Therapy Areas: Infectious Diseases
First Autoimmune Disease Indication for Tolerizing Antigen Carrier Platform IND filing for Celiac Disease Anticipated in 3Q22
13 September 2021 - - The first clinical translation of US-based cell therapies specialist SQZ Biotechnologies' (NYSE: SQZ) Tolerizing Antigen Carrier platform in autoimmune diseases will be for celiac disease, a chronic autoimmune disorder that afflicts millions of patients and has no approved drug treatment, the company said.

The company anticipates an IND filing in 3Q22.

In preclinical models, SQZ TACs have demonstrated the ability to induce multi-mechanism antigen-specific tolerance relevant to many immune mediated disorders.

The company's celiac disease program may support expansion into additional autoimmune diseases.

SQZ TACs leverage the body's natural mechanisms of red blood cell clearance and antigen presentation to induce immune tolerance.

TACs are derived from patient RBCs and are designed to carry disease-specific antigen cargos to specialized immune cells that are capable of inducing tolerance through multiple mechanisms.

Earlier this year, the company presented preclinical findings at the Antigen-Specific Immune Tolerance Digital Summit and the Federation of Clinical Immunology Societies demonstrating that its engineered TACs can drive antigen-specific immune tolerance in complex models of autoimmune disease.

SQZ TACs were shown to delete antigen-specific T cells, without causing broad immune suppression.

Importantly, SQZ TACs also increased antigen-specific regulatory T cells (Tregs) that exerted potent bystander suppression, showing the ability to suppress pathogenic T cells with different autoantigen specificities.

The company will leverage its rapid manufacturing system for the development of SQZ TACs.

Earlier this year, the company presented clinical trial findings at the American Society of Clinical Oncology demonstrating the clinical feasibility of its manufacturing system.

In the Phase 1 trial of the company's APC therapeutic candidate for HPV positive tumors, patient batches of the investigational cell therapy were produced in less than 24 hours.

The flexibility and scalability of the company's manufacturing system allows it to be used for both the TAC and Oncology platforms despite different cell types and antigen cargos.

SQZ TAC therapeutic candidates are also expected to be compatible with potential future point of care implementations.

Celiac disease is a chronic autoimmune disorder that occurs in genetically predisposed people.

The disease is triggered by eating foods containing gluten, which is found in wheat, barley, and rye. Disease symptoms can include abdominal pain, diarrhea, nausea, vomiting, and other common signs.

When gluten is ingested the body mounts an immune response that attacks and damages the villi that line the small intestine, which can impact nutrient absorption.

Many people who have celiac disease have not been diagnosed,4 however population-based studies indicate that the disease affects about 2m people in the United States and approximately 1% of the population worldwide, with regional differences.

There is currently no approved drug treatment and patients must therefore maintain a gluten-free diet, which involves strict, lifelong avoidance of exposure to gluten proteins.

Long-term complications of celiac disease may include malnutrition, accelerated osteoporosis, nervous system problems and issues related to reproduction.

Rare complications can include cancer of the small intestine, cirrhosis, and non-Hodgkin lymphoma.

SQZ TACs are a red blood cell-derived cell therapy platform being developed as an antigen-specific immune tolerance approach for autoimmune diseases.

The platform is designed to leverage the natural process of RBC clearance by professional antigen presenting cells in the lymphoid organs.

This physiological mechanism is tolerogenic by default, instructing the immune system not to mount an attack.

SQZ TACs are generated by squeezing RBCs with disease-specific antigens and are made to appear aged. SQZ TACs are designed to be rapidly engulfed by professional APCs and to act as a "Trojan horse" to present antigens in a non-inflammatory context, inducing tolerization of the patient's T cells against the specific target.

Preclinical data has demonstrated deletion and anergy of antigen-specific T cells as well as induction of disease specific Tregs capable of bystander suppression.

SQZ Biotechnologies company is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies for patients around the world and has active programs in Oncology, Autoimmune and Infectious Diseases, as well as additional exploratory initiatives to support future pipeline growth.

The company's proprietary Cell Squeeze technology offers the unique ability to deliver multiple biological materials into many cell types to engineer what we believe can be a broad range of potential therapeutics.

With demonstrated production timelines under 24 hours and the opportunity to eliminate preconditioning and lengthy hospital stays, our approach could significantly broaden the therapeutic range and accessibility of cell therapies.

The company's first therapeutic applications seek to generate target-specific immune responses, both in activation for the treatment of solid tumors and infectious diseases, and in immune tolerance for the treatment of unwanted immune reactions and autoimmune diseases.


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