Our Approach
Nck modulation to stop self-reaction without immunosuppression
Targeted modulation of Signal 1 activation forms the core of everything we do at Artax Biopharma.
Signal 1 is the universal requirement for T cell activation. We develop candidates that inhibit Nck binding to the TCR, preventing inappropriate activation by self-antigens—resulting in immunomodulation without causing immunosuppression. This truly novel mechanism has the potential to be effective across the spectrum of Th-mediated autoimmune diseases.
In pre-clinical models, our Nck-directed therapeutics are highly differentiated from other approaches to Signal 1. AX-158 demonstrates broad modulation of T helper cell (Th2, Th1, Th17) cytokine production yet leaves required markers of Tregs (e.g. CD69) intact. Uniquely, Nck is both at the headwaters of the Signal 1 cascade and serves as a modulator of activation.
- Without AX-158
- With AX-158
Without AX-158
With AX-158
Signal 1 Activation
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. Signal 1 is central to healthy T cell function and a well-functioning immune system. When the immune system malfunctions and the T cell receptor (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 plays a direct role in T cell mediated diseases by amplifying the Signal 1 pathway. Through selectively modulating Nck, Artax’s approach resets the immune response, helping restore normal T cell activity without compromising the ability to fight harmful pathogens.
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 modulators selectively block Nck’s amplification of the TCR, resulting in reduced T cell activation and response.
Our novel approach with Nck modulation aims to assist the immune system in maintaining healthy control and function, thereby eliminating a direct cause of T cell mediated diseases, without immune suppression. 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)
Modulation
Targeted TCR calibration without immunosuppression (Novel class of Nck modulators)
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
Compelling clinical results, with the potential to treat a wide spectrum of autoimmune diseases
Artax Biopharma is developing first-in-class, oral small molecules that inhibit Nck binding to the TCR. Through this novel mechanism, Artax’s Nck modulators selectively block Nck’s amplification of Signal 1, resulting in reduced T cell activation and response.
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. The positive results from our Phase 2a study with lead program AX-158 in psoriasis patients underscore the promise of this completely novel mechanism for treating autoimmune diseases.