were pyrexia, chills, erythema, vomiting, cough, urticaria, rash, and conjunctivitis. Females of Reproductive Potential Advise females of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if Lamzede is discontinued. For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with Lamzede. Embryo-Fetal Toxicity Based on findings from animal reproduction studies, Lamzede may cause embryo-fetal harm when administered to a pregnant female. Common Adverse Reactions The most common adverse reactions (incidence >20%) are hypersensitivity reactions including anaphylaxis, nasopharyngitis, pyrexia, headache, and arthralgia. Please see Full Prescribing Information for Lamzede. About Chiesi Global Rare Diseases Chiesi Global Rare Diseases is a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people affected by rare diseases. As a family business, Chiesi Group strives to create a world where it is common to have a therapy for all diseases and acts as a force for good, for society and the planet. The goal of the Global Rare Diseases unit is to ensure equal access so as many people as possible can experience their most fulfilling life. The unit collaborates with the rare disease community around the globe to bring voice to underserved people in the health care system. For more information visit . About Chiesi Group Chiesi is an international, research-focused biopharmaceuticals group that develops and markets innovative therapeutic solutions in respiratory health, rare diseases, and specialty care. The company's mission is to improve people's quality of life and act responsibly towards both the community and the environment. By changing its legal status to a Benefit Corporation in Italy, the US, and France, Chiesi's commitment to create shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, we're part of a global community of businesses that meet high standards of social and environmental impact. The company aims to reach Net-Zero greenhouse gases (GHG) emissions by 2035. With over 85 years of experience, Chiesi is headquartered in Parma (Italy), operates in 31 countries, and counts more than 6,500 employees. The Group's research and development centre in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden. For further information please visit . Chiesi Group Media Contacts Chiara Travagin Rare Communication Manager Tel: +39 348 8818985 Email: [email protected] Alessio Pappagallo Press Office Manager Tel: +39 339 5897483 Email: [email protected] Adam Daley Berry & Company Public Relations Tel: +1 212 253 8881 Email: [email protected] PP-MULTI-0288 V2.0 SOURCE Chiesi Global Rare Diseases

By Seth Bogner, HeartPoint Global In pediatric cardiology, a persistent challenge revolves around ensuring accessible and effective care for children grappling with congenital heart disease (CHD). CHD affects approximately 1.7% of newborns globally, or 2.4 million, of which 90% have the urgent need for affordable and specialized treatments that call for innovative solutions. According to a recent article in The Journal of the American College of Cardiology (JACC), economic constraints in many developing nations contribute to delayed diagnosis and treatment for up to 90% of children with CHD, leading to severe consequences such as organ dysfunction and complications like profound cyanosis and polycythemia. A few years ago, I met with an interventional cardiologist in his office. I couldn’t help but notice a cardiac guidewire displayed on the wall behind his desk. When I asked about it, he shared an astonishing fact — it had been used in surgeries over 200 times in Myanmar. This highlighted the severe shortage of medical supplies and expertise in many developing nations. Typically, a guidewire is a single-use item meant to be discarded after one use. The cardiologist, amazed by the guidewire’s extensive use, felt the need to commemorate this as a testament to the challenges faced in those regions. This encounter sparked my inspiration and determination to bring easily accessible technology to the developing world, especially for individuals who often lack the means or access to surgeries that we take for granted in Western countries. Developing IntelliStent The journey with my team began in the lab, focusing on innovation around a transcatheter pulmonary artery band, an intervention that can be placed and adjusted without the risks associated with surgery. A transformation in pediatric cardiac care emerged with IntelliStent — a transcatheter device designed to regulate blood flow within the intravascular space , addressing the urgent need for affordable and specialized care. With traditional therapeutic strategies, the emphasis is on symptom improvement, leaving a significant unmet clinical need, especially in the pediatric population, where heart transplantation is the only life-saving option for end-stage dilated cardiomyopathy (DCM). IntelliStent introduces a paradigm shift, especially concerning existing therapies for pediatric dilated cardiomyopathy. Current treatments often fall short, leading to considerations of left ventricular assist devices (LVAD) and transplantation which is not available for patients that don’t live in a