Optic Nerve Glioma

Researchers have discovered that an FDA-approved epilepsy drug can prevent or slow the growth of NF1-linked optic gliomas in mice, laying the groundwork for a clinical trial. A drug used to treat children with epilepsy prevents brain tumor formation and growth in two mouse models of neurofibromatosis type 1 (NF1), according to a study by researchers at Washington University School of Medicine in St. Louis. NF1 is a genetic condition that causes tumors to grow on nerves throughout the body, including the optic nerves, which connect the eyes to the brain. The findings lay the groundwork for a clinical trial to assess whether the drug, lamotrigine, can prevent or delay brain tumors in children with NF1. The study is online in the journal Neuro-Oncology. "Based on these data, the Neurofibromatosis Clinical Trials Consortium is considering launching a first-of-its-kind prevention trial," said senior author David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology and the director of Washington University's Neurofibromatosis Center. The clinical trials consortium is an international network of NF scientists that was formed by the U.S. Department of Defense in 2006 to find therapies for all forms of neurofibromatosis. "The plan is to enroll kids without symptoms, treat them for a limited time, and then see whether the number of children who develop tumors that require treatment goes down. "This is a novel idea, so we took it to an NF1 patient focus group," Gutmann continued. "They said, 'This is exactly what we're looking for.' A short-term treatment with a drug that has been used safely for 30 years was acceptable to them if it reduced the chance their children would develop tumors and need chemotherapy that might have all kinds of side effects." The most serious tumors that people with NF1 get affect the optic nerve and are known as optic gliomas. Such tumors typically appear between ages 3 to 7. While they are rarely fatal, they cause vision loss in up to a third of patients as well as other symptoms, including early puberty. Standard chemotherapy for optic gliomas is only moderately effective at preventing further vision loss and can affect children's developing brains, resulting in cognitive and behavioral problems. In a previous study, Gutmann and Corina Anastasaki, PhD, an assistant professor of neurology and the first author on the new paper, showed that lamotrigine stopped optic glioma growth in NF1 mice by suppressing neuronal hyperactivity. The Neurofibromatosis Clinical Trial Consortium found their data intriguing but demanded more evidence before they would consider launching a clinical trial. The consortium members asked Gutmann and Anastasaki to clarify the connection between Nf1 mutation, neuronal excitability and optic gliomas; assess whether lamotrigine was effective at the doses already proven safe in children with epilepsy; and conduct these studies in more than one strain of NF1 mice. In people, NF1 is a highly variable disease. It can be caused by any one of thousands of different mutations in the NF1 gene, where different mutations could be associated with different medical problems. Repeating experiments in multiple strains of mice was a way of gauging whether lamotrigine was likely to work in people regardless of the underlying mutation. Anastasaki and Gutmann not only showed that lamotrigine worked in two strains of NF1 mice, they also showed that the drug worked at lower doses than those used for epilepsy, meaning that it was probably safe. Even better, they found that a short course of the drug had lasting effects, both as a preventive and a treatment. Mice that had tumors and that were treated for four weeks starting at 12 weeks of age saw their tumors stop growing and even showed no further damage to the retinas of their eyes. Mice that received a four-week course of the drug starting at 4 weeks of age, before tumors typically emerge, showed no tumor growth even four months after treatment had ended. These findings have led Gutmann to suggest that a one-year course of treatment for young children with NF1, maybe between the ages of 2 to 4, might be enough to reduce their risk of brain tumors. "The idea that we might be able to change the prognosis for these kids by intervening within a short time window is so exciting," Gutmann said. "If we could just get them past the age when these tumors typically form, past age 7, they may never need treatment. I'd love it if I never again had to discuss chemotherapy for kids who aren't even in first grade yet."

