HMR-59 (AAVCAGsCD59 / JNJ-1887): An Investigational Gene Therapy for Age-Related Macular Degeneration

1. Executive Summary

HMR-59, also identified by the codenames AAVCAGsCD59 and JNJ-1887, represents an investigational gene therapy employing an adeno-associated virus serotype 2 (AAV2) vector. It is designed as a potential one-time intravitreal treatment for advanced forms of Age-Related Macular Degeneration (AMD), including Geographic Atrophy (GA) and neovascular (wet) AMD.[1] The therapeutic strategy is centered on the intraocular expression of a soluble form of the human CD59 protein (sCD59). This protein is a natural inhibitor of the terminal complement pathway, specifically targeting the Membrane Attack Complex (MAC), a key mediator of cellular damage in AMD. By augmenting local sCD59 levels, HMR-59 aims to protect retinal cells from complement-mediated destruction, thereby slowing disease progression.[2]

The therapy was initially developed by Hemera Biosciences [1] and subsequently acquired by Janssen Pharmaceuticals, a Johnson & Johnson company, in December 2020, after which it also became known as JNJ-1887 or JNJ-81201887.[7] HMR-59 has completed Phase 1 clinical trials for both GA (NCT03144999) and wet AMD (NCT03585556). These early-phase studies established a manageable safety profile, with ocular inflammation being the most notable adverse event, generally mild to moderate and responsive to steroid treatment. Preliminary efficacy signals, such as a potential reduction in GA lesion growth rate and a decreased need for anti-VEGF injections in wet AMD, were also observed.[1]

Currently, HMR-59 is being evaluated in a more definitive Phase 2b clinical trial, PARASOL (NCT05811351), for patients with GA, with primary results anticipated in late 2025.[4] A long-term extension study (NCT06635148) is also underway to monitor the extended safety and durability of the treatment.[14] The development of HMR-59 from a smaller biotechnology company to its acquisition and continued advancement by a major pharmaceutical corporation suggests a strong perceived potential for this single-administration gene therapy to address the significant unmet medical needs in advanced AMD. This transition often signifies a greater capacity for navigating the extensive and costly later phases of clinical development and regulatory approval. The success of HMR-59 could offer a paradigm shift by significantly reducing the treatment burden associated with current AMD management strategies.

2. Introduction to HMR-59 (AAVCAGsCD59 / JNJ-1887)

Overview of the Therapeutic Agent

HMR-59 is an investigational gene therapy product designed for ocular administration. Its scientific nomenclature, AAVCAGsCD59, denotes its composition: it utilizes an Adeno-Associated Virus serotype 2 (AAV2) as a vector to deliver a transgene encoding a soluble, secreted form of the human CD59 protein (sCD59).[1] The "CAG" element in its name refers to a synthetic strong promoter (composed of the cytomegalovirus (CMV) early enhancer element, the promoter, first exon and first intron of chicken beta-actin gene, and the splice acceptor of the rabbit beta-globin gene) frequently employed in gene therapy constructs to ensure robust and sustained transgene expression within target cells.

Following the acquisition of its development rights by Janssen Pharmaceuticals (a Johnson & Johnson company) from Hemera Biosciences in December 2020, HMR-59 is also identified by the development codes JNJ-1887 and JNJ-81201887.[2] The therapy is administered as a single intravitreal injection, a standard and minimally invasive procedure commonly performed in ophthalmic practice, intended for an outpatient setting.[1]

Rationale for Development in Age-Related Macular Degeneration (AMD)

Age-Related Macular Degeneration (AMD) stands as a principal cause of irreversible vision impairment and blindness among the elderly population in developed countries. The disease manifests in advanced stages as either Geographic Atrophy (GA), the "dry" form, or neovascular AMD (nAMD), the "wet" form.[2]

GA is characterized by the progressive and irreversible loss of photoreceptors, retinal pigment epithelium (RPE), and the underlying choriocapillaris in the macula, leading to gradually worsening central vision.[11] For many years, no approved treatments existed for GA. However, in 2023, two therapies targeting the complement cascade, pegcetacoplan (Syfovre, an inhibitor of C3) and avacincaptad pegol (Izervay, an inhibitor of C5), received FDA approval. While representing a significant advancement, these therapies require frequent intravitreal injections (monthly or every other month) to slow GA progression.[2]

Neovascular AMD involves the growth of abnormal new blood vessels from the choroid into the subretinal space (choroidal neovascularization, CNV). These vessels are prone to leakage and bleeding, causing rapid and severe vision loss.[8] The standard of care for nAMD involves recurrent intravitreal injections of anti-Vascular Endothelial Growth Factor (anti-VEGF) agents. While effective in many patients, the necessity for frequent and often indefinite injections imposes a substantial treatment burden on patients, caregivers, and healthcare systems.[1]

HMR-59 is being developed with the therapeutic goal of providing a long-lasting protective effect from a single administration. By enabling sustained intraocular production of sCD59, it aims to reduce the need for repeated interventions, thereby potentially improving patient compliance, reducing treatment-associated risks, and enhancing the overall quality of life for individuals with advanced AMD.[1]

The choice of an AAV2 vector for intravitreal delivery represents a strategic decision. While subretinal delivery might achieve more direct and potentially higher transduction of RPE cells and photoreceptors, it is a surgical procedure associated with greater risks and complexity.[8] Intravitreal injection is a significantly less invasive, commonly performed outpatient procedure, making it more suitable for a therapy intended for a broad AMD patient population.[1] AAV2 vectors are known to transduce various retinal cells, including those in the inner retina, following intravitreal administration. The therapeutic premise of HMR-59 relies on the transduced retinal cells acting as "biofactories" to secrete sCD59. This soluble protein can then diffuse within the ocular environment to protect a wider area of retinal cells, potentially obviating the need for direct transduction of every photoreceptor or RPE cell at risk. This approach is particularly relevant for GA, where a diffuse area of the macula is affected. The ultimate success of HMR-59 will therefore depend on achieving adequate sCD59 expression levels and ensuring its sufficient diffusion and penetration to the relevant retinal layers to exert a clinically meaningful protective effect.

3. Mechanism of Action

The Complement Cascade in AMD Pathogenesis

The complement system, an integral part of the innate immune response, plays a crucial role in host defense. However, its dysregulation and chronic overactivation have been robustly implicated in the pathogenesis of both dry (GA) and wet forms of AMD.[1] Genetic association studies have identified polymorphisms in several complement pathway genes (e.g., CFH, CFI, C2, C3, CFB) as significant risk factors for AMD. Histopathological analyses of AMD eyes have revealed the presence of complement activation products, including the Membrane Attack Complex (MAC), in drusen, the RPE, Bruch's membrane, and the choriocapillaris.

The complement cascade can be initiated via three main pathways: the classical pathway (typically antibody-mediated), the lectin pathway (activated by microbial carbohydrates), and the alternative pathway (subject to spontaneous low-level activation and amplification on surfaces lacking appropriate regulators). All three pathways converge at the cleavage of complement component C3 into C3a (an anaphylatoxin) and C3b (an opsonin and component of C5 convertase). C3b then participates in the cleavage of C5 into C5a (a potent anaphylatoxin and chemoattractant) and C5b. C5b initiates the assembly of the terminal pathway components (C6, C7, C8, and multiple C9 molecules) to form the MAC (C5b-9).[11]

In the context of AMD, MAC deposition on retinal cells, particularly RPE cells and photoreceptors, is believed to induce sublethal injury and chronic inflammation, eventually leading to cell dysfunction and death, characteristic of GA.[1] In nAMD, complement activation and MAC formation are also thought to contribute to the inflammatory milieu and promote angiogenesis, partly through the upregulation of pro-angiogenic factors such as VEGF.[1]

Role of CD59 and the Membrane Attack Complex

CD59, also known as protectin, is a small, 18-20 kDa glycosylphosphatidylinositol (GPI)-anchored membrane protein expressed on the surface of most host cells. Its primary physiological function is to protect cells from autologous complement-mediated damage by inhibiting the formation of the MAC at the terminal stage of the complement cascade.[2] CD59 achieves this by binding to C8 within the C5b-8 complex and to C9 molecules, thereby sterically hindering the polymerization of C9 into the transmembrane pore that constitutes the lytic MAC.

A deficiency or dysfunction of CD59 can render cells susceptible to complement attack. Evidence suggests that CD59 levels may be reduced in the retinas of AMD patients, potentially contributing to the complement-driven pathology observed in the disease.[2]

HMR-59: AAV2-Mediated Gene Therapy for sCD59 Expression

HMR-59 is an AAV2-based gene therapy designed to augment the eye's natural defense against complement-mediated damage. It employs an AAV2 vector to deliver a transgene encoding a soluble, secreted form of human CD59 (sCD59) directly into the vitreous cavity.[1] The rationale for using a soluble form of CD59 is to allow the protein to diffuse within the retinal microenvironment and act on cells beyond those directly transduced by the AAV vector.

Following intravitreal injection, the AAV2 vector is intended to transduce retinal cells (e.g., ganglion cells, other inner retinal cells, and potentially RPE cells via diffusion or indirect transduction). These transduced cells then serve as local "biofactories," continuously synthesizing and secreting sCD59 protein into the surrounding ocular tissues.[1] The secreted sCD59 is hypothesized to circulate within the retina and choroid, where it can interact with assembling MAC complexes on the surface of nearby photoreceptors, RPE cells, and other vulnerable cell types. By binding to C5b-8 and C9, sCD59 inhibits the final steps of MAC assembly, thereby preventing cell lysis and reducing inflammation. This targeted inhibition of the terminal complement pathway is expected to slow the progression of GA and potentially mitigate the inflammatory and angiogenic processes contributing to nAMD.[1]

The therapeutic strategy of HMR-59, by focusing on the inhibition of MAC formation via sCD59, presents a distinct approach compared to other complement-modulating therapies for AMD. Upstream inhibitors, such as those targeting C3 (e.g., pegcetacoplan) or C5 (e.g., avacincaptad pegol), block the complement cascade at earlier stages.[2] This can lead to a broader suppression of complement functions, including the generation of anaphylatoxins (C3a, C5a) and opsonins (C3b), which have roles in inflammation and immune cell recruitment but also in beneficial processes like pathogen clearance. By specifically targeting the terminal MAC, sCD59 aims to prevent direct cell lysis and MAC-mediated inflammation while potentially preserving some of the upstream physiological functions of the complement system. This nuanced immunomodulation might offer a different balance of efficacy and safety, particularly concerning the risk of ocular infections or the overall impact on the ocular immune environment. The clinical implications of this targeted approach will be further elucidated through ongoing and future clinical trials.

