Blindness, Cortical

• Statistically significant difference in arrested disease in leriglitazone treated patients when compared to the natural history of the disease • Submission of European marketing authorization application (MAA) for leriglitazone expected mid-2025. BARCELONA, Spain and DÜSSELDORF, Germany I December 11, 2024 I Minoryx Therapeutics, a late-stage biotech company focused on the development of therapies for orphan central nervous system (CNS) disorders and Neuraxpharm Group (Neuraxpharm), a leading European specialty pharmaceutical company focused on the treatment of CNS disorders, today announced that the NEXUS trial has been completed and that the primary endpoint has been met. The parties intend to file for European Marketing Authorization of leriglitazone in pediatric and adult cerebral Adrenoleukodystrophy (cALD) patients by mid-2025. The NEXUS trial was a 96-week, pivotal, open-label study designed to evaluate the efficacy and safety of once-daily oral dosing of leriglitazone in pediatric patients with cALD. The primary endpoint assessed the proportion of patients that had clinical and radiological arrested disease at week 96 or at a visit prior to hematopoietic stem cell transplant (HSCT). The evaluable population in the study consisted of 20 patients treated for a minimum of 24 weeks. All 20 patients remained clinically stable whilst on treatment and 7 out of 20 patients (35%) met the arrested disease criteria, which is significantly greater than the 10% self-arrested patients that would be expected from natural history (p<0.05). Leriglitazone was well tolerated in all children, there were no treatment-related serious adverse events nor discontinuations due to treatment related adverse events. The full results of the NEXUS trial will be presented at upcoming neurology conferences. “Cerebral ALD in boys is a devastating disease both for the patients and their families. Treatment options are limited, physicians and families of patients have constantly been searching for better tools and therapies to manage cALD in boys.” said Patricia Musolino, Global Principal Investigator of Nexus. “The NEXUS results attest that leriglitazone addresses a critical unmet need for non-invasive treatments that can be administered at the moment brain lesions are identified to arrest or slow down lesion growth.” “We are very pleased with the positive results from NEXUS demonstrating that leriglitazone not only arrests the demyelinating brain lesions in children with cALD but also arrests clinical progression. These results are further supported by evidence from the cALD related endpoints of ADVANCE1 in adult patients and the findings reported in cALD patients treated under compassionate use1” said Marc Martinell, CEO, Minoryx. ”Together with our partner, Neuraxpharm, we intent to submit the MAA to the EMA for this life-threatening condition as soon as possible.” Dr. Jörg-Thomas Dierks, CEO, Neuraxpharm said; “cALD is a very serious neurological disorder with devastating outcomes for patients and their families. The results from this trial are extremely encouraging and we are fully committed to working with Minoryx to swiftly provide patients with an effective new treatment for this otherwise fatal and cruel disease.” Based on the successful results from NEXUS, Minoryx and Neuraxpharm have begun to compile the regulatory file for MAA submission in the European Union. About leriglitazone Leriglitazone is Minoryx Therapeutics’ novel orally bioavailable, selective PPAR gamma agonist with a potential first-in-class and best-in-class profile for CNS diseases. It has demonstrated brain penetration and a favorable safety profile. It showed robust preclinical proof-of-concept in animal models of multiple diseases by modulating pathways leading to neuroinflammation, demyelination, mitochondrial dysfunction, oxidative stress, and axonal degeneration. In clinical trials, leriglitazone showed clinical benefit in both pediatric X-ALD patients in NEXUS and adult X-ALD patients in ADVANCE. Results from NEXUS demonstrate that pediatric cALD patients are clinically and radiologically stable after 96 weeks of treatment or at a visit prior to HSCT. Data from ADVANCE showed that leriglitazone reduces the progression of lesions and the development of progressive cALD in adult patients. Another clinical trial in adult male patients with progressive cALD (CALYX2) is currently recruiting in the US, Argentina, Brazil and Europe. Leriglitazone has been granted orphan drug status for X-ALD from the FDA and the EMA and Fast Track and Rare Pediatric Disease designation from the FDA for the treatment of X-ALD. About NEXUS NEXUS is a 96-week, pivotal, open-label, multicenter study (NEXUS; NCT04528706) of once-daily oral leriglitazone in pediatric patients with cALD. NEXUS has enrolled 23 patients and the evaluable population consisted of those patients treated for a minimum of 24 