CNGA3

Uni-Rare Study will improve clinical understanding of more IRDs and boost development of potential therapies. COLUMBIA, Md., Nov. 10, 2022 /PRNewswire/ -- The Foundation Fighting Blindness, the world's leading organization committed to finding treatments and cures for blinding retinal diseases, is committing at least $8.6 million for its Uni-Rare Study, a new natural history study for approximately 1,500 people with one of more than 300 rare genes associated with inherited retinal diseases (IRDs) including: retinitis pigmentosa, Leber congenital amaurosis, Usher syndrome, and a broad range of other conditions. The study, due to begin recruitment in December, will help clinical researchers gain a better understanding of the course of retinal degeneration and vision loss for people with mutated genes that have not been well-characterized in the clinic. The study will also help the IRD research and therapeutic development community: 1) identify more people for clinical trials of therapies, 2) inform design of clinical trials, and 3) identify therapeutic targets for more people. "A majority of the 300 genes linked to inherited retinal diseases have not been well characterized in the clinic. That is, we do not have a good understanding of retinal degeneration and disease progression for those affected by these mutated genes," says Todd Durham, PhD, senior vice president, clinical development, at the Foundation Fighting Blindness. "We are excited to launch a highly inclusive study to benefit a large segment of the population affected by IRDs, which are so genetically diverse." "We are at a promising juncture in the clinical development of genetic therapies for inherited retinal diseases," says José-Alain Sahel, MD , distinguished professor and chairman of the department of ophthalmology at the University of Pittsburgh School of Medicine and Uni-Rare Study chair. "With dozens of emerging treatments in, or moving toward, clinical trials, the Uni-Rare Study will be invaluable in defining and validating outcome measures for clinical trials and establishing the infrastructure for multicenter studies. The Foundation Fighting Blindness, with its strong presence and relationships in the global IRD research community, is the ideal partner to lead the effort." The two-part Uni-Rare Study will be conducted by the Foundation's Clinical Consortium, a global, 40-site network of clinical research centers equipped with the experts and resources needed to launch IRD clinical trials and natural history studies. The Jaeb Center for Health Research will serve as the coordinating center. In the first part of the study, all participants will have an initial evaluation to collect their genetic data and clinical measures. When the study is initiated, study participants whose IRD is caused by variants in the RDH12 and MYO7A genes may qualify for the second part of the study, which involves collecting clinical measures for an additional four years. Additional gene cohorts for this part of the study are expected to be added in the future. The Foundation has received support for the study from families affected by Usher syndrome type 1B, Save Sight Now, Opus Genetics, Atsena Therapeutics, and Cove Therapeutics and is seeking additional support to add further gene cohorts to the second part of the study. "Opus is pleased to be an early supporter of this first-of-its-kind in ophthalmology initiative to understand natural histories around rare diseases of the retina in order to accelerate research and therapeutic development for these blinding conditions," said Jennifer Hunt, chief development officer at Opus Genetics. "Atsena Therapeutics is pleased to support the Uni-Rare natural history study and the inherited retinal disease community as we continue advancing the preclinical development of our dual AAV vector-based gene therapy to prevent blindness from USH1B," said Kenji Fujita, MD, chief medical officer at Atsena Therapeutics. "We are proud to sponsor such a robust interrogation of natural history that will be used to inform future clinical development plans and improve patient outcomes; these data will be fundamental for our understanding of several diseases and will serve to accelerate the development of Cove's non-viral gene therapies," said Niren Shah, PharmD, MBA, CEO and co-founder of Cove Therapeutics. IRD patients and physicians with IRD patients can get more information at clinicaltrials.gov. Patients with IRDs caused by mutations in the following genes are not eligible for the study: ABCA4, CEP290, CHM, CNGA3, CNGB3, EYS, GUCY2D, PCDH15, PROM1, RHO, RPE65, RPGR, USH2A. These genes are or have been part of other natural history studies or clinical trials. About the Foundation Fighting Blindness Established in 1971, the Foundation Fighting Blindness is the world's leading private funding source for retinal degenerative disease research. The Foundation has raised more than $891 million toward its mission of accelerating research for preventing, treating, and curing blindness caused by the entire spectrum of blinding retinal diseases including: retinitis pigmentosa, macular degeneration, and Usher syndrome. Visit FightingBlindness.org for more information. About Opus Genetics Opus Genetics is a