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CAMBRIDGE, Mass., November 12, 2018鈥� Torque, an immuno-oncology company developing first-in-class Deep Primed鈩� T Cell Therapeutics to direct immune power deep within the tumor microenvironment, announced today the presentation of new preclinical data for its lead Deep IL-15 Primed T Cell and Deep Il-12 Primed T Cell therapeutics programs as well as for the company鈥檚 proprietary Slipstream鈩� process for manufacturing these first-in-class, multi-target cellular immunotherapies. The data were presented at the Society for Immunotherapy of Cancer鈥檚 (SITC) 33rd Annual Meeting, November 7鈥�11, 2018 in Washington, D.C.

Torque is developing a new class of Deep-Primed鈩� 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.

鈥淭hese studies demonstrate the potential for the Deep-Primed technology platform to create a new class of multi-target T cell therapy that targets tumor antigens with specificity, with integrated and coordinated cytokine activation,鈥� said Thomas Andresen, PhD, Chief Scientific Officer of Torque. 鈥淭hese preclinical studies are the foundation for Torque鈥檚 first clinical trials for Deep IL-15 Primed multi-target T cells that will begin soon, and for the Deep IL-12 program that we are now preparing to move into clinical trials in 2019.鈥�

Highlights of the four preclinical presentations follow, and copies of the posters are available for download on the Torque website:

Poster #P226: 鈥淒eep鈩� IL-15 primed multi-targeted T cells demonstrate potent antigen-specific cytotoxic activity against human cancer cells鈥�

Presenter: Shawn Carey, PhD, Torque

Key findings from the study:

• Tumor-directed T cells generated using Torque鈥檚 modular tumor-associated antigen (TAA)-priming approach elicit potent and antigen-specific cytotoxicity against human solid tumor cells expressing multiple TAAs.
• Deep IL-15 enhances the potency of anti-cancer cell activity by increasing antigen-specific cytotoxicity at low CD8 effector:target cell ratios and increases the persistence and depth of this tumor cell killing.
• By acting as a prolonged cell-tethered source of autocrine IL-15, Deep IL-15 enhances T cell survival and proliferation.

Poster #P227: 鈥�Tethering IL-12 to the surface of T cells induces broad immune activation and potent anti-tumor activity in mice without inducing systemic toxicities鈥�

Presenter: De-Kuan Chang, PhD, Torque

Key findings from the study:

Tethering IL-12 to the immune cell surface using Deep IL-12 dramatically improves the efficacy of tumor-targeted cell therapy, while mitigating toxicities associated with systemic IL-12:

• Deep IL-12 Primed T Cells demonstrated superior tumor-killing efficacy and anti-tumor T cell activity in the tumor microenvironment compared with systemically administered IL-12.
• Deep IL-12 Primed T cells demonstrated superior efficacy compared to systemically administered IL-12, including increased survival, increased T cell expansion and activation in the tumor microenvironment, and low systemic exposure, with no observed systemic toxicity.

Poster #P215: 鈥�Preclinical evaluation of Deep鈩� IL-15 Primed PMEL cells demonstrates highly improved safety compared to systemic administration of IL-15鈥�

Presenter: Philip Bardwell, PhD, Torque

Key findings from the study:

• When compared to systemic IL-15, Deep IL-15 tethered to PMEL cells had lower levels of IL-15 in serum, lower interferon gamma (IFN-y) release, and no lymphopenia.
• Deep IL-15 Primed T Cells demonstrated superior safety compared with systemically administered IL-15. Specifically, Deep IL-15 Primed T Cells:
• were well tolerated, with no overt toxicity findings
• did not expand endogenous cells, while systemic IL-15 did increase endogenous lymphocytes
• had significantly lower levels of IL-15 and lower IFN-y release in the blood
• resulted in minimal histopathological changes

Poster #P272: 鈥淎 fully-closed, high-efficiency manufacturing technology platform for the production of T cell therapies targeting multiple tumor antigens鈥�

Presenter: Jonas Bruun, PhD, Torque

Key findings from the study:

Torque鈥檚 Deep-Primed鈩� cell therapy platform uses novel cell process engineering to generate multi-targeted T cells that recognize multiple tumor antigens with Deep IL-15 tethered to their surface. Torque鈥檚 Slipstream鈩� cell engineering process is semi-automated and fully closed, and its modular automation design enables both large-scale and decentralized manufacturing.

• Slipstream manufacturing produces high-purity, tumor antigen-reactive T cells with Deep IL-15 loading that drives survival, expansion, and reactivity of the multi-target T cells.

About Deep-Primed鈩� Immune Cell Therapeutics

Torque鈥檚 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鈥攊nitially IL-15 and IL-12 cytokines, and TLR agonists鈥攖hat 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 ()

Torque is an immuno-oncology company developing Deep Primed鈩� T cell therapeutics to direct immune power deep within the tumor microenvironment. Torque鈥檚 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.