Ganglioglioma

Treatment with targeted therapies Tafinlar + Mekinist resulted in 47% ORR versus chemotherapy (11%) and reduced risk of progression or death by 69%, showing significant efficacy improvement in patients ages 1 to 17 years old with BRAF V600 low-grade gliomas (LGG) requiring first systemic treatment1 If approved, Tafinlar + Mekinist may offer a potential new standard-of-care for pediatric patients with this brain cancer who are in need of a more efficacious and convenient option that can be administered orally and may also improve quality of life1 Results add to body of evidence demonstrating efficacy and safety of Tafinlar + Mekinist across multiple BRAF V600 solid tumors Data highlighted as part of ASCO official press briefing and will form basis of upcoming regulatory submissions Basel, June 6, 2022 — Novartis today announced Tafinlar® (dabrafenib) + Mekinist® (trametinib) significantly improved efficacy in patients ages 1 to 17 years old with BRAF V600 pediatric low-grade glioma (pLGG) requiring first systemic treatment compared to chemotherapy, the current standard-of-care for these patients1. In this study, patients randomized to receive Tafinlar + Mekinist experienced a statistically significant overall response rate (ORR) of 47% (CI: 35-59%) compared to 11% (CI: 3-25%, p<0.001) for those randomized to receive chemotherapy. A new liquid formulation of Tafinlar + Mekinist that can be easier to administer than chemotherapy was used in this trial. The data will be highlighted today as part of an official press briefing and oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA2002). “These results show dabrafenib and trametinib demonstrate an improvement over chemotherapy for children and adolescents with BRAF V600 low-grade gliomas,” said Eric Bouffet, MD, FRCPC, Senior Associate Scientist Emeritus at The Hospital for Sick Children (SickKids) in Toronto, Canada. “This work highlights the importance of testing for mutations like BRAF in patients with low-grade gliomas.” LGG is the most common pediatric brain cancer and BRAF V600 mutations are present in 15-20% of pLGGs2,5. Currently, standard chemotherapy is associated with poor outcomes and a high burden of care6. Additional results from the Phase II/III trial showed at a median follow-up of 18.9 months, median progression-free survival (PFS) was 20.1 months with Tafinlar + Mekinist (CI: 12.8 months-not estimable) compared to 7.4 months with chemotherapy (CI: 3.6-11.8 months, hazard ratio=0.31 [CI: 0.17-0.55] [p<0.001])1. Additionally, tumors shrank or remained stable in 86% of patients in the Tafinlar + Mekinist arm (n=73; CI: 76-93%) compared to 46% of patients in the chemotherapy arm (n=37; CI: 30-63%). After one year of follow-up, nearly all patients on Tafinlar + Mekinist (89%) had a reduction in tumor size compared with baseline versus 70% of patients in the chemotherapy arm. Results from a quality-of-life analysis favored Tafinlar + Mekinist compared to chemotherapy at all time points1. “These young patients and their families experience a heavy burden of care as BRAF V600 low-grade glioma poses a risk of neurological impairment and current standard-of-care treatment is intravenous and associated with frequent trips to the cancer clinic or hospital,” said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development at Novartis. “Tafinlar + Mekinist has shown unprecedented efficacy, and we will work with health authorities to bring these children the possibility of a more effective and easier to administer liquid oral treatment option as quickly as possible.” The safety profile of Tafinlar + Mekinist was generally consistent with established safety observed in previous studies. Patients in the Tafinlar + Mekinist arm had fewer grade 3 or higher adverse events (AEs; 47% vs 94%) and fewer discontinuations due to AEs (4% vs 18%) than patients in the chemotherapy arm evaluated for safety (n=33)1. The most frequent AEs in the Tafinlar + Mekinist arm were pyrexia, headache and vomiting1. In a separate single-arm cohort of this study evaluating pediatric patients with relapsed or refractory BRAF V600 high-grade gliomas (HGG), treatment with Tafinlar + Mekinist showed an independently assessed ORR of 56.1% [CI: 39.7%-71.5%] and generally consistent safety results4. These data were presented in a poster discussion at the 2022 ASCO Annual Meeting (Abstract #2009). Tafinlar + Mekinist was granted Breakthrough Therapy designation by the US Food and Drug Administration for the