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Molecular brush-conjugated antisense oligonucleotide as a pan-KRAS depletion agent

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R42CA275425-02
Agency Tracking Number: R42CA275425
Amount: $1,030,054.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: NCI
Solicitation Number: PA21-262
Timeline
Solicitation Year: 2021
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-01
Award End Date (Contract End Date): 2025-08-31
Small Business Information
13 ELIOT ST
Natick, MA 01760-6040
United States
DUNS: 117142176
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 KE ZHANG
 (617) 373-2000
 k.zhang@neu.edu
Business Contact
 KE ZHANG
Phone: (617) 373-2000
Email: pacdnatx@gmail.com
Research Institution
 NORTHEASTERN UNIVERSITY
 
360 HUNTINGTON AVE, 177-500
BOSTON, MA 02115-5005
United States

 Nonprofit College or University
Abstract

Project Summary/Abstract
Mutant forms of KRAS are a key driver in human tumors but remain partially refractory to therapeuticintervention. After over three decades of research, only a single inhibitor (sotorasib) targeting a singlemutation (KRASG12C) have reached market. The difficulty for developing small molecule KRAS inhibitorshas heightened the importance of alternative methods targeting the oncogene. One such strategyinvolves therapeutic nucleic acids, which make it possible to deplete target proteins that are intractable toconventional drug modalities. We have developed a novel form of nucleic acid therapeutics, termedBrushield™ conjugate, which substantially enhances the antitumor activity of antisense oligonucleotides
by elevating in vivo stability, accelerating cellular uptake, and improving plasma pharmacokinetics andtumor accumulation, allowing for a much lower dosage to be used compared to conventional methods.The conjugate also suppresses nearly all side effects associated with traditional nucleic acid drugs byreducing unwanted nucleic acid-protein interactions. The goal of this proposal is to lay the groundworkfor translating the technology towards the clinic. In Phase I, we will optimize the structure of theBrushield™ conjugate, and enhance current indication using a panel of non-small cell lung cells andmouse xenograft models. Upon reaching set quantitative milestones, we will subject the conjugate tomore relevant animal models (orthotopic and patient-derived xenograft models), and perform tolerability
and pharmacokinetic studies in mice and monkeys (Phase II). These studies will allow us to pursue anIND filing at the end of the project.

* Information listed above is at the time of submission. *

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