8-K

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): December 09, 2021

SQZ BIOTECHNOLOGIES COMPANY

(Exact name of Registrant as Specified in Its Charter)

Delaware	001-39662	46-2431115
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)
200 Arsenal Yards Blvd Suite 210
Watertown, Massachusetts		02472
(Address of Principal Executive Offices)		(Zip Code)

Registrant’s Telephone Number, Including Area Code: 617 758-8672

N/A

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.001 par value per share	SQZ	The New York Stock Exchange

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 8.01 Other Events.

On December 9, 2021, SQZ Biotechnologies Company (the “Company”) presented interim results from the highest-dose cohort of its ongoing Phase 1/2 clinical trial of lead Antigen Presenting Cell (“APC”) therapy candidate targeting Human Papillomavirus positive (“HPV16+”) solid tumors at the European Society for Medical Oncology Immuno-Oncology (“ESMO-IO”) Congress. Of the five patients in this cohort evaluable for efficacy, one checkpoint refractory head-and-neck cancer patient showed a radiographic response and symptomatic improvement. The target lesion demonstrated a complete response at both radiographic assessments. At the most recent assessment, the major oropharyngeal lesion demonstrated continued improvement upon physical examination; however, a new dermal lesion was detected. The investigational therapy was well-tolerated, and no dose-limiting toxicities were observed as of October 8, 2021.

Responder Patient Characteristics & Treatment Journey

The patient in the highest-dose cohort who achieved a complete response in the target lesion (patient 17) was a 52-year-old male diagnosed over three-and-a-half years prior to first dose with a locally advanced squamous cell carcinoma of the tonsil, a part of the oropharynx. He initially had chemo-radiation treatment but developed recurrence in the throat and the chest almost two years prior. At trial entry, patient 17 had received six prior lines of therapy, including two combination approaches with the checkpoint inhibitor pembrolizumab.

Patient 17 did not require pre-conditioning. Following a single leukapheresis session, his cell therapy was manufactured in 18 hours and produced 7 doses.

Clinical Results

Patient 17 had marked improvement of the target lesion on physical examination and reported that his ability to swallow had substantially improved

Patient 17 experienced two low grade treatment related adverse events, i.e., grade 1 flushing and grade 1 fatigue

As of October 20, 2021, he received all seven doses of SQZ-PBMC-HPV and the investigational therapy was well tolerated

Radiographic Response

Patient 17’s main lesion was a large, diffuse, non-measurable oropharyngeal lesion

The target tumor lesion selected for response assessment was a mediastinal lymph node measuring 17.1mm in diameter, which decreased at second assessment below 10.0mm resulting in a complete response of the target lesion according to RECIST 1.1

At the second on treatment tumor assessment, despite continuing improvement of the target lesion and patient symptoms, a new dermal lesion was found in the previously irradiated region

Histologic Assays

At day 28 on treatment, patient 17’s matched tumor biopsy samples from the main oropharyngeal lesion showed an 8-fold increase in CD8 T cell tumor infiltration and a conversion of the tumor phenotype from desert to inflamed

PD-L1 expression, an additional maker of tumor inflammation, increased from 2 percent at baseline to 100 percent in the matched tumor biopsies

An RNA in situ hybridization (“ISH”) assay used for the detection of E6 and E7 expression demonstrated a dramatic reduction in the number of cells with high E6 and E7 antigen expression. E6 and E7 are the two antigens targeted by the SQZ APC cell therapy

Highest Dose Monotherapy Cohort Interim Safety and Manufacturing Findings as of October 8, 2021

There were no observed treatment-related serious or severe (grade 3 or greater) adverse events in the highest-dose cohort

The investigational therapy was generally well-tolerated, and no dose-limiting toxicities were observed

All patient batches were produced in less than 24 hours and yielded multiple cryopreserved doses

Clinical Trial Progress

The combination stage of SQZ-PMBC-HPV-101 trial with checkpoint inhibitors (“CPI”) is now enrolling

The highest-dose monotherapy stage of the trial continues enrollment to further evaluate the investigational candidate in single agent settings

A copy of the press release issued in connection with the announcement is being furnished as Exhibit 99.1 to this Current Report on Form 8-K. Additionally, copies of the oral presentation presented at the ESMO-IO Congress on December 9 and the Company’s presentation to be shared with investors and others from time to time in connection with today’s announcement are being furnished as Exhibits 99.2 and 99.3, respectively, to this Current Report on Form 8-K.

The information in Exhibits 99.1, 99.2, and 99.3 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended or the Exchange Act, except as expressly set forth by specific reference in such filing.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements relating to events and presentations, our platform development, our product candidates, clinical activities, progress and outcomes, development plans, manufacturing, clinical safety and efficacy results, therapeutic impact, market opportunities and disease prevalence. These forward-looking statements are based on management's current expectations. Actual results could differ from those projected in any forward-looking statements due to several risk factors. Such factors include, among others, risks and uncertainties related to our limited operating history; our significant losses incurred since inception and expectation to incur significant additional losses for the foreseeable future; the development of our initial product candidates, upon which our business is highly dependent; the impact of the COVID-19 pandemic on our operations and clinical activities; our need for additional funding and our cash runway; the lengthy, expensive, and uncertain process of clinical drug development, including uncertain outcomes of clinical trials and potential delays in regulatory approval; our ability to maintain our relationships with our third party vendors and strategic collaborators; and protection of our proprietary technology, intellectual property portfolio and the confidentiality of our trade secrets. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K, as updated by our Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2021 and other filings with the U.S. Securities and Exchange Commission could cause actual results to differ materially from those indicated by the forward-looking statements. Any forward-looking statements represent management's estimates as of this date and we undertake no duty to update these forward-looking statements, whether as a result of new information, the occurrence of current events, or otherwise, unless required by law.

