Theravance Biopharma,a biopharmaceutical company,  and Mylan announced that the two companies will partner on the development and, subject to FDA approval, commercialisation of TD-4208, a novel investigational once-daily nebulized long-acting muscarinic antagonist (LAMA) for chronic obstructive pulmonary disease (COPD) and other respiratory diseases.

COPD is a growing and devastating disease that is the third leading cause of death in the US. An estimated 12.7 million American adults are diagnosed with COPD and an almost equal number are believed to be undiagnosed. Once-daily LAMAs are currently the cornerstone of maintenance therapy for patients with COPD, but existing LAMAs are only available in handheld devices. Approximately 9 per cent of the treated COPD patients in the US either need or prefer a nebulized product for delivery of their ongoing maintenance therapy and a further 30 per cent of COPD patients use nebulized treatment on an intermittent basis. In the nebulizer segment, there is no once-daily or twice-daily muscarinic antagonist therapy available.

TD-4208 has shown positive top-line results in COPD patients in multiple phase 2 studies, and the FDA recently agreed to the design of the phase 3 registrational program, which is anticipated to begin this year. Theravance Biopharma and Mylan believe that TD-4208 has the potential to be a best-in-class once-daily single-agent nebulized product for COPD patients who require, or prefer, nebulized therapy.  

"This exciting development and commercialisation collaboration leverages Mylan's expertise in manufacturing and marketing complex respiratory products and Theravance Biopharma's respiratory clinical development capabilities. The addition of TD-4208 to our pipeline is highly complementary with our existing respiratory portfolio, including our marketed nebulized COPD product, Perforomist Inhalation Solution, and reinforces Mylan's leadership in nebulized respiratory therapy," says Mylan CEO Heather Bresch.

"Partnering with a world leader in nebulized respiratory therapies enables us to expand the breadth of our TD-4208 development programmes and extend our commercial reach beyond the acute care setting where we currently market Vibativ (telavancin). Funding of the phase 3 registrational program by Mylan strengthens our company's capital position and enhances our financial flexibility to advance other high-value pipeline assets alongside TD-4208," says Rick E Winningham, chairman and chief executive officer, Theravance Biopharma.  "We look forward to working with Mylan to bring this potential first-in-class, once-daily nebulized therapy to COPD patients."

Under the terms of the agreement, Mylan and Theravance Biopharma will co-develop nebulized TD-4208 for COPD and other respiratory diseases. Theravance Biopharma will lead the US registrational development programme and Mylan will be responsible for reimbursement of Theravance Biopharma's costs for that programme up until the approval of the first new drug application, after which costs will be shared. In addition, Mylan will be responsible for commercial manufacturing. In the US, Mylan will lead commercialisation and Theravance Biopharma will retain the right to co-promote the product under a profit-sharing arrangement. Outside the US (excluding China), Mylan will be responsible for development and commercialisation and pay Theravance Biopharma a royalty on net sales. Theravance Biopharma retains worldwide rights to TD-4208 delivered through other dosage forms, such as a metered dose inhaler or dry powder inhaler (MDI/DPI).

In addition to funding the US registrational development programme, Mylan will pay Theravance Biopharma an initial payment of $15 million in cash and has agreed to make a $30 million equity investment in Theravance Biopharma by purchasing newly issued Ordinary Shares at a price of $18.92 per share, which is equal to a 10 per cent premium over the 5-day trailing volume-weighted average price ending January 30. Under the terms of the agreement, Theravance Biopharma is eligible to receive potential development and sales milestone payments totaling $220 million in the aggregate, with $175 million associated with TD-4208 monotherapy and $45 million for future potential combination products.

Mylan and Theravance Biopharma believe that TD-4208 has the potential to be the only FDA-approved once-daily nebulized LAMA product for COPD patients in the near term and it may offer longer-term opportunities for combination with other nebulized products. In addition, the patent portfolio for TD-4208 is currently expected to provide a TD-4208 nebulized product with exclusivity in the US until at least 2025, which does not include any potential patent term extensions. Given the short- and long-term potential of this differentiated product, and in an effort to optimise its uses of capital, Mylan has decided to redeploy resources from the development of its combination nebulized ICS/LABA product (Combo) to TD-4208.

TD-4208 is an investigational long-acting muscarinic antagonist (LAMA) in development for the treatment of chronic obstructive pulmonary disease (COPD). In September 2014, Theravance Biopharma announced positive top-line results from its Phase 2b dose-ranging study of TD-4208. TD-4208 met the primary efficacy endpoint (change from baseline in trough FEV1 [forced expiratory volume in one second] following the last dose on Day 28) with statistically significant responses at once-daily doses of 88, 175 and 350 mcg. The lowest dose of 44 mcg once-daily produced a sub-therapeutic response that was not statistically different from placebo.

In November 2014, Theravance Biopharma announced positive top-line results from the once- versus twice-daily (QD versus BID) study of TD-4208. The study compared 175 mcg once-daily against 44 mcg twice-daily in a 3-period, 7-day placebo-controlled crossover study conducted in 64 COPD patients. The study met its primary endpoint and demonstrated that the lower dose (44 mcg) administered twice-daily did not produce greater bronchodilation than the higher dose (175 mcg) administered once-daily.  The frequency of adverse events was low and consistent across all three treatments including placebo. There was one death in the study that was assessed by the study investigator as unrelated to study medication.

The mission of Theravance Biopharma (Nasdaq: TBPH) is to create value from a unique and diverse set of assets: an approved product; a development pipeline of late-stage assets; and a productive research platform designed for long-term growth.Our pipeline of internally discovered product candidates includes potential best-in-class opportunities in underserved markets in the acute care setting, representing multiple opportunities for value creation. Vibativ (telavancin), our first commercial product, is a once-daily dual-mechanism antibiotic approved in the US and Europe for difficult-to-treat infections. TD-4208 is a long-acting muscarinic antagonist (LAMA) being developed as a potential once-daily, nebulized treatment for COPD. Axelopran (TD-1211) is a potential once-daily, oral treatment for opioid-induced constipation (OIC). Our earlier-stage clinical assets represent novel approaches for potentially treating diseases of the lung and gastrointestinal tract - our core areas of therapeutic focus - and infectious disease. In addition, we have an economic interest in future payments that may be made by GSK pursuant to its agreements with Theravance, Inc. relating to certain drug programs, including the combination of umeclidinium, vilanterol and fluticasone furoate (or the "Closed Triple").

With our successful drug discovery and development track record, commercial infrastructure, experienced management team and efficient corporate structure, we believe that we are well positioned to create value for our shareholders and make a difference in the lives of patients.