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Syntrix Receives $1.725M Grant to Conduct a Phase II Clinical Trial for the treatment of Psoriasis with (L/D)-Aminopterin

Congratulations to Syntrix scientists on their new grant for $1.725M from the National Institute of Allergy and Infectious Disease (NIAID) of the National Institutes of Health (NIH).  The project title is “Efficacy and Resistance Mechanisms of (L/D)-Aminopterin in Psoriasis.”  Here is the public health relevance from the proposal:  “Psoriasis is a chronic scaly and inflammatory skin disorder that affects 1-3% of the world’s population.  Current treatments often involve the use of methotrexate (MTX), which is not effective in many patients or causes side effects, or exceedingly expensive biologic therapies that can cost $20,000 to $30,000 per year.  This proposal aims to develop a drug, (L/D)-aminopterin, that is better than MTX and less expensive than biologics.  Also, we aim to carry out studies that we hope will tell us how drugs like MTX and LD-aminopterin fail in patients.”

Abstract from the proposal:  Psoriasis is a chronic, genetically influenced, remitting and relapsing scaly and inflammatory skin disorder that affects 1-3% of the world’s population, resulting in total annual costs of $5.2 billion in the United States in 2012.  Approximately 20% of patients with moderate-to-severe chronic plaque psoriasis require phototherapy and/or a variety of systemic treatments, where methotrexate (MTX) is the mostly widely used oral systemic agent.  Despite the relative effectiveness of MTX, as a monotherapy, it does not achieve greater than a 75% reduction in the baseline psoriasis area-and-severity index (PASI 75) in 40% of patients, and fails to achieve remission (i.e. > PASI 90) in 60% of patients.  Furthermore, up to 30% of patients with moderate-to-severe plaque psoriasis discontinue oral MTX primarily because of intolerance to the drug.  While much effort has been directed to identifying the mechanism behind poor and/or toxic responses to MTX based on genetic factor and quantitation of its active metabolites, the majority of MTX failures remain unexplained.  Given the efficacy and safety limitations of MTX and the cost of biologics compared to MTX (~$20,000 vs. $300 per year), there is a clear market opportunity for an improved antifolate with better efficacy and/or safety than MTX, but that is priced between MTX and biologics.  (L/D)-Aminopterin (L/D-AMT) is a patented composition developed by Syntrix Biosystems that studies indicate has greater cellular uptake (i.e. polyglutamylation to the active metabolites) than MTX, and less liver and CNS toxicity, properties that may translate into better efficacy and/or safety.  In addition to identifying L/D-AMT as a potential improvement on MTX, gaining a mechanistic understanding of antifolate resistance in general has important clinical implications for treating inflammation with L/D-AMT or MTX, by possibly identifying clinical biomarkers to predict optimal response or risk of toxicity in advance of initiating treatment. This U44 Fast-Track proposal aims to advance L/D-AMT to the clinic by testing L/D-AMT for efficacy in a placebo-controlled phase 2 trial and advancing a novel hypothesis-driven mechanistic explanation for antifolate resistance.

Read about (L/D)-Aminopterin in our pipeline.