Melanoma Research Alliance-Pfizer Academic-Industry Partnership Awards

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Melanoma Research Alliance-Pfizer Academic-Industry Partnership Awards Wendy K.D. Selig, President & CEO, MRA Julia Perkins, M.D. Medical Director, Oncology, Pfizer

Melanoma Research Alliance Mission: Accelerate the pace of scientific discovery and clinical translation to eliminate suffering and death due to melanoma Founded in 2007 under the auspices of the Milken Institute with the generous founding support of Debra and Leon Black. Programmatic ties to FasterCures and the Prostate Cancer Foundation. With more than $48M awarded to date worldwide, MRA is the largest private funder of melanoma research. Focus on translational research with potential for near-term clinical impact

Melanoma: An ideal case study Need for new treatments: Aggressive cancer, poor prognosis in late stage, incidence rising dramatically Scientifically and clinically: At crossroads of molecular biology and immunology New drug approvals: Four newly approved agents since 2011 have changed the landscape for patients and forged new ground in cancer Rx development Companion Dx and biomarkers: Melanoma is leading the way in building this field

Academic-Industry Partnership Awards Objective: Facilitate public-private partnerships to accelerate melanoma research with a high potential for clinical impact Catalyze synergistic interactions between corporate and academic melanoma researchers to fast-forward progress in the field Accelerate contracts process between academia and industry Expedite early sharing of research information Leverage MRA funds with corporate investments

Partnership Strategy Industrial Partner Academic Researcher Nonprofit Foundation Matches MRA funding 1:1 in $ or in-kind support May collaborate scientifically in research project Primary driver of project MRA and industry dispense funds/resources directly Projects selected by peer review process and Board Programmatic oversight

History of Awards (2010-2013) 46 proposals received Variety of industrial partners, including drug, diagnostic, and device companies Industry contributions mainly inkind (drugs/reagents, services, industry scientist effort) 8 awards granted UVA-Celldex Therapeutics MSKCC-Canfield Scientific University of Washington-Altor Bioscience Corp University of Pittsburgh-Merck Johns Hopkins University-Aduro Biotech MSKCC-JHU-Bristol Myers Squibb UCSF- Pfizer Thomas Jefferson University-Pfizer

Pfizer Partnership Together, reach out to the scientific community to offer an opportunity that builds on existing MRA Partnership mechanism for a specific topic of mutual interest. Highlight a promising new area for melanoma Enhance resources for melanoma research Strengthen MRA-Pfizer relationship Applications solicited to evaluate the therapeutic potential of CDK4/6 inhibition in melanoma.

Pfizer Inc and oncology At Pfizer, there is a focus on innovation to bring therapies to patients that have the potential to significantly improve their lives Working together, our goal is to advance the science to deliver the right drug, at the right time, for each patient Within the oncology business unit, our mission is to cure or control cancer with breakthrough medicines Our business unit has almost 1200 colleagues located across 26 countries worldwide We have recently been able to bring three new medicines to patients with different tumor types We are excited about the oncology pipeline, having three additional Phase 3 compounds in development with the potential to help more patients in the next couple of years

CDK4/6 inhibition Cyclin Dependent Kinases (CDKs) are key regulators of sequential progression through the G1, S, G2 and M phases of the cell cycle; deregulation has been shown to contribute to the development of cancer Preclinical models show that inhibition of CDK 4 and 6 may control tumor growth Palbociclib (PD-0332991) is an oral selective inhibitor of the CDK 4 and 6 kinases which inhibits cell proliferation and cellular DNA synthesis by preventing cell-cycle progression from G1 to S phase Preclinical research supports activity in melanoma, but the agent is not yet in clinical trials for melanoma A partnership between Pfizer and MRA may accelerate preclinical science of CDK4,6 in melanoma has the potential to advance the understanding of melanoma biology and advance the development a new therapeutic target.

Process and Timeline Request for Proposals announced: August, 2012 $100,000/year for 2-3 years from MRA for an established investigator with matching support from Pfizer Proposals were due to MRA: Nov. 15, 2012 Letter of support from Pfizer required at the time of application Six proposals received by MRA MRA Grant Review Committee review: February, 2013 Two awarded granted: April, 2013 One award was offered in the RFP, but given the high quality of the applications, MRA and Pfizer agreed to support two projects at $550,000 each over three years

Awards Two distinct but complementary projects: Martin McMahon, University of California, San Francisco: Study the role of CDK4/6 in melanoma and utilize genetically engineered mouse models of BRAF mutated melanoma to test the potential of CDK4/6 inhibitors in combination with BRAF inhibitors Andrew Aplin, Thomas Jefferson University: Define biomarkers for response to CDK4/6 inhibitors and analyze the potential of these drugs to treat melanomas that are resistant to BRAF inhibition

Future MRA milestones Current open RFP for Academic-Industrial Partnership Award proposals www.curemelanoma.org Deadline November 13, 2013 Established investigators will receive up to $100,000/year for 2 to 3 years from MRA plus matching support from industry partner Ongoing assessment and improvement of program