Norrie Disease

ROCHESTER, Mich.--(BUSINESS WIRE)-- Caeregen Therapeutics announced today that it has been awarded a $1.4 million Phase 2 Small Business Innovation Research (SBIR) grant from the National Institutes of Health (NIH) and National Eye Institute to advance the development of CTR-107 (Noregen™), a novel regenerative therapeutic for the treatment of retinal-related vision loss due to a wide range of inherited and age-related diseases. Caeregen is initially developing CTR-107 for the treatment of a rare inherited disorder of retinal blood vessel formation, Familial Exudative Vitreoretinopathy (FEVR). “The NIH grant will support the nonclinical development program of CTR-107 and accelerate our investigational new drug (IND) submission to begin clinical trials," said Walter Capone, CEO of Caeregen Therapeutics. “This award provides further, important validation for CTR-107 and our novel approach to retinal disease treatment, the first with the potential to restore retinal function and reverse vision loss,” said Dr. Kimberly Drenser, Chief Scientific Officer of Caeregen Therapeutics. Retinal disease is the leading cause of vision loss in developed countries and is the fastest growing cause of blindness globally. Currently, it is estimated that vision-depriving retinal diseases, such as macular degeneration, diabetic retinopathy, retinal vein occlusion, and ischemia affect more than 10 million people in the United States and Europe, respectively, and more than 50 million people worldwide1,2,3. Less common, but equally devastating causes of retina-related vision loss are driven by genetic alterations or mutations that impair normal cellular formation, or retinal structure or function, including Norrie Disease, Osteoporosis Pseudoglioma Syndrome, and FEVR. Both age-related and acquired retinal disorders share an underlying deterioration of the retinal vascular bed and related neurovascular structure. Current therapies slow the progression of vision loss but do not repair, nor reverse, retinal damage that has already occurred. CTR-107 is a synthetic targeted growth factor that mimics the properties of norrin, a naturally occurring human protein that promotes the development of organized blood vessels and neurons in the human eye, ear, and central nervous system. When injected into the eye, CTR-107 may regenerate retinal blood vessels and neurons, restoring retinal function and counteracting vision loss due to FEVR and other retinal diseases. The Phase 2 SBIR grant builds on prior research, including in a Phase 1 STTR grant, that demonstrated production feasibility, safety/tolerability, modulation of target gene expression in vitro, and in vivo functional activity. During Phase 2 SBIR grant-supported research, the company will optimize dosing through in vitro and in vivo studies, further develop analytical methods for product characterization, and conduct pharmacokinetic studies to support an IND submission. CTR-107 is the first program to obtain U.S. FDA Rare Pediatric Disease (RPD) Designation for treatment of FEVR, a designation that makes Caeregen eligible to obtain a Priority Review Voucher at the time of marketing approval. The RPD designation for CTR-107 (Noregen™) follows the Orphan Drug Designations by both the FDA and European Commission European Medicines Agency (EMA). About CTR-107 (Noregen™) CTR-107 (Noregen™) is a synthetic targeted growth-factor for retina-related vision loss modeled after norrin, a naturally occurring human protein that guides retinal formation in fetal development. CTR-107 may promote development of organized blood vessels and neurons in the human eye, ear, and central nervous system for individuals with inherited or acquired retinal diseases and potential applications in other neurosensory disorders. As a first-in-class therapeutic candidate to regenerate and repair the retinal vasculature to restore and preserve vision in patients with ischemic vitreoretinopathies, CTR-107 is currently being developed for Familial Exudative Vitreoretinopathy (FEVR), a rare disease of urgent, unmet medical need. About FAMILIAL EXUDATIVE VITREORETINOPATHY (FEVR) Familial Exudative Vitreoretinopathy, or ‘FEVR’ is a rare inherited disorder of retinal angiogenesis, leading to incomplete vascularization of the peripheral retinal and poor vascular differentiation. FEVR most often presents in childhood but may progress at any age with sight-threatening manifestations4 It is characterized by abnormal retinal vascular development with progressive vitreoretinal features, including retinal capillary dropout, vessel dragging; retinal folds, vessel leakage and exudation; hemorrhage, neovascularization, vitreoretinal interface changes, and serous, tractional, or combined retinal detachment5 - all contributing to or causing visual impairment and blindness. Currently there are no approved pharmacological therapies for FEVR. About Caeregen Therapeutics Caeregen Therapeutics, LLC, based in Rochester, MI with offices in Chapel Hill, N.C., is a regenerative medicines company developing therapeutics for neurosensory diseases. By exploiting biological pathways and signaling related to cellular and organ development, Caeregen is focused on advancing targeted therapies with the ability to repair, restore and protect neurosensory tissues affected by inherited or acquired diseases. Caeregen is currently developing Noregen, a unique, novel, recombinant protein mimetic of human norrin-derived growth factor for the potential treatment of retinal-related vision loss. For more information, visit: . 1Prevalence of Age-Related Macular Degeneration in the US in 2019”, JAMA Ophthalmology, Dec. 1, 2022 2Global epidemiology of retinal vein occlusion: a systematic review and meta-analysis of prevalence, incidence and risk factors”, Global Health, June 2019 3Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: A Systematic Review and Meta-Analysis,” Ophthalmology, November 2021 4Clinical presentation of Familial Exudative Vitreoretinopathy,” Ophthalmology, October 2011 5Symmetry of Folds in FEVR: a genotype-phenotype correlation study,” Experimental Eye Research, September 2019

