MRA, Including the Approved by the U.S

Melanoma. ResearchAlliance

Accelerating Progress: Moving Toward a Cure for Melanoma 2008-2011 Report Our First Four Years A period of landmark advances in melanoma research and treatment. “This is clearly the year of melanoma…”

George W. Sledge, Jr., M.D., American Society of Clinical Oncology Past President - June 2011

LETTER FROM THE CHAIR AND PRESIDENT

n March, an This report offers a immunotherapy called retrospective of the four I Yervoy (ipilimumab) years since the founding became the first drug of MRA, including the approved by the U.S. Food progress we have made, and Drug Administration a highlight of scientific (FDA) in 13 years for findings, and a look to metastatic melanoma. Then the molecularly the future of melanoma research. MRA funding has targeted agent Zelboraf (vemurafenib), an been vital to unlocking the best treatments and inhibitor of a mutated protein found in about continues to offer hope for better therapies and half of melanomas, was approved by the FDA ultimately a cure. in August. These breakthroughs underscore As the pace of progress quickens, MRA is remarkable progress that has been unfolding in re-doubling its efforts to accelerate research. the four years since the founding of the Melanoma With more than $30 million awarded for promising Research Alliance (MRA), a unique organization research, MRA has catalyzed strategic and collabo- whose mission is to find and fund the most rative research efforts to discover new biomarkers promising research worldwide. MRA is working of treatment response, demystify drug resistance to better prevent, detect early and treat deadly mechanisms, and improve effectiveness through skin cancer, toward a day when no one suffers combination therapies. MRA is working with all or dies from melanoma. who care about defeating melanoma, moving from No one person or organization can win the “the year of melanoma” to “the year of the battle against melanoma alone. We are thankful melanoma cure” as quickly as possible. to all who have engaged with us in this fight— DEBRA BLACK, co-founder and chair researchers, supporters, allies, partners, and more. WENDY K.D. SELIG, president and CEO

MRA 2008-2011 About MRA 03

Thanks to the ongoing generous support of About MRA its founders, MRA applies 100 percent of Strategic public donations to its research program.

under MRA is a public charity formed in 2007 GROWTH OF MRA’S RESEARCH PROGRAM the auspices of the Milken Institute, with generous $35 founding support from Debra and Leon Black. The 2011 $30 mission of MRA is to accelerate the pace of scientific discovery and its translation in order to eliminate $25 2010

suffering and death due to melanoma. Thanks to the $20 ongoing support of its founders, MRA applies 100 2009 percent of public donations to its research program. $15 Funding (Millions) $10 2008 In its first four years, MRA has committed $30.4 million $5 to 73 research programs with the potential to make significant, near-term clinical impact in prevention, 0 diagnosis, staging, and treatment. MRA is the largest pri- MRA research awards provide an important and unique vate funder of melanoma research in the United States. source of funding that addresses the gap in translational science, which is a critical stage in moving scientific TOTAL COMMITMENTS BY AWARD TYPE discoveries into tools and treatments for patients. Pilot/Dev Young ($0.7M) Hallmarks of the MRA research portfolio include: ($2.8M) Partnership ($0.3M)

Established • Focus on collaborative team science: Team ($4.2M) Science Awards, which fund multidisciplinary research groups, account for almost three-quarters of research funding to date, followed by a variety of individual Team awards: Established Investigator, Young Investigator, ($22.4M) Pilot/Development Awards, and Partnership Awards.

THE FIRST FOUR YEARS

MRA has committed $30.4 million to 73 research programs. It is the largest private funder of melanoma research in the United States. $30.4 MILLION Melanoma. www.curemelanoma.org 04 ResearchAlliance Strategic

About MRA Strategic

• Investment in developing new treatments for metastatic disease: Nearly 80 percent of research funding is directed at melanoma treatment, followed by diagnosis/staging and prevention. In particular, MRA is investing significant resources to improve upon the two new treatment approaches— immune checkpoint targeting and selective BRAF inhibition.

• Advances in key scientific and clinical areas: MRA-funded research has made progress in all of the key areas of opportunity identified at its inaugural Call to Action meeting in 2007. Because of

TOTAL COMMITMENTS BY SCIENCE AREA the rapid progress that has been made, MRA has

Prevention updated and revised this agenda for the next four years. ($2.8)

Diagnosis/Staging • Treatment ($3.7M) Support for a diverse group of melanoma ($24.0M) researchers worldwide: MRA is funding 114 Principal Investigators at 56 institutions in 10 countries (Australia, Belgium, Canada, Germany, Israel, Netherlands, New Zealand, Sweden, Switzerland, and the United States).

NEARLY 80 PERCENT Nearly 80 percent of research funding is directed at melanoma treatment, followed by diagnosis/ 114 staging and prevention. PRINCIPAL INVESTIGATORS

MRA 2008-2011 Strategic 05

Global Presence Location of Principal Investigators leading MRA-funded awards, 2008-2011

Canada Europe

United States 8 G Israel

New VZealand Australia B Cs9 F D L

Australia Canada Israel New Zealand United States Chicago, IL Cleveland, OH Westmead Toronto Jerusalem Wellington Phoenix, AZ Boston, MA Philadelphia, PA Herston Montreal Ramat Gan La Jolla, CA Cambridge, MA Providence, RI Melbourne Sweden Los Angeles, CA Baltimore, MD Nashville, TN Sydney Germany Netherlands Lund Oakland, CA Ann Arbor, MI Houston, TX Frankfurt Amsterdam Pasadena, CA Detroit, MI Salt Lake City, UT Belgium Heidelberg Groningen Switzerland San Francisco, CA St. Louis, MO Charlottesville, VA Leuven Leiden Zurich Santa Monica, CA Princeton, NJ Seattle, WA Maastricht Stanford, CA Cold Spring Harbor, NY Rotterdam Tampa, FL New York, NY Champaign, IL Rochester, NY

