Revolutionizing the Treatment of Solid Tumors

What Makes SynKIR™ Uniquely Effective

SynKIR™ is a CAR T cell therapy that uses a novel KIR-CAR platform technology to transform the treatment of solid tumors via a nature-inspired multichain receptor.

Designed to Decouple when at rest

The independent binding and signal chains are designed to separate tumor binding from T cell activation and demonstrate long-term T cell function.

… AND COUPLE WHEN TUMOR IS ENGAGED

The dual binding and signal chains are designed to come together to form a single receptor complex when bound to a tumor target. Dual chain signaling provides prolonged T cell activation even in challenging solid-tumor environments.

Inspired by Nature.
Engineered to Perfection.

Natural Switch Design for Solid Tumors

The KIR-CAR platform (SynKIR™) is the first CAR T cell therapy with long-term T cell functionality. Its naturally-inspired unique structure designed to couple and decouple to allow T cells to remain effective even under repeated tumor encounters in the harshest of solid tumor microenvironments.

Powerful Parallel Activation Pathway Independent of Costimulation

SynKIR™ uses a parallel DAP12 activation pathway, bypassing the high-traffic CD3-ζ pathway used by CAR and TCR T cell therapies. In preclinical in vivo studies, SynKIR™ T cells maintained activation and potent cytotoxic activities in solid tumors compared with the CD28 and 4-1BB co-stimulated CD3-ζ -based traditional CAR T cells. The DAP12 signal functions as both activation and co-stimulation for T cells, circumventing the CD3-ζ pathway to allow prolonged KIR-CAR function.

Long-term T Cell Function & Sustained Efficacy in Aggressive Tumor Models

Inspired by Natural Killer (NK) cell Killer Immunoglobulin-like Receptors (KIR), SynKIR™ provides a naturally-induced stimulation to T cells. This more natural signaling is designed to prolong KIR-CAR T cells’ efficacy period by coupling the receptor chains during activation and decoupling them during rest, avoiding T cell exhaustion. SynKIR™ has shown sustained efficacy in CAR T-resistant mouse models of mesothelioma and glioblastoma leading to complete tumor remissions.

Enhanced Surface Stability

KIR-CARs have shown long-term sustained receptor expression on both activated and resting T cell surfaces. This sustained KIR-CAR expression coincides with ongoing continued anti-tumor functions, even in demanding solid tumor microenvironments. As a result, KIR-CAR T cells have shown superior anti-tumor function including complete tumor eradications in mouse models where CD3-ζ-based CAR T have failed.

Best of Both Worlds

NK cells are known for their powerful innate activity against tumors, but are short-lived. T cells, on the other hand, have durable persistence, up to years or decades. SynKIR™ combines the power of NK cell KIR receptors with the long-term durability of T cells, resulting in a long-lasting and powerful anti-cancer efficacy in mouse models.

The Past Paradigm of CAR T

A traditional CAR consists of multiple parts combined into a single (mono-chain) protein. Different parts are borrowed from other proteins that do not normally combine in the body. This multi-part recombined unit is called the chimeric receptor.

A traditional CAR consists of a mono-chain protein, comprising an intracellular domain, a transmembrane domain, a spacer domain, and a targeting scFv portion.

A traditional CAR consists of a mono-chain protein, comprising an intracellular domain, a transmembrane domain, a spacer domain, and a targeting extracellular scFv portion. To date, seven CAR T therapies (all 2nd generation) have been approved using this mono-chain design, all for cancers originating from blood cells: Kymriah®, Yescarta®, Tecartus®, Breryanzi®, Abecma®, Carvykti®, and Carteyva®.

The KIR-CAR Paradigm Shift of CAR T

Verismo Therapeutics’ scientific founders recognized that the classic mono-chain CAR design could be improved with a dual-chain coupling/decoupling design that acts as a natural on/off switch.

Inspired by Natural Killer cell KIR receptors, the KIR-CAR platform provides a naturally evolved stimulation signal to T cells. This more natural signaling may increase T cells’ efficacy period by coupling the receptor chains for activation and decoupling them for rest, improving functional persistence and limiting exhaustion.

The Future of SynKIR™

SynKIR™ is eliminating solid tumors in models where traditional CAR T have failed. Learn more about how Verismo Therapeutics is transforming the treatment of solid tumors.

View our pipeline >