Data subsets to be shared today in plenary oral presentations at the 2023 Society for Neuro-Oncology Annual MeetingBRISBANE, Calif., Nov. 17, 2023 (GLOBE NEWSWIRE) -- Day One Biopharmaceuticals (Nasdaq: DAWN) (“Day One” or the “Company”), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, today announced the publication of the registrational Phase 2 FIREFLY-1 trial results evaluating the investigational agent tovorafenib in patients with BRAF-altered, relapsed or progressive pediatric low-grade glioma (pLGG) in Nature Medicine. Subsets of the data will also be presented today in two oral plenary presentations at the 2023 Society for Neuro-Oncology (SNO) Annual Meeting in Vancouver, Canada. “The study results published in Nature Medicine demonstrate promising evidence with respect to the the impact of tovorafenib for children and young adults with BRAF-altered relapsed or progressive pLGG, a debilitating form of brain tumor that currently has no approved systemic therapies,” said Dr. Samuel Blackman, co-founder and head of research and development, Day One. “We look forward to continued development of tovorafenib.” Details on today’s oral presentations and corresponding abstracts: Title: *Clinical Activity and Safety of the RAF Inhibitor Tovorafenib in Patients with Optic Pathway Gliomas in the Registrational Pediatric Low-Grade Glioma Arm of the Phase 2 FIREFLY-1 (PNOC026) StudyAbstract Number: CTNI-24Time: 10:15 – 10:25 AM PT Location: Exhibit Hall CPresenter: Karsten Nysom, MD, PhD, Copenhagen University Hospital - Rigshospitalet*Presenter Karsten Nysom, MD, PhD received the 2023 SNO Annual Meeting Abstract Award for Excellence in Clinical Trials in connection to this oral presentation. Title: Clinical Activity of RAF Inhibitor Tovorafenib According to Prior MAPK Inhibitor Treatment in the Registrational Pediatric Low-Grade Glioma Arm of the Phase 2 FIREFLY-1 (PNOC026) StudyAbstract Number: CTNI-37Time: 10:25 – 10:35 AM PT Location: Exhibit Hall CPresenter: Daniel Landi, MD, Duke University A New Drug Application for tovorafenib monotherapy in BRAF-altered relapsed or progressive pLGG is currently under priority review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act target action date of April 30, 2024. In addition to FIREFLY-1, the Phase 3 FIREFLY-2/LOGGIC randomized clinical trial is evaluating tovorafenib frontline therapy for patients newly diagnosed with pLGG. About Tovorafenib Tovorafenib is an investigational, oral, brain-penetrant, highly-selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors or brain metastases of solid tumors. Tovorafenib has been studied in over 350 patients to date and is currently under evaluation in two pivotal clinical trials for pLGG. Tovorafenib is also being evaluated as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1). Tovorafenib has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the FDA for the treatment of patients with pLGG harboring an activating RAF alteration. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma, and from the European Commission for the treatment of glioma. About Day One Biopharmaceuticals Day One Biopharmaceuticals is a clinical-stage biopharmaceutical company that believes when it comes to pediatric cancer, we can do better. We put kids first and are developing targeted therapies that deliver to their needs. Day One was founded to address a critical unmet need: the dire lack of therapeutic development in pediatric cancer. The Company’s name was inspired by “The Day One Talk” that physicians have with patients and their families about an initial cancer diagnosis and treatment plan. Day One aims to re-envision cancer drug development and redefine what’s possible for all people living with cancer—regardless of age—starting from Day One. Day One partners with leading clinical oncologists, families, and scientists to identify, acquire, and develop important emerging cancer treatments. The Company’s lead product candidate, tovorafenib, is an investigational, oral, brain-penetrant, highly-selective type II RAF kinase inhibitor. The Company’s pipeline also includes pimasertib, an investigational, oral, highly-selective small molecule inhibitor of mitogen‐activated protein kinases 1 and 2 (MEK-1/-2). Day One is based in Brisbane, California. For more information, please visit www.dayonebio.com or find the Company on LinkedIn or Twitter. Cautionary Note Regarding Forward-Looking StatementsThis press release contains “forward-looking” statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: Day One’s plans to develop cancer therapies, expectations from current clinical trials, the execution of the Phase 2 and Phase 3 clinical trial for tovorafenib as designed, any expectations about safety, efficacy, timing and ability to complete clinical trials, release data results, the ability of Day One to obtain regulatory approvals for and to commercialize tovorafenib and other candidates in development, and the ability of tovorafenib to treat pLGG or related indications. Statements including words such as “believe,” “plan,” “continue,” “expect,” “will,” “develop,” “signal,” “potential,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause Day One’s actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties in this press release and other risks set forth in our filings with the Securities and Exchange Commission, including Day One’s ability to develop, obtain regulatory approval for or commercialize any product candidate, Day One’s ability to protect intellectual property, the potential impact of global business or macroeconomic conditions, including as a result of inflation, rising interest rates, cybersecurity events, instability in the global banking system, government shutdowns, uncertainty with respect to the federal budget, global regional conflicts and the sufficiency of Day One’s cash, cash equivalents and short-term investments to fund its operations. These forward-looking statements speak only as of the date hereof and Day One specifically disclaims any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law. DAY ONE MEDIALaura Cooper, Head of Communications media@dayonebio.com DAY ONE INVESTORSLifeSci Advisors, PJ Kelleherpkelleher@lifesciadvisors.com

