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CHICAGO, Oct. 1, 2022 — The Janssen Pharmaceutical Companies of Johnson & Manley announced today the primary results from the particular Phase 1/2 study evaluating the investigational gene therapy botaretigene sparoparvovec (formerly AAV-RPGR) in patients with the inherited retinal disease X-linked retinitis pigmentosa (XLRP) associated with the particular retinitis pigmentosa GTPase regulator (RPGR) gene. Treatment with botaretigene sparoparvovec was found to have an acceptable safety profile, and efficacy assessments in this proof-of-concept study demonstrated encouraging improvements in retinal sensitivity, visual function and functional vision. 1 These findings and additional updates, including data from a Phase one trial of investigational gene therapy JNJ-81201887 (JNJ-1887) for patients along with geographic atrophy (GA), a late-stage plus severe form of age-related macular degeneration (AMD), were presented in late-breaking oral presentations today at the Retina Subspecialty Day program of the American School of Ophthalmology (AAO) 2022 Annual Meeting (Abstracts #30071754 and #30071749).

XLRP is a rare condition estimated to impact one in 40, 000 people globally. 2, 3 People with XLRP have progressive eyesight loss, starting in childhood with night blindness. 4 Over time, they lose their peripheral vision leading to legal blindness by middle age. 4 Botaretigene sparoparvovec is being investigated within collaboration with MeiraGTx Holdings plc to treat patients along with XLRP caused by disease-causing variants in the particular eye-specific form of the RPGR (RPGR ORF15) gene. Through an one-time administration, botaretigene sparoparvovec is designed to deliver functional copies of the RPGR gene to counteract the particular loss associated with retinal cells with the goal of preserving and potentially restoring vision for those living with XLRP. Currently, there are no approved treatments with regard to XLRP. 4

“Individuals living with XLRP often begin in order to experience symptoms in child years, and as retinal degeneration progresses toward loss of sight, they can start to feel a sense of hopelessness as you will find no treatments to turn to, ” said Michel Michaelides, B. Sc., M. B., W. S., M. D. (Res), FRCOphth, FACS, Consultant Ophthalmologist, Moorfields Eye Hospital, Professor of Ophthalmology, University College London and lead investigator. “These outcomes from the MGT009 study are promising, as they represent the particular potential regarding botaretigene sparoparvovec to preserve eyesight and ultimately restore hope for these patients. inch

The primary endpoint of the MGT009 study ( NCT03252847 ) was safety, with secondary endpoints measuring changes in assessments associated with three domains of vision—retinal sensitivity, visible function plus functional vision—at specified time points post-treatment. 1 In the study’s dose escalation and expansion phases, significant sustained or increased functional improvement in each visual domain was observed in participants treated with botaretigene sparoparvovec compared to the randomized untreated control arm of the study at six months post-treatment. 1

Analyses from the pooled low and intermediate dose cohorts demonstrated enhancement in retinal sensitivity in the treated eyes compared to untreated eye within the randomized concurrent control arm as measured by both full-field static perimetry and microperimetry. one An improvement within mean retinal sensitivity because measured simply by static perimetry in the central 10-degree area of the particular retina was observed at 6 months inside the treated eyes compared to untreated eyes in the randomized concurrent control arm [in the full analysis of pooled low and intermediate doses across adults: 1.96 decibel (dB); (±95% CI: 0.59, 3.34); and in the sensitivity analysis when applying the Phase 3 criteria: 2.42 (0.91, 3.93)]. 1

As part associated with the research, patients performed a functional vision assessment using a visual mobility maze to assess their ability to navigate through simulated real-life obstacles across a broad range of controlled light. At week 26, improvement in walk time has been observed between the handled eyes within the low plus intermediate dosage cohorts and the untreated eye in the particular randomized contingency control equip at lower illumination levels (full analysis nominal p-value < 0. 05 in lux one and lux 16; in the sensitivity analysis when applying the Phase 3 criteria nominal p-value < 0. 01 at lux 1, lux 4 and lux 16). 1

