Theravance Inc. said it will continue to advance its programs in gastrointestinal motility and infection into Phase III development, even though its big pharma collaborators declined to exercise their licensing options at this time.

London-based GlaxoSmithKline plc passed on TD-5108, a 5-HT4 agonist that has completed Phase II testing in chronic constipation, while Tokyo-based Astellas Inc. decided against licensing rights to TD-1792, an antibiotic that proved noninferior to vancomycin in a 200-patient Phase II study. Neither firm provided reasons for not opting in to the programs, but Theravance executives asked investors not to read too much into the decisions. "We're excited about the data" from both compounds, CEO Rick Winningham said during a conference call, adding that the news heralded "significant opportunities" for Theravance down the road.

Wall Street was not quite as optimistic, however, mostly on concerns of timing and cost. Shares of Theravance (NASDAQ:THRX) slid 10.6 percent Friday, dropping $3.37 to close at $28.38.

The company ended the second quarter with cash, cash equivalents and marketable securities totaling $150.6 million, not including a subsequent $25 million milestone payment from Astellas as part of the companies' ongoing telavancin collaboration, and has no immediate plans to raise additional funds, said Michael Aguiar, senior vice president and chief financial officer. Theravance has an upcoming end-of-Phase-II meeting with the FDA to determine how to proceed with a pivotal program for TD-5108 and is finishing up preclinical and early clinical testing of TD-1792, so Phase III trials wouldn't begin until 2008.

Aguiar also reminded analysts during the call that the company is awaiting other events that will affect its cash position, namely the approval of antibiotic telavancin in complicated skin and skin structure infections (cSSSI) - the PDUFA date is next month - and results from its ongoing Phase III study of telavancin in hospital-acquired pneumonia, expected before the end of the year.

"So a lot of these cards have yet to be played," he said. Those will "have to be overturned before we can make any final decisions."

Theravance will continue to scout out potential partnerships for those programs, since some sort of collaboration will be needed for marketing the drugs, but the company is willing to move into pivotal studies with or without a partner, Aguiar said. "We're comfortable with either scenario."

The company is developing TD-5108 for gastrointestinal motility disorders, such as chronic constipation, irritable bowel syndrome (IBS) with constipation, functional dyspepsia and delayed gastric emptying. Results from a 400-patient Phase II study showed that the drug met its primary endpoint of increased number of spontaneous bowel movements per week over baseline compared to placebo in chronic constipation. It also was found to be safe and well tolerated, and Theravance said that its specificity to the 5-HT4 receptor could help it avoid the potential link to cardiovascular risk that caused Basel, Switzerland-based Novartis AG to pull Zelnorm (tegaserod maleate), another drug targeting 5-HT4, off the market in March.

TD-5108 was one of several programs included in South San Francisco-based Theravance's 2004 collaboration with GSK. To date, the pharma firm has licensed rights to a long-acting muscarinic antagonist in development for asthma and chronic obstructive pulmonary disorder, and retains options for discovery programs in hypertension, neuropathic pain and opioid-induced bowel dysfunction. That alliance continues to remain intact, despite GSK's decision on TD-5108 and its decision two months ago not to exercise its option to purchase 50 percent of Theravance's outstanding stock. (See BioWorld Today, July 3, 2007.)

The same holds true for its 2005 partnership with Astellas, which offered the Japanese firm an option to TD-1792 as part of the worldwide collaboration for telavancin. TD-1792 is an antibiotic that has shown promise in cSSSI, and also might be effective in more severe infections, such as bacteremia. The drug met its endpoint in a 200-patient Phase II study in cSSSI caused by Gram-positive bacteria, including resistant strains such as methicillin-resistant Staphylococcus aureus, demonstrating noninferiority to vancomycin.

Even though the drugs are targeting similar indications, Theravance said TD-1792 is not expected to overlap too much with telavancin, should both products eventually reach market.

The FDA is expected to make a decision on telavancin next month. The new drug application, submitted in December, was based on two pivotal studies showing the drug's noninferiority to vancomycin in treating cSSSIs; however, the agency has indicated over the last year that noninferiority alone might not be sufficient for marketing approval of new antibiotics. Last fall, the FDA rejected an NDA from Louisville, Colo.-based Replidyne Inc. for faropenem, even though it met all its noninferiority endpoints in a pivotal program, and asked for additional superiority data. That may or may not end up being a sticking point for telavancin. Theravance executives have said the level of noninferiority of the telavancin pivotal studies was more than 20 percent in most measures, and the FDA also might consider the fact that cSSSIs, especially involving MRSA, can result in serious, life-threatening infections. (See BioWorld Today, Dec. 11, 2006.)

Upon approval, Astellas would pay Theravance an undisclosed milestone, and the companies will work together on U.S. marketing for the first three years. A separate marketing application for telavancin in cSSSI is under review in Europe.

No Comments