Melanoma. www.curemelanoma.org 06 ResearchAlliance Collaborative

About MRA Collaborative

Collaboration is at MRA's core—from the contributions from an industry partner whose team approaches to research that it funds participation is essential to the project. MRA and the to the way it finds partners who can help partner company will jointly support research with a realize its vision. Relationships built with high likelihood of clinical translation to help patients other nonprofits, corporations, and individuals and those at risk for melanoma. continue to increase: • MRA has co-funded research projects with fellow • MRA and Stand Up to Cancer (SU2C) are jointly cancer research foundations, including the Canadian funding a Melanoma Dream Team of at least $6 Cancer Society, Cancer Research Institute, and million beginning in early 2012. This ground- Melanoma Research Foundation. breaking award represents one of the largest single private grants for melanoma research and the first collaboration of its kind with SU2C.

• In its first ever such offering, MRA selected two Academic-Industry Partnership Awards in 2011 that will support projects in conjunction with matched

Relative Contribution of Pigmentation and PREVENTION Other Genes to Melanoma Risk Funded by an MRA Team Science Award, Drs. Nicholas Hayward and Nicholas Martin (Queensland Institute of Medical Research) and Dr. Graham Mann (Westmead Institute for Cancer Research and University of Sydney) discovered five new melanoma risk genes that conferred an increased risk of melanoma between 14 and 22 percent. In contrast to other known risk genes, none of these appear to be associated with Relative contribution of pigmentation physical characteristics such as fair and other genes to skin or moles. melanoma risk

MRA 2008-2011 Collaborative 07

• Through its growing Allies program, MRA has raised awareness of melanoma and funds for melanoma research with nearly 50 companies who believe in its mission. For example, with the help of key Corporate Allies, including Claire’s, SkinCeuticals, and The Sports Authority, MRA reached as many as 19 million people with information about melanoma while raising nearly $350,000 for melanoma research during Melanoma Awareness Month in May 2011. MRA also leveraged its affiliation with the Milken Institute by hosting an outreach event on the closing day of the 2011 Global Conference in Beverly Hills. The event, supported by Corporate Allies Graff, Montage and Style Network , introduced the work of MRA to dozens of new supporters. Expanded collaborations with additional companies that share the MRA mission, as well as non-profit organizations like the Girl Scout Council of the Nation’s Capital, When longtime member of Bruce Springsteen's E Street Band Danny Federici (center) was diagnosed with melanoma, the Danny Fund are underway. was launched.

• When Danny Federici, longtime member of Bruce Through its growing Allies program, Springsteen’s E Street Band, passed away from MRA has raised awareness of melanoma in April 2008, his family and friends melanoma and funds for melanoma received an outpouring of support. Together with research with nearly 50 companies MRA Co-Founders Debra and Leon Black, they brought their Danny Fund under the MRA umbrella, who believe in its mission. MRA working to bring melanoma to the forefront of reached as many as 19 million people public awareness and to fund research around the with information about melanoma world. Springsteen recorded a public service while raising nearly $350,000 for announcement to raise awareness of melanoma and melanoma research in May 2011, MRA, which aired during the 2009 Super Bowl and in during Melanoma Awareness Month. movie theaters across the country.

Melanoma. www.curemelanoma.org 08 ResearchAlliance Transformative

About MRA Transformative

In just a few years of active research, the INNOVATIVE MRA-FUNDED RESEARCH productivity of MRA-funded investigators WINS ADDITIONAL SUPPORT (IN MILLIONS) has been high, as measured by tangible outcomes and promising early research MRA-Funded Research results, advancing the understanding of $50

the causes, origins, and progression of leveraged $40 $ melanoma melanoma and developing new therapies 17.2 funding for patients with advanced disease: $30 MRA • 9 clinical trials supported by MRA to test promising Millions $20 $30.4 investment agents alone and in combination for the treatment of $10 metastatic melanoma. 0 • $17.2 million in additional research funding leveraged from other sources by MRA investigators. The majority of this funding was granted by the U.S. National Institutes of Health through a merit-based peer-review process. Combination Therapies

• 13 patent applications filed or new inventions disclosed for new technologies, which have the potential to be With an MRA Established Investigator Award that was leveraged to secure an developed into new tools or treatments for patients. NIH grant, Dr. Stephen Hodi (Dana-Farber • More than 100 collaborations initiated and Cancer Institute) conducted a Phase I trial strengthened between academic, government, and investigating ipilimumab with bevacizumab industry scientists, which enhance sharing of informa- in stage IV melanoma patients and worked to define the mechanism of action for this tion and fast-forwarding of the research. synergistic drug combination. Ipilimumab • More than 50 papers published in high-impact journals works to boost the immune system to fight describing research results supported by MRA, which cancer and bevacizumab blocks the growth of blood vessels to tumors. Based on this inform the scientific and clinical communities about work, Hodi secured an NIH R21 grant to promising new research findings so that others may continue the trial. In this small group of build upon the results to help patients. patients, some have experienced durable • Hundreds of presentations delivered by MRA clinical benefits, and side effects have been manageable. investigators at medical and scientific meetings around the world, where research results are shared and the profile of MRA is enhanced.

