Amendment dated April 9, 2021 to Letter Agreement between Evelo Biosciences, Inc. and David R. Epstein

“Effective on June 30, 2021, and subject to approval by the Board, the Company shall award to you a number of Restricted Stock Units (as defined in the Company’s 2018 Incentive Award Plan, “RSUs”) having an aggregate grant date fair value equal to approximately $375,000, as determined by the Board in its discretion based on a ten-day trailing average of the closing price of a share of the Company’s common stock on the Nasdaq Global Select Market. The RSUs shall be granted under and shall be subject to the terms and provisions of the Company’s 2018 Incentive Award Plan (the “Plan”) and shall be granted subject to a restricted stock unit agreement. The RSUs shall vest in 12 substantially equal monthly installments following June 30, 2021, such that the RSUs shall be fully vested on June 30, 2022, subject to your continuing service as the Chairman through each such vesting date. Unless the Board otherwise determines, any portion of the RSUs which is unvested at the time of the termination of your service as the Chairman shall be immediately forfeited upon such termination and shall not thereafter become vested. The RSUs shall vest in full immediately prior to the occurrence of a Change in Control (as defined in the Plan), to the extent outstanding at such time. The provisions of Section A and the first two paragraph of Section B above shall cease to operate as of June 30, 2021 and thereafter your sole compensation (other than previously granted and then outstanding stock options) for service on the Board and its committees or subcommittees, including as Chairman, shall be as set forth in this third paragraph of Section B.”