EnVivo initiates EVP-0962 GSM Phase 1 clinical trial for Alzheimer’s disease

EnVivo Pharmaceuticals, a company dedicated to developing a broad range of novel central nervous system (CNS) therapies, announced today that it recently initiated a Phase 1 clinical trial of EVP-0962, its potent and selective gamma secretase modulator (GSM), in healthy volunteers. The trial is a double-blind, ascending single and multiple dose study designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and food effect of EVP-0962. To date, EVP-0962 has shown promising activity in preclinical cellular and transgenic models of Alzheimer's disease.

“This launch of our clinical studies of EVP-0962 marks an important step forward for the program as we continue to build upon our foundation of encouraging preclinical data”

"This launch of our clinical studies of EVP-0962 marks an important step forward for the program as we continue to build upon our foundation of encouraging preclinical data," said Dana C. Hilt, M.D., senior vice president, clinical development and chief medical officer of EnVivo. "In preclinical studies, EVP-0962 has demonstrated a significant reduction in amyloid plaques, which are believed to be a cause of Alzheimer's disease, and reversed behavioral deficits. We are encouraged by these findings and believe that gamma secretase modulators like EVP-0962 could represent the next generation of novel, disease modifying treatments for patients with Alzheimer's."

EVP-0962 is a proprietary small molecule that has been shown to selectively modulate gamma secretase, a key enzyme involved in the processing of amyloid and its toxic AB1-42 peptide, which is a key component of amyloid plaques in the brain. In a one-year preclinical study in transgenic Alzheimer's models, EVP-0962 reduced AB1-42 peptide levels, decreased amyloid plaque build up, reversed behavioral deficits and reduced brain inflammation associated with Alzheimer's disease. These findings were presented at the Alzheimer's Association 2010 International Conference on Alzheimer's Disease (ICAD). As EVP-0962 is a selective GSM and does not inhibit other gamma secretase substrates required for normal function (such as Notch), it is believed that it could demonstrate efficacy comparable to gamma secretase inhibitors, but with a more attractive safety profile.

The EVP-0962 program is part of EnVivo's broader efforts to leverage novel mechanisms of action to treat CNS diseases like Alzheimer's disease by altering the progression of disease and providing improvement in cognitive and overall function. This Phase 1 trial of EVP-0962 joins EnVivo's currently ongoing Phase 2b clinical trial of its lead alpha-7 agonist program, EVP-6124, which is a selective, potent, oral compound being developed as a long-term treatment to restore and improve cognitive function with sustained effect in patients with Alzheimer's disease. EVP-6124 has been shown to enhance synaptic transmission in the brain and act as a co-agonist in combination with Acetylcholine (ACh) to enhance cognition. The potentially synergistic effect of EVP-6124 and Acetylcholinesterase inhibitors (AChEIs) could further enhance the efficacy of EVP-6124 while minimizing the known dose-limiting side effects of currently available AChEI-based therapy. Data from the ongoing Phase 2b clinical trial of EVP-6124 are expected in early 2012.

Alzheimer's disease (AD) is a complex neurodegenerative disease characterized by abnormal protein deposits - amyloid plaques (containing the AB1-42 peptide) and neurofibrillary tangles (containing tau protein) - in the brain. Over time, AD leads to cellular loss and dysfunction, a gradual loss of memory, problems with reasoning or judgment, disorientation, difficulty in learning, loss of language skills, and decline in the ability to perform routine tasks. There are currently 5.3 million people in America with AD - or one in eight Americans over age 65 - and that number is projected to rise to 13.5 million by 2030.