treatment of pediatric patients one year of age and older with LGG with a BRAF V600E mutation who require systemic therapy. About the TADPOLE trialThis global Phase II/III, multicenter, open-label trial is evaluating patients aged 1 to 17 with BRAF V600 LGG (n=110) or relapsed or refractory HGG (n=41)1. Tafinlar + Mekinist is administered orally either as new liquid formulations, or as capsules and tablets, respectively. The primary endpoint in both cohorts is overall response rate. Secondary outcome measures include duration of response, progression-free survival, overall survival and other endpoints1. About pediatric gliomas Gliomas are the most common pediatric central nervous system tumor type, representing about half of all pediatric brain cancers5,7,8. Gliomas are classified as either low-grade (grades 1 and 2) or high-grade (grades 3 and 4)7. Pediatric low-grade gliomas positive for the BRAF V600E mutation have been associated with worse survival outcomes (OS/PFS) and are found in approximately 15-20% of pLGG2,3. BRAF mutations are found in approximately 3% to 7% of people with HGG (all ages combined)9,10. BRAF mutations have been identified as drivers of cancer growth across a wide range of solid tumors and often have limited treatment options11,12. About Tafinlar + MekinistThe combination of Tafinlar + Mekinist, the worldwide targeted therapy leader in BRAF/MEK-inhibition research and patients reached, may help to slow tumor growth by blocking signals associated with the BRAF and MEK kinases, which are implicated in the growth of various types of cancer11-15. Tafinlar + Mekinist has been studied in more than 6,000 BRAF-positive patients in more than 20 ongoing and completed trials and has been prescribed to more than 200,000 patients worldwide15. Tafinlar + Mekinist is currently not approved for pediatric patients with LGG or HGG. These results will form the basis of regulatory discussions with global health authorities. DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About NovartisNovartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com. Novartis is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnewsFor Novartis multimedia content, please visit https://www.novartis.com/news/media-libraryFor questions about the site or required registration, please contact media.relations@novartis.com References Bouffet, E MD. Primary analysis of a phase II trial of dabrafenib plus trametinib (dab + tram) in BRAF V600–mutant pediatric low-grade glioma (pLGG). 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract #LBA2002.Lassaletta A, et al. J Clin Oncol. 2017;35:2934-2941Mistry M, et al. J Clin Oncol. 2015;33:1015-1022Hargrave, D MD. Dabrafenib + trametinib (dab + tram) in relapsed/refractory (r/r) BRAF V600–mutant pediatric high-grade glioma (pHGG): Primary analysis of a phase II trial. 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract #2009.Ostrom QT, et al. Neuro Oncol. 2021;23(12 suppl 2):iii1-iii105Oberheim Bush NA, Chang S. Treatment Strategies for Low-Grade Glioma in Adults. J Oncol Pract. 2016 Dec;12(12):1235-1241. doi: 10.1200/JOP.2016.018622. PMID: 27943684.ESMO/Anticancer Fund. Glioma Guide for PatientsLouis DN, et al. Acta Neuropathol. 2016;131:803-82Ballester LY, Fuller GN, Powell SZ, Sulman EP, Patel KP, Luthra R, et al. Retrospective analysis of molecular and immunohistochemical characterization of 381 primary brain tumors. J Neuropathol Exp Neurol. 2017 Mar 1;76(3):179-88Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol. 2011 Mar;121(3):397-405Turski ML, et al. Mol Cancer Ther. 2016;15:533-547Pratilas C, et al. Curr Top Microbiol Immunol. 2012;355:82-98Tafinlar [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022.Mekinist [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022.Data on file. # # # Novartis Media RelationsE-mail: media.relations@novartis.com Anja von TreskowNovartis External Communications+41 79 392 8697 (mobile)anja.von_treskow@novartis.com Julie MasowNovartis US External Communications+1 862 579 8456julie.masow@novartis.comDan ConnellyNovartis Oncology Communications+1 862 210 0217 (mobile)daniel.connelly@novartis.com Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com Central North America Samir Shah+41 61 324 7944Sloan Simpson+1 862 345 4440Nicole Zinsli-Somm+4 16 132 43809Alina Levchuk+1 862 778 3372Isabella Zinck+41 61 324 7188Parag Mahanti+1 973-876-4912

