Crouzon Syndrome With Acanthosis Nigricans

Pictured: 3D illustration of arrows reflecting changes in direction/iStock/Olivier Le Moal Despite having an FDA-approved product, Gamida Cell is entering into a restructuring agreement in which it will become a private company under the ownership of Highbridge Capital Management amid financial struggles, the company announced Wednesday. Under the agreement, Gamida Cell will become a private company wholly owned by Highbridge Capital Management—the biotech’s principal lender. The move is designed to give the company some long-term runway and support the commercialization of Omisirge, an FDA-approved nicotinamide modified allogeneic hematopoietic progenitor cell therapy. This comes after the biotech announced in January that it was seeking “strategic alternatives” and was focused on an asset sale, merger, or other deal. “In March 2023, Gamida Cell embarked on an extensive strategic process to address its capital structure and liquidity constraints by partnering Omisirge with a third party,” Gamida Cell CEO Abbey Jenkins said in Wednesday’s statement. “Unfortunately, that process did not yield any actionable alternatives. This restructuring will enable Gamida Cell to remain a going concern. It will support our ongoing efforts to make Omisirge available to more transplant centers and their patients as a potentially lifesaving donor source option.” The terms of the restructuring will see Highbridge convert $75 million of its existing unsecured convertible senior note into equity for Gamida Cell. The biotech will also get $30 million of new capital from Highbridge when the restructuring goes into effect. The biotech will now be off the stock market and wholly owned by Highbridge, with all ordinary shares expected to be canceled. The reorganized Gamida Cell will also issue contingent value rights with a maximum value of $27.5 million to shareholders. Gamida Cell’s main product, Omisirge, was approved by the FDA in April 2023 after a lengthy regulatory road and is indicated for patients who are scheduled to undergo umbilical cord blood transplantation after chemotherapy or radiotherapy. However, the therapy does come with a boxed warning for potentially fatal conditions such as infusion reactions, graft failure, engraftment syndrome, and graft-versus-host disease. The company revealed in a third-quarter report in 2023 that 17 transplant centers were onboarded to provide Omisirge to patients, exceeding the company’s target of 10 to 15. However, the company said that it would continue to have a “lean launch effort” in 2024 due to “resource constraints” and—contingent on additional funding to extend its cash runway—would plan to onboard at least 40 transplant centers by the end of this year. “Despite Gamida Cell’s financial struggles, we believe in the potential of Omisirge to fulfill an important unmet need in stem cell transplant,” Jonathan Segal, co-chief investment officer at Highbridge Capital Management, said in a statement. “Subject to an approved budget from the Company’s new board of directors, we intend to provide the Company with additional capital to fund this potentially life-saving therapy.” The deal is expected to close in the second quarter of 2024 upon being approved by an Israeli court. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

First and only long-acting C5 complement inhibitor offers patients with AQP4 Ab+ NMOSD the potential to live relapse-free Unprecedented relapse risk reduction observed in CHAMPION-NMOSD trial underscores how ULTOMIRIS may redefine patient journey for rare neurological disease WILMINGTON, Del.--(BUSINESS WIRE)-- ULTOMIRIS® (ravulizumab-cwvz) has been approved in the United States (US) as the first and only long-acting C5 complement inhibitor for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD).1 The approval by the US Food and Drug Administration (FDA) was based on positive results from the CHAMPION-NMOSD Phase III trial, which were published in the Annals of Neurology.2 In the trial, ULTOMIRIS was compared to an external placebo arm from the pivotal SOLIRIS® PREVENT clinical trial. ULTOMIRIS met the primary endpoint of time to first on-trial relapse as confirmed by an independent adjudication committee. Zero relapses were observed among ULTOMIRIS patients with a median treatment duration of 73 weeks (relapse risk reduction: 98.6%, hazard ratio (95% CI): 0.014 (0.000, 0.103), p<0.0001).2 NMOSD is a rare and debilitating autoimmune disease that affects the central nervous system (CNS), including the spine and optic nerves.3-5 Most people living with NMOSD experience unpredictable relapses, characterized by a new onset of neurologic symptoms or worsening of existing neurologic symptoms, which tend to be severe and recurrent and may result in permanent disability.6-8 The diagnosed prevalence of adults with NMOSD in the US is estimated at approximately 6,000.9-11 Sean J. Pittock, MD, Director of Mayo Clinic's Center for Multiple Sclerosis and Autoimmune Neurology and of Mayo's Neuroimmunology Laboratory and lead primary investigator in the