Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES For the Fiscal Year Ended December 31, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES AND EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38473 Evelo Biosciences, Inc. (Exact name of registrant as specified in its charter) Delaware 2834 46-5594527 (State or other juris ...

Evelo Biosciences, Inc. (OTC:EVLO) Q4 2021 Earnings Conference Call March 24, 2022 8:30 AM ET Company Participants Kendra Sweeney - Investor Relations Simba Gill - Chief Executive Officer Mark Bodmer - President of R&D, Chief Scientific Officer Jonathan Zung - Chief Development Officer Conference Call Participants Chris Howerton - Jefferies Gary Nachman - BMO Capital Markets Joseph Thome - Cowen Kristen Kluska - Cantor Gospel Asonye - Morgan Stanley Disclaimer*: This transcript is designed to be used alongs ...

| --- | --- | --- | |---------------------------------------------------------------------------------------------------------------------|-------|-------| | | | | | | | | | Harnessing the Small Intestinal Axis, SINTAX ™ , to Create Big Change Evelo Corporate Presentation February 2022 | | | | | | | Legal Disclaimer 2 This presentation contains forward-looking statements, including within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that ...

Financial Data and Key Metrics Changes - The company reported positive top-line results from a Phase II trial of EDP1815 in patients with mild and moderate psoriasis, demonstrating the potential of SINTAX medicines [7][8] - The Phase II clinical data indicated that EDP1815 has safety and tolerability comparable to placebo, supporting its advancement towards registration trials [8][26] Business Line Data and Key Metrics Changes - EDP1815 is positioned as a significant new medicine for treating psoriasis, addressing an unmet need for over 55 million patients worldwide, with mild and moderate cases representing over 90% of this population [8][9] - The Phase II trial showed that approximately 30% of patients achieved a PASI-50 response by the 16-week endpoint, with continuous distribution of responses suggesting potential for higher rates with longer treatment [21][22] Market Data and Key Metrics Changes - The global market for mild and moderate inflammatory diseases is substantial, with over 200 million people suffering from dermatological conditions and about 1 billion needing better treatments for broader inflammatory diseases [10][12] - The company aims to leverage the SINTAX platform to address a wide range of inflammatory conditions, potentially impacting millions of patients globally [15][35] Company Strategy and Development Direction - The company is focused on developing a new class of medicines that harness the SINTAX platform, aiming to transform healthcare rather than provide incremental improvements [12][35] - Future versions of SINTAX medicines are expected to reach biologic levels of efficacy in humans, with ongoing efforts to enhance drug delivery and formulation [33][34] Management's Comments on Operating Environment and Future Outlook - Management expressed high confidence in the potential of SINTAX medicines to drive clinical effects throughout the body, with ongoing studies expected to refine clinical plans and regulatory discussions [14][36] - The company is optimistic about the future of its EV development platform, anticipating significant advancements in the clinic and potential applications in neuroinflammation [43][70] Other Important Information - The company has lifted a clinical hold on the EDP1815 Phase II atopic dermatitis trial and expects to begin dosing in late Q4 2021 [38] - The TACTIC-E trial for COVID-19 treatment is progressing well, with recruitment nearing its initial goals [40][41] Q&A Session All Questions and Answers Question: Thoughts on regulatory path for atopic dermatitis using EASI-50 as primary endpoint - Management indicated that the bar is low for a safe, well-tolerated oral drug in atopic dermatitis, and they expect to see EASI-50 responses in a reasonable percentage of patients [45][48] Question: Comparison of cohort B and cohort A in psoriasis study - Management clarified that cohort B consists of the same patients from cohort A, and the data will inform the Phase III design moving forward [46][55] Question: Level of additional follow-up expected in Part B of psoriasis study - Management expects a significant number of subjects to complete the additional 20 weeks in Part B, with data to be reported in Q1 2022 [58][61] Question: Recruitment challenges for EDP1867 - Management noted that recruitment may have been impacted by COVID-19, particularly in the UK, and they are currently assessing the situation [60] Question: Enrollment of patients with comorbidities in atopic dermatitis study - Management stated that while they won't specifically recruit patients with comorbidities, they will analyze any data that emerges regarding these conditions [64][66] Question: Differences in profile between EDP1815 and EDP1867 - Management emphasized the need for human clinical data to determine similarities or differences in responses between the two drugs, with ongoing research into their distinct molecular backgrounds [67][70]

