LMTX

Drug Overview

LMTX (leuco-methylthioninium), developed solely by TauRx Therapeutics, is an orally available tau aggregation inhibitor and the most advanced tau-based approach in the clinical pipeline. Alongside amyloid-beta, tau is one of the two proteins thought to be fundamental to the pathogenesis of Alzheimer’s disease, although it is greatly underrepresented in the clinical pipeline. In Alzheimer’s disease, intracellular tau tangles destroy nerve cells critical for memory, then the aggregation of tau spreads to other neuronal networks which face a similar fate. LMTX is believed to block the formation of tau oligomers and dissolve them into short truncated monomers. Once reduced to their constituent monomers, the truncated tau monomers become susceptible to proteases and can be cleared efficiently through the proteosomal clearance pathway.

Supported by private funding, including a $112m grant from Singapore gaming operator Genting, TauRx Therapeutics has initiated a large Phase III program for LMTX to evaluate its efficacy in the treatment of cognitive decline in mild to moderate Alzheimer’s disease. LMTX represents a follow-on product to rember, TauRx Therapeutics’ proof-of-concept tau aggregation inhibitor which was investigated in a Phase IIb study. The active ingredient of rember is methylthioninium chloride, a widely used histology dye (methylene blue). According to TauRx Therapeutics, LMTX is designed to have superior bioavailability and tolerability to rember

Analyst Outlook

While LMTX (leuco-methylthioninium; TauRx Therapeutics) failed to demonstrate a significant treatment benefit in mild to moderate Alzheimer’s disease patients when used predominantly as an add-on to the standard of care (SOC), an additional subgroup analysis revealed an efficacy signal in patients that are exclusively receiving LMTX as monotherapy. As an oral molecule with a differentiated mechanism potentially capable of halting and theoretically reversing the disease, LMTX has the potential to transform the Alzheimer’s disease treatment landscape as the first disease-modifying drug to reach the market. Mindful of the significant revenue potential LMTX may carry, TauRx was adamant it would present this dataset to the US Food and Drug Administration (FDA), despite the questionable findings. Comparing LMTX monotherapy to a pooled placebo group, and the lack of a benefit in patients that are on the SOC without any scientific rationale, however, will make the case particularly challenging.