edp1815datapresentationv

Broad Platform Opportunity and New Therapeutic Modality Supported by Positive Interim Clinical Data EDP1815 Advancing to Phase 2 August 6, 2019

Legal Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including our development plans and new formulations, the promise and potential impact of any of our monoclonal microbials or preclinical or clinical trial data, the timing of and plans to initiate clinical studies of EDP1815, and the timing and results of any clinical studies or readouts. These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding; our limited operating history; our unproven approach to therapeutic intervention; the lengthy, expensive, and uncertain process of clinical drug development, including potential delays in regulatory approval; our reliance on third parties and collaborators to expand our microbial library, conduct our clinical trials, manufacture our product candidates, and develop and commercialize our product candidates, if approved; our lack of experience in manufacturing, selling, marketing, and distributing our product candidates; failure to compete successfully against other drug companies; protection of our proprietary technology and the confidentiality of our trade secrets; potential lawsuits for, or claims of, infringement of third-party intellectual property or challenges to the ownership of our intellectual property; our patents being found invalid or unenforceable; risks associated with international operations; our ability to retain key personnel and to manage our growth; the potential volatility of our common stock; our management and principal stockholders have the ability to control or significantly influence our business; costs and resources of operating as a public company; unfavorable or no analyst research or reports; and securities class action litigation against us. These and other important factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2019, and our other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any such forward-looking statements represent management's estimates as of the date of this presentation. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this presentation. 2

Key Highlights • Interim clinical data supports Evelo’s platform opportunity and vision • EDP1815 and EDP1066 were well tolerated • EDP1815 in psoriasis • Reduction in mean Lesion Severity Score vs. placebo • Consistent skin and blood immune cell biomarker responses • Advancing into Phase 2 in early 2020 • EDP1066 in psoriasis • Pharmacodynamic responses on blood immune cell biomarkers at high dose • No further development in psoriasis • Investigating more potent formulation in atopic dermatitis patients in ongoing study 3

EDP1815 in Psoriasis 4

Targeting EDP1815 to Address Unmet Needs of Psoriasis Patients Mild Moderate Severe 71% 22% 7% • Future opportunity to treat any stage of disease given differentiated profile of Evelo’s oral biologics • Initial focus on mild to moderate populations with potential to address over 3.5 millionof these patients in US and EU5 and expand globally (2018 company-sponsored market research; EU consisting of France, Germany, Italy, Spain and the UK 5

EDP1815 Low Dose Psoriasis Cohort • 12 patients with mild to moderate psoriasis • Randomized 2:1 (active:placebo) with 550mg dose (enteric capsule formulation) for 28 days; daily oral administration • Primary endpoint of safety and tolerability • EDP1815 was well tolerated with no overall difference reported from placebo • Signal finding study, low dose and short duration of dosing 6

Secondary and Exploratory Endpoints Reported • Lesion Severity Score • Cellular biomarkers from skin biopsies • Blood immune cell biomarkers of cytokine production 7

Lesion Severity Score is a Sensitive Clinical Measure • Clinical measure of disease change in psoriasis • Lesion Severity Score is a component of the PASI scoring system • Uses the same underlying changes as lesion severity element of the PASI score • Tracks an individual lesion across dosing period • Measures redness, thickness and scaling on a 12-point scale • Sensitive short-term measure in patients with mild to moderate disease 8

Statistically Significant Reduction in Lesion Severity Score Mean change (+/- SE) in lesion severity score over dosing period 9

Patient Data Showed Reduction in Lesion Severity Score of 0-67% 25% 0% Percent change in Group lesion severity score at −25% Placebo end of dosing period EDP1815 −50% −75% 1 2 3 4 5 6 7 8 9 10 11 12 ID 10

Reductions in Skin Cellular Biomarkers were Consistent with Improvement in Lesion Severity Score • Psoriasis pathology is driven by epithelial hyperplasia • Reductions observed in basal Mean (+/- SE) change in basal epithelium mitotic epithelium mitotic counts across cell count over dosing period (cells/mm2) patients dosed with EDP1815 11

