Wilson Therapeutics AB
Wilson Therapeutics AB (Wilson Tx) is a privately-held biopharmaceutical company focused on improving the lives of patients with Wilson Disease (WD) through development of new treatment options and support for increased awareness and education about WD. The Company’s lead product candidate, WTX101, a novel de-coppering agent, is currently in clinical development. Wilson Tx is a Swedish based company founded in 2012 by venture capital firm HealthCap.
Wilson Disease is a rare autosomal recessive disorder caused by mutations in the ATP7B gene resulting in deficient production of the copper (Cu) transporter Adenosine Triphosphatase 2 (ATPase2), which in turn lead to impaired incorporation of Cu into ceruloplasmin as well as impaired biliary excretion of Cu. Consequently, there is an increase of Cu in liver, brain, and other tissues. Beyond the capacity of metallothionein to bind and buffer Cu, the excessive amount of intracellular free Cu triggers pro-oxidant properties leading to organ damage and dysfunction. The overall prevalence of WD is estimated at 1-2 in 30,000, corresponding to approximately 25,000 – 50,000 individuals in the EU and US combined. The clinical presentation of WD typically occurs in adolescence to early adulthood. Initial signs and symptoms of WD are hepatic (~40%), neurological (~40%) or psychiatric (~20%) although patients often develop combined hepatic and neuropsychiatric symptoms. Untreated or inadequately treated patients have progressive morbidity, and mortality is usually secondary to hepatic cirrhosis.
The treatment goals in WD are to reduce Cu to normal levels and then maintaining these levels. The current treatments available for WD are chelator therapies which non-specifically chelate Cu and promote urinary Cu excretion. In addition, zinc, which blocks dietary uptake of Cu, is used mainly as a maintenance treatment. Currently available therapies need approximately 6-12 months to control the Cu levels. Control of symptoms can take significantly longer. Disease control in patients with neurological symptoms at their WD diagnosis is areas of particular concern as up to 50 % of patients treated for their WD have residual neurological symptoms despite years of therapy on a de-coppering agent. Also, worsening of neurological symptoms can also occur on initiation of treatment in as many as 25% of patients. Around 50% of these patients who deteriorate never improve and stay worse. Currently available drugs also have high rates of treatment discontinuation due to adverse events. They also need to be dosed 2-4 times per day and must be taken in the fasted state. Their adverse event profiles and complicated dosing regimens leads to poor treatment compliance and high rates of treatment failure a major concern in a disease that requires life-long treatment such as WD.
Wilson Therapeutics’ lead compound WTX101 is the proprietary bis-choline salt of tetrathiomolybdate (TTM), which has been evaluated for various indications in clinical studies involving over 500 patients. WTX101 has received orphan drug designation in both the United States and the European Union. Through its unique mechanism of action by which is forms stable tripartite complexes with Cu and proteins, WTX101 has been shown to rapidly control Cu levels in approx. 4-6 weeks in patients with Wilson Disease. Previous data also suggest that WTX101 may stabilize neurological function and reduce the risk of neurological deterioration after initiation of treatment in Wilson Disease patients with neurological involvement. WTX101 has been shown to lower and maintain copper levels with once or twice daily oral dosing.