Ardea seeks $144.5M in public offering as it advances PhIII oral gout drug
This article was originally published in Scrip
Ardea BioSciences, a biotech focused on small molecule therapeutics for serious diseases is seeking $144.5 million before expenses from a public offering of 8.5 million shares at $17 per share, a 7% discount to its closing price on 1 February when the company proposed the offering..
Ardea was not running short of cash: its liquid assets were valued at about $96 million as of 31 December.
The most advanced candidate of the San Diego, California-based company is lesinurad (formerly RDEA594) which is in Phase III testing for chronic treatment of gout. The drug is a once-daily oral inhibitor of URAT1, a transporter in the kidney that regulates uric acid excretion from the body. The product’s mechanism is complementary to the mechanism of allopurinol (the standard of care for the disease).
Lesinurad has been shown to normalise the amount of uric acid excreted by gout patients. Ardea states in its prospectus that since the majority of gout patients are "under-excreters", normalising uric acid excretion by moderating URAT1 transporter activity with lesinurad may provide the most physiologically appropriate means of reducing serum uric acid (sUA) levels. In addition, because increasing the excretion of sUA is additive to the efforts of urate-lowering therapies that decease the production of uric acid, such as allopurinol and febuxostat (Takeda's Uloric), the company claims that lesinurad in combination with such drugs has the potential to treat the significant portion of the gout population that is not adequately treated with existing therapies.
Ardea is developing lesinurad to be used in combination with allopurinol to treat the large numbers of patients who do not reach target sUA levels taking allopurinol alone (defined as achieving sUA levels of less than 6mg/dL, the medically recommended target), and in combination with febuxostat in patients with tophaceous gout, a condition characterised by the presence of disfiguring deposits of uric acid crystals in and around the joints.
The company began the first of four planned Phase III trials in December 2011, and said that the entire Phase III programme is expected to involve about 2,000 gout patients at sites around the world.
In November 2011, Ardea had presented data at the 2011 annual meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals in Chicago showing that, in the ongoing extension period of a Phase IIb study (Study 203) of lesinurad, there were sustained reductions in sUA levels, with 90% of patients on combination therapy with allopurinol at week 44 reaching the target of sUA of less than 6ml/dL.
The company is also developing lesinurad to be used as monotherapy for those patients who are intolerant to either allopurinol or febuxostat.
Ardea has in development a next-generation URAT1 inhibitor, RDEA3170, and it claims that based on preclinical results, the candidate demonstrates many of the same positive attributes as lesinurad, but with greater potency against the URAT1 transporter.
Aside from the gout therapy, the company can point to early-stage development of BAY 86-9766 (formerly known as RDEA119), a potent and specific inhibitor of mitogen-activated ERK kinase (MEK) for the treatment of cancer being developed by Bayer Healthcare under a global licence agreement (scripintelligence.com, 13 January 2011). BAY 86-9766 is currently in a Phase II study in patients with hepatocellular carcinoma in combination with sorafenib (Bayer and Onyx' Nexavar) and a Phase I/II study in patients with advanced pancreatic cancer in combination with gemcitabine.
The offering is underwritten by Jefferies & Co, Cowen & Co, Lazard Capital Markets, Leerink Swann, Oppenheimer & Co, and Wells Fargo Securities.
There are other novel oral gout treatments in development, including BioCryst's candidate BCX4208, which recently cleared a Phase IIb hurdle; it has shown a significant improvement in patients reaching the treatment goal of sUA levels of less than 6mg/dL when given in combination with allopurinol, compared to patients receiving allopurinol alone (scripintelligence.com, 6 October 2011).