Collaboration Will Accelerate Development of Treatments for Neurofibromatosis and Schwannomatosis Patients NEW YORK, Oct. 5, 2023 /PRNewswire/ -- The Children's Tumor Foundation (NEW YORK, NY and BRUSSELS, BELGIUM) and the Global Coalition for Adaptive Research (LARKSPUR, CA) – The Children's Tumor Foundation (CTF) and Global Coalition for Adaptive Research (GCAR), today announced their alliance to accelerate the development of treatments for patients with NF (neurofibromatosis or schwannomatosis) – a group of rare and often debilitating diseases with high unmet medical need. CTF and GCAR are partnering to operationalize a first-of-its-kind clinical trial for patients with NF that was initially designed through the EU-PEARL initiative. The announcement of this strategic alliance follows a 3-year, 26-million-euro investment from the Innovative Health Initiative (IHI), formerly called the Innovative Medicines Initiative (IMI). EU-PEARL was a public-private partnership dedicated to transforming clinical trials by making them more efficient and patient-centered. Through this partnership, leading organizations representing patients, clinicians, researchers, health authorities and industry collaborated to design the first-ever Phase 1 / Phase 2 global platform basket trial for patients with neurofibromatosis type 1 (NF1) or schwannomatosis (SWN), including NF2-related schwannomatosis (NF2-SWN). CTF is the global leader in neurofibromatosis and schwannomatosis research, dedicated to funding and driving innovative research that will result in effective treatments for the 4 million people worldwide living with NF, a group of genetic disorders that causes tumors to grow on nerves throughout the body. One in every 2,000 people is born with neurofibromatosis or schwannomatosis, which may lead to blindness, deafness, bone abnormalities, disfigurement, learning disabilities, disabling pain, or cancer. "Central to CTF's mission is advancing care and treatments for the NF community. The establishment of the NF platform trials will expedite the development of effective treatments for patients," said Dr. Annette Bakker, President of the Children's Tumor Foundation. "We are delighted to partner with GCAR, a leading expert in developing and operationalizing master protocols and adaptive platform trials to actualize this innovative trial." GCAR was formed with the mission to speed the discovery and development of treatments for patients with rare and deadly diseases by serving as the sponsor of innovative trials. Its first initiative was to implement the clinical trial GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment) into a self-sustaining engine of therapeutic and biomarker development for patients with glioblastoma. Since the launch of GBM AGILE, GCAR also initiated U.S. sponsorship for innovative global trials in COVID-19 and is advancing platform trials for other rare and deadly diseases such as high-grade ovarian cancer. "We are excited to work with the Children's Tumor Foundation to build a patient-centric clinical trial that will rapidly and efficiently evaluate multiple investigational therapies for the treatment of NF," said Dr. Meredith Buxton, CEO & President of the Global Coalition for Adaptive Research. "GCAR is committed to leading the way in clinical trial innovation by uniting stakeholders to advance new therapies for patients. Our alliance with CTF exemplifies a collaboration that places patients and the community at the forefront of clinical research." The NF platform trials will be built to complement CTF's NF Preclinical Hub, a comprehensive infrastructure to accelerate the availability of clinical trial-ready treatments, including gene therapy. The preclinical hub will provide access to a pipeline from concept to clinic, pre-negotiated master service agreements, protocols for compound testing, as well as access to testing models, data tools, libraries, and biomarkers. The plan is to launch an NF1 platform trial for four different manifestations including plexiform neurofibroma, cutaneous neurofibroma, optic pathway glioma, and low-grade glioma, with future plans to build a platform trial to support SWN patients. Additionally, the Foundation's NF Patient Registry provides dependable access to NF patients available to participate in NF clinical trials and research studies. With the establishment of the NF platform trials (an NF1 trial followed by an SWN trial), pharma companies are invited to explore testing of their therapies, as well as investors interested in the opportunity to fuel the progress to approved treatments. About the Children's Tumor Foundation (CTF) The Children's Tumor Foundation (CTF) is the world's leading nonprofit dedicated to funding and driving innovative research resulting in effective treatments for the millions of people worldwide living with NF. Guided by a bold and innovative strategic plan, CTF is laser-focused on delivering therapies (right treatments at the right time) to patients who are accurately diagnosed. In addition to driving bench to bedside research, CTF manages global public-private multi-disciplinary consortia, and has invested in a gene therapy and small molecule company. The Foundation is now actively working with ten pharma/ biotech companies to advance therapies for NF, and is inviting other companies to join. CTF recognizes the unique niche role of disease foundations in the R&D ecosystem, involving the patient voice in every initiative. While being committed to building an enterprise that will benefit patients with NF, CTF hopes that the model can act as a blueprint to accelerate drug discovery and development in the larger rare disease community. CTF acknowledges Goodwin for its continuous pro bono support. For more information, please visit: ctf.org. About Global Coalition for Adaptive Research (GCAR) The Global Coalition for Adaptive Research (GCAR) unites physicians, clinical researchers, advocacy and philanthropic organizations, biotech/pharma, health authorities, and other key stakeholders in healthcare to expedite the discovery and development of treatments for patients with rare and deadly diseases. As Sponsor of innovative trials, including master protocols and adaptive platform trials, GCAR is dedicated to the advancement of science by modernizing clinical trials that support more efficient, less costly drug development. Adaptive platform trials can accelerate the time from discovery in the lab to implementation in the clinic resulting in better treatments and lives saved. To learn more about GCAR and its initiatives, visit gcaresearch.org. View original content to download multimedia: SOURCE Children's Tumor Foundation