Certain information contained in this press release relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this press release, we have not independently verified, and we make no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.	Description
99.1	Press release issued by SQZ Biotechnologies Company on December 9, 2021
99.2	ESMO-IO Congress Oral Presentation, dated December 9, 2021
99.3	Presentation of SQZ Biotechnologies Company, dated December 9, 2021
104	Cover Page Interactive Data File (embedded with the Inline XBRL document)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

			SQZ BIOTECHNOLOGIES COMPANY
Date:	December 9, 2021	By:	/s/ Lawrence Knopf
			Lawrence Knopf General Counsel

EX-99.1

Empowering Cells to Change Lives

Exhibit 99.1

SQZ Biotechnologies Announces Lead Cell Therapy Candidate Induced Radiographic, Symptomatic and Immune Response as Monotherapy in Post-Checkpoint HPV+ Solid Tumor Patient

Patient’s Clinical, Radiographic and Histologic Results Support Potential

Impact of SQZ Investigational Therapeutic

 Patient Demonstrated Symptomatic Improvement

Radiographic Response Observed in Target Lesion

Tumor Conversion from Desert to Inflamed Phenotype with 8-Fold Increase in CD8 T Cell Tumor Infiltration and 50-Fold Increase in Tumor PD-L1 Expression

Interim Results from Ongoing Phase 1/2 Trial Showed Favorable Safety Data and Investigational Therapy was Generally Well Tolerated

Company to Host Conference Call Today at 8:00 a.m. ET

WATERTOWN, Mass., December 9, 2021 – SQZ Biotechnologies Company (NYSE: SQZ), a cell therapy company developing novel treatments for multiple therapeutic areas, today presented interim results from the highest-dose cohort of its ongoing Phase 1/2 clinical trial of lead Antigen Presenting Cell (APC) therapy candidate targeting Human Papillomavirus positive (HPV16+) solid tumors at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress. Of the five patients in this cohort evaluable for efficacy, one checkpoint refractory head-and-neck cancer patient showed a radiographic response and symptomatic improvement. The target lesion demonstrated a complete response at both radiographic assessments. At the most recent assessment, the major oropharyngeal lesion demonstrated continued improvement upon physical examination; however, a new dermal lesion was detected. The investigational therapy was well-tolerated, and no dose-limiting toxicities were observed as of October 8, 2021.

“The combined radiographic response and symptomatic improvement observed in this patient and the strong correlation with histological data demonstrated the investigational therapy’s intended cellular vaccine mechanism at work,” said study first author and presenter Jong Chul Park, MD, Medical Oncologist and Investigator, Massachusetts General Hospital Cancer Center. “This heavily treated patient with significant tumor burden in the neck had marked increases in CD8 T cell tumor infiltration which correlated with clinical improvement, including the ability to swallow more easily. SQZ-PBMC-HPV showed favorable safety data and was generally well tolerated in this patient and across all patients in the highest-dose cohort.”

“While our clinical study is ongoing, we believe that this is a ‘Kitty-Hawk moment’ for the SQZ APC cell therapy platform,” said Armon Sharei, Ph.D., Chief Executive Officer and Founder of SQZ Biotechnologies. “Our goal has been to develop a new generation of cell therapies - one that could potentially enable significant and broad patient impact by unlocking historically challenging biology while remaining practical and accessible. We believe this patient’s journey is consistent with the trial’s practical and rapid approach. We manufactured a cell therapy in under a day, administered it with mild treatment-related adverse events, and generated clinical benefit by marshalling the power of endogenous killer T cells. We are very excited for the advancement of this program into combination therapy and the broader future potential of SQZ cell therapy candidates.”

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Empowering Cells to Change Lives

Responder Patient Characteristics & Treatment Journey

The patient in the highest-dose cohort who achieved a complete response in the target lesion (patient 17) was a 52-year-old male diagnosed over three-and-a-half years prior to first dose with a locally advanced squamous cell carcinoma of the tonsil, a part of the oropharynx. He initially had chemo-radiation treatment but developed recurrence in the throat and the chest almost two years prior. At trial entry, patient 17 had received six prior lines of therapy, including two combination approaches with the checkpoint inhibitor pembrolizumab.

Patient 17 did not require pre-conditioning. Following a single leukapheresis session, his investigational therapy was manufactured in 18 hours and produced 7 doses.

Clinical Results

Patient 17 had marked improvement of the target lesion on physical examination and reported that his ability to swallow had substantially improved

Patient 17 experienced two low grade treatment related adverse events, i.e., grade 1 flushing and grade 1 fatigue

As of October 20, 2021, he received all seven doses of SQZ-PBMC-HPV and the investigational therapy was well tolerated

Radiographic Response

Patient 17’s main lesion was a large, diffuse, non-measurable oropharyngeal lesion

The target tumor lesion selected for response assessment was a mediastinal lymph node measuring 17.1mm in diameter, which decreased at second assessment below 10.0mm resulting in a complete response of the target lesion according to RECIST 1.1

At the second on treatment tumor assessment, despite continuing improvement of the target lesion and patient symptoms, a new dermal lesion was found in the previously irradiated region

Histologic Assays

At day 28 on treatment, patient 17’s matched tumor biopsy samples from the main oropharyngeal lesion showed an 8-fold increase in CD8 T cell tumor infiltration and a conversion of the tumor phenotype from desert to inflamed

•PD-L1 expression, an additional maker of tumor inflammation, increased from 2 percent at baseline to 100 percent in the matched tumor biopsies

An RNA in situ hybridization (ISH) assay used for the detection of E6 and E7 expression demonstrated a dramatic reduction in the number of cells with high E6 and E7 antigen expression. E6 and E7 are the two antigens targeted by the SQZ APC cell therapy candidates

Highest Dose Monotherapy Cohort Interim Safety and Manufacturing Findings as of October 8, 2021

There were no observed treatment-related serious or severe (grade 3 or greater) adverse events in the highest-dose cohort

The investigational therapy was generally well-tolerated, and no dose-limiting toxicities were observed

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Empowering Cells to Change Lives

All patient batches were produced in less than 24 hours and yielded multiple cryopreserved doses

Clinical Trial Progress

The combination stage of SQZ-PBMC-HPV-101 trial with checkpoint inhibitors (CPI) is now enrolling. The company believes the increase in PD-L1 expression observed in the patient 17 data suggests potential synergy with a CPI combinatory approach

The highest-dose monotherapy stage of the trial continues enrollment to further evaluate the investigational candidate in single agent settings

Today’s ESMO-IO presentation can be found on the Events & Presentations section of the company’s website.

Conference Call

The company will host a conference call and webcast today at 8:00 a.m. ET to discuss the ESMO-IO presentation. Participants can join via webcast link or by dialing 1-877-805-7920 (domestic) or 1-629-228-0702 (international) five minutes prior to the start of the call. An archived webcast will be accessible for 90 days after the event.