4. Development History and Sponsorship

Initial Development by Hemera Biosciences

HMR-59, scientifically designated as AAVCAGsCD59, was originally conceived and developed by Hemera Biosciences, LLC, a privately-owned biotechnology company.[1] Hemera Biosciences was responsible for the early preclinical development and for advancing HMR-59 into initial human clinical trials. The company successfully filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA), receiving 'safe to proceed' status for HMR-59 in early 2017 for the treatment of dry AMD (GA).[18] Subsequently, Hemera initiated Phase 1 clinical studies for HMR-59 in patients with GA (HMR-1001, NCT03144999) and in patients with nAMD (HMR-1002, NCT03585556).[1]

Acquisition by Janssen Pharmaceuticals (Johnson & Johnson)

On December 2, 2020, Janssen Pharmaceuticals, Inc., one of the pharmaceutical companies of Johnson & Johnson, announced the acquisition of all rights to HMR-59 from Hemera Biosciences.[7] The financial terms of the acquisition were not publicly disclosed. Following this transaction, the investigational therapy also became known by the Janssen development codes JNJ-1887 and JNJ-81201887.[2] Janssen assumed full responsibility for the ongoing development and potential future global commercialization of the gene therapy candidate.[7]

The acquisition by Janssen occurred after Hemera Biosciences had completed the Phase 1 study of HMR-59 in patients with GA and while the Phase 1 study in wet AMD was in its long-term safety follow-up phase.[7] This timing suggests that the decision by Janssen to acquire the asset was likely influenced by the emerging data from these early human studies, particularly concerning safety and preliminary biological activity. Janssen's press release at the time of acquisition highlighted the potential of HMR-59 to preserve vision and underscored their strategic commitment to advancing gene therapies for significant unmet needs in eye diseases.[7] The involvement of a large pharmaceutical company like Janssen, with its extensive resources and experience in late-stage clinical development and regulatory affairs, is anticipated to facilitate the progression of HMR-59 through more comprehensive clinical trials and towards potential market approval.

5. Preclinical Evidence

The provided research materials primarily focus on the clinical development of HMR-59, with limited specific details on its preclinical data package. Standard IND-enabling preclinical studies would have been required by regulatory authorities, such as the FDA, before human trials could commence.[18] These studies typically involve in vitro experiments to demonstrate transgene expression and activity (e.g., sCD59 production and MAC inhibition) and in vivo studies in relevant animal models to assess biodistribution, preliminary efficacy, and toxicology.

While specific HMR-59 preclinical results are not detailed in the provided snippets [1], the scientific rationale underpinning HMR-59 is based on:

• The established role of complement dysregulation and MAC-mediated damage in AMD pathogenesis.[1]
• The known protective function of endogenous CD59 in inhibiting MAC formation.[2]
• The observation that CD59 levels may be deficient in AMD-affected retinas.[2]
• The extensive preclinical and clinical experience with AAV vectors, particularly AAV2, for ocular gene delivery, demonstrating their capability to mediate sustained transgene expression in retinal cells.[8]

The progression of HMR-59 to Phase 1 clinical trials under FDA IND implies that such preclinical proof-of-concept and safety assessments were successfully completed and reviewed by regulatory authorities.

6. Clinical Development in Geographic Atrophy (GA)

The clinical development of HMR-59 (JNJ-1887) for Geographic Atrophy secondary to AMD has progressed through Phase 1 and is currently in Phase 2b.

Table 1: Overview of HMR-59 (JNJ-1887) Clinical Trials

Trial ID (NCT #)	Other ID	Phase	Indication(s)	Status	Est. Enrollment	Key Objective(s)	HMR-59 Dose(s) Administered	Source Snippets
NCT03144999	Study 1001 / HMR-1001	Phase 1	GA secondary to AMD	Completed	17	Evaluate safety and tolerability of single intravitreal injection of JNJ-1887.	Low (3.56x10^10 vg/eye), Intermediate (1.071x10^11 vg/eye), High (3.56x10^11 vg/eye)	1
NCT05811351	PARASOL / 81201887MDG2001	Phase 2b	GA secondary to AMD	Active, not recruiting / Recruiting*	300	Evaluate efficacy (change in GA lesion area) and safety of intravitreal JNJ-1887 vs sham.	Two experimental dose arms + sham. Includes steroid prophylaxis.	4
NCT06635148	81201887MDG3002 (LTE)	Phase 2	GA, AMD	Recruiting	Not specified	Assess long-term safety and tolerability of JNJ-1887 from parent studies.	No new intervention; follow-up of patients from parent studies.	14

*Recruitment status for NCT05811351 varies by source: "Active, not recruiting" [[1212]], "Recruiting" [[14] (Janssen Global Trial Finder as of Mar 26, 2025)]. This may reflect overall trial status versus site-specific recruitment or database update lags.

Phase 1 Study (NCT03144999 / Study 1001 / HMR-1001)

• Study Design and Objectives: This was an open-label, single-center, first-in-human study conducted over 24 months. Its primary objective was to evaluate the safety and tolerability of a single intravitreal injection of JNJ-1887 (AAVCAGsCD59) in patients with GA. Secondary objectives included assessing changes in GA lesion size and growth rate.[1]
• Patient Population: The study enrolled 17 adult patients (aged ≥50 years) diagnosed with GA secondary to dry AMD. Eligibility criteria included specific Best Corrected Visual Acuity (BCVA) (≤20/200 Snellen equivalent initially for the first 3 patients, then ≤20/80) and total GA lesion size (between 5 mm² and 20 mm²). All enrolled patients had foveal center-involved GA.[2]
• Intervention and Dosing: Participants received a single intravitreal injection of JNJ-1887 in one eye. They were sequentially enrolled into three dose cohorts:
• Low dose: 3.56×1010 viral genomes (vg)/eye (n=3)
• Intermediate dose: 1.07×1011 vg/eye (n=3)
• High dose: 3.56×1011 vg/eye (n=11) No prophylactic corticosteroids were administered in this initial Phase 1 study for GA.[2]
• Safety and Tolerability Results: JNJ-1887 was reported to be well-tolerated across all three dose cohorts, with no dose-limiting toxicities observed.[5] No serious adverse events (SAEs) or systemic AEs were deemed related to the study intervention.[5] Ocular inflammation was the principal treatment-emergent adverse event (TEAE). Five of 17 patients (29.4%) experienced a total of six events of mild ocular inflammation.[21] reports a similar incidence (4 eyes). These inflammatory events generally resolved with topical steroid treatment or observation. One patient with an unresolved vitritis event (managed with observation) experienced an unrelated fatal AE (leukemia).[2] Two patients experienced increased intraocular pressure (IOP) associated with inflammation, which was mild and considered unrelated to the treatment.[2] No cases of endophthalmitis or new-onset CNV were reported during the study.[1]
• Efficacy Findings (GA Lesion Growth, Visual Acuity): The GA lesion growth rate over 24 months was similar among the three dose cohorts.[5] However, in the high-dose cohort, there was a trend towards a continued decline in the GA lesion growth rate through the 24-month follow-up period. The mean square root lesion growth in this cohort decreased from 0.211 mm (during months 0-6) to 0.056 mm (during months 18-24).[5] It was noted in [1] that the majority of patients in the high-dose group exhibited a slower rate of GA progression compared to historical controls from other studies, though such comparisons are inherently limited. Conversely, two patients who experienced inflammation showed accelerated GA growth.[1]

Phase 2b PARASOL Study (NCT05811351 / 81201887MDG2001)

• Study Design and Objectives: The PARASOL study is a Phase 2b, randomized, double-masked, multicenter, dose-ranging, sham-controlled clinical trial. Its primary objective is to evaluate the efficacy and safety of intravitreal JNJ-81201887 (AAVCAGsCD59) compared to a sham procedure in patients with GA secondary to AMD.[4]
• Patient Population and Interventions: The study aims to enroll approximately 300 participants. It includes two experimental treatment arms receiving different doses of JNJ-81201887 (specific doses not detailed in the provided snippets but are likely informed by Phase 1 outcomes) and one sham comparator arm. A key modification from the initial Phase 1 GA study is the implementation of a prophylactic steroid regimen for participants in the experimental arms: a 20-day course of oral prednisone starting on day 1, and a single long-acting periocular triamcinolone injection on day 4. This is intended to mitigate the risk of ocular inflammation observed in Phase 1.[12] Inclusion criteria target patients with non-subfoveal GA, a lesion area between 2.5 mm² and 17.5 mm² (with at least one focal lesion ≥1.25 mm² if multifocal), and a BCVA in the fellow eye of counting fingers or better.[12]
• Primary and Key Secondary Outcome Measures:
• The primary outcome measure is the change from baseline in the square root of GA lesion area in the study eye at month 18, as measured by fundus autofluorescence (FAF).[12]
• Secondary outcome measures, also assessed as change from baseline at month 18, include reading speed (using Radner reading charts), retinal sensitivity (evaluated by mesopic microperimetry), and BCVA (measured using ETDRS charts).[12]
• Current Status and Anticipated Timelines: The PARASOL study is currently ongoing. Initial reports indicated it was "active, not recruiting" [[12] (ClinicalTrials.gov as of April 2024)], while more recent updates suggest it is "recruiting" [[14] (Janssen Global Trial Finder as of March 2025)]. Such discrepancies can occur due to varying update frequencies of different trial registries or reflect changes in site-specific recruitment activities. Results from the PARASOL study are anticipated by late 2025.[4]

Long-Term Extension (LTE) Study (NCT06635148 / ISRCTN11083692 / 81201887MDG3002)