CHAMPION-NMOSD trial, said: “C5 inhibition has been proven to offer efficacy in reducing the risk of NMOSD relapses by blocking the complement system, a part of the immune system, from attacking healthy cells in the spinal cord, optic nerve and brain. With today’s FDA approval, patients now have the option of a long-acting C5 inhibitor treatment that showed zero relapses in the pivotal CHAMPION-NMOSD trial, supporting the primary goal of relapse prevention in treating NMOSD.” Marc Dunoyer, Chief Executive Officer, Alexion, said: “Alexion has been at the forefront of innovation in NMOSD, striving to offer patients a future without fear of life-altering or even fatal relapses. Building on the established efficacy of C5 inhibition for people living with AQP4 Ab+ NMOSD, we are proud to deliver a transformative, long-acting treatment option that has the potential to eliminate relapses with a convenient dosing schedule every eight weeks. We are grateful to the NMOSD community for their ongoing collaboration and input, which enables us to advance science for rare diseases.” Overall, the safety and tolerability of ULTOMIRIS in the CHAMPION-NMOSD trial were consistent with previous clinical studies and real-world use, and no new safety signals were observed. The most common adverse events (AEs) were COVID-19, headache, back pain, arthralgia and urinary tract infection.2 ULTOMIRIS is also approved for certain adults with NMOSD in Japan and the European Union (EU). Regulatory reviews are ongoing in additional countries. INDICATION(S) & IMPORTANT SAFETY INFORMATION INDICATION(S) What is ULTOMIRIS? ULTOMIRIS is a prescription medicine used to treat: adults and children 1 month of age and older with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH). adults and children 1 month of age and older with a disease called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not used in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). adults with a disease called generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive. adults with a disease called Neuromyelitis Optica Spectrum Disorder (NMOSD) who are anti-aquaporin 4 (AQP4) antibody positive. It is not known if ULTOMIRIS is safe and effective in children younger than 1 month of age. It is not known if ULTOMIRIS is safe and effective for the treatment of gMG or NMOSD in children. IMPORTANT SAFETY INFORMATION What is the most important information I should know about ULTOMIRIS? ULTOMIRIS is a medicine that affects your immune system and may lower the ability of your immune system to fight infections. ULTOMIRIS increases your chance of getting serious meningococcal infections that may quickly become life-threatening or cause death if not recognized and treated early. You must complete or update meningococcal vaccine(s) at least 2 weeks before your first dose of ULTOMIRIS. If you have not completed your meningococcal vaccines and ULTOMIRIS must be started right away, you should receive the required vaccine(s) as soon as possible. If you have not been vaccinated and ULTOMIRIS must be started right away, you should also receive antibiotics for as long as your healthcare provider tells you. If you had a meningococcal vaccine in the past, you might need additional vaccines before starting ULTOMIRIS. Your healthcare provider will decide if you need additional meningococcal vaccines. Meningococcal vaccines do not prevent all meningococcal infections. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection: fever, fever with high heart rate, headache and fever, confusion, muscle aches with flu-like symptoms, fever and a rash, headache with nausea or vomiting, headache with a stiff neck or stiff back, or eyes sensitive to light. Your healthcare provider will give you a Patient Safety Card about the risk of serious meningococcal infection. Carry it with you at all times during treatment and for 8 months after your last ULTOMIRIS dose. Your risk of meningococcal infection may continue for several months after your last dose of ULTOMIRIS. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly. ULTOMIRIS is only available through a program called the ULTOMIRIS and SOLIRIS Risk Evaluation and Mitigation Strategy (REMS). Before you can receive ULTOMIRIS, your healthcare provider must: enroll in the REMS program; counsel you about the risk of serious meningococcal infections; give you information about the signs and symptoms of serious meningococcal infection; make sure that you are vaccinated against serious infections caused by meningococcal bacteria, and that you receive antibiotics if you need to start ULTOMIRIS right away and are not up to date on your vaccines; give you a Patient Safety Card about your risk of meningococcal infection. ULTOMIRIS may also increase the risk of other types of serious infections, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae. Your child should receive vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) if treated with ULTOMIRIS. Certain people may be at risk of serious infections with gonorrhea. Who should not receive ULTOMIRIS? Do not receive ULTOMIRIS