Amendment#1 Continued... - Added an open-label option for high-risk patients starting 18 months after randomization. - Modification of the inclusion criteria to show that proteinuria history must be: a documented history of proteinuria of > 1 g/day within 6 months prior to Screening, or urine protein/creatinine ratio (uPCR) > 0.75 by spot urine at Screening and mean proteinuria > 1 g/day at baseline. - Removed the upper cap on eGFR at Screening and baseline. - Deletion of the inclusion criterion specifying that the patient be: currently on physician-directed, stable treatment with RAS blockade and have a systolic BP of < 150 mm Hg and diastolic BP of < 100 mm Hg at rest. - Modification of the exclusion criterion for immunosuppressant use to narrow the disallowed window to 8 weeks from 24 weeks and to provide a caveat if the treatment is given for indications other than IgAN. - Modification of the exclusion criterion for corticosteroid use to narrow the disallowed window to within 8 weeks prior to Screening, previously within 12 weeks prior to Randomization. - Re-positioning of an inclusion criterion to exclusion criteria. The re-phrased criterion specifies the exclusion of patients who have: uncontrolled BP, a systolic BP of > 150 mm Hg and a diastolic BP of > 100 mm Hg at rest despite the combination of two or more anti-hypertensives including ACEIs, ARBs, or direct renin inhibitors. - Deletion of the exclusion criterion denying the participation of patients with a BMI ≥ 35 kg/m2. - Modified the retreatment following initial treatment. Instead of retreatment for 12 weeks, those with 24-hour UPE > 1 g/day after initial treatment will receive 6 weeks of extended treatment. - Changed the primary endpoint from 24 weeks to 36 weeks. - Revised the organization of the Secondary Endpoints from one list into Key Secondary Endpoints, Other Secondary Endpoints, and Safety and Other Endpoints. - Addition of new secondary endpoint.

Amendment#1 Continued... - Addition of new secondary endpoint: Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 48 weeks. - Addition of new secondary endpoint: Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 72 weeks. - Addition of new secondary endpoint: Time-averaged 24-hour UPE from 36 weeks to 48 weeks to a level at least 50% reduced from the baseline 24-hour UPE (patients with ≥ 2 g/day UPE at baseline only). - Addition of new secondary endpoint: Time-averaged 24-hour UPE from 36 weeks to 72 weeks to a level at least 50% reduced from the baseline 24-hour UPE (patients with ≥-2 g/day UPE at baseline only). - Addition of new Safety and Other Endpoint: Change from baseline in log-transformed 24-hour uPCR over time. - Removed a secondary endpoint: Achievement of a partial response defined as a reduction between ≥ 15% and < 30% from baseline in 24-hour UPE at 24 weeks.

Amendment #1: - Increase in the number of study sites from 100 to 140 and addition of region (Asia). - Changed the primary objective from 24 weeks to 36 weeks from baseline. - Addition of new secondary objective: Durability of proteinuria response from 36 weeks. - Revised the secondary objective to assess proteinuria at 36 weeks (instead of 24 weeks) in the subset of patients with high baseline proteinuria. - Deleted secondary objectives: Per protocol defined responder at 24-weeks and per protocol defined partial responder at 24 weeks. - Moved secondary objective to other endpoints: Time-averaged change in urine protein/creatinine ratio (uPCR). - Moved secondary objective to other endpoints: Proportion of patients who achieve partial proteinuria remission (24-hour UPE < 0.6 g/day). - Moved secondary objective to other endpoints: Proportion of patients who achieve complete proteinuria remission (24-hour UPE < 0.3 g/day). - Moved secondary objective to other endpoints: Proportion of patients who received rescue therapy for IgAN at any time during the study. - Revision of the number of patients of special interest to be enrolled (those with a baseline 24-hour UPE ≥ 2 g/day) from 50 to 78. - Run-In Period: Changed the length of the Run-In period to 4 weeks for those who have been on RAS blockade for 8 or more weeks, and to a 12-week Run-In for all other patients. - Response Evaluation Period: Changed the length of the Response Evaluation Period from Week 13 – Week 24 to Week 13 – Week 36. - Removed the description categories of responders, partial responders, and non-responders. - Deletion of Response Evaluation visits at Week 18 and 24. - Length of the Follow-Up Period was changed from 25 weeks – 144 weeks, to 37 weeks – 144 weeks. - Changed retreatment criteria at Week 24. - Modification of criteria for timing of rescue therapy. Also added the criteria that the patient has 100% increase in 24-hr UPE from baseline and patient has a 30% decrease in eGFR from baseline.

