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2017 Annual Report

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Translating Discovery

Translating Discovery into Life-Changing Care When it comes to defeating cancer and Parkinson’s disease, collaboration is one of our strongest assets. That’s why Van Andel Research Institute (VARI) teamed up with Stand Up To Cancer, the American Association for Cancer Research, The Cure Parkinson’s Trust, The Michael J. Fox Foundation for Parkinson’s Research and other leading organizations, scientists and physicians — to see what we can do when our collective expertise and resources are combined. The result is a slate of clinical trials, critical steps on the road from the lab to the doctor’s office that ensure new treatments are safe and effective. If successful, these therapies could help improve the lives of millions of people suffering from these devastating diseases. Active clinical trials include the following. Cancer The VARI–SU2C Epigenetics Dream Team has six ongoing clinical trials at medical centers across the U.S. and in Copenhagen, Denmark. Two of these trials — non-small cell lung cancer and bladder cancer — are supported by two of 10 inaugural SU2C Catalyst ® grants, totaling nearly .5 million. The trials are evaluating new combination treatments for: Acute myeloid leukemia (AML), an aggressive blood cancer that is notoriously difficult to treat and has poor long-term survival. Bladder cancer, a tough-to-treat cancer that is the sixth most common type of cancer diagnosed in the U.S. *Supported by a SU2C Catalyst ® grant Metastatic colorectal cancer, the second leading cause of cancer death in men and women combined in the U.S. Myelodysplastic syndrome (MDS) and AML, which also are the subjects of a small pilot study that is investigating whether a simple addition to the standard care regimen may improve the current therapy’s ability to impede cancer cell growth and destroy cancer cells. This combination is also being explored in patients with clonal cytopenia of undetermined significance (CCUS) — thought to be a potential precursor to MDS in some patients. MDS and chronic myelomonocytic leukemia (CMML), two blood cancers that are incurable with current drugs and that may progress to AML, a much more aggressive cancer. Non-small cell lung cancer, the most common type of lung cancer, which accounts for more than 80 percent of cases. Lung cancers are a major public health problem and claim more lives annually than any other type of cancer. *Supported by a SU2C Catalyst ® grant 8 | VAN ANDEL INSTITUTE ANNUAL REPORT 2017

RESEARCH Parkinson's disease The Linked Clinical Trials (LCT) initiative, spearheaded by The Cure Parkinson’s Trust and supported by VARI, aims to shift the paradigm on Parkinson’s treatment from managing symptoms to slowing or stopping the disease’s progress. By investigating medications that are already approved to treat other conditions and that impact the same biological processes that are at play in Parkinson’s, scientists hope to cut the time it takes for new, more effective medications to be approved, getting them to the people who need them faster. Medications being investigated by LCT include the following. Ambroxol, a medication originally developed to treat respiratory ailments, which has shown promise in correcting an underlying molecular problem in Parkinson’s. Deferiprone, a medication that removes excess iron from the blood and that is being investigated for its potential to reduce high iron levels in the area of the brain most affected by Parkinson’s. EPI-589, an experimental drug originally designed to treat rare mitochondrial diseases in children. A growing body of evidence suggests similar dysfunctions in mitochondria, the power plants of cells, may also contribute to Parkinson’s. Exenatide, a Type 2 diabetes medication that has shown outstanding promise in lab experiments and clinical trials as a therapy that may slow the progression of Parkinson’s. Following positive results from a phase two trial reported in 2017, plans for a larger, phase three trial are in the works. Liraglutide, a Type 2 diabetes medication that belongs to a class of drugs called GLP-1 agonists and prompts the release of insulin, thereby lowering glucose levels in the blood when bound to its receptor. Recent findings suggest that when liraglutide activates these receptors in the brain, the drug provides protection against degenerative damage to key brain cells, specifically those affected in Parkinson’s disease. Nilotinib, a medication originally developed to treat the blood cancer leukemia. This multicenter trial is supported by The Michael J. Fox Foundation for Parkinson’s Research, The Cure Parkinson’s Trust and VARI. Simvastatin, a cholesterol-lowering medication that is part of the PD-STAT trial, which is underway at 21 medical centers across the United Kingdom. Learn more at vai.org/clinical-trials. VAN ANDEL INSTITUTE ANNUAL REPORT 2017 | 9

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