SQZ Biotechnologies Stock

SQZ Biotechnologies Company, a clinical-stage biotechnology company, focuses on unlocking the full potential of cell therapies to benefit patients.

The company was founded on the therapeutic potential of the Cell Squeeze process, the company's proprietary technology which allows for rapid delivery of a variety of cargo into different cell types. It intends to create multiple cell therapies that drive the immune system to combat diseases.

In oncology, the company is developing cell therapy platforms that are based on directing tumor antigen-specific immune activation via engineered antigen presentation. By engineering physiological antigen presentation signals in subsets of peripheral blood cells that act on immune priming pathways, the company has the potential to develop cell therapies that are designed to be potent drivers of tumor-specific immunity, well-tolerated, administered without lymphodepleting, preconditioning or hospitalization, and produced in under 24 hours.

In 2022, the company executed on several key areas of its pipeline. On January 24, 2022, the company announced the U.S. Food and Drug Administration, or FDA, allowance to proceed under its Investigational New Drug application, or IND, for SQZ-eAPC-HPV and began enrolling patients in its Phase 1/2 clinical trial for the treatment of HPV16+ advanced solid tumors. In December 2022, the company presented interim safety, biomarker and clinical data from the monotherapy part of the study at the 2022 European Society for Medical Oncology Immuno-Oncology, or ESMO-IO, Congress.

First-Generation SQZ-PBMC-HPV

As of December 31, 2022, the company had dosed 30 patients in its Phase 1 trial for its first-generation antigen presenting cells, or APC, candidate, SQZ-PBMC-HPV, in HPV16+ advanced solid tumors. The company reported preliminary biomarker and safety results at the recommended Phase 2 dose, or RP2D, of 5 million cells per kilogram (double prime) for 10 monotherapy patients and 7 patients in combination with checkpoint inhibitors (3 patients in combination with atezolizumab, or atezo, and 4 patients in combination with ipilimumab, or ipi) at the 2022 ESMO-IO Congress.

As of December 31, 2022, the company decided to no longer enroll patients in the SQZ-PBMC-HPV trial as it transitions to its second-generation SQZ enhanced Antigen Presenting Cells (eAPC) therapeutic candidate.

Second-Generation SQZ-eAPC-HPV

The company's lead eAPC product candidate leverages the added capabilities and functionality of multiple antigen presentation and immunological signals achieved through multiplexed mRNA delivery to diverse immune cell types. In January 2022, the company received allowance to proceed with clinical trials from the FDA under its IND forSQZ-eAPC-HPV, its eAPC candidate engineered with HPV16 antigens, a costimulatory signal and membrane bound cytokines.

The company initiated the SQZ-eAPC-HPV trial, the COMMANDER-001 Phase ½ study, in patients with HPV16+ advanced solid tumors in the first half of 2022 and provided initial interim data for 4 evaluable patients in the lowest-dose monotherapy cohort at the 2022 ESMO-IO Congress.

Clinical-Stage Cell Therapy Candidates

The company is developing two therapeutic candidates with unique product characteristics and mechanistic benefits based on the principles of antigen-specific immune stimulation:

SQZ Enhanced APC Platform: The eAPC platform has the potential to yield novel multi-engineered cell therapy candidates comprising antigenic, costimulatory and membrane-bound cytokine components. SQZ eAPCs are designed to potentially augment the T cell activation signal and to elicit a polyclonal T cell response. In addition, eAPCs are engineered with mRNAs that encode full-length antigenic proteins, potentially eliminating existing HLA restrictions with the intent to substantially broaden the addressable patient population. The company's first eAPC platform candidate, SQZ-eAPC-HPV, was developed by multiplexed engineering of PBMCs with five different mRNAs.

SQZ Activating Antigen Carrier Platform: SQZ AACs are derived from engineering red blood cells, or RBCs, with the Cell Squeeze technology to comprise tumor-specific antigens and adjuvant. The company published preclinical research on its AAC program in Frontiers in Immunology in October 2022. AACs are designed to take advantage of the natural physiological process of aged RBC clearance to target resident, professional APCs in lymphoid organs that can subsequently prime endogenous T cells to drive antitumor activity. The company is enrolling patients in the Phase 1 ENVOY-001 trial for the SQZ-AAC-HPV investigational therapy in HPV16+ advanced or metastatic tumors.

Programs Available for Partnership or Collaboration

Autoimmune Diseases

SQZ Tolerizing Antigen Carrier Platform: In 2022, the company completed a pre-IND meeting with the FDA and performed IND-enabling activities for SQZ Tolerizing Antigen Carrier (TAC) platform with the aim to treat autoimmune diseases by inducing antigen-specific immune tolerance. The company published preclinical research on its TAC program in Frontiers in Immunology in April 2022. The company's research, as of December 31, 2022, had been focused on Type 1 Diabetes and Celiac Disease. The company's TACs are derived from engineering RBCs to comprise disease-specific antigens and are designed to leverage the natural physiological process of aged RBC clearance. SQZ TACs have demonstrated the potential to induce multiple mechanisms of immune tolerance, including the deletion of disease-driving T cells, in preclinical mouse models.

Infectious Diseases

The company's SQZ APC, eAPC and AAC platforms have the potential to provide therapeutic benefit by driving antigen-specific immune responses in chronic and acute infectious disease settings. In preclinical studies, the company has demonstrated the versatility of its eAPCs to elicit targeted CD8+ T cell activation for multiple well-known disease antigens, including in hepatitis B virus, or HBV, cytomegalovirus, or CMV, influenza A virus, or IAV, and simian immunodeficiency virus, or SIV. Chronic HBV represents a large patient population with significant unmet need, and clinical evidence suggests that the levels of virus-specific T cells are correlated with patient outcomes and disease control.

Strategy

The key elements of the company's strategy are to advance human papilloma virus (HPV)-specific cell therapy for the treatment of HPV-associated solid tumor malignancies; and invest in its innovative manufacturing capabilities and advance its point-of-care system.

The company, through partnership or collaboration, has the potential to broaden and deepen its pipeline by expanding to additional disease antigen targets within oncology, as well as autoimmune and infectious disease areas.

Product Candidate Pipeline

SQZ Enhanced Antigen Presenting Cell (eAPC) Platform

eAPC Platform

The SQZ eAPC platform is the second-generation product candidate designed to generate tumor-specific CD8+ T cell activation to drive the antitumor immune response. eAPCs utilize direct antigen presentation to engineer the three canonical T cell activation signals of peptide-MHC (Signal 1), costimulatory proteins (Signal 2) and cytokines (Signal 3), into the antigen presenting cells in an effort to create novel, multi-functional cell therapy product candidates for driving antitumor immunity. CD8+ T cells are known to be important effectors of the adaptive immune system, and are foundational to the recent clinical success of immunotherapy in oncologic indications.

In preclinical studies, the company's microfluidic Cell Squeeze technology demonstrated abilities to deliver a variety of antigens directly into the cytosol, enabling potent antigen presentation for CD8+ T cell priming. In January 2022, the company published peer-reviewed in vitro potency data for its first-generation SQZ APCs in the Journal of Immunology, where it demonstrated Cell Squeeze-mediated cytosolic delivery yielded 1000-fold more efficient CD8+ activation relative to cross-presentation in dendritic cells.

Based on the company's preclinical research, the SQZ eAPC platform demonstrated the potential to achieve several coordinates of a T cell response. SQZ eAPCs is an autologous product candidate and is generated through the engineering of patient B cells, T cells, Natural killer, or NK, cells, and monocytes with 5 mRNAs encoding antigen-specific and immunological functions in a single Cell Squeeze step.

SQZ eAPC Product Candidate: SQZ-eAPC-HPV

Preclinical Development of SQZ-eAPC-HPV in Solid Tumors

The company's lead eAPC product candidate, SQZ-eAPC-HPV, is engineered with mRNA cargo encoding the full-length HPV16+ E6 and E7 antigenic proteins and is in development for the treatment of HPV16+ tumors. Additionally, SQZ-eAPC-HPV is designed to express CD86 as a costimulatory molecule for T cell activation, as well as proprietary, membrane-bound versions of IL-2 and IL-12 (mbIL-2 and mb-IL-12) in an effort to further potentiate T cell activation and expansion. The company's IND for a Phase 1/2 clinical trial to study SQZ-eAPC-HPV was allowed to proceed by the FDA in January 2022. In November 2021, the company presented preclinical data for SQZ-eAPC-HPV at the SITC Annual Meeting.

