Dantrolene Sodium

Acquisition of Theravia from Mérieux Equity Partners represents meaningful step forward in Norgine’s strategy for sustainable growth, adding a complementary portfolio of rare disease medicines Transaction further establishes Norgine’s position as a partner of choice for commercialising rare and specialty pharmaceuticals in Europe Paris, France, April 15, 2025: Norgine and Theravia announced today that they have entered into a definitive agreement under which Norgine will acquire Theravia, an international pharmaceutical company specialising in cutting-edge treatments for patients with rare and debilitating conditions. Recent deals with Fennec Pharma for PEDMARQSI® and X4 Pharma for mavorixafor demonstrate Norgine’s strong emphasis on driving growth in rare disease and specialty medicines through acquisitions and in-licensing. Theravia’s innovations have resulted in successful launches of life-saving medications which have changed patient outcomes worldwide. Theravia has several products in the rare disease space, including SIKLOS®, for adults and children with sickle cell disease, and ORPHACOL®, a medicine for adults and children who have a genetic disorder that affects bile production by the liver. These products span both the rare haematology and rare hepatology therapeutic areas and are complementary to Norgine’s existing rare and specialty portfolio. The development of Theravia in the past few years has been supported by its majority shareholder Mérieux Equity Partners, a healthcare dedicated investment firm based in France. “said Janneke van der Kamp, Chief Executive Officer, Norgine. “ Franck Hamalian, Chief Executive Officer, Theravia, added: With the acquisition of Theravia, Norgine will now have six core products in its rare disease portfolio (PEDMARQSI®, eflornithine, mavorixafor, AGILUS®, SIKLOS® and ORPHACOL®) thereby comprising a franchise of critical scale with the ability to be a key growth driver in the medium-to-long-term. Norgine looks forward to building on this transaction as we continue to strengthen our platform for future acquisitions and in-licensing opportunities to drive growth. The transaction remains subject to obtaining customary regulatory approvals from the competent authorities. Notes About Theravia Theravia is an international pharmaceutical laboratory specializing in rare or neglected diseases. Formed through the merger of Addmedica and CTRS, Theravia is dedicated to addressing the unmet medical needs of patients with these challenging conditions. About SIKLOS® SIKLOS® is used in adults, adolescents and children over two years of age who have sickle-cell syndrome, a genetic disease where the red blood cells become rigid and sticky and change from being disc-shaped to being crescent-shaped (like a sickle). It is used to prevent recurrent, painful vaso-occlusive crises that happen when blood vessels become blocked by the abnormal red blood cells, restricting the flow of blood to an organ. They can include acute chest syndrome, a life-threatening condition when the patient has sudden chest pain, fever, hard breathing or signs of fluid in the lungs on an X-ray. SIKLOS® is marketed in 17 countries around the world. About ORPHACOL® ORPHACOL® is a medicine containing cholic acid, a substance found in the bile, which is used to digest fats. It is approved in the US and Europe used to treat adults and children from one month of age who have a genetic abnormality that makes them unable to produce bile. The therapy is used in patients who do not have enough of two specific liver enzymes which makes their liver unable to produce enough of the main components of bile, called primary bile acids, such as cholic acid. When these primary bile acids are lacking, the body produces abnormal bile acids instead which can damage the liver, potentially leading to life-threatening liver failure. ORPHACOL® is marketed in 23 countries around the world. About PEDMARQSI® PEDMARQSI® is a novel formulation of anhydrous sodium thiosulfate, specifically developed and manufactured for the prevention of cisplatin-induced hearing loss in patients 1 month to <18 years of age. It is the first and only preventative treatment developed for cisplatin-induced ototoxicity to support children and adolescent patients with localised, non-metastatic solid tumour cancers. It was granted marketing authorisation by the EMA in May 2023 (under the paediatric-use marketing authorisation (PUMA) programme) and the MHRA in October 2023. About Mavorixafor Mavorixafor is a selective CXCR4 receptor antagonist approved in the U.S. and marketed by X4 as XOLREMDI®, an oral, once-daily treatment for patients 12 years of age and older with WHIM syndrome, a rare primary immunodeficiency. In January 2025, X4 submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for mavorixafor for the treatment of WHIM syndrome, for which it has been granted Orphan Drug Designation by both the EMA and the U.S. Food and Drug Administration. X4 is also developing the medicine to treat chronic