XLRS1

Subretinal injection of ATSN-201 was well tolerated in all patients in first cohort with no serious adverse events reported Enrollment is ongoing in first clinical trial utilizing AAV.SPR, the company’s novel spreading capsid March 13, 2024 -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced dosing has been initiated in the second cohort of the LIGHTHOUSE study, a Phase I/II clinical trial evaluating subretinal injection of ATSN-201 for the treatment of X-linked retinoschisis (XLRS). ATSN-201, a best-in-class gene therapy product candidate, leverages AAV.SPR, the company’s novel spreading capsid, to achieve therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment. ATSN-201 was well tolerated in all three XLRS patients in the first cohort and no serious adverse events were reported. The Data and Safety Monitoring Board recommended proceeding with the second cohort, in which patients will receive the next dose level of ATSN-201. "We are encouraged by the excellent safety observed with the low dose of ATSN-201 in the LIGHTHOUSE study, which represents the first clinical utilization of AAV.SPR. Additionally, initial indications of structural and functional improvement observed within and beyond the injection areas suggest successful lateral spread of the vector,” said Kenji Fujita, MD, Chief Medical Officer of Atsena Therapeutics. “Advancing into the second cohort brings us one step closer to potentially bringing a much-needed one-time treatment to patients with XLRS, an inherited retinal disease that causes progressive vision loss and can lead to blindness.” The LIGHTHOUSE study is a Phase I/II, open-label, dose-escalation and dose-expansion clinical trial evaluating the safety and tolerability of ATSN-201 in male patients ages 6 and older with a clinical diagnosis of XLRS caused by pathogenic or likely pathogenic mutations in RS1. Enrollment in the LIGHTHOUSE study is ongoing. For more information, visit ClinicalTrials.gov (Identifier: NCT05878860). XLRS is a monogenic X-linked disease caused by mutations in the RS1 gene which encodes retinoschisin, a protein secreted primarily by photoreceptors. RS1 is localized to the extracellular surface of rods, cones, and bipolar cells. XLRS is characterized by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and leads to progressive vision loss and ultimately blindness. XLRS primarily affects males and is typically diagnosed in early childhood. Approximately 30,000 males in the U.S. and EU have XLRS, for which there are currently no approved treatments. AAV.SPR, one of Atsena’s novel capsids, spreads laterally beyond the subretinal injection site to enable safe and efficient transduction of the central retina (where schisis cavities predominate in XLRS patient retinas) when injected into areas outside the macula. A preclinical study in non-human primates demonstrated that AAV.SPR promotes transgene expression well beyond subretinal injection bleb margins. This is in stark contrast to benchmark AAV vectors, which remain confined to the original bleb margins. At clinically relevant doses, AAV.SPR efficiently transduces foveal cones without the need for surgical detachment and does not cause inflammation. For more information about the preclinical study and how AAV.SPR works, visit https://atsenatx.com/our-approach/laterally-spreading-aav/. Atsena Therapeutics is a clinical-stage gene therapy company developing best-in-class treatments for the reversal or prevention of blindness from inherited retinal diseases. The company’s lead program is evaluating ATSN-201 in an ongoing Phase I/II clinical trial for X-linked retinoschisis (XLRS), a progressive genetic condition affecting boys and men that is typically diagnosed in childhood. Another ongoing Phase I/II clinical trial is evaluating ATSN-101 for Leber congenital amaurosis type 1 (LCA1), one of the most common causes of blindness in children. Atsena’s pipeline is powered by novel adeno-associated virus (AAV) technology tailored to overcome the hurdles presented by inherited retinal diseases. Founded by pioneers in ocular gene therapy, Atsena is led by an experienced team dedicated to addressing the needs of patients with vision loss. The content above comes from the network. if any infringement, please contact us to modify.

The LIGHTHOUSE study evaluating the safety and tolerability of investigational gene therapy ATSN-201 is enrolling male patients ages 6-64 with RS1-associated XLRS ATSN-201 leverages novel spreading capsid to overcome challenges associated with intravitreally delivered AAVs in the treatment of XLRS DURHAM, N.C., Aug. 28, 2023 (GLOBE NEWSWIRE) -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced the first patient has been dosed in its Phase I/II clinical trial, the LIGHTHOUSE study, evaluating subretinal injection of ATSN-201 for the treatment of X-linked retinoschisis (XLRS). ATSN-201 leverages AAV.SPR, the company’s novel spreading capsid, to achieve therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment. “Dosing the first patient in the LIGHTHOUSE study marks a significant milestone for Atsena and the XLRS community,” said Kenji Fujita, MD, Chief Medical Officer of Atsena Therapeutics. “We are excited to be utilizing AAV.SPR in the clinic, as it has the potential to revolutionize the treatment of XLRS, as well as other inherited retinal disorders. Spreading laterally beyond the subretinal injection site, AAV.SPR facilitates the safe delivery of RS1 to photoreceptors in the central retina/fovea. We look forward to advancing the LIGHTHOUSE study and the continued development of our novel gene therapies to reverse or prevent blindness.” The LIGHTHOUSE study is a Phase I/II, open-label, dose-escalation and dose-expansion clinical trial evaluating the safety and tolerability of ATSN-201 in male patients ages 6-64 with a clinical diagnosis of XLRS caused by pathogenic or likely pathogenic mutations in RS1. For more information, visit ClinicalTrials.gov (Identifier: NCT05878860). "Considering the lack of available therapies for X-linked retinoschisis, this is very exciting news for the inherited retinal disease community," said Mark Pennesi, MD, PhD, Professor in Ophthalmology and Chief of the Paul H. Casey Ophthalmic Genetics Division Molecular and Medical Genetics, School of Medicine at Oregon Health & Science University (OHSU). "While attempts to deliver gene therapy through intravitreal routes faced challenges, subretinal treatment utilizing spreading AAV vectors has the potential to be the breakthrough we need to achieve efficacy." About X-linked Retinoschisis (XLRS)XLRS is a monogenic X-linked disease caused by mutations in the RS1 gene which encodes retinoschisin, a protein secreted primarily by photoreceptors. RS1 is localized to the extracellular surface of rods, cones, and bipolar cells. XLRS is characterized by schisis, or abnormal splitting of the layers of the retina, which causes impaired visual acuity that is not correctable with glasses and leads to progressive vision loss. XLRS primarily affects males and is typically diagnosed in early childhood. Approximately 30,000 males in the U.S. and EU have XLRS, for which there are currently no approved treatments. About AAV.SPRAAV.SPR, one of Atsena’s novel spreading capsids, spreads laterally beyond the subretinal injection site to enable safe and efficient transduction of the central retina (where schisis cavities predominate in XLRS patient retinas) when injected into areas outside the macula. A preclinical study in non-human primates demonstrated that AAV.SPR promotes transgene expression well beyond subretinal injection bleb margins. This is in stark contrast to benchmark vector AAV5, which remains confined to the original bleb margins. At clinically relevant doses, AAV.SPR efficiently transduces foveal cones without the need for surgical detachment and does not cause inflammation. For more information about the preclinical study and how AAV.SPR works, visit https://atsenatx.com/our-approach/laterally-spreading-aav/. About Atsena TherapeuticsAtsena Therapeutics is a clinical-stage gene therapy company developing novel treatments for inherited forms of blindness. The company has two clinical-stage programs, ATSN-201 for X-linked retinoschisis (XLRS) and ATSN-101 for GUCY2D-associated Leber congenital amaurosis (LCA1). ATSN-201, which leverages the company’s novel spreading capsid AAV.SPR, is being evaluated in XLRS patients in a Phase I/II clinical trial known as the LIGHTHOUSE study. The company's additional proprietary asset is ATSN-301, a dual AAV vector-based gene therapy to prevent blindness from MYO7A-associated Usher syndrome (USH1B). Interim safety and efficacy data from the company’s ongoing Phase I/II clinical trial in patients with LCA1 have demonstrated ATSN-101 is well tolerated and clinically meaningful improvements in vision were observed 6 months post-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. Media Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com Business Contact:info@atsenatx.com

Animal proof-of-concept for AAV-based gene therapies for Stargardt disease, X-linked retinoschisis and autosomal dominant optic atrophyCLEVELAND, May 16, 2023 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (Nasdaq: ABEO) today announced new data regarding three internally developed preclinical gene therapy product candidates from its adeno-associated virus (AAV) ophthalmology program that will be presented at the 26th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), taking place from May 16-20, 2023 in Los Angeles, CA. “The preclinical proof-of-concept data being presented at ASGCT provides early evidence of the potential of our proprietary AAV capsids and gene constructs to express the recombinant protein in target tissues and rescue mutant phenotypes in mouse disease models,” said Brian Kevany, Ph.D., Chief Technical Officer and Head of Research at Abeona. “We look forward to pre-Investigational New Drug Application meetings with the FDA for two of our programs to take place in the second quarter of 2023.” Details for the poster presentations are as follows. Wednesday, May 17, 2023 at 12:00 PM PT In the presentation, entitled, “In Vivo Production of Full-Length ABCA4 Protein