SQZ Biotech IPO’d in November with a $350 million+/- market cap on the basis of a new technology called Cell Squeeze®. What we can observe about this company in the present is limited to a very short history and is mostly anecdotal and risky. The company and the science is a good example of how the time period between scientific curiosity and engineered scaling is narrowing. There is something in this company’s story capable of producing extreme outcomes based on a simple new innovation in cell therapy that could become one of the essential “picks and shovels” for its own products and also for a wide variety of other companies innovating in the rapidly emerging reaction pot called synthetic biology.
The company is currently developing cell therapies for cancer, infectious diseases, and other serious conditions. Its most advanced platform, SQZ Antigen Presenting Cells (SQZ APC), is currently in a Phase 1 trial in HPV+ tumors, with initial data expected in the 2H21. The aim is to develop monotherapies and, in combination with other immuno-oncology agents, treatment for HPV16+ advanced or metastatic solid tumors, including cervical, head-and-neck, anal, penile, vulvar and vaginal cancer. The SQZ APC for oncology, one of three current platforms, is being developed as part of a collaboration with Roche in a relationship that started in SQZ’s very early stages in 2015 when (I assume) strong pre-clinical data emerged.
SQZ’s three current platforms are designed to activate immune cells against the target antigens and drive killing of specific diseased cells, while in contrast, the SQZ TAC platform is designed to tolerize against the target antigen. Each platform has demonstrated robust activity across antigens, and antigen selection is a defining factor for each individual product.
The Watertown, MA-based company announced in January that the first patient in its Phase 1 clinical trial of SQZ-PBMC-HPV received their first dose. SQZ-PBMC-HPV is an autologous cell therapy candidate comprised of SQZ-engineered antigen presenting cells (APCs) designed to induce CD8 T cell responses against HPV16. The doses for the patient were manufactured in under 24 hours, leveraging SQZ’s novel technology and rapid manufacturing process. The first dose was administered to the patient while additional doses are cryopreserved and available on-demand. This marks the first patient dosed with a cell therapy candidate developed from SQZ’s proprietary Cell Squeeze® cell engineering technology – a milestone for the company.
Notes from video: The company mostly uses red blood cells to impart therapeutic benefit. The throughput is indicated at more than ten billion per minute.
Simple novelty plus scalability – this is what SQZ is all about.
SQZ Technology
Generating cell therapy candidates with Cell Squeeze® is simple, as illustrated below: the technology physically squeeze cells at high speeds through a microfluidic constriction to temporarily disrupt the cell membrane and enable the target cargo to enter directly into the cytosol. Cell Squeeze® is able to process over 10 billion patient cells per minute at current clinical scale and introduce virtually any cargo of interest into any cell type to create what the company believe to be an unprecedented range of potential therapeutics. This unique technology and its products are covered by 25 patent families.
To date, the company has leveraged Cell Squeeze® to build three cell therapy platforms that it is applying to multiple therapeutic areas. These platforms are designed to modulate the immune system in a target-specific manner with initial applications in oncology, infectious disease and immune disorders. The company’s platforms are designed to be able to manufacture product candidates in under 24 hours and administered without any pre-conditioning and without any planned hospitalization, creating what the company believe is a more streamlined, accessible patient experience and a lower burden on the health system, from a time and cost perspective.
<<Do natural voltage gradients in cells (not just neurons) regulate cell behavior and gene expression in ways that undermine electroporation? One way to think about the interworkings of a living being is to look at each cell membrane as a computational surface that interacts with its surroundings (ie. other cells and perturbations) to orchestrate homeostasis. Existing cell therapies, including electrical, chemical and viral agents, miss the mark because of incompatibility with the computational surface. To wit: maybe it was always about the hardware.>>
I have not witnessed the company’s CEO, Dr. Sharei, wade too deep into the limp theater of saucy TAM porn (regulations limit TAM discussions too). Instead, the company’s potential is easy enough to surmise given a little knowledge about the limitations of current cell therapies that have been afflicted with the subvirus of failure. I’ve seen this quality before in other early-stage companies where serendipity tempers expectations and moderates the evil forces of bravado. It is possible that Dr. Sharei and SQZ Biotech have opened up a new frontier of space – the intracellular space – mediated by this company’s novel membrane-disruption-based techniques.
Gene Editing
Cell Squeeze® could solve the problem of intracellular delivery of gene editing components and gene editing complexes to target cells. SQZ believes the delivery of gene editing components, e.g., protein, ribonucleic acid (RNA), and deoxyribonucleic acid (DNA), by mechanical disruption of cell membranes improves gene editing. The technology provides a mechanism to engineer target cells without the use of potentially harmful viral vectors or electric fields. The scalability and relative simplicity of the process make it suitable for broad adoption. The strategy and methods are suitable for genome engineering applications in research and therapeutics.
Source: SQZ Biotechnologies Company
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