SQZ-PBMC-HPV-101 Trial Design

SQZ-PBMC-HPV is being evaluated in a Phase 1/2 clinical trial for the treatment of HPV16+ advanced or metastatic solid tumors. Patients must be positive for the human leukocyte antigen serotype HLA-A*02. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immuno-oncology agents. The study’s primary outcome measures in the monotherapy and combination phases of the trial include safety and tolerability. Antitumor activity is a secondary outcome measure in both the monotherapy and combination stages of the trial, and manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. The monotherapy phase of the study includes escalating dose cohorts with a dose-limiting toxicity (DLT) window of 28 days and is designed to identify a recommended phase 2 dose. The planned combination phase of the study will include SQZ-PBMC-HPV and checkpoint inhibitors. DLT will be measured over 42 days.

About Human Papillomavirus Positive Cancers

Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer HPV+ tumors account for 4.5% of all cancers worldwide, resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.

About SQZ Biotechnologies

SQZ Biotechnologies Company is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies for patients around the world and has active programs in Oncology, Autoimmune and Infectious Diseases, as well as additional exploratory initiatives to support future

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Empowering Cells to Change Lives

pipeline growth. The company’s proprietary Cell Squeeze® technology offers the unique ability to deliver multiple biological materials into many cell types to engineer what we believe can be a broad range of potential therapeutics. With demonstrated production timelines under 24 hours and the opportunity to eliminate preconditioning and lengthy hospital stays, our approach could significantly broaden the therapeutic range and accessibility of cell therapies. The company’s first therapeutic applications seek to generate target-specific immune responses, both in activation for the treatment of solid tumors and infectious diseases, and in immune tolerance for the treatment of autoimmune diseases. For more information, please visit www.sqzbiotech.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements relating to events and presentations, our platform development, our product candidates, clinical activities, progress and outcomes, development plans, manufacturing, clinical safety and efficacy results, therapeutic impact, market opportunities and disease prevalence. These forward-looking statements are based on management's current expectations. Actual results could differ from those projected in any forward-looking statements due to several risk factors. Such factors include, among others, risks and uncertainties related to our limited operating history; our significant losses incurred since inception and expectation to incur significant additional losses for the foreseeable future; the development of our initial product candidates, upon which our business is highly dependent; the impact of the COVID-19 pandemic on our operations and clinical activities; our need for additional funding and our cash runway; the lengthy, expensive, and uncertain process of clinical drug development, including uncertain outcomes of clinical trials and potential delays in regulatory approval; our ability to maintain our relationships with our third party vendors and strategic collaborators; and protection of our proprietary technology, intellectual property portfolio and the confidentiality of our trade secrets. These and other important factors discussed under the caption "Risk Factors" in our Annual Report on Form 10-K, as updated by our Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2021 and other filings with the U.S. Securities and Exchange Commission could cause actual results to differ materially from those indicated by the forward-looking statements. Any forward-looking statements represent management's estimates as of this date and we undertake no duty to update these forward-looking statements, whether as a result of new information, the occurrence of current events, or otherwise, unless required by law.

Certain information contained in this press release relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this press release, we have not independently verified, and we make no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources.

Investor Relations Contact

investors@sqzbiotech.com

Media Contact

John Lacey

Corporate Communications

john.lacey@sqzbiotech.com

781-392-5514

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EX-99.2

Preliminary results of a first-in-human, dose-escalation study of a cell-based vaccine in HLA A*02+ patients with recurrent, locally advanced, or metastatic HPV16+ solid tumors SQZ-PBMC-HPV-101: Jong Chul Park, Joaquina Baranda, Monica Mita, Wade T Iams, Michael S Gordon, Matthew Taylor, Neesha Dhani, Scott Loughhead, Rui Ru Ji, Ricardo F Zwirtes, Martin Kornacker, Oliver Rosen, Howard Bernstein, and Antonio Jimeno Massachusetts General Hospital, Boston, MA; University of Kansas Cancer Center, Fairway, KS; Cedars-Sinai Medical Center, Los Angeles, CA; Division of Hematology/Oncology, Department of Medicine, Vanderbilt University, Nashville, TN; Pinnacle Oncology Hematology, Arizona Center for Cancer Care, HonorHealth Research Institute Clinical Trials Program, Virginia G. Piper Cancer Center, Scottsdale, AZ; Providence Cancer Institute, Portland, OR; University Health Network Princess Margaret Cancer Centre, Toronto, Canada; SQZ Biotechnologies, Watertown, MA; Hoffmann-La Roche, Basel, Switzerland; University of Colorado Comprehensive Cancer Center, Aurora, CO ESMO-IO December 9th, 2021

Declaration of Interest Consulting and Advisory Role: ALB, Merck, I-Mab, Mito Research funding: ALX (Inst), Inhibrx (Inst), Merck (Inst), Monopteros (Inst), Novartis (Inst), Oncorus (Inst), SQZ (Inst) Jong Chul Park

SQZ-PBMC-HPV-101: Underlying Technology and Mechanism Prior cancer vaccines relied on cross-presentation, resulting in ineffective MHC-I presentation to CD8 T cells, limiting T cell activation and efficacy. Squeezed Antigen MHC-I = CD8 T Cell Activation SQZTM APC Mechanism: Direct Presentation Typical Cancer Vaccine Mechanism: Cross-Presentation Primarily generates MHC-II presentation for CD4 and antibody responses Suited for prophylactic vaccines Prioritizes creation of: Prioritizes creation of: Primarily generates MHC-I presentation to CD8 T cells CD8 T cell responses in the tumor are highly correlated with patient outcomes MHC-II = CD4 + antibodies MHC-I = CD8 Endocytosis CD8 Killer T cells SQZTM vs. Cross Presentation Data Antibodies CD4 helper cells The Cell Squeeze® Technology The Cell Squeeze® technology has demonstrated robust abilities to deliver antigens directly to the cytosol, thereby circumventing the cross-presentation process most vaccines rely on and enabling efficient MHC-I presentation and antigen-specific CD8 T cell activation. 1. Cells and target cargo together in suspension 2. Cells are squeezed through SQZ chip at high speeds 3. Cell membranes are temporarily disrupted 4. Target cargo enters the cytosol of the cells 5. Membranes reseal Hlavaty KA et al. AACR 2019 Abstract #3187.

Study Design and Cell Therapy Production Cell Therapy Production Monotherapy Escalation Combination De-escalation Recurrent or metastatic HPV-driven cancer HPV-16+ HLA-A *02+ Platinum experienced CPI offered Inclusion Criteria Treatment until PD, unacceptable toxicity or 2 years SQZ-PBMC-HPV 5.0e6/kg Q3W Double Prime (n = 6) SQZ-PBMC-HPV 2.5e6/kg Q3W Double Prime (n = 4) SQZ-PBMC-HPV 2.5e6/kg Q3W (n = 5) SQZ-PBMC-HPV 0.5e6/kg Q3W (n = 3) SQZ-PBMC-HPV RP2D + Atezolizumab 1200mg Q3W SQZ-PBMC-HPV RP2D + Ipilimumab 3mg/kg Q3W x 4 SQZ-PBMC-HPV RP2D + Nivolumab 360mg Q3W SQZ-PBMC-HPV RP2D + Nivo 360mg Q3W + Ipi 1mg/kg Q6W The median time for manufacturing was 17 hours and allowed for a vein-to-vein time of about a week. Among all lots produced, the median viability was 91%. In the highest dose cohort, a median of 5 doses were available for each patient. Patient Leukapheresis Day 1 SQZ Process <24-hours Day 2 QC and Batch Release Day 2-8 Administration to Patient ~1 week

SQZ-PBMC-HPV Evaluated in Advanced Patient Population Characteristic 0.5 M cells/kg SP (n=3) 2.5 M cells/kg SP (n=5) 2.5 M cells/kg DP (n=4) 5.0 M cells/kg DP (n=6) Total (n=18) Median Age, years (min, max) 65 (60, 68)  65 (54, 68) 49 (47, 66) 57.5 (52, 78) 60 (47, 78) Female, n (%)  3 (100) 3 (60) 3 (75) 0 9 (50) Caucasian Race, n (%) 3 (100)  5 (100) 3 (75) 5 (83) 16 (89) Baseline ECOG PS of 1, n (%) 2 (67) 3 (60) 4 (100) 3 (50) 12 (67) Phase 1 RMH Score High, n (%) 0 3 (60) 4 (100) 1 (33) 8 (44) Site of primary tumor, n (%) Anus Cervix Head & Neck   2 (66) 1 (33) 0   3 (60) 0 2 (40)   2 (50) 1 (25) 1 (25) 0 0 6 (100) 7 (39) 2 (11) 9 (50) Metastatic Disease, n (%) 3 (100) 5 (100) 4 (100) 6 (100) 18 (100) Median Number of Prior Lines, n (min, max)  4 (2, 5) 3 (1, 7) 4 (3, 4) 3.5 (2, 6) 4 (1,7) Prior Systemic Therapy, n (%) Chemotherapy Checkpoint Inhibitor Refractory to ICI (PD as BOR) 3 (100) 3 (100) 2/3 5 (100) 4 (80) 3/4 4 (100) 4 (100) 3/4 6 (100) 6 (100) 4/6 18 (100) 17 (94) 12/17 Heavily pretreated patient population with advanced disease at study entry. All but one patient (in the 2nd cohort) were treated with anti-PD-(L)1 checkpoint inhibitor, and the majority of them were considered refractory to a PD-1 inhibition. Patient Characteristics M=millions, SP=single-prime, DP=double-prime, ECOG PS=Eastern Cooperative Oncology Group Performance Status, ICI=immune checkpoint inhibitors, PD=Progressive Disease, BOR=Best Overall Response, RMH=Royal Marsden Hospital

SQZ-PBMC-HPV Was Considered Safe and Well-Tolerated Event, n (%) 0.5 M cells/kg SP (n=3) 2.5 M cells/kg SP (n=5) 2.5 M cells/kg DP (n=4) 5.0 M cells/kg DP (n=6) Total (n=18) Related AEs in >1 Patient 3 (100) 4 (80) 2 (50) 5 (83) 14 (78) Fatigue 0 1 (20) 0 4 (67) 5 (28) Flushing 1 (33) 0 0 2 (33) 3 (17) Hypotension 2 (67) 1 (20) 0 0 3 (17) Infusion Related Reaction (IRR) 1 (33) 0 1 (25) 0 2 (11) Nausea 0 0 0 2 (33) 2 (11) Pruritus 0 1 (20) 0 1 (20) 2 (11) Related Grade ≥3 AEs 0 1 (20%)1 0 0 1 (6%) Related Serious AEs 1 (33%)2 0 0 0 1 (6%) AEs of Special Interest3 1 0 1 0 2 (11%) Dose-Limiting Toxicity 0 0 0 0 0 Related AEs leading to d/c 0 0 0 0 0 Fatal Related AEs 0 0 0 0 0 1Grade 3 anemia. 2Grade 2 cytokine release syndrome (CRS). 3AEs of medical concern related to SQZ-PBMC-HPV mechanism of action (CRS, IRR). M=millions, SP=single-prime, DP=double-prime, AE=adverse events Adverse Events Safety profile of SQZ-PBMC-HPV was consistent across all dose levels. Most related AEs were of low grade. One case of grade 2 cytokine release syndrome in a 1st cohort patient, which resolved in <24h, considered a related serious AE. Only grade ≥3 related adverse event was a case of grade 3 anemia in a 2nd cohort patient. No patients met the DLT criteria.

