A Disease Modifying Drug Candidate for Alzheimer’s Disease
In collaboration with the Mount Sinai School of Medicine (Mt. Sinai), we are developing NIC5-15 as a drug to treat the cause, rather than just the symptoms, of Alzheimer’s disease. This compound, currently in a Phase II trial, has been shown in preclinical studies and animal models to be effective in preventing the formation of beta-amyloid plaques, which are believed to be a leading cause of Alzheimer’s disease. Multiple clinical studies in non-Alzheimer’s populations have demonstrated the safety and phamacokinetics of NIC5-15.
NIC5-15 is a non-synthetic single molecular agent that we believe has the potential to prevent or slow the progression of Alzheimer’s disease. It has the ability to prevent the formation of amyloid plaque through selective inhibition of certain insulin mechanisms and a key enzyme called gamma secretase. NIC5-15 is being developed as an oral drug for daily chronic administration.
We have entered into exclusive license and research agreements with Mt. Sinai to further develop and commercialize NIC5-15 to combat Alzheimer’s disease. Under the license agreement, we have exclusive rights covered by pending patent applications for NIC5-15. Mt. Sinai is a leading NIH-funded clinical research center for Alzheimer’s disease.
An estimated 4.5 million Americans have Alzheimer’s disease and 18 million are afflicted worldwide. The market in the U.S. for drugs to treat Alzheimer’s disease is estimated to be $2 billion, with the worldwide market in excess of $4 billion. There are no drugs approved for use that can prevent or reduce amyloid plaques. For more information on Alzheimer’s disease, click here.
NIC5-15 - Mechanism of Action
NIC5-15 has shown promise as an orally administered agent for the prevention of beta-amyloid plaques in preclinical experiments conducted at the Mount Sinai School of Medicine. Additional in-vitro and in-vivo experiments have confirmed that the mechanism of action through which it achieves this effect is through the selective inhibition of gamma secretase activity targeting Amyloid Precursor Protein or APP. NIC5-15 achieves this effect by directly inhibiting gamma secretase and also through an indirect inhibition via its actions involving insulin sensitization. Our preclinical studies confirm that NIC5-15 has the unique ability of specifically inhibiting gamma secretase activity without influencing the generation of the Notch cleavage product Notch-1. The ability to spare Notch is a significant finding that points to the potential favorable safety profile of NIC5-15 in chronic administration.
NIC5-15 - Preclinical testing
NIC5-15 has been the subject of multiple preclinical studies for the assessment of toxicology, safety, pharmacokinetics, mechanism of action, and proof of efficacy. Preclinical assessments for mutagenicity, acute safety, and chronic safety have been completed and reveal a very favorable safety profile. Preclinical research has also been completed demonstrating that NIC5-15 has an ability to enhance glucose transport intracellularly via a mechanism that is independent of insulin.
In extensive preclinical testing at the Mount Sinai School of Medicine, NIC5-15 was found to selectively inhibit the enzyme gamma secretase and reduce amyloidogenic Ab1-40 peptide without influencing the generation of the Notch cleavage product Notch-1 in in vitro cell culture. Later in vivo studies in an AD mouse model revealed that orally administered NIC5-15 positively influenced memory impairment and significantly reduced the amount of amyloidogenic Ab1-40 and Ab1-42 peptide in the brains of these mice.
NIC5-15 - Clinical Studies
Six clinical studies have been performed with NIC5-15, which have demonstrated the safety of orally administered NIC5-15 in addition to a known pharmacokinetic profile for the compound. These clinical studies were in non-Alzheimer’s populations.