Reduction in Blood Immune Cell Cytokine Production Indicative of a Systemic Anti-inflammatory Response Changes over Dosing Period in Cytokine Production After Stimulation of Blood Immune Cells with Lipopolysaccharide • Reduction in systemic cytokine Increased Production Increased production consistent with clinical signal and histological biomarkers • No reduction observed in placebo Decreased production Decreased Cytokines detected: IL10, IL8, TNFα, IL6, IL1B, IFN-γ Decrease or increase in cytokine production defined as a change of 2 pg/ml over dosing period 12

Positive Interim Data for 1st Cohort with Low Dose Over 28 Days Supports Advancing into Phase 2 • EDP1815 was well tolerated with no overall difference reported from placebo • Statistically significant reduction vs. placebo in Lesion Severity Score • Reduction in Lesion Severity Score of 0-67% in patients dosed with EDP1815 • Cellular biomarker changes consistent with reduction in Lesion Severity Score • Reduction in blood immune cell cytokine production indicative of a systemic anti- inflammatory response 13

Planning for EDP1815 Phase 2 and Indication Expansion Placebo-controlled dose and formulation optimization study in mild to moderate psoriasis patients planned for early 2020 initiation • Primary endpoint: change in PASI score at 24 weeks • Interim analysis at 12 weeks Part A Part B Goal: Formulation selection Goal: Dose selection n~180, 3 arms, original formulation vs. n~250, 4 arms, 3 different doses of optimal new formulation vs. placebo formulation vs. placebo Opportunity to expand into additional diseases following Part A interim analysis 14

Novel Formulation was Up to 30-fold More Potent Preclinically 15

EDP1066 in Psoriasis 16

Dose-dependent Response Observed on Blood Immune Cell Cytokine Production in Phase 1b Clinical Trial • EDP1066 was well tolerated with no overall difference reported from placebo • Reduction in blood immune cell cytokines which indicates a pharmacodynamic response in patients at the high dose; no effect at low dose • Evidence that EDP1066 may modulate systemic immunology • No effects observed on cellular biomarkers or clinical measures of disease at either dose 17

Reduction in Blood Immune Cell Cytokine Production Indicate a Pharmacodynamic Response at High Dose Changes over Dosing Period in Cytokine Production After Stimulation of Blood Immune Cells with Lipopolysaccharide • 3.3g EDP1066 dose group caused a Increased Production Increased decreased production of cytokines • No reduction observed in patients receiving the 660mg dose of EDP1066 or placebo Decreased production Decreased Cytokines detected: IL10, IL8, TNFα, IL6, IL1B, IFN-γ Decrease or increase in cytokine production defined as a change of 2 pg/ml over dosing period 18

Next Steps for EDP1066 • Focusing current Phase 1b trial on investigating activity of new formulation in atopic dermatitis • Data from 24 patient atopic dermatitis cohort with new formulation expected early 2020 • No further development in psoriasis 19

Summary 20

EDP1815 Phase 2a 12-week Interim Data Expected in Late 2020 Candidate 2019 2020 Phase 1b Phase 1b Phase 2a 12-week interim Psoriasis 5x dose Psoriasis & atopic dermatitis Psoriasis EDP1815 Original formulation New formulation Original and new formulation 4Q 2019 Early 2020 Late 2020 Phase 1b Atopic dermatitis EDP1066 New formulation 1Q 2020 Phase 1/2 MSS Colorectal Carcinoma EDP1503 Triple negative breast cancer PD-1 Relapsed 1H 2020 21

Today’s Highlights and Next Steps • Interim clinical data supports Evelo’s potential platform opportunity and vision • Oral biologics acting on cells in the small intestine can modulate systemic immunology • Developing effective, safe and affordable medicines for major chronic diseases • EDP1815 - Consistent clinical and biomarker responses signal potential in psoriasis • Advancing into Phase 2 in psoriasis in early 2020 • Expect to expand into other indications after interim 12-week Phase 2 data • EDP1066 – Pharmacodynamic biomarker response at high dose in psoriasis • Focusing current Phase 1b trial on new formulation in atopic dermatitis 22

Broad Platform Opportunity and New Therapeutic Modality Supported by Positive Interim Clinical Data EDP1815 Advancing to Phase 2

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