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SQZ Biotechnologies (SQZ) Reports Strong Preclinical Data SQZ TIL


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SQZ Biotechnologies Company (NYSE: SQZ), focused on harnessing the full potential of cell therapies for multiple therapeutic areas, today presented preclinical data supporting that tumor-infiltrating lymphocytes (TILs) are engineered with membrane-bound cytokines IL-2 (mbIL-2) and IL-12 (mbIL-12) may eliminate the need for high-dose systemic IL-2 and lymphodepleting preconditioning used with current TIL therapies. SQZ® TILs have shown the ability to induce desirable cytokine signaling for over 48 hours, which is comparable to the duration of exogenous IL-2 support in current TIL therapies. SQZ® TILs have also demonstrated enhanced donor-matched tumor cell killing, up-regulated markers associated with central memory T cells, and persistence in vivo. The data was presented today at the European Society for Medical Oncology (ESMO) Congress 2022.

“TIL therapies have shown exciting clinical results in solid tumors, but to overcome the challenges of engraftment and persistence, they also require lymphodepletion and systemic IL-2, which are toxic to patients and prevent repeated doses,” said Jonathan Gilbert, Ph.D., Vice President of Exploratory Research at SQZ Biotechnologies. “By providing cytokine support at the cell surface, SQZ® TILs can simultaneously eliminate the need for these toxic co-treatments and improve T-cell function. Together, this could potentially increase potency while moving TILs to an outpatient procedure that allows repeat dosing and combination therapies.

The ZSQ® The TIL platform is based on the company’s mbIL-2 and mbIL-12 constructs used in its enhanced antigen-presenting cell (eAPC) clinical trial. Both approaches are designed to take advantage of the transient expression of membrane-bound cytokines so that potent cytokines such as IL-12 can be expressed without systemic toxicity. Further TIL engineering with membrane-bound IL-7 (mbIL-7) and BCL-2, an anti-apoptotic factor, may further enhance SQZ capabilities® TIL to be grafted without preconditioning.

Main results of preclinical research

Poster #761: Tumor-infiltrating lymphocytes expressing membrane-bound IL-2 and IL-12 show enhanced proliferation, function, and persistence without requiring exogenous IL-2 support

  • Expression and function of cytokines: TILs engineered with mbIL-2 and mbIL-12 induced high levels of expression and sustained >70% viability in the absence of external cytokine support for 5 days, a longer time than IL-2 is usually dosed in the clinic after TIL infusion. Membrane-bound cytokines produced nearly 4-fold expansion in vitro, which was comparable to unmodified TILs grown in media containing IL-2
  • Kill tumor cells: TILs from primary solid tumors engineered with mbIL-2 and mbIL-12 and subsequently cultured with donor-matched tumor cell lines showed 3.5 times higher IFN-γ release than the current clinical standard of unmodified TILs with exogenous IL-2, as well as increased tumor killing as measured by apoptotic cell staining
  • Memory T cell reprogramming: TILs engineered to express CD62L upregulated by mbIL-2 and mbIL-12, a classical marker of central memory T cells (>80% positive, vs.
  • In vivo survival and phenotype: TILs mbIL-2 and mbIL-2/12 adoptively transferred into a mouse model each showed more than 200% higher cell persistence in vivo compared to unmodified TILs, and mbIL-12 resulted in enrichment 3.5-fold in CD62L expression in vivo for at least 5 days after transfer
  • Promising targets: TILs engineered with mbIL-7 and BCL2, which can support cell survival, have demonstrated strong benefit in the absence of exogenous cytokine support and could serve as potential future TIL activators.

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 exclusive Cell Squeeze® The technology offers the unique ability to deliver multiple biological materials into many patient cell types to design what we believe to be a wide range of potential therapies. Our goal is to create well-tolerated cell therapies that can provide therapeutic benefit to patients and improve patient experience over existing cell therapy approaches. With accelerated production times of less than 24 hours and the ability to eliminate preconditioning and long hospital stays, our approach could change the way people think about cell therapies. The company’s first therapeutic applications aim to generate targeted immune responses, both in activation for the treatment of solid tumors and in immune tolerance for the treatment of adverse 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. Any statements contained herein that do not relate to historical facts 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 results, development plans, 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 the forward-looking statements due to several risk factors. These factors include, among others, the risks and uncertainties associated with our limited operating history; our material losses incurred since inception and the expectation of incurring additional material losses in the foreseeable future; the development of our initial product candidates, upon which our business is heavily dependent; the impact of the COVID-19 pandemic on our clinical operations and activities; our need for additional financing and our cash flow; the lengthy, costly and uncertain process of developing clinical drugs, including uncertain clinical trial results and potential delays in regulatory approval; our ability to maintain our relationships with our third-party vendors; and protecting our proprietary technology, intellectual property portfolio and the confidentiality of our trade secrets. These and other important factors discussed under “Risk Factors” in our Annual Report on Form 10-K and other filings with the United States Securities and Exchange Commission could cause results actuals differ materially from those indicated by the forward-looking statements. All forward-looking statements represent management’s estimates as of this date and SQZ undertakes no obligation to update such forward-looking statements, whether as a result of new information, the occurrence of current events or otherwise, unless the law requires it.

Certain information contained in this press release concerns or is based on studies, publications, surveys and other data obtained from third party sources and on our own internal estimates and research. Although 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 representations as to the adequacy, fairness, accuracy or completeness of any information obtained from third parties. sources.

Media:

Erin Phelps

[email protected]

857-760-0920

Investor:

Mike Kaiser

[email protected]

857-760-0398

Source: SQZ Biotechnologies Company