country with a well-developed and funded healthcare system This presents significant challenges, especially in the pediatric age range. IntelliStent emerges as a viable and cost-effective alternative, providing a temporary bridge to improve left ventricle function. When pharmaceutical interventions fall short; the next step may be the use of a LVAD and transplantation, but these options are not widely available, creating challenges even in the U.S. due to the scarcity of organ transplants in the pediatric age group. Consequently, the rationale behind placing a band into the pulmonary arteries becomes evident — a strategy to elevate the pressure in the right ventricle and reshape the interventricular septum’s morphology. This approach proves beneficial for infants, either leading to improvement with the band alone or serving as a bridge to transplant. The placement procedure is straightforward and has minimal risk compared to installing an artificial heart. IntelliStent, a specific arrangement of stents applicable throughout the vascular system, holds the potential for various scenarios requiring pressure or flow reduction in vessels. Looking ahead, there is a growing interest in exploring the translation of this experience for adults. Notably, the cost comparison is striking. While an LVAD in the U.S. incurs a million-dollar annual expense per patient, IntelliStent, by an order of magnitude, is significantly more cost-effective, with costs centered around the intervention rather than an annual basis. The ability to place and adjust this band without resorting to surgical procedures is a highly sought-after advancement. While pulmonary artery band surgery is an option for specific cases, the global limitations in congenital cardiac surgery often mean that complete repair or pulmonary artery band placement is not readily available, especially for left-to-right shunts resulting from common congenital defects. The introduction of a transcatheter pulmonary artery band becomes crucial in regions where access to congenital cardiac surgery is restricted, offering a potential lifeline for children at risk of developing Eisenmenger syndrome. This approach serves as a means of safeguarding the lungs from excess flow and pressure in the presence of unrepaired congenital cardiac defects, providing a life-saving option for both children and adults with congenital heart malformations. The timing of pulmonary artery band placement hinges on preventing progression to the irreversible stage of shunting, offering flexibility for intervention at any age for those at risk of Eisenmenger syndrome. IntelliStent’s global impact Once granted public approval, this groundbreaking device will be disseminated globally, catering to both the developing and developed worlds. The immediate focus lies on meeting the unmet needs, providing access to cardiac care for pediatric patients currently devoid of such resources in the U.S., marking a pivotal step in extending life-saving interventions to those in need. In developing nations, left ventricular dilated cardiomyopathy is left untreated. Collaborations with organizations like the Eurasia Heart Foundation aim to make a significant impact globally, focusing on working closely with the FDA to bring affordable and specialized care to those in need. The significance of transcatheter procedures becomes clear when considering the risks associated with general anesthesia during surgery. IntelliStent offers a safer alternative with the ability to conduct transcatheter procedures under moderate sedation. The flexibility to adjust flow and pressure over time, its lower cost, and reduced risk of complications position IntelliStent as a groundbreaking solution. The unique adaptability of IntelliStent is highlighted by its adjustability, allowing modifications that are not only available during the initial intervention but also at later stages as patient conditions evolve. The importance of accurate restriction of flow is paramount, with the capability to adjust allowing it to be a patient-centric approach with minimal risks. Imaging studies can be conducted while the patient is awake and follow-ups are less frequent, reducing the burden on both patients and healthcare resources. Four successful rounds of preclinical studies have laid the foundation for IntelliStent’s safety and efficacy. The system’s ability to achieve the desired effect at a lower rate of pressure reduction enhances patient safety. In-human clinical trials are imminent, focusing on evaluating safety before exploring applications in small children. The future looks bright, with cardiovascular medtech innovation as a beacon of hope for improved and affordable pediatric cardiac care globally. Seth Bogner is chair and CEO of HeartPoint Global Inc., which provides global, breakthrough medical solutions for cutting-edge cardiac care that are affordable, safe, and minimally invasive. Heartpoint Global is the Cardiovascular Research Foundation (CRF) TCT 2023 Shark Tank (Innovation) Competition winner. How to submit a contribution to MDO The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of Medical Design & Outsourcing or its employees.