FLORHAM PARK, N.J., April 13, 2021 (GLOBE NEWSWIRE) -- Celularity Inc. (“Celularity”), a clinical-stage biotechnology company, leading the next evolution in cellular medicine with the development of off-the-shelf allogeneic therapies derived from the postpartum human placenta, announced today the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to the company’s non-genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy, CYNK-001, for the treatment of patients with malignant gliomas. CYNK-001 is currently being investigated in a phase 1 clinical trial (NCT04489420) for the treatment of patients with glioblastoma multiforme (GBM), an indication within the scope of this orphan designation. “We are very pleased the FDA has granted Orphan Designation in malignant gliomas to continue to develop off-the-shelf therapies for serious unmet clinical needs,” said Robert J. Hariri, M.D., Ph.D., founder, Chairperson and Chief Executive Officer of Celularity. “Building on the FDA’s recent decision to grant Fast Track status to CYNK-001, we view the Orphan Drug Designation as yet another milestone on our journey to deliver patients a potentially novel treatment. To date, we have observed the potential of CYNK-001 in multiple preclinical models as well as early evidence of activity in the clinic and believe this approach may shift the paradigm in augmenting the body’s natural immune response to diseases such as glioblastoma, other cancer indications and infectious diseases. We are very excited to continue working with the FDA on the development of this exciting therapy.” About Orphan Drug Designation The Orphan Drug Act (ODA) encourages biotechnology and pharmaceutical companies to develop drugs for conditions which affect fewer than 200,000 people in the United States by providing economic incentives. To qualify for orphan designation, both the drug and the condition must meet criteria specified in the ODA and FDA’s implementing regulations 21 CFR Part 316. Orphan designation qualifies the drug sponsor for development incentives including tax credits for qualified expenses, reduction in the FDA user fee, and seven years of exclusivity for a drug that obtains approval. About Malignant Gliomas Glioma is a type of tumor that occurs in the brain and spinal cord. Malignant gliomas consist of glioblastoma multiforme (GBM), anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, anaplastic ependymoma, and anaplastic ganglioglioma. Malignant gliomas are associated with high morbidity and mortality. GBM accounts for the majority of malignant gliomas. Currently there are no effective long-term treatments for the disease. Patients with GBM usually survive less than 15 months following diagnosis. In most patients, the rapidly growing malignant tumor tends to recur within 6-8 months following treatment. Patients with recurrent GBM have even poorer prognosis. Therefore, malignant gliomas, such as GBM, are serious diseases with high unmet medical needs. About CYNK-001 Celularity’s lead therapeutic program based on its placental-derived unmodified NK cell type is CYNK-001, an allogeneic unmodified NK cell being developed as a treatment for hematologic malignancies, solid tumors, and infectious diseases. About Celularity Celularity, headquartered in Florham Park, N.J., is a clinical stage biotechnology company leading the next evolution in cellular medicine by developing off-the-shelf placental-derived allogeneic cell therapies, including unmodified NK cells, genetically-modified NK cells, T cells engineered with a CAR (CAR T-cells), and mesenchymal-like adherent stromal cells (ASCs) targeting indications across cancer, infectious and degenerative diseases. Celularity believes that by harnessing the placenta’s unique biology and ready availability, it will be able to develop therapeutic solutions that address significant unmet global needs for effective, accessible, and affordable therapies. In January 2021, Celularity entered into a definitive merger agreement with GX Acquisition Corp. to create a publicly listed leader in allogeneic cellular therapy. GX Acquisition Corp. is listed on Nasdaq under the ticker symbol “GXGX.” Upon closing of the business combination, expected to be completed in the second quarter of 2021, shares of the combined company will be listed on Nasdaq under the ticker symbol "CELU." To learn more, visit celularity.com. Celularity Investor Contacts: Carlos Ramirez Celularity carlos.ramirez@celularity.com Alexandra Roy Solebury Trout aroy@troutgroup.com Celularity Media Contact Jason Braco, Ph.D. LifeSci Communications (646)-751-4361 jbraco@lifescicomms.com