Melanoma

Melanoma Research Alliance December 22, 2017 Mr. Jeffrey Epstein 9 East 71st Street New York, NY 10021-4102 Delivered via email: [email protected] Dear Mr. Epstein, On behalf of the Melanoma Research Alliance (MRA), it is my pleasure to update you on the progress of Ian Watson, PhD, of McGill University, who is conducting research supported by you under his MRA Young Investigator Award, Identification of therapeutic strategies to target NF1 mutant melanomas. Dr. Watson and his research team made significant progress in the first year of his award, which supports research aimed at identifying melanoma treatments that are likely to work for the 15 percent of melanoma patients whose tumors contain mutations in the gene NFl. Normally, NF1 functions to suppress tumor growth. Some patients with NF1 mutations respond to the FDA-approved therapy veramafinib (Zelboraf), whereas others do not. To better understand and predict on a molecular level the response of melanoma patients whose tumors contain NF1 mutations to various treatments, Dr. Watson genetically analyzed 318 melanoma samples from such patients to determine common genetic changes in addition to the flawed NF1 gene. He then created cell and mouse models in which to assess the influence of these additional genetic changes common in melanomas with NF1 mutations, including how these additional mutations affect responses to approved targeted treatments. These studies are expected to suggest new treatments appropriate for this subtype of melanoma, including experimental therapies. Dr. Watson also assessed how the loss of NF1 affects the function of other proteins in tumor cells. This research found NF1 regulates molecules that affect how the immune system functions, including influencing the production of a molecule that is a major target in several approved immune "checkpoint inhibitor" therapies, such as pembrolizumab (Keytruda). Dr. Watson and his research team are currently collaborating with several oncologists, dermatology pathologists, and surgeons at McGill University Health Center and the Jewish General Hospital in Montreal to confirm whether genetic alterations in NF1 affect how melanoma patients respond to immune checkpoint treatments. Dr. Watson presented his team's findings at the 2017 Cancer Trials Group Annual Spring Meeting, at the Cancer Research Program Research Institute of the McGill University Health Center and at the Lady Davis Institute Seminar Series at Jewish General Hospital in Montreal. We appreciate your ongoing support of this promising Young Investigator Award and of the goal of the MRA to foster the next generation of melanoma research leaders. Sincerely, Michael Kaplan President and Chief Executive Officer The Melanoma Research Alliance Foundation is a 501(c)3 nonprofit organization. 1101 New York Avenue, NW, Suite 620, Washington, DC 20005 Telephone: www.curemelanoma.org EFTA00810760