•Incorporated EudraCT number •Updated all sections that include endpoints and endpoint analysis from “daily average” to “time-weighted average” •Changed “pneumonia” to “LRTI” in all references to definitions of LRTC •Added text to include Optional Extended Viral Monitoring •Added text to ensure subjects avoid direct UV exposure for 8 days after receiving IMP •Updated all references of “urine pregnancy test” to “urine or serum pregnancy test” •Updated all chest X-ray references of “within 2 days” to “< 48 hours” •Removed all references of vital signs needing to be obtained 5 – 10 minutes prior to IMP dosing •Updated “will” to “should” for study visit assessments being performed in order •Corrected spelling/grammatical errors and made formatting changes for consistency throughout the protocol •Updated section titles to reflect changes •Updated the Protocol Synopsis to ensure consistency with changes made to the main body of the protocol (changes to the Protocol Synopsis are not reflected herein)

•Exclusion Criterion 2 washout period for strong cytochrome P450 enzyme (CYP) inducers extended from 1 to 2 weeks to reflect a more conservative washout period. •Addition of pregnancy testing at all dosing visits for females of childbearing potential for consistency with Appendix 5. •Extension of male contraceptive and sperm donation requirements from 30 to 90 days after last dose of study drug for consistency with the Investigator’s Brochure (IB). •Inclusion Criterion 8 modified in alignment with changes made to contraceptive requirements in Appendix 5.

Removal of double-barrier method as contraceptive method to ensure all contraception is in accordance with the ICH M3 guidance that birth control methods need to be highly effective (ie, < 1% failure rate).

•Background Section 1.2.2 updated for consistency with the IB •Secondary and exploratory objectives and endpoints reprioritized and updated due to changes in design strategy •New Inclusion Criterion 1 added to clarify age ranges allowed in study •Inclusion Criterion 4 updated to clarify chronic respiratory conditions •Exclusion Criterion 2 and Section 5.4 updated to further exclude moderate CYP inducers •Exclusion Criterion 8 updated to exclude coronaviruses due to severe clinical disease now known to be associated with MERS •Exclusion Criterion 14 updated to clarify the criterion applies to sulfa reactions that are of most concern •MRI removed from SOC chest image collection •Hepatic monitoring and statistical texts updated for clarity •Protocol version and date were updated in all applicable sections, headers, and footers •Corrected spelling/grammatical/consistency errors throughout the protocol •Glossary of abbreviations was updated to reflect corresponding changes throughout the protocol •Corresponding changes made to the protocol body text were also made to the Protocol Synopsis and Study Procedures Table, where appropriate

•Added ECGs, troponin testing, and collection of standard of care clinical data for central review •Prior and concomitant mediations section updated to attribute part of cyclosporine effect as a weak CYP3A inhibitor, to clarify that presatovir is not expected to alter PK of concomitant medications that are substrates of major CYP enzymes or drug transporters, and to note that the potential effect of strong and moderate CYP3A inhibitors on presatovir PK are under investigation. •Added vital signs and oxygen saturation added to Visits 3 and 5, if not home visits, and study-specific assessments added to Visits 3 and 5, if not home visits, and post-randomization assessments for consistency with other study visits. •Interim analysis removed. Extending the duration for assessing these clinical endpoints that occur at lower frequencies may be useful for registrational trials

•Increased the number of study centers participating to 80 and added Japan to the list of countries •Modified Screening procedures such that subjects who were not tested for RSV as standard of care may consent to the study and be tested for RSV during the Screening visit. •Modified primary endpoint to include development of lower respiratory tract complication (LRTC) co-primary endpoint, which was previously listed as a secondary endpoint •Included Japan specific definition of adult to the inclusion criteria •Included Sweden specific requirements for obtaining consent via legal guardian to the inclusion criteria •Modified Screening procedures to allow for RSV testing on subjects after consent •Updated text to allow subjects who screen fail out of GS-US-218-1502 due to absence of LRTI to screen into GS-US-218-0108 and vice versa •Included Japan specific instructions for obtaining nasal swab samples at Visit 1: Screening and Visit 2: Baseline •Updated Visit 3: Day 3 to an optional visit for subjects who are not participating in the PK subgroup •Updated Statistical Methods and Sample Size sections to reflect changes in primary and secondary endpoints •Updated Appendix 5 contraception language to include Japan specific requirements