BOSTON, Nov. 28, 2023 (GLOBE NEWSWIRE) -- Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today announced that it will deliver presentations on its epilepsy programs at the following upcoming meetings in Orlando, Florida. Presentations at the American Epilepsy Society (AES) Annual Meeting, as well as related scientific and patient advocacy meetings, will cover new patient data, updates on clinical progress and new paradigms for developing epilepsy therapies. AES Annual Meeting, being held December 1-5, 2023Behind the Seizure (BTS) Scientific Exhibit, being held on December 3, 2023Partners Against Mortality in Epilepsy (PAME) Conference, being held on November 30, 2023SYNGAP1 Conference, being held on November 30, 2023The Cute Syndrome Foundation (TCSF) SCN8A Clinician, Researcher, and Family Gathering, being held on December 1, 2023 “It’s an incredibly exciting time for Praxis and our epilepsy portfolio, as we share updates from first-in-patient and Phase 2 studies for elsunersen (PRAX-222), PRAX-562 and PRAX-628,” said Marcio Souza, president and chief executive officer of Praxis. “We look forward to presenting data spanning our Solidus and Cerebrum platforms at AES and related meetings in Florida, with presentations also set to highlight novel approaches to define efficient preclinical models and sensitive biomarkers for accelerating drug development for the patient populations we are seeking to serve. Our epilepsy programs have the potential to significantly impact the lives of patients and their families, and we are grateful for the opportunity to discuss these programs with the epilepsy community at multiple important meetings this week.” Praxis at AES 2023 | Orange County Convention Center Meet us at booth #421 to learn about the largest pipeline of precision epilepsy programs Head to one of our presentations listed below or visit us at the BTS Scientific Exhibit on December 3, 08:00 a.m. - 11:00 a.m. ET EMBRAVE: A Clinical Trial of PRAX-222, a Novel Antisense Oligonucleotide, in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy Session Date/Time: Monday, December 4, 12:00 p.m. - 2:00 p.m. ETAbstract number: 3.198Summary: Preliminary results from Part 1 of the EMBRAVE study demonstrate elsunersen tolerability and unprecedented efficacy, highlighting its potential to be the first disease-modifying treatment in early onset SCN2A developmental and epileptic encephalopathy (SCN2A-DEE). PRAX-628 is a Next Generation, Functionally Selective Small Molecule with Potent Anti-Seizure Activity and Potential as Best-in-Class Treatment for Focal Epilepsy Session Date/Time: Monday, December 4, 12:00 p.m. - 2:00 p.m. ET; platform talk at 5:00 p.m. ET [Platform D | Epilepsy Therapies] Abstract number: 3.258Summary: Combined preclinical and clinical data demonstrate PRAX-628 is differentiated from standard of care, with the potential to be best-in-class for focal epilepsy. In vivo studies demonstrate unprecedented potent anticonvulsant activity in the maximal electroshock seizure (MES) model, a highly predictive translational model for efficacy in focal epilepsy, while first-in-human findings demonstrate that PRAX-628 is well tolerated at exposures >15x the predicted efficacious exposure from mouse MES. A Novel Method to Define an EEG Composite for the Detection of Drug Effects of Next Generation Small Molecules for Epilepsy Session Date/Time: Monday, December 4, 12:00 p.m. - 2:00 p.m. ETAbstract number: 3.455Summary: Application of machine learning methods to complex EEG data has the potential to accelerate drug development in epilepsy by revealing pharmacodynamic effects of novel agents that are clearly distinguishable from placebo. In this study, we demonstrate applicability of a quantitative EEG composite to three distinct next generation small molecules, with expected generalizability to any small molecule, independent of class/target. Translational Concordance of Preclinical Seizure Models in Focal and Generalized Epilepsies Session Date/Time: Monday, December 4, 12:00 p.m. - 2:00 p.m. ETAbstract number: 3.458Summary: This study provides novel insights into the clinical validity of commonly used preclinical seizure models across the clinical epilepsy spectrum. Using a newly developed scoring matrix to assess translational concordance and predictability, mouse MES, audiogenic and 6-Hz 32 mA emerge as three acute seizure models with greatest predictive validity and versatility for ASM drug discovery. Praxis