• Purpose and Design: This study is designed to assess the long-term safety and tolerability of JNJ-81201887 in participants who received the investigational therapy or sham procedure in parent clinical studies. These parent studies include NCT03144999 (Phase 1, GA), NCT05811351 (PARASOL, Phase 2b, GA), and NCT03585556 (Phase 1, wet AMD). Participants will be followed for up to 5 years from their initial administration of JNJ-81201887. No new investigational product will be administered as part of this LTE study itself. However, participants who received a sham procedure in the PARASOL study (NCT05811351) may have the option to receive open-label JNJ-81201887 under a separate study protocol.[14]
• Primary Outcome: The primary outcome focuses on long-term safety, assessed by the number of participants experiencing ocular and systemic TEAEs, abnormal clinical laboratory assessments, and abnormal findings on retinal imaging (FAF, Spectral Domain Optical Coherence Tomography, Color Fundus Photography) and eye examinations over the 5-year follow-up period.[15]
• Status: The LTE study is currently recruiting participants.[14]

The progression from a small, open-label Phase 1 study for GA, which did not include prophylactic steroids, to a larger, randomized, sham-controlled Phase 2b study (PARASOL) that incorporates such prophylaxis, illustrates a data-driven evolution in the clinical development program. The initial Phase 1 trial (NCT03144999) was crucial for establishing the preliminary safety profile of HMR-59 and identifying ocular inflammation as a TEAE.[1] The PARASOL study's design, with its robust controls and proactive management strategy for inflammation [12], aims to rigorously assess the efficacy of HMR-59 while minimizing known risks. This adaptive approach is standard in gene therapy development, where early human data informs the design of subsequent, more definitive trials. The inclusion of functional endpoints like reading speed and microperimetry in PARASOL, alongside anatomical measures, will provide a more holistic understanding of HMR-59's potential clinical benefit for patients with GA. Furthermore, the establishment of a long-term extension study underscores the commitment to understanding the multi-year durability and safety of this one-time gene therapy, which is paramount for a treatment modality intended to have lasting effects.

7. Clinical Development in Wet Age-Related Macular Degeneration (nAMD)

Phase 1 Study (NCT03585556 / Study 1002)

• Study Design and Objectives: This was an open-label, multi-center, 24-month Phase 1 study. The primary objective was to assess the efficacy of AAVCAGsCD59 (JNJ-1887), specifically by evaluating the number of intravitreal anti-VEGF injections required from month 1 through month 12. This was in treatment-naïve nAMD patients who received a single intravitreal anti-VEGF injection at Day 0, followed by a single intravitreal injection of AAVCAGsCD59 on Day 7. Safety was a key secondary objective.[2]
• Patient Population: The trial enrolled 25 treatment-naïve nAMD patients, aged 50 years or older. Eligibility was based on specific BCVA criteria (Snellen equivalent 20/25 to 20/400) and the presence of intraretinal and/or subretinal fluid on OCT.[2]
• Intervention (including use with anti-VEGF): Participants received a standard-of-care anti-VEGF injection on Day 0. Seven days later (Day 7), they received a single intravitreal injection of AAVCAGsCD59. Two dose levels of AAVCAGsCD59 were evaluated: 3.56×1011 vg/eye (for subjects 1-22) and 1.071×1012 vg/eye (for subjects 23-25). Patients were monitored monthly and received anti-VEGF rescue therapy as needed, based on protocol-defined criteria such as an increase in central subfoveal thickness (CST) of >50 micrometers on OCT, new subretinal hemorrhage, or a loss of 10 or more ETDRS letters from the previous month's examination.[25] Prophylactic oral steroids were administered to patients in this trial.[1]
• Safety and Tolerability Results: The treatment was generally well-tolerated.[1] Ocular inflammation was observed in 4 out of 25 patients (16%), manifesting as 6 events (4 mild, 2 moderate). All instances of inflammation resolved following treatment with oral and/or topical steroids.[1] No dose-limiting toxicities, serious systemic AEs, or fatal AEs related to JNJ-1887 were reported.[2]
• Efficacy Findings (Reduction in anti-VEGF Treatment Burden): The primary efficacy endpoint was the number of anti-VEGF injections required between month 1 and month 12. Among the 11 subjects who had completed the 12-month visit at the time of an interim report, the mean number of anti-VEGF injections was 2.5.[1] Notably, 18% of patients (4 out of 22 who had at least 6 months of follow-up) did not require any additional anti-VEGF injections from month 1 through month 12.[1] An interesting observation was that eyes demonstrating a very rapid response to the initial anti-VEGF injection (defined as no fluid on OCT at Day 7 and Day 30) appeared to have a better response to AAVCAGsCD59, requiring a mean of only 1.2 anti-VEGF injections during the follow-up period.[1]

The approach of administering HMR-59 after an initial anti-VEGF injection in nAMD is strategically sound. It aims to first control the acute exudative activity with a proven anti-VEGF agent, creating a more stable retinal environment before the gene therapy-mediated sCD59 expression begins to exert its longer-term modulatory effects on the complement system and associated inflammation.[1] The finding that patients who respond rapidly and completely to initial anti-VEGF treatment might derive greater benefit from HMR-59 is particularly noteworthy. This could suggest that in these "good responder" eyes, the underlying disease process might have a more significant complement-driven inflammatory component that HMR-59 can effectively target once the acute VEGF-driven neovascularization is controlled. Alternatively, a less disrupted retinal architecture following effective initial anti-VEGF treatment might allow for better distribution or cellular uptake of the AAV vector and more effective sCD59 action. This observation could be pivotal for refining patient selection criteria in any future, larger-scale trials for nAMD, potentially enriching the study population for those most likely to benefit from this gene therapy approach. While an 18% injection-free rate is a promising signal, achieving a more substantial and widespread reduction in treatment burden will be necessary for HMR-59 to become a transformative therapy in the nAMD landscape, which is already served by several effective (albeit frequently administered) anti-VEGF agents.

8. Overall Safety and Tolerability Profile

Summary of Common and Serious Adverse Events

Across the Phase 1 clinical trials for both GA (NCT03144999) and nAMD (NCT03585556), HMR-59 (JNJ-1887) has demonstrated a generally manageable safety profile.[1] No dose-limiting toxicities were identified in these early-phase studies.[2] Furthermore, no serious adverse events (SAEs) or systemic AEs were reported as being related to the study intervention in either trial.[2]

The most consistently observed treatment-emergent adverse event (TEAE) related to HMR-59 administration was ocular inflammation, typically presenting as mild to moderate uveitis or vitritis.[1] In the GA study (NCT03144999), where no prophylactic steroids were used, 5 out of 17 patients (29.4%) experienced such inflammation.[2] In the nAMD study (NCT03585556), which did include prophylactic oral steroids, 4 out of 25 patients (16%) developed ocular inflammation.[1] These inflammatory events were generally manageable, resolving with topical or oral steroid treatment, or with observation alone.[2]

A few cases of transiently increased intraocular pressure (IOP) were reported, often in association with the ocular inflammation.[1] No instances of endophthalmitis or, in the GA trial, new-onset CNV were reported as related to the gene therapy.[1]

Management of Ocular Inflammation

The management of ocular inflammation evolved during the Phase 1 program.

• The initial Phase 1 GA study (NCT03144999) did not include a prophylactic steroid regimen; inflammation was treated if it occurred.[2]
• The subsequent Phase 1 nAMD study (NCT03585556) incorporated a short course of prophylactic oral steroids.[1]
• The ongoing Phase 2b PARASOL study (NCT05811351) for GA employs a more comprehensive prophylactic approach, consisting of a 20-day course of oral prednisone combined with a single long-acting periocular triamcinolone injection.[12]

The consistent observation of ocular inflammation, even if mostly mild and manageable, across different AMD populations and vector doses points towards an inherent immunogenic potential associated with either the AAV2 vector capsid or the expressed sCD59 transgene product within the specific immune environment of the eye. AAV vectors are known to be capable of eliciting immune responses.[19] The proactive implementation and subsequent intensification of prophylactic steroid regimens in later-stage trials, such as PARASOL [12], represent a critical and standard measure in ocular gene therapy development. This strategy aims to preemptively control and minimize such inflammatory responses, thereby enhancing the overall safety and tolerability of HMR-59. The efficacy of this enhanced prophylactic steroid protocol in the PARASOL trial will be a key determinant of the therapy's future viability, as sustained or severe inflammation could compromise both visual outcomes and patient acceptance of a one-time treatment.

Table 2: Summary of Key Safety Findings from HMR-59 Phase 1 Trials.

Adverse Event Type	NCT03144999 (GA, N=17) Frequency/Details	NCT03585556 (Wet AMD, N=25) Frequency/Details	Management	Source Snippets
Ocular Inflammation (any)	5/17 patients (29.4%), 6 events, all mild	4/25 patients (16%), 6 events, mild (n=4) or moderate (n=2)	Topical/oral steroids or observation	1
Increased IOP	2 patients (associated with inflammation, mild, unrelated to tx in GA study)	Not specifically detailed as frequent in nAMD study snippets	Pressure-lowering drops if needed	1
Serious AEs (related)	None	None	N/A	2
Systemic AEs (related)	None	None	N/A	2
Discontinuations due to AEs (related)	None	None	N/A	2

Long-Term Safety

The ongoing LTE study (NCT06635148) will be crucial for characterizing the long-term safety profile of HMR-59, including the potential for delayed adverse events or waning of transgene expression over a 5-year period.[14]

9. Regulatory Status

FDA IND 'Safe to Proceed'

Hemera Biosciences received clearance from the U.S. Food and Drug Administration (FDA) for their Investigational New Drug (IND) application for HMR59 for the treatment of dry AMD. This "safe to proceed" status, granted in early 2017, permitted the initiation of the Phase 1 clinical trial (NCT03144999) in patients with GA.[18]

Other Regulatory Designations

The provided research snippets do not contain information regarding any specific expedited regulatory designations for HMR-59/JNJ-1887, such as Fast Track, Breakthrough Therapy, or Orphan Drug status from the FDA, nor similar designations like PRIME (Priority Medicines) from the European Medicines Agency (EMA).[5]

The absence of such designations in the available information, particularly for a therapy targeting GA—a condition with significant unmet medical need until very recently—may be attributable to several factors. When Janssen acquired HMR-59, the clinical data was still in early Phase 1. Regulatory agencies often require more substantial efficacy data, typically from well-controlled Phase 2 studies, before granting designations like Breakthrough Therapy, which are reserved for treatments demonstrating potential for substantial improvement over available therapies. With the approval of two complement inhibitors for GA in 2023 (pegcetacoplan and avacincaptad pegol) [2], the landscape for demonstrating "significant benefit" or addressing an "unmet need" for GA has evolved. HMR-59 would now likely need to show compelling advantages over these existing therapies, such as superior long-term efficacy, a better safety profile, or a significantly reduced treatment burden, to qualify for such expedited pathways. The results from the ongoing Phase 2b PARASOL trial will be instrumental in determining if HMR-59 meets these criteria and warrants applications for such designations in the future.