MRA 2008-2011 Accountable 09

MRA has become the largest private About MRA funder of melanoma research. Accountable

At the first gathering of the world's leading melanoma and unbiased process. Final funding decisions are researchers and clinicians convened by MRA in 2007, ratified by the MRA Board of Directors. the group identified the crucial scientific and clinical questions that need to be addressed in order to transform The MRA Scientific Advisory Panel (pages 19-20) the field of melanoma prevention, detection and treat- advises, assists, and makes recommendations to the ment, and to begin to map out concrete ways to effect that MRA leadership team on the scientific matters and transformation. It has been nearly four years since that policies of MRA, including research needs and Call to Action meeting and the launch of MRA. In this opportunities that may be targeted for funding and short time, MRA has become the largest private funder planning scientific symposia. of melanoma research, with programs delving into each Each year, MRA hosts a Scientific Retreat that attracts of the 17 scientific and clinical questions prioritized by more than 150 attendees, including the world’s leading that distinguished group. scientists, as well as senior leaders from nonprofit In 2011, MRA released its revised and updated Strategic foundations, government agencies, industry, and other Research Plan, which recognizes the enormous strides key stakeholders. The retreat features focused sessions on that have been made and identifies areas of greatest need key topics of interest, invited speakers and presentations for scientific discovery. The updated research plan will from MRA-funded investigators. To summarize the guide the development of the MRA scientific portfolio meeting’s key themes, MRA publishes a report of over the next granting cycles. highlights. Since its inception, MRA has hosted four major meetings, with the next one planned for March 2012. Research proposals submitted to MRA are reviewed by MRA’s Grant Review Committee (pages 19-20), a group Each year, MRA leadership and staff conduct outreach of leading experts in melanoma and cancer research. and site visits to MRA-funded institutions to learn more Review is based on MRA’s key criteria: innovation, scien- about their melanoma programs, hear about progress tific merit, and potential for rapid progression to clinical being made thanks to their MRA award funding, and testing. MRA’s conflict-of-interest guidelines ensure a fair further develop relationships with awardees.

Above left: Drs. Adrian Senderowicz of AstraZeneca, Richard Pazdur of the U.S. Food and Drug Administration, George Demetri of the Dana-Farber Cancer Institute, Jonathan Cebon of the Ludwig Institute for Cancer Research, Melbourne Clinical Sciences Center, F. Stephen Hodi of the Dana-Farber Cancer Institute, and Paul Chapman of the Memorial Sloan-Kettering Cancer Center discussed regulatory approval pathways for new melanoma therapies during the 2011 scientific retreat. Above right: Tony Ressler, Debra Black, MRA co-founder and chair, and Michael Milken, MRA board member, listened to presentations at the 2010 scientific retreat.

Melanoma. www.curemelanoma.org 10 ResearchAlliance Strategic Research Portfolio

Strategic Research Portfolio Funding by Research Area

MRA focuses on innovative translational In 2011, Yervoy (ipilimumab/ research that has the potential to impact melanoma anti-CTLA-4) became the first prevention, diagnosis/ staging, and treatment in the near drug approved by the FDA in 13 and intermediate future. years for metastatic melanoma.

Prevention: Research focusing on the biological researchers are working to identify new molecular prog- causative factors in melanoma carcinogenesis includes nostic biomarkers and to develop better imaging agents. studies of skin pigmentation biology and genetic mutations in melanoma driving downstream biochemical Treatment: In March 2011, an immunotherapy called pathways. By investigating the mechanisms involved in Yervoy (ipilimumab/anti-CTLA-4) became the first the development of melanoma, this work will inform bio- drug approved by the FDA in 13 years for metastatic logically-based strategies for prevention and therapy. melanoma. The molecularly targeted agent Zelboraf (vemurafenib), an inhibitor of mutant BRAF found Diagnosis and staging: There are significant chal- in approximately 50 percent of melanomas, was lenges in diagnosing and staging for primary melanoma. approved in August 2011. These breakthroughs The current system based on visual clues and histology underscore remarkable progress. Yet, these will not is not adequate, particularly in defining metastatic provide cures for most patients, and much more potential, resulting in either over-treatment or under- remains to be done until melanoma is effectively treatment of some patients. New imaging technology addressed. MRA is funding key areas to accelerate the is also needed in the metastatic setting. MRA-funded next generation of treatments.

IMMUNOTHERAPIES

Drs. Antoni Ribas (University of California, Los Angeles) and James Heath and David Baltimore (California Institute of Technology), with funding from an MRA Team Science Award, developed a new tool for improving adoptive T cell transfer therapy (ACT). Immune cells are very complex and diverse, and current technologies limit the full understanding of how these cells behave to combat melanoma cells in patients during treatment. This The SCBC consists of microchannels that contain cells new tool, called a single-cell barcode chip (SCBC) is a complex from a patient’s blood sample, valves and ports that isolate the cells and control reagents, and a barcode nanotechnology-based platform that enables researchers for the glass substrate for protein detection (pictured as red first time to look at the single T cells during ACT treatment. and green lines)

MRA 2008-2011 Strategic Research Portfolio 11

Drug dramatically helps melanoma patients. “This news about vemurafenib is the latest in a positive year for melanoma research, and a significant milestone.” Dr. Suzanne Topalian, MRA’s chief science officer, quoted in The Washington Post, June 5, 2011

• Immunotherapies: Melanoma is one of the • Molecularly targeted therapies: Targeted most immunogenic human cancers and can induce cancer therapies block the growth and spread of cancer specific anti-tumor immune responses in patients by interfering with specific cellular signaling pathways that are potentially capable of eliminating tumor involved in tumor growth and progression. MRA is cells. MRA-funded projects include characterizing funding research on therapies directed at multiple immunological signatures of successful therapies, molecular targets in melanoma as well as identifying developing better melanoma vaccine strategies, drug resistance mechanisms and strategies to overcome and improving adoptive T cell transfer protocols. them. MRA is investing $6 million in research involving MRA has invested nearly $5 million in funding to BRAF, including discovering drug resistance mecha- research projects aiming to improve melanoma nisms and combining BRAF inhibitors with other agents. checkpoint blockade such as elucidating immune correlates of response and combining these agents • Combinatorial therapies: Cancers are dependent with other therapies. on a number of altered molecular pathways and can develop resistance to single agent therapy; thus, combi- MRA has invested nearly $5 million nation regimens may provide the best hope for durable in projects to improve melanoma effects. MRA-funded studies in this area include checkpoint blockade and $6 development of two investigation agents and combina- million in BRAF-related studies. tions of investigational agents with approved agents.

