Pipeline update: Catch up on recent updates in the retina pipeline

Retina continues to see big moves in the US Food and Drug Administration (FDA) pipeline, advancing clinical trials and receiving designations leading to hopeful approvals for treatments in wet and dry age-related macular degeneration (AMD), geographic atrophy (GA), diabetic macular edema (DME), and other retinal diseases.

4D-150

4D Molecular Therapeutics (4DMT) is advancing its treatment, 4D-150, for the treatment of wet AMD. As of July 2025, the company announced an accelerated phase 3 development of the drug, and a streamlined organization to drive late-stage execution.¹

4FRONT-1, the North American phase 3 clinical trial of 4D-150 in wet AMD, has exceeded initial projections for enrollment and site activation, the company said in July.¹ Because of the program advancing ahead of the original timeline, 52-week topline data are now expected in H1 of 2027, rather than H2 of 2027. 4FRONT-2 (NCT07064759), the second phase 3 trial of 4D-150, was initiated in June 2025, also ahead of schedule.¹ 52-week topline data of 4FRONT-2 are expected in H2 2027.

“We are thrilled with the strong interest in 4D-150 from investigators and patients in both 4FRONT phase 3 studies, reflecting their belief in the phase 1/2 data demonstrating the tolerability and robust, durable clinical activity of this potential foundational backbone therapy for retinal vascular diseases,” Dhaval Desai, chief development officer of 4DMT, said in a press release.

4D-150 is described by the company as, “a potential backbone therapy that is designed to provide multi-year sustained delivery of anti-VEGF from the retina with a single, safe, intravitreal injection.”¹

The drug is not only being developed for the treatment of wet AMD but is also being investigated for the treatment of DME.

4DMT presented positive 60-week results from the SPECTRA clinical trial (NCT05930561), evaluating 4D-150 for the treatment of DME.²

SPECTRA is a prospective, multicenter, randomized, active-controlled, double-masked dose-ranging trial, which was conducted in two parts: dose confirmation and dose expansion.³ The data was presented in an oral presentation by Almeida during the 43^rd Annual American Society of Retina Specialists (ASRS) Scientific Meeting.

“The positive results from the SPECTRA trial demonstrate the tolerability and consistent, durable clinical activity of 4D-150 in DME, highlighting the potential for the product candidate to become a backbone therapy that can dramatically reduce treatment burden compared to the labeled regimen of standard-of-care aflibercept 2mg every eight weeks,” David Almeida, MD, MBA, PhD, said in a release.²

“4D-150 has the potential to fundamentally transform the treatment of DME by reducing treatment burden with a product that has adherence by design, while providing meaningful, lasting vision improvement. This is especially important in DME, which frequently occurs in a working-age population.”

Highlights from the 60-week data include:

1. 4D-150 was well-tolerated with no intraocular inflammation at any timepoint.²
2. No reports of hypotony, endophthalmitis, vasculitis, choroidal effusions, or retinal artery occulsions.²
3. Patient safety was maximized while assessing initial clinical activity using stringent supplemental aflibercept criteria.²
4. Sustained gain of best corrective visual acuity (BCVA) of +9.7 letters was seen in the phase 3 dose.²

In addition to the positive topline data, 4DMT also received the regenerative medicine advanced therapy (RMAT) designation from the FDA, and the next steps for approval are pending the final FDA and EMA alignment on a phase 3 clinical trial design and funding pathway.²

AAVB-039

In August 2025, the FDA granted fast track designation to AAVantgarde Bio’s gene therapy program, AAVB-039 for the treatment of Stargardt disease.⁴

“This designation represents an important milestone for our program and enables us to accelerate development efforts as we work to bring a potentially transformative therapy to patients as quickly as possible,” Natalia Misciattelli, PhD, chief executive officer of AAVantgarde, said in a press release.⁴

AAVB-039 aims to address the underlying cause of Stargardt disease secondary to biallelic mutation in ABCA4 by providing the full-length ABCA4 protein.⁴ The therapy’s safety, tolerability, and preliminary efficacy is patients with Stargardt disease is currently being evaluated in the phase 1/2 CELESTE (NCT07161544) clinical trial.⁴ Additionally, AAVantgarde is conducting a prospective natural history study, STELLA, across the US, Europe, and the UK. STELLA has informed the clinical trial design of CELESTE.⁵

According to previous reporting from Ophthalmology Times, AAVantgarde also has its first clinical-stage product, AAVB-081, in phase 1/2 development for the treatment of retinitis pigmentosa.⁵

Ixo-vec ARTEMIS trial

Adverum Biotechnologies initiated the ARTEMIS phase 3 study earlier this year in March, with the screening completed in September.^6,7

