Optic Atrophy, Hereditary, Leber

Rate of visual improvement (Clinically Relevant Recovery, or CRR) among patients treated with LUMEVOQ® gene therapy is greater than that of idebenone-treated patients and untreated patients First set of meta-analyses to compare visual outcomes in Leber Hereditary Optic Neuropathy (LHON) patients with the ND4 mutation only PARIS--(BUSINESS WIRE)-- Regulatory News: This press release features multimedia. View the full release here: Figure 1. Visual Recovery (CRR from Nadir) Among ND4 LHON Patients – Results from Three New Meta-Analyses (Graphic: Business Wire) GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced initial results of new meta-analyses in Leber Hereditary Optic Neuropathy (LHON), which show those treated with LUMEVOQ® (GS010; lenadogene nolparvovec) gene therapy experienced a rate of visual recovery greater than that of idebenone-treated patients and untreated (natural history) patients. The meta-analyses are the first to focus solely on patients with the m.11778G>A ND4 mutation, which is the most common mutation and one with a poor visual prognosis1. Figure 1. Visual Recovery (CRR1 from Nadir2) Among ND4 LHON Patients – Results from Three New Meta-Analyses3,4 (See Figure 1) The meta-analyses depict a gradient of efficacy of visual recovery with LUMEVOQ® intravitreal gene therapy resulting in greater recovery rates than that of idebenone treatment, and both greater than that in the natural history of the disease. This gradient of recovery, based on the CRR measure of visual improvement, is observed at both eye level and patient level (response in one or both eyes). There is no overlap in confidence intervals when LUMEVOQ® is compared to idebenone and to natural history, indicating a positive difference in visual outcomes. The results were presented at the 2024 annual meeting of the North American Neuro-Ophthalmology Society (NANOS) and will also be presented at other major ophthalmology, neurology and neuro-ophthalmology medical conferences in Europe and the US later this year. Dr. Nancy J. Newman, LeoDelle Jolley Professor of Ophthalmology and Neurology at the Emory University School of Medicine in Atlanta, United-States, presented the findings at NANOS 2024. She noted, “This study is very important in order to compare these therapies’ abilities to achieve equivalent end-point metrics. It is clear that the degree of efficacy of the gene therapy was greater than the other currently available options of no treatment and idebenone use as previously administered in studies.” Based on the pre-defined statistical analysis plan, the three meta-analyses were performed on three groups of ND4-LHON patients according to therapy: LUMEVOQ® gene therapy one-time intravitreal injection, idebenone therapy and no treatment (natural history). To be included in the meta-analyses, studies had to satisfy a number of criteria that ensured comparability: for example, at least 3 data points per eye, information on the type of mutation with inclusion of ND4 patients only, and availability of visual outcomes data such as CRR. Clinically Relevant Recovery (CRR) is an accepted criterion of clinically meaningful visual improvement in LHON patients6 and could be extracted from all three patient samples. The final set of qualifying studies consisted of five natural history studies (173 patients), six idebenone studies (201 patients) and three LUMEVOQ® studies (174 patients). “The meta-analyses formalize the patient testimonies we have received that attest to the difference LUMEVOQ can make in patients’ lives: this treatment transforms the natural history of the disease,” said Laurence Rodriguez, Chief Executive Officer of GenSight. “The team is working hard to make sure that patients and clinicians facing the visual emergency that is LHON have access to an efficacious treatment.” The Company is currently engaging with authorities in the US, EU, and UK to align on the regulatory path for LUMEVOQ®. The Company aims to restart the Early Access Program (AAC) in France in Q3 2024. Follow-up of patients in the Phase III REFLECT study of LUMEVOQ® is ongoing, with topline results at Year 4 of follow-up expected this month. About GenSight Biologics GenSight Biologics S.A. is a clinical-stage biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics’ pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics’ lead product candidate, GS010, is in Phase III trials in Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease that leads to irreversible blindness in teens and young adults. Using its gene therapy-based approach, GenSight Biologics’ product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery. About Leber Hereditary Optic Neuropathy (LHON) Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of subjects have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. About LUMEVOQ® (GS010; lenadogene nolparvovec) LUMEVOQ® (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. “LUMEVOQ” was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018. LUMEVOQ® (GS010; lenadogene nolparvovec) has not been registered in any country at this stage. _________________________ 1 Newman et al: J Neuro-Ophthalmol 2020 Dec;40(4):547-557. 