Mast Therapeutics Changes Its Name In Hopes Of A Fresh Start

Formerly called Adventrx, the company says the name Mast better reflects its current strategy, which includes a focus on a Phase III asset for sickle cell disease. With a new name and a late-stage trial underway, management is hoping to persuade skeptical investors to take a second look.

It has been a long road for Adventrx Pharmaceuticals, which went public in 2000 and has weathered its share of drug development failures since. But the company is looking to turn the page on the past. It has new management, a new lead asset, and as of March 11, a new name, Mast Therapeutics Inc.

The new moniker is derived from the Molecular Adhesion and Sealant Technology (MAST) platform on which the company’s lead program is based. The name better reflects the company’s current focus, developing the poloxamer MST-188 in multiple indications starting with sickle cell disease, CEO Brian Culley said in an interview. But the company is also hoping the new name will inspire investors to look at the company anew.

The current company isn’t even a distant relation to its former incarnation, when it focused on the development of reformulated chemotherapeutics. As Adventrx, the firm was forced to reinvent itself after its Phase III chemo-enhancer CoFactor failed in a Phase III trial in late 2007 and FDA refused to file a second drug, Exelbine, in 2008 (Also see "Troubled Biotechs: Adventrx, EntreMed, Peregrine, Anesiva" - Pink Sheet, 6 Jan, 2009.). The company had slashed its workforce from 55 to just two by 2010 and had ceased almost all business operations. Culley, who worked for the company since 2004 and was previously chief business officer, was one of the two who stayed on and took over as CEO in February 2010.

“One of the reasons for changing the name was certainly to get people to look de novo, to look fresh, at the company,” Culley said. The company’s stock is trading below $1, a low entry point for a company that has a drug in Phase III development for a rare debilitating disease, given investor enthusiasm for orphan drugs (Also see "The Orphan Drug Boom: Gold Rush Or Flash In The Pan?" - In Vivo, 26 Nov, 2012.).

The company out-licensed or shelved its legacy chemotherapeutics and acquired the privately-held biotech SynthRx Inc. in April 2011 in a stock transaction, gaining the drug that is now MST-188 (Also see "AdventRx Showing Signs Of Life With SynthRx Acquisition, NDA For Exelbine" - Pink Sheet, 14 Feb, 2011.). It has completed several public financings and had $39.9 million in cash and equivalents at the end of September, the last time it reported. The company has also padded its management ranks, adding a chief financial officer, chief medical officer, head of development and commercial head. Its new board members include Ted Love, the former head of R&D at Onyx Pharmaceuticals Inc.

Ahead Of The Pack

Big pharmas such as Pfizer Inc. and Novartis AG are investing in the development of novel treatments for sickle cell disease through recent transactions, but the initiation of Mast’s pivotal Phase III trial for MST-188 in children with sickle cell disease catapults Mast into the lead with the most advanced drug in development.

The company announced the initiation of the EPIC study Jan. 30, enrolling 388 patients aged 8 to 17 who have sickle cell disease. The study is testing the effect of MST-188 on vaso-occlusive crisis, the painful episodes that characterize the disease and often lead to hospitalization. The primary endpoint of the placebo-controlled trial is reduction in duration of vaso-occlusive crisis measured from the time a subject is randomized to the time they receive the last dose of parenteral opioid analgesic prior to hospital discharge. Secondary endpoints will evaluate re-hospitalization rate and occurrence of acute chest syndrome within 120 hours of randomization.

Mast expects data will be available in 2015 and serve as the basis for a regulatory filing.

Sickle cell disease is an inherited disorder that affects the red blood cells, which are normally round and flexible and easily able to travel through the blood vessels. But in patients with the disease, the red blood cells can be rigid and concave in shape, and can get stuck in the blood vessels, depriving the body of vital oxygen it needs, causing pain and potentially organ damage. The disease is estimated to affect about 100,000 people in the U.S., primarily people of African descent.

MST-188 is a rheologic and antithrombotic agent that is believed to work in sickle cell disease through an anti-adhesive approach by lowering the viscosity of the blood. The company believes it has promise in other areas as well like acute limb ischemia and potentially significantly larger indications including stroke. Earlier this year, Mast announced plans to initiate a Phase II trial in acute limb ischemia, a complication of peripheral arterial disease, as an add-on to thrombolytics by the end of the year – as long as FDA agrees on the plan. While acute limb ischemia is a niche area, successful clinical results in that indication could pave the way for expansion into significantly larger indications such as stroke.

A Dated Drug

But MST-188 is a drug with a long history dating back to the 1990s, and investors may want to see some tangible evidence of efficacy – namely positive late-stage clinical data – before getting behind the Mast story. Failed attempts by multiple previous owners to bring MST-188 to market in indications ranging from myocardial infarction to sickle cell disease may well be tainting investors’ impressions.

The drug was originally developed under a partnership between CytRx Corp. and Glaxo Wellcome (now GlaxoSmithKline PLC) for myocardial infarction, but Glaxo terminated its license for the drug in 1995 after a safety signal arose.

CytRx reformulated it into a purified version that eliminated the impurities it said led to the safety issue. The company then initiated a Phase III trial studying it in sickle cell disease (Also see "CytRx' purified RheothRxpf for sickle cell crisis awaiting FDA Phase III trial green light." - Pink Sheet, 23 Sep, 1996.). That trial missed its primary endpoint – decrease in the length of vaso-occlusive crisis – for the study population as a whole, but did show a statistically significant benefit in patients 15 and younger. At the time the data appeared in late 1999, CytRx said the trial design was flawed and decided to seek a partner for further development rather than finance additional studies.

Eventually, in October 2003, CytRx licensed rights to the drug to Synthrx, a start-up that never got together the financing to run additional studies.

A statistically significant efficacy result in either sickle cell disease or acute limb ischemia could make MST-188 an attractive partnering asset. Partnering is a key strategy for Mast, not only for the financial resources, but for validation, according to Culley. The company might initially consider a regional deal for a territory outside the U.S., he said. But, he added, “If the economics make sense I’m not going to be shy or reluctant about doing a deal that includes the U.S.”