ARTEMIS (NCT06856577) is a US-based, multicenter, randomized, double-masked, active-comparator-controlled phase 3 study evaluating a single intravitreal injection of Ixo-vec compared to an active comparator, in a broad participant population with neovascular (wet) AMD (nAMD).⁸

The first of two planned phase 3 registrational trials, the primary endpoint is the mean change in best corrected visual acuity (BCVA) of Ixo-vec (6E10/ vg/eye) compared to aflibercept (2mg) every 8 weeks in both treatment-naïve and previously treated patients, measured at weeks 52 and 56.^6-8 The second study, AQUARIUS, is expected to be conducted globally, with more details to come.⁶

“Leveraging our robust data for Ixo-vec, the ARTEMIS phase 3 trial was designed to enhance the potential for clinical, regulatory, and commercial success,” Rabia Gurses Ozden, MD, chief medical officer at Adverum, said in a press release.⁶

“We have been thrilled by the enthusiasm of retina specialists for this design, including studying Ixo-vec in both treatment-naïve and previously treated patients, which we expect will increase the speed of enrollment and generate a registrational dataset representative of real-world patient demographics. We are eager to generate the data necessary to seek regulatory approval and ultimately establish Ixo-vec as a transformative treatment option for a broad spectrum of wet AMD patients.”

The company expects to complete enrollment of ARTEMIS of at least 284 treatment-naïve and treatment experienced patients in Q4 2025, with a data readout expected in Q1 2027.⁷

ANXV

Annexin Pharmaceuticals has received approval from the UK Medicines and Healthcare products Regulatory Agency (MHRA) to begin a clinical Proof of Concept phase 2a study for the company’s drug candidate, ANXV.⁹ ANXV is intended for the treatment of diabetic retinopathy (DR).

The company describes ANXV as, “an investigational new drug containing the human protein Annexin A5, produced by the recombinant techniques in the bacteria Escherichia Coli (E. coli). Like endogenous Annexin A5, ANXV can protect cells, reduce adhesive properties and influence the actions by immune cells.”¹⁰

In addition to DR patients, patients with newly diagnosed retinal vein occlusion (RVO) will be included in the proof of concept in preparation for an upcoming phase 2b study.⁹

Prof Paulo-Eduardo Stanga will serve as principal investigator of the phase 2a study, which will be conducted at The Retina Clinic in London.⁹ 

According to Annexin, the first patients are expected to be treated in Q3 2025, with initial data expected approximately 3 months later and thereafter on an ongoing basis.⁹

“I have reviewed the phase 2a data in RVO (NCT05532735) and ANXV appears as a safe and promising drug candidate for the treatment of RVO and DR. I believe we will be able to further document safety and tolerability and capture potential early and beneficial effects in both diseases with the benefit of our clinical research experience and state-of-art functional and imaging equipment for assessing the retina,” Stanga said in a press release.⁹

Annexin previously concluded a phase 2a study on ANXV for the treatment of RVO, resulting in positive topline results.¹¹ The drug demonstrated a favorable safety profile and the data support further clinical development of ANXV in RVO, the company said.¹¹

Vonaprument, formerly ANX007

In July 2025, Annexon announced the completion of its enrollment in the phase 3 ARCHER II trial (NCT06510816) of vonaprument (formerly ANX007) for the treatment of dry age-related macular degeneration (AMD) with geographic atrophy (GA).¹²

The primary purpose of the study is to determine if monthly IVT injections of vonaprument reduce vision loss in participants with GA secondary to AMD^.13

Granted fast track designation by the FDA, vonaprument is also the first therapeutic candidate for the treatment of GA to receive priority medicine (PRIME) designation in the European Union.¹¹

“The global reach of ARCHER II has increased awareness of vonaprument’s innovative mechanism and compelling phase 2 results,” David Eichenbaum, MD, director of research at Retina Vitreous Associates of Florida, said in a release.

“With no approved therapies in Europe and limited options in the US, there is an urgent need for a treatment for GA that protects vision, the most clinically meaningful outcome for patients.”

Eichenbaum caught up with Modern Retina to talk about the ARCHER II study during the 2025 American Society of Retina Specialists (ASRS) meeting.

Topline data from the phase 3 ARCHER II trial is expected in H2 2026.¹¹

Migaldendranib (MGB)

During the 2025 European Society of Retina Specialists (EURETINA) held September 4-7 in Paris, Ashvattha Therapeutics shared positive topline 40-week phase 2 data of MGB for the treatment of DME and nAMD.¹⁴

“These phase 2 results demonstrate the potential of MGB to address one of the biggest challenges in retinal care today – the treatment burden associated with frequent in-office intravitreal injections,” Susan Schneider, MD, acting chief medical officer of Ashvatta, said in a press release.

“With the safe systemic and ocular outcomes seen to date, MGB offers a differentiated approach that has the possibility to enable monthly at-home subcutaneous administration and could meaningfully reduce the burden of care for patients with DME and nAMD, conditions that are chronic and typically bilateral.”

As previously reported on Ophthalmology Times, key findings of the 40-week phase 2 clinical trial include:¹⁵

• The annualized rate of IVT injections in all study eyes (DME and nAMD) decreased from 8.4 to 1.6 per year, or a 78.6% (4.7-fold) DME (n=8) and an 83.4% (6-fold) nAMD (n=14) reduction in the need for supplemental anti-VEGF versus pre-study IVT.
• A bilateral MGB treatment benefit was demonstrated with the annualized rate of IVT injections in all fellow eyes, decreasing from 8.3 to 0.6 per year, or an 89.1% (9.1-fold) reduction in the need for supplemental anti-VEGF versus pre-study IVT.
• The mean change from baseline out to week 40 was +6.1 ETDRS letters in best corrected visual acuity (BCVA) and -23.3 μm in central subfield thickness (CST) in DME study eyes.
• Improvements in BCVA and CST were also observed in nAMD study eyes.
• SubQ MGB is safe and well tolerated, with no treatment-related systemic or ocular serious adverse events reported and no clinically significant changes from baseline in renal, hepatic, or cardiac values.

Laru-zova

During this busy conference season, Beacon Therapeutics shared positive topline data for two of the company’s phase 2 trials – SKYLINE (NCT06333249) and DAWN (NCT06275620), both investigating laruparetigene zovaparvovec (laru-zpva) for the treatment of X-linked retinitis pigmentosa (XLRP).¹⁶

The data showed that laru-zova was well-tolerated by SKYLINE participants through month 36 and DAWN patients at month 9 or longer.¹⁶

Currently, laru-zova has regenerative medicine advancement therapy (RMAT) and fast track designations from the FDA, priority medicines (PRIME) designation from the European Medicines Agency (EMA), innovative licensing and access pathway (ILAP) from the MHRA, as well as orphan drug designation (ODD) from both the FDA and EMA.¹⁷

“We are pleased to be sharing key data from our DAWN and SKYLINE trials, building on one of the most significant bodies of evidence for a gene therapy in ocular disease,” Daniele Chung, DO, MA, chief medical officer of Beacon Therapeutics, said in a press release.¹⁷

“These new data updates reinforce our belief in the potential for laru-zova through clinical development while engaging with regulators and the patient community.”

Additionally, LLVA is being evaluated as the primary endpoint in Beacon’s ongoing pivotal phase 2/3 VISTA trial (NCT04850118) of laru-zova for the treatment of XLRP.¹⁷ The company completed enrollment of VISTA in July 2025 and expects to report topline data is H2 of 2026.¹⁷

Beacon plans to support its regulatory submissions to the US and Europe with the data from the VISTA trial alongside long-term data from the ongoing phase 2 DAWN trial, the phase 1/2 HORIZON and phase 2 SKYLINE studies.18

“The VISTA study has been carefully designed to provide the clinical evidence needed to demonstrate laru-zova’s potential to improve functional vision in patients with XLRP,” Chung said in a release.18

“We are applying our deep understanding of both ocular disease and gene therapy by using a highly efficient AAV capsid and a stabilized gene cassette that expresses the full-length RPGR protein, to support better vision outcomes.”

Modern Retina intends to cover the latest in FDA news. Stay tuned for more updates as they become available.

References:

1. 4DMT Announces Accelerated 4D-150 Phase 3 Development in Wet AMD and Streamlined Organization to Drive Late-Stage Execution | 4D Molecular Therapeutics. 4D Molecular Therapeutics. Published 2025. Accessed October 13, 2025. https://4dmt.gcs-web.com/news-releases/news-release-details/4dmt-announces-accelerated-4d-150-phase-3-development-wet-amd

2. 4DMT Presents Positive 60-Week Results from 4D-150 SPECTRA Clinical Trial in DME and Regulatory Update | 4D Molecular Therapeutics. 4D Molecular Therapeutics. Published 2025. Accessed October 13, 2025. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-presents-positive-60-week-results-4d-150-spectra-clinical

3. Clinicaltrials.gov. Published 2025. Accessed October 13, 2025. https://clinicaltrials.gov/study/NCT05930561?term=4D-150&rank=1

4. AAVantgarde Bio Announces FDA Fast Track Designation for AAVB-039 for the Treatment of Stargardt Disease. AAVantgarde. Published August 12, 2025. Accessed October 13, 2025. https://www.aavantgarde.com/en/news/aavantgarde-bio-announces-fda-fast-track-designation-for-aavb-039-for-the-treatment-of-stargardt-disease/ 

5. Harp MD. FDA grants fast track designation to AAVantgarde Bio for AAVB-039. Ophthalmologytimes.com. Published August 12, 2025. Accessed October 13, 2025. https://www.ophthalmologytimes.com/view/fda-grants-fast-track-designation-to-aavantgarde-bio-for-aavb-039

6. Adverum Biotechnologies Initiates ARTEMIS Phase 3 Study Evaluating Ixo-vec for Wet AMD. Adverum.com. Published 2022. https://investors.adverum.com/press_releases/news-details/2025/Adverum-Biotechnologies-Initiates-ARTEMIS-Phase-3-Study-Evaluating-Ixo-vecfor-Wet-AMD/default.aspx

7. Adverum Biotechnologies Announces Completion of Screening for Pivotal Phase 3 ARTEMIS Trial of Ixo-vec for Wet Age-Related Macular Degeneration. Adverum.com. Published 2022. Accessed October 13, 2025. https://investors.adverum.com/press_releases/news-details/2025/Adverum-Biotechnologies-Announces-Completion-of-Screening-for-Pivotal-Phase-3-ARTEMIS-Trial-of-Ixo-vec-for-Wet-Age-Related-Macular-Degeneration/default.aspx

8. Clinicaltrials.gov. Published 2025. Accessed October 13, 2025. https://clinicaltrials.gov/study/NCT06856577?term=ARTEMIS%20IXO-VEC&rank=1

9. Annexin receives approval for Phase 2a study in diabetic retinopathy and RVO - Annexin Pharmaceuticals EN. Annexin Pharmaceuticals EN. Published 2025. Accessed October 13, 2025. https://annexinpharma.com/mfn_news/annexin-receives-approval-for-phase-2a-study-in-diabetic-retinopathy-and-rvo/

10. ANXV - Annexin Pharmaceuticals EN. Annexin Pharmaceuticals EN. Published November 14, 2023. Accessed October 13, 2025. https://annexinpharma.com/anxv/

11. Annexin reports promising topline results in RVO Phase 2a study - Annexin Pharmaceuticals EN. Annexin Pharmaceuticals EN. Published 2024. Accessed October 13, 2025. https://annexinpharma.com/mfn_news/annexin-reports-promising-topline-results-in-rvo-phase-2a-study/

12. Harp MD. Annexon completes enrollment in phase 3 ARCHER II trial of vonaprument for geographic atrophy. Ophthalmologytimes.com. Published July 24, 2025. Accessed October 13, 2025. https://www.ophthalmologytimes.com/view/annexon-completes-enrollment-in-phase-3-archer-ii-trial-of-vonaprument-for-geographic-atrophy

13. Clinicaltrials.gov. Published 2025. Accessed October 13, 2025. https://clinicaltrials.gov/study/NCT06510816

14. Hennings D. Ashvattha Therapeutics Announces Positive Topline 40-Week Phase 2 Results for Migaldendranib in Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration – Ashvattha Therapeutics. Avttx.com. Published September 4, 2025. Accessed October 13, 2025. https://avttx.com/ashvattha-therapeutics-announces-positive-topline-40-week-phase-2-results-for-migaldendranib-in-diabetic-macular-edema-and-neovascular-age-related-macular-degeneration/

15. Filkins K. Ashvattha reports positive phase 2 results for migaldendranib in DME and nAMD. Ophthalmologytimes.com. Published September 5, 2025. Accessed October 13, 2025. https://www.ophthalmologytimes.com/view/ashvattha-reports-positive-phase-2-results-for-migaldendranib-in-dme-and-namd

16. Filkins K. Beacon Therapeutics announces positive topline data from DAWN and SKYLINE trials. Modernretina.com. Published September 8, 2025. Accessed October 13, 2025. https://www.modernretina.com/view/beacon-therapeutics-announces-positive-topline-data-from-dawn-and-skyline-trials

17. Beacon Therapeutics Announces Positive Interim 9+ Month Results fromDAWN Trial and 36-Month Phase 2 SKYLINE Trial Data for Laru-zova in Patients with X-linked Retinitis Pigmentosa (XLRP) at EURETINA 2025 - Beacon Therapeutics. Beacon Therapeutics. Published September 4, 2025. https://www.beacontx.com/news-and-events/beacon-therapeutics-announces-positive-interim-9-month-results-fromdawn-trial-and-36-month-phase-2-skyline-trial-data-for-laru-zova-in-patients/

18. Beacon Therapeutics completes enrollment in registrational Phase 2/3 VISTA trial of laru-zova for patients with XLRP - Beacon Therapeutics. Beacon Therapeutics. Published July 8, 2025. Accessed October 13, 2025. https://www.beacontx.com/news-and-events/beacon-therapeutics-completes-enrollment-in-registrational-phase-2-3-vista-trial-of-laru-zova-for-patients-with-xlrp/