Clinical Development of SQZ-eAPC-HPV in Solid Tumors

The company is evaluating SQZ-eAPC-HPV in the Phase 1/2 COMMANDER-001 trial for recurrent, locally advanced, or metastatic HPV16+ solid tumors. The trial is an open-label, multicenter, dose escalation and expansion study to evaluate the safety and tolerability, immunogenic effects, antitumor activity, and pharmacodynamics of SQZ-eAPC-HPV as monotherapy and in combination with immune checkpoint inhibitors, including pembrolizumab. By not requiring any HLA inclusion criteria in the study, the company expects to increase patient eligibility by approximately two- to three-fold.

The primary objectives of the trial are to evaluate safety and tolerability, as assessed by the number of participants with treatment-related adverse events and identify the RP2, of SQZ-eAPC-HPV monotherapy, which will be the dose utilized in combination with checkpoint inhibitors. The secondary objectives of the trial are evaluate antitumor activity in patients with recurrent, locally advanced, or metastatic solid tumors, based on tumor assessments using RECIST 1.1, and manufacturing feasibility, as assessed by individual patient batch yields. Initial safety data from the dose escalation / expansion trial were presented at the ESMO-IO annual congress in December 2022.

In December 2022, the company presented initial interim results from the monotherapy dose escalation portion of the SQZ-eAPC-HPV trial in HPV16+ solid tumors at the ESMO-IO congress. Interim data were reported for four evaluable monotherapy patients in the lowest dose cohort-there was one patient in the second cohort that was not evaluable for the DLT. In an advanced population with a median of 3 prior lines of therapy. The interim results demonstrated that SQZ-eAPC-HPV was well-tolerated with stable disease as the best response.

SQZ Activating Antigen Carrier (AAC) Platform

AAC Platform

The SQZ AAC platform is designed to induce antigen presentation in vivo by deriving antigen carriers from engineering RBCs with tumor-specific antigens and adjuvant. The company generated AACs by engineering red blood cells (RBCs) to encapsulate relevant tumor antigens and the adjuvant polyinosinic-polycytidylic acid (poly I:C) for use as a tumor-specific cancer vaccine. The processing method and conditions used to create the AACs are designed to promote phosphatidylserine exposure on RBCs and thus harness the natural process of aged RBC clearance to enable targeting of the AACs to endogenous professional antigen presenting cells (APCs). The company's preclinical data support further development of AACs as a potential vector-free immunotherapy strategy to enable potent antigen presentation and T cell stimulation by endogenous APCs with broad therapeutic potential.

Preclinical Development of SQZ-AAC-HPV in Solid Tumors

In preclinical studies, the company has shown that AACs were rapidly taken up by professional APCs, such as macrophages and dendritic cells, or DCs, in the spleen and liver, and that AACs loaded with target antigens and adjuvant subsequently drove antigen-specific CD8+ T cell responses. At the 2020 SITC Annual Meeting, the company presented murine data on the in vivo pharmacokinetics and functional activity of SQZ AAC therapeutic immunization, which support the potential of AACs as a differentiated, directed immunity platform. In October 2022, the company published its preclinical work in a peer-reviewed journal, Frontiers in Immunology, which showcases how AACs drove potent T Cell Responses and tumor regression in mice.

Clinical Development of SQZ-AAC-HPV in Solid Tumors

The ENVOY-001 trial is a Phase 1 open-label trial of the company's AAC HPV therapy candidate, or SQZ-AAC-HPV, as a monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with HPV16+ recurrent, locally advanced or metastatic solid tumors. The company decided to continue to enroll patients in the SQZ-AAC-HPV clinical trial. The company has completed the dose-limiting toxicity period for the lowest-dose cohort. Following review and recommendation by the Study Safety Committee, the company is advancing SQZ-AAC-HPV-101 trial to the highest-dose cohort. The company anticipates initial clinical data from the highest-dose cohort in the fourth quarter of 2023.