groundbreaking gene therapy company for inherited retinal diseases with a unique model and purpose. Backed by Foundation Fighting Blindness's venture arm, the RD Fund, Opus combines unparalleled insight and commitment to patient need with wholly owned programs in numerous orphan retinal diseases. Its AAV-based gene therapy portfolio tackles some of the most neglected forms of inherited blindness while creating novel orphan manufacturing scale and efficiencies. Based in Research Triangle Park, N.C., the company leverages knowledge of the best science and the expertise of pioneers in ocular gene therapy to transparently drive transformative treatments to patients. For more information, visit opusgenetics.com. About Atsena Therapeutics Atsena Therapeutics is a clinical-stage gene therapy company developing novel treatments for inherited forms of blindness. The company's ongoing Phase I/II clinical trial is evaluating a potential therapy for a form of LCA, one of the most common causes of blindness in children. Its additional pipeline of leading preclinical assets is powered by an adeno-associated virus (AAV) technology platform tailored to overcome significant hurdles presented by inherited retinal disease, and its unique approach is guided by the specific needs of each patient condition to optimize treatment. Founded by ocular gene therapy pioneers Dr. Shannon Boye and Sanford Boye of the University of Florida, Atsena is based in North Carolina's Research Triangle, an environment rich in gene therapy expertise. For more information, please visit atsenatx.com. About Cove Therapeutics Cove Therapeutics is a privately held biotechnology company focused on developing non-viral, non-lipid, nanoparticle gene therapies for orphan and chronic prevalent indications. The Company utilizes a nanoparticle technology that overcomes limitations in gene therapy by enabling cell-specific tropism, scalable manufacturing, redosing, and packaging of large genes while maintaining a favorable safety profile. Together with these nanoparticles, Cove's lead franchise for ophthalmic conditions leverages a novel outpatient suprachoroidal device that enables broad distribution of therapeutics. Learn more about the Company through direct contact — Stephen Jasper, Gilmartin Group, [email protected], 858-525-2047. Media Contact: Chris Adams Vice President, Marketing & Communications [email protected] 410-423-0585 SOURCE Foundation Fighting Blindness

Applied Genetic Technologies Corporation (Nasdaq: AGTC), a clinical stage biotechnology company focused on the development and commercialization of adeno-associated virus (AAV)-based gene therapies for the treatment of rare and debilitating diseases with an initial focus on inherited retinal diseases, today reported updated interim three-month pediatric results and additional adult safety results out to as long as 24 months from its ongoing Phase 1/2 dose escalation study of AGTC-401. AGTC-401 is a recombinant AAV viral vector-based gene therapy targeting mutations in the CNGB3 gene in patients with achromatopsia (ACHMB3). Data from seven pediatric patients support previously reported findings from adults treated with AGTC-401, which demonstrated encouraging biologic activity and a favorable safety profile. There were no new Suspected Unexpected Serious Adverse Reactions (SUSARs) and for the three previously reported SUSARs, the inflammation continues to improve with steroid treatment. Based on the totality of the ACHMB3 data generated to date from 31 patients over as long as 24 months, AGTC plans to advance the clinical development of AGTC-401 subject to consultation with the U.S. Food and Drug Administration (FDA) at an End-of-Phase 2 (EOP2) meeting in the first half of 2022. The Company also reported updated results from a parallel study of AGTC-402 targeting CNGA3 mutations in patients with achromatopsia that are consistent with previously reported results in adults, provide no indication of clinical improvements, and do not support further clinical development. Most patients with CNGA3 mutations express a mutant protein that is not typically found in patients with CNGB3 mutations, which the Company believes may have impacted results seen in patients that received AGTC-402. AGTC will continue to follow the ACHMA3 patients for long-term safety observations. “The three-month pediatric findings provide further evidence for the strong potential of our product candidate for patients with ACHMB3, and we look forward to continuing our discussions with the regulatory agencies to determine the best path forward to bring this important therapy to patients,” said Sue Washer, President and Chief Executive Officer of AGTC. “We understand the challenges that patients with achromatopsia face in their daily lives and our team remains dedicated to advancing this program toward commercialization. These additional data provide us the opportunity to help inform the next phase of clinical development and we thank the patients and investigators for their participation in this important clinical trial.” In the Phase 1/2 dose escalation study of AGTC-401 in ACHMB3 patients, a total of 21 adults were treated over a 100-fold dose range in five groups and a total of ten pediatric patients were treated at the three highest dose groups. The primary purpose of any Phase1/2 clinical trial is to identify a well-tolerated dose that provides clinical benefit to patients. The Company believes that the data to date support that the 1.1E+12vg/mL dose is well tolerated and provides clinical benefit in both adult and pediatric patients. “We’re pleased to have identified a generally safe and well tolerated dose of AGTC-401 for both adults and pediatric patients when inflammation is controlled,” said Dr. Robert Sisk, MD, Director of Pediatric Vitreoretinal Surgery and Director of Ophthalmic Genetics – Cincinnati Children’s Hospital and the Cincinnati Eye Institute and an investigator in the ongoing AGTC achromatopsia Phase 1/2 trials. “Based on the available pediatric data at three months, which are consistent with previously reported results in adults with ACHMB3, we are encouraged by the biologic activity observed in patients treated with AGTC-401. The achromatopsia community currently faces a significant unmet need and the totality of this data reinforces the promise of AGTC-401 as a potential treatment option if confirmed in future studies.” As previously reported, in both the ACHMB3 and ACHMA3 trials, treatment with the highest doses of AGTC-401 and AGTC-402, respectively, led to three cases of severe ocular inflammation in pediatric patients, which were reported as SUSARs. No new additional SUSARs have been reported and the inflammation in all previously reported SUSARs improved with an adjusted steroid regimen. Two SUSARs (one in ACHMA3 and one in ACHMB3) have since fully resolved and one (ACHMA3) continues to resolve, with all three patients’ best corrected visual acuity returning to baseline. Secondary outcome measures evaluating efficacy were assessed by standard visual function tests such as perimetry. We defined two pediatric patients (17 and 7 years old) in the 1.1E+12 vg/mL dose group as responders based on improvements in visual sensitivity. Therefore, of the three adults and four children (total n=7) in the 1.1E+12 vg/mL dose group, four (>50%) are visual sensitivity responders. These patients also had improvements in quality of life as measured by a patient reported outcome survey developed specifically for patients with achromatopsia. The two other pediatric patients in the 1.1E+12 vg/mL dose group and three pediatric patients ages 7 years and younger in the 3E+12vg/mL dose group (total n=5) could not sufficiently concentrate and consistently complete the visual sensitivity testing. Similar to other trials where endpoints are adapted for young children, AGTC plans to work closely with clinicians and regulators to develop potential adaptations for younger patients for visual sensitivity testing. The Company is currently working on an EOP2 meeting package for the FDA and expects to receive feedback in the first half of 2022. Subject to these discussions with FDA, the Company plans to initiate the next phase of AGTC-401 clinical development. The clinical program will be based on the favorable risk benefit pro the 1.1E+12 vg/mL dose, which had a generally safe and well tolerated safety pro all patients and signs of biologic response based on improvements in visual sensitivity and other measures of visual function. Final data and analysis of both ACHMA3 and ACHMB3 studies will be presented at relevant conferences and published for the ophthalmology community. About Achromatopsia (ACHM) Achromatopsia (ACHM) is an inherited condition caused by mutations in one of several genes, with the two most common being mutations in either the CNGB3 or CNGA3 genes. ACHM is associated with extremely poor visual acuity (most affected individuals are legally blind), extreme light sensitivity resulting in daytime blindness, and complete loss of color discrimination. AGTC is currently developing two separate AAV gene therapy product candidates for the two most prevalent forms of ACHM, caused by either a genetic mutation in the CNGB3 or CNGA3 genes. Together, these two genetic mutations account for up to 75% of the ACHM patient population. About AGTC AGTC is a clinical-stage biotechnology company developing genetic therapies for people with rare and debilitating ophthalmic, otologic and central nervous system (CNS) diseases. AGTC is a leader in designing and constructing all critical gene therapy elements and bringing them together to develop customized therapies with the potential to address unmet patient needs. AGTC’s most advanced clinical programs leverage its best-in-class technology platform to potentially improve vision for patients with inherited retinal diseases. AGTC has active clinical trials in X-linked retinitis pigmentosa (XLRP) and achromatopsia (ACHM CNGB3 and ACHM CNGA3). Its preclinical programs build on the company’s industry leading AAV manufacturing technology and scientific expertise. AGTC is advancing multiple important pipeline candidates to address substantial unmet clinical needs in optogenetics, otology and CNS disorders, and has entered strategic collaborations with companies including Otonomy, Inc., a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology, and Bionic Sight, LLC, an innovator in the emerging field of optogenetics and retinal coding.

Pavlo Gonchar/SOPA Images/LightRocket via Getty Images Johnson & Johnson is inching closer to seeking authorization of its COVID-19 vaccine. The life sciences giant indicated it will soon release Phase III data and could Emergency Use Authorization (EUA) with the U.S. Food and Drug Administration (FDA) by the end of the month. If authorized, J&J said it will be on track to deliver up to 100 million doses of the vaccine to the United States by the end of June, The Hill reported. If the Phase III data expected to be released next week leads to authorization in the U.S., that will speed up vaccination efforts across the country. Unlike the two authorized mRNA vaccines, J&J’s vaccine is a single-dose regimen. Between the already authorized vaccines in the U.S. and J&J’s, if data is positive, the U.S. would be on track to vaccinate more than 250 million people by the end of the summer. Earlier this month, J&J released interim data that showed its vaccine was safe and effective. As BioSpace previously reported, after a single vaccination, neutralizing antibodies against COVID-19 were observed in more than 90% of volunteers at Day 29 and 100% of the volunteers between the ages of 18 and 55 at Day 57. To measure the level of efficacy from the vaccine, total data from the Phase III study will be needed. Those results are dependent upon a percentage of people in the trial actually being diagnosed with COVID-19 following vaccination. Elsewhere: Mother’s Milk – The University of Texas Medical Branch received a three-year, $300,000 grant to determine whether breast milk has an innate ability to stop the spread of COVID-19. The study will determine if an infected mother who has recovered from the virus can pass antibodies to her child through her milk. The research team will examine the breast milk of women who have recovered from COVID-19. Their milk will be tested for antibodies. Also, the researchers will look for viral particulates in the milk as well, The Houston Chronicle reported. Metformin Recall – Nostrum Laboratories has recalled its diabetes medicine for the second time due to concerns over an ingredient used in the manufacturing being linked to a carcinogen. ArkLatex reported Nostrum has voluntarily recalled one lot of the Metformin HCl extended-release tablets, USP 750 mg, the generic equivalent to Glucophage Tablets. The recall is due to the presence of N-nitrosodimethylamine (NDMA) levels above the acceptable daily intake levels established by the regulatory agency. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products and vegetables. In large amounts, NDMA can cause health severe problems. Last year, the FDA announced that high levels of NDMA had been discovered in some of the ER metformin medications it had tested. High levels of NDMA have previously led to the recall of some hypertension and heartburn medications. Big IPO – Foresite Development II, a blank-check company formed by Foresite Capital, is aiming for a $100 million initial public offering. The company will offer 10 million shares at $10 per share. FS Development II was founded in 2020 and plans to list on the Nasdaq under the symbol FSII, according to a report on Nasdaq.com. Additionally, Foresite Development II plans to raise another $25 million in a concurrent private placement. Foresite Development II will be Foresite Capital’s second SPAC company. Its previous SPAC, FS Development, went public in August 2020. It has a pending merger agreement with Gemini Therapeutics. Edible Antibodies -- Seattle-based Lumen Bioscience snagged $14.5 million from CARB-X to fund the development of an oral monoclonal antibody cocktail to prevent serious diarrheal diseases. The CARB-X project will develop an antibiotic-alternative that targets two key pathogens behind the diarrheal diseases that are prevalent in the developing world. The intended product is a low-cost, edible antibody cocktail that can be easily shipped, stored, and used worldwide, including in regions like Africa and parts of Southeast Asia that lack refrigerated distribution. Fast Track – MeiraGTx secured Fast Track designation for its AAV-CNGA3 gene therapy product candidate for the treatment of achromatopsia (ACHM) caused by mutations in the CNGA3 gene. ACHM is an inherited retinal disease that severely limits a person’s sight by preventing cone photoreceptors in the eye from functioning. Individuals with ACHM are often legally blind from birth and have extremely debilitating sensitivity to light. AAV-CNGA3 is an investigational gene therapy treatment designed to restore cone function, delivered to the cone receptors at the back of the eye via subretinal injection. Most Read Today