Amendment#2 Continued... - Addition of text to the section entitled, Electrocardiogram, to note that at visits conducted virtually, this procedure will not be completed. - Addition of text to the section entitled, Laboratory Assessments, to note that at visits conducted virtually, it may be allowable for CMP, CBC+diff, UA, uACR, and uPCR to be performed by a local commercial laboratory in cases where the patient is unable to travel to the study site or the study site is unable to receive or process the samples for delivery to the central laboratory. - Addition of text to the section entitled, 24-hour Urine Collection. - Addition of language to section entitled, Serum and Urine Biomarkers and Antidrug Antibodies, to note that during the COVID-19 pandemic, it may be allowable for a commercial lab to prepare and ship protocol-specified biomarker samples, and if applicable, optional research biomarker samples, to the central laboratory. - Addition of language to section entitled, Run-In Visit 1 (RI1), that notes that this visit may be performed virtually (over the phone or video conference) or at the patient’s home during the COVID-19 pandemic. - Addition of language to section entitled, Run-In Visit 2 (RI2), that notes that this visit may be performed at home during the COVID-19 pandemic regardless of whether the visit is an ongoing Run-In Visit or whether it is the final Run-In Visit. - Addition of language to section entitled, Run-In Visit 3 (RI3), that notes that this visit may be performed virtually (over the phone or video conference) or at the patient’s home during the COVID-19 pandemic. - Addition of language to section entitled, Run-In Visit 4 (RI4), that notes that this visit may be performed at the patient’s home during the COVID-19 pandemic. - Addition of language to section entitled, Treatment Visit 1 (T1/Week1) to note that randomization will not be repeated for patients who resume or reinitiate study treatment at T1.

Amendment#2 Continued... - Addition of text to section entitled, Extended Treatment Following Week 12, to describe changes in Extended Treatment Period study visits and procedures during the COVID-19 pandemic. - Addition of text to describe changes in Response Evaluation study conduct during the COVID-19 pandemic. - Addition of language to the section entitled, Response Evaluation Telephone Calls (Weeks 16, 20, 24, 30 and 34) +/- 7 days, to note that the 24-hour urine collection specimen may be delivered to the study site or central lab by the specialty courier service selected by the sponsor, provided the patient has granted consent. - Addition of language to the section entitled, Response Evaluation Visit (Week 36) +/- 7 days Primary Endpoint, to describe changes in Response Evaluation study visits and procedures during the COVID-19 pandemic. - Addition of text to describe changes in Follow-Up Period study visits and procedures during the COVID-19 pandemic. - Addition of text to section entitled, Follow-Up Visits 1 and 3 (FU1 and FU3) (Week 48 and Week 96) +/- 14 days, to describe changes in study visits and procedures during the COVID-19 pandemic. - Addition of text to section entitled, Follow-Up Visits 2 and 4 (FU2 and FU4) (Week 72 and Week 120) +/- 14 days, to describe changes in study visits and procedures during the COVID-19 pandemic. - Addition of text to section entitled, Follow-Up Visit 5 (FU5/EOS) Week 144 +/- 14 days, to note that during the COVID-19 pandemic, FU5/EOS should be conducted at the study site in order to ensure completion of all required end of study assessments. - Addition of text to describe changes in 6-Week Relapse Retreatment Period study visits and procedures during the COVID-19 pandemic. - Addition of text to describe changes in 12-Week Relapse Retreatment Period study visits and procedures during the COVID-19 pandemic. - Addition of text to describe changes in Open-Label (OL) Extended Treatment Period study conduct during COVID-19.

Amendment#2 Continued... - Addition of text to describe changes in Open-Label (OL) Relapse Retreatment Period study conduct during the COVID-19 pandemic. - Addition of text to section entitled, Timing of Study Procedures, to note that study procedures may be missed or delayed in which case the resulting protocol deviations must be clearly documented in source documents and the eCRF as related to the COVID-19 pandemic. - Addition of text to section entitled, Visit Windows, to note that study visits may be missed, canceled or delayed in which case the resulting protocol deviations must be clearly documented in source documents and the eCRF as related to the COVID-19 pandemic. - Addition of text to section entitled, Timing Between Assessments, to note that the timing of study procedures maybe impacted in which case the resulting protocol deviations must be clearly documented in source documents and the eCRF as related to the COVID-19 pandemic. - Addition of text to section entitled, Concomitant Therapy, to note that during delays in study visits as a result of the COVID-19 pandemic, investigators should make every effort to ensure patient adherence to the concomitant therapy requirements outlined in the protocol. - Addition of text to section entitled, Treatment Compliance, to note that study treatment visits may be missed or delayed in which case the resulting protocol deviations must be clearly documented in source documents and the eCRF as related to the COVID-19 pandemic. - Addition of text to section entitled, Adverse Event Reporting, to note that any COVID-19 related adverse events will be clearly documented as such in the source documents and the eCRF. -Addition of text to section entitled, General Considerations, to note that study week is defined from study Day 1 and will be determined by analysis visit windows which are defined approximately equally over adjacent scheduled visits.

Amendment#2 Continued... - Addition of text to section entitled, Analysis of Primary Efficacy Endpoint, to note that the four timepoints will be determined from study Day 1 using analysis visit windows with equal width over adjacent visits. -Addition of text to the section entitled, Monitoring, to describe how study monitoring activities may be adjusted during the COVID-19 pandemic. -Addition of text to section entitled, Informed Consent Process, to note that during the COVID-19 pandemic, it may not be possible to obtain patient consent in person.

