2321926
Project Grant
Overview
Grant Description
SBIR PHASE I: CELL-PENETRATING MONOBODIES TARGETING ONCOGENIC KRAS -The broader impact of this Small Business Innovation Research (SBIR) Phase I project lies in technological development of a new pharmaceutical intervention called cell-penetrating monobodies (CPM). The validation of this new CPM intervention will be demonstrated by designing potent and selective CPM-based inhibitors targeting certain cancers.
The success of this project will establish a powerful pharmaceutical technology for designing personalized therapies to treat the oncogenic mutant-driven lung, pancreatic, and colorectal cancers, where treatment options are extremely limited. This project will also enhance the academia-industry partnership, strengthen a burgeoning life science ecosystem in the Buffalo area, and develop a globally competitive STEM workforce for the Western New York region.
The proposed project addresses a critical barrier in the clinical translation of monobodies - a class of powerful tool biologics that are not cell-permeable despite their small size. The CPM technology overcomes this barrier by combining orthogonal crosslinking ? a proprietary method to rigidify monobody structure through site-specific inter-strand crosslinking - with monobody surface supercharging.
As a result, the CPM technology potentially possesses several innovative features: 1) genetic modifications facilitate recombinant production of CPM in bacteria both at research scale and for manufacturing; 2) high binding affinity and specificity toward intracellular oncogene targets can be readily obtained using well-established display technologies; and 3) robust cytosolic transport efficiency can be obtained owing to the rigid scaffold and tunable surface charge.
This project aims to unlock the commercial value of CPM technology by identifying potent and selective inhibitors oncogenic KRAS mutants that proved to be elusive with the small-molecule approach. Extensive optimizations of charge distribution and physicochemical properties will be performed using a reported monobody-based KRAS inhibitor as a template, with a goal to identify one CPM with sub-micromolar inhibitory activity in the KRAS mutant-harboring cell lines.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. - Subawards are not planned for this award.
The success of this project will establish a powerful pharmaceutical technology for designing personalized therapies to treat the oncogenic mutant-driven lung, pancreatic, and colorectal cancers, where treatment options are extremely limited. This project will also enhance the academia-industry partnership, strengthen a burgeoning life science ecosystem in the Buffalo area, and develop a globally competitive STEM workforce for the Western New York region.
The proposed project addresses a critical barrier in the clinical translation of monobodies - a class of powerful tool biologics that are not cell-permeable despite their small size. The CPM technology overcomes this barrier by combining orthogonal crosslinking ? a proprietary method to rigidify monobody structure through site-specific inter-strand crosslinking - with monobody surface supercharging.
As a result, the CPM technology potentially possesses several innovative features: 1) genetic modifications facilitate recombinant production of CPM in bacteria both at research scale and for manufacturing; 2) high binding affinity and specificity toward intracellular oncogene targets can be readily obtained using well-established display technologies; and 3) robust cytosolic transport efficiency can be obtained owing to the rigid scaffold and tunable surface charge.
This project aims to unlock the commercial value of CPM technology by identifying potent and selective inhibitors oncogenic KRAS mutants that proved to be elusive with the small-molecule approach. Extensive optimizations of charge distribution and physicochemical properties will be performed using a reported monobody-based KRAS inhibitor as a template, with a goal to identify one CPM with sub-micromolar inhibitory activity in the KRAS mutant-harboring cell lines.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. - Subawards are not planned for this award.
Awardee
Funding Goals
THE GOAL OF THIS FUNDING OPPORTUNITY, "NSF SMALL BUSINESS INNOVATION RESEARCH (SBIR)/ SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAMS PHASE I", IS IDENTIFIED IN THE LINK: HTTPS://WWW.NSF.GOV/PUBLICATIONS/PUB_SUMM.JSP?ODS_KEY=NSF23515
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Getzville,
New York
14068-1463
United States
Geographic Scope
Single Zip Code
Covalabio was awarded
Project Grant 2321926
worth $275,000
from National Science Foundation in March 2024 with work to be completed primarily in Getzville New York United States.
The grant
has a duration of 1 year and
was awarded through assistance program 47.084 NSF Technology, Innovation, and Partnerships.
The Project Grant was awarded through grant opportunity NSF Small Business Innovation Research / Small Business Technology Transfer Phase I Programs.
SBIR Details
Research Type
SBIR Phase I
Title
SBIR Phase I: Cell-penetrating monobodies targeting oncogenic KRAS
Abstract
The broader impact of this Small Business Innovation Research (SBIR) Phase I project lies in technological development of a new pharmaceutical intervention called cell-penetrating monobodies (CPM). The validation of this new CPM intervention will be demonstrated by designing potent and selective CPM-based inhibitors targeting certain cancers. The success of this project will establish a powerful pharmaceutical technology for designing personalized therapies to treat the oncogenic mutant-driven lung, pancreatic, and colorectal cancers, where treatment options are extremely limited. This project will also enhance the academia-industry partnership, strengthen a burgeoning life science ecosystem in the Buffalo area, and develop a globally competitive STEM workforce for the Western New York region.
The proposed project addresses a critical barrier in the clinical translation of monobodies - a class of powerful tool biologics that are not cell-permeable despite their small size. The CPM technology overcomes this barrier by combining orthogonal crosslinking a proprietary method to rigidify monobody structure through site-specific inter-strand crosslinking - with monobody surface supercharging. As a result, the CPM technology potentially possesses several innovative features: 1) genetic modifications facilitate recombinant production of CPM in bacteria both at research scale and for manufacturing; 2) high binding affinity and specificity toward intracellular oncogene targets can be readily obtained using well-established display technologies; and 3) robust cytosolic transport efficiency can be obtained owing to the rigid scaffold and tunable surface charge. This project aims to unlock the commercial value of CPM technology by identifying potent and selective inhibitors oncogenic KRAS mutants that proved to be elusive with the small-molecule approach. Extensive optimizations of charge distribution and physicochemical properties will be performed using a reported monobody-based KRAS inhibitor as a template, with a goal to identify one CPM with sub-micromolar inhibitory activity in the KRAS mutant-harboring cell lines.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
Topic Code
PT
Solicitation Number
NSF 23-515
Status
(Complete)
Last Modified 3/5/24
Period of Performance
3/1/24
Start Date
2/28/25
End Date
Funding Split
$275.0K
Federal Obligation
$0.0
Non-Federal Obligation
$275.0K
Total Obligated
Activity Timeline
Additional Detail
Award ID FAIN
2321926
SAI Number
None
Award ID URI
SAI EXEMPT
Awardee Classifications
For-Profit Organization (Other Than Small Business)
Awarding Office
491503 TRANSLATIONAL IMPACTS
Funding Office
491503 TRANSLATIONAL IMPACTS
Awardee UEI
WQNNR7LE5Y99
Awardee CAGE
None
Performance District
NY-26
Senators
Kirsten Gillibrand
Charles Schumer
Charles Schumer
Modified: 3/5/24