if you have a serious meningococcal infection when you are starting ULTOMIRIS. Before you receive ULTOMIRIS, tell your healthcare provider about all of your medical conditions, including if you: have an infection or fever, are pregnant or plan to become pregnant, and are breastfeeding or plan to breastfeed. It is not known if ULTOMIRIS will harm your unborn baby or if it passes into your breast milk. You should not breastfeed during treatment and for 8 months after your final dose of ULTOMIRIS. Tell your healthcare provider about all the vaccines you receive and medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements which could affect your treatment. If you have PNH and you stop receiving ULTOMIRIS, your healthcare provider will need to monitor you closely for at least 16 weeks after you stop ULTOMIRIS. Stopping ULTOMIRIS may cause breakdown of your red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: drop in your red blood cell count, tiredness, blood in your urine, stomach-area (abdomen) pain, shortness of breath, blood clots, trouble swallowing, and erectile dysfunction (ED) in males. If you have aHUS, your healthcare provider will need to monitor you closely for at least 12 months after stopping treatment for signs of worsening aHUS or problems related to a type of abnormal clotting and breakdown of your red blood cells called thrombotic microangiopathy (TMA). Symptoms or problems that can happen with TMA may include: confusion or loss of consciousness, seizures, chest pain (angina), difficulty breathing and blood clots or stroke. What are the possible side effects of ULTOMIRIS? ULTOMIRIS can cause serious side effects including infusion-related reactions. Symptoms of an infusion-related reaction with ULTOMIRIS may include lower back pain, abdominal pain, muscle spasms, changes in blood pressure, tiredness, feeling faint, shaking chills (rigors), discomfort in your arms or legs, bad taste, or drowsiness. Stop treatment of ULTOMIRIS and tell your healthcare provider right away if you develop these symptoms, or any other symptoms during your ULTOMIRIS infusion that may mean you are having a serious infusion-related reaction, including: chest pain, trouble breathing or shortness of breath, swelling of your face, tongue, or throat, and feel faint or pass out. The most common side effects of ULTOMIRIS in people treated for PNH are upper respiratory tract infection and headache. The most common side effects of ULTOMIRIS in people treated for aHUS are upper respiratory tract infection, diarrhea, nausea, vomiting, headache, high blood pressure and fever. The most common side effects of ULTOMIRIS in people with gMG are diarrhea and upper respiratory tract infections. The most common side effects of ULTOMIRIS in people with NMOSD are COVID-19 infection, headache, back pain, urinary tract infection, and joint pain (arthralgia). Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of ULTOMIRIS. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider right away if you miss an ULTOMIRIS infusion or for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please see the accompanying full Prescribing Information and Medication Guide for ULTOMIRIS, including Boxed WARNING regarding serious meningococcal infections. Notes NMOSD NMOSD is a rare disease in which the immune system is inappropriately activated to target healthy tissues and cells in the CNS.3,4 Approximately three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce antibodies that bind to a specific protein, aquaporin-4 (AQP4).5,12 This binding can inappropriately activate the complement system, which is part of the immune system and is essential to the body’s defense against infection, to destroy cells in the optic nerve, spinal cord and brain.3,13,14 It most commonly affects women and begins in the mid-30s. Men and children may also develop NMOSD, but it is even more rare.15,16 People with NMOSD may experience vision problems, intense pain, loss of bladder/bowel function, abnormal skin sensations (e.g., tingling, prickling or sensitivity to heat/cold) and impact on coordination and/or movement.5-7,17,18 Most people living with NMOSD experience unpredictable relapses, also known as attacks. Each relapse can result in cumulative disability including vision loss, paralysis and sometimes premature death.6-8 NMOSD is a distinct disease from other CNS diseases, including multiple sclerosis. The journey to diagnosis can be long, with the disease sometimes misdiagnosed.19-21 CHAMPION-NMOSD CHAMPION-NMOSD is a global Phase III, open-label, multicenter trial evaluating the safety and efficacy of ULTOMIRIS in adults with NMOSD. The trial enrolled 58 patients across North America, Europe, Asia-Pacific and Japan. Participants were required to have a confirmed NMOSD diagnosis with a positive anti-AQP4 antibody test, at least one attack or relapse in the twelve months prior to the screening visit, an Expanded Disability Status Scale Score of 7 or less and body weight of at least 40 kilograms at trial entry. Participants could stay on stable supportive immunosuppressive therapy