timrepigene emparvovec (BIIB111) / Biogen - LARVOL DELTA

To report a novel OCT clinical sign in choroideremia patients associated with a focal outer foveal defect (ARVO 2025) - "One patient was one-month post-choroideremia (timrepigene emparvovec) gene therapy...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Inherited Retinal Dystrophy • Macular Degeneration • Macular Edema • Ophthalmology • Retinal Disorders

An Open-Label Phase II Study Assessing the Safety of Bilateral, Sequential Administration of Retinal Gene Therapy in Participants with Choroideremia: The GEMINI Study. (PubMed, Hum Gene Ther) - P2 | "GEMINI was a multicenter, open-label, prospective, two-period, interventional Phase II study assessing the safety of bilateral sequential administration of timrepigene emparvovec, a gene therapy, in adult males with genetically confirmed choroideremia (NCT03507686, ClinicalTrials.gov)...Presence of anti-vector neutralizing antibodies at baseline was potentially associated with a higher percentage of TEAEs related to ocular inflammation or reduced visual acuity after injection of the first eye. The GEMINI study results may inform decisions regarding bilateral sequential administration of other gene therapies for retinal diseases."

Gene therapy • Journal • P2 data • Gene Therapies • Genetic Disorders • Hepatology • Inflammation • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders

Subretinal timrepigene emparvovec in adult men with choroideremia: a randomized phase 3 trial. (PubMed, Nat Med) - P3 | "Potential opportunities to enhance future gene therapy studies for choroideremia include optimization of entry criteria (more preserved retinal area), surgical techniques and clinical endpoints. EudraCT registration: 2015-003958-41 ."

Journal • P3 data • Diabetic Retinopathy • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

SOLSTICE: Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa (clinicaltrials.gov) - P3 | N=330 | Enrolling by invitation | Sponsor: NightstaRx Ltd, a Biogen Company | Trial completion date: Mar 2027 ➔ Jun 2026 | Trial primary completion date: Mar 2027 ➔ Jun 2026

Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

GEMINI: A Safety Study of Retinal Gene Therapy for Choroideremia With Administration of BIIB111 (clinicaltrials.gov) - P2 | N=66 | Completed | Sponsor: NightstaRx Ltd, a Biogen Company | Active, not recruiting ➔ Completed

Trial completion • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

GEMINI: A Safety Study of Retinal Gene Therapy for Choroideremia With Administration of BIIB111 (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: NightstaRx Ltd, a Biogen Company | Trial completion date: Feb 2022 ➔ Jun 2022 | Trial primary completion date: Feb 2022 ➔ Jun 2022

Trial completion date • Trial primary completion date • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

SOLSTICE: Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa (clinicaltrials.gov) - P3; N=440; Enrolling by invitation; Sponsor: NightstaRx Ltd, a Biogen Company; Phase classification: P=N/A ➔ P3

Clinical • Phase classification • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

"$BIIB investors react to gosuranemab (and Waterfall and BIIB111)" (@ByMadeleineA)

SOLSTICE: Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa (clinicaltrials.gov) - P=N/A; N=440; Enrolling by invitation; Sponsor: NightstaRx Ltd, a Biogen Company; N=100 ➔ 440; Trial completion date: Apr 2024 ➔ Mar 2027; Trial primary completion date: Apr 2024 ➔ Mar 2027

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

STAR: Efficacy and Safety of BIIB111 for the Treatment of Choroideremia (clinicaltrials.gov) - P3; N=170; Completed; Sponsor: NightstaRx Ltd, a Biogen Company; Active, not recruiting ➔ Completed

Clinical • Trial completion • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

"$BIIB pretty much keeps on pushing their readouts Jan 2020 July 2020 BIIB111 end 2020 H1 2021 BIIB054 H2 2020 H1 2021 TMS 007 end 2020 H1 2021" (@BursatilBiotech)

REGENERATE: REP1 Gene Replacement Therapy for Choroideremia (clinicaltrials.gov) - P2; N=30; Recruiting; Sponsor: University of Oxford; Trial primary completion date: Aug 2018 ➔ Aug 2019

Trial primary completion date • Biosimilar • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology

Nightstar Therapeutics reports 2017 financial results and business highlights (GlobeNewswire) - P=Obs, N=300, NCT03359551; Sponsor: Nightstar Therapeutics; "Preliminary top-line data from the NIGHT natural history observational study at 20 months follow-up...indicated that 22% of choroideremia eyes experienced a loss in visual acuity of five or more ETDRS letters, compared to less than 8% for patients treated with the high-dose of NSR-REP1."

