Mesothelioma Applied Research Foundation www.curemeso.org



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Mesothelioma Applied Research Foundation www.curemeso.org

Board of Directors Michael Becich PhD Gen. Steven Blum Lee Krug MD David Ettinger MD Axel Ranier Richard Mosca Erica Iacono Terry Lynch Hanne Minz Michael Lagana Jocelyn Farrar DNP Ted Lackner Leon Pendarvis

Descriptors Board Board Members are selected to represent the stakeholders in mesothelioma Three attributes are considered of high importance time, talent and capacity to advance the mission Advocates bring additional talent to board in addition to their personal relationship to the disease

Scientific Advisory Board Dr. Lee Krug Dr. Raffit Hassan Dr. Michele Carbone Dr. Steven Albelda Dr. Edward Levine Dr. Robert Taub Dr. Anne Tsao Dr. Petr Hausner Dr. Anna Nowak Dr. Steven Mutsaers Dr. Jeremy Steele Dr. Marc De Perrot Dr. Hedy Lee Kindler

Challenges in MPM Clinical Trials Mesothelioma is a rare disease, and as a result.. Large trials take a long time to complete Less research funding available so fewer investigators interested Less interest by pharma companies due to low profitability

But there is a need Mesothelioma has an extremely high rate of relapse after surgical resection Pemetrexed + cisplatin is the only FDAapproved chemotherapy regimen for advanced disease Improves median survival by 3 months Disease ultimately progresses after treatment Very limited data on the efficacy of second-line therapy

Approaches for Development of Novel MPM Therapies Adjuvant: After surgery or combined modality therapy First-line: Add new agent in combination with pemetrexed / cisplatin Develop new regimen Maintenance: After treatment with pemetrexed / cisplatin to maintain response Second-line: At progression after 1 st line therapy

The Clinical Trial Process Preclinical: Discover new compounds in the laboratory. Assess their efficacy and toxicity in animals. Phase I: Administration of new drugs or combinations of drugs to patients to determine safety and proper dose Phase II: Use one dose in a select patient population to determine efficacy Phase III: Compare new treatment to standard therapy by randomization 15 Y E A R S

What Needs To Be Done? 1. Unify the strong voices from patients and their families 2. Expand funding opportunities 3. Encourage collaboration among investigators 4. Increase enrollment on clinical trials 5. Develop a patient registry The Meso Foundation is helping with all of these needs

1. Unify the strong voices from patients and their families Symposium brings community together for education and support Lobbying on Capitol Hill for asbestos legislation Establishment of Mesothelioma Awareness Day (September 26)

2. Expand funding opportunities The Meso Foundation has provided $7.6 million in grants to researchers High level peer review process by the Scientific Advisory Board This seed money has allowed submission of larger grants to other funding sources Solicitation with members in Congress led to grant appropriations through the Department of Defense 4 DOD meso grants, all previously funded by Meso Foundation

Advocacy Efforts As a direct result of Foundation s advocacy, the Department of Defense (DoD) has awarded a total of $8.8 million to mesothelioma research since 2008

WT-1 Peptide Vaccine Initial Pilot Trial WT1 is a tumor suppressor gene highly expressed in mesothelioma We developed a vaccine comprised of 4 modified peptides that would induce an immune response against WT1 We conducted a pilot trial in patients with MPM to show that it was safe and immunogenic SUPPORTED BY $100,000 GRANT FROM MESO FOUNDATION

WT-1 Peptide Vaccine Adjuvant Study Design Malig Pleural Meso WT-1 positive 4-12 weeks since completion of multi-modality treatment including surgery PS > 70% R A N D O M I Z E Specific Immunotherapy: WT-1 vaccine / Montanide + GM-CSF Non-specific Immunotherapy: Montanide + GM-CSF Primary endpoint: 1-year PFS Aim to increase from 50% to 70% N=78 patients (39 per arm) SUPPORTED BY $1.5 MILLION GRANT FROM DEPT OF DEFENSE

3. Encourage collaboration among investigators Annual Symposium brings researchers together Support of the National Mesothelioma Virtual Bank Involvement in the SPORE grant application

4. Increase enrollment on clinical trials Meso Foundation provides a resource for patients, and refers patients to appropriate centers for trials Future establishment of a mesothelioma clinical trials consortium

Ongoing (or Recently Completed) Large Clinical Trials in Advanced MPM Drug Line Phase Sponsor Bevacizumab 1 st with pem/cis II/III French Intergroup CBP 501 1 st with pem/cis RP II CanBas Cediranib 1 st with pem/cis I/II SWOG Everolimus 2 nd or 3 rd II SWOG MORAb-009 1 st with pem/cis II Morphotek NGR-hTNF Maintenance RP II MolMed Thalidomide Maintenance III Netherlands Cancer Institute Vorinostat 2 nd or 3 rd III Merck WT-1 vaccine Adjuvant RP II MSKCC

The Meso Foundation is the only 501 (c)3 non-profit that: The Meso Funds leading peerreviewed research Provides complimentary educational and support resources Advocates for increased federal funding of mesothelioma research

Conclusions Despite many hurdles, advances are being made in the treatment of mesothelioma, but too slowly Collaboration across institutions is necessary to more rapidly develop ideas and to complete large studies Support from patients and foundations will increase the chance of success