AFFINITY DUCHENNE: RGX-202 Gene Therapy in Participants with Duchenne Muscular Dystrophy (DMD)

Part 1 - Key Inclusion Criteria:

• The participant's legal guardian(s) is (are) willing and able to provide written,signed informed consent prior to any study-related procedures; and, whereapplicable, the minor participant has provided written or verbal assent according tolocal requirements.

• Is a male at least 4 years of age and less than 12 years of age at consent or 1 to <4 years of age at the time of dosing and ≥ 10 kg at the time of screening.

• Must meet any of the following criteria:

• DMD gene mutation in exons 18 and above, and a clinical picture consistent withtypical DMD with the exception of a participant (Cohort 1b) with DMD genemutation in exons 12-17.

• Participant is able to walk 100 meters independently without assistive devices.Cohort 2c participant must be able to walk 10 meters independently withoutassistive devices. Cohort 1b The participant must be able to walk with orwithout assistive devices.

• Participant is able to complete the TTSTAND per protocol-specific criteria.

• Participant has been on a stable dose of systemic glucocorticoids according tothe standard of care for at least 12 weeks. Cohort 2c participants must beconsistently on or off a stable dose of systemic glucocorticoids according tothe standard of care for at least 12 weeks.

• Clinical laboratory test results, including hepatic and renal function, arewithin the normal range during screening, or if abnormal, are not clinicallysignificant, in the opinion of the investigator.

• Documentation is provided at screening visit for participant's adherence to thelocal country's vaccination schedule. The parent(s) or legal guardian(s) mustbe willing to have their child receive a meningococcal vaccine, if not alreadyvaccinated.

• Participant and parent(s)/legal guardian(s) are willing and able to comply withscheduled visits, study intervention administration plan, and study procedures.

Part 2 and 3 Inclusion Criteria:

• The participant's legal guardian(s) is (are) willing and able to provide written,signed informed consent prior to any study-related procedures; and, whereapplicable, the minor participant has provided written or verbal assent according tolocal requirements.

• DMD gene mutation in exons 18 and above, and a clinical picture consistent withtypical DMD.

• Participant is able to complete the TTSTAND per protocol-specific criteria.

• Clinical laboratory test results, including hepatic and renal function, are withinthe normal range during screening, or if abnormal, are not clinically significant,in the opinion of the investigator.

• Documentation is provided at screening visit for participant's adherence to thelocal country's vaccination schedule. The parent(s) or legal guardian(s) must bewilling to have their child receive a meningococcal vaccine, if not alreadyvaccinated.

• Participant and parent(s)/legal guardian(s) are willing and able to comply withscheduled visits, study intervention administration plan, and study procedures.

• Is a male at least 1 year of age and ≥ 10 kg at the time of screening.

• Participants 1 to <4 years of age must meet the following criteria:

• is able to walk 10 meters independently without assistive devices.

• must be consistently on or off a stable dose of systemic glucocorticoidsaccording to the standard of care for at least 12 weeks.

• Participants 4 years and older must meet the following criteria:

• are able to walk 100 meters independently without assistive devices.

• have been on a stable dose of systemic glucocorticoids according to thestandard of care for at least 12 weeks.

• have a NSAA total score ≥16.

Part 1 Exclusion Criteria:

• Participant has any condition that would contraindicate treatment withimmunosuppression.

• Participant has received ataluren (a protein restoration therapy) or anexon-skipping therapy for the treatment of DMD within 6 months of study entry or isunable to refrain from taking ataluren or exon-skipping therapy for a duration of 5years from the time of RGX-202 administration.

• Participant has received any investigational or commercial gene therapy product overhis lifetime.

• Participant is currently taking any other investigational intervention (other thancorticosteroids) or has taken any other investigational intervention (other thancorticosteroids) within 3 months prior to the scheduled Day 1 intervention. If thecorticosteroid is vamorolone, the participant must be converted to equivalent dailyprednisolone or prednisone dose on Day -1 and remain on this for 12 weeks. Twelveweeks after the dosing of RGX-202, the participant will be allowed to resumevamorolone at the original per kilogram dose at which he entered the study andshould remain on this for 24 months unless the investigator determines that this isnot clinically indicated or possible.

• Participant has detectable AAV8 total binding antibodies in serum.

• Participant has impaired cardiac function defined as a left ventricular ejectionfraction of < 55% on screening cardiac assessments (echocardiogram or MRI).

• Participant is not a good candidate for the study, in the opinion of theinvestigator.

Part 2 and 3 Exclusion Criteria:

• Participant has any condition that would contraindicate treatment withimmunosuppression.

• Participant has received givinostat within 3 months of study entry or has receivedataluren (a protein restoration therapy) or an exon-skipping therapy for thetreatment of DMD within 6 months of study entry or is unable to refrain from takingataluren or exon-skipping therapy for a duration of 5 years from the time of RGX-202administration.

• Participant has received any investigational or commercial gene therapy product overhis lifetime.

• Participant is currently taking any other investigational intervention (other thancorticosteroids) or has taken any other investigational intervention (other thancorticosteroids) within 3 months prior to the scheduled Day 1 intervention. If thecorticosteroid is vamorolone, the participant must be converted to equivalent dailyprednisolone or prednisone dose on Day -1 and remain on this for 12 weeks. Twelveweeks after the dosing of RGX-202, the participant will be allowed to resumevamorolone at the original per kilogram dose at which he entered the study andshould remain on this for 24 months unless the investigator determines that this isnot clinically indicated or possible.

• Participant has detectable AAV8 total binding antibodies in serum.

• Participant has impaired cardiac function defined as a left ventricular ejectionfraction of < 55% on screening cardiac assessments echocardiogram or MRI).

• Participant is not a good candidate for the study, in the opinion of theinvestigator.