2 “Clinically Relevant Recovery”, or CRR, denotes an improvement in Best-Corrected Visual Acuity (BCVA) that satisfies one of two conditions: (1) A 10-letter (≥0.2 LogMAR) improvement for an on-chart starting visual acuity. (2) Improvement from “off-chart” to “on-chart” (≤1.6 LogMAR). 3 Nadir = lowest observation of visual acuity between baseline and time point of interest. 4 Three meta-analyses pre-definedin a statistical analysis plan 5 Sources of data: For idebenone and natural history data, systematic review of the literature and available clinical/regulatory reports on ND4 LHON patients; for Lumevoq, all phase 3 studies (RESCUE/RESTORE, REVERSE/RESTORE and REFLECT). 6 Carelli et al: J Neuro-Ophthalmol 2017; 0: 1-11 View source version on businesswire.com: Contacts GenSight Biologics Chief Financial Officer Ivan Tortet itortet@GENSIGHT-BIOLOGICS.com LifeSci Advisors Investor Relations Guillaume van Renterghem gvanrenterghem@lifesciadvisors.com +41 (0)76 735 01 31 Source: GenSight Biologics S.A. Smart Multimedia Gallery Photo Figure 1. Visual Recovery (CRR from Nadir) Among ND4 LHON Patients – Results from Three New Meta-Analyses (Graphic: Business Wire) Logo View this news release and multimedia online at:

Clinically meaningful improvement in visual acuity confirmed in a real-world setting: on-chart mean visual acuity at 9 months after injection, compared to off-chart mean at baseline Eyes of bilaterally treated patients improve more than those of unilaterally treated patients: +23 ETDRS letters vs. +18 ETDRS letters, with a higher responder rate (63% vs. 58%), with a similar and favorable safety pro > PARIS--(BUSINESS WIRE)-- Regulatory News: This press release features multimedia. View the full release here: (Graphic: Business Wire) GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that recent prospective real-world data from early access programs (EAP) confirm the benefit of LUMEVOQ® in patients with Leber Hereditary Optic Neuropathy from the ND4 mutation (ND4-LHON), as observed in clinical trials. One year after treatment, eyes of bilaterally injected patients experienced an average gain from nadir1 in best-corrected visual acuity (BCVA) equal to +23 ETDRS letters, greater than the 18-letter average gain among patients with only one eye injected. In both groups, the clinical improvement exceeded the conventional definition of clinical meaningfulness, in which a 15-letter gain is considered meaningful. The safety pro the gene therapy continues to be favorable and comparable between bilaterally treated patients and unilaterally treated patients. The results were presented at the 2024 annual meeting of the North American Neuro-Ophthalmology Society (NANOS) and will also be presented at other major medical conferences in Europe and the US later this year. Dr. Chiara La Morgia, MD, PhD, of the IRCCS Institute of Neurological Sciences of Bologna and the University of Bologna, Italy, presented the results at NANOS and commented, “It is very reassuring to clinicians that as successive waves of data become available, we continue to obtain a consistent picture of significant visual improvement among most patients treated with lenadogene nolparvovec. The evidence is becoming more robust, which is relevant for patients who are struck by a severe blinding disease such as LHON.” These latest analyses are able to draw upon a more robust sample than the early view of the data released in March 20232. In particular, the improvements at one year post-treatment and beyond provide a more definitive view of the upward trajectory of mean visual acuity (see Figure 1). One year after treatment, responder analyses show that the visual improvements accrue to the majority of patients: 63.2% of the eyes of bilaterally injected patients reached a clinically meaningful level of improvement in BCVA (≥0.3 LogMAR or +15 ETDRS letters), as did 57.9% of eyes of unilaterally injected patients. Nine months after injection, the average visual acuity corresponded to on-chart vision, compared to off-chart average visual acuity at baseline. The safety results obtained in the EAPs were consistent with those observed in the clinical studies, showing a favorable safety pro lenadogene nolparvovec. Notably, intraocular inflammation events reported in LUMEVOQ®-treated eyes were comparable in frequency, intensity, and location to those observed in the clinical studies. “Witnessing results like these energizes the GenSight team’s drive to restore early access availability for eligible patients by Q3 this year,” said Laurence Rodriguez, Chief Executive Officer of GenSight. “As the evidence accumulates that access to LUMEVOQ helps LHON patients, in clinical trials and in real-life settings, we are working on all options to bring LUMEVOQ to patients as quickly as possible.” LUMEVOQ® (GS010; lenadogene