Cell Squeeze^® Platform Offers Advantages for GMP Engineering of Multiple Cell Types and Reduced Manufacturing Time and Cost through its Point-of-Care System

mRNA Constructs Encoding Multiple Linked Antigens Could Allow for a Multiantigen-Specific CD8+ T Cell Response

SQZ^® eAPCs Contain Five mRNAs Encoding for Proteins Stimulating the Key T Cell Activation Signals to Potentially Mount Potent Immune Response Against Tumors

SQZ Biotechnologies (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, will present preclinical research demonstrating the potential of its Cell Squeeze^® technology to multiplex engineer a diverse set of cell types, including hematopoietic stem cells (HSCs) and induced pluripotent stem cells (iPSCs), to potentially support the creation of new therapeutic candidates. This capability builds upon the GMP capable system and SQZ^® Point-of-Care system that can process more than 10 billion cells per minute. The data will be presented at the 37^th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) being held November 8-12, 2022, in Boston, MA.

“Our presentation at SITC demonstrates the broad potential of our Cell Squeeze^® technology to reliably deliver materials into cells without disrupting cell function, reduce manufacturing times, improve the safety of cell therapies, and support the creation of new therapies,” said Jonathan Gilbert, Ph.D., Vice President of Exploratory Research at SQZ Biotechnologies.

The company will also present a COMMANDER-001 Phase 1/2 Trial in Progress poster demonstrating how its Enhanced Antigen Presenting Cell (eAPC) therapeutic candidate is designed to leverage the delivery of five mRNAs encoding for proteins stimulating the key T cell activation signals required to generate an immune response against tumors, including membrane-bound IL-2 and IL-12. By presenting all three canonical signals, the eAPC approach can potentially amplify the T cell response. Additionally, the ability to deliver E6 and E7 mRNA encoding full-length proteins to eAPCs removes the HLA restriction for trial screening, increasing the addressable patient population by two-to-three times when compared to the company’s Antigen Presenting Cell (APC) program.

Lastly, the company will present preclinical research outlining a potential new therapeutic approach linking multiple antigens together to create a single mRNA and delivering it into eAPCs to generate a personalized neoantigen medicine for mutations like the KRAS mutation.

“One of the latest examples of our platform’s potential is its capability to deliver multiple linked antigens to eAPCs, which could potentially be used to develop bespoke vaccines for patients based on their cancer’s specific mutations or vaccines for a larger set of patients with a shared mutation such as KRAS,” said Marshelle Warren, M.D., Chief Medical Officer at SQZ Biotechnologies. “Additionally, we are presenting our eAPC Trial in Progress and look forward to sharing our initial data by the end of the year.”

Major Findings from Research:

Poster #224: Generation of Cell Therapies for Diverse Applications Using Microfluidic Cell Squeeze^® Manufacturing Technology

Date: Friday, November 11, 2022

• The Cell Squeeze^® system can be leveraged to engineer a diverse set of cell types, including HSCs and iPSCs, and potentially allows for improved product quality and manufacturing cost relative to other common cell therapy approaches. Advantages include limited required rest time after the engineering step, faster proliferation, and fewer operator hours needed
• Transient engineering of a broad set of cell types with membrane-bound cytokines could lead to new therapeutic approaches for cell therapy. Preclinically, we show the ability to potentially improve safety by eliminating cytokine support as well as increase the frequency of a desirable cell phenotype
• SQZ^® Point-of-Care (POC) system enables more cell engineering possibilities while demonstrating a >90% reduction in operator hours with total process time under six hours. The POC system also offers the potential to eliminate the need for an ISO 7 clean room

Poster #321: Single mRNA Constructs Encoding Multiple Linked Antigens Allow for a Multiantigen-Specific CD8+ T Cell Response Driven by SQZ^® eAPCs

