Torque Announces the Presentation of Preclinical Data for Deep IL-15 Primed T Cells Demonstrating Superior T Cell Expansion, Persistence, and Safety Compared with Systemically Administered IL-15

CAMBRIDGE, Mass., October 1, 2018— Torque, an immuno-oncology company developing first-in-class Deep Primed™ T Cell Therapeutics to direct immune power deep within the tumor microenvironment, announced today preclinical data demonstrating superior T cell expansion, persistence, and safety for the company’s Deep IL-15 Primed T cells compared to systemically administered IL-15. The data were presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference taking place September 30-October 3, 2018 in New York, NY.

Torque is developing a new class of Deep-Primed™ cellular immunotherapy designed to overcome the key challenges limiting broad use of cellular therapy in oncology, including the capability to target tumors that express multiple heterogeneous antigens, the ability to overcome the immunosuppressive microenvironment that shuts down T-cell function, and the need for outpatient treatment with a high margin of safety. Torque uses its Deep-Priming technology to develop multi-targeted, antigen-primed T cells that carry surface-anchored immune-stimulatory drugs to drive a full immune response within the tumor microenvironment against tumors with heterogenous antigens. In contrast to other classes of cellular immunotherapy, Deep Priming does not require genetic engineering and enables outpatient treatment and repeat dosing.

“To date, clinical use of IL-15—a potent cytokine that expands and activates tumor-killing CD8+ T cells—has been limited in cancer therapy due to immunotoxicity, primarily from the expansion of NK cells in systemic circulation,” said Thomas Andresen, PhD, Chief Scientific Officer of Torque. “In this preclinical study, our data demonstrated that Deep IL-15 Primed T cells drive a fundamentally different immune activation dynamic compared to systemic IL-15—increasing activation and expansion of cytotoxic CD8+ T cells within the tumor microenvironment, without the expansion of NK cells in the systemic circulation. Our preclinical studies are the foundation for Torque’s first clinical trials of Deep IL-15 Primed multi-target T cells that will begin within the next few months.”

Highlights of the preclinical presentation follow, and a copy of the poster is available for download on the Torque website: https://bit.ly/2FZtPOW

Poster A188: “T cell priming with Deep™ IL-15 improves preclinical safety compared to systemic IL-15, and increases in vivo persistence and activity”
Presenter: Elena Geretti, PhD, Torque
Key findings from the study:

• Anchoring Deep IL-15 to T cells prior to adoptive cell transfer (ACT) increased persistence and expansion of ACT in circulation and at the tumor site, and improved anti-tumor activity compared to ACT alone
• Deep IL-15 anchored to ACT compared to soluble, systemically administered IL-15 with ACT:
  • Increased expansion and persistence of CD8+ T cells in circulation and intratumorally
  • Resulted in dramatically lower systemic exposure to IL-15
  • Did not induce systemic cytokine release
  • Did not increase bystander circulating neutrophils or lymphocytes and, in particular, NK cells that are associated with the immunotoxicity of systemic IL-15
  • Did not cause body weight loss and resulted in histopathology findings of lower severity across multiple organs

About Deep-Primed™ Immune Cell Therapeutics
Torque’s Deep-Priming platform uses advanced cell process engineering to:

• prime and activate T cells to target multiple tumor antigens and
• tether immune-stimulatory drugs to the surface of these multi-target T cells to direct immune activation in the tumor microenvironment
• using a proprietary technology platform, without genetic engineering, for a high margin of safety.

Deep-Primed T cells both target multiple tumor antigens and pharmacologically activate an immune response with anchored cytokines. This process does not require genetic engineering of the T cells and so preserves the natural T cell receptor for delivering a regulated immune response, with the potential for a high margin of safety. In addition to antigen priming, immunomodulators are tethered to the surface of Deep-Primed T cells—initially IL-15 and IL-12 cytokines, and TLR agonists—that activate both innate and adaptive immunity. Administering these immunomodulators systemically to a patient can cause lethal toxicity by activating immune cells throughout the body. By loading precise doses of cytokines onto the surface of T cells, Deep Priming focuses the immune response to target the tumor, without systemic exposure.

In hematologic cancers, this new class of immune cell therapeutics has the potential to improve on the initial success of single-target CAR T therapeutics with expanded efficacy and also move cell therapy treatment out of the hospital with a high margin of safety. For solid tumors, Deep-Primed T cells have the potential to enable efficacy against tumors with heterogeneous antigens protected by hostile microenvironments, which are not readily addressable with the first generation of immune cell therapies.

About Torque (www.torquetx.com)
Torque is an immuno-oncology company developing Deep Primed™ T cell therapeutics to direct immune power deep within the tumor microenvironment. Torque’s lead product candidate is Deep IL-15, which is in pre-IND development for hematologic and solid tumors. The company is based in Cambridge, Massachusetts.