Potential Proof-of-Concept for SQZ-PBMC-HPV in anti-PD-1 Refractory Patient 52-year-old man with squamous cell carcinoma of the oropharynx. Large primary lesion with significant symptoms burden. Initial diagnosis 3.7 years ago, with 6 prior lines of systemic therapy including carbo/5FU/pembro and anti-TGFβ/pembro (BOR=PD) 9 months before SQZ-PBMC-HPV dosing. Received all 7 doses of SQZ-PBMC-HPV, with excellent tolerability (G1 flushing, G1 fatigue). Marked symptomatic improvement (dysphagia and neck swelling) and improvement of the lesion on physical examination. Case Study: Patient 17 % Change from Baseline Study Day Highest dose cohort changes in CD8 TILs Highest dose cohort tumor measurements Cells/mm2 Patient 17 Post Pre Day-28 on treatment biopsy demonstrated an 8-fold increase in tumor infiltrating CD8 cells. Radiographic response, including confirmed CR on target lesion (mediastinal lymph node (RECIST 1.1)) with a new dermal lesion at the last tumor assessment. 7 Patient 17 Treatment Start (n = 5 patients) (n = 5 patients)

SQZ-PBMC-HPV Turns TME into Inflamed Phenotype in Responding Patient Massive influx of CD8 cells into the tumor changed immunophenotype from desert to inflamed. Increase in HLA-I expression likely due to CD8 driven IFN-γ secretion. Significant reduction in frequency of E6 expressing cells as measured by RNA-ISH. E7 expressing cells follow the same pattern (not shown). Increase in PD-L1 expression suggests potential synergy with a combinatory approach. Case Study: Patient 17 Screening Day 28 CD8 Increase CD8 PanCK 8 % of HPV16+ Cells 93% 23% Cells/mm2 HLA-I Increase HLA-I H-Score (0-300) E6 Reduction HPV16 E6 transcript PD-L1 Increase PD-L1 % of PD-L1+ Tumor Cells

Conclusions and Future Development for SQZ-PBMC-HPV Future Development SQZ-PBMC-HPV at 5.0M cells/kg dose was endorsed by study DSMB to move into PD-(L)1 & CTLA-4 combination cohorts. The highest dose cohort is still enrolling to further characterize efficacy of SQZ-PBMC-HPV as monotherapy. Conclusion Safety: SQZ-PBMC-HPV was considered safe and well-tolerated at all dose levels. Safety profile consisted of mostly low grade (grades 1 and 2) non-specific AEs, only one related serious adverse event, and no dose-limiting toxicities observed. Manufacturability: All batches produced under cGMP yielding multiple cryopreserved doses in <24hrs with ~1wk vein-to-vein. Product characterization confirmed antigen presentation and high viability in all patient batches. Clinical Activity: Radiographic and pathological correlation in patients deriving clinical benefit. Patient 17's clinical response consistent with expected SQZ APC mechanism: increased CD8 tumor infiltration, reduction of E6 and E7 expressing cells suggests antigen-specific killing, increased PD-L1 expression consistent with tumor inflammation.

We thank the patients and their families! Additional information may be found at:

EX-99.3

SQZ-PBMC-HPV-101 Clinical Program Updates at ESMO Immuno-Oncology Congress 2021 Conference Call and Webcast December 9th, 2021

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Welcome to the SQZ Conference Call and Webcast SQZ-PBMC-HPV-101 Clinical Program Updates at ESMO Immuno-Oncology Congress 2021

Agenda Welcome Micah Zajic, Chief Business Officer SQZ Oncology Portfolio Armon Sharei, PhD, Chief Executive Officer and Founder SQZ-PBMC-HPV-101 Phase 1/2 Trial Highest-Dose Cohort Findings Jong Chul Park, MD, Massachusetts General Hospital Monotherapy Summary & Clinical Development Ricardo Zwirtes, MD, Oncology Clinical Development Combination Strategies and Manufacturing Howard Bernstein, MD, PhD, Chief Scientific Officer Summary & 2022 Oncology Portfolio Outlook Armon Sharei, PhD, Chief Executive Officer and Founder Questions & Answers Management Team Members

Agenda Welcome Micah Zajic, Chief Business Officer SQZ Oncology Portfolio Armon Sharei, PhD, Chief Executive Officer and Founder SQZ-PBMC-HPV-101 Phase 1/2 Trial Highest-Dose Cohort Findings Jong Chul Park, MD, Massachusetts General Hospital Monotherapy Summary & Clinical Development Ricardo Zwirtes, MD, Oncology Clinical Development Combination Strategies and Manufacturing Howard Bernstein, MD, PhD, Chief Scientific Officer Summary & 2022 Oncology Portfolio Outlook Armon Sharei, PhD, Chief Executive Officer and Founder Questions & Answers Management Team Members

An exciting milestone for the SQZTM APC approach in solid tumors Biomarkers support expected APC mechanism Clinical and immune response in heavily treated patient Motivates program expansion with systemic combos and eAPCs Manufacturing data highlights rapid production Additional clinical data readouts and INDs expected in 2022

SQZ™ Technology Can Underpin a New Generation of Cell Therapies Universe of Possible SQZ™ Cell Therapies Hematology Oncology Solid Tumors Autoimmune Infectious Disease Regenerative Medicine SQZ™ Technology Potentially enables engineering of many previously challenging biologies Robust process allows for rapid manufacturing and future point of care potential

Engineering Antigen Presentation in a Natural Way to Direct the Immune System 1. Antigen (What to target) Antigen presenting cells (APCs) show peptide antigen on MHC-I and MHC-II that T cells look at using their T cell receptors (TCR) 2. Context (Activation vs. Tolerance) Once a T cell’s TCR is engaged, it looks for clues via APC surface receptors and cytokines for whether to become activated or tolerized Determinants of an Immune Reaction APC T Cell Cytokines Surface receptors + Context Indications: Activating cells (e.g., CD8, CD4) are deleted or anergized and Tregs are upregulated, blocking unwanted immune response against the target CD8 Killer T cells are activated to attack desired target and CD4 T cells are activated to support a broader reaction (e.g., antibodies) Anticipated Outcome: Antigen: Immune Tolerance Immune Activation CD8 Killer T cells CD8 Killer T cells CD4 Helper T cells Regulatory T cells T Cells APC …tolerization against the target …activation against the target T Cells

Diverse Pipeline: Synergistic in Execution yet Independent in Mechanism 9 PLATFORM CELL SOURCE / CARGO INDICATION PRE-CLINICAL PHASE 1/2 ONCOLOGY SQZ APCs PBMC + Peptide H&N, Cervical, Anal Other Solid Tumors SQZ AACs RBC + Peptide + Adjuvant H&N, Cervical, Anal KRAS mut Solid Tumors Other Solid Tumors SQZ eAPCs PBMC + mRNA Solid Tumors AUTO-IMMUNITY SQZ TACs RBC + Protein Celiac disease Type 1 Diabetes INFECTIOUS DISEASE SQZ eAPCs PBMC + mRNA Chronic Hepatitis B Virus Rapid Response Vaccines 9