for the duration of the trial.22 Due to the potential long-term functional impact of NMOSD relapses and available effective treatment options, a direct placebo comparator arm was precluded for ethical reasons. The active treatment was compared to an external placebo arm from the pivotal SOLIRIS PREVENT clinical trial. Over a median treatment duration of 73 weeks, all enrolled patients received a single weight-based loading dose of ULTOMIRIS on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15, every eight weeks. The primary endpoint was time to first on-trial relapse, as confirmed by an independent adjudication committee. The end of the primary treatment period could have occurred either when all patients completed or discontinued prior to the Week 26 visit and two or more adjudicated relapses were observed, or when all patients completed or discontinued prior to the Week 50 visit if fewer than two adjudicated relapses were observed. In the trial, there were zero adjudicated relapses, so the end of the primary treatment period occurred when the last enrolled participant completed the 50-week visit. Patients who completed the primary treatment period were eligible to continue into a long-term extension period, which is ongoing. ULTOMIRIS® (ravulizumab-cwvz) ULTOMIRIS® (ravulizumab-cwvz), the first and only long-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. ULTOMIRIS is administered intravenously every eight weeks in adult patients, following a loading dose. ULTOMIRIS is approved in the US, EU, Japan and other countries for the treatment of certain adults with generalized myasthenia gravis (gMG). ULTOMIRIS is also approved in the US, EU, Japan and other countries for the treatment of certain adults with paroxysmal nocturnal hemoglobinuria (PNH) and for certain children with PNH in the US and EU. Additionally, ULTOMIRIS is approved in the US, EU, Japan and other countries for certain adults and children with atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy (aHUS). Further, ULTOMIRIS is approved in the US, EU and Japan for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD). As part of a broad development program, ULTOMIRIS is being assessed for the treatment of additional hematology and neurology indications. Alexion Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for more than 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialization of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on hematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in 70 countries. For more information, please visit . AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit and follow the Company on social media @AstraZeneca. References Ultomiris (ravulizumab-cwvz) US prescribing information; 2024. Pittock, SJ, et al. Ravulizumab in aquaporin-4–positive neuromyelitis optica spectrum disorder. Ann Neurol, 2023; 93: 1053-1068. Wingerchuk DM, et al. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6(9):805-815. Wingerchuk DM. Diagnosis and treatment of neuromyelitis optica. Neurologist. 2007;13(1):2-11. Hamid SHM, et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol. 2017;264(10):2088-2094. Wingerchuk DM, et al. Neuromyelitis optica. Curr Treat Options Neurol. 2008;10(1):55-66. Kitley J, et al. Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. 2012;135(6):1834-1849. Jarius S, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14. Papp V, et al. A population-based epidemiological study of neuromyelitis optica spectrum disorder in Hungary. Eur J Neurol. 2020;27(2):308-317. Flanagan EP, et al. Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Ann Neurol. 2016;79:775–783. Bukhari W, et al. Incidence and Prevalence of NMOSD in Australia and New Zealand. J Neurol Neurosurg Psychiatry. 2017;88(8):632-638. Wingerchuk DM, et al. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53(5):1107-1114. Cossburn M, et al. The Prevalence of Neuromyelitis Optica in South East Wales. Eur J Neurol. 2012;19(4): 655-659. Papadopoulos MC, et al. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol. 2014;10(9):493. Takata K, et al. Aquaporins: water channel proteins of the cell membrane. Prog Histochem Cytochem. 2004;39(1):1-83. Mori M, et al. Worldwide prevalence of neuromyelitis optica spectrum disorders. J Neurol Neurosurg Psychiatry. 2018;89(6):555-556. Quek AML, et al. Effects of age and sex on aquaporin-4 autoimmunity. Arch Neurol. 2012;69:1039–43. Tüzün E, et al. Enhanced complement consumption in neuromyelitis optica and Behcet’s disease patients. J Neuroimmunol. 2011;233(1-2):211-215. Kuroda H, et al. Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica. J Neuroimmunol. 2013;254(1-2):178-182. Jarius S, et al.. The History of Neuromyelitis Optica. J Neuroinflammation. 2013;10, 797. Mealy MA, et al. Assessment of Patients with Neuromyelitis Optica Spectrum Disorder Using the EQ-5D. Int J MS care. 2019;21(3), 129–134. ClinicalTrials.gov. An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD. NCT Identifier: NCT04201262. Available here. Accessed March 2024. Dr. Pittock has provided consulting services to Alexion.

