This grant is for systematically evaluating the diastereomeric composition and understanding the biological and pharmacological activity of each diastereomer of the FDA-approved siRNA drug, LEQVIO (Inclisiran). The research involves the stereochemically-controlled synthesis of pure LEQVIO diastereomers. Subsequently, their biological activity, specifically inhibiting PCSK9, will be assessed using in vitro assays and transgenic mouse models. The project also aims to develop robust analytical methods for identifying and characterizing the stereochemical structure of each diastereomer within LEQVIO. Ultimately, this research will determine the individual contribution of each diastereomer to LEQVIO’s overall pharmacological activity, providing valuable tools applicable to other GalNAc-conjugated siRNAs, aiding in generic siRNA evaluation and oligonucleotide drug quality control.
Opportunity ID: 344261
General Information
| Document Type: | Grants Notice |
| Funding Opportunity Number: | RFA-FD-23-012 |
| Funding Opportunity Title: | Synthesis and Biological Activity Assessment of Different Diastereomers in siRNA Drug LEQVIO (Inclisiran) (U01) Clinical Trial Not Allowed |
| Opportunity Category: | Discretionary |
| Opportunity Category Explanation: | – |
| Funding Instrument Type: | Cooperative Agreement |
| Category of Funding Activity: | Consumer Protection Science and Technology and other Research and Development |
| Category Explanation: | – |
| Expected Number of Awards: | 1 |
| Assistance Listings: | 93.103 — Food and Drug Administration Research |
| Cost Sharing or Matching Requirement: | No |
| Version: | Synopsis 1 |
| Posted Date: | Dec 01, 2022 |
| Last Updated Date: | Dec 01, 2022 |
| Original Closing Date for Applications: | Mar 22, 2023 |
| Current Closing Date for Applications: | Mar 22, 2023 |
| Archive Date: | Apr 21, 2023 |
| Estimated Total Program Funding: | $1,200,000 |
| Award Ceiling: | $1,200,000 |
| Award Floor: | $50,000 |
Eligibility
| Eligible Applicants: | Private institutions of higher education Others (see text field entitled “Additional Information on Eligibility” for clarification) County governments Native American tribal governments (Federally recognized) For profit organizations other than small businesses Independent school districts Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Special district governments Public and State controlled institutions of higher education Public housing authorities/Indian housing authorities City or township governments Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education Small businesses State governments Native American tribal organizations (other than Federally recognized tribal governments) |
| Additional Information on Eligibility: | Eligible OrganizationsHigher Education InstitutionsPublic/State Controlled Institutions of Higher EducationPrivate Institutions of Higher EducationThe following types of Higher Education Institutions are always encouraged to apply for FDA support as Public or Private Institutions of Higher Education:Hispanic-serving InstitutionsHistorically Black Colleges and Universities (HBCUs)Tribally Controlled Colleges and Universities (TCCUs)Alaska Native and Native Hawaiian Serving InstitutionsAsian American Native American Pacific Islander Serving Institutions (AANAPISIs)Nonprofits Other Than Institutions of Higher EducationNonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)For-Profit OrganizationsSmall BusinessesFor-Profit Organizations (Other than Small Businesses)Local GovernmentsState GovernmentsCounty GovernmentsCity or Township GovernmentsSpecial District GovernmentsIndian/Native American Tribal Governments (Federally Recognized)Indian/Native American Tribal Governments (Other than Federally Recognized)U.S. Territory or PossessionOtherIndependent School DistrictsPublic Housing Authorities/Indian Housing AuthoritiesNative American Tribal Organizations (other than Federally recognized tribal governments)Faith-based or Community-based OrganizationsRegional OrganizationsNon-domestic (non-U.S.) Entities (Foreign Institutions) |
Additional Information
| Agency Name: | Food and Drug Administration |
| Description: |
The purpose of this research is to systematically evaluate the diastereomeric composition of LEQVIO (Inclisiran), an FDA-approved, N-acetylgalactosamine (GalNAc)-conjugated siRNA drug, and to understand the biological/pharmacological activity of each diastereomer in LEQVIO through stereochemically-controlled synthesis and biological activity assessment using in vitro and animal models. The proposed studies will focus on 1) synthesis of each diastereomer of LEQVIO (Inclisiran) in stereochemically pure form; 2) assessment of the biological activity of each stereochemically pure diastereomer in inhibiting PCSK9 activity using in vitro assays and in a transgenic mouse model; 3) development of analytical methods to identify and characterize the stereochemical structure of each diastereomer in LEQVIO; and 4) assessment of the individual contribution of each diastereomer to the overall pharmacological activity of LEQVIO. Tools developed in this research can also be applied to other similar GalNAc-conjugated siRNAs specifically, and other siRNAs in general. Knowledge gained from this research will also contribute to the sameness evaluation of generic siRNAs, and to the quality control of oligonucleotide drugs. |
| Link to Additional Information: | FULL ANNOUNCEMENT |
| Grantor Contact Information: | If you have difficulty accessing the full announcement electronically, please contact:
Shashi Malhotra
Grants Management Specialist Phone 2404027592 Email:shashi.malhotra@fda.hhs.gov |
Version History
| Version | Modification Description | Updated Date |
|---|---|---|
Related Documents
Folder 344261 Full Announcement-NOFO -> FINAL-RFA-FD-23-012.pdf
Packages
| Agency Contact Information: | Shashi Malhotra Grants Management Specialist Phone 2404027592 Email: shashi.malhotra@fda.hhs.gov |
| Who Can Apply: | Organization Applicants |
| Assistance Listing Number | Competition ID | Competition Title | Opportunity Package ID | Opening Date | Closing Date | Actions |
|---|---|---|---|---|---|---|
| 93.103 | RFA-FD-23-012 | FORMS H | PKG00278684 | Nov 28, 2022 | Mar 22, 2023 | View |
Package 1
Mandatory forms
344261 RR_SF424_5_0-5.0.pdf
344261 PHS398_CoverPageSupplement_5_0-5.0.pdf
344261 RR_OtherProjectInfo_1_4-1.4.pdf
344261 PerformanceSite_4_0-4.0.pdf
344261 RR_KeyPersonExpanded_4_0-4.0.pdf
344261 RR_Budget_3_0-3.0.pdf
344261 PHS398_ResearchPlan_5_0-5.0.pdf
344261 PHSHumanSubjectsAndClinicalTrialsInfo_3_0-3.0.pdf
Optional forms
344261 RR_SubawardBudget30_3_0-3.0.pdf
344261 PHS_AssignmentRequestForm_3_0-3.0.pdf
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