Indication(s): Multiple sclerosis; other autoimmune/inflammatory disorders, incl. atherosclerosis

Modality: Small-molecule prodrug that targets the IL-6/STAT3 signaling pathway

Stage of Development: Extensive in vitro and in vivo efficacy (3 MS models, incl. relapsing-remitting EAE); preliminary safety

Patent Status: Pat. no. 11,420,946 (US); appl. 17/821,286 (US); appl. 18860926.7 (EP); appl. 3,077,053 (CA); background IP (T2009-002): Pat. no. 8,883,749 (US)

THE UNMET NEED

Current MS treatments typically employ broad immunosuppression rather than targeting specific pathways, resulting in significant side effects and inadequate responses in many patients. The IL-6/STAT3 pathway is critical for balancing inflammatory T effector cells and protective regulatory T cells. In MS patients, dysregulation of this pathway is well-documented, with increased IL-6 receptor expression and STAT3 phosphorylation correlating with disease activity. Moreover, the STAT3 inhibitor market remains largely untapped with only one approved medication (Goltimod) available as of 2025.

THE PROPOSED SOLUTION

LLL12b directly targets the STAT3 signaling pathway central to MS pathogenesis. This prodrug inhibits STAT3 phosphorylation, blocking IL-6/STAT3 signaling by suppressing pathogenic Th17 cells and promoting regulatory T cells. This targeted approach corrects immune imbalance without broad suppression. The prodrug improves bioavailability and efficacy over the parent compound. LLL12b shows efficacy in human MS cells by inhibiting STAT3 phosphorylation, reducing inflammation, and boosting regulatory T cells, supporting clinical potential.

APPLICATIONS

• Treatment of relapsing-remitting MS: Potential first-line or add-on therapy for RRMS patients with active disease
• Treatment of progressive MS forms: Potential therapy for progressive MS forms where effective treatments are limited
• Treatment of other autoimmune disorders: Potential application in other STAT3-mediated inflammatory conditions like rheumatoid arthritis, psoriasis, and inflammatory bowel disease

ADVANTAGES

• Dual MoA: Suppresses pathogenic Th17 responses while enhancing protective regulatory T cell function, addressing the fundamental immune imbalance in MS
• Targeted approach: Inhibits the STAT3 pathway rather than causing broad immunosuppression, potentially reducing side effects vs. current therapies
• Translational potential: Demonstrates efficacy in human cells from MS patients, providing strong evidence for clinical translatability