weeks (n=20). The primary endpoint assesses the proportion of evaluable patients that have clinically and radiologically arrested disease at week 96 or at a visit prior to HSCT (success criteria: one-sided 95% [CI] > 10%). Secondary endpoints include change from baseline in NFS and Loes score (LS). Change from baseline in lesion volume and plasma biomarker concentrations are exploratory endpoints. About X-ALD and cALD X-linked adrenoleukodystrophy (X-ALD) is an orphan neurodegenerative disease. The global incidence of X-ALD is approximately 6-8/100,000 live births. Boys and adult men with X-ALD can, at any point in their lifetime, develop cALD, which is characterized by demyelinating brain lesions that may become rapidly progressive, leading to acute neurological decline and death. These lesions can produce severe symptoms such as loss of voluntary movements, inability to swallow, loss of communication, cortical blindness and total incontinence and death with a mean survival of 3 to 4 years. Progressive cALD occurs in 31-35% of ALD patients in childhood with typical onset between the age of 2-12 and up to 60% of adult patients with X-ALD will develop progressive cALD over time. There is currently no pharmacological treatment available for cALD. In childhood, Hematopoietic Stem Cell Transplantation (HSCT) can arrest the disease. However, it is an aggressive procedure and is only available for a portion of patients. Gene therapy based HSCT is not globally available, and it requires myeloablative chemotherapy with associated comorbidities. In adults, experience in HSCT is very limited and this intervention is often not recommended. In addition, all X-ALD patients reaching adulthood develop adrenomyeloneuropathy (AMN). This form progresses chronically and cALD patients with advanced AMN are largely ineligible to HSCT due to the poor prognosis of the treatment. About Minoryx Minoryx Therapeutics is a registration stage biotech company focusing on the development of novel therapies for orphan central nervous system (CNS) diseases with high unmet medical needs. The company’s lead program, leriglitazone (MIN-102), a novel, brain penetrant and selective PPAR gamma agonist, is being developed to treat X-linked adrenoleukodystrophy (X-ALD) and other orphan CNS diseases. The company is backed by a syndicate of experienced investors, which includes Columbus Venture Partners, CDTI Innvierte, Criteria BioVentures, Fund+, Ysios Capital, Roche Venture Fund, Kurma Partners, Chiesi Ventures, S.R.I.W, Idinvest Partners / Eurazeo, SFPI-FPIM, HealthEquity, Sambrinvest and Herrecha, and has support from a network of other organizations. Minoryx was founded in 2011, is headquartered in Spain with Belgian facilities and has so far raised more than €120 million. For more information, please visit https://www.minoryx.com/ . About the Neuraxpharm Group Neuraxpharm is a leading European specialty pharmaceutical company focused on the treatment of the central nervous system (CNS), including both psychiatric and neurological disorders. It has a unique understanding of the CNS market built over 35 years. Neuraxpharm is constantly innovating, with new products and solutions to address unmet patient needs and is expanding its portfolio through its pipeline, partnerships and acquisitions. The company has more than 1,000 employees and develops and commercializes CNS products through a direct presence in more than 20 countries in Europe, two in Latin America, one in the Middle East and globally via partners in more than 50 countries. Neuraxpharm is backed by funds advised by Permira. Neuraxpharm manufactures many of its pharmaceutical products at Neuraxpharm Pharmaceuticals (formerly Laboratorios Lesvi) in Spain. For more information, please visit www.neuraxpharm.com . 1 ADVANCE, a pivotal phase 2/3 randomized, double-blind, placebo-controlled, clinical study with an open-label extension, was designed to assess the efficacy and safety of leriglitazone in male patients with X-ALD. 2 CALYX, a phase 3, multicenter, randomized (1:1), double-blind, placebo-controlled, clinical study, has been designed to compare the efficacy and safety of leriglitazone in male adult patients with progressive cALD ( https://clinicaltrials.gov/study/NCT05819866 ). SOURCE: Neuraxpharm

