On May 18, 2022 SQZ Biotechnologies (NYSE: SQZ) reported that the company’s first generation, integrated point-of-care (POC) cell therapy manufacturing system demonstrated superior process performance and comparable or improved product specifications relative to current clean room-based processes used in clinical development (Press release, SQZ Biotech, MAY 18, 2022, View Source [SID1234614824]). The non-clinical studies showed that the SQZ POC system could produce the company’s red blood cell derived SQZ Activating Antigen Carrier (AAC) therapeutic candidate for the treatment of HPV16 positive solid tumors in half the time (under 6 hours), with 90 percent fewer operator hours, while producing comparable drug product. The system is also compatible with hematopoietic stem cells and peripheral immune cells, including B cells, T cells, NK cells, and Monocytes. Data was presented today at the 2022 American Society for Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) annual meeting.

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"We are tremendously excited with the cell therapy production data from our prototype point-of-care manufacturing system, which has the potential to produce cell therapies using a range of cell types," said Howard Bernstein, M.D., Ph.D., Chief Scientific Officer at SQZ Biotechnologies. "Our current clinical manufacturing process is under 24 hours – comparatively faster than other cell therapy manufacturing approaches. Our integrated point-of-care platform represents a further leap with faster production in a closed system that could eliminate the need for an ISO 7 clean room. We look forward to its planned first clinical use in our red blood cell derived SQZ TAC program for celiac disease."

The company anticipates a SQZ TAC IND submission for celiac disease in the first half of 2023. Celiac disease impacts a large patient population globally and it, like many other diseases, could benefit from a scalable, decentralized cell therapy manufacturing model. Manufacturing the first SQZ TAC clinical candidate on the SQZ POC system will further the development of this decentralized model and support potential future use of the POC system across disease areas.

The SQZ POC manufacturing system integrates and automates, among other things, cell isolation, cell washing, Cell Squeeze intracellular delivery technology, and product filling. The system is designed to process patient material within a closed, single-use sterile disposable kit. The system architecture offers the potential to be operated outside of an ISO 7 clean room typically required of cell therapies—which could ultimately allow cell therapy manufacturing by SQZ POC systems in a variety of care settings.

In addition to the SQZ POC presentation at ASGCT (Free ASGCT Whitepaper), preclinical data were presented on the first study findings of the planned commercial research-use-only (RUO) microfluidic delivery system. The RUO presentation highlighted the gentle, yet efficient, nature of the intracellular delivery system. Data demonstrated the ability to effectively deliver and express mRNA in unactivated T and NK cells as well as to gene edit unactivated T cells with limited impact to viability and downstream function.

Cell Squeeze gene editing of autologous hematopoietic stem cells (HSCs) was also presented at the conference. The HSC editing preclinical data demonstrated that the Cell Squeeze platform could efficiently deliver mRNA and RNPs into HSCs, a sensitive cell type that has been limited previously by toxicity, cargo restrictions, and scalability using other cell engineering approaches. Analysis of the Cell Squeeze processed HSCs determined that their phenotype was maintained in vitro and in vivo illustrating its broad potential for use in certain rare and genetic disease indications.

ASGCT POINT-OF-CARE MANUFACTURING DATA HIGHLIGHTS

Average processing time per batch run reduced by 55 percent, from 12 hours 45 minutes to 5 hours 45 minutes
Required person-hours reduced by 90 percent, from 150 hours to 15 hours
Batches showed comparable attributes, including drug and adjuvant content, cell purity, and interferon gamma secretion (a measure of T cell activation)
ASGCT RESEARCH-USE-ONLY (RUO) SYSTEM DATA HIGHLIGHTS

RUO system demonstrated robust CRISPR-Cas9 editing in unactivated human T cells, and efficient delivery and expression of mRNA to unactivated T and NK cells
The gentle nature of the RUO system’s intracellular delivery mechanism resulted in limited impact to T cells. Unactivated T cells retained their unactivated phenotype and demonstrated similar activation and expansion compared to untreated samples
In contrast, electroporation of unactivated T cells resulted in spontaneous increases in pro-inflammatory cytokine transcripts and secretion, independent of TCR engagement
ASGCT HEMATOPOIETIC STEM CELL (HSC) DATA HIGHLIGHTS

Cell Squeeze technology efficiently delivered mRNA and RNPs into HSCs; 90 percent of HSCs expressed transferred mRNA, and high editing rates were achieved using B2M and CCR5 targeting RNPs
HSC phenotype was maintained following Cell Squeeze treatment compared to controls as determined by microarray analysis, CFC assay, and NBSGW mouse engraftment study
Cell Squeeze treated HSCs could be transferred immediately following treatment, and demonstrated superior engraftment versus electroporation
R&D INVESTOR EVENT DETAILS

The company will host a live R&D Investor event with optional virtual participation on Thursday, May 19, 2022, beginning at 4:05 p.m. ET. Onsite and virtual participants can register in advance by completing the registration form on the event website: View Source Following the event, a webcast replay will be made available on the company’s investor website: investors.sqzbiotech.com.

ASGCT PRESENTATION TITLES AND TIMING

SQZ Point-of-Care Manufacturing Presentation
Title: A Decentralized and Integrated Manufacturing System for the Rapid and Cost-Effective Production of Cell Therapy Drug Products
SQZ Presenter: Maisam Dadgar
Session Title: Cell Therapy Product Engineering, Development or Manufacturing
Abstract Number: 1171
Date & Time: Wednesday, May 18, 2022, from 5:30-6:30 PM

STEMCELL TECHNOLOGIES Immune Cell Engineering Poster Presentation
Title: A New Benchtop System for Simple and Versatile Introduction of Macromolecules into Human Lymphocytes by Microfluidic Squeezing
STEMCELL Presenter: Eric Ouellet, Ph.D.
Session Title: Synthetic/Molecular Conjugates and Physical Methods for Delivery II
Abstract Number: 997
Date & Time: Wednesday, May 18, 2022, from 5:30-6:30 PM

SQZ Hematopoietic Stem Cell Research Presentation
Title: Rapid, Gentle, and Scalable Engineering of Hematopoietic Stem Cells Using Vector-Free Microfluidic Cell Squeeze Technology
SQZ Presenter: Murillo Silva, Ph.D.
Session Title: Cell Therapy Product Engineering, Development or Manufacturing
Abstract Number: 1176
Date & Time: Wednesday, May 18, 2022, from 5:30-6:30 PM