Observational data • Inherited Retinal Dystrophy • Ophthalmology

NSR-REP1: "21% Hyper-response (15-Letter Gained) Observed in Treated Patients in Phase 1/2 Studies" (NightstaRx) - Corporate Overview: "Over 90% of NSR-REP1 Treated Patients Maintained Visual Acuity"

Clinical data • Inherited Retinal Dystrophy • Ophthalmology

Nightstar Therapeutics receives Regenerative Medicine Advanced Therapy (RMAT) designation for NSR-REP1 in choroideremia (GlobeNewswire) - "Nightstar Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to NSR-REP1...currently in Phase 3 development for the treatment of choroideremia...RMAT allows companies developing regenerative medicine and gene therapies to work more closely and frequently with the FDA, and grants all of the benefits of Breakthrough Therapy Designation, including eligibility for priority review, rolling review and accelerated approval."

FDA event • Inherited Retinal Dystrophy • Ophthalmology

Nightstar Therapeutics announces initiation of STAR phase 3 registrational trial for NSR-REP1 in choroideremia (NightstaRx Press Release) - "Nightstar Therapeutics...announced the initiation of the company’s STAR Phase 3 registrational trial to study the safety and efficacy of NSR-REP1 in patients with choroideremia. In data from 32 patients treated with NSR-REP1 across four open-label Phase 1/2 clinical trials, over 90% of treated patients maintained or improved their visual acuity over a one-year follow-up period."

New P3 trial • Ophthalmology

"$BIIB fresh new pipeline? New programs MS:BTK inh SMA: BIIB078/110/100 Pain: BIIB095 Ophtalmology: BIIB111/112 Neurocognitive disorders: BIIB104 Out MS: BIIB098 Ophthalmolog: BIIB087 Acute neurology: Natalizumab AD: Elembecestast Switch Parkinson to AD & Dementia: BIIB092 https://t.co/Vr96h9huu9" (@BursatilBiotech)

Alzheimer's Disease • CNS Disorders • Dementia • Gene Therapies • Genetic Disorders • Movement Disorders • Pain • Parkinson's Disease • Tauopathies And Synucleinopathies

BIIB111: Data from P3 STAR trial (NCT03496012) for choroideremia by end of 2021 (38th Annual J.P. Morgan Healthcare Conference, Biogen)

P3 data

BIIB111: Data from P3 STAR trial (NCT03496012) for choroideremia by end of 2021 (38th Annual J.P. Morgan Healthcare Conference, Biogen)

P3 data

Biogen announces enrollment completion of global phase 3 gene therapy study for an inherited retinal disorder (Biogen Press Release) - "Biogen Inc...announced today the enrollment of the last patient in the global Phase 3 STAR clinical study, which is evaluating the investigational gene therapy timrepigene emparvovec (BIIB111/AAV2-REP1) for the treatment of choroideremia (CHM)."

Enrollment closed

BIIB111: Data from P3 STAR trial (NCT03496012) for choroideremia in H2 2020 (Biogen) - Q3 2019 Results

P3 data

Development of 'gene therapy', a rare ophthalmologic disease, after LuxTina [Google Translation] (Biospectator) - "'It is expected to be approved soon as soon as NSR-REP1 of NightStar is in phase III clinical trials.' The target candidate is AAV2 vector carrying recombinant human cDNA to generate REP1 in the eye, and clinical trials are under way to complete the recruitment of about 140 patients by the first quarter of 2020."

Enrollment status

Biogen completes acquisition of Nightstar Therapeutics for approximately $800 million (GlobeNewswire) - "Biogen...announced that it has completed its acquisition of Nightstar Therapeutics...As a result of the acquisition, Biogen now has added two mid- to late-stage clinical assets, as well as preclinical programs, in ophthalmology. The total transaction value was approximately $800 million, after taking into account expected transaction expenses and cash at closing...NST’s lead asset is NSR-REP1 for the treatment of choroideremia..."

Licensing / partnership

NSR-REP1: Protection of patents related to product and methods of treating CHM until 2032 (NightstaRx) - Annual Report 2018

Patent

NSR-REP1: Data from P3 STAR trial (NCT03496012) for choroideremia in H2 2020 (Biogen) - Biogen Planned Acquisition of Nightstar Therapeutics

P3 data