[Forward-Looking Statements](index=3&type=section&id=FORWARD-LOOKING%20STATEMENTS) The report contains forward-looking statements subject to significant known and unknown risks and uncertainties - This report contains forward-looking statements regarding future operations, financial position, business strategy, clinical trials, and product development. These statements are subject to known and unknown risks and uncertainties[7](index=7&type=chunk) - Key risks highlighted include the company's **development-stage status**, expectation of **future losses**, need for **additional funding**, unproven therapeutic approach (SINTAX™), reliance on clinical trial success, manufacturing dependencies, and the impact of the COVID-19 pandemic[8](index=8&type=chunk) [Summary Risk Factors](index=4&type=section&id=SUMMARY%20RISK%20FACTORS) The company faces substantial risks including its development-stage status, going concern uncertainty, and reliance on third parties - The company is a **development-stage entity** with significant losses and a limited operating history, making future viability difficult to assess[13](index=13&type=chunk) - There is **substantial doubt** about the company's ability to continue as a **going concern**, as it requires additional funding to complete product development and commercialization[14](index=14&type=chunk) - The company's therapeutic approach, targeting the small intestinal axis (SINTAX™), is **unproven**, and its product candidates must successfully complete clinical development and receive regulatory approval[15](index=15&type=chunk) - Evelo **relies on third parties** for conducting clinical trials and manufacturing, which increases risks related to timelines, costs, and supply sufficiency[17](index=17&type=chunk)[18](index=18&type=chunk) - The COVID-19 pandemic has adversely impacted and may continue to affect the company's business, including preclinical studies and clinical trials[23](index=23&type=chunk) [PART I: FINANCIAL INFORMATION](index=8&type=section&id=PART%20I%3A%20FINANCIAL%20INFORMATION) This part presents the unaudited condensed consolidated financial statements and management's analysis for the period [Item 1. Financial Statements (Unaudited)](index=8&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) Unaudited statements show increased assets and liabilities, a growing net loss, and a significant going concern uncertainty [Condensed Consolidated Balance Sheets](index=8&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The balance sheet reflects increased cash, total assets, and liabilities, with a widening accumulated deficit by Q3 2021 Condensed Consolidated Balance Sheets (in thousands) | | September 30, 2021 | December 31, 2020 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $95,938 | $68,857 | | Total current assets | $97,915 | $70,980 | | Total assets | $116,458 | $90,639 | | **Liabilities and Stockholders' Equity** | | | | Total current liabilities | $20,727 | $19,833 | | Long-term debt | $46,520 | $30,048 | | Deferred revenue | $7,500 | $0 | | Total liabilities | $83,382 | $60,154 | | Accumulated deficit | ($386,043) | ($292,519) | | Total stockholders' equity | $33,076 | $30,485 | [Condensed Consolidated Statements of Operations](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) The company reported no revenue and a significantly wider net loss driven by increased R&D and G&A expenses Condensed Consolidated Statements of Operations (Unaudited, in thousands) | | Three Months Ended Sep 30, 2021 | Three Months Ended Sep 30, 2020 | Nine Months Ended Sep 30, 2021 | Nine Months Ended Sep 30, 2020 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $22,599 | $14,910 | $64,762 | $47,503 | | General and administrative | $10,111 | $5,272 | $23,075 | $16,185 | | **Total operating expenses** | **$32,710** | **$20,182** | **$87,837** | **$63,688** | | Loss from operations | ($32,710) | ($20,182) | ($87,837) | ($63,688) | | Loss on extinguishment of debt | $0 | $0 | ($3,226) | $0 | | **Net loss** | **($33,730)** | **($20,923)** | **($93,524)** | **($64,616)** | | Net loss per share, basic and diluted | ($0.63) | ($0.45) | ($1.77) | ($1.74) | [Condensed Consolidated Statements