PHILADELPHIA--( BUSINESS WIRE )--GSK plc (LSE/NYSE: GSK) today announced statistically significant and clinically meaningful overall survival (OS) results from Part 1 and progression-free survival (PFS) results from Part 2 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial in adult patients with primary advanced or recurrent endometrial cancer. These data were presented today in a late-breaking plenary session at the Society of Gynecologic Oncology 2024 Annual Meeting on Women’s Cancer (March 16-18). The goal of the RUBY phase III trial program is to evaluate which patients with primary advanced or recurrent endometrial cancer could potentially benefit from treatment with Jemperli (dostarlimab-gxly) plus chemotherapy, with or without the addition of Zejula (niraparib) maintenance. Part 1 of the RUBY phase III trial is investigating dostarlimab-gxly plus standard-of-care chemotherapy (carboplatin-paclitaxel) followed by dostarlimab-gxly compared to chemotherapy plus placebo followed by placebo. Part 2 of the RUBY phase III trial is evaluating dostarlimab-gxly plus standard-of-care chemotherapy, followed by dostarlimab-gxly plus niraparib as maintenance therapy compared to chemotherapy plus placebo followed by placebo. The safety and tolerability profiles of dostarlimab-gxly plus carboplatin-paclitaxel and dostarlimab-gxly plus carboplatin-paclitaxel followed by dostarlimab-glxy plus niraparib were generally consistent with the known safety profiles of the individual medicines. Previous data showed a statistically significant and clinically meaningful improvement in PFS with Jemperli plus chemotherapy versus chemotherapy alone in frontline mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer. These data led to regulatory approvals for this patient population in the US, EU and certain other countries. Data presented today show additional potential benefit of dostarlimab-gxly plus chemotherapy, with or without the addition of niraparib, in the overall population of patients with primary advanced or recurrent endometrial cancer, including patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, for which there are currently no approved immuno-therapy-based regimens. Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK said : “ The positive data presented today further show how dostarlimab-gxly-based regimens could benefit a broader set of patients with endometrial cancer. The results we’ve seen to date comprise the growing body of evidence supporting the role of dostarlimab-gxly as the backbone of our immuno-oncology development program. Our goal is to continue to identify ways to use dostarlimab-gxly alone and in combination with other therapies to help improve outcomes for patients with limited treatment options.” RUBY Part 1: a statistically significant and clinically meaningful improvement in OS was observed for dostarlimab-gxly plus chemotherapy versus placebo plus chemotherapy, meeting a primary endpoint of the study. Dostarlimab-gxly plus chemotherapy versus chemotherapy alone showed: In the overall population: a statistically significant reduction in the risk of death by 31% (Hazard Ratio [HR]: 0.69; [95% CI: 0.539–0.890]) a clinically meaningful improvement of 16.4 months in median OS (44.6 months vs 28.2 months) In a prespecified exploratory analysis of the MMRp/MSS population: a clinically meaningful trend in reduced risk of death by 21% (HR: 0.79; [95% CI: 0.602–1.044]) a clinically meaningful improvement of seven months in median OS (34.0 months vs 27.0 months) Full OS summaries are shown below. dostarlimab-gxly + carboplatin-paclitaxel placebo + carboplatin-paclitaxel Overall population, Number (N) 245 249 OS, HR (95% CI) 0.69 (0.539–0.890) P -value 1 0.002 OS, median (95% CI), mo. 44.6 (32.6–NR) 28.2 (22.1–35.6) dMMR/MSI-H population 2 , N 53 65 OS, HR (95% CI) 0.32 (0.166–0.629) OS, median 3 (95% CI), mo. NR (NR–NR) 31.4 (20.3–NR) MMRp/MSS2, N 192 184 OS, HR (95% CI) 0.79 (0.602–1.044) OS, median (95% CI), mo. 34.0 (28.6–NR) 27.0 (21.5–35.6) 1 One-sided p-value based on stratified log-rank test. 2 Exploratory analyses of OS in dMMR/MSI-H and OS in MMRp/MSS populations were pre-specified with no planned hypothesis testing. 3 Although the median OS was not reached, at 30 months the estimated reduction in the risk of death was 82.8% for patients who received dostarlimab plus chemotherapy vs. 54.1% for patients who received chemotherapy alone. Matthew Powell, MD, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial said: “ RUBY Part 1 is the first clinical trial to show a statistically significant and clinically meaningful improvement in overall survival for an immuno-oncology therapy in combination with chemotherapy in the overall population of patients with primary advanced or recurrent endometrial cancer. As a clinician, I celebrate the results of the RUBY Part 1 trial presented today, which show how dostarlimab-gxly added to chemotherapy could potentially benefit a broader set of patients with this type of cancer.” In RUBY Part 1, grade 3 or higher and serious treatment-emergent adverse events (AEs) were approximately 12% higher in the dostarlimab-gxly plus carboplatin-paclitaxel arm (treatment arm) compared with the placebo plus carboplatin-paclitaxel arm (control arm). The nature and types of immune-related AEs in the dostarlimab-gxly plus chemotherapy safety profile were consistent with the mechanism of action of dostarlimab-gxly and similar to those reported for other PD-(L)1 inhibitors. In the trial, 40.7% of participants in the treatment arm and 