Date: Thursday, November 10, 2022

• Using Cell Squeeze^® technology, investigators successfully generated SQZ^® eAPCs with mRNA encoding for up to 10 linked antigen fragments, including E6, E7, KRAS G12V, and KRAS G12D
• SQZ^® eAPCs engineered with linked antigen mRNA constructs containing KRAS antigens drove KRAS-specific T cell responses in vitro, suggesting a potential model for a personalized neoantigen medicine for KRAS mutations
• mRNA constructs encoding multiple linked antigens drove increased CD8+ T cell response, further enhancing the versatility of the Cell Squeeze^® technology to potentially target multiple tumor-associated neoantigens in a single mRNA construct

Poster #638: COMMANDER-001: A Phase 1/2, First-in-Human, Multicenter, Open Label Study of SQZ-eAPC-HPV as Monotherapy and with Pembrolizumab in Patients with HPV16+ Recurrent, Locally Advanced, or Metastatic Solid Tumors (Trial in Progress)

Date: Friday, November 11, 2022

• SQZ-eAPC-HPV is an enhanced SQZ^® clinical therapeutic candidate with no HLA restrictions, which increases the eligible patient population by 2-3 times compared to the company’s SQZ-PBMC-HPV clinical candidate
• SQZ^® Enhanced Antigen Presenting Cells (eAPCs) are engineered by using the Cell Squeeze^® technology to simultaneously deliver five mRNAs encoding for full-length HPV16 E6 and E7 proteins (signal 1), CD86 (signal 2), and membrane-bound (mb) IL-2 and mbIL-12 cytokines (signal 3)
• Eligible patients undergo a single leukapheresis, from which all doses have been manufactured in under 24 hours. Patients do not require a preconditioning regimen prior to receiving the therapeutic candidate

About SQZ-eAPC-HPV

SQZ^® Enhanced Antigen Presenting Cells (eAPC) are derived from peripheral blood mononuclear cells (PBMCs), which are primarily composed of monocytes, T cells, B cells, and NK cells, and engineered with various mRNA encoding for multiple target antigens and immuno-stimulatory signals, including CD86 and membrane-bound IL-2 and IL-12. The company has presented preclinical findings showing that SQZ^® eAPCs have generated robust T cell responses in human in vitro and in vivo models. Additionally, it was demonstrated that HPV16-encoding mRNA delivery to PBMCs stimulated CD8+ T cells across a range of HLA haplotypes, supporting eAPC clinical development in broader HPV16+ patient populations.

COMMANDER-001 Trial Design

SQZ-eAPC-HPV is being evaluated in a Phase 1/2 clinical trial (COMMANDER-001) for the treatment of HPV16+ advanced or metastatic solid tumors. The clinical candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with pembrolizumab, an immune checkpoint inhibitor. The study consists of two parts. The first part is designed to assess safety and tolerability of multiple doses of SQZ-eAPC-HPV in treatment-experienced patients, following a dose-escalation scheme for monotherapy, and a dose de-escalation for the combination with pembrolizumab. The second part of the study will assess clinical response of SQZ-eAPC-HPV in combination with pembrolizumab in immune checkpoint inhibitor treatment-naïve patient populations.

About Human Papillomavirus Positive Cancers

Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years, often 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 is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies to benefit patients with cancer, autoimmune and infectious diseases. The company’s proprietary Cell Squeeze^® technology offers the unique ability to deliver multiple biological materials into many patient cell types to engineer what we believe can be a broad range of potential therapeutics. Our goal is to create well-tolerated cell therapies that can provide therapeutic benefit for patients and improve the patient experience over existing cell therapy approaches. With accelerated production timelines under 24 hours and the opportunity to eliminate preconditioning and lengthy hospital stays, our approach could change the way people think about cell therapies. The company’s first therapeutic applications seek to generate target-specific immune responses, both in immune activation for the treatment of solid tumors and in immune tolerance for the treatment of unwanted immune reactions and 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, platform and clinical development, product candidates, preclinical and clinical activities, progress and outcomes, development plans, manufacturing capabilities, clinical safety and efficacy results, and therapeutic potential. 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 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 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 SQZ undertakes 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.

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