1. LIFE RAFT GROUP A New Model for Cancer Research December 2009

2. THE LIFE RAFT GROUP Dedicated to finding a cure for Gastrointestinal Stromal Tumors (GIST)

7. Potential Therapies Genotype Current Initial Therapy Potential Initial Therapies Imatinib-Resistance KIT exon 11 Imatinib Masitinib Nilotinib Sorafenib Imatinib + PI3K inhibitor Sunitinib (poor) Sorafenib HSP90 inhibitors KIT exon 9 Standard dose imatinib High dose imatinib Sunitinib Sunitinib HSP90 inhibitors Wild-type Imatinib (poor response) Sunitinib Nilotinib Masitinib IGF1R inhibitors Sunitinib Nilotinib Masitinib IGF1R inhibitors PDGFRA D842V (exon 18) Imatinib (very poor) Dasatinib HSP90 inhibitors Dasatinib HSP90 inhibitors

8. KIT Gleevec - Sunitinib - Dasatinib-Sorafenib-Nilotinib PKC412-AMG706-MP470-HSP-90 inhibitors (indirect) PI3K BEZ235 - GDC0941 SF1125-XL765 AKT Perifosine mTOR RAD001 - CCI779 AP-23573-Rapamycin PKC-θ RAS R115777-SCH66336 RAF-1 Sorafenib MEK MAPK BCL-2 Gentasense BCL-X L BAD Src/Fyn/Lyn Dasatinib Survive Proliferate VEGFR (antiangiogenesis) Sunitinib-AMG706-PKC412 Sorafenib-Avastin Progress in understanding GIST Targets and Treatments HSP90 IPI504 - BIIB021 AUY922-STA9090 SNX5422 Other Receptors IGF1R (wild-type) AXL HDAC LBH589-SAHA STAT3 Survive-grow

9. Gleevec Resistance: Median Time to Progression is 24 Months

10. ABOUT THE LIFE RAFT GROUP

11. Our Mission LRG Member & GIST Patient Andrea Fuller SURVIVAL

16. Networking Dr. David Epstein, head of Novartis Oncology worldwide Dr. James Watson, Nobel Prize Winner Ted Kennedy and Dan Vasella, CEO of Novartis ACOR Pres., Gilles Frydman and Dana-Farber Sarcoma Chief, George Demetri

18. CHALLENGES FOR CANCER RESEARCH

19. What’s wrong with this? ASCO 2007: “Major Research Advances in Cancer Treatment” Treatment Improvement Avastin Doubled Progression Free Survival Sorafenib 44% longer life Radiotherapy 53% longer life Improvement OUTCOME FOR PATIENTS 5.4 months to 10.2 months 4.8 months 7.9 months to 10.7 months 2.8 months 17 weeks to 29 weeks 3 months

21. The LRG Response

22. LRG’S RESEARCH STRATEGY

32. Our Collaborators: LRG Research Team Dr. Brian Rubin, TheCleveland Clinic Dr. Jonathan Fletcher, Brigham & Women’s Hospital Dr. Chris Corless, Oregon Health & Science University Dr. Michael Heinrich, Oregon Health & Science University Dr. Cristina Antonescu, Memorial Sloan Kettering Cancer Center Dr. Anette Duensing, University of Pittsburgh Cancer Center Dr. Matt van de Rijn, Stanford University Dr. Maria Debiec-Rychter, University of Leeuven, Belgium Dr. Sebastian Bauer, University of Essen, Germany Dr. Peter Besmer, Memorial Sloan Kettering Cancer Center

33. LRG’s Research Priorities

39. For More Information Norman J. Scherzer Executive Director 973-837-9092 [email_address] www.liferaftgroup.org