16.3% of participants in the control arm had immune-related AEs assessed by the investigator as related to dostarlimab-gxly or placebo, respectively. Discontinuation of dostarlimab-gxly or placebo due to a treatment-emergent AE occurred in 19.1% of patients in the treatment arm and 8.1% of patients in the control arm. GSK expects US Food and Drug Administration regulatory submission acceptance based on RUBY Part 1 data for an expanded indication in the overall population in the first half of this year. RUBY Part 2: addition of niraparib to dostarlimab-gxly in maintenance setting significantly improved PFS in first-line primary advanced or recurrent endometrial cancer compared to chemotherapy alone, meeting the primary endpoint of the trial. Dostarlimab-gxly plus chemotherapy followed by dostarlimab-gxly plus niraparib compared to placebo plus chemotherapy followed by placebo showed: In the overall population: a statistically significant reduction in the risk of disease progression or death by 40% (HR: 0.60 [95% CI: 0.43–0.82]) a clinically meaningful improvement of 6.2 months in median PFS (14.5 months vs 8.3 months) In the MMRp/MSS population: a statistically significant reduction in the risk of disease progression or death by 37% (HR: 0.63 [95% CI: 0.44–0.91]) a clinically meaningful improvement of 6.0 months in median PFS (14.3 months vs 8.3 months) Dr Mansoor Raza Mirza, Chief Oncologist, Copenhagen University Hospital, Denmark, and RUBY principal investigator said : “ In RUBY Part 2, we observed that the use of dostarlimab-gxly in combination with niraparib in the maintenance therapy setting further improved progression-free survival versus placebo for patients with primary advanced or recurrent endometrial cancer. These findings are particularly important for patients who have MMRp/MSS tumors as the data help build on the initial benefit observed with an immuno-oncology plus chemotherapy regimen, reflecting the potential for the addition of niraparib maintenance to address unmet medical need for these patients.” In RUBY Part 2, grade 3 or higher and serious treatment-emergent AEs were approximately 36% and 24% higher, respectively, in the dostarlimab-gxly plus chemotherapy followed by dostarlimab-gxly plus niraparib arm (treatment arm) compared with the placebo plus chemotherapy followed by placebo arm (control arm). In the trial, 36.6% of participants in the treatment arm and 6.3% of participants in the control arm had immune-related AEs assessed by the investigator as related to dostarlimab-gxly or placebo, respectively. No cases of myelodysplastic syndrome/acute myeloid leukemia were reported; other secondary primary malignancies occurred in 1 patient each in both treatment arms. Discontinuation of dostarlimab-gxly or placebo due to a TEAE occurred in 24.1% of patients in the treatment arm and 5.2% of patients in the control arm. Discontinuation of niraparib or placebo due to a treatment-emergent AE occurred in 15.7% of patients in the treatment arm and 4.2% of patients in the control arm. About endometrial cancer Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynecologic cancer in developed countries, with approximately 417,000 new cases reported each year worldwide 1 , and incidence rates are expected to rise by almost 40% between 2020 and 2040. 2,3 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis. 4 About RUBY RUBY is a two-part global, randomized, double-blind, multicenter phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab-gxly plus carboplatin-paclitaxel followed by dostarlimab-gxly versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab-gxly plus carboplatin-paclitaxel followed by dostarlimab-gxly plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo. In Part 1, the dual-primary endpoints are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumors v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the dMMR/MSI-H and overall populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma. In Part 2, the primary endpoint is investigator-assessed PFS in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability. RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organization dedicated to transforming the standard of care in gynecologic oncology. About Jemperli (dostarlimab-gxly) Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2. 