neutropenia (CN) and is currently conducting a global, pivotal Phase 3 clinical trial in certain CN disorders. Norgine has responsibility for commercialisation in Europe, Australia, and New Zealand following regulatory approvals. About Eflornithine Eflornithine has been investigated for use as a post maintenance treatment for high-risk neuroblastoma (HRNB) in paediatric patients with no active disease (NAD) / no evidence of disease (NED) after first line multiagent, multimodality therapy. It is a targeted therapy that blocks an enzyme called ornithine decarboxylase (ODC), responsible for producing polyamines, which are important to tumour growth and development. The medicine is approved by the FDA for a maintenance therapy for high-risk neuroblastoma in adult and pediatric patients. In April 2024, an application for approval was submitted by Norgine for the use of eflornithine in high-risk neuroblastoma (HRNB), via Project Orbis in Australia, Switzerland and the United Kingdom. In January 2025, a marketing authorisation application was filed to the European Medicines Agency (EMA) for the medicine in high-risk neuroblastoma (HRNB). About AGILUS® AGILUS® is a medicine used to treat malignant hyperthermia (rapid rise in body temperature caused by uncontrolled muscle contractions) in adults and children. Malignant hyperthermia is a serious reaction to certain medicines used for general anaesthesia during surgery or other medical procedures. AGILUS® is approved for use by the EMA for for the treatment of malignant hyperthermia in adults and children in combination with adequate support measures. About Mérieux Equity Partners Founded in 2009, Mérieux Equity Partners (“MxEP”) is a leading European healthcare-specialized investment firm, with two dedicated platforms, Venture Capital and Buyout, supporting companies ranging from start-ups to established leaders. Benefiting from a longstanding expertise and a large network, MxEP invests in companies with ambitious growth projects and transformative products or services in healthcare. MxEP is AMF-accredited and currently manages c.€1.5bn of AuM. About Norgine Norgine is a uniquely positioned, specialty pharmaceutical and consumer healthcare company, with over €550 million of annual revenues and a 120-year track record of bringing life-changing products to patients and consumers across our core markets of Western Europe, Australia and New Zealand. Norgine’s integrated approach – strong commercial capabilities, as well as deep medical, regulatory and clinical expertise, in-house manufacturing, robust supply networks, and best-in-class enabling functions – ensures that Norgine can deliver high-quality, transformative medicines quickly and effectively to over 25 million patients annually. Norgine is a nimble, innovative, and high-performing company that has been transformed by a relentless focus on operational excellence. This focus will enable us to secure the legacy of more than a century of innovation and doing the right thing by our patients, as we push the boundaries and take strides into therapeutic innovation. NORGINE and the sail logo are trademarks of the Norgine group of companies. Media Contacts: Norgine: Annabel Cowper ACowper1@Norgine.com MHP Group (for Mérieux): James McFarlane james.mcfarlane@mhpgroup.com and Matthew Taylor matthew.taylor@mhpgroup.com

Biomedical engineers have grown muscles in a lab to better understand and test treatments for a group of extremely rare muscle disorders called dysferlinopathy or limb girdle muscular dystrophies 2B (LGMD2B). The research revealed the biological mechanisms underlying the disease and showed that a combination of existing treatments could alleviate its symptoms. Biomedical engineers at Duke University have developed a new technique to better understand and test treatments for a group of extremely rare muscle disorders called dysferlinopathy or limb girdle muscular dystrophies 2B (LGMD2B). The approach grows complex, functional 3D muscle tissue from stem cells in the laboratory, creating a platform that replicates patient symptoms and treatment responses. In its debut study, researchers reveal some of the biological mechanisms underlying the characteristic loss of mobility caused by LGMD2B. They also demonstrate that a combination of existing treatments may be able to alleviate some of the worst symptoms of the disease. The results appear online June 18 in the journal Advanced Science. LGMD2B affects only about eight people per million around the world. Unlike it's more well-known and more common cousin Duchenne muscular dystrophy, the disease affects both men and women, presents later in life -- in the late teens or early 20s -- and is rarely fatal. However, LGMD2B patients develop severe weakness in the legs and shoulders, typically requiring them to use wheelchairs for the rest of their lives. Caused by a genetic disorder, LGMD2B stops the body from creating a fully functional form of a protein called dysferlin. There are currently no approved treatments or cures. Part