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A multitargeted nanocarrier inhibitor of undruggable transcription factors for treating castration resistant prostate cancer

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA257001-01A1
Agency Tracking Number: R41CA257001
Amount: $400,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 102
Solicitation Number: PA20-265
Solicitation Year: 2020
Award Year: 2021
Award Start Date (Proposal Award Date): 2021-06-01
Award End Date (Contract End Date): 2022-11-30
Small Business Information
Reston, VA 20190-5203
United States
DUNS: 828881305
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (703) 689-9689
Business Contact
Phone: (703) 689-9689
Research Institution
BOX 400195
United States

 Nonprofit College or University

Project Summary
This project addresses the critical need for treatments of castration resistant prostate cancer
(CRPC) by proposing to engineer and develop a novel, nanostructured pharmaceutical
(P-TRIS5) which will target tumor cells and deliver two potent, synergistic therapeutics (an
siRNA and a small molecule) to inhibit the androgen receptor and RUNX, two commonly
implicated transcription factors in CRPC.
We will study the new compound using in vitro and in vivo models that are well-established for
CRPC and seek to show 1) effective in vitro targeting and cellular uptake, and 2) effective
delivery and efficacy in two xenograft mouse models. Parabon NanoLabs has significant
experience in the development and validation of rationally designed, nanostructured
pharmaceuticals and will leverage existing infrastructure, expertise, and collaborations to
investigate the potential for the proposed CRPC targeted drug.
Our synthesis methodology begins with the design of P-TRIS5 using Parabon’s Essemblix™ Drug
Development Platform, a powerful combination of computer-aided design (CAD) software for
designing self-assembling DNA nanocarriers and proprietary nanofabrication methods for their
production. Next, the two therapeutics and a targeting peptide will be conjugated to the
nanocarrier using commercially available compounds and purified by standard protocols.
We will measure the performance of P-TRIS5 by monitoring a fluorescent label on the
compound for targeting (via fluorescent confocal microscopy in vitro) and tumor growth via
bioluminescent full-body live imaging. Off-target cytotoxicity will also be measured in vivo to
demonstrate selective targeting of the tumor. Post-mortem excised tissues will be analyzed to
determine the extent of inhibition of downstream targets in the animal model.
The success of this project will create new avenues to rationally design nanostructured
pharmaceuticals against many kinds of cancer. Our focus on CRPC, a prostate cancer with a
critical need for new therapies, is driven by an abundance of knowledge about the molecular
biology involved and the synergy formed by a combination of small molecules and siRNA to
target drivers of the most dangerous variants of this deadly disease.Project Narrative
This NIH STTR Phase I project will create a novel therapeutic for the treatment of castration
resistant prostate cancer (CRPC). The proposed therapeutic will incorporate targeting molecules
specific to prostate cancer that will enable it to bind and be taken up by prostate cancer cells.
The therapeutic will carry a dual payload to inhibit the activity of key CRPC transcription
factors, a class of proteins previously considered to be “undruggable.”

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

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