The Therapeutic Potential and Historical Challenges of Driving CD8 Tumor Responses Responders Progressors …However, there has been limited success in the vaccine field to date. The only approved cell-based cancer vaccine did not induce T cell infiltration into tumor centers in a Phase 2 neoadjuvant trial – immune responses were limited to tumor margins. L Fong et. al. J Natl Cancer Inst. 2014 Limited clinical benefit shown to date as monotherapy or in combination V “Positive prognostic value of CD8 T cells was confirmed in more than 18,700 patients across 17 solid cancer types” Bruni et al, Nature Reviews 2020 PC Tumeh et. al. Nature. 2014 Correlation of CD8 TIL with clinical benefit has been a strong motivation for developing therapeutic vaccines… Current vaccine primary mode of action: Desired mode of action: CD8 Killer T Cells Antibodies CD4 Helper Cells

SQZTM APCs are Designed to Overcome Historical Challenge of CD8 T cell Activation Squeezed Antigen SQZTM APC vs. Cross-Presentation Potency Data: Cell Squeeze® mediated cytosolic delivery demonstrated 1000x More Efficient CD8 Activation versus cross-presentation in dendritic cells % CD8 T Cell Activation Typical Vaccine Mechanism: Cross-Presentation CD4 T Cell, Antibody responses Antigen Endocytosis MHC-I MHC-II Endocytic uptake of antigen Primarily MHC class II presentation to CD4 helper T cells SQZTM APC Mechanism: Direct Antigen Presentation MHC-I CD8 T Cell Activation Suited for prophylactic applications Direct cytosolic delivery Primarily MHC class I presentation to CD8 T cells Suited for therapeutic applications Presented at AACR 2019 by SQZ

SQZTM APC Approach to Direct Endogenous T Cells Against Solid Tumors Lead APC Candidate: SQZ-PBMC-HPV-101 Peripheral blood mononuclear cells (PBMCs) engineered with HPV16 E6 and E7 synthetic long peptide cargo

Agenda Welcome Micah Zajic, Chief Business Officer SQZ Oncology Portfolio Armon Sharei, PhD, Chief Executive Officer and Founder SQZ-PBMC-HPV-101 Phase 1/2 Trial Highest-Dose Cohort Findings in Advanced Solid TumorsJong Chul Park, MD, Massachusetts General Hospital Monotherapy Summary & Clinical Development Ricardo Zwirtes, MD, Oncology Clinical Development Combination Strategies and Manufacturing Howard Bernstein, MD, PhD, Chief Scientific Officer Summary & 2022 Oncology Portfolio Outlook Armon Sharei, PhD, Chief Executive Officer and Founder Questions & Answers Management Team Members

SQZ-PBMC-HPV-101 Evaluated in Advanced, Heavily Pretreated Patients Confirmed HPV16+ recurrent or metastatic cancers, progressed after at least 1 available standard therapy Heavily pretreated patient population at study entry, with median 4 prior lines of therapy across cohorts (n=18) All patients in the highest dose cohort were treated with anti-PD-(L)1 checkpoint inhibitor, and the majority were considered refractory to CPI Patient Baseline Characteristics M=millions, SP=single-prime, DP=double-prime, ECOG PS=Eastern Cooperative Oncology Group Performance Status, CPI=checkpoint inhibitors, PD=Progressive Disease, BOR=Best Overall Response, RMH=Royal Marsden Hospital Trial ID: NCT04084951 Characteristic 0.5 M cells/kg SP (n=3) 2.5 M cells/kg SP (n=5) 2.5 M cells/kg DP (n=4) 5.0 M cells/kg DP (n=6) Total (n=18) Median Age, years (min, max) 65 (60, 68)  65 (54, 68) 49 (47, 66) 57.5 (52, 78) 60 (47, 78) Female, n (%)  3 (100) 3 (60) 3 (75) 0 9 (50) Caucasian Race, n (%) 3 (100)  5 (100) 3 (75) 5 (83) 16 (89) Baseline ECOG PS of 1, n (%) 2 (67) 3 (60) 4 (100) 3 (50) 12 (67) Phase 1 RMH Score High, n (%) 0 3 (60) 4 (100) 1 (33) 8 (44) Site of primary tumor, n (%) Anus Cervix Head & Neck   2 (66) 1 (33) 0   3 (60) 0 2 (40)   2 (50) 1 (25) 1 (25) 0 0 6 (100) 7 (39) 2 (11) 9 (50) Metastatic Disease, n (%) 3 (100) 5 (100) 4 (100) 6 (100) 18 (100) Median Number of Prior Lines, n (min, max)  4 (2, 5) 3 (1, 7) 4 (3, 4) 3.5 (2, 6) 4 (1,7) Prior Systemic Therapy, n (%) Chemotherapy Checkpoint Inhibitor Refractory to CPI (PD as BOR) 3 (100) 3 (100) 2/3 5 (100) 4 (80) 3/4 4 (100) 4 (100) 3/4 6 (100) 6 (100) 4/6 18 (100) 17 (94) 12/17

SQZ-PBMC-HPV-101 was Well-Tolerated At All Dose Levels; No Related Grade ≥3 AEs at Highest Dose 1Grade 3 anemia. 2Grade 2 cytokine release syndrome (CRS). 3AEs of medical concern related to SQZ-PBMC-HPV mechanism of action (CRS, IRR). M=millions, SP=single-prime, DP=double-prime, AE=adverse events Safety and Tolerability Safety data for SQZ-PBMC-HPV was consistent across all dose levels. Most related AEs were of low grade and no patients met the DLT criteria One case of grade 2 cytokine release syndrome in a 1st cohort patient, which resolved in <24h, considered a related serious AE Only grade ≥3 related adverse event was a case of grade 3 anemia in a 2nd cohort patient Trial ID: NCT04084951 Event, n (%) 0.5 M cells/kg SP (n=3) 2.5 M cells/kg SP (n=5) 2.5 M cells/kg DP (n=4) 5.0 M cells/kg DP (n=6) Total (n=18) Related AEs in >1 Patient 3 (100) 4 (80) 2 (50) 5 (83) 14 (78) Fatigue 0 1 (20) 0 4 (67) 5 (28) Flushing 1 (33) 0 0 2 (33) 3 (17) Hypotension 2 (67) 1 (20) 0 0 3 (17) Infusion Related Reaction (IRR) 1 (33) 0 1 (25) 0 2 (11) Nausea 0 0 0 2 (33) 2 (11) Pruritus 0 1 (20) 0 1 (20) 2 (11) Related Grade ≥3 AEs 0 1 (20%)1 0 0 1 (6%) Related Serious AEs 1 (33%)2 0 0 0 1 (6%) AEs of Special Interest3 1 0 1 0 2 (11%) Dose-Limiting Toxicity 0 0 0 0 0 Related AEs leading to d/c 0 0 0 0 0 Fatal Related AEs 0 0 0 0 0

