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Nck modulators, a new class of agents aimed at stopping self-reaction without causing immunosuppression

Targeted modulation of T cell receptor (TCR) activation forms the core of everything we do at Artax Biopharma. We develop candidates that act to inhibit Nck binding to the TCR, preventing inappropriate activation by self-antigens — and therefore resulting in immunomodulation without causing immunosuppression.

  • Without AX-158
  • With AX-158
Without AX-158
With AX-158

T cell mediated autoimmune diseases: a large and still unmet medical need

A healthy immune system eliminates harmful foreign pathogens, while being tolerant of self-tissues and organs. The T cell receptor (or TCR) is central to healthy T cell function and a well-functioning immune system. When the immune system malfunctions and the TCR becomes dysregulated, T cells behave abnormally, attacking a patient’s own tissues and organs. This results in autoimmune diseases in which TCRs with higher affinity to self-antigens drive T cell activation and cytokine production.

Nck is an adaptor protein which plays a direct role in T cell mediated diseases. Nck directly amplifies TCR responses and reduces the dysregulated TCR signaling which contributes to T cell mediated diseases.

Introducing Nck modulators, a new way to reset the immune system for healthy responses

Artax Biopharma is developing first-in-class, oral small molecules that inhibit Nck binding to the TCR. Through this novel mechanism, Artax’s Nck inhibitors selectively modulate Nck’s amplification of the TCR, resulting in a lower T cell activation and less T cell response. Our novel approach with Nck modulation has the goals of assisting the immune system to maintain healthy control, thereby eliminating a direct cause of T cell mediated diseases, while not impacting patients’ ability to fight foreign pathogens properly. We believe this process of resetting the body’s immune response holds great therapeutic and commercial potential across a wide range of T cell mediated autoimmune diseases.

Тreating autoimmune diseases: stopping self-reaction without causing immunosuppression

Current therapeutic approaches attempt to reduce the immune response by targeting specific cytokine pathways. Unfortunately, this can lead to immunosuppression, thereby increasing the risk of serious infections and malignancy, especially given the long-term use. Instead of suppressing the response after it has been triggered, we believe the solution lies in modulating the activation as it happens at the T cell receptor. This ensures that only strong signals from foreign antigens can trigger an immune response.

Suppress responses

Generalized inhibition of several immune pathways (e.g. cyclosporine)

Specific suppression

Targeted inhibition of specific immune pathways (e.g. TNF-alpha inhibitors)

  • Modulation
  • Suppression
Modulation
AX-158 modulates 

IL-2 expression
Suppression
PP2 (Lck inhibitor)
suppresses IL-2 expression

Strong preclinical results, with the potential to treat a wide spectrum of autoimmune diseases

Artax Biopharma is developing first-in-class, oral small molecules that modulate Nck binding to the TCR. Through this novel mechanism, Artax’s drug candidates selectively inhibit Nck’s amplification of the TCR signaling, resulting in modulated T cell activation and responses.

This novel approach is aimed at maintaining healthy immune responses and eliminating a direct cause of T cell mediated diseases, while not impacting patients’ ability to fight foreign pathogens properly. We believe this process of restoring the body’s healthy immune response through Nck modulation holds great therapeutic and commercial potential across many T cell mediated autoimmune diseases.