of Cash Flows](index=12&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Financing activities provided $97.7 million in cash, offsetting the $68.9 million used in operations for the nine-month period Condensed Consolidated Statements of Cash Flows (Unaudited, in thousands) | | Nine Months Ended Sep 30, 2021 | Nine Months Ended Sep 30, 2020 | | :--- | :--- | :--- | | Net cash used in operating activities | ($68,879) | ($54,110) | | Net cash used in investing activities | ($1,956) | ($906) | | Net cash provided by financing activities | $97,666 | $58,763 | | **Net increase in cash, cash equivalents and restricted cash** | **$26,831** | **$3,747** | [Notes to the Condensed Consolidated Financial Statements](index=13&type=section&id=Notes%20to%20the%20Condensed%20Consolidated%20Financial%20Statements) Key disclosures include a going concern uncertainty, a new license agreement, an amended credit facility, and stock compensation details - Management has concluded that **substantial doubt exists** about the Company's ability to continue as a **going concern**, as cash and cash equivalents of **$95.9 million** at September 30, 2021, are not sufficient to fund operations for at least twelve months[53](index=53&type=chunk)[55](index=55&type=chunk) - In March 2021, the company entered into a commercialization and license agreement with ALJ for EDP1815, receiving a **$7.5 million non-refundable upfront payment** recorded as deferred revenue[92](index=92&type=chunk)[93](index=93&type=chunk)[95](index=95&type=chunk) - In June 2021, the company amended its credit facility with K2HV, drawing down a new **$15.0 million tranche**, resulting in a non-cash loss on debt extinguishment of **$3.2 million**[106](index=106&type=chunk)[109](index=109&type=chunk)[112](index=112&type=chunk) - Stock-based compensation expense for the nine months ended September 30, 2021, was **$11.5 million**, a significant increase from **$6.1 million** in the same period of 2020[137](index=137&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=31&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses clinical program progress, financial results, and liquidity issues, reiterating the going concern uncertainty [Clinical Programs](index=32&type=section&id=Clinical%20Programs) The company's lead candidate EDP1815 shows positive Phase 2 data, with other pipeline candidates advancing toward clinical trials - In the Phase 2 psoriasis trial for EDP1815, **25% to 32% of patients achieved a PASI-50 response** at week 16, compared to 12% for placebo, with plans to advance towards registration trials[163](index=163&type=chunk) - A Phase 2 trial of EDP1815 in atopic dermatitis is ongoing after the FDA lifted a clinical hold, with results expected in **Q4 2022**[169](index=169&type=chunk)[170](index=170&type=chunk) - The company is advancing EDP1867 in a Phase 1b trial for atopic dermatitis, with interim data now expected in the **first half of 2022** due to slow enrollment[177](index=177&type=chunk) - Two new candidates, **EDP2939 (inflammation)** and **EDP1908 (oncology)**, are expected to enter clinical development in 2022[179](index=179&type=chunk)[180](index=180&type=chunk) [Results of Operations](index=39&type=section&id=Results%20of%20Operations) The net loss widened year-over-year due to increased R&D and G&A expenses from clinical trial progression and higher headcount Comparison of Operating Expenses (in thousands) | Expense Category | Nine Months Ended Sep 30, 2021 | Nine Months Ended Sep 30, 2020 | Change | | :--- | :--- | :--- | :--- | | Research and development | $64,762 | $47,503 | $17,259 | | General and administrative | $23,075 | $16,185 | $6,890 | | **Total operating expenses** | **$87,837** | **$63,688** | **$24,149** | - The **$17.3 million increase** in nine-month R&D expense was driven by **$12.1 million** in higher inflammation program costs and **$6.2 million** in higher personnel costs[224](index=224&type=chunk) - The **$6.9 million increase** in nine-month G&A expense was primarily due to a **$5.3 million** increase in personnel costs and **$1.3 million** in professional fees[227](index=227&type=chunk) - Total other expense for the nine months ended Sep 30, 2021, was **$5.4 million**, a **$4.6 million increase** from the prior year, mainly due to a **$3.2 million** non-cash loss on debt extinguishment[228](index=228&type=chunk) [Liquidity and Capital Resources](index=42&type=section&id=Liquidity%20and%20Capital%20Resources) Current cash of $95.9 million is only expected to fund operations into late Q3 2022, raising substantial going concern doubts - The company had cash and cash equivalents of **$95.9 million** and an accumulated deficit of **$386.0 million** as