This Project Grant award from the National Eye Institute (NEI), under the Vision Research federal grant program (CFDA 93.867), provides $1,440,325 to the University of Oklahoma Health Sciences Center to study the role of Surfactant Protein A (SP-A) in preventing retinopathy of prematurity (ROP), a potentially blinding vaso-proliferative disease in premature infants. The key objectives are to characterize the SP-A/chaperone/VEGF axis, confirm the SP-A receptor MYO18A, and examine the impact of...
This Project Grant award from the National Eye Institute (NEI) under the Vision Research federal grant program (CFDA 93.867) provides funding of $933,533 to Revopsis Therapeutics, Inc. to support preclinical development of RO-104, a first-in-class trispecific surrobody targeting VEGF-A, VEGF-C, and Ang-2 for the treatment of retinal diseases. The project aims to evaluate RO-104's in vivo toxicology, pharmacokinetics, and dose-range in a relevant preclinical animal model. This work will enable...
The National Eye Institute (NEI) awarded a $580,331 Project Grant (CFDA 93.867 - Vision Research) to The Trustees of the Stevens Institute of Technology in Hoboken, New Jersey. This 4-year grant, effective September 1, 2024, aims to develop a deep learning-based diagnostic tool for detecting retinopathy of prematurity (ROP), a leading cause of childhood blindness globally. The key products and services to be delivered under this award include: Optimizing and testing an animal-to-human (A2H)...
The National Eye Institute (NEI) awarded a $462,072 Project Grant (CFDA 93.867 - Vision Research) to Tufts Medical Center to study the metabolic basis of retinopathy of prematurity (ROP) and investigate the potential of using anaplerotic substrates as a treatment. The project aims to examine the fatty acid metabolic exchanges between the liver and retina, and utilize adeno-associated viruses to genetically manipulate fatty acid metabolism genes in order to prevent oxygen-induced retinopathy. The...
The National Eye Institute (NEI) awarded a $2,270,408 Project Grant (CFDA 93.867 - Vision Research) to Wake Forest University Health Sciences to develop and evaluate RXR-based therapies for treating diabetic retinopathy. The overarching goal is to determine if intravitreal delivery of RXR agonist microparticles (UAB126-MP and UAB30-MP) can activate RXR signaling to normalize retinal lipid metabolism and reduce inflammation, thereby preventing and reversing diabetic retinopathy. The project...
This $1,066,178 Project Grant award from the National Eye Institute (NEI) under the Vision Research program (CFDA 93.867) supports the late-stage preclinical development and GMP production of a first-in-class extended release intraocular pressure (IOP)-lowering formulation for the treatment of glaucoma. The awardee, Tavo Biotherapeutics, Inc. (operating as Oculo Therapy LLC), is a woman-owned small business focused on developing innovative ophthalmic products. The funding will enable the company...
The National Eye Institute (NEI) awarded a $853,894 Project Grant under the Vision Research program (CFDA 93.867) to Childrens Hospital Medical Center to investigate the "Mechanisms of Placentally-Mediated ROP Protection". The research aims to characterize how placental factors like the LHX5 transcription factor may contribute to postnatal vascular protection and reduced risk of retinopathy of prematurity (ROP) in preterm infants, a leading cause of childhood blindness. The project...
This Project Grant awarded by the National Eye Institute (NEI) under the Vision Research program (CFDA 93.867) funds the development and evaluation of novel surrogate augmented deep predictive learning algorithms to predict referral-warranted retinopathy of prematurity (RW-ROP). The primary goals are to: Develop algorithms that leverage early retinal images and demographic factors to accurately predict RW-ROP, enabling earlier identification of high-risk infants for close monitoring and...
The National Eye Institute (NEI) awarded a $623,090 Project Grant (CFDA 93.867 - Vision Research) to Oregon Health & Science University (OHSU) to develop a wide-field visible-light optical coherence tomography (WF-VIS-OCT) device optimized for the rat eye model of oxygen-induced retinopathy (OIR). The goals are to: 1) Build the new WF-VIS-OCT system capable of high-resolution 5-mm field-of-view imaging; 2) Develop deep learning algorithms to quantify retinal capillary vasculature, blood...
This Project Grant award of $745,607 from the National Eye Institute (CFDA 93.867 Vision Research) supports the development of the RETIVUE ENTIREEYE, a handheld, high-resolution, non-contact retinal screening camera for premature and healthy newborn babies. The RETIVUE ENTIREEYE is designed to overcome limitations of current screening technologies and enable widespread, simplified screening for retinopathy of prematurity (ROP), a leading cause of infant blindness. The 12-month...
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 (TNFA, IL-1SS, 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.