10. Discussion and Future Perspectives

Therapeutic Potential of HMR-59

HMR-59 (JNJ-1887) holds considerable therapeutic potential as a novel treatment modality for advanced forms of AMD. Its primary appeal lies in its design as a one-time intravitreal gene therapy, which, if successful, could dramatically reduce the treatment burden associated with current standards of care for both GA and nAMD.[1] For GA, current approved therapies require frequent (monthly or bimonthly) intravitreal injections.[2] For nAMD, anti-VEGF therapy also necessitates a chronic regimen of repeated injections.[8] A single, durably effective administration of HMR-59 could transform patient management, improve long-term adherence, and enhance quality of life.

The mechanism of action, which involves augmenting the natural protective protein sCD59 to inhibit MAC formation, is scientifically well-grounded in the understanding of complement-mediated pathology in AMD.[1] Targeting the terminal step of the complement cascade may offer a nuanced approach to immunomodulation compared to broader upstream complement inhibitors.

Challenges and Unanswered Questions

Despite its promise, the development of HMR-59 faces several challenges and unanswered questions common to ocular gene therapies:

• Durability of Expression and Clinical Effect: A critical determinant of success will be the longevity of therapeutic sCD59 expression from the AAV2 vector and the persistence of its clinical benefit. Long-term follow-up from the LTE study (NCT06635148) will be essential to address this.
• Optimal Dosing and Patient Selection: Phase 1 studies explored several dose levels, but the optimal therapeutic window that balances maximal efficacy with minimal adverse events, particularly inflammation, needs to be definitively established in the Phase 2b PARASOL trial. Identifying patient subgroups most likely to respond—perhaps based on baseline CD59 levels, genetic markers of complement activity, or disease stage—could enhance treatment outcomes. The observation in the nAMD Phase 1 trial that rapid responders to initial anti-VEGF therapy might benefit more from HMR-59 warrants further investigation.[1]
• Management and Minimization of Ocular Inflammation: While generally mild to moderate, ocular inflammation is a recurrent safety signal.[1] The efficacy and long-term tolerability of the prophylactic steroid regimen implemented in the PARASOL study [5] will be a key factor.
• Translation of Anatomical to Functional Benefit: For GA, it is crucial to demonstrate that slowing lesion growth, the primary endpoint in PARASOL [12], translates into meaningful preservation or improvement in visual function (e.g., reading speed, visual field sensitivity, BCVA), which are being assessed as secondary endpoints.

Comparison with Other Complement Inhibitors

HMR-59's single-administration gene therapy approach fundamentally differs from the currently approved complement inhibitors for GA, pegcetacoplan (anti-C3) and avacincaptad pegol (anti-C5). These drugs require repeated intravitreal injections, typically monthly or every other month, to maintain their therapeutic effect.[2] This frequent dosing regimen poses a significant burden on patients and healthcare systems.

The primary differentiating factor for HMR-59 is its potential for a "one-and-done" or significantly less frequent treatment schedule. However, this advantage is counterbalanced by the irreversible nature of gene therapy and the consequent necessity for an exceptionally robust long-term safety profile. The efficacy bar for HMR-59 will also be substantial; it will need to demonstrate a reduction in GA progression that is at least comparable, and ideally superior or more sustained, than that achieved with the regular injection therapies. The approved GA drugs have shown modest efficacy, typically reducing GA lesion growth by around 14-22% over 1-2 years.[2] For HMR-59 to be a compelling alternative, it must deliver significant and durable efficacy while minimizing risks of chronic inflammation or other long-term AAV-related adverse events.

Recommendations for Future Development

Future development of HMR-59 should prioritize:

• Rigorous Analysis of Phase 2b Data: Comprehensive evaluation of the PARASOL trial results, with a keen focus on the correlation between anatomical outcomes (GA lesion growth) and patient-relevant functional outcomes (BCVA, reading speed, microperimetry).
• Long-Term Safety and Durability Monitoring: Continued diligent follow-up in the LTE study is essential to confirm the multi-year safety profile and the persistence of sCD59 expression and clinical benefit.
• Biomarker Development: Exploration and validation of biomarkers (e.g., aqueous humor sCD59 levels, systemic or ocular complement activity markers, genetic markers) to predict treatment response, optimize patient selection, or identify individuals at higher risk of ocular inflammation.
• Refinement of nAMD Strategy: If the nAMD program is pursued further, studies should aim to confirm the finding that initial anti-VEGF responders benefit more and potentially explore HMR-59 in patients who are stable on anti-VEGF but require frequent injections to maintain that stability.
• Exploration of Earlier Disease Stages or Combination Therapies: Should HMR-59 prove safe and effective in advanced AMD, its potential in earlier stages of the disease or in combination with other neuroprotective or anti-angiogenic therapies could be considered to maximize visual preservation.

11. Conclusion

HMR-59 (JNJ-1887 / AAVCAGsCD59) is an innovative gene therapy candidate that targets a key pathological mechanism in AMD—complement-mediated retinal damage—by promoting sustained intraocular production of the MAC inhibitor sCD59. Early Phase 1 clinical trials in patients with GA and nAMD have provided initial evidence of a manageable safety profile, with ocular inflammation being the primary concern, and have hinted at potential efficacy in terms of slowing GA progression and reducing anti-VEGF treatment burden in nAMD.

The ongoing, more definitive Phase 2b PARASOL study for GA, which incorporates prophylactic steroid treatment, will be critical in establishing the efficacy and further characterizing the safety of HMR-59. The long-term extension study will provide vital insights into the durability of treatment effect and late-onset safety. If HMR-59 successfully demonstrates significant and lasting clinical benefit with a favorable safety profile, it could offer a transformative treatment paradigm for patients with advanced AMD, substantially alleviating the current high burden of frequent intravitreal injections and potentially preserving vision for longer periods. The journey of HMR-59 from a small biotech innovation to a major pharmaceutical development program highlights the significant scientific and clinical interest in finding durable solutions for these debilitating retinal diseases.

Table 3: Key Efficacy Outcomes from HMR-59 Phase 1 Trials.

Indication	Trial ID (NCT #)	Endpoint	Result	Timepoint	Source Snippets
GA	NCT03144999	GA Lesion Growth Rate (mean square root) - High Dose Cohort	Reduction from 0.211 mm (months 0-6) to 0.056 mm (months 18-24)	24 months	5
GA	NCT03144999	GA Lesion Growth Rate vs Historical Controls (Qualitative)	Majority in high-dose cohort showed slower progression	24 months	1
Wet AMD	NCT03585556	Mean number of anti-VEGF injections (Month 1-12) for completers	2.5 injections (n=11)	12 months	1
Wet AMD	NCT03585556	Proportion of patients needing no anti-VEGF injections (Month 1-12)	18% (4/22 with ≥6mo follow-up)	12 months	1
Wet AMD	NCT03585556	Mean anti-VEGF injections in rapid anti-VEGF responders (Month 1-12)	1.2 injections	12 months	1

1. Executive Summary

HMR-59, also identified by the codenames AAVCAGsCD59 and JNJ-1887, represents an investigational gene therapy employing an adeno-associated virus serotype 2 (AAV2) vector. It is designed as a potential one-time intravitreal treatment for advanced forms of Age-Related Macular Degeneration (AMD), including Geographic Atrophy (GA) and neovascular (wet) AMD.[1] The therapeutic strategy is centered on the intraocular expression of a soluble form of the human CD59 protein (sCD59). This protein is a natural inhibitor of the terminal complement pathway, specifically targeting the Membrane Attack Complex (MAC), a key mediator of cellular damage in AMD. By augmenting local sCD59 levels, HMR-59 aims to protect retinal cells from complement-mediated destruction, thereby slowing disease progression.[2]

The therapy was initially developed by Hemera Biosciences [1] and subsequently acquired by Janssen Pharmaceuticals, a Johnson & Johnson company, in December 2020, after which it also became known as JNJ-1887 or JNJ-81201887.[2] HMR-59 has completed Phase 1 clinical trials for both GA (NCT03144999) and wet AMD (NCT03585556). These early-phase studies established a manageable safety profile, with ocular inflammation being the most notable adverse event, generally mild to moderate and responsive to steroid treatment. Preliminary efficacy signals, such as a potential reduction in GA lesion growth rate and a decreased need for anti-VEGF injections in wet AMD, were also observed.[1]

Currently, HMR-59 is being evaluated in a more definitive Phase 2b clinical trial, PARASOL (NCT05811351), for patients with GA, with primary results anticipated in late 2025.[4] A long-term extension study (NCT06635148) is also underway to monitor the extended safety and durability of the treatment.[14] The development of HMR-59 from a smaller biotechnology company to its acquisition and continued advancement by a major pharmaceutical corporation suggests a strong perceived potential for this single-administration gene therapy to address the significant unmet medical needs in advanced AMD. This transition often signifies a greater capacity for navigating the extensive and costly later phases of clinical development and regulatory approval. The success of HMR-59 could offer a paradigm shift by significantly reducing the treatment burden associated with current AMD management strategies.

2. Introduction to HMR-59 (AAVCAGsCD59 / JNJ-1887)

Overview of the Therapeutic Agent

HMR-59 is an investigational gene therapy product designed for ocular administration. Its scientific nomenclature, AAVCAGsCD59, denotes its composition: it utilizes an Adeno-Associated Virus serotype 2 (AAV2) as a vector to deliver a transgene encoding a soluble, secreted form of the human CD59 protein (sCD59).[1] The "CAG" element in its name refers to a synthetic strong promoter (composed of the cytomegalovirus (CMV) early enhancer element, the promoter, first exon and first intron of chicken beta-actin gene, and the splice acceptor of the rabbit beta-globin gene) frequently employed in gene therapy constructs to ensure robust and sustained transgene expression within target cells.

Following the acquisition of its development rights by Janssen Pharmaceuticals (a Johnson & Johnson company) from Hemera Biosciences in December 2020, HMR-59 is also identified by the development codes JNJ-1887 and JNJ-81201887.[2] The therapy is administered as a single intravitreal injection, a standard and minimally invasive procedure commonly performed in ophthalmic practice, intended for an outpatient setting.[1]

Rationale for Development in Age-Related Macular Degeneration (AMD)

Age-Related Macular Degeneration (AMD) stands as a principal cause of irreversible vision impairment and blindness among the elderly population in developed countries. The disease manifests in advanced stages as either Geographic Atrophy (GA), the "dry" form, or neovascular AMD (nAMD), the "wet" form.[2]

GA is characterized by the progressive and irreversible loss of photoreceptors, retinal pigment epithelium (RPE), and the underlying choriocapillaris in the macula, leading to gradually worsening central vision.[11] For many years, no approved treatments existed for GA. However, in 2023, two therapies targeting the complement cascade, pegcetacoplan (Syfovre, an inhibitor of C3) and avacincaptad pegol (Izervay, an inhibitor of C5), received FDA approval. While representing a significant advancement, these therapies require frequent intravitreal injections (monthly or every other month) to slow GA progression.[2]

Neovascular AMD involves the growth of abnormal new blood vessels from the choroid into the subretinal space (choroidal neovascularization, CNV). These vessels are prone to leakage and bleeding, causing rapid and severe vision loss.[8] The standard of care for nAMD involves recurrent intravitreal injections of anti-Vascular Endothelial Growth Factor (anti-VEGF) agents. While effective in many patients, the necessity for frequent and often indefinite injections imposes a substantial treatment burden on patients, caregivers, and healthcare systems.[1]

HMR-59 is being developed with the therapeutic goal of providing a long-lasting protective effect from a single administration. By enabling sustained intraocular production of sCD59, it aims to reduce the need for repeated interventions, thereby potentially improving patient compliance, reducing treatment-associated risks, and enhancing the overall quality of life for individuals with advanced AMD.[1]

The choice of an AAV2 vector for intravitreal delivery represents a strategic decision. While subretinal delivery might achieve more direct and potentially higher transduction of RPE cells and photoreceptors, it is a surgical procedure associated with greater risks and complexity.[8] Intravitreal injection is a significantly less invasive, commonly performed outpatient procedure, making it more suitable for a therapy intended for a broad AMD patient population.[1] AAV2 vectors are known to transduce various retinal cells, including those in the inner retina, following intravitreal administration. The therapeutic premise of HMR-59 relies on the transduced retinal cells acting as "biofactories" to secrete sCD59. This soluble protein can then diffuse within the ocular environment to protect a wider area of retinal cells, potentially obviating the need for direct transduction of every photoreceptor or RPE cell at risk. This approach is particularly relevant for GA, where a diffuse area of the macula is affected. The ultimate success of HMR-59 will therefore depend on achieving adequate sCD59 expression levels and ensuring its sufficient diffusion and penetration to the relevant retinal layers to exert a clinically meaningful protective effect.

3. Mechanism of Action

The Complement Cascade in AMD Pathogenesis

The complement system, an integral part of the innate immune response, plays a crucial role in host defense. However, its dysregulation and chronic overactivation have been robustly implicated in the pathogenesis of both dry (GA) and wet forms of AMD.[1] Genetic association studies have identified polymorphisms in several complement pathway genes (e.g., CFH, CFI, C2, C3, CFB) as significant risk factors for AMD. Histopathological analyses of AMD eyes have revealed the presence of complement activation products, including the Membrane Attack Complex (MAC), in drusen, the RPE, Bruch's membrane, and the choriocapillaris.

The complement cascade can be initiated via three main pathways: the classical pathway (typically antibody-mediated), the lectin pathway (activated by microbial carbohydrates), and the alternative pathway (subject to spontaneous low-level activation and amplification on surfaces lacking appropriate regulators). All three pathways converge at the cleavage of complement component C3 into C3a (an anaphylatoxin) and C3b (an opsonin and component of C5 convertase). C3b then participates in the cleavage of C5 into C5a (a potent anaphylatoxin and chemoattractant) and C5b. C5b initiates the assembly of the terminal pathway components (C6, C7, C8, and multiple C9 molecules) to form the MAC (C5b-9).[11]

In the context of AMD, MAC deposition on retinal cells, particularly RPE cells and photoreceptors, is believed to induce sublethal injury and chronic inflammation, eventually leading to cell dysfunction and death, characteristic of GA.[1] In nAMD, complement activation and MAC formation are also thought to contribute to the inflammatory milieu and promote angiogenesis, partly through the upregulation of pro-angiogenic factors such as VEGF.[1]

Role of CD59 and the Membrane Attack Complex

CD59, also known as protectin, is a small, 18-20 kDa glycosylphosphatidylinositol (GPI)-anchored membrane protein expressed on the surface of most host cells. Its primary physiological function is to protect cells from autologous complement-mediated damage by inhibiting the formation of the MAC at the terminal stage of the complement cascade.[2] CD59 achieves this by binding to C8 within the C5b-8 complex and to C9 molecules, thereby sterically hindering the polymerization of C9 into the transmembrane pore that constitutes the lytic MAC.

A deficiency or dysfunction of CD59 can render cells susceptible to complement attack. Evidence suggests that CD59 levels may be reduced in the retinas of AMD patients, potentially contributing to the complement-driven pathology observed in the disease.[2]

HMR-59: AAV2-Mediated Gene Therapy for sCD59 Expression

HMR-59 is an AAV2-based gene therapy designed to augment the eye's natural defense against complement-mediated damage. It employs an AAV2 vector to deliver a transgene encoding a soluble, secreted form of human CD59 (sCD59) directly into the vitreous cavity.[1] The rationale for using a soluble form of CD59 is to allow the protein to diffuse within the retinal microenvironment and act on cells beyond those directly transduced by the AAV vector.

Following intravitreal injection, the AAV2 vector is intended to transduce retinal cells (e.g., ganglion cells, other inner retinal cells, and potentially RPE cells via diffusion or indirect transduction). These transduced cells then serve as local "biofactories," continuously synthesizing and secreting sCD59 protein into the surrounding ocular tissues.[1] The secreted sCD59 is hypothesized to circulate within the retina and choroid, where it can interact with assembling MAC complexes on the surface of nearby photoreceptors, RPE cells, and other vulnerable cell types. By binding to C5b-8 and C9, sCD59 inhibits the final steps of MAC assembly, thereby preventing cell lysis and reducing inflammation. This targeted inhibition of the terminal complement pathway is expected to slow the progression of GA and potentially mitigate the inflammatory and angiogenic processes contributing to nAMD.[1]

The therapeutic strategy of HMR-59, by focusing on the inhibition of MAC formation via sCD59, presents a distinct approach compared to other complement-modulating therapies for AMD. Upstream inhibitors, such as those targeting C3 (e.g., pegcetacoplan) or C5 (e.g., avacincaptad pegol), block the complement cascade at earlier stages.[2] This can lead to a broader suppression of complement functions, including the generation of anaphylatoxins (C3a, C5a) and opsonins (C3b), which have roles in inflammation and immune cell recruitment but also in beneficial processes like pathogen clearance. By specifically targeting the terminal MAC, sCD59 aims to prevent direct cell lysis and MAC-mediated inflammation while potentially preserving some of the upstream physiological functions of the complement system. This nuanced immunomodulation might offer a different balance of efficacy and safety, particularly concerning the risk of ocular infections or the overall impact on the ocular immune environment. The clinical implications of this targeted approach will be further elucidated through ongoing and future clinical trials.

4. Development History and Sponsorship

Initial Development by Hemera Biosciences

HMR-59, scientifically designated as AAVCAGsCD59, was originally conceived and developed by Hemera Biosciences, LLC, a privately-owned biotechnology company.[1] Hemera Biosciences was responsible for the early preclinical development and for advancing HMR-59 into initial human clinical trials. The company successfully filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA), receiving 'safe to proceed' status for HMR-59 in early 2017 for the treatment of dry AMD (GA).[18] Subsequently, Hemera initiated Phase 1 clinical studies for HMR-59 in patients with GA (HMR-1001, NCT03144999) and in patients with nAMD (HMR-1002, NCT03585556).[1]

Acquisition by Janssen Pharmaceuticals (Johnson & Johnson)

On December 2, 2020, Janssen Pharmaceuticals, Inc., one of the pharmaceutical companies of Johnson & Johnson, announced the acquisition of all rights to HMR-59 from Hemera Biosciences.[7] The financial terms of the acquisition were not publicly disclosed. Following this transaction, the investigational therapy also became known by the Janssen development codes JNJ-1887 and JNJ-81201887.[2] Janssen assumed full responsibility for the ongoing development and potential future global commercialization of the gene therapy candidate.[7]

The acquisition by Janssen occurred after Hemera Biosciences had completed the Phase 1 study of HMR-59 in patients with GA and while the Phase 1 study in wet AMD was in its long-term safety follow-up phase.[7] This timing suggests that the decision by Janssen to acquire the asset was likely influenced by the emerging data from these early human studies, particularly concerning safety and preliminary biological activity. Janssen's press release at the time of acquisition highlighted the potential of HMR59 to preserve vision and underscored their strategic commitment to advancing gene therapies for significant unmet needs in eye diseases.[7] The involvement of a large pharmaceutical company like Janssen, with its extensive resources and experience in late-stage clinical development and regulatory affairs, is anticipated to facilitate the progression of HMR-59 through more comprehensive clinical trials and towards potential market approval.

5. Preclinical Evidence

The provided research materials primarily focus on the clinical development of HMR-59, with limited specific details on its preclinical data package. Standard IND-enabling preclinical studies would have been required by regulatory authorities, such as the FDA, before human trials could commence.[18] These studies typically involve in vitro experiments to demonstrate transgene expression and activity (e.g., sCD59 production and MAC inhibition) and in vivo studies in relevant animal models to assess biodistribution, preliminary efficacy, and toxicology.

While specific HMR-59 preclinical results are not detailed in the provided snippets [1], the scientific rationale underpinning HMR-59 is based on:

• The established role of complement dysregulation and MAC-mediated damage in AMD pathogenesis.[1]
• The known protective function of endogenous CD59 in inhibiting MAC formation.[2]
• The observation that CD59 levels may be deficient in AMD-affected retinas.[2]
• The extensive preclinical and clinical experience with AAV vectors, particularly AAV2, for ocular gene delivery, demonstrating their capability to mediate sustained transgene expression in retinal cells.[8]

The progression of HMR-59 to Phase 1 clinical trials under FDA IND implies that such preclinical proof-of-concept and safety assessments were successfully completed and reviewed by regulatory authorities.

6. Clinical Development in Geographic Atrophy (GA)

The clinical development of HMR-59 (JNJ-1887) for Geographic Atrophy secondary to AMD has progressed through Phase 1 and is currently in Phase 2b.

Table 1: Overview of HMR-59 (JNJ-1887) Clinical Trials

Trial ID (NCT #)	Other ID	Phase	Indication(s)	Status	Est. Enrollment	Key Objective(s)	HMR-59 Dose(s) Administered	Source Snippets
NCT03144999	Study 1001 / HMR-1001	Phase 1	GA secondary to AMD	Completed	17	Evaluate safety and tolerability of single intravitreal injection of JNJ-1887.	Low (3.56×1010 vg/eye), Intermediate (1.071×1011 vg/eye), High (3.56×1011 vg/eye)	1
NCT05811351	PARASOL / 81201887MDG2001	Phase 2b	GA secondary to AMD	Active, not recruiting / Recruiting*	300	Evaluate efficacy (change in GA lesion area) and safety of intravitreal JNJ-1887 vs sham.	Two experimental dose arms + sham. Includes steroid prophylaxis.	4
NCT06635148	81201887MDG3002 (LTE)	Phase 2	GA, AMD	Recruiting	Not specified	Assess long-term safety and tolerability of JNJ-1887 from parent studies.	No new intervention; follow-up of patients from parent studies.	14

*Recruitment status for NCT05811351 varies by source: "Active, not recruiting" [[1212]], "Recruiting" [[14] (Janssen Global Trial Finder as of Mar 26, 2025)]. This may reflect overall trial status versus site-specific recruitment or database update lags.

Phase 1 Study (NCT03144999 / Study 1001 / HMR-1001)

• Study Design and Objectives: This was an open-label, single-center, first-in-human study conducted over 24 months. Its primary objective was to evaluate the safety and tolerability of a single intravitreal injection of JNJ-1887 (AAVCAGsCD59) in patients with GA. Secondary objectives included assessing changes in GA lesion size and growth rate.[1]
• Patient Population: The study enrolled 17 adult patients (aged $\ge$50 years) diagnosed with GA secondary to dry AMD. Eligibility criteria included specific Best Corrected Visual Acuity (BCVA) ($\le$20/200 Snellen equivalent initially for the first 3 patients, then $\le$20/80) and total GA lesion size (between 5 mm² and 20 mm²). All enrolled patients had foveal center-involved GA.[2]
• Intervention and Dosing: Participants received a single intravitreal injection of JNJ-1887 in one eye. They were sequentially enrolled into three dose cohorts:
• Low dose: 3.56×1010 viral genomes (vg)/eye (n=3)
• Intermediate dose: 1.07×1011 vg/eye (n=3)
• High dose: 3.56×1011 vg/eye (n=11) No prophylactic corticosteroids were administered in this initial Phase 1 study for GA.[2]
• Safety and Tolerability Results: JNJ-1887 was reported to be well-tolerated across all three dose cohorts, with no dose-limiting AEs observed.[5] No serious adverse events (SAEs) or systemic AEs were deemed related to the study intervention.[5] Ocular inflammation was the principal treatment-emergent adverse event (TEAE). Five of 17 patients (29.4%) experienced a total of six events of mild ocular inflammation.[21] reports a similar incidence (4 eyes). These inflammatory events generally resolved with topical steroid treatment or observation. One patient with an unresolved vitritis event (managed with observation) experienced an unrelated fatal AE (leukemia).[2] Two patients experienced increased intraocular pressure (IOP) associated with inflammation, which was mild and considered unrelated to the treatment.[2] No cases of endophthalmitis or new-onset CNV were reported during the study.[1]
• Efficacy Findings (GA Lesion Growth, Visual Acuity): The GA lesion growth rate over 24 months was similar among the three dose cohorts.[5] However, in the high-dose cohort, there was a trend towards a continued decline in the GA lesion growth rate through the 24-month follow-up period. The mean square root lesion growth in this cohort decreased from 0.211 mm (during months 0-6) to 0.056 mm (during months 18-24).[5] It was noted in [1] that the majority of patients in the high-dose group exhibited a slower rate of GA progression compared to historical controls from other studies, though such comparisons are inherently limited. Conversely, two patients who experienced inflammation showed accelerated GA growth.[1]

Phase 2b PARASOL Study (NCT05811351 / 81201887MDG2001)

• Study Design and Objectives: The PARASOL study is a Phase 2b, randomized, double-masked, multicenter, dose-ranging, sham-controlled clinical trial. Its primary objective is to evaluate the efficacy and safety of intravitreal JNJ-81201887 (AAVCAGsCD59) compared to a sham procedure in patients with GA secondary to AMD.[4]
• Patient Population and Interventions: The study aims to enroll approximately 300 participants. It includes two experimental treatment arms receiving different doses of JNJ-81201887 (specific doses not detailed in the provided snippets but are likely informed by Phase 1 outcomes) and one sham comparator arm. A key modification from the initial Phase 1 GA study is the implementation of a prophylactic steroid regimen for participants in the experimental arms: a 20-day course of oral prednisone starting on day 1, and a single long-acting periocular triamcinolone injection on day 4. This is intended to mitigate the risk of ocular inflammation observed in Phase 1.[12] Inclusion criteria target patients with non-subfoveal GA, a lesion area between 2.5 mm² and 17.5 mm² (with at least one focal lesion $\ge$1.25 mm² if multifocal), and a BCVA in the fellow eye of counting fingers or better.[12]
• Primary and Key Secondary Outcome Measures:
• The primary outcome measure is the change from baseline in the square root of GA lesion area in the study eye at month 18, as measured by fundus autofluorescence (FAF).[12]
• Secondary outcome measures, also assessed as change from baseline at month 18, include reading speed (using Radner reading charts), retinal sensitivity (evaluated by mesopic microperimetry), and BCVA (measured using ETDRS charts).[12]
• Current Status and Anticipated Timelines: The PARASOL study is currently ongoing. Initial reports indicated it was "active, not recruiting" [[12] (ClinicalTrials.gov as of April 2024)], while more recent updates suggest it is "recruiting" [[14] (Janssen Global Trial Finder as of March 2025)]. Such discrepancies can occur due to varying update frequencies of different trial registries or reflect changes in site-specific recruitment activities. Results from the PARASOL study are anticipated by late 2025.[4]

Long-Term Extension (LTE) Study (NCT06635148 / ISRCTN11083692 / 81201887MDG3002)

• Purpose and Design: This study is designed to assess the long-term safety and tolerability of JNJ-81201887 in participants who received the investigational therapy or sham procedure in parent clinical studies. These parent studies include NCT03144999 (Phase 1, GA), NCT05811351 (PARASOL, Phase 2b, GA), and also mentions 81201887MDG1003 which corresponds to NCT03585556 (Phase 1, wet AMD). Participants will be followed for up to 5 years from their initial administration of JNJ-81201887. No new investigational product will be administered as part of this LTE study itself. However, participants who received a sham procedure in the PARASOL study (NCT05811351) may have the option to receive open-label JNJ-81201887 under a separate study protocol.[14]
• Primary Outcome: The primary outcome focuses on long-term safety, assessed by the number of participants experiencing ocular and systemic TEAEs, abnormal clinical laboratory assessments, and abnormal findings on retinal imaging (FAF, Spectral Domain Optical Coherence Tomography, Color Fundus Photography) and eye examinations over the 5-year follow-up period.[15]
• Status: The LTE study is currently recruiting participants.[14]

The progression from a small, open-label Phase 1 study for GA, which did not include prophylactic steroids, to a larger, randomized, sham-controlled Phase 2b study (PARASOL) that does incorporate such prophylaxis, illustrates a standard, data-driven evolution in clinical trial design for gene therapy. The initial Phase 1 trial (NCT03144999) was crucial for establishing the preliminary safety profile of HMR-59 and identifying ocular inflammation as a TEAE.[1] The PARASOL study's design, with its robust controls and proactive management strategy for inflammation [12], aims to rigorously assess the efficacy of HMR-59 while minimizing known risks. This adaptive approach is standard in gene therapy development, where early human data informs the design of subsequent, more definitive trials. The inclusion of functional endpoints like reading speed and microperimetry in PARASOL, alongside anatomical measures, will provide a more holistic understanding of HMR-59's potential clinical benefit for patients with GA. Furthermore, the establishment of a long-term extension study underscores the commitment to understanding the multi-year durability and safety of this one-time gene therapy, which is paramount for a treatment modality intended to have lasting effects.

