At Artax Biopharma our objective is to develop therapies that allow lasting and specific responses against T-cell mediated inflammatory and autoimmune diseases. Our science focuses on the interaction between T-cell Receptors (TCR) and Nck, a cytoplasmic adapter protein that plays a role in T-cell activation.
Selective compounds targeting the adaptor protein Nck and modulating TCR signaling
Once TCR is activated, it undergoes a conformational change that results in the recruitment of different proteins, including Nck, constituting the “TCR signalosome,” which is responsible for signal transduction and cell activation. As a result, the TCR conformational change is stabilized and TCR activation is efficiently transmitted. Scientific evidence points to Nck recruitment as a fundamental early step in TCR signaling, representing a target to modulate the immune response selectively.
Artax compounds are effective on a EAE MOG induced model
Spinal cord & Cerebellum
CNS infiltration analysis in a EAE model after animal sacrifice. A massive infiltration of blood vessels and neural parenchyma by CD4+ T cells and macrophages was detected in the cerebellum and spinal cord of the vehicle group, but not of the AX-024–treated group
Neurological score & Weight loss
AX-024 has a therapeutic effect in the MS model, starting administration after disease onset on day 13, once the symptoms of neurological impairment (clinical score, ?2) and weight loss were already evident. Fingolimod was also included as a positive control. Both treated groups rapidly recovered from neurological symptoms and gained weight. However, upon drug discontinuation, neurological symptoms and weight loss began worsening in the fingolimod group while the AX-024–treated mice maintained low clinical scores and kept gaining weight.
T cell polaritzation conditions
Differentiation of naïve CD4+ T cells toward effector T cells not only depends on the presence of polarizing cytokines and their receptors but also on the signal strength of the TCR. To test this idea, we explored the effect of AX-024 on the differentiation of naïve human CD4+ T cells to effector cells in polarizing media favoring differentiation toward TH1, TH2, TH17, or Tregs. As a result AX-024 inhibited the differentiation of human CD4+ T cells toward TH1-, TH2 and TH17 while increased differentiation towards Treg (regulatory T cell).