Novel Extracorporeal Device 'Amytrapper' To Remove Beta Amyloid In Alzheimer'sDisease

Abstract Alzheimer’s disease is the most common cause of dementia and fourth most common cause of death. Amyloid-beta (Aβ) plays a crucial role in initiation and progression of Alzheimer’s disease (AD). Removal of circulating Aβ would shift the equilibrium in Aβ levels between brain and blood towards blood. This shift would deplete brain amyloid levels and improve memory. Three commercial monoclonal antibodies Adecanumab (Biogen), Lacenumab (Eisai) and Donanemab (Eli Lilly) have been approved by the FDA after showing cognitive improvement by reducing amyloid. Recombinant Technologies [RT] has developed an extracorporeal apheresis device, namely, Amytrapper Catheter to sequester blood Aβ. The device is built on our IP-protected active pharmacological ingredient [API], a tetrameric retro-inverso (RI) peptide, named Amytrap peptide. The device is a medically viable catheter which is coated inside with the API. Amytrap peptide prevents Aβ self-aggregation by binding to a specific motif on Aβ that promotes its misfolding and self-aggregation. Amytrap peptide has been shown to bind both soluble and insoluble forms of amyloid efficiently with little side effects. The API is superior in that it is a small peptide, not an antibody and it does not trigger any immunological side effects. Previous research through SBIR phases I and II met or exceeded the intended goals. We completed the following quantitative milestones: 1) we obtained proof of concept for a prototype Amytrapper Catheter device in vitro. It bound and retained biotinylated Aβ42 (spiked) in a concentration dependent manner from circulating fluids including sera or plasma from mice, rat and humans, in vitro. 2) we have obtained in vivo proof of concept for the device in AD model rats. Blood amyloid reduction coupled with behavioral improvement was observed in these rats after catheter-apheresis. 3) we have obtained preliminary proof of concept with the device to remove native amyloid from blood samples of a small number of patients with AD. 4) Completed market research for the device by partnering with Bio Heath Innovations (MD) with the help of an NIA-sponsored TABA program which produced encouraging feedback from key opinion leaders including end users 5) We have raised outside funds through partnership with Start Engine Capital LLC via Regulation CF and we plan to continue this effort. This phase IIB proposal is a necessary and logical extension of our ongoing research and commercialization efforts that will bring the device from bench to the patient. We plan to improvise and optimize the Amytrapper catheter device. Reflecting on these goals, in this proposal, we plan: in aim 1. Scaled up synthesis (GLP grade), optimization and characterization of API, in aim 2. Fine-tune and improvise Amytrapper Catheter device utilizing amyloid-spiked human blood samples, in aim 3. Confirm preclinical POC on the streamlined catheter device by testing Amytrapper Catheter on blood samples from AD patients and in aim 4. Complete regulatory filing and FDA clearance for Amytrapper Catheter. We have partnered with Connecticut Innovations Inc, a local biotech venture investment firm and SA Capital Partners NY, to raise additional private funds. This phase 2B award is likely to attract a syndicate of investors to help us succeed in our commercialization efforts. At the end of this study, we would have completed an IDE (investigational new device exemption) with the FDA for an eventual first in human [FIH] study. We present well defined goals with realistic milestones and deliverables that is supported by established players and partners. We believe that removal of amyloid by this device in AD patients will significantly improve their living conditions and complement existing therapeutic regimen.