The safety user profile of botaretigene sparoparvovec observed in MGT009 was consistent along with previous reports. one Botaretigene sparoparvovec demonstrated a good adverse event (AE) profile that had been anticipated plus manageable. 1 Most AEs were related to the particular surgical delivery procedure, had been transient and resolved without intervention. 1 There were no dose-limiting events. 1 A total of three serious adverse events (SAEs) were noticed in the overall Phase 1/2 MGT009 clinical study; two SAEs, which were previously reported, were seen in the dose-escalation phase of the study (n=10; one retinal detachment and one panuveitis in the low dose cohort), and a single additional SAE associated with increased intraocular pressure was observed inside the dosage escalation phase and resolved with treatment. one

“Without an authorized treatment option available, people with XLRP are faced with the inevitable fate of going blind in the prime associated with life, inches said James List, Meters. D., Ph. D., Global Therapeutic Area Head, Cardiovascular, Metabolism, Retina & Pulmonary Hypertension, Janssen Research & Development, LLC. “We’re in a race to save sight intended for these individuals and are encouraged by the strength of the particular data that we’ve shared so far. We look forward to advancing the medical development of botaretigene sparoparvovec as part of our mission aid plus potentially restore vision to get these sufferers. ”

Further sensitivity analysis was conducted on study participants by applying the Phase 3 LUMEOS ( NCT04671433 ) research eligibility criteria that corroborated the endpoints selected for the Phase a few study. 1 Currently, the LUMEOS study associated with botaretigene sparoparvovec for the treatment of patients with XLRP with disease-causing variants inside the RPGR gene will be actively dosing patients.

Phase 1 Data Evaluating JNJ-1887 in Geographic Atrophy
Janssen also presented late-breaking data from the Phase one, open-label, multicenter, dose-escalation, security and tolerability study ( NCT03144999 ) of the single intravitreal injection of JNJ-1887 within patients with advanced non-exudative (dry) age-related macular degeneration (AMD) along with GA. GA is an irreversible condition that will affects more than five million individuals worldwide. 5 It has a devastating impact on GA patients’ health-related quality of life, including their ability to read, drive and perform other day-to-day activities. 5 In this study, patients (n=17) were sequentially enrolled from a low, intermediate plus high dose without steroid prophylaxis, and all three doses of JNJ-1887 met the main endpoint associated with safety over the two-year follow-up period. 6 In addition , the supportive efficacy measures, including evaluation of GA lesion growth rates, showed a continual decline in lesion development over six-month increments. 6 These types of results are usually the first discussed from the Company’s common eye disease portfolio and indicate further assessment of this investigational gene therapy is warranted. 6

About the particular Phase 1/2 MGT009 Trial and Botaretigene Sparoparvovec
The particular Phase 1/2 MGT009 trial ( NCT03252847 ) has been an open-label, multicenter dosage escalation research that enrolled patients aged five years and older with X-linked retinitis pigmentosa (XLRP) brought on by disease causing variants within the retinitis pigmentosa GTPase limiter (RPGR) gene at multiple sites in the United States and the United Kingdom. The primary endpoint was protection and tolerability; secondary endpoints assessed retinal sensitivity, visible function and functional vision.

The scientific study has been composed of three parts: dose-escalation, pediatric dose-confirmation plus an expansion phase. In the dose escalation stage, adult patients were dealt with at 3 escalating doses of botaretigene sparoparvovec; a low (2×10 11 vg/mL), an advanced (4×10 11 vg/mL), and a high (8×10 11 vg/mL) dosage. In the growth phase, 42 adult male patients were randomized in order to either immediate treatment with one of two low or intermediate doses or an untreated concurrent manage arm along with deferred therapy. At six months, the particular untreated control arm had been randomized to receive either the low or more advanced treatment dosages. Botaretigene sparoparvovec was administered through subretinal delivery in only one eye. The adult patients received treatment with three amounts. The pediatric cohort (n=3) was only treated with an more advanced dose associated with botaretigene sparoparvovec.

Botaretigene sparoparvovec has been granted Fast Track and Orphan Drug designations simply by the U. S. Food and Drug Administration (FDA) plus PRIority MEdicines (PRIME), Advanced Therapy Medicinal Product (ATMP) and Orphan designations by the European Medicines Agency (EMA).

About the Janssen and MeiraGTx Strategic Collaboration
In January 2019, Janssen Research & Development, LLC entered into a worldwide collaboration plus license agreement  along with MeiraGTx Holdings plc, the clinical-stage gene therapy company, to develop, manufacture and commercialize its clinical-stage inherited retinal disease profile. Botaretigene sparoparvovec has been developed as part of a collaboration and license agreement. In addition to forming a research collaboration to explore new targets pertaining to other inherited retinal diseases, Janssen is usually working with MeiraGTx to build core capabilities inside viral vector design, optimization and manufacturing.

