LIFE RAFT GROUPA New Model for Cancer Research

December 2009

THE LIFE RAFT GROUP

Dedicated to finding a cure for Gastrointestinal Stromal Tumors (GIST)

Gastro-

Intestinal

Stromal

Tumors

A rare type of cancer--5,000 to 10,000 US cases/year

One type of Sarcoma

Sarcoma’s are a group of rare cancers that arise from cells of connective tissues, muscles, cartilage, bone, blood vessels, etc.

What Is GIST?

Survival History of GIST

Treatment response went from <5% to 85%

2000 brought Gleevec

Why is GIST relevant to other cancers?

It serves as a model for other more common cancers “By studying GIST, we expect to learn new things about the big four killers -

breast, colon, lung, and prostate cancers. Science and medicine often make the biggest leaps forward in unusual, rare diseases.“ George Demetri, Harvard Gazette

“GISTs appear to serve as a model for molecule-based diagnosis and treatment of solid tumors.” Y. Kitamura; Cancer Sci 2003

“There is considerable optimism that the targeted molecular approach being applied to the treatment of GISTs will serve as a model for the development of similar approaches to other more common tumors.” MS Saund, George Demetri; Curr Opin Gastroenterol, 2005

GIST Approved Drugs

FDA 2008

Approved Sales

Gleevec 2002 $3.7 B

Sutent 2006 $ .8 B

The GIST community has led the way in the development of molecularly targeted drugs in solid tumors…

Potential TherapiesGenotype Current Initial Therapy Potential Initial

TherapiesImatinib-Resistance

KIT exon 11 Imatinib MasitinibNilotinibSorafenibImatinib + PI3K inhibitor

Sunitinib (poor)SorafenibHSP90 inhibitors

KIT exon 9 Standard dose imatinibHigh dose imatinib

Sunitinib SunitinibHSP90 inhibitors

Wild-type Imatinib (poor response)

SunitinibNilotinibMasitinibIGF1R inhibitors

SunitinibNilotinibMasitinibIGF1R inhibitors

PDGFRA D842V (exon 18)

Imatinib (very poor) DasatinibHSP90 inhibitors

DasatinibHSP90 inhibitors

KITGleevec-Sunitinib-Dasatinib-Sorafenib-Nilotinib

PKC412-AMG706-MP470-HSP-90 inhibitors (indirect)

PI3KBEZ235-GDC0941

SF1125-XL765

AKTPerifosine

mTORRAD001-CCI779

AP-23573-Rapamycin

PKC-θ

RASR115777-SCH66336

RAF-1Sorafenib

MEK

MAPKBCL-2Gentasense

BCL-XL

BAD

Src/Fyn/LynDasatinib

STAT3

Survive-growSurvive Proliferate

VEGFR (antiangiogenesis)Sunitinib-AMG706-PKC412

Sorafenib-Avastin

Progress in understanding GIST Targets and Treatments

HSP90IPI504-BIIB021

AUY922-STA9090SNX5422

Other ReceptorsIGF1R (wild-type)AXL

HDACLBH589-SAHA

Gleevec Resistance: Median Time to Progression is 24 Months

ABOUT THE LIFE RAFT GROUP

Our Mission

LRG Member & GIST Patient Andrea Fuller

SURVIVAL

Patient Support

We intervene in cases where patients have needed to gain access to treatment, doctors and other life-saving options.

We consult with patients on individualized treatment issues.

Our monthly newsletter reaches thousands of patients, caregivers and medical professionals.

We hold “webcasts”, online video seminars that enable us to bring up-to-date information to the public by experts in the field.

We then archive these webcasts so that they can be viewed later at any time.

Webcasts

Clinical Trials Database We maintain an

extensive on-line Clinical Trials database to help patients and physicians stay informed about up-to-the-minute treatment options

 

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

Global Global GIST NetworkGIST Network The LRG has expanded and strengthened the Global GIST Network. Representativesare now available in 50 countries.

Global Outreach

The LRG will be launching an extensive Latin American initiative in 2010

CHALLENGES FOR CANCER RESEARCH

What’s wrong with this?

Treatment 

Improvement 

AvastinDoubled Progression Free Survival

Sorafenib44% longer life 

Radiotherapy53% longer life

ASCO 2007: “Major Research Advances in

Cancer Treatment”

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 to29 weeks

3 months

Issues with the Clinical Trials Process

The current system is:

Too slow

Too costly

Too ineffective

Studies have shown that “NCI cooperative groups routinely take 2 years to bring a trial from concept to active accrual, that nearly 60% of such trials opened for 5 years had fewer than five patients enrolled at each site, and that in more than 20% of the studies, not a single subject had been accrued.” (JNCI, 2009)

The LRG Response

LRG’S RESEARCH STRATEGY

GIST Research Strategy

Recruit a world class pre-clinical research teamCreate a strategic planEstablish agreement to collaborate and

coordinateMake longer grant commitmentsReduce overheadRequire in-person team meetings

GIST Research Strategy

Strengthen data sharing capacity of teamCreate Patient Registry with comprehensive

clinical histories across national and institutional boundaries

Expand researcher’s access to patient tissue through a GIST Collaborative Tissue Bank

Create link between lab-based research efforts and patient registry database

Build a GIST Clinical Trial Model

About the Patient Registry

LRG maintains a sophisticated patient database Over 1,200 patient-provided medical histories including mutational and plasma level testing

Data cuts across institutional and international boundaries

Secure, online access for research team

Patient Data linked to tissue bank

Comprehensive information is collected on every new patient including:DiagnosisEvaluationTreatment

About the Patient Registry

Other tabs :Current StatusTimeLineOutreach

About the Patient Registry

Other features:GistoryMass mailingStatisticsStudy GroupsClinical TrialTissue Bank

Outcomes

Unique information not being addressed by clinical trials Actual Dosage vs. Starting Dosage demonstrates that higher

doses are related both to longer progression-free survival and longer overall survival

Quality of life information supplements NCI toxicity-based side-effects data

Timely information that cannot wait for formal trial results

Outcomes Quality control of formal clinical trial data

Capture information which patient may not be willing to share with doctor

Complete GIST clinical histories not interrupted by change in medical care provider

Link patients clinical histories to their tissue samples to create unique resource for GIST researchers

What We Have Learned So Far

Patients/caregivers can reliably report treatment efficacy Shrinkage Stability Progression

Patients/caregivers can reliably report quality of life side-effects

Patients/caregivers can reliably report survival

GIST Collaborative Tissue Bank and the Patient Registry Partnership between Patients, GIST Researchers and the LRG

Patient Registry Patient-driven process GIST researchers share tissue and data

Efficient use of rare tissue Online access for researchers of de-identified clinical histories Research-generated data shared through Stanford Tissue Microarray

website (www.tma.stanford.edu) Maintains patient privacy and provides direct patient benefits including

free mutational testing

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

LRG’s Research Priorities

Research Budget

Annual research expenditure of $1,000,000 for the last 3 years.

We want to expand pre-clinical research to $2,000,000 per year

Invest an additional $10-15 million dollars to create a clinical trial consortium in 2012.

What We Are Looking For

People and companies that can think outside of the box and help us build a new model for finding the first cure for cancer

What We Are Looking For

Venture Philanthropists who want to support a better way to find a cure for cancer

Partnerships with investors and companies to bring drugs to market through a more efficient and effective clinical trials process

Feedback

Summary

1. We have a world class research team collaborating to implement a strategic plan.

2. We have made major progress in identifying mutational targets and treatments, including Gleevec.

3. We have access to a worldwide and motivated patient community.

Summary

4. We have the largest GIST patient medical database in the world and a collaborative tissue bank of rare GIST tumors.

5. We have the perfect cancer research model.

For More Information

Norman J. ScherzerExecutive Director973-837-9092nscherzer@liferaftgroup.orgwww.liferaftgroup.org