of September 30, 2021[230](index=230&type=chunk) - In the first nine months of 2021, the company raised **$97.7 million** from financing activities, including **$82.0 million** from common stock sales and **$14.8 million** from long-term debt[244](index=244&type=chunk) - Existing cash is expected to fund operations and capital expenditures only into the **late third quarter of 2022**, excluding funds for Phase 3 trials[195](index=195&type=chunk)[237](index=237&type=chunk) - The company has concluded that its financial condition raises **substantial doubt** about its ability to continue as a **going concern** for at least one year[195](index=195&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=46&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosure%20About%20Market%20Risk) As a smaller reporting company, this information is not required - As a smaller reporting company, Evelo Biosciences is not required to provide quantitative and qualitative disclosures about market risk[253](index=253&type=chunk) [Item 4. Controls and Procedures](index=46&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of the end of the quarter - Management concluded that the company's disclosure controls and procedures were **effective** as of September 30, 2021[255](index=255&type=chunk) - There were **no changes** in internal control over financial reporting during the quarter that materially affected, or are reasonably likely to materially affect, such controls[256](index=256&type=chunk) [PART II: OTHER INFORMATION](index=47&type=section&id=PART%20II%3A%20OTHER%20INFORMATION) This part covers legal proceedings, risk factors, and other required disclosures [Item 1. Legal Proceedings](index=47&type=section&id=Item%201.%20Legal%20Proceedings) The company is not subject to any material legal proceedings - The company is **not a party to any material legal proceedings**[259](index=259&type=chunk) - An opposition was filed against a European patent held by the company, but it does not relate to current product candidates and is not expected to impact development[260](index=260&type=chunk) [Item 1A. Risk Factors](index=47&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant financial, developmental, third-party dependency, and intellectual property risks - **Financial Risks**: The company has a history of significant losses, expects to incur losses for the foreseeable future, and has identified conditions that raise **substantial doubt** about its ability to continue as a **going concern**[262](index=262&type=chunk)[269](index=269&type=chunk)[277](index=277&type=chunk) - **Development and Regulatory Risks**: The company's SINTAX therapeutic approach is **unproven**, clinical development is lengthy and uncertain, and the COVID-19 pandemic may cause delays[292](index=292&type=chunk)[298](index=298&type=chunk)[311](index=311&type=chunk) - **Third-Party and Manufacturing Risks**: The company **relies on third parties** to conduct clinical trials and for all manufacturing, which increases risks related to quality, cost, and supply[363](index=363&type=chunk)[368](index=368&type=chunk)[375](index=375&type=chunk) - **Intellectual Property Risks**: The company's success depends on its ability to obtain and maintain patent protection and faces risks of patent challenges and infringement claims[444](index=444&type=chunk)[459](index=459&type=chunk)[478](index=478&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=105&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered sales of equity securities were made during the period beyond what was previously reported - There were no unregistered sales of equity securities during the period, other than what was previously reported on a Form 8-K on February 2, 2021[580](index=580&type=chunk) [Item 3. Defaults Upon Senior Securities](index=106&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reports no defaults upon senior securities - None[582](index=582&type=chunk) [Item 4. Mine Safety Disclosures](index=106&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - Not applicable[583](index=583&type=chunk) [Item 5. Other Information](index=106&type=section&id=Item%205.%20Other%20Information) The company reports no other information for this item - None[584](index=584&type=chunk) [Item 6. Exhibits](index=107&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the quarterly report, including corporate governance documents and officer certifications

| --- | --- | --- | |-------|-------|-------| | | | | | | | | 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 statements concerning the development of EDP1815, EDP1867, and EDP2939, the promise and potential impact of our product candidates, the timing of and ...