Partnership or Collaboration Platforms

Autoimmune Diseases

SQZ Tolerizing Antigen Carrier (TAC) Platform

TAC Platform Overview

The company's SQZ TAC platform is designed to induce antigen-specific immune tolerance in vivo by utilizing a similar approach to the AAC platform, whereby TACs are derived from engineering RBCs to modulate and suppress unwanted immune responses in a targeted manner.

As with its AAC platform, the company utilizes proprietary methods and processes for generating TACs, which induce changes associated with RBC senescence, to enable targeting to resident populations of professional APCs, such as macrophages, in lymphoid organs. SQZ TACs are designed to take advantage of the naturally tolerogenic process of aged RBC clearance and are subsequently aimed to drive antigen-specific immune tolerance through multiple cellular mechanisms considered relevant to the pathology of complex autoimmune diseases. In preclinical studies with transgenic OT-I and OT-II murine models, the company evaluated multi-modal mechanisms of tolerance induced by TAC treatment, including upregulation of markers of anergy associated with functional inactivation of CD8+ and CD4+ T cells, targeted deletion of antigen-specific T cells, and expansion of antigen-specific regulatory T cells, or Tregs.

The potential of TACs to regulate both autoreactive CD4+ T cells and CD8+ T cells through multiple pathways may enable the development of differentiated therapeutic candidates for the treatment of diverse autoimmune diseases.

Infectious Diseases

The company's cell therapy platforms aimed at antigen-specific immune activation have therapeutic potential across multiple infectious disease indications. Virus-specific CD8+ T cell activity has been shown to be associated with disease control and improved outcomes in certain diseases, such as chronic HBV, which could be a promising avenue for the company's directed immunity approach.

Collaboration, Research and License Agreements

Roche Collaboration

In October 2018, the company entered into a License and Collaboration Agreement, or the Roche Collaboration Agreement, under which it is collaborating with Hoffman-La Roche Inc. and F. Hoffman-La Roche Ltd., or together, Roche, in the development and commercialization of certain nucleated cell therapy product candidates that incorporate antigens for the treatment of oncologic indications in accordance with mutually agreed upon collaboration plans. The Roche Collaboration Agreement enhanced, replaced and terminated a 2015 collaboration agreement between the company and Roche.

The company agreed, under the Roche Collaboration Agreement, to collaborate with Roche in the development of a cell therapy for oncologic indications made from PBMCs. The initial mutually selected antigen target is HPV, which is the focus of the company's ongoing SQZ-PBMC-HPV Phase 1 clinical trial. The company also agreed to use commercially reasonable efforts to mutually select additional antigens to develop collaboratively.

MIT License Agreement

The company exclusively license certain foundational technology from the Massachusetts Institute of Technology, or MIT, pursuant to an Amended and Restated Exclusive Patent License Agreement dated as of December 2, 2015, or the MIT License Agreement. The MIT License Agreement replaced an earlier Exclusive Patent License Agreement dated as of May 10, 2013, which was entered into in connection with the organization of the company. Under the MIT License Agreement, MIT granted the company a worldwide, royalty bearing license to develop, make, have made, use, sell, offer to sell, lease, and import products incorporating the patent rights and to develop use, sell, offer to sell and perform processes incorporating the patent rights for all research and therapeutic applications for the term of the MIT License Agreement. The company's rights under the license are exclusive in its fields of use, except with respect to MIT and Harvard University (which owns the patent rights jointly with MIT), each of which retain rights for research, teaching and educational purposes on their own behalf and on behalf of all other non-profit research institutions; Howard Hughes Medical Institution, which has an irrevocable, non-exclusive, non-assignable, non-sublicensable, license to use the patent rights for its own research purposes; and the federal government, which retains a non-exclusive and non-transferable license to practice any government-funded invention claimed in the patent rights, as provided by law. The company also has the right to grant sublicenses to third parties, subject to written agreements containing similar protections of MIT and certain third-party beneficiaries as contained in the agreement.