at PAME 2023 | Rosen Centre Hotel EMBRAVE: A Clinical Trial of PRAX-222, a Novel Antisense Oligonucleotide, in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy Session Date/Time: Thursday, November 30, 5:00 p.m. - 6:30 p.m. ETPoster number: 32Summary: Preliminary results from Part 1 of the EMBRAVE study demonstrate elsunersen tolerability and unprecedented efficacy, highlighting its potential to be the first disease-modifying treatment in early onset SCN2A-DEE. EMBOLD: A Clinical Trial of PRAX-562 in Subjects with Developmental and Epileptic Encephalopathies Followed by an Open-Label Extension Session Date/Time: Thursday, November 30, 5:00 p.m. - 6:30 p.m. ETPoster number: 38Summary: EMBOLD is the first and only DEE trial to offer a decentralized clinical trial option, balancing clinical rigor with flexibility and convenience for participants and their families. EMBOLD will provide important findings regarding the safety, tolerability, efficacy and pharmacokinetics of PRAX-562 as a potential first- and best-in-class treatment for pediatric patients with SCN2A-DEE and SCN8A-DEE. Praxis at SYNGAP1 2023 | Embassy Suites Hotel Progress Toward the Discovery of an ASO for Therapeutic Upregulation of SYNGAP1 Session Date/Time: Thursday, November 30, 1:30 p.m. - 1:45 p.m. ET | Session 4: Therapeutic Strategies to Fix SYNGAP1Oral presentation highlighting preclinical updates from our SYNGAP1 ASO platform at the annual scientific conference hosted by the SYNGAP Research Fund Praxis at TCSF 2023 | Sheraton Orlando Lake Buena Vista Resort PRAX-562: Reflection and Direction on a Next Generation Anti-Seizure Small Molecule in Development for SCN8A-DEE Session Date/Time: Friday, December 1, 6:15 p.m. ETOral presentation highlighting clinical updates from our PRAX-562 small molecule platform at the annual clinician, researcher, and family gathering for SCN8A About elsunersen (PRAX-222)Elsunersen is an ASO designed to selectively decrease SCN2A gene expression, directly targeting the underlying cause of early-seizure-onset SCN2A-DEE to treat seizures and other symptoms in patients with gain-of-function SCN2A mutations. In vitro studies of elsunersen have demonstrated reduction in both SCN2A gene expression and protein levels. In vivo, elsunersen has demonstrated significant, dose-dependent reduction in seizures, improvement in behavioral and locomotor activity and increased survival in SCN2A mouse models, with potential to be the first disease-modifying treatment for SCN2A-DEE. Elsunersen has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPD) from the FDA, and ODD and Priority Medicines (PRIME) designation from the European Medicines Agency (EMA) for the treatment of SCN2A-DEE. The elsunersen program is ongoing under a collaboration with Ionis Pharmaceutics, Inc., and RogCon, Inc. About PRAX-562PRAX-562 is a first-in-class small molecule in development for the treatment of DEE as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in early onset SCN2A-DEE and SCN8A-DEE. PRAX-562’s mechanism of sodium channel block is consistent with superior selectivity for disease state sodium channel (NaV) channel hyperexcitability. In vivo studies of PRAX-562 have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. PRAX-562 has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel blocking effects. PRAX-562 has received ODD and RPD from the FDA, and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE. To learn more about the EMBOLD study, please visit https://www.emboldstudy.org/. About PRAX-628PRAX-628 is a next-generation, functionally selective small molecule targeting the hyperexcitable state of sodium-channels in the brain that is currently being developed as a once daily, oral treatment for adult focal onset epilepsy. Preclinical data demonstrates PRAX-628 is differentiated from standard of care, with the potential to be best-in-class for focal epilepsy. In vitro, PRAX-628 has demonstrated superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of PRAX-628 have demonstrated unprecedented potency in the maximal electroshock seizure (MES) model, a highly predictive translational model for efficacy in focal epilepsy. Data from the PRAX-628-101 study demonstrated that PRAX-628 can be safely dosed in healthy subjects to greater than 15 times the predicted human equivalent of the rodent MES EC50. About SCN2A-DEESCN2A-DEE is a debilitating monogenic epilepsy disorder caused by a variant in the SCN2A gene, associated