NUMBER OF MRA-FUNDED PROJECTS IN MELANOMA PREVENTION, DIAGNOSIS/STAGING, AND TREATMENT

Prevention Diagnosis/Staging Treatment

biological mechanisms identifying new immunotherapy 5 of carcinogenesis 5 biomarkers 22

supporting skin developing prevention molecular targets screening agents based on 2 22 for therapy 2 studies of ultraviolet light on fair-skinned funding imaging of combination individuals 1 metastases 14 therapy

Melanoma. www.curemelanoma.org 12 ResearchAlliance Strategic Research Portfolio

Strategic Research Portfolio Funding by Type of Award

MRA has funded 24 Teams, 20 Established “MRA support is critical to starting Investigators, 19 Young Investigators, 8 Pilot new lines of research and has and Development projects, and 2 Academic- a multiplier effect on funding, Industry Partnership Awards. collaborations, and progress for Team Science Awards fulfill one of MRA’s primary goals: patients.” Dr. Patrick Ott, 2009 to foster a collaborative research process. Multidiscipli- MRA Young Investigator, New nary teams consist of Principal Investigators with York University complementary expertise who may be from the same institution, inter-institutional, and/or international Pilot Awards test potentially transformative ideas that institutions. Team science projects promote transforma- do not have extensive preliminary data but articulate a tional melanoma research advances with the potential clear hypothesis and translational goals. Resources for for rapid clinical translation. such “high-risk, high-reward” projects are important to establish proof-of-concept, which may then leverage Established Investigator Awards support senior inves- additional funding through more traditional avenues. tigators with an established record of scientific productiv- Development Awards are a subtype in which one year of ity and accomplishment and who are past the initial four funding is provided. years of their first academic faculty appointment. Partnership Awards are designed to facilitate interac- Young Investigator Awards aim to tions between sectors, including industry and other non- attract early career scientists with profit organizations. novel ideas into melanoma research, thereby recruiting and supporting the next generation of The Young Investigator Award melanoma researchers. Young Program grew dramatically Investigators are scientists within in 2011 through a focused Dr. Patrick Ott, 2009 four years of their first academic MRA Young Investigator, MRA funding campaign, New York University faculty appointment. A mentorship commitment from a senior investigator is required. The almost doubling the cohort Young Investigator Award Program grew dramatically in and bringing the total program 2011 through a focused MRA funding campaign, almost to $2.8 million awarded to doubling the cohort and bringing the total program to 19 investigators since 2008. $2.8 million awarded to 19 investigators since 2008.

MRA 2008-2011 Outreach 13

Outreach

Melanoma. In 2011, MRA unveiled a new logo and ResearchAlliance Fast-Forwarding a Cure for Deadly Skin Cancer website—www.curemelanoma.org—launching a new brand that symbolizes its vision for accelerating the pace of scientific discovery and translation.

The internet and social media have proven to be . effective ways to reach audiences. The MRA website Melanoma receives tens of thousands of visits from people in more than 100 countries looking for information about MRA, ResearchAlliance melanoma, and the latest in research. With more than www.curemelanoma.org 2,000 followers on Facebook and Twitter who receive daily updates on melanoma news, MRA saw a 35 percent MRA saw a 35 percent increase increase in social media followers in 2011. in social media followers in 2011. JENNIFER BERRY GOODEN - MISS AMERICA 2006

JENNIFER BERRY GOODEN A week or so later, I got the call telling me the biopsy MISS AMERICA 2006 on my lymph node had come back completely clear. I was 25 years old in March 2009 I was cancer free. For the first time in over a month, when I realized I needed to go in I could breathe. for my yearly skin check. There had been a small spot on my left I continued to allow my leg to heal, and around the ankle and every time I looked at it 10-week mark, it finally felt normal again, and I could I somehow knew the spot just walk. The swelling was gone, and although I had an didn't look right. interesting scar, I was amazed at my body's ability to heal. During my appointment, the dermatologist told me he'd like to biopsy the spot. The biopsy showed that This entire experience changed my life forever. I now it was melanoma. visit the dermatologist and my surgeon every three to six months. This will be a part of my life forever. But On the day of the surgery I arrived at the hospital with these small inconveniences are well worth the chance butterflies in my stomach. I was given all the scary to live and be cancer free. potentials as I signed all my consent forms. I wear sunscreen every single day, and the days of After the surgery, they told me that everything had lying out in the sun are long gone. But I am embracing gone superbly. my skin and don't take healthy skin for granted.

