A Study to Investigate Faricimab Treatment Response in Treatment-Naive, Underrepresented Patients With Diabetic Macular Edema

Inclusion Criteria:

Main Phase General Inclusion Criteria:

• Self-identify as Black/African American, Hispanic/Latino American, or NativeAmerican/Alaska Native/Native Hawaiian or other Pacific Islander; or self-identifyas Asian Indian residents of the Indian subcontinent

• Diagnosis of diabetes mellitus (type 1 or type 2), as defined by the World HealthOrganization (WHO) and/or American Diabetes Association, and current regular use ofinsulin or other injectable drugs (e.g., dulaglutide and liraglutide) and/or oralanti-hyperglycemic agents for the treatment of diabetes

• Hemoglobin A1c (HbA1c) ≤10% (Note: up to 20% of participants enrolled may have HbA1cup to 12%)

• For women of childbearing potential: Agreement to remain abstinent (refrain fromheterosexual intercourse) or use acceptable contraception methods as defined in theprotocol

Main Phase Ocular Inclusion Criteria for Study Eye:

• Intravitreal (IVT) treatment-naïve in the study eye (i.e., have not receivedprevious treatment with any anti-VEGF IVT or any corticosteroids periocular or IVTin the study eye)

• Diabetic macular edema, defined as macular thickening by SD-OCT involving the centerof the macula

• BCVA letter score of 73 to 20 letters (both inclusive) using the ETDRS protocol atthe initial testing distance of 4 meters at the baseline visit (Day 1)

• Clear ocular media and adequate pupillary dilation to allow acquisition of goodquality retinal images to confirm diagnosis

Long-Term Extension (LTE) Inclusion Criteria:

• Enrollment in and completion of the main study, without discontinuation from studyor study drug treatment

• Signed LTE-phase Informed Consent Form

• Ability to comply with the study protocol, in the investigator's judgment

• For women of childbearing potential: Agreement to remain abstinent (refrain fromheterosexual intercourse) or use acceptable contraception methods as defined in theprotocol

Exclusion Criteria:

Main Phase General Exclusion Criteria:

• Diabetes mellitus (type 1 or type 2) that is currently medically untreated

• Previously untreated diabetes mellitus (type 1 or type 2) who started on oral orinjectable anti-diabetic medication within 3 months prior to Day 1

• Any known hypersensitivity to any of the components in the faricimab injection

• Any known hypersensitivity to any contrast media (e.g., fluorescein), dilating eyedrops, disinfectants (e.g., iodine), or any of the anesthetics and antimicrobialpreparations used by the patient during the study

• History of other diseases, other non-diabetic metabolic dysfunction, physicalexamination finding, or historical or current clinical laboratory finding givingreasonable suspicion of a condition that contraindicates the use of the faricimab orthat might affect interpretation of the results of the study or renders the patientat high-risk for treatment complications, in the opinion of the investigator

• Active cancer within the past 12 months prior to Day 1 except for appropriatelytreated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostatecancer with a Gleason score of ≤6 and a stable prostate-specific antigen for >12months

• Stroke (cerebral vascular accident) or myocardial infarction within 12 months priorto Day 1

• Any febrile illness within 1 week prior to Day 1

• Pregnant or breastfeeding, or intending to become pregnant during the study orwithin 3 months after the final dose of faricimab

• Uncontrolled blood pressure, defined as systolic >180 mmHg and/or diastolic >100mmHg (while patient is at rest in a sitting position); if a patient's initialreading exceeds these values, a second reading may be taken ≥30 minutes later on thesame day

• Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysiswithin 6 months prior to Day 1 or anticipated to require hemodialysis or peritonealdialysis at any time during the study

• Any condition resulting in a compromised immune system that is likely to impact theaqueous humor inflammatory biomarkers

• Participation in an investigational trial that involves treatment with any drug ordevice (with the exception of vitamins or minerals) within 3 months (or 5half-lives, whichever is longer) prior to Day 1, or during the course of this study

• Substance abuse occurring within 12 months prior to screening, in the investigator'sjudgment

• Use of systemic immunomodulatory treatments (e.g., IL-6 inhibitors) within 6 monthsor 5 half-lives (whichever is longer) prior to Day 1

