What exactly is the Technosphere® Platform?

One of the largest organs in your body are the lungs. Picture the size of a full tennis court and that is roughly the surface area of both lungs in a typical adult. Running through those lungs are airways whose total length measures 1,500 miles – that’s the distance between Chicago and Las Vegas, New York to Albuquerque, and Los Angeles to Nashville.

Simply put, the lungs create a wonderful platform for effective drug delivery. MannKind’s Technosphere technology recognizes this and provides the distinct advantage of rapid, deep lung drug delivery. The effect is similar to intravenous delivery (I.V.; within a vein) and has the added benefit of bypassing the liver which can be especially helpful in reducing systemic side effects.

Examining it closer, it helps to look at inhalation, air flow travel, and the exhale. When you breathe in, air is drawn into the lung and flows down curving, narrowing airways that end in the air sacs or alveoli. When air is exhaled, the flow is reversed. Between the end of an inhalation and the start of exhalation, the air in the lung is stationary. To reach the deep lung, inhaled particles must be carried by the air stream and have enough momentum to continue through the stationary air to collide with the lung surface.

Particles that can reach the lung have aerodynamic diameters between 0.5 µm and 5-6 µm (1 µm is 1 micro-meter or about 0.00004 inches). Particles that are larger than 6 µm will leave the air stream and hit the back of your mouth and throat; smaller than 0.5 µm wouldn’t have the ability to reach the lungs and would simply get exhaled.

“The average Technosphere particle is about 2-2.5 µm which is in the middle of the respirable range,” explains Marshall Grant, PhD, MSc, Executive Director, Clinical Pharmacology & Research for MannKind Corporation. “The particle size distribution is a major reason Technosphere powders are highly efficient in delivering drug to the lungs than other dry powder inhalers (DPIs).”

The Technosphere particles in FDA-approved Afrezza® (insulin human) Inhalation Powder and Tyvaso DPI™ (treprostinil) Inhalation Powder are manufactured by different processes and possess different characteristics. But both are made up of small crystals of FDKP (fumaryl diketopiperazine), MannKind’s proprietary molecule. FDKP provides high solubility and fast dissolution at physiologic pH – and more importantly – can crystallize and form particles in the range appropriate for optimum delivery to the lungs.

When Technosphere powder reaches the lung surface, the FDKP and drug dissolve. The FDKP is then rapidly cleared from the lung into systemic circulation. The FDKP is not metabolized, but rather excreted primarily in the urine. Another value of Technosphere powders has been their versatility – they are compatible with a wide range of doses with different types of drugs.

MannKind’s Technosphere powders are delivered into the lung’s airstream via an inhalation device or DPI (dry powder inhaler). The breath-powered inhalers (Dreamboat® being the most common version) provide excellent delivery efficiency and are proven to deliver up to 70% of the dry-powder dose deep into the lungs. Our DPI are designed to be simple, easy to use and discreet. For patients, imagine having a drug in the convenient form of an inhaler that fits in the palm of your hand. This approach allows patients to not only take control of their health but do it while going about their day and enjoying life more humann.

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NTM Lung Disease on the Rise

“I cough every morning upon waking, so I don’t feel rested.” “Imagine not being able to breathe.” “Anxiety ruins everything about you – it’s not a normal life.” “You just exist from day to day and week to week.” These are a sampling of comments about the most bothersome symptoms from living with Nontuberculous Mycobacteria (NTM) shared in a study from NTM Info & Research, Inc. The statements are unfortunately typical and those with NTM often have unpredictable day-to-day health functioning and reduced quality of life.

NTM lung disease is a serious infection that is caused by bacteria that are common in the environment and can cause lung damage. The reality is that we are all exposed to these bacteria in our day-to-day lives – more than 120 species of mycobacteria have been identified. These common bacteria exist in water and soil particles that are in the air, wet places like hot tubs, steamy bathrooms, dishwashers, and even the dewy ground we walk on at the park. But not everyone is at risk of getting NTM lung disease just because they are exposed.

Those predisposed often have underlying conditions such as asthma, COPD, and bronchiectasis, which makes them prone to NTM infection. NTM is not considered to be contagious. Women over the age of 65 make up the majority of those impacted, with a predominance in those of Caucasian and Asian descent.

A rare disease, NTM can often be difficult to diagnose. Many will experience coughing, fatigue, weight loss and shortness of breath – all of which are common with other lung disease symptoms and other conditions like tuberculosis. With NTM, symptoms often worsen, and that is a marker not to be ignored.

It is estimated that some 86,000 individuals are living with NTM lung diseases, and it is on the rise growing 8% each year. Coastal regions including Gulf States have higher rates of infection accounting for 70% of annual NTM cases.

