SQZ Biotechnologies Announces Generation of Dopaminergic Neurons from Human Pluripotent Stem Cells Through Single-Step Delivery of Six Cell-Fate Encoding RNAs

Rhea-AI Summary

SQZ Biotechnologies (NYSE: SQZ) presented promising preclinical research demonstrating its Cell Squeeze® technology's ability to generate dopaminergic neurons from human-induced pluripotent stem cells (iPSCs). This was achieved through the delivery of six RNA transcription factors, enhancing gene expression significantly—by up to 25,000-fold for the FOXA2 gene within four days. The findings are part of the company's NIH-funded program aimed at developing scalable therapies for Parkinson's disease. The results were showcased at the 2022 ISSCR annual meeting, indicating a step forward in regenerative medicine.

Positive

• Demonstrated ability to generate dopaminergic neurons from iPSCs using Cell Squeeze® technology.
• Achieved a 25,000-fold increase in expression of the FOXA2 gene within four days.
• Aligned with NIH-funded efforts to develop cell replacement therapies for Parkinson's disease.

Negative

• None.

Pre-Clinical Research Could Lead to Rapid Development of Dopamine-Producing Neurons; Part of Company’s NIH-Funded Program Seeking Scalable Cell Replacement Therapy Approaches for Parkinson’s Disease

Use of Non-Viral, Self-Amplifying RNA Enhanced and Lengthened Transcription Factor Expression, Driving the Signaling Required for Dopamine-Producing Neuron Development

Findings Presented at 2022 International Society for Stem Cell Research Annual Meeting

WATERTOWN, Mass.--(BUSINESS WIRE)-- SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, presented preclinical regenerative medicine data showing that the company’s proprietary Cell Squeeze^® technology can effectively generate dopaminergic (DA) neurons from human-induced pluripotent stem cells (iPSCs) through the single-step delivery of six RNA that encode for specific fate-determining transcription factors. The inclusion of non-viral, self-amplifying RNA in particular was shown to enhance and lengthen transcription factor expression and support DA neuron development. The new findings build upon the company’s recent regenerative medicine research presentations and are aligned with the company’s NIH-funded effort to generate cell replacement therapies for neurodegenerative conditions like Parkinson’s disease. The research was presented at the 2022 International Society for Stem Cell Research (ISSCR) annual meeting.

“Effective cell replacement therapies for diseases including Parkinson’s disease could have significant benefit for patients,” said Jonathan Gilbert, Ph.D., Vice President and Head of Exploratory Research at SQZ Biotechnologies. “Our early preclinical work demonstrates that a single-step delivery of six RNA into iPSCs using the Cell Squeeze^® platform can effectively generate dopaminergic neurons. Our continued development of these cell engineering capabilities could potentially enable the creation of future cell replacement therapies.”

While other methods of differentiating iPSCs into specific cell types may often include a lengthy and variable process, the non-viral Cell Squeeze^® technology is designed to generate reprogrammed cells through the delivery of fate-determining transcription factors while preserving cell health and limiting adverse effects on baseline gene expression. Cell Squeeze^® technology may also allow for control of the timing, intensity, and combination of transcription factor expression to generate high-quality and functional cell products.

Major Findings from Cell Reprogramming Research Presented at ISSCR:

• Generation of Dopaminergic Neurons: By combining and delivering Ascl1 saRNA, a key neuronal transcription factor, with five mRNA transcription factors, SQZ scientists were able to differentiate iPSCs into dopaminergic neurons
  
  
• Significant Increase in Target Gene Expression: A single Cell Squeeze^® delivery of saRNA and mRNA transcription factors into human iPSCs induced a 25,000-fold increase in the expression of the FOXA2 gene, a key marker for dopaminergic neurons, in four days
  
  
• Appearance of Dopaminergic Lineage Markers: After 14 days, the cells expressed dopamine neuronal marker TH and mature neuronal marker MAP2, demonstrating the generation of dopaminergic neurons
  
  
• Preservation of Cell Health: Findings verified that 24 hours after processing the iPSCs through a SQZ^® chip, there was no significant difference in the expression of 32 common housekeeping genes as well as no meaningful disruption in pluripotent stem cell marker gene and protein expression

Together, these data show the potential of the Cell Squeeze^® technology to reprogram cells for regenerative medicine applications, including Parkinson’s disease.

ISSCR Poster Presentation Details

Title: Directed Differentiation of Dopaminergic Neurons from Human Induced Pluripotent Stem Cells through Microfluidic Cell Squeeze^® Delivery of Multiple mRNA Encoding Transcription Factors
Poster Board Number: 756
Poster Session: Poster Session 1 Even; Wednesday, June 15, 2022, 7:30 PM – 8:30 PM PST

About SQZ Biotechnologies

SQZ Biotechnologies Company is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies for patients around the world. The company has active programs in oncology, autoimmune and infectious diseases, as well as additional exploratory initiatives to support future pipeline growth. SQZ’s proprietary Cell Squeeze^® technology can deliver multiple biological materials into many cell types, offering the ability to engineer a broad range of potential therapeutics. With clinical production timelines already under 24 hours, the company has the potential to enable broader patient accessibility through point-of-care manufacturing implementation across multiple therapeutic programs. Our approach could also improve a patient’s treatment journey with no planned hospitalization or preconditioning treatment. The company’s first therapeutic efforts seek to generate target-specific immune responses, both through activation for the treatment of solid tumors and infectious diseases, and by immune tolerance for the treatment of 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, 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 strategic collaborators; 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 most recent 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 we undertake 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220616005145/en/

Media Contact:

Erin Phelps

erin.phelps@sqzbiotech.com

857-760-0920



Investor Contact:

Mike Kaiser

michael.kaiser@sqzbiotech.com

857-760-0398

Source: SQZ Biotechnologies Company

FAQ

What did SQZ Biotechnologies present at the ISSCR 2022 annual meeting?

SQZ Biotechnologies presented preclinical research on generating dopaminergic neurons from human-induced pluripotent stem cells using their Cell Squeeze® technology.

How does SQZ Biotechnologies' Cell Squeeze® technology work?

Cell Squeeze® technology delivers six RNA transcription factors into iPSCs in a single step, enhancing the production of dopaminergic neurons.

What is the significance of the 25,000-fold increase in FOXA2 gene expression?

This significant increase indicates the effectiveness of the technology in inducing targeted gene expression necessary for dopaminergic neuron development.

How is this research related to Parkinson's disease?

The research aims to contribute to scalable cell replacement therapies for Parkinson's disease, part of SQZ's NIH-funded initiatives.