Intellectual Property

Patents

The company's patent portfolio includes more than 40 patent families that it owns or has licensed, that have been prosecuted and maintained to potentially secure exclusivity for various SQZ candidates and platforms through to 2028-2043, without taking into account any patent term adjustments or extensions it may obtain. As of February 27, 2023, the company's portfolio consisted of over 147 U.S. and foreign patents (including over 85 patents in various European countries) and over 227 U.S., Patent Cooperation Treaty (international), and foreign patent applications. These applications are designed to provide protection for various SQZ product candidates and platforms, including the Cell Squeeze technology and clinical candidates. In addition, these patents and applications contain a suite of claims directed to the SQZ systems, devices, composition of matter and methods of use, including methods of inducing an immune response, tolerance, treating cancer, treating various autoimmune diseases, and various other diseases.

The company diligently evaluate its intellectual property strategy as it develops new platform technologies and product candidates. The company is positioned to file additional patent applications based on its patenting strategy, or where it seeks to adapt to competition or seize business opportunities. The company continues to prosecute its portfolio aggressively.

The Cell Squeeze Platform

As of February 27, 2023, the company's Cell Squeeze platform, which included the Cell Squeeze technology, methods and use, apparatus and components, and system, consisted of 67 U.S. and foreign patents and 49 U.S., Patent Cooperation Treaty (international), and foreign patent applications. The patents and applications in this category are relevant or may be relevant to a variety of SQZ technologies, platforms, and product candidates.

The Immune Activation Platform

As of February 27, 2023, the company's immune cell platform, which included the SQZ-PBMC-HPV and SQZ-eAPC-HPV clinical candidates, as well as confidential candidates and technology, specialized Cell Squeeze methods and use, as well as clinical formulations and protocols, consisted of 6 U.S. and foreign patents and 118 U.S., Patent Cooperation Treaty (international), and foreign patent applications.

As of February 27, 2023, the company's anucleate cell platform, which included the SQZ-AAC-HPV clinical candidate, as well as confidential candidates and technology, specialized Cell Squeeze methods and use, as well as clinical formulations and protocols, consisted of 33 U.S. and foreign patents and 23 U.S., Patent Cooperation Treaty (international), and foreign patent applications.

The Immune Tolerance Platform

As of February 27, 2023, the company's autoimmune platform, which included the TAC technology, as well as confidential candidates and technology, specialized Cell Squeeze methods and use, consisted of 30 U.S. and foreign patents and 20 U.S., Patent Cooperation Treaty (international), and foreign patent applications.

Exploratory Work

As of February 27, 2023, the company's earlier research and exploratory work, which included confidential early-stage project candidates and specialized Cell Squeeze methods and use, consisted of 11 U.S. and foreign patents and 21 U.S., Patent Cooperation Treaty (international), and foreign patent applications.

Trademarks

The company owns 35 allowed or registered trademarks in various jurisdictions worldwide, including four registered trademarks in the United States. The company has 12 pending trademark applications worldwide, including 10 in the United States. The company's trademark portfolio includes the following pending, allowed, or registered marks registered in the United States and certain other countries: Cell Squeeze, SQZ, SQZ Biotech, Empower Cells to Change Lives, SQZ Therapeutics, SQZ Activating Antigen Carriers, SQZ Antigen Carriers, SQZ Tolerizing Antigen Carriers, SQZ TX, SQZ-AC, SQZ-AAC, and SQZ-TAC.

Research and Development

The company's research and development expenses were $71.0 million for the year ended December 31, 2022.

Government Regulation

Biological products, including the company's product candidates, are subject to extensive regulation by the FDA under the Federal Food, Drug, and Cosmetic Act, or FDCA, and the Public Health Service Act.

Prior to beginning the first clinical trial with a product candidate in the United States, the company must submit an IND to the FDA. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting requirements upon the company.

History

SQZ Biotechnologies Company was founded in 2013. The company was incorporated in 2013 under the laws of the state of Delaware.