While no cure is available, treatments to manage NTM are available. Treatment for NTM involves antibiotic and multidrug regimens with duration lasting from months to years with tolerability and adverse reactions to treatment which often leads to a lack of adherence to therapy.

There is a valuable need to develop medicines that are well tolerated and effective that lends to consistent patient use and alleviates symptoms of NTM lung disease. MannKind continues to progress MNKD-101 (Clofazimine) for the treatment of NTM.

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Release Details

Tolero and MannKind Sign Collaboration and License Agreement to Develop and Commercialize Novel BTK Inhibitors for Hematological Malignancies and Inflammatory Diseases

04/30/12
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Tolero and MannKind Sign Collaboration and License Agreement to Develop and Commercialize Novel BTK Inhibitors for Hematological Malignancies and Inflammatory Diseases

SALT LAKE CITY & VALENCIA, Calif.--(BUSINESS WIRE)--Apr. 30, 2012-- Tolero Pharmaceuticals, a biopharmaceutical company focused on the discovery and development of novel therapeutics to treat cancer and other serious human diseases, and MannKind Corporation (Nasdaq: MNKD), focused on discovering, developing and commercializing therapeutic products for diabetes and cancer, today announced a license agreement granting Tolero exclusive worldwide rights to develop and commercialize compounds from MannKind’s novel BTK (Bruton’s tyrosine kinase) program, which are currently being developed for the treatment of hematological malignancies and inflammatory diseases.

Under the terms of the agreement, Tolero will pay MannKind upfront and milestone payments linked to the development, approval and commercialization of products, for total potential upfront and milestone payments of approximately $130 million. MannKind will also receive tiered royalties on sales of products and a percentage of sublicensing revenue. In addition, MannKind has an option to re-acquire the rights to the program at pre-specified terms until 60 days after the conclusion of the first Phase 1 study. If MannKind exercises this option, then MannKind would assume responsibility for developing and commercializing products and Tolero would become entitled to receive the milestone payments, royalties and sublicensing revenues specified in the agreement.

“We are really excited about this opportunity and pleased to be working with an experienced drug development team at MannKind that is passionate about moving this program forward. BTK currently represents one of the most exciting therapeutic targets in oncology, and we feel that our collaborative approach to targeting BTK may uncover some novel utilities not yet fully realized,” said Dallin Anderson, Chairman and President of Tolero.

Dr. David Bearss, Founder of Tolero, added, “BTK has already been demonstrated to be a validated clinical target in multiple disease settings. We believe that MannKind has developed a series of novel compounds with unique mechanisms of action that may lead to important treatments for cancer and autoimmune diseases, such as rheumatoid arthritis. We are excited to be a strategic partner with MannKind.”

About Tolero Pharmaceuticals

Tolero is a biopharmaceutical company dedicated to the discovery and development of novel therapeutics to treat and cure cancer and other life-threatening diseases. Tolero has used its innovative drug development platform to create a diverse portfolio of drug candidates targeting several cancer-associated cellular pathways. Tolero Pharmaceuticals is a privately held company founded in 2011 and headquartered in Salt Lake City, Utah.

About MannKind Corporation

MannKind Corporation (Nasdaq: MNKD) focuses on the discovery, development and commercialization of therapeutic products for patients with diseases such as diabetes and cancer. Its lead product candidate, AFREZZA®, is in late stage clinical investigation for the treatment of adults with type 1 or type 2 diabetes for the control of hyperglycemia. MannKind maintains a website at http://www.mannkindcorp.com to which MannKind regularly posts copies of its press releases as well as additional information about MannKind. Interested persons can subscribe on the MannKind website to e-mail alerts that are sent automatically when MannKind issues press releases, files its reports with the Securities and Exchange Commission or posts certain other information to the website.

This press release contains forward-looking statements, including statements regarding our expectations and beliefs regarding the collaboration and license agreement with Tolero, that involve risks and uncertainties. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon our current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks regarding reliance on Tolero to develop and commercialize products from the BTK program, including risks that Tolero may not devote sufficient efforts to those activities, whether due to lack adequate financial or other resources, a strategic decision to focus on other initiatives or otherwise, and risks that the agreement with Tolero may be terminated, as well as risks associated with the progress, timing and results of clinical trials, difficulties or delays in seeking or obtaining regulatory approval, competition from other pharmaceutical or biotechnology companies, and other risks detailed in our filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2011. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release.

Source: MannKind Corporation and Tolero Pharmaceuticals

For Tolero Pharmaceuticals:
Dallin Anderson
Chairman and President
(801) 285-7570
danderson@toleropharma.com
or
For MannKind Corporation:
Matthew Pfeffer
Chief Financial Officer
(661) 775-5300
mpfeffer@mannkindcorp.com