Potential Proof-of-Concept for SQZ-PBMC-HPV-101 in anti-PD-1 Refractory Patient 52-year-old man with squamous cell carcinoma of the oropharynx. Large primary lesion with significant symptom burden Initial diagnosis 3.7 years ago, with 6 prior lines of systemic therapy including carbo/5FU/pembro and anti-TGFβ/pembro (BOR=PD) 9 months before SQZ-PBMC-HPV dosing Received all 7 doses of SQZ-PBMC-HPV, with excellent tolerability (G1 flushing, G1 fatigue) Marked symptomatic improvement (dysphagia and neck swelling) and improvement of the lesion on physical examination Case Study: Patient 17 % Change from Baseline Study Day Highest dose cohort changes in CD8 TILs Highest dose cohort tumor measurements Cells/mm2 Patient 17 Post Pre Day-28 on treatment biopsy demonstrated an 8-fold increase in tumor infiltrating CD8 cells. Radiographic response, including confirmed CR on target lesion (mediastinal lymph node (RECIST 1.1)) with a new dermal lesion at the last tumor assessment. 16 Patient 17 Treatment Start (n = 5 patients) (n = 5 patients)

Patient 17: Immune Markers in Tumor Further Demonstrate APC Mechanism At Work Pre-treat Post-treat CD8 TIL Increase CD8 PanCK CD8 Cells/mm2 HLA-I Increase HLA-I H-Score (0-300) PD-L1 Increase PD-L1 % of PD-L1+ Tumor Cells Pre-treat Post-treat Pre-treat Post-treat Case Study: Patient 17 Influx of CD8 cells into the tumor changed immunophenotype from desert to inflamed Increase in HLA-I expression likely due to CD8 driven IFN-γ secretion Increase in PD-L1 expression suggests potential synergy with a combinatory approach Matched tumor biopsy samples from the main oropharyngeal lesion, taken at screening (Pre-treat) and day-28 on treatment (Post-treat)

Patient 17: Evidence of HPV Antigen-Specific Tumor Targeting Proportion of HPV16 E6 High-Expressing Cells Meaningfully Decreases After APC Treatment RNA ISH Assay Proportion of HPV16 E7 High-Expressing Cells Meaningfully Decreases After APC Treatment RNA ISH Assay Substantial reduction in frequency of HPV16 E6 and E7 expressing tumor cells as measured by RNA in situ hybridization (ISH) E6 and E7 reduction in tumor tissue provides supportive evidence for antigen-specific T cell action in responder patient Patient 17’s HPV16 E6 and E7 Expression Post-Treatment % of HPV16+ Cells % of HPV16+ Cells Matched tumor biopsy samples from the main oropharyngeal lesion, taken at screening (Pre-Treat) and day-28 on treatment (Post-Treat)

Agenda Welcome Micah Zajic, Chief Business Officer SQZ Oncology Portfolio Armon Sharei, PhD, Chief Executive Officer and Founder SQZ-PBMC-HPV-101 Phase 1/2 Trial Highest-Dose Cohort Findings Jong Chul Park, MD, Massachusetts General Hospital Monotherapy Summary & Clinical Development Ricardo Zwirtes, MD, Oncology Clinical Development Combination Strategies and Manufacturing Howard Bernstein, MD, PhD, Chief Scientific Officer Summary & 2022 Oncology Portfolio Outlook Armon Sharei, PhD, Chief Executive Officer and Founder Questions & Answers Management Team Members

Target Lesion Response SD SD CR Survival (days)* 492+ 467+ 105+ RMH 1 0 1 Pre Post Pre Post Pre Post Patient 2 7 17 Dose 0.5 e6/kg 2.5 e6/kg 5.0 e6/kg (DP) Summary: Lead APC Candidate Induced Immune, Clinical Responses in Certain Post-CPI Patients 2x 6x 8x Safety and Tolerability Favorable safety and well-tolerated at all dose levels No pre-conditioning and no severe CRS Clinical and Histologic Activity CD8 TIL increase observed across multiple patients despite advanced population Clinical benefit and ongoing survival among CD8 TIL responders Patient 17's clinical response consistent with expected SQZTM APC mechanism: Increased CD8 tumor infiltration converting phenotype from desert to inflamed Increased PD-L1 expression consistent with tumor inflammation Reduction of E6 and E7 expressing cells suggests antigen-specific killing CD8 Cells/mm2 *Survival follow-up: Patient 2 and 7 survival at the time of the data cut-off October 8, 2021. Patient 17 survival at the time of last dose. CPI=checkpoint inhibitors, RMH=Royal Marsden Hospital, DP=double-prime, SD=stable disease, CR=complete response, TIL=tumor infiltrating lymphocytes

SQZ-PBMC-HPV-101 Clinical Plan and Milestones SQZ-PBMC-HPV-101 at 5.0M cells/kg dose was endorsed by study DSMB to move into PD-(L)1 & CTLA-4 combination stages, with no dose escalation required in combination cohorts The highest dose cohort is still enrolling to further evaluate efficacy of SQZ-PBMC-HPV as monotherapy Next stages of trial provide further opportunity to access earlier-line and low ECOG and RMH patients SQZ-PBMC-HPV-101 Highlights Combination De-escalation Recurrent or metastatic HPV-driven cancer HPV-16+ HLA-A *02+ Platinum experienced CPI offered Inclusion Criteria Treatment until PD, unacceptable toxicity or 2 years Monotherapy Escalation SQZ-PBMC-HPV 5.0e6/kg Q3W Double Prime (n = 6) SQZ-PBMC-HPV 2.5e6/kg Q3W Double Prime (n = 4) SQZ-PBMC-HPV 2.5e6/kg Q3W (n = 5) SQZ-PBMC-HPV 0.5e6/kg Q3W (n = 3) SQZ-PBMC-HPV RP2D + Atezolizumab 1200mg Q3W SQZ-PBMC-HPV RP2D + Ipilimumab 3mg/kg Q3W x 4 SQZ-PBMC-HPV RP2D + Nivolumab 360mg Q3W SQZ-PBMC-HPV RP2D + Nivo 360mg Q3W + Ipi 1mg/kg Q6W SQZ-PBMC-HPV-101 Study Currently Enrolling

