We all are searching for a universal way to treat autoimmune disease: an oral to address a wide range of autoimmune diseases, without causing the immune suppression that drives so many unwanted side effects, and while still preserving the body’s normal immune responses.
A new approach to autoimmune treatments
Artax Biopharma is developing first-in-class treatments for autoimmune diseases aimed at achieving just that. Rather than suppressing or blocking the immune response, our approach focuses on modulating activation at the T cell receptor. This prevents self-activation without causing immune suppression. Targeted modulation of the T-cell receptor (TCR) activation forms the core of everything we do at Artax Biopharma. We develop medicines that act to specifically modulate Nck recruitment upon TCR activation, preventing inappropriate activation by self-antigens — and therefore resulting in immunomodulation without causing immunosuppression.
Modulating Nck: unique opportunity in T cell mediated diseases
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 several T cell mediated diseases, including autoimmune diseases in which TCRs with higher affinity to self-antigens drives 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 the dysregulated TCR signaling which contributes to T cell mediated diseases.
At Artax Biopharma we are developing first-in-class, oral small molecules that modulate Nck binding to the TCR. We believe this process of immunomodulation – during which our candidate medicines assist the immune system to maintain healthy control and eliminate a direct cause of T cell mediated diseases while not impacting patients’ ability to properly fight foreign pathogens – holds great potential.
Our lead Nck modulator candidate, AX-158, is currently being evaluated in psoriasis patients and represents the pioneering drug in the novel class of Nck modulators. AX-158, a small molecule oral drug candidate, has demonstrated a well-established tolerability profile and holds promise for addressing a wide spectrum of autoimmune diseases.
Convincing data package for AX-158
On our journey towards generating first patient data, we built a convincing data package demonstrating the mode of action, activity, and tolerability of AX-158. Our first-in-class Nck modulator has shown strong cytokine modulation of healthy donor PBMC’s following TCR stimulation as well as modulation of mixed lymphocyte reaction responses. We saw therapeutic efficacy in murine models of self-antigen activation (EAE), with a prolonged pharmacodynamic effect in EAE, suggesting durable immune modulation. There was discrimination of neo-antigen and self-antigen in an immune/oncology model as well as a lack of immunosuppression supported by data in models of strong antigen stimulation, which was very exciting for us to see.
We were highly encouraged by observations of efficacy in dermal models of immune activation, as well in multiple other models in T cell mediated autoimmune diseases, supporting the potentially broad application of Nck modulators. We have seen strong preclinical evidence of activity in the Th2, Th17, Th1/Th0 pathways, suggesting that applications could be quite broad across the autoimmune space.
Phase 1 work with AX-158 in healthy volunteers showed good tolerability of single and multiple doses at all dose levels tested, with no serious adverse or related events. Bioavailability was excellent, showing a consistent and predictable PK profile.
Patient data with first-in-class Nck modulator AX-158 coming soon
Our randomized, placebo-controlled Phase 2a proof-of-concept trial in psoriasis patients is currently underway in the UK, with a preliminary data readout anticipated in Q4 2024. This trial will provide multiple insights into the mechanism of our Nck modulator approach and also inform our further clinical work with AX-158 and other molecules in the portfolio. We intend to initiate a Phase 2 trial in atopic dermatitis in centers in the US with AX-158 later this year.
Soon we will know how close our efforts have brought us to finding a successful new approach to autoimmune treatments. And we are just getting started.
