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

MannKind Wins Two Facility of the Year 2010 Category Awards

01/11/10
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MannKind Wins Two Facility of the Year 2010 Category Awards

DANBURY, Conn., Jan 11, 2010 (BUSINESS WIRE) -- MannKind Corporation (Nasdaq: MNKD) today announced that its commercial manufacturing facility, custom-built for the production of its proprietary insulin therapy, has been awarded two Facility of the Year 2010 category awards for process innovation and equipment innovation.

The Facility of the Year Awards, sponsored by the International Society for Pharmaceutical Engineering (ISPE), INTERPHEX, and Pharmaceutical Processing Magazine, were created six years ago to showcase the best of each year's new, state-of-the-art pharmaceutical manufacturing facilities across seven categories: equipment innovation, facility integration, operational excellence, process innovation, project execution, regional excellence, and sustainability. For 2010, twenty-one companies from twelve countries were considered. MannKind's facility was the first in the history of the awards ever to win in two categories.

Begun in early 2007 and completed in mid-2008, MannKind's $163 million, 23,400 square meter facility was part renovation and part new construction. Roughly 20 percent of the facility is earmarked for future expansion, which MannKind can use to increase production of its insulin therapy or begin production on new Technosphere-based therapies.

While the facility itself is a striking merger of form, function, and efficiency, the Facility of the Year Award judges were most impressed with the custom process line that the facility houses. MannKind engineered an innovative manufacturing process line from start to finish. It begins with the creation of the Technosphere® particle. The particle is then combined with insulin in a specialty mixer, and the resultant slurry is freeze dried to isolate the powder. Once dried, the powder is transported to the fillers, and then filled into capsules and packaged for distribution. At every point in this process, MannKind designed new technology or applied innovative adaptations to existing technology to meet their needs.

Another distinguishing feature of the facility is a first-ever solid-dosage pharmaceutical adaptation of a cryopelletizer. MannKind, together with Cryogenic Equipment Services, modified the cryopelletizer to create uniform pellets from the slurry so that the water could be removed quickly and consistently during the bulk lyophilization (freeze drying) process. This revolutionary adaptation dramatically improved the quality of the drug and the efficiency of its production.

In addition to the new lyophilization technique, MannKind also made unique adaptations to the specialty mixer where the Technosphere particle and the insulin are combined; designed a highly cost-effective method to move bulk powder from the lyophilizer to the filler; and designed a filling system that could work at high speed while remaining safe for the operators and supremely precise in the metering of the bulk powder.

For these reasons, MannKind received special recognition for the new facility. Marni Schribman, ISPE Communications Manager, said of MannKind's project, "This is the first time in the program's history that the judges have named one project to two categories. However, the judges felt very strongly that MannKind Corporation excelled in each of these categories during the construction of its facility. Congratulations on this tremendous accomplishment."

Juergen Martens, Chief Technology Officer of MannKind, stated, "Our adaptations of cross-sector technologies for novel applications in the pharmaceutical industry not only made possible the commercial production of the innovative Technosphere® particle, but it also made possible multiple new drug therapies for the future. Our cryopelletization technology can improve the quality and lower the cost of countless drugs worldwide that require bulk lyophilization in their manufacture, and our innovative, non-invasive drug delivery system can transport a potentially endless variety of macromolecules into the systemic circulation via the pulmonary route."

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 diabetes pipeline includes AFREZZA™ (formerly AFRESA®) and MKC253. MannKind has submitted an NDA to the FDA requesting approval of AFREZZA for the treatment of adults with type 1 or type 2 diabetes for the control of hyperglycemia. MKC253 is currently in phase 1 clinical trials. 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.

SOURCE: MannKind Corporation

MannKind Corporation
Matthew Pfeffer
Chief Financial Officer
661-775-5300
mpfeffer@mannkindcorp.com