Change to the reference of enteric-coated capsules to polymer-coated capsules and addition of a footnote to the schedule of activities in Part A to clarify an end of study pregnancy test was to be carried out in all participants. This was not submitted to the competent authorities and ethics committee .

• Change in study design such that Part B could commence dosing following SRC review of Part A, Cohort 1 (3.9 × 1012 eTPN QD dose level). • Change in Phase 2 (Part B) dose from 7.5 × 1013 to 3.9 × 1012 eTPN QD. • Deletion of reference to Data Monitoring Committee and change in the safety committee from Dose-Level Review Committee to SRC. • Change in minimum number of participants with safety data required for each SRC (changed from 8 to 10 participants). • Update the requirement in Part A for blood samples for biomarkers and systemic levels of EDP2939 to be taken predose on Day 10. • Separate text for Part A and Part B permitted and contraindicated immunizations. • Iteration of specific study halting criteria for Part B. • Specification that SRC review was to be initially performed in a blinded manner. Unblinded review was only to be done if a potential safety signal needed to be confirmed or rejected. This was not submitted to the competent authorities and ethics committee.

• Change in exclusion criterion number 22 that participants in Part B would be permitted to use unmedicated emollients and moisturizers during the study (but were to be withheld on visit days when skin assessments were made). Other topical treatments were excluded if used within 14 days of randomization. • Change in exclusion criterion number 24 with deletion of “bilirubin >1.5 × upper limit of normal”. • Inclusion of monkeypox vaccine in list of live vaccines. • Update of description of the VAS to be rated between 0 (fatigue is no problem) to 100 (fatigue is major problem). • Addition of the Declaration and Signature of the investigator page. This was the first version submitted to regulatory authorities and ethics committees.

• Change in grading of intensity of AEs for healthy participants in Part A to be mild, moderate, or severe. The CTCAE grading scale was only to be used for participants in Part B. • Deletion of bilateral tubal ligation as a reason to consider a female to be of nonchildbearing potential. • Update in highly effective contraception methods text to change “tubal occlusion” to “tubal occlusion/ligation”. • Clarification that Part B investigators would have immediate and unrestricted access within the IRT system to unblind in case of emergency. Additionally, the investigator responsibilities in determining the need for unblinding were clarified and the time frame for sponsor notification were kept the same for Parts A and B.