http://www.melanomaresearchalliance.org/about_melanoma/about.taf?cat=stories

Melanoma. www.curemelanoma.org 14 ResearchAlliance Outreach

Outreach

Wendy Selig hosted a panel that featured (left to right) Dr. Jonathan Simons, president and CEO of the Prostate Cancer Foundation, Dr. John Mendelsohn, president of The University of Texas MD Anderson Cancer, Gregory Lucier, chairman and CEO of Life Technologies, Jill Kargman, author of "Sometimes I Feel Like a Nut,” and Amy Harmon, Pulitzer Prize-winning reporter for The New York Times

yielded $5 million, all of which is funding transformative melanoma research programs. The dinner featured a live auction led by Jamie Niven, Sotheby’s chairman of North and South America, an exclusive preview of Impressionist and Modern MRA leadership reaches out to a broad audience through Art, and the opportunity to meet with some of the most conferences and panel discussions that focus on forward-thinking minds in cancer research. A highlight of melanoma and lessons from this field that can be applied the auction came when supporters pledged sponsorship to other areas of medical research. For example, the 2011 for nine Young Investigator awards, nearly doubling the Milken Institute Global Conference included an MRA number of these awards funded by MRA to date. panel, "Exploring the Frontiers of Medicine: How We Will Save Lives from Cancer.” The session was moderated by Wendy Selig, MRA’s president and CEO. The panel used melanoma as a case study to discuss innovative approaches to cancer research and treatment.

MRA also expands its reach by hosting gatherings across the country throughout the year to engage new people and elevate the importance of melanoma among various audiences.

Patient advocates, philanthropists, scientists, and Corporate Allies At the Sotheby’s benefit dinner, Dr. Padmanee Sharma discusses convened for the first annual MRA benefit dinner at how her MRA Young Investigator Award advanced her research Sotheby’s in New York City on Oct. 28, 2010. The event to better treat melanoma patients..

MRA 2008-2011 Outreach 15

Outreach

Christie's is a long term MRA partner Design Center. MRA Young Investigator, Dr. Roger Lo and collaborator. The company has from UCLA, gave a brief overview of his research and how engaged with MRA in a variety of MRA has dramatically improved the field for young awareness and fundraising initiatives including support doctors and researchers. The luncheon concluded with of Dr. Christian Blank at the Netherlands Cancer board member, Maria Bell, sharing her personal experi- Institute through the Christie's —MRA Young ences with melanoma. The event introduced over 150 Investigator Award. women in the Los Angeles area to the MRA and raised critical funds for research. A highlight of this collaboration came as Chairman of Christie's Americas, Marc Porter joined with Wells Fargo In December to co-host the first official Los Angeles showing of the 2010, Cartier's traveling Elizabeth Taylor exhibit in April 2011. The exhibit president and CEO, Emmanuel featured Ms. Taylor's jewelry collection and was followed Perrin, and vice president of by a luncheon in honor of MRA at the MOCA Pacific retail, Mercedes Abramo, co- hosted a holiday celebration with MRA chair and co-founder, Debra Black, and MRA board Debra Black, MRA co-founder member, Susan Hess, honoring and chair, and Emmanuel Perrin, Cartier's president and MRA. The event was held at the CEO, at Cartier's 2010 holiday Cartier Mansion in New York celebration honoring MRA. City and was a spectacular evening. In addition to the many events Cartier hosts in honor of MRA, the company also supports Dr. Remco van Doorn at Leiden University Medical Centre, through the Cartier—MRA Young MRA co-founder Debra Black (right) and Board Member Maria Bell attend the Christie's LA luncheon in honor of MRA. Investigator Award.

YOUNG INVESTIGATORS INCREASED A highlight of the Sotheby's event auction came when supporters pledged sponsorship for nine Young Investigator awards, nearly doubling the number of these 10 19 awards funded by MRA to date.

Melanoma. www.curemelanoma.org 16 ResearchAlliance Looking Ahead

Looking Ahead

Although melanoma poses many difficult challenges, MRA and its DIAGNOSIS Benign Nevus Primary Melanoma AND STAGING Melanoma Metastase funded researchers are making een)

significant progress toward develop- While most early tments: stage melanomas Nucleus (blue) Compar

ing better diagnostic and preventive Cytoplasm (gr are cured with measures, improved treatments, surgery, some recur ed) and a deeper understanding of this and metastasize even after removal complex and deadly disease. of the primary tumor.

MRA Established ACPS Staining (r The recent advances in the development of Investigator Dr. ACP5 Protein Level new therapeutic approaches have generated Lynda Chin (then at ACP5 protein expression is greatest in melanoma excitement and optimism for a better outlook Dana-Farber Cancer Institute, now at MD metastases compared with primary melanomas and benign nevi. for melanoma patients. With the significant Anderson Cancer infusion of research funding from MRA, Center) identified six “proinvasion oncogenes” that are signifi- cantly overexpressed in metastatic lesions compared to primary investigators are finding ways to improve upon melanomas in preclinical models. The protein expression level of these results as well as create new strategies one of them, called APC5, was correlated with shorter survival to combat melanoma. MRA seeks to engage all of melanoma patients and, thus, may be a prognostic biomarker in human melanomas. This work is being clinically developed by stakeholders in working toward a day when no a company to build prognostic tests based on the molecular one suffers or dies from melanoma. characteristics of early stage melanoma.

MOLECULARLY TARGETED THERAPY Approval of vemurafenib, an inhibitor of mutant BRAF involved in about half of melanomas, is a major breakthrough. While this drug has benefitted some patients, most relapse due to drug resistance. Research suggests that secondary mutations in BRAF are not a common cause of resistance to BRAF inhibitors, but that multiple other mechanisms may be playing a role. Melanoma cells have additional ways to survive and grow, and emerging research has identified mutations and alterations in genes and proteins involved in resistance. It is likely that others remain to be identified and confirmed in patients. An MRA Team Science Award accelerating research to solve this problem is being led by Drs. David Solit and Paul Chapman (Memorial Sloan-Kettering Cancer Center), Hensin Tsao, David Fisher, and Keith Flaherty (Massachusetts General Hospital), Michael Davies (MD Anderson Cancer Center), Roger Lo (University of California, Los Angeles), Katherine Nathanson (University of Pennsylvania), BRAF mutant melanoma cells have highly altered genomic profiles, including loss of a tumor suppressor gene called and Jeffrey Sosman PTEN on chromosome 10 (white=copy number neutral; (Vanderbilt University). blue=copy number loss; red=copy number gain)