About the Stage 1 JNJ-1887 Trial plus JNJ-1887
JNJ-81201887 (JNJ-1887), formerly referred to as AAVCAGsCD59, is an investigational gene therapy meant for the remedying of people with geographic atrophy (GA) supplementary to dry age-related macular degeneration (AMD). JNJ-1887 is designed in order to increase the expression of a soluble type of CD59 (sCD59) intended to protect retinal tissues to slow and prevent disease progression. JNJ-1887 was evaluated in a Phase 1 clinical trial ( NCT03144999 ), an open-label, single-center dose escalation study to determine the basic safety of JNJ-1887 in adults 50 or even older along with advanced dry out AMD with GA. The particular patients had been treated on three escalating doses of JNJ-1887 without having steroid prophylaxis through a single intravitreal injection in one vision.

This Phase 1 research met its primary endpoint of safety in all doses of JNJ-1887 (n=17), along with supportive effectiveness measures which includes evaluation associated with GA lesion growth rates, which demonstrated a constant decline in lesion growth over six-month increments.

JNJ-1887 continues to be given Steps for success designation from the U. S. Food and Drug Administration (FDA) and Sophisticated Therapy Therapeutic Product (ATMP) designation with the European Medicines Agency (EMA).

Concerning the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating the future where disease is definitely a thing of the past. We’re the Pharmaceutic Companies associated with Johnson & Johnson, working tirelessly to make that future a reality for individuals everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. All of us focus upon areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism, & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

Learn more at . Follow us at  @JanssenGlobal . Janssen Research & Development, LLC is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Dr. Michaelides is a scientific founder of, plus consultant in order to, and has the financial relationship with MeiraGTx.

Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” while defined within the Private Securities Litigation Reform Act of 1995 regarding botaretigene sparoparvovec and JNJ-81201887. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from your expectations plus projections associated with Janssen Research & Advancement, LLC, any of the other Janssen Pharmaceutical Businesses and/or Johnson & Manley. Risks and uncertainties include, but are not limited to: challenges plus uncertainties inherent in product research and development, including the uncertainty of medical success and of obtaining regulatory approvals; doubt of commercial success; production difficulties and delays; competition, including technological advances, brand new products plus patents attained by competitors; challenges in order to patents; item efficacy or even safety concerns resulting inside product recalls or regulating action; changes in behavior and spending patterns of purchasers associated with health care products and services; changes to applicable laws and regulations, including global healthcare reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and some other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for that fiscal year ended  January 2, 2022, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” plus “Item 1A. Risk Factors, ” and in Johnson & Johnson’s subsequent Quarterly Reports on Type 10-Q and other filings using the Securities and Exchange Commission. Copies of those filings are available online at ,   or on request through Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Manley & Johnson undertakes in order to update any forward-looking statement as a result of new information or potential events or developments.

Michaelides, M et al. Ph1/2 AAV5-RPGR (Botaretigene Sparoparvovec) Gene Therapy Test in RPGR-associated X-linked Retinitis Pigmentosa (XLRP). Abstract #30071754. Presented at the 2022 American Academy of Ophthalmology Annual Meeting.

Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa. Am J Hum Genet . 1980; 32(2): 223–235.

Fishman GA. Retinitis pigmentosa. Genetic percentages. Arch Ophthalmol . 1978; 96(5): 822–826. doi: 10. 1001/archopht. 1978. 03910050428005.

4 Wang DY, Chan WM, Tam PO, ainsi que al. Gene mutations in retinitis pigmentosa and their own clinical implications. Clin Chim Acta . 2005; 351(1-2): 5-16.

5 Cohen, MN ou al. Stage 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy (GA) Due to Age-related Macular Degeneration (AMD). Abstract #30071749. Presented in the 2022 American School of Ophthalmology Annual Conference.

six Singh RP, Patel SS, Neilsen JS, et al. Patient-, caregiver- and attention care professional-reported burden associated with geographic atrophy secondary in order to age-related macular degeneration. Feel J Ophthalmic Clin Trials . 2019; 2(1): 1-6.

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