Following Cre-Mediated Recombination from Dual AAV Vectors in ABCA4-/- Mice,” Dr. Paul Wille, Director, Product Development, Abeona Therapeutics will present key findings: A dual AAV vector strategy using Cre recombinase efficiently reconstituted the ABCA4 gene, leading to full-length hABCA4 protein expression both in vitro via viral transduction of HEK293 cells and in vivo in photoreceptor cells after subretinal injection into ABCA4-/- mouse eyes.Cre-mediated recombination of ABCA4 was confirmed by mRNA sequencing of RNA from transfected HEK293 cells and AAV-dosed animals.Immunohistochemistry results confirmed correct localization of recombinant hABCA4 protein in photoreceptor cells. Thursday, May 18, 2023 at 12:00 PM PT In the presentation, entitled, “ABO-503, a Novel Gene Therapy for Treatment of X-Linked Retinoschisis,” Dr. Joseph Fogerty, Senior Scientist, Product Development, Abeona Therapeutics will present key findings: Robust RS1 expression was observed in photoreceptor cells near the injection site and in the adjacent inner retina in mutant mice six months after treatment with ABO-503.RS1 expression was associated with improvement in cone photoreceptor density and increased thickness of the photoreceptor outer nuclear layer.Full-field flicker electroretinogram (ERG) analysis showed significant improvement in cone photoreceptor function. Friday, May 19, 2023 at 12:00 PM PT In the presentation, entitled, “AAV Gene Therapy for Autosomal Dominant Optic Atrophy Caused by Mutation in the Opa1 Gene,” Dr. Rachel Stupay, Senior Scientist, Product Development, Abeona Therapeutics will present key findings: Vectors expressing Opa1 showed robust expression at both RNA and protein levels both in vitro and in vivo.In Opa1 knockout mouse fibroblasts, isoform variants 1, 5 and 7 expressed both RNA and protein with each variant corresponding to the expected cleavage pattern.Following intravitreal injection in wild type mice, variants 1 and 7 showed robust protein expression. The posters presented at ASGCT are available on ASGCT’s ePoster site and the Events page of Abeona’s website at https://investors.abeonatherapeutics.com/events. About Abeona’s AAV Ophthalmology Program Abeona’s preclinical programs are investigating the use of novel adeno-associated virus (AAV) strategies in therapies for serious genetic eye diseases. The most common form of Stargardt disease is caused by mutations in the ABCA4 gene, which prevents removal of toxic compounds from photoreceptor cells that results in photoreceptor cell death and progressive vision loss. ABO-504 is designed to efficiently reconstitute the full-length ABCA4 gene by implementing a dual AAV-vector strategy using the Cre-LoxP recombination system. XLRS is a rare, monogenic retinal disease that results in the irreversible loss of photoreceptor cells and severe visual impairment. XLRS is caused by mutations in the RS1 protein, which is normally secreted by retinal photoreceptors and bipolar neurons and functions to mediate cell-cell adhesion. ABO-503, composed of a functional human RS1 packaged in the novel AIM™ capsid AAV204, has shown preclinical efficacy following delivery to the retina in a mouse model of XLRS. ADOA, a form of hereditary vision loss associated with retinal ganglion cell (RGC) death, is predominantly caused by mutations in the Opa1 gene. ABO-505 is designed to express a functional copy of human Opa1 in the retina following para-retinal injection. ABO-505 aims to take advantage of the robust optic nerve and RGC transduction ability of AAV204 to deliver its genetic payload to the cells most affected by ADOA. About Abeona Therapeutics Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing cell and gene therapies for serious diseases. Abeona’s lead clinical program is EB-101, its investigational autologous, engineered cell therapy currently in development for recessive dystrophic epidermolysis bullosa. The Company’s development portfolio also features AAV-based gene therapies for ophthalmic diseases with high unmet medical need. Abeona’s novel, next-generation AAV capsids are being evaluated to improve tropism profiles for a variety of devastating diseases. Abeona’s fully integrated cell and gene therapy cGMP manufacturing facility produces EB-101 for the pivotal Phase 3 VIITAL™ study and is capable of clinical and potential commercial production of AAV-based gene therapies. For more information, visit www.abeonatherapeutics.com. Forward-Looking Statements This press release contains certain statements that are forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and that involve risks and uncertainties. We have attempted to identify forward-looking statements by such terminology as “may,” “will,” “believe,” “anticipate,” “expect,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances), which constitute and are intended to identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, numerous risks and uncertainties, including but not limited to, the timing and outcome of our Biologics License Application submission to the FDA for EB-101; continued interest in our rare disease portfolio; our ability to enroll patients in clinical trials; the outcome of future meetings with the FDA or other regulatory agencies, including those relating to preclinical programs; the ability to achieve or obtain necessary regulatory approvals; the impact of any changes in the financial markets and global economic conditions; risks associated with data analysis and reporting; and other risks disclosed in the Company’s most recent Annual Report on Form 10-K and subsequent periodic reports filed with the Securities and Exchange Commission. The Company undertakes no obligation to revise the forward-looking statements or to update them to reflect events or circumstances occurring after the date of this press release, whether as a result of new information, future developments or otherwise, except as required by the federal securities laws.