MRA 2008-2011 Financials 17

Financials (as of Dec. 31, 2010)

Thanks to the generous ongoing 2010 FUNCTIONAL EXPENSES support of its founders, 100 percent of public donations to MRA directly Management Fundraising and General 2.1% 3.6% support melanoma research. Non-Grants Scientific Program The independently audited financial 5.7% statements of Melanoma Research Alliance Foundation form the basis for the following information. Grants and Awards Program 88.6%

Assets 12/31/2010 12/31/2009 12/31/2008 Cash and Cash Equivalents $6,661,152 $2,228,522 $110,296 Investments - - 2,878,106 Accounts Receivable 55,025 - - Contributions Receivable 9,468,362 - - Prepaid Expenses and Other Assets 517,846 10,000 - Property and Equipment (Net) 5,395 5,116 -

Total Assets $16,707,780 $2,243,638 $2,988,402

Liabilities and Net Assets Liabilities: Accounts Payable and Accrued Liabilities 59,716 54,478 67,921 Due to Affiliate 10,281 291 286,735 Deferred Revenue 25,000 - - Deferred Rent 9,680 10,057 -

Total Liabilities 104,677 64,826 354,656 Net Assets: Unrestricted 6,249,741 2,178,812 2,633,746 Temporarily Restricted 10,353,362 - - Net Assets 16,603,103 2,178,812 2,633,746

Total Liabilities and Net Assets $16,707,780 $2,243,638 $2,988,402

Melanoma. www.curemelanoma.org 18 ResearchAlliance Financials

Financials (as of Dec. 31, 2010)

Statement of Activities

Revenues, Public Support 2010 2009 2008 and Other Income Contributions (including Founders’ Gift) $18,563,318 $6,533,950 6,001,150 Special Events 5,025,867 - - Investment Income (Loss) (Net) 25,642 8,718 106,106

Total Revenues, Public Support 23,614,827 6,542,669 6,107,256 and Other Income

Functional Expenses: Program Services: Grants 8,668,371 6,828,183 3,423,577 Fundraising 194,989 - - Management and General 327,176 169,420 49,933

Total Functional Expenses 9,190,536 6,997,603 3,473,510

Change in Net Assets 14,424,291 (454,934) 2,633,746 Net Assets - Beginning of Year 2,178,812 2,633,746

NET ASSETS - END OF YEAR 16,603,103 2,178,812 2,633,746

MRA 2008-2011 Committees 19

Board of Directors Scientific Advisory Panel

• Debra Black, Chair, MRA Co-Founder, Broadway • Elizabeth A. Grimm, M.D., Frances King Black Producer, Melanoma Survivor Memorial Professorship of Cancer Research and • Leon Black, MRA Co-Founder, Board Member Deputy Chair, Department of Experimental Faster Cures, CEO Apollo Management LP Therapeutics, The University of Texas MD • Maria Bell, Head Writer and Co-Executive Anderson Cancer Center Producer/Head Writer, The Young & the Restless • Martin Mihm, M.D., Director, Melanoma Program • Jason Federici, Art Director, Graphic Designer, in Dermatology, Brigham and Women's Hospital; Photographer Associate Director, Melanoma Program, • Jami Gertz, TV and Film Actress Dana-Farber/Brigham and Women's Cancer Center • Susan Hess, Vice Chairman, Whitney Museum • Donald Morton, M.D., Chief, Melanoma Program; • Michael Klowden, President and CEO, Director, Surgical Oncology Fellowship Program, Milken Institute John Wayne Cancer Institute • Connie Mack, Senior Policy Advisor, Liberty • Neal Rosen, M.D., Ph.D., Enid A. Haupt Chair in Partners Group LLC; Former U.S. Senator Medical Oncology, Memorial Sloan-Kettering • Nancy Marks, Artist Cancer Center • Michael Milken, Chairman, Milken Institute; • Steven Rosenberg, M.D., Chief, Surgery Branch, Founder and Chairman, Faster Cures; Founder and National Cancer Institute (Dr. Rosenberg serves on Chairman, Prostate Cancer Foundation the MRA Scientific Advisory Panel in his personal • Richard Ressler, Founder, Orchard Capital capacity) Corporation and CIM Group • Wendy K.D. Selig, President and CEO, MRA • Henry Silverman, Non-executive Chairman of the • Suzanne Topalian, M.D., Professor of Surgery and Board of Directors, Realogy Corporation; Senior Oncology, Johns Hopkins Medicine; Director, Advisor, Apollo Global Management; Former Melanoma Program, Sidney Kimmel Chairman and CEO, Cendant Corporation Comprehensive Cancer Center, Johns Hopkins • Greg Simon, SVP Worldwide Policy, Pfizer, Inc. University; Chief Science Officer, MRA • Jonathan W. Simons, M.D., President and CEO, David H. Koch Chair, Prostate Cancer Foundation; Professor, Biomedical Engineering and Material Grant Review Committee Sciences, Georgia Institute of Technology, NCI Center of Cancer Nanotechnology Excellence • Jonathan Cebon, M.B.B.S., F.R.A.C.P., Ph.D., • Jonathan Sokoloff, Managing Partner, Leonard Director of Medical Oncology, Austin Health, Green and Partners, L.P. Head Cancer Vaccine Laboratory, Ludwig • Elizabeth Stanton, President, Elizabeth and Oliver Institute for Cancer Research, Professor of Stanton Foundation Medicine, University of Melbourne • Wendy Selig, President and CEO, MRA • Meenhard Herlyn, D.V.M., D.Sc., Professor of • Margaret Anderson, Secretary Dermatology, Pathology and Laboratory Medicine, Executive Director, Faster Cures University of Pennsylvania; Chairman, Molecular • Kamyab Hashemi-Nejad and Cellular Oncogenesis Program, Treasurer, Director of Finance, Milken Institute Wistar Institute

