Familial Exudative Vitreoretinopathies

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

SAN FRANCISCO, CA, USA I June 15, 2023 I AntlerA Norrin/Wnt-agonist antibody through a strategic partnership with EyeBio enters clinical trials for treatment of retinopathies. AntlerA previously reported the development of a Norrin/Wnt-mimetic for treatment of leaky blood vessels in the eye. “We are pleased to support EyeBio in the development and advancement of EYE103, a Norrin/Wnt-mimetic, into the clinic. Built based on AntlerA’s ANT-Pharm platform the tetravalent antibody molecule binds specifically to FZD4/LRP5 receptors leading to Wnt-signaling and restoration of blood vessels integrity in the eye.” said Dr. Sekar Seshagiri, CEO, AntlerA Therapeutics. He further added “This is a first-in class molecule for treatment of diabetic retinopathy and several pediatric retinal diseases such as FEVR/Norrie, Coats, and ROP” About AntlerA Therapeutics, Inc. AntlerA Therapeutics is a regenerative medicines company focused on developing novel protein therapeutics that function by modulating Wnt signaling to harness the regenerative potential of tissue resident stem cells. For more information, please visit www.antlera.com

First potential FEVR therapy to obtain U.S. FDA Rare Pediatric Disease Designation Designation provides Noregen™ Rare Pediatric Disease Priority Review Voucher Eligibility Follows earlier Orphan Drug Designations in FEVR by both US FDA and EC EMA December 8, 2022, Rochester, MI – Caeregen Therapeutics, LLC, a Michigan-based, regenerative medicine therapeutics company, today announced the U.S. Food and Drug Administration (FDA) designated Noregen™ for treatment of Familial Exudative Vitreoretinopathy (FEVR) as a drug for “rare pediatric disease*”. Through attainment of FDA’s Rare Pediatric Disease (RPD) designation, Noregen™ (CTR-107) is eligible to obtain a Priority Review Voucher at the time of marketing approval. This PRD designation for Noregen™ is the first to be granted by FDA for children with FEVR. The RPD designation for Noregen™ in FEVR follows the attainment of Orphan Drug Designation (ODD) by both the FDA and European Commission (EC) European Medicines Agency (EMA) earlier this year. Noregen™ is a synthetic targeted growth-factor that mimics the properties of norrin, a naturally occurring human protein that promotes development of normal, organized blood vessels and neurons in the human eye, ear, and central nervous system. Noregen™ is being developed for FEVR, a genetic disorder of retinal blood vessel formation, resulting in partial or complete vision loss. When injected into the eye, Noregen™ may regenerate retinal blood vessels and neurons restoring normal retinal function and counteracting vision loss due to FEVR. "The U.S. FDA’s Rare Pediatric Disease Designation for Noregen™ in FEVR provides important validation of our development efforts and the urgent need for new treatment options for patients,” said Kimberly A. Drenser M.D. Ph.D., co-Founder and Chief Scientific Officer of Caeregen Therapeutics. “As new, regenerative medicine activating growth of normal retinal blood vessels and neuronal cells, Noregen™ has the exciting potential to restore, protect and maintain healthy retinal function” added Dr. Drenser. The FDA’s RPD designation is intended to stimulate new drug development for rare pediatric diseases by offering additional incentives for obtaining FDA approval of these products, including eligibility for obtaining a Priority Review Voucher (PRV) that can be used for a subsequent human drug application. Drug companies receiving a PRV can obtain a Priority Review of any drug in their pipeline, which allows for a shorter clock for review of a marketing application (6 months compared with the 10-month standard review), or they can monetize the PRV by selling it to another drug company. Under the current statutory sunset provisions, FDA states that after September 30, 2024, it may only award vouchers for approved rare pediatric disease product applications if companies have an RPD designation for a drug granted by September 30, 2024 and may not award any RPD PRV after September 30, 2026. “Obtaining U.S. FDA’s Rare Pediatric Disease Designation for Noregen™ in FEVR after securing Orphan Drug Designations enables us to accelerate our development progress,” said Walter Capone, Chief Executive Officer of Caeregen Therapeutics. “Regulatory agency endorsement of our urgent mission to help patients with FEVR at risk of vision loss provides critical momentum on our path to the clinic.” ***** *“Rare Pediatric Disease” as defined in section 529(a)(3) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360ff(a)(3)) 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 manifestations (Ranchod et al., 2011). 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 detachment (Wood et al., 2019) - all contributing to or causing visual impairment and blindness. Currently there are no approved pharmacological therapies for FEVR. For more information, please visit: . About Noregen™ NoregenÔ 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. NoregenÔ may promote development of normal, 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 diseases. As a first-in-class therapeutic candidate to regenerate and repair the retinal vasculature in order to restore and preserve vision in patients with ischemic vitreoretinopathies, NoregenÔ is currently being developed for Familial Exudative Vitreoretinopathy (FEVR), a rare disease of urgent, unmet medical need. For more information, please visit: . 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, please visit: . Contacts: Caeregen Therapeutics, LLC. Walter M. Capone CEO & President Email: wmcapone@caeregen.com Mobile: 203-278-1172