Wilson Therapeutics

Wilson Therapeutics AB
Private Company
Industry Pharmaceutical Industry
Founded 2012
Headquarters Stockholm, Sweden
Products Choline tetrathiomolybdate; Bis(-choline) tetrathiomolybdate; ATN-224; WTX101
Website www.wilsontherapeutics.com

Wilson Therapeutics is a privately held biopharmaceutical company focused on developing novel treatments for Wilson's disease, a rare genetic disease that affects approximately 1 in 15,000.[1] Wilson Therapeutics was founded in 2012 by HealthCap, one of the leading European life science venture capital funds.[2] In April 2014, Wilson Therapeutics announced that it had closed a $40 million Series B financing co-led by new investors, Abingworth LLP and MVM Life Science Partners LLP. HealthCap, also participated in the round. The funds will be used to advance the clinical development of WTX101.[3][4] Wilson Therapeutics’ lead compound, WTX101 (previously called ATN-224), is the proprietary bis-choline salt of tetrathiomolybdate. Tetrathiomolybdate is a novel de-coppering agent, meaning it reduces the body’s level of copper with high affinity and selectivity for copper. Tetrathiomolybdate has been tested in several clinical trials in Wilson's disease where it has been shown to rapidly lower copper levels, stabilizing neurological function with a reduced risk of neurological deterioration after initiation of treatment in Wilson’s disease patients with neurological disease. WTX101 has been granted orphan drug designation for the treatment of Wilson's disease in both Europe and the United States[5]

Clinical trial results and studies in progress

As of 2014, tetrathiomolybdate had been tested in over 500 patients for up to seven years, primarily in oncology[6][7][8][9][10][11][12][13][14][15] and Wilson's disease,[16][17][18][19] as well as some other clinical pathologies.[20][21]

Two noteworthy trends are supported by the data collected from these initial studies. Firstly, TTM more rapidly lowers copper levels than previously studied de-coppering agents. Secondly, the initial neurological deterioration frequently observed with de-coppering agents is noted in fewer Wilson disease patients when they are treated with TTM.[22][23][24]

As of November 2014, a Phase 2, multi-centre, open-label, study is recruiting newly diagnosed Wilson disease patients 18 and older to evaluate the efficacy and safety of bis-choline tetrathiomolybdate (WTX101) administration over a 24-week period.[25][26]