7. Clinical Development in Wet Age-Related Macular Degeneration (nAMD)

Phase 1 Study (NCT03585556 / Study 1002)

• Study Design and Objectives: This was an open-label, multi-center, 24-month Phase 1 study. The primary objective was to assess the efficacy of AAVCAGsCD59 (JNJ-1887), specifically by evaluating the number of anti-VEGF injections required from month 1 through month 12. This was in treatment-naïve nAMD patients who received a single intravitreal anti-VEGF injection at Day 0, followed by a single intravitreal injection of AAVCAGsCD59 on Day 7. Safety was a key secondary objective.[2]
• Patient Population: The trial enrolled 25 treatment-naïve nAMD patients, aged 50 years or older. Eligibility was based on specific BCVA criteria (Snellen equivalent 20/25 to 20/400) and the presence of intraretinal and/or subretinal fluid on OCT.[2]
• Intervention (including use with anti-VEGF): Participants received a standard-of-care anti-VEGF injection on Day 0. Seven days later (Day 7), they received a single intravitreal injection of AAVCAGsCD59. Two dose levels of AAVCAGsCD59 were evaluated: 3.56×1011 vg/eye (for subjects 1-22) and 1.071×1012 vg/eye (for subjects 23-25). Patients were monitored monthly and received anti-VEGF rescue therapy as needed, based on protocol-defined criteria such as an increase in central subfoveal thickness (CST) of >50 micrometers on OCT, new subretinal hemorrhage, or a loss of 10 or more ETDRS letters from the previous month's examination.[25] Prophylactic oral steroids were administered to patients in this trial.[1]
• Safety and Tolerability Results: The treatment was generally well-tolerated.[1] Ocular inflammation was observed in 4 out of 25 patients (16%), manifesting as 6 events (4 mild, 2 moderate). All instances of inflammation resolved following treatment with oral and/or topical steroids.[1] No dose-limiting toxicities, serious systemic AEs, or fatal AEs related to JNJ-1887 were reported.[2]
• Efficacy Findings (Reduction in anti-VEGF Treatment Burden): The primary efficacy endpoint was the number of anti-VEGF injections required between month 1 and month 12. Among the 11 subjects who had completed the 12-month visit at the time of an interim report, the mean number of anti-VEGF injections was 2.5.[1] Notably, 18% of patients (4 out of 22 who had at least 6 months of follow-up) did not require any additional anti-VEGF injections from month 1 through month 12.[1] An interesting observation was that eyes demonstrating a very rapid response to the initial anti-VEGF injection (defined as no fluid on OCT at Day 7 and Day 30) appeared to have a better response to AAVCAGsCD59, requiring a mean of only 1.2 anti-VEGF injections during the follow-up period.[1]

The approach of administering HMR-59 after an initial anti-VEGF injection in nAMD is strategically sound. It aims to first control the acute exudative activity with a proven anti-VEGF agent, creating a more stable retinal environment before the gene therapy-mediated sCD59 expression begins to exert its longer-term modulatory effects on the complement system and associated inflammation.[1] The finding that patients who respond rapidly and completely to initial anti-VEGF treatment might derive greater benefit from HMR-59 is particularly noteworthy. This could suggest that in these "good responder" eyes, the underlying disease process might have a more significant complement-driven inflammatory component that HMR-59 can effectively target once the acute VEGF-driven neovascularization is controlled. Alternatively, a less disrupted retinal architecture following effective initial anti-VEGF treatment might allow for better distribution or cellular uptake of the AAV vector and more effective sCD59 action. This observation could be pivotal for refining patient selection criteria in any future, larger-scale trials for nAMD, potentially enriching the study population for those most likely to benefit from this gene therapy approach. While an 18% injection-free rate is a promising signal, achieving a more substantial and widespread reduction in treatment burden will be necessary for HMR-59 to become a transformative therapy in the nAMD landscape, which is already served by several effective (albeit frequently administered) anti-VEGF agents.

8. Overall Safety and Tolerability Profile

Summary of Common and Serious Adverse Events

Across the Phase 1 clinical trials for both GA (NCT03144999) and nAMD (NCT03585556), HMR-59 (JNJ-1887) has demonstrated a generally manageable safety profile.[1] No dose-limiting toxicities were identified in these early-phase studies.[2] Furthermore, no serious adverse events (SAEs) or systemic AEs were reported as being related to the study intervention in either trial.[2]

The most consistently observed treatment-emergent adverse event (TEAE) related to HMR-59 administration was ocular inflammation, typically presenting as mild to moderate uveitis or vitritis.[1] In the GA study (NCT03144999), where no prophylactic steroids were used, 5 out of 17 patients (29.4%) experienced such inflammation.[2] In the nAMD study (NCT03585556), which did include prophylactic oral steroids, 4 out of 25 patients (16%) developed ocular inflammation.[1] These inflammatory events were generally manageable, resolving with topical or oral steroid treatment, or with observation alone.[2]

A few cases of transiently increased intraocular pressure (IOP) were reported, often in association with the ocular inflammation.[1] No instances of endophthalmitis or, in the GA trial, new-onset CNV were reported as related to the gene therapy.[1]

Management of Ocular Inflammation

The management of ocular inflammation evolved during the Phase 1 program.

• The initial Phase 1 GA study (NCT03144999) did not include a prophylactic steroid regimen; inflammation was treated if it occurred.[2]
• The subsequent Phase 1 nAMD study (NCT03585556) incorporated a short course of prophylactic oral steroids.[1]
• The ongoing Phase 2b PARASOL study (NCT05811351) for GA employs a more comprehensive prophylactic approach, consisting of a 20-day course of oral prednisone combined with a single long-acting periocular triamcinolone injection.[12]

The consistent signal of ocular inflammation across different patient populations (GA and wet AMD) and vector doses, albeit mostly mild and manageable, highlights an inherent immunogenic potential of the AAV2 vector or the sCD59 transgene product in the ocular environment. AAV vectors are known to be capable of eliciting immune responses.[19] The proactive implementation and subsequent intensification of prophylactic steroid regimens in later-stage trials, such as PARASOL [12], represent a critical and standard measure in ocular gene therapy development. This strategy aims to preemptively control and minimize such inflammatory responses, thereby enhancing the overall safety and tolerability of HMR-59. The efficacy of this enhanced prophylactic steroid protocol in the PARASOL trial will be a key determinant of the therapy's future viability, as sustained or severe inflammation could compromise both visual outcomes and patient acceptance of a one-time treatment.

Table 2: Summary of Key Safety Findings from HMR-59 Phase 1 Trials.

Adverse Event Type	NCT03144999 (GA, N=17) Frequency/Details	NCT03585556 (Wet AMD, N=25) Frequency/Details	Management	Source Snippets
Ocular Inflammation (any)	5/17 patients (29.4%), 6 events, all mild	4/25 patients (16%), 6 events, mild (n=4) or moderate (n=2)	Topical/oral steroids or observation	1
Increased IOP	2 patients (associated with inflammation, mild, unrelated to tx in GA study)	Not specifically detailed as frequent in nAMD study snippets	Pressure-lowering drops if needed	1
Serious AEs (related)	None	None	N/A	2
Systemic AEs (related)	None	None	N/A	2
Discontinuations due to AEs (related)	None	None	N/A	2

Long-Term Safety

The ongoing LTE study (NCT06635148) will be crucial for characterizing the long-term safety profile of HMR-59, including the potential for delayed adverse events or waning of transgene expression over a 5-year period.[14]

9. Regulatory Status

FDA IND 'Safe to Proceed'

Hemera Biosciences received clearance from the U.S. Food and Drug Administration (FDA) for their Investigational New Drug (IND) application for HMR59 for the treatment of dry AMD. This "safe to proceed" status, granted in early 2017, permitted the initiation of the Phase 1 clinical trial (NCT03144999) in patients with GA.[18]

Other Regulatory Designations

The provided research snippets do not contain information regarding any specific expedited regulatory designations for HMR-59/JNJ-1887, such as Fast Track, Breakthrough Therapy, or Orphan Drug status from the FDA, nor similar designations like PRIME (Priority Medicines) from the European Medicines Agency (EMA).[5]

The absence of such designations in the available information, particularly for a therapy targeting GA—a condition with significant unmet medical need until very recently—may be attributable to several factors. When Janssen acquired HMR-59, the clinical data was still in early Phase 1. Regulatory agencies often require more substantial efficacy data, typically from well-controlled Phase 2 studies, before granting designations like Breakthrough Therapy, which are reserved for treatments demonstrating potential for substantial improvement over available therapies. With the approval of two complement inhibitors for GA in 2023 (pegcetacoplan and avacincaptad pegol) [2], the landscape for demonstrating "significant benefit" or addressing an "unmet need" for GA has evolved. HMR-59 would now likely need to show compelling advantages over these existing therapies, such as superior long-term efficacy, a better safety profile, or a significantly reduced treatment burden, to qualify for such expedited pathways. The results from the ongoing Phase 2b PARASOL trial will be pivotal in determining if HMR-59 meets these criteria and warrants applications for such designations in the future.

10. Discussion and Future Perspectives

Therapeutic Potential of HMR-59

HMR-59 (JNJ-1887) holds considerable therapeutic potential as a novel treatment modality for advanced forms of AMD. Its primary appeal lies in its design as a one-time intravitreal gene therapy, which, if successful, could dramatically reduce the treatment burden associated with current standards of care for both GA and nAMD.[1] For GA, current approved therapies require frequent (monthly or bimonthly) intravitreal injections.[2] For nAMD, anti-VEGF therapy also necessitates a chronic regimen of repeated injections.[8] A single, durably effective administration of HMR-59 could transform patient management, improve long-term adherence, and enhance quality of life.

The mechanism of action, which involves augmenting the natural protective protein sCD59 to inhibit MAC formation, is scientifically well-grounded in the understanding of complement-mediated pathology in AMD.[1] Targeting the terminal step of the complement cascade may offer a nuanced approach to immunomodulation compared to broader upstream complement inhibitors.

Challenges and Unanswered Questions

Despite its promise, the development of HMR-59 faces several challenges and unanswered questions common to ocular gene therapies:

• Durability of Expression and Clinical Effect: A critical determinant of success will be the longevity of therapeutic sCD59 expression from the AAV2 vector and the persistence of its clinical benefit. Long-term follow-up from the LTE study (NCT06635148) will be essential to address this.
• Optimal Dosing: While Phase 1 studies explored several dose levels, the optimal therapeutic window that balances maximal efficacy with minimal adverse events, particularly inflammation, needs to be definitively established in the Phase 2b PARASOL trial.
• Patient Selection: Are there specific patient subgroups (e.g., based on genetic markers of complement activity, stage of disease, prior treatment response) who would benefit most? The nAMD trial hinted at better responses in initial anti-VEGF responders.[1]
• Inflammation Management: Will the prophylactic steroid regimen in PARASOL be sufficient and well-tolerated for long-term inflammation control?
• Functional Outcomes: Critically, will anatomical improvements (e.g., slowed GA growth) translate into meaningful preservation or improvement of visual function for patients? The PARASOL trial includes functional secondary endpoints to address this.[12]

Comparison with Other Complement Inhibitors

HMR-59's single-administration gene therapy approach fundamentally differs from the currently approved complement inhibitors for GA, pegcetacoplan (anti-C3) and avacincaptad pegol (anti-C5). These drugs require repeated intravitreal injections, typically monthly or every other month, to maintain their therapeutic effect.[2] This frequent dosing regimen poses a significant burden on patients and healthcare systems.

