Amendment #1: 27 January 2017 Changes made included the addition of a patient-reported outcome (PRO) tool (health survey questionnaire, SF-36 v.2) and clarification of storage conditions throughout the duration of the study.

Amendment #2: 07 April 2017 (Country Specific - UK) Changes made to the Protocol include: • Amendment of the investigator requirements in case of emergency unmasking. • Amendment to the Safety Section with specific reference to reactions not listed in the AR-13324 Ophthalmic Solution (Netarsudil Ophthalmic Solution) / PG324 Ophthalmic Solution Investigator Brochure and/or in Section 4.8 of Ganfort® SmPC. • Clarification to contraception guidance section with specific reference to sexual abstinence. • Amendment to the Protocol Deviation section to clarify that Protocol deviations are not acceptable and clarification of Sponsor responsibilities for the assessment and reporting to the MRHA if any non-compliances considered as a serious breach of GCP and the protocol, and other minor clarifications. • Administrative changes to numeration errors in the summary of changes section for Amendment #1: 27 January 2017.

Amendment #3: 05 June 2017 Changes to the protocol have been made in accordance with observations made by the following Competent Authorities and/or Ethics Committees in participating countries. These changes included the following: • Clarification of eligibility criteria • Guidance on use of the NEI VFQ-25 questionnaire • Details on contraception use • Instructions for the washout period (duration, monitoring of subjects, etc.) • Clarification on subjects capable of giving consent to participate • Addition of a pregnancy test type and timepoints • Justification for the 30-day period post-study to refrain from breast feeding • Introduction of drug interactions indicated in the GANFORT SmPC • Various administrative changes and updates

Amendment #4: 19 March 2018 1. Changes to inclusion and exclusion criteria were made based on feedback from Investigators to reflect current clinical practice and facilitate patient screening: a. Revision to medicated IOP required for a subject to enter screening from > 18mmHg and < 25mmHg in both eyes to ≥ 17mmHg in at least one eye and < 28mmHg in both eyes. b. Clarification of the GANFORT® exclusion criteria. c. Revision of the criteria regarding prior systemic medications (including corticosteroids) that affect IOP. d. Clarification of the use of topical steroids. 2. Changes to Section 5.6 Concomitant Medications to clarify the use of steroids by various routes. 3. To allow investigators (at their discretion) to record images of ocular events. 4. Removal of the requirement at Visits 7, 8, and 9 to measure IOP at 08:00 and 16:00. All assessments previously required to be performed at 08:00 and 16:00 visits would be performed at one 10:00 visit. 5. Increase window for 08:00 IOP assessments to +/- 1 hour. In addition to the feedback from investigators the following changes were made: 1. From the time that the subject gives written consent events that occur to be recorded as adverse events and not as previously stated as medical history until the time of randomization. 2. Updated references to ICH E6 (R2) throughout. 3. Abbreviation QD changed to Q.D. throughout. 4. To clarify that Investigational Product will be administered to both eyes for the duration of the study. 5. INC Research has changed name to Syneos Health. INC research has been updated to the new company name Syneos Health throughout. Other changes were made to correct typographical errors and inconsistencies.

Amendment #5: 06 August 2018 (Country Specific – Hungary) Changes to the protocol were made in accordance with observations made by the Hungary Medical Research Council Ethics Committee for Clinical Pharmacology (MRC ECCP) 23 July 2018. The changes were to amend the study title to clarify that PG324 is a fixed dose combination of netarsudil and latanoprost.

Amendment #6: 27 May 2020 Changes have been made primarily to reflect updates that will be made to the statistical analysis plan (SAP), and a decision to stop screening activities when the study was >90% enrolled. The decision to stop screening was not the result of any safety concerns, but a Sponsor administrative decision.

Amendment #7: 27 May 2020 (Country Specific Hungary) Changes have been made primarily to reflect updates that will be made to the statistical analysis plan (SAP), and a decision to stop screening activities when the study was >90% enrolled. The decision to stop screening was not the result of any safety concerns, but a Sponsor administrative decision.