with early mortality. The SCN2A gene is critical in the formation of sodium channel proteins in the brain, which control the flow of sodium ions into neurons. This movement of sodium ions is a major component of generating electrical signals called action potentials, the way in which the cells communicate. SCN2A-DEE is characterized by a broad spectrum of phenotypes. Early-onset SCN2A-DEE presents before three months and can lead to profound impact on patients, including drug-resistant seizures, significant cognitive impairment, movement disorders such as dystonia or ataxia and problems in other body systems such as gastrointestinal or ocular. Currently there are no approved treatments for SCN2A-DEE, and the standard-of-care typically involves a regimen of many concurrent anti-seizure medications as well as medications to manage co-morbidities. Despite these interventions, more than 70% of early-onset SCN2A-DEE patients live with uncontrolled seizures, and approximately 75% live with severe intellectual disability with patients rarely surviving beyond their teenage years. About SCN8A-DEESCN8A-DEE is a rare developmental and epileptic encephalopathy caused by a variant in the SCN8A gene. The SCN8A gene is critical in the formation of sodium channel proteins in the brain, which control the follow of sodium ions into neurons. This movement of sodium ions is a major component of generating electrical signals called action potentials, the way in which the cells communicate. Patients suffer from recurrent, typically drug-resistant seizures which start as early as the first day of life. The seizures can be of multiple different types, up to dozens per day, with poor response to current treatment options. Patients with SCN8A-DEE have significant cognitive disabilities, ranging from moderate to severe; often movement disorders, such as dystonia or ataxia; and problems in other body systems such as gastrointestinal or ocular. SCN8A-DEE patients also may experience autonomic features such as increases or decreases in heart rate, abnormal breathing and cyanosis. About PraxisPraxis Precision Medicines is a clinical-stage biopharmaceutical company translating insights from genetic epilepsies into the development of therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance. Praxis is applying genetic insights to the discovery and development of therapies for rare and more prevalent neurological disorders through our proprietary small molecule platform, Cerebrum™, and antisense oligonucleotide (ASO) platform, Solidus™, using our understanding of shared biological targets and circuits in the brain. Praxis has established a diversified, multimodal CNS portfolio including multiple programs across movement disorders and epilepsy, with four clinical-stage product candidates. For more information, please visit www.praxismedicines.com and follow us on Facebook, LinkedIn and Twitter/X. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Praxis’ future expectations, plans and prospects, including, without limitation, statements regarding the development of our product candidates, including the design of clinical trials and the treatment potential of Praxis’ product candidates, as well as other statements containing the words “anticipate,” “believe,” “continue,” “could,” “endeavor,” “estimate,” “expect,” “anticipate,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “target,” “will” or “would” and similar expressions that constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical trials; reported interim data from ongoing studies and trials differing materially from final data from preclinical studies and completed clinical trials; the expected timing of clinical trials, data readouts and the results thereof, and submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials; Praxis’ anticipated cash runway; and other risks concerning Praxis’ programs and operations as described in its Annual Report on Form 10-K for the year ended December 31, 2022, its Quarterly Reports on Form 10-Q and other filings made with the Securities and Exchange Commission. Although Praxis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on information and factors currently known by Praxis. As a result, you are cautioned not to rely on these forward-looking statements. Any forward-looking statement made in this press release speaks only as of the date on which it is made. Praxis undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.