Melanoma. www.curemelanoma.org 20 ResearchAlliance Committees

• James Allison, Ph.D., Chair of Immunology • Michal Lotem, M.D., Sharett Institute of Oncology, Program; Director of Ludwig Center for Cancer Hadassah Hebrew University Hospital, Kiryat Immunotherapy, Investigator, Howard Hughes Hadassah Medical Center, Memorial Sloan-Kettering • Richard Marais, Ph.D., Professor of Molecular Cancer Center Oncology, The Institute of Cancer Research • Boris Bastian, M.D., Clinical Professor, • Kim Margolin, M.D., Physician, University of Department of Dermatology, University of Washington/Seattle Cancer Center California, San Francisco • Glenn Merlino, Ph.D., Chief, Laboratory of Cancer • Marcus Bosenberg, M.D., Ph.D., Associate Professor Biology and Genetics, National Cancer Institute, of Dermatology and Pathology, Yale School of • Stan Riddell, M.D., Member, Department of Medicine Immunology, Fred Hutchinson Cancer Research • Steven Burakoff, M.D., Professor of Medicine, Center Hematology and Medical Oncology, Professor, • Jonathan Simons, M.D., President and CEO, David Oncological Sciences, Mount Sinai School of H. Koch Chair, Prostate Cancer Foundation Medicine • David Solit, M.D., Assistant Member, Human • Paul Chapman, M.D., Attending Physician, Oncology and Pathogenesis Program, Memorial Melanoma/Sarcoma Service, Memorial Sloan- Sloan-Kettering Cancer Center; Elizabeth and Felix Kettering Cancer Center; Professor of Medicine, Rohatyn Chair for Junior Faculty Weill Medical College of Cornell University • Howard Soule, Ph.D., Executive Vice President, • Tanja de Gruijl, Ph.D., Associate Professor, VU Discovery and Translation, Prostate Cancer University Medical Center Foundation • Charles Drake, M.D., Ph.D., Associate Professor - • Suzanne Topalian, M.D., MRA Chief Science Officer, Oncology, Immunology and Urology; Director - Professor of Surgery and Oncology, Johns Multidisciplinary Prostate Cancer Clinic, Johns Hopkins Medicine, Director, Melanoma Program, Hopkins Sidney Kimmel Comprehensive Sidney Kimmel Comprehensive Cancer Center Cancer Center • Michael Weber, Ph.D., Director, Cancer Center, • Glenn Dranoff, M.D., Director, Human Gene Weaver Professor of Oncology, University of Transfer Laboratory Core, Dana-Farber Cancer Virginia Institute • David Fisher, M.D., Ph.D., Chief, Department of Dermatology; Director, Melanoma Program, MGH Cancer Center; Director, Cutaneous Biology Research Center, Massachusetts General Hospital; Edward Wigglesworth Professor of Dermatology, Harvard Medical School • Allan C. Halpern, M.D., Chief, Dermatology Service, Memorial Sloan-Kettering Cancer Center • Thomas Hornyak, M.D., Ph.D., Chief, Dermatology, VA Maryland Healthcare System; Associate Professor of Dermatology and Biochemistry and Molecular Biology, University of Maryland School of Medicine

MRA 2008-2011 Donors 21

Donors $50,000-$99,999 * Multi-year support --- Barclays Capital $500,000 and Above Citi Global Banking --- Ernst & Young LLP* Akin Gump Strauss Hauer & Feld LLP* Larry Gagosian The Jeffrey A. Altman Foundation* General Nutrition Corporation Anonymous* Judy and John Hannan Debra and Leon Black* Gail and Carl Icahn Gagosian Gallery JPMorgan Chase & Co. Rahr Enterprises* The LeBow Family Jami Gertz and Tony Ressler* Jane Goldman and Benjamin Lewis The Ressler Family Foundation* Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.E.* Sokoloff Family Trust* Paul, Weiss, Rifkind, Wharton & Garrison LLP* Jenny and John Paulson SkinCeuticals $250,000-$499,999 Susan and Eric Smidt --- Sotheby's The Carson Family Charitable Trust* Katherine and Jerry Speyer Credit Suisse* The Thompson Family Ellen and Gary Davis Foundation* Andrew H. & Ann R. Tisch Foundation Caryl and Israel Englander The Winnick Family Foundation O'Melveny & Myers LLP PricewaterhouseCoopers* Elizabeth and Oliver Stanton Foundation* $25,000-$49,999 US Trust/Bank of America* --- Wachtell, Lipton, Rosen & Katz* Debbie and Mark Attanasio Emily and Len Blavatnik The Brown Foundation, Inc. $100,000-$249,999 Kathryn and Kenneth Chenault --- Citi Private Wealth Management Donna and William Acquavella Sir Ronald Cohen and Sharon Harel-Cohen Aon Risk Services* Susan and Peter Evensen Katie and Todd Boehly* Fribourg Family Foundation Sunny and Norman Brownstein Genentech, Inc. Brownstein, Hyatt, Farber & Schreck* The Perry & Martin Granoff Family Foundation, Inc. Cartier The Joshua & Marjorie Harris Family Foundation Christie's Kristy and Robert Harteveldt Deloitte* Suzette and Steven Kolitch Hess Foundation, Inc. Marie Josee & Henry R. Kravis Foundation Latham & Watkins, LLP* Jo Carole and Ronald Lauder Susan and Martin Lipton Richard S. and Karen LeFrak Charitable Foundation, Inc. Nancy and Howard Marks Live4Life Foundation, Inc. Montage Hotels & Resorts Janet Wallach and Robert Menschel Morgan Stanley* Myriam Barenbaum and Jonathan F. Miller Jane and Daniel Och Family Foundation Morgan, Lewis & Bockius, LLP Lizanne and Barry Rosenstein Kate and Robert Niehaus The Lawrence and Carol Saper Foundation, Inc.* Sandy and Paul Norman Sony Music Pfizer Inc. Merryl and James Tisch The Raiff Foundation Daryl & Steven Roth Foundation Rowan Family Foundation, Inc. Lily Safra Andree and Howard Shore TG Holdings, Ltd. UBS Financial Services The Viola Fund Wagner Family Foundation

