Next-generation ACT

ACT at a glance

Immatics is committed to developing its ACTengine® programs with the goal of delivering the potential benefits of its innovative science to cancer patients as soon as possible. At the same time, in order to achieve the best outcomes for cancer patients in the longer term, Immatics strives to enhance the tolerability, potency and ease of use of its product candidates. To accomplish these goals, Immatics has taken the following steps:

Immatics is actively investigating multiple next-generation strategies to enhance the potency of ACT product candidates to combat solid tumors. For the success of immunotherapies in solid tumors, the complex tumor microenvironment is regarded as one of the biggest challenges. Immatics believes that targeting stroma targets (such as COL6A3 exon 6 in IMA204), as well as Immatics’ next-generation enhancement technologies to generate more potent T cells, may address this unmet need.

Aside from improving commercially compatible manufacturing of autologous ACT, Immatics aims to decrease the cost of goods and to reach patients more quickly with its off-the-shelf cell therapy, ACTallo®.

As part of its next-generation strategy Immatics is pursuing a stepwise approach towards highly personalized multi-TCR-T therapy designed to combat target heterogeneity and tumor escape for deeper and longer clinical responses.

Immatics believes that its pool of more than 200 prioritized targets combined with the capability to develop the right TCRs offers a possibly unique foundation to develop treatments for almost any patient in an efficient and cost-effective manner.

Off-the-shelf Adoptive Cell Therapy

ACTallo® is Immatics’ proprietary allogeneic, off-the-shelf adoptive cell therapy platform based on gamma delta T cells sourced from healthy donors.

We believe that gamma delta T cells are well suited for an off-the-shelf cell therapy approach, because gamma delta T cells:

are abundant in the peripheral blood

show intrinsic anti-tumor activity

naturally infiltrate solid tumors & correlate with favorable prognosis

are HLA-independent, thus do not cause graft-vs-host disease in allogeneic setting

can be expanded to high numbers in a cGMP-compatible manner

can be effectively redirected using αβ TCR or CAR constructs

Our manufacturing process is designed to create hundreds of doses from one single donor leukapheresis. The ACTallo® process engineers gamma delta T cells with chimeric antigen receptors (CARs) or T cell receptors (TCRs), thus accessing cancer cell surface targets as well as intracellular proteins that are presented as peptides on the surface of the cancer cell. This enables the redirection of gamma delta T cells to cancer cell targets. ACTallo® products will be available for patient treatment without the requirement for personalized manufacturing. Since these T cells originate from healthy individuals, they are not reliant on the potentially encumbered immune system of the cancer patient.

Tumor Stroma

The rigid stroma and the immunosuppressive microenvironment of solid tumors pose a significant challenge for T cell accessibility and activity. Targeting this compartment could provide a novel approach for the treatment of many solid tumors either as single attack or as part of a multi-TCT-T concept. Immatics’ fourth ACTengine® program IMA204 is directed against COL6A3 exon 6, a novel tumor stroma target identified and validated by Immatics’ XPRESIDENT® technology platform. COL6A3 exon 6 is highly expressed in the stroma of a variety of solid tumors. Thus, IMA204 is designed to disrupt the tumor’s protective microenvironment in order to make a therapeutic impact.