Autoimmune diseases occur as a result of the immune system attacking the body’s own organs, tissues, and cells. They impact over 23 million in the US alone with the cost to the healthcare system exceeding $100bn annually. Further, approximately 4% of the world’s population suffer of the disease. Some of the more common autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes.
While considerable progress has been made in treating autoimmune diseases, significant unmet need remains due to insufficient response rates, drug resistance and unfavourable therapeutic index with current treatment options. New approaches to treat autoimmune diseases are urgently required to help millions of patients currently suffering.
Rebalancing the immune system without switching off immunity altogether is the ultimate goal of immunotherapy and is yet to be optimally achieved by any existing therapeutic approach to date. Mysthera’s first-in-class approach, via PIM kinase inhibition, is designed to achieve this balance.
Proviral Integration of melony murine leukemia virus (PIM) kinases belong to a family of serine/threonine kinases with three members, PIM1, PIM2 and PIM3 with greatly similar sequence and function. While PIM expression is generally low in healthy tissue, high expression is specifically induced in immune cell during inflammation. At a site of persistent inflammation PIM is involved in the pathogenic T and B cell effector responses and immune escalation.
Mysthera combines the therapeutic potency of an oral kinase inhibitor with target mediated specificity focussing the drug effect to the accelerating pathogenic adaptive immune response. By sparing patient’s immune homeostasis, this therapeutic approach may offer significantly enhanced tolerability for patients versus currently available therapeutics. Furthermore, the anti-inflammatory multi-lineage effect of Mysthera’s approach directly answers to the pathophysiological complexity of the autoimmune disease with high unmet medical need.
Tertiary Lymphoid Structures
Tertiary lymphoid structures (TLS) are ectopic, vascularized hubs of lymphocyte interaction and activation that arise in tissues during chronic inflammation. The interaction of activated T and B cell via CD40L-CD40 and STAT3 signalling cytokines are central elements in the initiation of these structures frequently found in many autoimmune diseases, including lupus nephritis, rheumatoid arthritis and inflammatory bowel disease. Their presence is typically associated with disease severity and progression. In the autoimmunity field it is envisioned that the disruption of these hubs of autoreactive lymphocyte activation can curtail autoimmune disease progression.
PIM kinases plays a significant role in key pathways of TLS formation offering a novel approach to successfully address the unmet needs in complex autoimmune diseases.
PIM Kinase Program
Mysthera is developing a portfolio of small molecule, orally available, pan-PIM kinase inhibitors, licensed from Inflection Biosciences Ltd. The molecules have been rationally designed to offer favourable drug like properties, high potency and best in class selectivity. The company is uniquely profiling its PIM kinase inhibitors for use in chronic autoimmune disease. On-going de-risking and benchmarking is aimed at nominating the best clinical candidate to take forward into IND enabling studies.