Melanoma. www.curemelanoma.org 22 ResearchAlliance Donors

Leslie and Daniel Ziff Dana Hammond and Patrick Stubgen $5,000-$24,999 Barbara and John Vogelstein --- Gregg S. Weinstein Anonymous Brigitte and Alain Wertheimer Laura Anreder Patty Newburger and Brad Wechsler Renee and Richard Barasch Chef Michael White Baron Capital Foundation Dror Bar-Ziv The Bell Family Foundation, Inc. $1,000-$4,999 Milton Berlinski --- Jill and Jay Bernstein A G Foundation Barbara and James Block Ann and Steven Ames Alison Mass and Sal Bommarito Judith and John Angelo The Daniel & Estrellita Brodsky Family Foundation Anonymous Christian Dior Anonymous Chantal and Stephen Cloobeck Anthony Aufiero Joyce and Barry Cohen Susan and William Belfiore Concerts East, Inc. Biotechnology Industry Organization (BIO) Vanessa and Henry Cornell BRELLI Jim Ehrlich Memorial Family Foundation, Inc Michele and Martin Cohen Pamela and Jimmy Finkelstein Robert de Rothschild Susan and Richard Friedman Jean Doumanian Andrew Gn Phillip Dunn Golden Door Spa Therese Wareham and Merrick Elfman Audrey and Martin Gruss Jason Federici Mimi and Peter Haas Fund Olivia and Adam Flatto Ashley Leeds and Christopher Harland Bruce Glassman Henry Crown and Company Goldberg/Nash Family Foundation Herring Finn Foundation Deborah and Allen Grubman Ronnie F. Heyman Hard Rock Cafe Foundation, Inc. Caroline P. Hirsch Foundation The Hedges Family Hudson News Huberfeld Family Foundation Adam Kalish Janklow Foundation Robin and Joel Kassimir Liz Robbins and Doug Johnson George Klein Susan Scott and Robert J. Kaufman Evelyn and Leonard Lauder Mitchell Kline James B. Lee, Jr. LA Smooch LLC Lorber Charitable Fund Joel Lawson, IV Luxembourg Dayan Ninah and Michael Lynne Merkin Family Foundation Madison Cox Ken & Julie Moelis Foundation Roxanne and Andrew Majka Margo and Jimmy Nederlander Michael Margitich The New York Community Trust Mizel International Cultural Fund Northeast Theater Group Carol Morgan PhRMA The Daniel M. Neidich and Brooke Garber Foundation Leon Polsky and Cynthia Hazen Polsky The New York Community Trust Peggy and Gary Reiner Jill and Mark Rachesky Charitable Foundation The Reiss Family Foundation Denise Radesky Jonathan Ressler Redburn Partners USA LP Jacqueline and Mortimer Sackler Ellen and Bruce Ressler Mary and David Solomon Fiona and Eric Rudin The Thomas Spiegel Family Foundation Jane and Ned Sadaka Ambassador Carl Spielvogel and Dr. Barbaralee Diamonstein- Denise and Andrew Saul Foundation Spielvogel Schlosstein-Hartley Family Foundation Ruth Stanton Jean and Martin Shafiroff Alison and Leonard Stern Mia and Sheldon Solow Beatrice Stern Source of Hope Foundation The Sternlicht Family Foundation, Inc. Jane and James Spingarn Jennifer and David Stockman Pamela Sztybel and Elliott Stein

MRA 2008-2011 Support & Staff 23

Thomas D. & Denise R. Stern Family Foundation Supporters Matthew Stopnik Fern and Lenard Tessler Altamarea Group C. George van Kampen Foundation Anreder & Company Lauren and John Veronis Axcess Luxury & Lifestyle Marla and Craig Wasserman Carol & Michael Weisman Family Charitable Trust Birds Nest Foundation WellNest Bloomberg LP Constance and Sankey Williams Casa Dragones Lucy Halperin and Jerold Zaro Marcie and Howard Zelikow Chapstick Château d'Aussières CIM Group Inc. Danny Fund Entertainment Industry Foundation FasterCures Patricia and Michael Klowden Los Angeles County Museum of Art Lux Capital Management, LLC Marissa Alperin Studios The Milken Institute Lori and Michael Milken Museum of Contemporary Art, Los Angeles NGK Global Sirius Satellite Radio Bruce Springsteen & the E Street Band The Style Network Tribeca Entertainment David Yurman

Staff • Wendy K.D. Selig, President and CEO • Suzanne Topalian, M.D., Chief Science Officer • Laura M. Brockway-Lunardi, Ph.D. Scientific Program Director • Lauren C. Leiman, Development Director • Karen Rogers, Communications Manager • Ilyona Carter, Executive and Projects Assistant