of the reason for this lack of options is the many functions of dysferlin, including sealing holes in muscle membranes, regulating calcium balances required for muscle contraction and controlling cellular metabolism. And for reasons unknown, affected muscles initially accumulate fat within the muscle fibers themselves before degenerating and ultimately being replaced by fat cells. "This phenomenon is very rare even for muscular dystrophies," said Nenad Bursac, professor of biomedical engineering at Duke. "It's a burning question within the community of why that happens." One of the challenges facing researchers trying to solve these problems is that the mouse model used to approximate LGMD2B shows very mild symptoms compared to patients. Mice with the disease are still able to walk, and it does not present until nearly a year into their two-year long lifespan, making studies of the disease extremely slow. Dysferlin is expressed in other cell types, and blood levels of metabolic fuels such as cholesterol are also altered in mice and patients. Together, this complicates LGMD2B research by making it difficult to assess what cell types are responsible for the disease and if metabolic changes are due to the loss of dysferlin itself or whole-body effects. To get around these challenges, Bursac and his research scientist Alastair Khodabukus turned to an engineered muscle platform that they have been developing for nearly a decade. The Bursac Lab was the first to grow contracting, functional human skeletal muscle in a Petri dish and has been improving its processes ever since to enable studies of muscle strength, metabolism and repair. This system allowed them to focus their study on only the effects of dysferlin on skeletal muscle without the complications of other cell types or altered blood metabolite pro In the study, the researchers began with induced pluripotent stem cells (IPSCs) derived from patients living with LGMD supplied by The Jain Foundation, a charity focused on finding a cure for LGMD2B. Using their muscle-growing techniques, the lab matured these stem cells into muscle fibers and ran them through a battery of tests over the course of six weeks. Like muscles found in patients themselves, the lab-grown versions displayed a wide variety of issues. "Overall, our model repeated a lot of the clinical manifestations of the disease and observations made in real patients, but it was all done in a Petri dish," said Bursac. "We've been able to gain new insights into the muscle-specific aspects of the disease." The researchers discovered that the loss in muscle strength was not the result of deficiencies in muscle structure or size, but in its handling of calcium. Muscle contractions are physically caused by reservoirs of calcium in muscle cells being released and binding to muscle proteins. Tests showed that the diseased muscle cells had sprung leaks in their calcium reserves, resulting in less calcium to release and weaker contractions. The researchers also showed that the lack of dysferlin caused damage to the muscle cells to go unrepaired, and that an inability to burn fatty acids for energy production was at least partially to blame for the accumulation of fat within muscle fibers that has long puzzled the medical community. "We replicated something seen in patients and showed that it's not due to environmental factors within the body, but issues within the muscle itself," Khodabukus said. The researchers then tested the effects of two drug candidates to potentially treat the disease that have been identified through mouse models but have not yet been tested in humans. One called dantrolene is supposed to stop calcium from leaking from muscle cells' reservoirs. The second, called vamorolone, was recently approved for use with Duchenne muscular dystrophy patients, although researchers do not fully understand how it works. Together, the drugs prevented the calcium leak and helped the cell membrane repair itself, restoring much of the muscles' strength. And while they also helped reduce the amount of fat accumulated within the muscles, they did not fully prevent it, nor did they help the muscles efficiently burn fats for fuel. Moving forward, the group is planning to add immune and fat cells to their experiments for greater complexity. They also are looking to further understand disruptions to cellular metabolism and to find new drugs that fully restore all strength, repair and metabolic deficit. "Right now, we have a basic muscle-only system, which is great to see the effects of the disease within the muscle itself, but what is also important is the crosstalk between immune cells, fat cells and muscle cells," Khodabukus said. "By building out our system more, we'll hopefully be able to fully figure out what is driving the loss of muscle and its replacement by fat in these patients." This research was supported by the National Institutes of Health (UG3TR002142, U01EB028901, R01AR070543, R01AR079223, R01ARO82979, R21AR078269, UH3TR002142) and the Jain Foundation.