The figures for Rights of Use assets (6,620 KSEK) were missing in the previous report and have now been added. The total sums for Fixed Assets and the Balance Sheet remain the same. MÖLNDAL, Sweden, Feb. 29, 2024 /PRNewswire/ -- THIRD QUARTER 2023/24 (NOV - JAN) Net sales amounts to 30.1 (18.7) MSEK, which is an increase of 61% compared with the corresponding period last year. The growth in the US market is 43% compared with the corresponding period last year. Operating profit amounts to 0.3 (-13.8) MSEK (EBIT 1.1%). The operating profit amounted to 6.1 MSEK (EBIT 20.2%) excluding currency effects of -5.7 MSEK, most of which are unrealized internal accounts receivables. Profit/loss after tax amounts to 0.8 (-13.6) MSEK, which resulted in profit per share of SEK 0.05 (-0.74). Cash flow from operating activities amounts to 2.0 MSEK (-14.1), change in working capital was -2.9 MSEK (8.2) and investing activities -4.0 (-1.2). Total cash flow for the period was -5.0 (-7.1) MSEK. Liquid assets as of 2024-01-31 amount to 28.4 (46.3) MSEK, not including 29.2 MSEK in accounts receivables. Significant events in the third quarter The US Department of Defense decided to fully fund a clinical study of OPRA™ Implant System on up to 30 patients with transtibial (below-knee) amputations. The study will be performed by the Walter Reed National Military Medical Center. Integrum will supply OPRA™ Implant Systems on commercial terms. The company held a pre-submission meeting with the US Food and Drug Administration (FDA). Based on the conclusions from the meeting, Integrum plans to submit a Pre-Market Approval (PMA) application for Integrum's OPRA™ Implant System in transhumeral amputations based on existing clinical data. Integrum received its final MDR certification. The company's OPRATM Implant System product portfolio has thereby been granted MDR certification and may be freely distributed within the EU for treatment in individuals living with disabilities because of limb loss. The company established a Center of Excellence at the Center for Complex Endoprosthetics, Osseointegration and Bionics in Kyiv, with the intention to spearhead orthopedic treatment using OPRA™ Implant System in individuals who have suffered limb loss. 1 MAY - 31 JANUARY 2022/23 (9 MONTHS) Net sales amounts to 78.1 (56.1) MSEK, which is an increase of 39% compared with the corresponding period last year. The growth in the US market is 29% compared with the corresponding period last year Operating profit amounts to 3.9 (-12.5) MSEK (EBIT 5.0%). The operating profit amounted to 2.5 MSEK (EBIT 3.2%), excluding currency effects of 1.4 MSEK, most of which are unrealized internal accounts receivables. Profit/loss after tax amounts to 1.9 (-10.1) MSEK, which resulted in earnings per share of SEK 0.1 (-0.55). Cash flow from operating activities amounts to 2.6 (-17.1) MSEK. Total cash flow was -13.6 (-29.0) MSEK. During the year, The Centers for Medicare and Medicaid Services (CMS) granted the osseointegrated external prosthetic connection device Axor II™ a new reimbursement code. The new code is connected to a set reimbursement that will help to drive growth in the US. CEO's statement The third quarter has been characterized by record sales figures, mainly driven by our continued expansion in the US and a recent accelerating growth in emerging markets. Yet another quarter with record sales and profit Revenues amounted to 30.1 MSEK in the third quarter, corresponding to an increase of 61.2 percent compared to the same period last year. Excluding direct currency effects, operating profit amounted to 6.1 MSEK leading to an EBIT margin of 20.2%. Enhanced collaborations in the US In the US, which is our prioritized market, we have worked to deepen existing collaborations with hospitals offering treatment with our innovative products. The work is based on Integrum's network model to collect and connect healthcare professionals that surround the patient undergoing treatment with the OPRA™ Implant system. By building an ecosystem with all key players, we lessen