A Study to Evaluate the Efficacy and Safety of Orally Administered VX-01

Inclusion Criteria:

• Written informed consent must be obtained from the subject prior to anystudy-related procedures.

• Subject must be aged > 18 years at the time of Screening.

• Subject must have a body mass index (BMI) of between 18 and 40 kg/m2, inclusive.

• Subject has a documented diagnosis of T1DM or T2DM.

• Subject has moderate to severe NPDR, as determined by a Central Reading Centre (CRC)using DRSS in at least one eye

• Subject must have clear ocular media and be able to undergo adequate pupil dilationto allow adequate fundus imaging of both eyes.

• Female subject must be either:

1. Of non-childbearing potential: post-menopausal or documented surgically sterilepost hysterectomy (at least 1 month prior to Screening)

2. Or, if of childbearing potential, must have a negative serum pregnancy test atScreening and must use 2 acceptable forms of contraception, starting atScreening and throughout the study period and for 28 days after the final IPadministration.

• Female subject must not be breastfeeding at Screening or during the study period,and for 28 days after the final IP administration.

• Male subject must be surgically sterile (> 30 days since vasectomy with no viablesperm), or if engaged in sexual relations with a female of childbearing potential,the couple should agree to use 2 acceptable contraceptive methods from Screening,during the study, and for 28 days after last IP administration.

Female subject must not donate ova or male subject must not donate sperm starting at Screening and throughout the study period, and for 28 days after the final IP administration.

• Subject must have Best Corrected Visual Acuity (BCVA) assessed by Early TreatmentDiabetic Retinopathy Study (ETDRS) protocol letters score of ≥ 70 letters in studyeye, and ≥ 20 letters in the non-qualified fellow eye.

• Subject must have the ability, in the opinion of the Investigator, and willingnessto return for all scheduled visits and perform all assessments.

• Subject agrees not to participate in another interventional study after signing theinformed consent and until the End of Study (EOS) visit has been completed.

Exclusion Criteria:

Ophthalmic:

• Presence of CI-DME (with central subfield thickness [CST] measured greater than 325 μm on spectral domain optical coherence tomography [SD-OCT]) threatening the centerof the macula (within 1,000 μm of the foveal center) in either eye, or presence ofDME requiring treatment.

• Presence of moderate to high-risk PDR (DRSS level 65 or higher).

• Any prior treatment (in either eye) with:

1. Focal or grid laser photocoagulation within the past 6 months prior toScreening or pan-retinal photocoagulation (PRP) at any time.

2. Systemic or intravitreal anti-vascular endothelial growth factor (VEGF) agentswithin the last 12 months prior to Screening.

3. Intraocular, sub-tenon or periocular steroids, including triamcinolone anddexamethasone implant within the last 6 months, or suprachoroidal triamcinolonewithin the last 3 months prior to Screening.

4. Fluocinolone implant within the last 3 years prior to Screening.

5. Prior treatment for NPDR with any other treatment which is not labelled forNPDR within 1 year prior to Screening (e.g., calcium dobesilate, fibratemedication).

6. Vitrectomy at any timepoint prior to Screening.

7. Yttrium-Aluminium-Granate (YAG) capsulotomy within 3 months prior to Screening.

• Active uveitis, vitritis, or infection in either eye including infectiousconjunctivitis, keratitis, scleritis, or endophthalmitis.

• History of corneal transplant and/or vitrectomy or any other ocular incisionalsurgery in either eye (e.g., shunt surgery). Note: Subjects who have had cataract orrefractive surgery in either that was more than 3 months prior to Screening may bepermitted at the discretion of the Investigator.

• Uncontrolled glaucoma, as evidenced by intraocular pressure (IOP) > 25 mmHg despiteup to 4 glaucoma medications, or evidence of glaucomatous visual field loss or hasadvanced glaucoma (e.g., prior shunt surgery) in either eye.

• Clinically significant ocular disease in either eye that in the opinion of theInvestigator would preclude participation in the study.

• Presence of macular or retinal vascular disease including DME and/or retinopathyfrom causes other than diabetes, age-related macular degeneration, patterndystrophy, choroidal neovascularisation of any cause, retinal vein occlusion,retinal artery occlusion in either eye.

• History of retinal detachment or full-thickness macular hole post intraocularsurgery in either eye, or idiopathic or autoimmune uveitis in either eye.

• Any other ocular disease that may cause substantial reduction in BCVA.

Systemic:

• Known, suspected hypersensitivity or contraindication to IP.

• Uncontrolled diabetes mellitus with HbA1c of ≥ 12%.

• Initiation of treatment with glucagon-like peptide-1 (GLP-1) modulators forglycaemic control and other indications within the last 3 months prior to Screening.

• Initiation of intensive insulin treatment (a pump or multiple daily injections)within 3 months prior to Screening or plans to do so in the next 3 months.

• Current use of coumarin anticoagulants (Coumadin/Warfarin).

• On dialysis or an estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73m2as per CKD-EPI evaluation at Screening. (Active Diabetic Ketoacidosis orHyperglycemic Hyperosmolar Nonketotic State).

• Hypertension with resting diastolic blood pressure (BP) > 100 mmHg or systolic BP > 180 mmHg on 2 consecutive measurements at least 5 minutes apart. Note: If the resultis out of range, the assessment may be repeated once prior to randomisation forconfirmation.

• Resting heart rate outside the specified range (50 to 110 beats per minute). Note:If the result is out of range, the assessment may be repeated once prior torandomisation for confirmation.

• History of chronic liver disease or presence of elevated (defined as > 3 × upperlimit of normal) alanine aminotransferase (ALT) and aspartate aminotransferase (AST)consistent with such diagnosis.

• Known to be immunocompromised or receiving immunosuppressive therapy. Note: Subjectsreceiving low dose corticosteroids may be eligible, at the discretion of theInvestigator.

• Currently receiving treatment with a strong inhibitor of the P-glycoproteintransporter (see Section 6.4.2), which may interfere with the IP.

• History of allergy to fluorescein.

• Any disease or medical condition that in the opinion of the Investigator wouldinterfere with the study, prevent the subject from successfully participating in thestudy, or which might confound the study results.

• Participation in any investigational study within 30 days prior to Screening orplanning to participate in any other investigational drug or device clinical trialswithin 30 days of study completion.

• History of blood transfusion or severe blood loss within 3 months prior toScreening, known hemoglobinopathy, and severe anaemia.