Encouraging Results Reinforce Broader Potential Across Indications SQZTM APCs Squeezed with KRAS G12D or G12V Elicited Functional CD8 T Cell Responses ~100,000 patients per year in U.S. have KRAS G12D and G12V mutations Spans multiple tumor types, including pancreatic, colorectal and some lung cancers G12D G12V Presented at AACR 2021 by SQZ Scale of Difficulty for Generating Immune Response Opens potential for additional high-value SQZ product candidates Viral Antigen (e.g. HPV, EBV) Fusion Protein (e.g. BCR-ABL, EML-ALK) Point Mutant (e.g. KRAS) Self Most Difficult Least Difficult ELISpot analysis (IFN-γ )

Agenda Welcome Micah Zajic, Chief Business Officer SQZ Oncology Portfolio Armon Sharei, PhD, Chief Executive Officer and Founder SQZ-PBMC-HPV-101 Phase 1/2 Trial Highest-Dose Cohort Findings Jong Chul Park, MD, Massachusetts General Hospital Monotherapy Summary & Clinical Development Ricardo Zwirtes, MD, Oncology Clinical Development Combination StrategiesHoward Bernstein, MD, PhD, Chief Scientific Officer Summary & 2022 Oncology Portfolio Outlook Armon Sharei, PhD, Chief Executive Officer and Founder Questions & Answers Management Team Members

SQZTM APCs + Systemic Combinations Improve T cell function in the tumor microenvironment Induce inflammation to improve tumor access Path to early line combinations with established treatments SQZTM eAPCs Integrated Combination Function Enhance T cell priming Polyclonal T cell response to expand addressable population T cell phenotype and proliferation enhancing signals Driving to Expand Impact Through Systemic and Integrated Combination Functions Advancing APC + CPI combinations and enhanced APCs (eAPCs) with built-in combination-like functionality Leveraging different biological and pharmacological advantages to direct immune system and counteract solid tumor biology SQZTM APCs Monotherapy Potential Potential Expansion Opportunities and Considerations for SQZTM APCs

Synergistic Combination Potential With Systemic Therapeutic Modalities *Presented at SITC 2020 in SQZ Poster and Roche Oral Presentation Preclinical data* demonstrated synergistic potential of SQZTM APCs in combination with Roche PD1-IL2v I-O Combinations SQZTM APCs and cisplatin chemotherapy combination resulted in enhanced tumor regression in mouse models Cisplatin is utilized as part of the standard-of-care treatment for multiple HPV-associated cancers, including anal, cervical, head & neck Chemo Combinations

Anticipated Clinical Translation of Multi-functional eAPCs eAPC IND targeted by end of 2021 SQZTM eAPC CD86 1 3 Signals CD8 T Cell SQZ eAPC IL-2 IL-12 TCR MHC-I Five mRNAs as cargo Broader antigen repertoire in mRNA potentially increases addressable population 2-3x Addition of co-stimulatory factors and cytokines: membrane-bound IL-2, IL-12 and CD86 Potential for combination-like functionality in single cell therapy Could reduce toxicity normally seen with traditional combinations Enhanced APCs (eAPCs) 2

Agenda Welcome Micah Zajic, Chief Business Officer SQZ Oncology Portfolio Armon Sharei, PhD, Chief Executive Officer and Founder SQZ-PBMC-HPV-101 Phase 1/2 Trial Highest-Dose Cohort Findings Jong Chul Park, MD, Massachusetts General Hospital Monotherapy Summary & Clinical Development Ricardo Zwirtes, MD, Oncology Clinical Development Manufacturing InnovationHoward Bernstein, MD, PhD, Chief Scientific Officer Summary & 2022 Oncology Portfolio Outlook Armon Sharei, PhD, Chief Executive Officer and Founder Questions & Answers Management Team Members

Robust Autologous Cell Therapy Manufacturing in <24 Hours for Phase 1/2 Patients Current Cell Therapy Production Patient Leukapheresis Day 1 SQZ Process <24-hours Day 2 QC and Batch Release Day 2-8 Administration to Patient ~1 week Median manufacturing time was 17 hours for SQZ-PMBC-HPV-101 and allowed for a vein-to-vein time of about a week Median viability was 91% among all patient lots produced HPV16 specific T cell clone assay verified all patient lots were presenting antigen on MHC-I Median of 5 doses available for each highest dose patient from a single leukapheresis session Ongoing In-House Testing to Enable Future Point-of-Care Vision On-site manufacturing without a clean room Same day production Could enable much broader accessibility

Agenda Welcome Micah Zajic, Chief Business Officer SQZ Oncology Portfolio Armon Sharei, PhD, Chief Executive Officer and Founder SQZ-PBMC-HPV-101 Phase 1/2 Trial Highest-Dose Cohort Findings Jong Chul Park, MD, Massachusetts General Hospital Monotherapy Summary & Clinical Development Ricardo Zwirtes, MD, Oncology Clinical Development Combination Strategies and Manufacturing Howard Bernstein, MD, PhD, Chief Scientific Officer Summary & 2022 Oncology Portfolio Outlook Armon Sharei, PhD, Chief Executive Officer and Founder Questions & Answers Management Team Members

Summary & 2022 Oncology Portfolio Outlook APC platform progress supports broader development for HPV+ solid tumors and expansion to new antigens Patient 17 illustrated differentiated clinical impact potential of SQZ™ APC program Increased CD8 TIL and PD-L1 expression underscores potential CPI synergy Systemic combination cohorts with CPI are enrolling. eAPCs with multiple combination-like functions on track for 2021 IND filing Oncology clinical data through end of 2022 SQZTM eAPCs IND on track for filing by YE ‘21 Phase 1/2 monotherapy data SQZTM AACs Phase 1/2 monotherapy data SQZTM APCs Phase 1/2 combination data

Questions & Answers SQZ-PBMC-HPV-101 Clinical Program Updates at ESMO Immuno-Oncology Congress 2021

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