Amendment #2: - Addition of text to highlight the changes made to protect patient safety during the COVID-19 pandemic. - Addition of text to describe changes in Screening Period activities during the COVID-19 pandemic. - Addition of text to describe changes in Run-In Period study visits and procedures during the COVID-19 pandemic. - Addition of text to describe changes in Initial Treatment Period study visits and procedures during the COVID-19 pandemic. - Addition of text to describe changes in Response Evaluation Period study conduct during the COVID-19 pandemic. - Addition of text to describe changes in Follow-Up study visits and procedures during the COVID-19 pandemic. - Addition of text to clarify that due to COVID-19 restrictions, patients who receive rescue therapy due to a treatment interruption of more than 2 consecutive study treatment visits may reinitiate study treatment after completing a wash-out period of 8 weeks. - Addition of text to describe changes in Open-Label (OL) Treatment Period study visits and procedures during the COVID-19 pandemic. -Addition of footnote to exclusion criterion 15, previously received OMS721, stating that this criterion does not apply to patients who resume or reinitiate study treatment after a COVID-19 related interruption. - Addition of text to section entitled, Informed Consent, to note that during the COVID-19 pandemic, it may not be possible to obtain patient consent in person. - Addition of text to the section entitled, Physical Examination, to note that at visits conducted virtually, the physical exam will not be completed. - Addition of text to the section entitled, Blood Pressure Optimization, to note that this procedure will be performed at virtual study visits. - Addition of text to the section entitled, Vital Signs, to note that during virtual study visits conducted during the COVID-19 pandemic, patients may obtain their blood pressure, pulse and oral body temperature using calibrated equipment provided to them.

Amendment #4: The following drug treatments are added to the exclusion criteria: 20. Treatment with sodium glucose co-transporter 2 inhibitors (SGLT2i) during Screening and Run-In Periods. However, a stable dose regimen established at least 8 weeks prior to Screening is acceptable. 21. Treatment with TARPEYO (budesonide) or other approved treatments for IgAN within 6 months prior to Screening. Treatment with TARPEYO is not allowed during Screening and Run-In Periods. -Treatment initiation during the study with SGLT2i or other drugs for the treatment of IgAN will result in early discontinuation of study drug treatment. -The following drug treatments are added to Concomitant Therapy: Treatment with sodium glucose co-transporter 2 inhibitors (SGLT2i) are prohibited from Screening onward. However, a stable dose regimen established at least 8 weeks prior to Screening is acceptable. Treatment with TARPEYO (budesonide) or other approved treatments for IgAN are prohibited within 6 months prior to Screening and throughout the study. Treatment with Kerendia (finerenone) is prohibited within 6 months prior to Screening and throughout the study.

Amendment #5: - The number of study sites increased from 140 to 200. - The duration of the study decreased from 160 weeks to 112 weeks. -Primary objective to include patients with high baseline proteinuria. -Two key secondary objectives are added to evaluate renal function up to 96 weeks from baseline in patient with high baseline proteinuria and in all the patients population. - The key secondary objective to durability of proteinuria response from 36 weeks is clarified to define the population in which this objective will be evaluated (patients with high baseline proteinuria and in all the patients population) - The primary efficacy analysis is expected to include the upset of patients with 24 UPE. - A pre-blinded sample size re estimation as defined in the statistical analysis plan.- A conditional power based SSRE for the key second endpoint of EGFR is added. - Exclusion criteria #14 relative to treatment with sodium glucose cotransporter to inhibitor is changed.- Two Addition exclusion criteria are added to exclude. - Treatment with Chinese traditional medicine with immunosuppressive function is added and excluded medication. - Patient receiving sparsentan (Filspari) for a minimum of 12 weeks prior to screening will remain on this drug. - Endpoints are amended to align with the changes to objectives. - The sample size determination is further clarified. - Statistical methodology is added for multiple comparison and multiplicity. - Statistical methodology is added for analysis of primary and key secondary efficacy endpoints. - Analysis Population of for the FAS is clarified- an additional criteria for treatment discontinuation for patients who initiate treatment with SGLT2i or other drugs to treat IgAn

Amendment #6: The Schedule of Events table for the open label extended treatment sub-group option has been added.

Amendment #7: -Text modification to exclusion criterion No. 20 (Section 8.2): • Treatment with or change in dosing of sodium glucose co-transporter 2 inhibitors (SGLT2i) during Screening and Run-In Periods. However, a stable dose regimen established at least 8 weeks prior to screening is acceptable. -Text modifications to Early Discontinuation of Study Drug Section 8.3.1): • The Investigator, Sponsor, or patient’s primary care provider decides to discontinue treatment for medical reasons other than nonresponse to study treatment, or due to the patient’s significant noncompliance with the protocol.