References

  1. ↑ Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. 2007. "Wilson's disease." Lancet 369:397-408.
  2. ↑ "Wilson Therapeutics" Life Science Sweden. April 17, 2014.
  3. ↑ "Wilson Therapeutics Raises $40M Series B to Rid Body of Excess Copper" Private Equity and Venture Capital Dow Jones. April 16, 2014.
  4. ↑ "Venture Capitalists support new approach to pain" MedNous Opportunities in European Medical Innovation. 8(5):19. May 2014
  5. ↑ U.S. Food and Drug Administration Orphan Drug Designations and Approvals
  6. ↑ Berenson JR, Boccia RV, Bashey A, Levine AM, Koc ON, Callahan JA, Mazar AP, Reich SD, 2006. "Phase I Study of the [Cu, Zn] Superoxide Dismutase (SOD1) Inhibitor ATN-224 (Bis-Choline Tetrathiomolybdate) in Patients with Advanced Hematologic Malignancies. Presentation at the Amer Soc Hematol 2006 Annual Meeting". Blood 108: Abstract 2593.
  7. ↑ Brewer GJ, Dick RD, Grover DK, LeClaire V, Tseng M, Wicha M, Pienta K, Redman BG, Jahan T, Sondak VK, Strawderman M, LeCarpentier G, Merajver SD, 2000. "Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: Phase I study". Clin Cancer Res 6: 1-10.
  8. ↑ Gartner EM, Griffith KA, Pan Q, Brewer GJ, Henja GF, Merajver SD, Zalupski MM, 2009. "A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer". Invest New Drugs 27: 159-165.
  9. ↑ Henry NL, Dunn R, Merjaver S, Pan Q, Pienta KJ, Brewer G, Smith DC, 2006. "Phase II trial of copper depletion with tetrathiomolybdate as an antiangiogenesis strategy in patients with hormone-refractory prostate cancer". Oncology 71: 168-175.
  10. ↑ Jain S, Cohen J, Ward MM, Kornhauser N, Chuang E, Cigler T, Moore A, Donovan D, Lam C, Cobham MV, Schneider S, Hurtado Rua SM, Benkert S, Mathijsen Greenwood C, Zelkowitz R, Warren JD, Lane ME, Mittal V, Rafii S, Vahdat LT, 2013. "Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse". Annals of Oncology.
  11. ↑ Lin J, Zahurak M, Beer TM, Ryan CJ, Wilding G, Mathew P, Morris M, Callahan JA, Gordon G, Reich SD, Carducci MA, Antonarakis ES, 2011. "A non-comparative randomized phase II study of 2 doses of ATN-224, a copper/zinc superoxide dismutase inhibitor, in patients with biochemically recurrent hormone-naive prostate cancer". Urologic oncology.
  12. ↑ Lowndes SA, Adams A, Timms A, Fisher N, Smythe J, Watt SM, Joel S, Donate F, Hayward C, Reich S, Middleton M, Mazar A, Harris AL, 2008. "Phase I study of copper-binding agent ATN-224 in patients with advanced solid tumors". Clin Cancer Res 14: 7526-7534.
  13. ↑ Pass HI, Brewer GJ, Dick R, Carbone M, Merajver S, 2008. "A phase II trial of tetrathiomolybdate after surgery for malignant mesothelioma: final results". Ann Thorac Surg 86: 383-389; discussion 390.
  14. ↑ Redman BG, Esper P, Pan Q, Dunn RL, Hussain HK, Chenevert T, Brewer GJ, Merajver SD, 2003. "Phase II trial of tetrathiomolybdate in patients with advanced kidney cancer". Clin Cancer Res 9: 1666-1672.
  15. ↑ Schneider BJ, Lee JS, Hayman JA, Chang AC, Orringer MB, Pickens A, Pan CC, Merajver SD, Urba SG, 2012. "Pre-operative chemoradiation followed by post-operative adjuvant therapy with tetrathiomolybdate, a novel copper chelator, for patients with resectable esophageal cancer". Invest New Drugs.
  16. ↑ Roberts EA, Schilsky L, 2008. "Diagnosis and Treatment of Wilson Disease: An Update." "AASDL Clinical Practice Guidelines in Wilson Disease." Hepatology 47,6:2089-2111.
  17. ↑ Brewer GJ, Askari F, Dick RB, Sitterly J, Fink JK, Carlson M, Kluin KJ, Lorincz MT, 2009. "Treatment of Wilson's disease with tetrathiomolybdate: V. Control of free copper by tetrathiomolybdate and a comparison with trientine". Translational Research 154: 70-77.
  18. ↑ Brewer GJ, Askari F, Lorincz, MT, Carlson M, Schilsky M, Kluin KJ, Hedera P, Moretti P, Fink JK, Tankanow R, Dick RB, Sitterly J, 2006. "Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease". Arch Neurol 63: 521-527.
  19. ↑ Brewer GJ, Hedera P, Kluin KJ, Carlson M, Askari F, Dick RB, Sitterly J, Fink JK, 2003. "Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy". Arch Neurol 60: 379-385.
  20. ↑ Askari F, Innis D, Dick RB, Hou G, Marrero J, Greenson J, Brewer GJ, 2010. "Treatment of primary biliary cirrhosis with tetrathiomolybdate: results of a double-blind trial." Translational Research 155: 123-130.
  21. ↑ Vine AK, Brewer GJ, 2002. "Tetrathiomolybdate as an antiangiogenesis therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration". Trans Am Ophthalmol Soc 100: 73-76; discussion 76-77.
  22. ↑ Brewer GJ, Askari F, Dick RB, Sitterly J, Fink JK, Carlson M, Kluin KJ, Lorincz MT, 2009. "Treatment of Wilson's disease with tetrathiomolybdate: V. Control of free copper by tetrathiomolybdate and a comparison with trientine". Translational Research 154: 70-77.
  23. ↑ Brewer GJ, Askari F, Lorincz MT, Carlson M, Schilsky M, Kluin KJ, Hedera P, Moretti P, Fink JK, Tankanow R, Dick RB, Sitterly J, 2006. "Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease". Arch Neurol 63: 521-527.
  24. ↑ Brewer GJ, Hedera P, Kluin KJ, Carlson M, Askari F, Dick RB, Sitterly J, Fink JK, 2003. "Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy". Arch Neurol 60: 379-385.
  25. ↑ "Efficacy and Safety Study of WTX101 in Adult Wilson Disease Patients". January 14, 2015.
  26. ↑ "Wilson Disease Clinical Trials"."Phase 2 Study in Newly Diagnosed Wilson Disease Patients with WTX101 (Tetrathiomolybdate)".
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