5 Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialization, and manufacturing of Jemperli , and cobolimab (GSK4069889), a TIM-3 antagonist. Indications and Important Safety Information for JEMPERLI (dostarlimab-gxly) JEMPERLI, in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC) that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H). JEMPERLI, as a single agent, is indicated for the treatment of adult patients with dMMR recurrent or advanced: EC, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation, or solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Important Safety Information Severe and Fatal Immune-Mediated Adverse Reactions Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue and can occur at any time during or after treatment with a PD-1/PD-L1–blocking antibody, including JEMPERLI. Monitor closely for signs and symptoms of immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. For suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Based on the severity of the adverse reaction, withhold or permanently discontinue JEMPERLI. In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to ≤Grade 1. Upon improvement to ≤Grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids. Immune-Mediated Pneumonitis JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Pneumonitis occurred in 2.3% (14/605) of patients, including Grade 2 (1.3%), Grade 3 (0.8%), and Grade 4 (0.2%) pneumonitis. Immune-Mediated Colitis Colitis occurred in 1.3% (8/605) of patients, including Grade 2 (0.7%) and Grade 3 (0.7%) adverse reactions. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis. In such cases, consider repeating infectious workup to exclude alternative etiologies. Immune-Mediated Hepatitis JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Grade 3 hepatitis occurred in 0.5% (3/605) of patients. Immune-Mediated Endocrinopathies Adrenal Insufficiency Adrenal insufficiency occurred in 1.2% (7/605) of patients, including Grade 2 (0.5%) and Grade 3 (0.7%). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity. Hypophysitis JEMPERLI can cause immune-mediated hypophysitis. Grade 3 hypophysitis occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypophysitis occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity. Thyroid Disorders Grade 2 thyroiditis occurred in 0.5% (3/605) of patients. Grade 2 hypothyroidism occurred in 12% (28/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypothyroidism occurred in 8% (46/605) of patients receiving JEMPERLI as a single agent. Hyperthyroidism occurred in 3.3% (8/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, including Grade 2 (2.9%) and Grade 3 (0.4%). Hyperthyroidism occurred in 2.3% (14/605) of patients receiving JEMPERLI as a single agent, including Grade 2 (2.1%) and Grade 3 (0.2%). Initiate thyroid hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity. Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Grade 3 type 1 diabetes mellitus occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 3 type 1 diabetes mellitus occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity. Immune-Mediated Nephritis with Renal Dysfunction JEMPERLI can cause immune-mediated nephritis, which can be fatal. Grade 2 nephritis, including tubulointerstitial nephritis, occurred in 0.5% (3/605) of patients. Immune-Mediated Dermatologic Adverse Reactions JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue JEMPERLI depending on severity. Other Immune-Mediated Adverse Reactions The following clinically significant immune-mediated adverse reactions occurred in <1% of the 605 patients treated with JEMPERLI or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions. Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy Cardiac/Vascular: Myocarditis, pericarditis, vasculitis Ocular: Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur Gastrointestinal: Pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica Endocrine: Hypoparathyroidism Other (Hematologic/Immune): Autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection Infusion-Related Reactions Severe or life-threatening infusion-related reactions have been reported with PD-1/PD-L1–blocking antibodies. Severe infusion-related reactions (Grade 3) occurred in 0.2% (1/605) of patients receiving JEMPERLI. Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion or permanently discontinue JEMPERLI based on severity of reaction. Complications of Allogeneic HSCT Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after treatment with a PD-1/PD-L1–blocking antibody, which may occur despite intervening therapy. Monitor patients closely for transplant-related complications and intervene promptly. Embryo-Fetal Toxicity and Lactation Based on its mechanism of action, JEMPERLI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after their last dose. Because of the potential for serious adverse reactions from JEMPERLI in a breastfed child, advise women not to breastfeed during treatment with JEMPERLI and for 4 months after their last dose. Common Adverse Reactions The most common adverse reactions (≥20%) in patients with dMMR/MSI-H EC who received JEMPERLI in combination with carboplatin and paclitaxel were rash, diarrhea, hypothyroidism, and hypertension. The most common Grade 3 or 4 laboratory abnormalities (≥10%) were decreased neutrophils, decreased hemoglobin, decreased white blood cell count, decreased lymphocytes, increased glucose, decreased sodium, and decreased platelets. The most common adverse reactions (≥20%) in patients with dMMR EC who received JEMPERLI as a single agent were fatigue/asthenia, anemia, nausea, diarrhea, constipation, vomiting, and rash. The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased lymphocytes, decreased sodium, increased alanine aminotransferase, increased creatinine, decreased neutrophils, decreased albumin, and increased alkaline phosphatase. The most common adverse reactions (≥20%) in patients with dMMR solid tumors who received JEMPERLI as a single agent were fatigue/asthenia, anemia, diarrhea, and nausea. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased sodium, increased alkaline phosphatase, and decreased albumin. Please see the full US Prescribing Information for JEMPERLI . About Zejula (niraparib) Zejula is an oral, once-daily poly(ADP-ribose) polymerase (PARP) inhibitor. Indication and Important Safety Information for ZEJULA (niraparib) ZEJULA (niraparib) tablets 100 mg/200 mg/300 mg are indicated: for first-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA- mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for ZEJULA Important Safety Information Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with a fatal outcome, have been reported in patients who received ZEJULA. In PRIMA, MDS/AML occurred in 6 out of 484 (1.2%) patients treated with ZEJULA, and in 3 out of 244 (1.2%) patients treated with placebo. The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer therapy-related AML varied from 3.7 months to 2.5 years. In NOVA , of patients within the g BRCA mut cohort, MDS/AML occurred in 10 out of 136 (7%) patients treated with ZEJULA and in 2 out of 65 (3%) patients treated with placebo. The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer therapy-related AML varied from 3.6 months to 5.9 years. All patients who developed secondary MDS/cancer therapy-related AML had received previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy. For suspected MDS/AML or prolonged hematological toxicities, refer the patient to a hematologist for further evaluation. Discontinue ZEJULA if MDS/AML is confirmed. Hematologic adverse reactions (thrombocytopenia, anemia, neutropenia, and/or pancytopenia) have been reported in patients receiving ZEJULA. The overall incidence of Grade ≥3 thrombocytopenia, anemia, and neutropenia were reported, respectively, in 39%, 31%, and 21% of patients receiving ZEJULA in PRIMA and 29%, 25%, and 20% of patients receiving ZEJULA in NOVA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 4%, 2%, and 2% of patients in PRIMA and 3%, 1%, and 2% of patients in NOVA. In patients who were administered a starting dose of ZEJULA based on baseline weight or platelet count in PRIMA, Grade ≥3 thrombocytopenia, anemia, and neutropenia were reported, respectively, in 22%, 23%, and 15% of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 3%, and 2% of patients. Do not start ZEJULA until patients have recovered from hematological toxicity caused by prior chemotherapy (≤Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months, and periodically thereafter. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a hematologist for further investigations. Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 6% of patients receiving ZEJULA vs 1% of patients receiving placebo in PRIMA, with no reported discontinuations. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in NOVA, with discontinuation occurring in <1% of patients. Monitor blood pressure and heart rate at least weekly for the first two months, then monthly for the first year, and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose if necessary. Posterior reversible encephalopathy syndrome (PRES) occurred in 0.1% of 2,165 patients treated with ZEJULA in clinical trials and has also been described in postmarketing reports. Monitor all patients for signs and symptoms of PRES, which include seizure, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. Diagnosis requires confirmation by brain imaging. If suspected, promptly discontinue ZEJULA and administer appropriate treatment. The safety of reinitiating ZEJULA is unknown. Embryo-fetal toxicity and lactation: Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving their final dose of ZEJULA. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women not to breastfeed during treatment with ZEJULA and for 1 month after receiving the last dose. First-line Maintenance Advanced Ovarian Cancer Most common adverse reactions (Grades 1-4) in ≥10% of all patients who received ZEJULA in PRIMA were thrombocytopenia (66%), anemia (64%), nausea (57%), fatigue (51%), neutropenia (42%), constipation (40%), musculoskeletal pain (39%), leukopenia (28%), headache (26%), insomnia (25%), vomiting (22%), dyspnea (22%), decreased appetite (19%), dizziness (19%), cough (18%), hypertension (18%), AST/ALT elevation (14%), and acute kidney injury (12%). Common lab abnormalities (Grades 1-4) in ≥25% of all patients who received ZEJULA in PRIMA included: decreased hemoglobin (87%), decreased platelets (74%), decreased leukocytes (71%), increased glucose (66%), decreased neutrophils (66%), decreased lymphocytes (51%), increased alkaline phosphatase (46%), increased creatinine (40%), decreased magnesium (36%), increased AST (35%), and increased ALT (29%). Maintenance Recurrent Germline BRCA -mutated Ovarian Cancer Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in NOVA g BRCA mut Cohort were nausea (77%), thrombocytopenia (71%), fatigue (61%), anemia (52%), vomiting (40%), constipation (38%), headache (35%), neutropenia (31%), decreased appetite (22%), hypertension (21%), insomnia (18%), dizziness (18%), dyspnea (17%), dyspepsia (17%), back pain (16%), cough (16%), nasopharyngitis (13%), dry mouth (13%), dysgeusia (13%), urinary tract infection (11%), rash (10%), and anxiety (10%). Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in NOVA g BRCA mut Cohort included: decrease in hemoglobin (85%), decrease in platelet count (81%), decrease in white blood cell count (71%), decrease in absolute neutrophil count (56%), increase in AST (35%), and increase in ALT (25%). Please see the US Prescribing Information for ZEJULA tablets. GSK in oncology Oncology is an emerging therapeutic area for GSK where we are committed to maximizing patient survival with a current focus on hematologic malignancies, gynecologic cancers and other solid tumors through breakthroughs in immuno-oncology and tumor-cell targeting therapies. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at us.gsk.com. Cautionary statement regarding forward-looking statements GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk factors” in the company's Annual Report on Form 20-F for 2023. Registered in England & Wales: No. 3888792 Registered Office: 980 Great West Road Brentford, Middlesex TW8 9GS References Faizan U, Muppidi V. Uterine Cancer. [Updated 2022 Sep 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available at: www.ncbi.nlm.nih.gov/books/NBK562313/ . Braun MM, et al. Am Fam Physician. 2016;93(6):468-474. International Research on Cancer. Global Cancer Observatory. Cancer Tomorrow. gco.iarc.fr/tomorrow/en/dataviz/ . Accessed 13 July 2022. CMP: CancerMPact® Patient Metrics Mar-2023, Cerner Enviza. Available at www.cancermpact.com . Accessed 29 Feb 2024. Laken H, Kehry M, Mcneeley P, et al. Identification and characterization of TSR-042, a novel anti-human PD-1 therapeutic antibody. European Journal of Cancer. 2016;69, S102. doi:10.1016/s0959-8049(16)32902-1.

BARCELONA, Spain and DÜSSELDORF, Germany, Feb. 29, 2024 /PRNewswire/ -- Neuraxpharm Group (Neuraxpharm), a leading European specialty pharmaceutical company focused on the treatment of central nervous system (CNS) disorders, and Minoryx Therapeutics, a late stage biotech company focused on the development of therapies for orphan central nervous system disorders, reaffirm their commitment on Rare Disease Day 2024 to finding better treatments for patients suffering from a range of rare diseases, such as leukodystrophy, including X-linked adrenoleukodystrophy (X-ALD) and more specifically cerebral adrenoleukodystrophy (cALD). This Rare Disease Day, to raise awareness of this disease, Neuraxpharm and Minoryx announce the publication of a special information film with the participation of world renowned expert Professor Fanny Mochel, the Director of the Reference Center for Leukodystrophies - La Pitié-Salpêtrière Hospital, Paris, and Karen Harrison, Support Services Manager of Alex, The Leukodystrophy Charity (Alex-TLC). In the film, Professor Mochel describes the disease and the need for regular screening to identify patients as early as possible, while Karen Harrison speaks powerfully about the patient experience and need for better treatments. The film can be found on Neuraxpharm's and Minoryx's websites, YouTube and LinkedIn channels. Watch the film here. Dr. Jörg-Thomas Dierks, Chief Executive Officer of Neuraxpharm, said: "The impact this disease has on patients and their families cannot be overstated. At Neuraxpharm, we are committed to bringing better treatment to patients so that we can improve the lives of those affected by this devastating disease. We hope that this film will raise awareness and understanding of the condition." Marc Martinell, Chief Executive Officer of Minoryx said: "The X-ALD community deserve all our support to help them face the extremely challenging consequences of this disease, which in the case of cALD are fatal. We want to raise awareness of the diseases and the importance of regular monitoring and early detection as these are critical factors for timely management of these patients." On 26 January 2024, Neuraxpharm and its partner Minoryx Therapeutics stated that they are seeking a re-examination of leriglitazone, Minoryx's novel brain-penetrant and selective PPAR gamma agonist, by