• Use of any systemic corticosteroids within 1 month prior to Day 1

• Systemic treatment for suspected or active systemic infection

• Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5half-lives (whichever is longer) prior to Day 1

• Use of systemic medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines, orethambutol) during the 6-months (or 5 half-lives, whichever is longer) prior to Day 1

• Receiving any treatment that leads to immunosuppression within 6 months (or 5half-lives, whichever is longer) prior to Day 1

• Requiring continuous use of any medications or treatments listed as prohibitedtherapy

Main Phase Ocular Exclusion Criteria for Study Eye:

• High-risk proliferative diabetic retinopathy (PDR) in the study eye, using any ofthe following established criteria for high-risk PDR: Any vitreous or pre-retinalhemorrhage; Neovascularization elsewhere ≥1/2 disc area within an area equivalent tothe mydriatic ETDRS 7 or 4 fields on clinical examination or on CFPs;Neovascularization at disc ≥1/3 disc area on clinical examination

• Tractional retinal detachment, pre-retinal fibrosis, vitreomacular traction, orepiretinal membrane involving the fovea or disrupting the macular architecture inthe study eye, as evaluated by the central reading center

• Any history of or ongoing rubeosis iridis

• Any panretinal photocoagulation or macular laser (focal, grid or micropulse)photocoagulation treatment received in the study eye prior Day 1

• Any history of treatment with anti-VEGF or any periocular or IVT corticosteroids inthe study eye prior to Day 1

• Any treatment for dry eye disease in the last month prior to Day 1 (e.g.,cyclosporine eye drops, lifitegrast eye drops). Lubricating eye drops and ointmentsare permitted.

• Any treatment with anti-inflammatory eye drops (e.g., doxycycline) within 1 monthprior to Day 1

• Any intraocular surgery (e.g., cataract surgery) within 3 months prior to Day 1 orany planned surgery during the study

• Any glaucoma surgery prior to the screening visit

• History of vitreoretinal surgery/pars plana vitrectomy, corneal transplant, orradiotherapy

• Uncontrolled glaucoma

• Any active or suspected ocular or periocular infections on Day 1

• Any presence of active intraocular inflammation on Day 1 (i.e., Standardization ofUveitis Nomenclature [SUN] criteria >0 or National Eye Institute [NEI] vitreous hazegrading >0) or any history of intraocular inflammation

• Any history of idiopathic, infectious, or noninfectious uveitis

• Any current ocular condition or other causes of visual impairment for which, in theopinion of the investigator, visual acuity loss would not improve from resolution ofmacular edema

Main Phase Ocular Exclusion Criteria for Non-Study Eye:

• Any history of idiopathic or immune-mediated uveitis

• Active ocular inflammation or suspected or active ocular or periocular infection onDay 1

• Currently receiving treatment with brolucizumab or bevacizumab in the non-study eyeand is unwilling to switch to a protocol-allowed, non-study eye anti-VEGF treatmentduring the study

• Any previous treatment with Iluvien® or Retisert® (fluocinolone acetonide IVTimplant) in the non-study eye

• Non-functioning non-study eye, defined as either: BCVA of hand motion or worse; Nophysical presence of non-study eye (i.e., monocular); or, Legally blind in thepatient's relevant jurisdiction

Long-Term Extension (LTE) Exclusion Criteria:

• Pregnant or breastfeeding, or intending to become pregnant during the study orwithin 3 months after the final IVT injection of faricimab

• Presence of other ocular diseases that give reasonable suspicion of a disease orcondition that contraindicates the use of faricimab, that might affectinterpretation of the results of the LTE, or that renders the patient at high riskfor treatment complications

• Presence of other diseases, metabolic dysfunction, or clinical laboratory findinggiving reasonable suspicion of a disease or condition that contraindicates the useof faricimab and that might affect interpretation of the results of the LTE, or thatrenders the patient at high risk of treatment complications

• History of a severe allergic reaction or anaphylactic reaction to a biologic agentor known hypersensitivity to any component of the faricimab injections, studytreatment procedure, dilating drops, or any of the anesthetic and antimicrobialpreparations used by a patient during the LTE phase

• Requirement for continuous use of any medications or treatments indicated asprohibited therapy (as defined in the protocol)