The primary differentiating factor for HMR-59 is its potential for a "one-and-done" treatment. However, this comes with the irreversibility of gene therapy and the need for an impeccable long-term safety profile. The efficacy bar will also be high, needing to be at least comparable to, if not better than, the regular injection therapies in terms of slowing GA progression. The approved GA drugs have shown modest efficacy, typically reducing GA lesion growth by around 14-22% over 1-2 years.[2] For HMR-59 to be a compelling alternative, it must deliver significant and durable efficacy while minimizing risks of chronic inflammation or other long-term AAV-related adverse events.

Recommendations for Future Development

Future development of HMR-59 should prioritize:

• Rigorous Analysis of Phase 2b Data: Comprehensive evaluation of the PARASOL trial results, with a keen focus on the correlation between anatomical outcomes (GA lesion growth) and patient-relevant functional outcomes (BCVA, reading speed, microperimetry).
• Long-Term Safety and Durability Monitoring: Continued diligent follow-up in the LTE study is essential to confirm the multi-year safety profile and the persistence of sCD59 expression and clinical benefit.
• Biomarker Development: Exploration and validation of biomarkers (e.g., aqueous humor sCD59 levels, systemic or ocular complement activity markers, genetic markers) to predict treatment response, optimize patient selection, or identify individuals at higher risk of ocular inflammation.
• Refinement of nAMD Strategy: If the nAMD program is pursued further, studies should aim to confirm the finding that initial anti-VEGF responders benefit more and potentially explore HMR-59 in patients who are stable on anti-VEGF but require frequent injections to maintain that stability.
• Exploration of Earlier Disease Stages or Combination Therapies: Should HMR-59 prove safe and effective in advanced AMD, its potential in earlier stages of the disease or in combination with other neuroprotective or anti-angiogenic therapies could be considered to maximize visual preservation.

11. Conclusion

HMR-59 (JNJ-1887) is a promising AAV2-sCD59 gene therapy candidate with a rational mechanism for treating advanced AMD by inhibiting MAC formation. Phase 1 trials have established initial safety and preliminary efficacy signals for both GA and wet AMD. The ongoing Phase 2b PARASOL trial for GA is a critical next step to provide robust, controlled evidence of its efficacy and further define its safety profile with prophylactic steroid use. Successful development could offer a transformative, long-acting treatment option, significantly reducing treatment burden for patients with these vision-threatening diseases. The long-term safety and durability of effect remain key areas for continued evaluation.

Table 3: Key Efficacy Outcomes from HMR-59 Phase 1 Trials.

Indication	Trial ID (NCT #)	Endpoint	Result	Timepoint	Source Snippets
GA	NCT03144999	GA Lesion Growth Rate (mean square root) - High Dose Cohort	Reduction from 0.211 mm (months 0-6) to 0.056 mm (months 18-24)	24 months	5
GA	NCT03144999	GA Lesion Growth Rate vs Historical Controls (Qualitative)	Majority in high-dose cohort showed slower progression	24 months	1
Wet AMD	NCT03585556	Mean number of anti-VEGF injections (Month 1-12) for completers	2.5 injections (n=11)	12 months	1
Wet AMD	NCT03585556	Proportion of patients needing no anti-VEGF injections (Month 1-12)	18% (4/22 with $\ge$6mo follow-up)	12 months	1
Wet AMD	NCT03585556	Mean anti-VEGF injections in rapid anti-VEGF responders (Month 1-12)	1.2 injections	12 months	1

Works cited

1. CLINICAL TRIAL DOWNLOAD: Data on a Gene Therapy for Dry and ..., accessed May 19, 2025, https://retinalphysician.com/issues/2020/april/clinical-trial-download-data-on-a-gene-therapy-for-dry-and-wet-amd/
2. Geographic Atrophy Treatments Under Investigation | Biopharma PEG, accessed May 19, 2025, https://www.biochempeg.com/article/327.html
3. Phase 1 Clinical Trials - J&J Medical Connect, accessed May 19, 2025, https://www.jnjmedicalconnect.com/products/jnj-81201887/medical-content/phase-1-clinical-trials
4. Complement Inhibition for Geographic Atrophy | Retinal Physician, accessed May 19, 2025, https://retinalphysician.com/issues/2025/march/complement-inhibition-for-geographic-atrophy/
5. HMR-59 - Drug Targets, Indications, Patents - Synapse, accessed May 19, 2025, https://synapse.patsnap.com/drug/d168bcdd8e67418cab5dfa2a929ef575
6. Gene therapy in AMD: Promises and challenges - Retina Specialist, accessed May 19, 2025, https://www.retina-specialist.com/article/gene-therapy-in-amd-promises-and-challenges
7. Janssen Acquires Rights to Novel Gene Therapy, Pioneering ..., accessed May 19, 2025, https://www.prnewswire.com/news-releases/janssen-acquires-rights-to-novel-gene-therapy-pioneering-treatment-solutions-for-late-stage-age-related-macular-degeneration-301183594.html
8. Gene Therapy for Neovascular AMD | Retinal Physician, accessed May 19, 2025, https://retinalphysician.com/issues/2020/special-edition/gene-therapy-for-neovascular-amd/
9. Janssen Acquires Hemera's Gene Therapy Candidate, with GA as First Target, accessed May 19, 2025, https://www.market-scope.com/pages/news/5019/janssen-acquires-hemera-s-gene-therapy-candidate-with-ga-as-first-target
10. WILLKIE'S BIOLOGICS AND BIOSIMILARS NEWSLETTER, accessed May 19, 2025, https://www.willkie.com/-/media/files/publications/2021/02/ip-newsletter_february-2021.pdf
11. Complement Inhibition for Geographic Atrophy | Retinal Physician, accessed May 19, 2025, https://www.retinalphysician.com/issues/2025/march/complement-inhibition-for-geographic-atrophy/
12. PARASOL Phase 2 Clinical Trial - J&J Medical Connect, accessed May 19, 2025, https://www.jnjmedicalconnect.com/products/jnj-81201887/medical-content/parasol-phase-2-clinical-trial
13. accessed January 1, 1970, https://clinicaltrials.gov/study/NCT05811351
14. A Long-term Extension Study of JNJ-81201887 (AAVCAGsCD59) Parent Studies in Participants With Geogra | Global Trial Finder, accessed May 19, 2025, https://globaltrialfinder.janssen.com/trial/81201887mdg3002
15. ISRCTN11083692: A long-term extension study of JNJ-81201887 (AAVCAGsCD59) parent studies in participants with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) - ISRCTN Registry, accessed May 19, 2025, https://www.isrctn.com/ISRCTN11083692
16. accessed January 1, 1970, https://clinicaltrials.gov/study/NCT03144999
17. Can Gene Therapy Cure Macular Degeneration? - Healthline, accessed May 19, 2025, https://www.healthline.com/health/eye-health/gene-therapy-for-macular-degeneration
18. Gene therapy for dry AMD allowed to proceed - American Academy of Ophthalmology, accessed May 19, 2025, https://www.aao.org/education/headline/gene-therapy-dry-amd-allowed-to-proceed
19. Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses - PubMed Central, accessed May 19, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9173725/
20. Sanofi's high hopes for $1.1B Kymab anti-inflammatory drug dented after phase 2 asthma failure - Fierce Biotech, accessed May 19, 2025, https://www.fiercebiotech.com/biotech/sanofis-high-hopes-11b-kymab-anti-inflammatory-drug-dented-after-phase-2-asthma-failure
21. Hemera Biosciences, Inc. - Synapse - Global Drug Intelligence Database, accessed May 19, 2025, https://synapse.patsnap.com/organization/7b5be2b80c9b1a975463e185cf262be0
22. UNITED STATES COURT OF APPEALS FOR THE FEDERAL CIRCUIT, accessed May 19, 2025, https://www.cafc.uscourts.gov/opinions-orders/05-1157.pdf
23. GEOGRAPHIC ATROPHY THERAPIES TO WATCH, accessed May 19, 2025, https://assets.bmctoday.net/retinatoday/pdfs/1124RT_Cover_Hepp.pdf
24. AAVCAGsCD59 for the Treatment of Wet AMD (NCT03585556) - ClinConnect, accessed May 19, 2025, https://clinconnect.io/trials/NCT03585556
25. AAVCAGsCD59 for the Treatment of Wet AMD | TrialScreen, accessed May 19, 2025, https://app.trialscreen.org/trials/phase-1-aavcagscd59-treatment-wet-amd-trial-nct03585556
26. Phase 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy Secondary to Age-Related Macular Degeneration - PubMed, accessed May 19, 2025, https://pubmed.ncbi.nlm.nih.gov/38909914/
27. Janssen Acquires Rights to Novel Gene Therapy, Pioneering Treatment Solutions for Late-Stage Age-Related Macular Degeneration, accessed May 19, 2025, https://www.jnj.com/media-center/press-releases/janssen-acquires-rights-to-novel-gene-therapy-pioneering-treatment-solutions-for-late-stage-age-related-macular-degeneration
28. (PDF) Dry and neovascular "wet" age-related macular degeneration: Upcoming therapies, accessed May 19, 2025, https://www.researchgate.net/publication/385245808_Dry_and_neovascular_wet_age-related_macular_degeneration_Upcoming_therapies
29. CD59 Protein - ACROBiosystems, accessed May 19, 2025, https://www.acrobiosystems.com/L-767-CD59.html
30. Dry Macular Degeneration (DBCOND0067350) | DrugBank Online, accessed May 19, 2025, https://go.drugbank.com/conditions/DBCOND0067350
31. Johnson & Johnson receives FDA approval for IMAAVY™ (nipocalimab-aahu), a new FcRn blocker offering long-lasting disease control in the broadest population of people living with generalized myasthenia gravis (gMG), accessed May 19, 2025, https://investor.jnj.com/news/news-details/2025/Johnson--Johnson-receives-FDA-approval-for-IMAAVY-nipocalimab-aahu-a-new-FcRn-blocker-offering-long-lasting-disease-control-in-the-broadest-population-of-people-living-with-generalized-myasthenia-gravis-gMG/default.aspx
32. Gene Therapy for Non-Hereditary Retinal Disease: Age-Related Macular Degeneration, Diabetic Retinopathy, and Beyond - ResearchGate, accessed May 19, 2025, https://www.researchgate.net/publication/381142202_Gene_Therapy_for_Non-Hereditary_Retinal_Disease_Age-Related_Macular_Degeneration_Diabetic_Retinopathy_and_Beyond
33. accessed January 1, 1970, https://clinicaltrials.gov/study/NCT03585556