ESMO Immuno-Oncology and Technology Article Details Importance of Intracellular Delivery to Drive Effective MHC-I Mediated Activation of CD8 T Cells

Paper Highlights Preclinical SQZ^® APC Combination Data with PD-1 IL2v and Manufacturing Benefits of the Cell Squeeze^® Technology

SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, today announced the publication of a technical review examining the ability of SQZ^® Antigen Presenting Cells (APCs) to activate CD8 T cells through MHC-I antigen presentation, an approach that may enable a more powerful T cell response and infiltration into solid tumors. Published in ESMO’s Immuno-Oncology and Technology (IOTECH) journal, the review further explores the advantages of the company’s Cell Squeeze^® technology in cell engineering and manufacturing as well as potential opportunities to develop additional clinical candidates with enhanced capabilities.

“In this review, for patients with solid tumors, we discuss the critical need to generate CD8 T cell penetration into the tumor microenvironment,” said lead author Jong Chul Park, MD, Medical Oncologist, Massachusetts General Hospital Cancer Center, and SQZ^® cell therapy trial site investigator. “Activation of CD8 T cells through MHC-I antigen presentation is a promising approach and is being tested in the SQZ-PBMC-HPV-101 clinical trial where we’ve seen increases in CD8 T cell tumor infiltration and clinical benefit in a refractory patient with HPV16-mediated cancer. We look forward to potentially building on these early results through combination with various immunomodulatory drugs, such as checkpoint inhibitors.”

SQZ has three ongoing Phase 1/2 clinical trials aiming to drive CD8 T cell responses against HPV16+ solid tumors. Given the broad relevance of CD8 T cell responses across tumors, the authors highlight potential for future expansion of development programs into additional areas such as mutant KRAS, mutant TP53, EBV, and other patient-specific antigens.

Review Highlights:

• Comparison of Intracellular Delivery Approaches: The Cell Squeeze^® engineering method has compelling features compared to viral or electroporation approaches across a number of categories, including cell perturbation, scalability, cell types, cargo types, targeting, dosage control, and cost per dose
• Enabling MHC-I Presentation and Multi-Dimensional Immune Engineering: SQZ’s approach has demonstrated preclinically dramatic improvements in potential CD8 T cell activation as well as synergy with next generation immuno-oncology drugs such as PD-1 IL2v
• Manufacturing and Patient Dose Timing: SQZ^® clinical candidates experienced an average vein-to-vein time of roughly one week, faster than most other therapeutic approaches for delivering sterile cell therapy

About SQZ-PBMC-HPV

SQZ-PBMC-HPV is the company’s Antigen Presenting Cell (APC) autologous cell therapy clinical candidate and is derived from peripheral blood mononuclear cells (PBMCs), primarily composed of monocytes, T cells, B cells, and NK cells, and engineered with tumor specific E6 and E7 peptide antigens. It received FDA fast track designation in April 2022. In December 2021, the company presented clinical data at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) congress that included a checkpoint refractory head-and-neck cancer patient who demonstrated a radiographic, symptomatic, and immune response in the monotherapy cohort of the Phase 1/2 clinical trial.

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 phases 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, 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 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 Statement

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, clinical safety and efficacy results, therapeutic potential 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 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.

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