Vitae is committed to creating superior products for important medical needs. Using our CONTOUR™ platform, we have rapidly advanced a broad portfolio of preclinical candidates that target major therapeutic categories including cardiovascular, metabolic, inflammation, cancer and CNS diseases.

Key programs in Vitae's Pipeline:

CARDIOVASCULAR: HYPERTENSION

Unmet Medical Need – Hypertension has long been known to directly and significantly contribute to the risk of heart disease and stroke. Today, nearly 70 million Americans suffer from hypertension; nearly half of all those diagnosed are inadequately controlled. By the end of this decade, the number of people in the United States suffering from hypertension is estimated to grow to nearly 100 million. Hypertension represents the single most valuable therapeutic category, with global sales in 2005 of approximately $40 billion.

Our Approach – Vitae is developing orally available renin inhibitors for management of hypertension and end-organ protection. Renin, an aspartyl protease, is the rate-limiting enzyme in the renin-angiotensin system (RAS) which plays a key role in regulating blood volume, arterial pressure and vascular function. Renin cleaves angiotensinogen into angiotensin, which is further processed into the vasopressor peptide, angiotensin II (ATII). Clinical studies have demonstrated that inhibition of renin can effectively control blood pressure. Renin inhibitors are desirable therapeutic agents, since they may possess increased efficacy with fewer side effects than existing therapies that target downstream events in the RAS cascade and prove superior to current therapies.

Cracking the Renin Challenge – The search for clinically acceptable renin inhibitors has lasted over 30 years. Historically, renin inhibitor programs have largely been unsuccessful in finding orally available small molecule compounds suitable for development. The first renin inhibitor, aliskiren, was approved by the FDA in March 2007. We have used our proprietary technology to generate potent, non-peptidic renin inhibitors that have been characterized in vitro and in vivo. In less than 12 months, Vitae discovered multiple series of novel, orally bioavailable and efficacious, small molecule inhibitors of this critical and challenging enzyme. Our goal is to develop a best-in-class compound.

Download Hypertension Fact Sheet

METABOLIC: DIABETES

Unmet Medical Need – Nearly 30 million adults suffer from Type 2 diabetes in the United States; 194 million worldwide. That number is expected to nearly double in the next twenty years. One in four Americans suffer from obesity/diabetes; in addition, over 40 million people are diagnosed in the pre-diabetic state. An aging population, sedentary lifestyle and rapidly growing incidence of obesity are all contributing to the dramatic rise in prevelance of diabetes, of which over 90% have Type 2 diabetes. The current U.S. market exceeds $10 billion, and is predicted to grow to $45 billion by 2020.

Our Approach – Vitae's lead diabetes program targets 11β HSD-1, an enzyme critical in the production of cortisol. The similarities between patients with cortisol excess, Cushing's syndrome, and those with obesity highlight the important role that glucocorticoids (GC) play in the control of metabolism. Recent experiments support this hypothesis. Overexpression of 11β HSD-1 in murine adipose leads to a metabolic syndrome-like phenotype, including increased central obesity, hypertension, impaired glucose tolerance, and hypertriglyceridemia. In contrast, 11β HSD-1 knockout (KO) mice resist visceral obesity and diabetes through improved liver and adipose tissue function, consistent with the beneficial effects of selective enzyme inhibition. These data indicate that elevated adipose or liver 11β HSD-1 is detrimental for metabolic control. Pharmacological inhibition of 11β HSD-1 represents an attractive therapeutic target for diabetes and treating cardiovascular effects associated with the metabolic syndrome.

Download Diabetes Fact Sheet

CANCER

Unmet Medical Need – Cancer is the second leading cause of death in the U.S. According to the American Cancer Society, approximately 1 million new cases of cancer are diagnosed each year. The National Cancer Institute estimates annual direct medical costs for cancer treatment to be $40 billion in the United States.

Our Approach – Vitae has discovered a series of potent inhibitors of Aurora A and B. These compounds display activity across a wide range of tumor types with potencies superior to current clinical stage compounds. Aurora A and Aurora B are structurally related serine/threonine protein kinases that are essential for mitosis (cell division). Aurora A acts early in mitosis and is important in formation of the mitotic spindles. Aurora A is oncogenic, directly causing cell transformation. The Aurora A gene is amplified and overexpressed in cancers from multiple tissue types. Inhibition or inactivation of Aurora A delays mitotic entry, resulting in the accumulation of cells in the G2/M cell cycle phase with rapid induction of apoptosis (programmed cell death). Aurora B has a role in chromosome movement, signaling of the spindle checkpoint, and cytokinesis (cell division). Aurora B, like A, is also overexpressed in many human tumors. Inhibition of Aurora B prevents proper alignment of chromosomes, inhibits cytokinesis, and results in the formation of multinucleated cells that undergo apoptosis over time.

CNS: ALZHEIMER'S DISEASE

Unmet Medical Need – Alzheimer's disease (AD) is the most common form of dementia in adults. It is estimated to affect 4.5 million American's and over 30 million worldwide with an average course of 8 -12 years. It is projected that the prevalence of AD will double over the next 20 years. The current U.S. market is approximately $3 billion per year, and estimated to double by 2010.

Our Approach – Vitae is developing orally active inhibitors of BACE1 for the treatment of Alzheimer's Disease. AD is a progressive neurodegenerative disorder characterized by deposition of plaques in the brain with aging dementia. The amyloid-β peptide is the major component of the plaques. Amyloid-β is generated from amyloid precursor protein (APP) by proteolytic processing of beta and gamma secretases. β-secretase (β-site APP cleaving enzyme 1, BACE1), is essential for amyloid-β biosynthesis. Since BACE1 cleavage of APP is critical in amyloidosis, inhibition of BACE1 would be an attractive strategy to ameliorate amyloid-β deposition in AD. Supporting this notion are studies demonstrating that deletion of BACE1 prevents amyloid-β secretion in cultured neurons and in brain. In addition, young (before amyloid-β deposition) mutant APP mice lacking BACE1 do not develop memory deficits. Inhibitors that block BACE1 will prevent the build up of beta-amyloid plaques and may help slow or stop the progression of disease.

Download Alzheimer's Fact Sheet

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