the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) for conditional approval for patients with cALD. Minoryx and Neuraxpharm strongly believe that leriglitazone has a positive benefit / risk balance in patients with cALD. About X-ALD and cALD X-linked adrenoleukodystrophy (X-ALD) is an orphan neurodegenerative disease. The global incidence of X-ALD is approximately 6-8/100,000 live births. Boys and adult men with X-ALD can, at any point in their lifetime, develop cALD, which is characterized by demyelinating brain lesions that may become rapidly progressive, leading to acute neurological decline and death. These lesions can produce severe symptoms such as loss of voluntary movements, inability to swallow, loss of communication, cortical blindness and total incontinence and death with a mean survival of 3 to 4 years. Progressive cALD occurs in 31-35% of ALD patients in childhood with typical onset between the age of 2-12 and up to 60% of adult patients, with X-ALD will develop progressive cALD over time. There is currently no pharmacological treatment available for cALD. In childhood, Hematopoietic Stem Cell Transplantation (HSCT) can arrest the disease. However, it is an aggressive procedure and only available for a portion of patients; autologous HSCT is not globally available; this still requires hemo-ablation therapy with associated comorbidities and long-term safety data is being gathered. In adults, experience in HSCT is very limited and the intervention is often not recommended. In addition, all X-ALD patients reaching adulthood develop adrenomyeloneuropathy (AMN), characterized by progressive spastic paraparesis, as well as progressive deterioration of balance and sensory function, and development of incontinence. This form progresses chronically with onset of symptoms typically in adulthood, affecting both men and women, and has poor prognosis. About leriglitazone Leriglitazone is Minoryx Therapeutics's novel orally bioavailable and selective PPAR gamma agonist with a potential first-in-class and best-in-class profile for CNS diseases. It has demonstrated brain penetration and a favorable safety profile. It showed robust preclinical proof-of-concept in animal models of multiple diseases by modulating pathways leading to mitochondrial dysfunction, oxidative stress, neuroinflammation, demyelination and axonal degeneration. In clinical trials, leriglitazone showed clinical benefit in both adult X-ALD patients in ADVANCE and pediatric X-ALD patients in NEXUS. Data from ADVANCE showed that leriglitazone reduces the progression of lesions and the development of progressive cALD. Results on radiological stabilization seen in NEXUS after 24 weeks of treatment were similar to those attained with Hematopoietic Stem Cell Transplant (HSCT) or ex-vivo gene therapy, hence it is expected that leriglitazone could provide a comparable clinical benefit to cALD patients. Leriglitazone has been granted orphan drug status for X-ALD from the FDA and the EMA and Fast Track and Rare Pediatric Disease designation from the FDA for the treatment of X-ALD. About the Neuraxpharm Group Neuraxpharm is a leading European specialty pharmaceutical company focused on the treatment of the central nervous system (CNS), including both psychiatric and neurological disorders. It has a unique understanding of the CNS market built over 35 years. Neuraxpharm is constantly innovating, with new products and solutions to address unmet patient needs and is expanding its portfolio through its pipeline, partnerships and acquisitions. The company has c.1,000 employees and develops and commercializes CNS products through a direct presence in more than 20 countries in Europe, two in Latin America, and globally via partners in more than 40 countries. Neuraxpharm is backed by funds advised by Permira. Neuraxpharm manufactures many of its pharmaceutical products at Neuraxpharm Pharmaceuticals (formerly Laboratorios Lesvi) in Spain. For more information, please visit About Minoryx Minoryx Therapeutics is a registration stage biotech company focusing on the development of novel therapies for orphan central nervous system (CNS) diseases with high unmet medical needs. The company's lead program, leriglitazone (MIN-102), a novel, brain penetrant and selective PPAR gamma agonist, is being developed to treat X-linked adrenoleukodystrophy (X-ALD) and other orphan CNS diseases. The company is backed by a syndicate of experienced investors, which includes Columbus Venture Partners, CDTI Innvierte, Caixa Capital Risc, Fund+, Ysios Capital, Roche Venture Fund, Kurma Partners, Chiesi Ventures, S.R.I.W, Idinvest Partners / Eurazeo, SFPI-FPIM, HealthEquity, Sambrinvest and Herrecha, and has support from a network of other organizations. Minoryx was founded in 2011, is headquartered in Spain with Belgian facilities and has so far raised more than €120 million. For more information, please visit SOURCE Neuraxpharm