ixoberogene soroparvovec (ADVM-022) / Adverum Biotech - LARVOL DELTA

ARTEMIS: Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration (clinicaltrials.gov) - P3 | N=284 | Recruiting | Sponsor: Adverum Biotechnologies, Inc. | Trial completion date: Mar 2030 ➔ Nov 2030 | Trial primary completion date: Apr 2027 ➔ Dec 2026

Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Lilly to Acquire Adverum Biotechnologies (PRNewswire) - "Under the terms of the merger agreement, Lilly will commence a tender offer to acquire all of the outstanding shares of Adverum common stock for a per share price of (1) $3.56 per share in cash payable at closing plus (2) one non-transferrable contingent value right (CVR) that entitles the holder to receive up to an additional $8.91 per CVR in cash upon the achievement of two milestones described below, for total potential per share consideration of up to $12.47."

M&A • Wet Age-related Macular Degeneration

Adverum Biotechnologies Announces Completion of Screening for Pivotal Phase 3 ARTEMIS Trial of Ixo-vec for Wet Age-Related Macular Degeneration (GlobeNewswire) - "Adverum Biotechnologies...announced it has notified sites that it plans to complete screening in ARTEMIS...by September 30, seven months after initiation, because the company now expects full enrollment of at least 284 treatment-naïve and treatment experienced patients in 4Q 2025 and data readout in 1Q 2027."

P3 data • Trial status • Wet Age-related Macular Degeneration

ARTEMIS: Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration (clinicaltrials.gov) - P3 | N=284 | Recruiting | Sponsor: Adverum Biotechnologies, Inc. | Trial primary completion date: Mar 2030 ➔ Apr 2027

Trial primary completion date • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

A Semimechanistic Ocular Pharmacokinetic Model for ADVM-022 Gene Therapy Describing the Dose-Exposure Relationship in Monkeys and the Scaling to Human. (PubMed, Mol Pharm) - "Increasing doses within the lower range of preclinical studies (3 × 1010-2 × 1013 vg/eye) lead to increased transduction and expression, plateauing at upper limits of approximately 12.7 μg/day·cm3 for the retina, and 0.785 μg/day for extra-retinal tissues at higher doses. Assuming similar transduction efficiency between humans and monkeys, with adjustments for anatomical differences, the model provided predictions of ocular aflibercept concentrations that aligned with observations from the two dose groups in the phase 1 OPTIC clinical trial, supporting the utility of this approach."

Journal • PK/PD data • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Gene Therapy in Age-related Macular Degeneration. (PubMed, Int Ophthalmol Clin) - "Current trials in wet AMD include ADVM-022 and RGX-314. Current trials in dry AMD include GT-005 and JNJ-1887."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Biodistribution and Expression of Ixoberogene Soroparvovec (Ixo-vec) in Non-Human Primates: A Comprehensive Study on Intraocular and Systemic Distribution (ASGCT 2025) - P1, P2 | "Additionally, these data confirm the potential to safely dose the second eye for patients with bilateral nAMD. Disease Focus of Abstract:Ophthalmic Diseases"

Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Gene Therapy in Diabetic Retinopathy and Diabetic Macular Edema: An Update. (PubMed, J Clin Med) - "Preliminary results from the SPECTRA (4D-150) and ALTITUDE (ABBV-RGX-314) studies are promising, demonstrating an improvement in the diabetic retinopathy severity score and a reduction in the treatment burden. In contrast, the INFINITY (ADVM-022) trial was complicated by several cases of severe inflammation and hypotony that led the sponsor to discontinue further development of this product for DME."

Journal • Review • Diabetic Macular Edema • Diabetic Retinopathy • Gene Therapies • Glaucoma • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis

Gene therapy in neovascular age related macular degeneration: an update. (PubMed, Graefes Arch Clin Exp Ophthalmol) - "Ixoberogene soroparvovec, RGX-314 and 4D-150 are the leading NV-AMD genetic treatment programs. Pre-clinical models suggest that genome surgery with clustered regularly interspaced short palindromic repeats (CRISPR) may be another option in the future."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Oncology • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Long-Term Follow-up Study of ADVM-022 in DME (INFINITY-EXT) (clinicaltrials.gov) - P=N/A | N=22 | Active, not recruiting | Sponsor: Adverum Biotechnologies, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Retinal Disorders

Adverum Biotechnologies Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Pipeline Highlights and Updates to Anticipated Milestones (GlobeNewswire) - "Upcoming Anticipated Milestones: 2H 2025: Initiate the global AQUARIUS Phase 3 trial; 4Q 2025: Present Phase 2 LUNA two-year long-term follow-up data."

New P3 trial • P2 data • Wet Age-related Macular Degeneration

Ixoberogene Soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular Age-Related Macular Degeneration: Phase 2 LUNA 52-Week Data (ARVO 2025) - P2 | "Methods Participants were randomized across two Ixo-vec doses, 6x1010 and 2x1011 vg/eye (6E10 and 2E11) across multiple corticosteroid prophylactic regimens including topical difluprednate ± IVT dexamethasone ± oral prednisone (NCT05536973). 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."

Gene therapy • P2 data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

ARTEMIS: Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration (clinicaltrials.gov) - P3 | N=284 | Recruiting | Sponsor: Adverum Biotechnologies, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Biodistribution and Expression of Ixoberogene soroparvovec (Ixo-vec) in Non-Human Primate Eye (ARVO 2025) - P1, P2 | "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."

Ophthalmology

Ixoberogene Soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular AMD: 4-Year Safety and Efficacy Results from the OPTIC Trial (ARVO 2025) - P | "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 • Gene therapy • Age-related Macular Degeneration • Cataract • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

In Situ Hybridization Demonstrates Ocular Distribution of Ixo-vec IVT Gene Therapy in Human Cadaver Eyes with wAMD and Supports Durable Clinical Efficacy (ARVO 2025) - "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 • Gene therapy • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Nonclinical study of ixo-vec gene therapy for nAMD supports efficacy for a human dose of 6E10 vg/eye and staggered dosing of fellow eyes. (PubMed, Mol Ther Methods Clin Dev) - P1, P2 | "Staggered dosing, administered 2 months apart, did not exacerbate IOI, and both eyes maintained therapeutic aflibercept levels. These findings support the tolerability and efficacy of staggered dosing, indicating the potential for bilaterally relevant aflibercept levels with ixo-vec, due to immune response confinement to the dosed eye."

Journal • Age-related Macular Degeneration • Gene Therapies • Inflammation • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

ARTEMIS: Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration (clinicaltrials.gov) - P3 | N=284 | Not yet recruiting | Sponsor: Adverum Biotechnologies, Inc.

New P3 trial • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Adverum Biotechnologies Initiates ARTEMIS Phase 3 Study Evaluating Ixo-vec for Wet AMD (GlobeNewswire) - "Adverum Biotechnologies, Inc...today announced the initiation of the ARTEMIS Phase 3 study. This pivotal trial is designed to evaluate the efficacy and safety of Ixo-vec (ixoberogene soroparvovec) as a one-time intravitreal (IVT) injection for patients with neovascular (wet) age-related macular degeneration (AMD)....ARTEMIS is a US-based study evaluating a single administration of Ixo-vec (6E10 vg/eye) compared to aflibercept (2mg) every 8 weeks in approximately 284 patients with wet AMD, including both treatment-naïve and previously treated patients."

New P3 trial • Wet Age-related Macular Degeneration

Safety and Efficacy of ADVM-022 in Treatment-Experienced Patients With Neovascular Age-related Macular Degeneration [LUNA] (clinicaltrials.gov) - P2 | N=69 | Active, not recruiting | Sponsor: Adverum Biotechnologies, Inc. | Trial completion date: Nov 2028 ➔ Aug 2028 | Trial primary completion date: Aug 2028 ➔ Aug 2024

Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Adverum Biotechnologies Announces Webcast to Report 52-Week LUNA Phase 2 Clinical Data and 4-Year OPTIC Clinical Data, and to Provide Key Pivotal Program Design Elements (GlobeNewswire) - "Adverum Biotechnologies, Inc...plans to host a webcast to report 52-week LUNA phase 2 clinical data and 4-year OPTIC clinical data, and to provide key pivotal program design elements Monday, November 18th at 7:30 a.m. EST."

P1 data • P2 data • Age-related Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

Adverum Biotechnologies Reports Third Quarter 2024 Financial Results, Provides Corporate Highlights and Updates Anticipated Milestones (GlobeNewswire) - "Upcoming Anticipated Milestones: 4Q 2024: LUNA 52-week data update, including all-available safety follow-up; 4Q 2024: OPTIC 4-year clinical data update; 4Q 2024: Phase 3 pivotal trial design update; H1 2025: Planned initiation of Phase 3 trial...Research and development expenses were $20.4 million for the three months ended September 30, 2024 compared to $20.7 million for the same period in 2023. Research and development expenses decreased due to lower facilities related expenses partially offset by higher spending on Ixo-vec clinical development and higher compensation expenses. Stock-based compensation expense included in research and development expenses was $1.1 million for the third quarter of 2024."

Commercial • New P3 trial • P1 data • P2 data • Age-related Macular Degeneration • Diabetic Macular Edema • Ophthalmology • Wet Age-related Macular Degeneration

Adverum Biotechnologies Appoints Jason L. Mitchell as Chief Commercial Officer as it Prepares to Initiate Pivotal Program (GlobeNewswire) - "Ixo-vec is currently being evaluated in the Phase 2 LUNA clinical trial. The company plans to announce LUNA 52-week data and pivotal program details in the 4th quarter of 2024. In addition, the company is on track to initiate the Ixo-vec pivotal program in the 1st half of 2025."

New trial • P2 data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues. (PubMed, Eye (Lond)) - "Gene therapies, including RGX-314 and Ixo-vec, express an anti-VEGF protein, and 4D-150, expresses an anti-VEGF protein and a VEGF-C inhibitory miRNA. Anti-VEGF associated therapeutics include OPT-302, targeting VEGF-C and VEGF-D, BI 836880, which inhibits VEGF-A and Ang-2 activity, and Tarcocimab tedromer, inhibiting all VEGF-A isoforms. Agents with novel mechanisms of action include UBX1325, which inhibits an anti-apoptotic protein, Restoret (EYE103), a Wnt agonist, and the tyrosine kinase inhibitors, EYP-1901, OTX-TKI, CLS-AX, and KHK4951."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC • VEGFD

Adverum Biotechnologies Reports Second Quarter 2024 Financial Results and Provides Program and Corporate Highlights (GlobeNewswire) - "Upcoming Anticipated Milestones...4Q 2024: Clinical data from the landmark LUNA 9-month analysis; 4Q 2024: Phase 3 pivotal trial design update; 1Q 2025: Clinical data from the landmark LUNA 52-week analysis; H1 2025: Planned initiation of Phase 3 trial."

Clinical protocol • New P3 trial • P2 data • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Wet Age-related Macular Degeneration