Q: What are the main areas of progress in Alzheimer's research?
Dr. Daniel G. Chain: The development of sensitive brain imaging techniques such as structural MRI to measure brain atrophy, FDG-PET to measure glucose metabolism, and PET amyloid imaging agents represent some of the most important recent advances in the field laying the foundation for studies such as by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Dominantly Inherited Alzheimer's Network (DIAN) that provided extremely valuable information regarding the sequence of changes preceding and leading to AD. In fact, these studies led to a new way to think about the disease in which presymptomatic AD is just as much a disease state as symptomatic disease.
Q: Describe the main programs at Intellect Neurosciences.
Dr. Daniel G. Chain: Intellect has four main programs underway at the moment: CONJUMAB-A, TAUC3, TOC-1 and RVO3.
We are pioneering the use of antibody-drug conjugates and bi-specific vaccines for the treatment and prevention of multifactorial neurodegenerative conditions such as Alzheimer's disease, Huntington's disease and age-related macular degeneration. Increasingly we hear researchers emphasizing the need to target more than one disease component where, for example, Aβ, tau protein and oxidative stress act in concert and synergistically causing irreversible damage to nerve cells. The use of combination therapies may even allow intervention after symptoms have begun in contrast to monotherapies, targeting only Aβ, for example. However, regulators are averse to the idea of combining two independent investigational drugs before testing each one singly in human clinical trials and demonstrating clinical benefit. That issue is circumvented by the use of antibody drug conjugates in which two different molecules are combined chemically into a single entity as is the case with our CONJUMAB platform.
I am excited about the therapeutic potential of CONJUMAB-A, our lead preclinical program which I believe offers important advantages to other Aβ antibodies currently in clinical development. All the other antibodies e.g. solanezumab, bapineuzumab, gantenerumab and crenzeumab are designed for a single purpose, namely to clear Aβ from the brain. None of these antibodies act on secondary neurotoxic mechanisms such as oxidative stress which causes most of the damage from Aβ. By contrast, CONJUMAB-A, an antibody drug conjugate, is empowered with additional neuroprotective properties to alleviate the damage while also potentially enhancing the clearance of Aβ. In principle our approach could be applied to improve many different types of antibodies including those that previously disappointed in clinical trials. However, we are currently focused on optimizing CONJUMAB-A using our own antibody IN-N01 which targets the N-terminus of Aβ. We believe IN-N01 to be superior to bapineuzumab because of its reduced potential to cause inflammation which results from our reengineering of the originally produced IG1 class antibody into an IgG4 class antibody. We believe this safety feature is particularly important for antibodies that bind Aβ aggregates and not just soluble single monomeric Aβ. Among several potential indications, we have decided to focus on age related macular degeneration (AMD) for proof of concept studies since AMD and AD share several similarities while the eye offers less challenge for delivering the drug.
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