Evelo Biosciences, Inc. (OTC:EVLO) Q2 2021 Earnings Conference Call July 29, 2021 8:30 AM ET Company Participants Jessica Cotrone - Investor Relations Simba Gill - Chief Executive Officer Mark Plinio - Chief Commercial Officer Jonathan Zung - Chief Development Officer Mark Bodmer - President, R&D and Chief Scientific Officer Conference Call Participants Vikram Purohit - Morgan Stanley Chris Howerton - Jefferies Matthew Luchini - BMO Capital Gobind Singh - JMP Securities Joe Thome - Cowen Operator Good morni ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 _______________ FORM 10-Q _______________ (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES AND EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES AND EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38473 Evelo Biosciences, Inc. (Exact name of registrant as specified i ...

Financial Data and Key Metrics Changes - The company reported continued strong execution in Q1 2021, with multiple clinical readouts expected across psoriasis, atopic dermatitis, and COVID-19 in the coming months [5][6][7] - The leadership team has been expanded with the appointment of a new CFO and a board member, indicating a strategic focus on growth and commercialization [6][7] Business Line Data and Key Metrics Changes - EDP1815 has shown anti-inflammatory effects in five studies, with approximately 300 patients treated, demonstrating its potential as a major medicine [16][17] - The company is advancing its extracellular vesicle product candidates in oncology and inflammatory diseases, with ongoing research to enhance their applications [6][23] Market Data and Key Metrics Changes - The collaboration with Abdul Latif Jameel Health aims to develop and commercialize EDP1815 in high-growth markets such as the Middle East, Turkey, and Africa [7] - The company is focused on addressing the unmet need for oral therapies in atopic dermatitis and psoriasis, which currently rely heavily on topical treatments [39][64] Company Strategy and Development Direction - The company is positioned at an inflection point with multiple clinical readouts ahead, aiming to optimize its drug development strategy based on data-driven decisions [33][86] - The strategic focus includes expanding into global markets and ensuring affordability of its products, which is expected to drive higher uptake compared to existing therapies [60][64] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clinical data generated, highlighting the potential of EDP1815 and the understanding of the small intestinal axis in driving systemic effects [86] - The ongoing COVID-19 studies are expected to take longer than originally planned due to changes in hospitalization rates, but safety data for EDP1815 remains positive [32][68] Other Important Information - The company is preparing for a phase two trial in atopic dermatitis, with a focus on oral therapies that could provide a competitive edge over existing topical treatments [26][39] - The development of extracellular vesicle products is seen as a transformative opportunity in oncology, with preclinical data showing promising results [44][47] Q&A Session Summary Question: Can you provide details on the phase two atopic dermatitis trial? - Management confirmed that preparations are well underway, including site identification and drug supply, with endpoints focusing on conventional measures and patient-reported outcomes [38][42] Question: How does the company view the competitive landscape for EDP1815? - Management sees Otezla as the key benchmark for moderate psoriasis, emphasizing the unmet need for oral therapies and the potential for EDP1815 to capture a larger market share [54][60] Question: What are the expected outcomes for the COVID-19 studies? - The primary outcome measures include mortality and the need for invasive interventions, with ongoing recruitment expected to take longer than initially planned due to changing hospitalization rates [30][68] Question: What insights have been gained from the phase one atopic dermatitis study? - Management indicated that while individual patient data is being analyzed, the small sample size limits the ability to draw significant conclusions [80] Question: How will the company approach the development strategy for EDP1815 and EDP1867? - The strategy will be data-driven, with flexibility to adapt based on the outcomes of ongoing trials in atopic dermatitis and psoriasis [63][64]

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES AND EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES AND EXCHANGE ACT OF 1934 For the transition period from to | --- | --- | |------------------------------------------------------------------------------------------------------|--------------------- ...