Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

First-in-class TREM-1 inhibitors for neovascular retinal diseases

Award Number: R44EY034015
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

First-in-class TREM-1 inhibitors for neovascular retinal diseases - Project Summary/Abstract Retinal neovascularization (RNV) is a major cause of vision loss in retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion. In the US, about 16,000 of premature infants are affected by ROP annually and about 4.1 million adults years have DR. Complications of conventional treatments suggest an unmet need for new therapies. The long-term objective of this project is to develop a systemic, new mechanism-based, efficient and well-tolerable therapy for ROP and other RNV diseases. Triggering receptor expressed on myeloid cells (TREM-1) is upregulated upon inflammation and is involved in angiogenic signaling pathways, suggesting TREM-1 as a promising target for treatment of RNV. Current TREM-1 inhibitors all attempt to block binding of TREM-1 to its still uncertain ligand(s). To minimize clinical failure risks, we developed well-tolerable TREM-1 inhibitory peptides GF9 and GA31 that employ a novel, ligand-independent mechanism of action. They can be used in a free form or formulated in macrophage-specific lipopeptide complexes (LPC) to improve half-life and reduce off-target risks. Previously, we showed that ligand-independent TREM-1 blockade using either a free (GF9) or LPC- formulated peptide (GA31-LPC): 1) prevents and treats RNV in mice with oxygen-induced retinopathy (OIR); 2) improves vessel sprouting during hypoxia, 3) inhibits retinal TREM-1 and CSF-1 expression, and 4) reduces cytokine release (TNFα, IL-1β, IL-6 and CSF-1) in vitro, while control peptides have no effect. The goal of the proposed project is to further develop this first-in-class TREM-1 therapy for neovascular retinal diseases. Considering pros and cons of GF9 and GA31-LPC, we suggest to start with both leads. Due to differences in the manifestation of vascular phenotypes, we suggest to use both OIR mice and rats. Phase I aims are to: 1) generate GMP-compliant formulations of free GF9 and GA31-LPC and test them in vitro, and 2) test the developed formulations of GF9 and GA31-LPC in the OIR mouse model. GMP-friendly tangential flow filtration technique to prepare GA31-LPC will be explored. Phase II aims are to: 1) develop an LC-MS-assay to measure GF9 and GA31 in ocular tissues, 2) test pharmacokinetics and ocular tissue distribution of GF9 and GA31-LPC in vivo, 3) test the preventative and therapeutic effects of GF9 and GA31-LPC in two OIR models and select the lead, and 4) test the lead in non-clinical toxicology studies. Comprehensive histology/IHC will be performed. Cytokines will be tested. Follow-up Phase IIb will include other administration and combination (eg, laser + GF9) regimens, GLP- TOX, ADME, CMC and other IND-enabling studies. The final product will represent safe and stable systemic therapy. Its anticipated safety is supported by safety of GF9 therapy in long-term treated healthy, cancer and arthritic mice. Prototypes of SignaBlok's LPC are well-tolerated in humans. TREM-1 blockade by SignaBlok competitor's peptide LR12 (Inotrem) is safe and well-tolerated in healthy and septic subjects.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $830,491 )
2025	2025	SIGNABLOK, INC.	61 FRANK ST	WORCESTER	MA	01604	WORCESTER	USA	Vision Research	001	2	4/7/2025	EXTENSION WITH OR WITHOUT FUNDS	$830,491
2025	2023	SIGNABLOK, INC.	61 FRANK ST	WORCESTER	MA	01604	WORCESTER	USA	Vision Research	000	1	11/13/2024	NEW	$0
														Subtotal = $830,491

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	SIGNABLOK, INC.	61 FRANK ST	WORCESTER	MA	01604	WORCESTER	USA	Vision Research	000	1	11/8/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $278,127 )
2023	2023	SIGNABLOK, INC.	61 FRANK ST	WORCESTER	MA	01604	WORCESTER	USA	Vision Research	000	1	9/6/2023	NEW	$278,127
														Subtotal = $278,127

Grand Total All Awards = $1,108,618

Top

All Categories

About

Search

Reports

Data Submission

Award Information

First-in-class TREM-1 inhibitors for neovascular retinal diseases

Award Number: R44EY034015

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer