With the help of patients, physicians, and researchers we aim to bring patients safe and effective therapies for NF2 and related disorders.
NF2 Therapeutics, Inc. (NF2TX) is a Cambridge based, dedicated, mission driven company focused on developing therapies for neurofibromatosis type 2 (NF2), leveraging relationships with key centers, individuals, and resources.
Neurofibromatosis 2 (NF2) is a rare genetic disorder caused by mutations in the Neurofibromatosis 2 tumor suppressor gene (NF2). These mutations lead to the malformation or absence of Merlin protein which regulates various cellular processes and is involved in contact inhibition, proliferation, and apoptosis. As a result, slow-growing tumors including schwannomas form in and around Schwann cells.
Typical symptoms of NF2 include bilateral vestibular schwannoma leading to hearing loss, ringing in the ears, deafness, dizziness, and loss of balance. Additional symptoms may include disfiguring facial weakness, headache, vision loss, and lumps or swelling under the skin caused by the development of schwannomas. NF2 can also lead to schwannomas in other nervous tissue such as the cranial and peripheral nerve and spinal ependymomas. Patients typically become deaf and lose balance, either because of the effects of tumor growth, or interventions to manage the tumors.
Almost all affected individuals develop vestibular schwannomas by age 30. The average age of onset of NF2 is between 18 to 24 years. Life expectancy for NF2 patients is 69 years of age, 11 years less than the life expectancy of the general population.
In addition to schwannomas, patients with NF2 have a 70-80% lifetime probability of developing a meningioma. The median number of meningiomas patients develop is three, with 33% of the tumors characterized as growing significantly (> 1mm/year). Meningiomas represent the most significant cause of morbidity and mortality for NF2 patients. Additionally, meningiomas can also occur in non-NF2 patients due to somatic mutations in the NF2 gene. Sporadic meningiomas are also the most common brain tumor (~ 30% of all brain tumors), and can cause neurological deficits due to compression of the brain or spine.
STANDARD OF CARE
There are currently no FDA-approved drugs for schwannomas or meningiomas. The current standard of care includes surgery and radiation therapy. While surgical options can be limited due to the location of the tumors, surgery is performed in 46% of NF2 patients. Patient survival has improved significantly as techniques have been developed that allow for earlier diagnosis and better treatment at specialty centers.
The Children’s Tumor Foundation (CTF) partnered with NF2TX and provided funding for phase I of a protein replacement therapy project, where a Merlin fusion was synthesized in the lab of Helen Morrison (FLI) and evaluated in a schwannoma cell line. Dr. Morrison demonstrated that the Merlin fusion was taken up by the cells with restoration of function, providing proof of concept that the presence of some full length Merlin can rescue the phenotype in a cell based disease model, opening the door to a gene replacement therapy which would restore Merlin in affected cells. The CTF has provided additional funding for NF2TX to evaluate NF2 gene therapy in primates and murine models of NF2, as the basis for the development of a first-in-class treatment.
Further details will be made available in 2020.
An Experienced Team of Experts and Professionals
Co-Founder and CEO
Michael is NF2 Therapeutics’ President and Chief Executive Officer, and also a Co-Founder. Michael is a Co-Founder, and former CEO of NFlection Therapeutics which developed the first topical MEK inhibitor for the treatment of cutaneous neurofibromas in NF1 and other disorders. Michael is Managing Partner of Vie Capital Partners, an investment and advisory services firm focused on early and growth stage life sciences and healthcare companies. He has over fifteen years of strategy and operations consulting experience working with life sciences and healthcare companies. He was formerly a Partner and Life Sciences Sector Head at Celerant Consulting (acquired by Hitachi Consulting) where he worked with an array of life sciences companies including Bayer, Wyeth, Abbott, Roche, Genzyme, Fresenius, CDC, and others, on large operational strategy programs. Michael has a bachelor’s degree in mechanical engineering from the University of Waterloo and an MBA from the Harvard Business School.
Mark de Souza, PhD
Mark de Souza is an entrepreneur in the rare disease and dermatology space. He is a co-founder and executive chairman of NFlection Therapeutics, and a co-founder and CEO of Chromaderm (PKC-beta inhibitor for melasma), FIBRX Derm (topical decorin for epidermolysis bullosa), FIBRX Tissue Repair (decorin for fibrotic diseases of the eye, liver, and lung), and SCIDEC Therapeutics (intrathecal decorin for hydrocephalus and spinal cord injury). He is a co-founder of Molecular Skin Therapeutics, a BridgeBio company developing a topical KLK5/7 inhibitor for Netherton Syndrome. He was previously the Executive Chairman of PellePharm (Phase 3 topical hedgehog inhibitor for Gorlin Syndrome, partnered with LEO Pharma), founding CEO of Lotus Tissue Repair (intravenous collagen type VII for dystrophic epidermolysis bullosa, acquired by Shire, and now being developed by Phoenix Tissue Repair), and VP of Business Development at Dyax Corp (two FDA-approved plasma kallikrein inhibitors for hereditary angioedema, acquired by Shire). He is an advisor to the CureGM1 Foundation and on the board of the Special Needs Aquatic Program. He co-founded NFlection Therapeutics and NF2 Therapeutics after his nephew was diagnosed with neurofibromatosis type 1.
Scott Plotkin, MD, PhD
Scott is a Professor of Neurology, Harvard Medical School, and Director, Neurofibromatosis Clinic, Massachusetts General Hospital (MGH). Scott is also a co-founder of NFlection Therapeutics. Scott is acting director of neuro oncology at MGH. He provides clinical care for patients with NF1, NF2, Scwhannomatosis and other disorders. He has led numerous clinical trial in the Neurofibromatoses. Scott is currently Co-Chair of Research Endpoints in Neurofibromatosis and Schwannomatosis (REiNS), an NIH sponsored group focused on the development of trial and endpoint development for the Neurofibromatoses. He is a key opinion leader in neurofibromatosis clinical trials and research and has published extensively on his work.
Marco Giovannini, MD, PhD
Marco Giovannini, M.D., Ph.D. is Professor-in-Residence of Head and Neck Surgery at the David Geffen School of Medicine of the University of California Los Angeles (UCLA) and Scientific Director of the UCLA NF2 Multidisciplinary Clinic. A native of Italy, Dr. Giovannini earned his M.D.;Ph.D at the University of Bologna. He conducted research in France at the Institut National Recherche Sante Medicale (INSERM) for many years, as the head of the Unit “Functional Genomic of Solid Tumors”, in Paris. A molecular geneticist by training, He is a physician-scientist who conducts laboratory and clinical research in the field of neurofibromatoses. His NIH, Department of Defense and private foundation-supported research laboratory develops models of disease to test new therapeutic options and studies mechanism of action of treatments in NF patients.