An ultra-rare hereditary immune disease, CHAPLE is driven by the overactivation of the complement system, in turn causing potentially life-threatening abdominal and cardiovascular symptoms. Credit: Darko Djurin / Pixabay. The US Food and Drug Administration (FDA) has accepted a priority review of the biologics license application (BLA) for Regeneron Pharmaceuticals’ pozelimab to treat children and adults with ultra-rare CHAPLE disease. Currently, there are no approved treatments for CHAPLE, a life-threatening hereditary immune disease caused by an overactivation of the complement system. The investigational, fully human monoclonal antibody, Pozelimab has been designed to block the complement factor C5 activity. C5 is a protein that is involved in the activation of the complement system. The antibody is developed using the company’s VelocImmune technology. The regulatory body is expected to decide on 20 August. The BLA submitted to the FDA is supported by the data obtained from an open-label Phase II/III trial, designed to evaluate the efficacy and safety of pozelimab in ten patients aged one year or above. The findings showed that 100% of patients had quick and sustained normalisation of serum albumin (a disease biomarker) and improvement or no worsening of clinical symptoms at 24 weeks. In the trial, the clinical symptoms were assessed, including the number of bowel movements per day, abdominal pain, and investigator-assessed facial and peripheral edema. In April 2020, pozelimab was designated as a drug for a “rare pediatric disease” to treat CHAPLE by the US FDA, with Regeneron having an opportunity to get a rare pediatric disease priority review voucher if pozelimab is approved for CHAPLE. It was also granted Orphan Drug Designation during the same time. It is also being assessed along with Alnylam’s cemdisiran (siRNAi C5 inhibitor) to treat other complement-mediated disorders, including myasthenia gravis (MG) and paroxysmal nocturnal hemoglobinuria (PNH). Earlier this month, Regeneron received US FDA approval for its Eylea (aflibercept) injection to treat the retinopathy of prematurity (ROP) in preterm infants.

Pittsburgh, Pennsylvania, May 17, 2021 (GLOBE NEWSWIRE) -- PITTSBURGH, Pennsylvania, May 17, 2021 – Cernostics () a pioneer in delivering spatialomics to the clinic, announced today that new results from clinical studies on the TissueCypher® Barrett’s Esophagus Assay will be presented at Digestive Disease Week® (DDW®) 2021 taking place May 21-23. Clinical studies by Mayo Clinic, and Academic Medical Center in The Netherlands, two of the world’s leading academic institutions in the area of diagnosis and treatment of Barrett’s esophagus (BE) and esophageal cancer prevention, will be presented during the oral lecture session focused on predicting progression to esophageal cancer in patients with BE. “New data accepted for presentation at this year’s DDW® point to the value of TissueCypher® for improving prevention of esophageal cancer, particularly to help physicians and patients make more informed management decisions based on the unique biology of individual patients’ esophageal biopsies,” said Mike Hoerres, Cernostics’ chief executive officer. “We believe such data demonstrate the value of precision medicine testing with the TissueCypher® Barrett’s Esophagus Assay, and greatly appreciate the Barrett’s esophagus clinical experts who led and participated in these studies.” Below are the details of the presentations on TissueCypher® at DDW® 2021: TissueCypher Objectively Risk Stratifies Barrett’s Esophagus Patients with Low Grade Dysplasia (lecture presentation) Presenter: Nicola Frei, MD (AMC, Amsterdam, Netherlands) Session Title: Prediction of Progression in Barrett's Esophagus Session Date/Time: May 21, 2021, 10:00 AM to 11:30 AM EDT (UTC –4) Prediction of Progression in Barrett’s Esophagus Using a Tissue Systems Pathology Test: A Pooled Analysis of International Multicenter Studies (lecture presentation) Presenter: Prasad Iyer, MD (Mayo Clinic) Session Title: Prediction of Progression in Barrett's Esophagus Session Date/Time: May 21, 2021, 10:00 AM to 11:30 AM EDT (UTC –4) The AMC study, led by Professor Jacques Bergman, MD, PhD,  evaluated the performance of the TissueCypher® Barrett’s Esophagus Assay versus the independent scoring of expert and generalist pathologists in the USA and Europe in a cohort of 155 patients previously diagnosed with Low-Grade Dysplasia (LGD) in the community practice setting. TissueCypher® demonstrated higher sensitivity and provided more objective risk stratification than the 12 participating pathologists, as well as identified a subset of progressor patients who had been down-staged to Non-dysplastic BE (ND BE) upon expert review. The Mayo Study, led by Dr Prasad Iyer, MD, analyzed four independent clinical validation studies (475 patients, including 152 progressors) to assess the performance of TissueCypher® in independently predicting incident progression. The results demonstrated TissueCypher® outperformed the expert pathologist as well as commonly-used clinical variables in risk stratifying patients for progression. Importantly, this study also demonstrated that TissueCypher® can identify high-risk progressor patients diagnosed with ND BE, and therefore can be missed by the standard of care. Due to the dangers of esophageal cancer and the challenges in identifying those patients who will likely progress to it, the management of Barrett’s esophagus and predicting progression are two of the major Education Tracks in DDW® 2021. Objectively and accurately predicting progression from ND BE to High-Grade Dysplasia (HGD) or esophageal adenocarcinoma (EAC) is critical as the incidence of esophageal cancers is growing at one of the fastest rates of all cancers, and once diagnosed, has extremely low survivability. About Cernostics and TissueCypher® Barrett’s Esophagus Assay Cernostics applies spatial biology and biologically aware AI to tissue diagnostics, delivering precision diagnostic testing to patients and gastroenterologists. This technology was used to develop the TissueCypher® Barrett’s Esophagus Assay, the world’s first precision medicine test that predicts future development of esophageal cancer in patients with Barrett’s esophagus. TissueCypher® is a proprietary Laboratory Developed Test (LDT) with its own unique CPT PLA code (0108U), available only from Cernostics’ CLIA-certified pathology laboratory. TissueCypher® has been on the Medicare Clinical Laboratory Fee Schedule since January 2021. ###