nolparvovec) was made available through EAPs in selected countries based on unsolicited requests from clinicians and where authorized for early access use by local regulations in those countries. The Company aims to resume early access in France under the Autorisation de l’accès compassionnel (AAC) program in Q3 2024. About GenSight Biologics GenSight Biologics S.A. is a clinical-stage biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics’ pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. Using its gene therapy-based approach, GenSight Biologics’ product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery. About Leber Hereditary Optic Neuropathy (LHON) Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of subjects have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. About LUMEVOQ® (GS010; lenadogene nolparvovec) LUMEVOQ® (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. “LUMEVOQ” was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018. LUMEVOQ® (GS010; lenadogene nolparvovec) has not been registered in any country at this stage. _________________________________ 1 Nadir = lowest observed visual acuity between baseline (time of treatment) and the time point of interest. 2 “GenSight Biologics Announces Presentation of LUMEVOQ® Efficacy and Safety Data from Early Access Programs for ND4-LHON Patients at NANOS 2023”, press release, March 15, 2023 View source version on businesswire.com: Contacts GenSight Biologics Chief Financial Officer Ivan Tortet itortet@GENSIGHT-BIOLOGICS.com LifeSci Advisors Investor Relations Guillaume van Renterghem gvanrenterghem@lifesciadvisors.com +41 (0)76 735 01 31 Source: GenSight Biologics S.A. Smart Multimedia Gallery Photo (Graphic: Business Wire) Logo View this news release and multimedia online at:

PARIS--(BUSINESS WIRE)-- Regulatory News: GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that new scientific data and analyses on the gene therapy LUMEVOQ® will be presented at the 50th Annual Meeting of the North American Neuro-Ophthalmology Society (NANOS) in Honolulu, Hawaii (March 2-7, 2024). Leading Leber Hereditary Optic Neuropathy (LHON) Key Opinion Leaders will provide updates on evidence related to the contralateral effect, on real-world experience with LUMEVOQ®, and on the comparison between LHON natural history, idebenone and LUMEVOQ®. Poster presentation: “Unilateral injection of lenadogene nolparvovec gene therapy induces successful transfection of retinal ganglion cells in both eyes” Presenter: Alfredo A. Sadun, MD, PhD, Doheny Eye Centers-UCLA, Pasadena, California, USA Time: Sunday, March 3rd, 2024, from 12:00 - 1:00 pm HST Location: Lanai room Poster presentation: “In the real-life setting, lenadogene nolparvovec gene therapy improves visual acuity in patients with MT-ND4 LHON” Presenter: Chiara La Morgia, MD, University of Bologna, Italy Time: Tuesday, March 5th, 2024, from 7:00 - 8:00 pm HST Location: Lanai room Poster presentation: “Lenadogene nolparvovec gene therapy improves visual recovery more than idebenone in m.11778G>A MT-ND4 LHON, and both treatments exceed the natural course of the disease” Presenter: Nancy J. Newman, MD, Emory University School of Medicine, Atlanta, Georgia, USA Time: Tuesday, March 5th, 2024, from 8:00 - 9:30 pm HST Location: Lanai room In addition, Benson S. Chen, MBChB, MSc, FRACP, Department of Clinical Neurosciences, University of Cambridge and Cambridge Eye Unit, Addenbrooke’s Hospital, United Kingdom, will present evidence on the quality of life of LHON patients in a platform presentation. Platform presentation: “Vision-Related Quality of Life in LHON Patients Treated with Lenadogene Nolparvovec Gene Therapy: Analysis of the VFQ-25 Using Rasch Measurement Theory” Scientific Platform Session III Time: Tuesday, March 5th, 2024, from 11:15 - 11:30 am HST Location: Kauai/Maui (GS) room About GenSight Biologics GenSight Biologics S.A. is a clinical-stage biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics’ pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics’ lead product candidate, GS010, is in Phase III trials in Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease that leads to irreversible blindness in teens and young adults. Using its gene therapy-based approach, GenSight Biologics’ product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery. About Leber Hereditary Optic Neuropathy (LHON) Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of subjects have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. About LUMEVOQ® (GS010; lenadogene nolparvovec) LUMEVOQ® (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. “LUMEVOQ” was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018. View source version on businesswire.com: Contacts GenSight Biologics Chief Financial Officer Ivan Tortet itortet@GENSIGHT-BIOLOGICS.com LifeSci Advisors Investor Relations Guillaume van Renterghem gvanrenterghem@lifesciadvisors.com +41 (0)76 735 01 31 Source: GenSight Biologics View this news release online at: