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SCIENCE

THE AUTOIMMUNITY CHALLENGE

Autoimmunity is an everyday burden
people carry for life.

A lifetime of treatment, follow-up visits and tests
Serious risks due to immunosuppression under therapy
Potential for multiple autoimmunities to present
Significant toll on mental health and financial well-being
Symptomatic treatments have no significant impact on lifelong disease burden

Immunosuppressive drugs treat inflammation, not the root cause of disease

Autoimmune diseases occur when the immune system mistakenly attacks the body’s own cells, leading to chronic inflammation. Immunosuppressive drugs (including steroids, cytotoxic agents, and biologics) reduce this inflammation by limiting immune cell activity or blocking inflammatory signals. This helps relieve symptoms, decrease tissue damage, and sometimes induce temporary remission. However, these treatments generally do not correct the underlying immune malfunction that triggers autoimmunity. As a result, the disease itself is not cured and regular maintenance therapy is required to control symptoms.

MECHANISM OF ACTION

Kv1.3 dependency is fundamental biology in T cell autoimmunity

Autoreactive T cells are Kv1.3 dependent

Kv1.3 and KCa3.1 are redundant potassium ion channels required for the activation and proliferation of T cells

Chronic stimulation by autoantigens induces a Kv1.3-dependent phenotype in autoreactive T cells – KCa3.1 expression drops, the redundant function is lost – the autoreactive T cells is sensitive to Kv1.3 blockade

Normal T cells are not affected by Kv1.3 blockers due to potassium channel redundancy

Autoreactive T cells are irreversibly disrupted by Kv1.3 blockers due to their Kv1.3 dependency

Kv1.3 targeted therapy eliminates autoreactive T cells and maintains full immune system functionality

The Voltage Gated Potassium Channel Kv1.3 plays a Key Role in Numerous Indications

T cells play a cardinal role in the human immune response system. Auto- or alloantigenic recognition or mutations can provoke undesirable immune responses that lead to autoimmune diseases. In such autoimmune diseases a T cell subset called effector memory T cells (T_EM) escapes the control of the immune system and destroy the body’s own tissues.

Therapeutic down-regulation of the complete T cell system eases harmful immune response, yet disrupts the protective immune response network. Therefore, it is desirable to focus on T_EM cell subsets to maintain the overall protective immune response.

Autoreactive T_EM cells become exclusively dependent on the potassium channel Kv1.3 for maintained activation and proliferation. Kv1.3 dependency is unique to these cells and Kv1.3 is therefore regarded as an ideal target for selective and specific deactivation of autoreactive T_EM cells.

selectION’s si-544 peptide blocks the Kv1.3 channel with high affinity and specificity. This irreversibly disrupts the signaling pathway necessary for maintaining T_EM cell activation and proliferation. Short si-544 exposure terminates the pathogenic activation and proliferation cascade of the autoreactive, disease-associated T_EM cell clone, while leaving the remaining immune system untouched.

selectION si-544

Mastering Kv1.3: si-544

Disease modifying therapy: si-544 eliminates selectively autoreactive T cells, the root cause of autoimmunity

si-544 is the first safe and effective Kv1.3 blocker that saturates Kv1.3 and deactivates only disease-causing T cell clones, while maintaining patients immunocompetence

Selective inhibition of Kv1.3 by si-544 disrupts the activation and proliferation of autoreactive T cells, promotes antigen-specific regulatory T cell-responses, and enhances checkpoint expression (e.g., PD-1)

Integrated rational drug design and multiple-epitope structure optimization for an exhaustive study of affinity and selectivity driving molecular features

si-544: best-in-class Kv1.3 channel blocker

The Company’s lead candidate, si-544, is a potent and highly specific immuno-selective agent addressing a significant unmet medical need by functionally inhibiting and eliminating disease-specific, chronically activated T_EM cells.

si-544 has demonstrated an excellent safety and tolerability profile in two completed Phase 1b clinical trials in atopic dermatitis patients and, more recently, in psoriasis vulgaris. An initial efficacy signal has been observed in the atopic dermatitis data set. Clinical proof of concept has been achieved in the larger psoriasis vulgaris trial.

CLINICAL TRIALS