hospitals' administrative burden and help them funnel patients through the treatment process. Ultimately, we believe this will increase patient turnover and, most importantly, improve the individual patient's healthcare experience. In November, we announced our plans to apply for pre-market approval (PMA) for the use of the OPRA™ Implant System in above-elbow treatment. Following a successful meeting with the FDA, we are working with high focus to compile the necessary regulatory documentation needed for a formal application. Expansion into new markets Integrum's innovative and bone-anchored OPRA™ Implant System restores mobility in a completely different way than traditional socket prostheses. To this end, our ambition is to treat as many amputees as possible, as quickly as possible, with the OPRA™ Implant System to improve their quality of life. Hence, during the fall, alongside our US operations, we have focused on making the OPRA™ Implant System available in Ukraine and Turkey - two countries that, for various reasons, have seen rapidly growing groups of amputees. In December, we announced the establishment of a clinical center of excellence in Kyiv - aimed at training Ukrainian surgeons in using the OPRA™ Implant System. During the fall, I visited the center three times to perform surgeries, initially pro bono to swiftly get the center into operations. In January, the center independently performed seven surgeries, and is now conducting self-sufficient clinical activities offering the OPRA™ Implant System. The collaboration has generated orders already in the short term; at the end of January, Integrum sold and delivered OPRATM Implant Systems to a value of SEK 3.5 million. The need for Integrum's bone-anchored prosthetic treatments in Ukraine is partly driven by an increased incidence of the tourniquet syndrome, which primarily affects soldiers at the front. The syndrome occurs when treatment of extensive injuries to limbs is delayed. Due to the restricted blood flow during acute treatment with torniquets, the affected individual is usually left with a short stump. In these cases, socket prostheses use is almost impossible, unlike the OPRA™ Implant System which can restore full mobility. During my last visit in Kyiv, I met with Ukraine's Minister of Health, Viktor Liashko, who expressed the country's extensive need for high-standard prosthetic treatments and its willingness to invest in restoring the population's health. According to the Ukrainian Ministry of Health, nearly 100,000 people are expected to have an amputation at the end of 2024. In Turkey, since the end of October, we have been working with our partner Medikon to establish a business solution to offer treatments for people injured in the country's extensive earthquake in early 2023. A skilful organization to achieve high growth We have, time and again, shown the overturning potential in our innovative bone-anchored solutions - based both on a large body of scientific and clinical evidence, as well as important public recognition. As the organization has grown with skilled experts in key positions, we now see an important shift in our regulatory and commercial activities laying the foundation for meaningful growth. Integrum is the world's foremost company in in advanced amputation treatment, and we look forward to leading the way in restoring mobility globally. Mölndal, 29 February 2024 Rickard Brånemark Chief Executive Officer The interim report can be found here: This disclosure contains information that Integrum AB is obliged to make public pursuant to the EU Market Abuse Regulation (EU nr 596/2014). The information was submitted for publication, through the agency of the contact person, on 29-02-2024 09:39 CET. For more information please contact: Rickard Brånemark, CEO. Phone: +46 70 846 10 61, E-mail: [email protected] Jörgen Svanström, CFO. Phone: +46 70 734 96 60, E-mail: [email protected] Certified Adviser: The Company's Certified Adviser is Carnegie Investment Bank AB (publ). The following files are available for download: SOURCE Integrum AB