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 Addresses Pfizer's Announcement Regarding Exubera

04/10/08
PDF Version
MannKind Addresses Pfizer's Announcement Regarding ExuberaVALENCIA, Calif., April 10 /PRNewswire-FirstCall/ -- MannKind Corporation (Nasdaq: MNKD) released the following statement in response to the announcement by Pfizer Inc. that over the course of Exubera's clinical trial program, 6 of the 4,740 patients treated with Exubera developed lung cancer, although Pfizer concluded that there were too few cases to determine whether this observation was related to Exubera. According to Pfizer's "Dear Doctor" letter, Exubera remains a safe and effective medication. It is important to note that each of the patients affected had a history of cigarette smoking, a known, major risk factor for lung cancer. Although the sugar-based Exubera formulation did have a small but statistically significant impact on pulmonary function, we are not aware of any specific carcinogenicity studies of Exubera to evaluate the potential of cancer risk.

In contrast, the safety profile of Technosphere® Insulin has been examined in an extensive pre-clinical program, including a two-year carcinogenicity study in rats, in which we observed that Technosphere® Insulin and Technosphere® particles alone were well tolerated after daily inhalations for 104 consecutive weeks. There were no indications that our product or the carrier material alone had carcinogenic potential or caused cellular proliferation in the lungs. We also recently completed a six-month carcinogenicity study in transgenic mice that are prone to cancer. We found no macroscopic indications of carcinogenicity in animals treated with Technosphere® Insulin or Technosphere® particles for 26 consecutive weeks. The analysis of the histology data is in progress and will be completed later this quarter.

Our Technosphere® Insulin clinical program is designed to provide data on safety and efficacy in a broad group of patients with diabetes. We have not observed a higher incidence of lung cancer in Technosphere® Insulin patients than that expected in the general population. Our independent Data Safety Monitoring Board (DSMB) regularly reviews all potential safety issues with our clinical trials and has consistently recommended that the trials continue without changes. Given Pfizer's announcement, the DSMB met again yesterday and found that on the basis of the current information our trials could continue.

Ensuring patient safety is always our primary concern. To date with our product, we have seen no adverse effects on the measures of pulmonary function that have been reported to occur with Exubera. We are working closely with the DSMB and regulatory agencies in order to understand the implications of the Exubera data.

Additionally, given the current market sentiment, we have decided to suspend partnership discussions. At this time, we believe that we will be unable to achieve an appropriate valuation for Technosphere Insulin until Phase 3 data are available that confirm our belief in the safety and efficacy of Technosphere Insulin.

About MannKind Corporation

MannKind Corporation (Nasdaq: MNKD) focuses on the discovery, development and commercialization of therapeutic products for diseases such as diabetes and cancer. Its lead product, the Technosphere® Insulin System, is currently in phase 3 clinical trials in the United States, Europe and Latin America to study its safety and efficacy in the treatment of diabetes. For more information on MannKind Corporation and its technology, visit http://www.mannkindcorp.com.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding a partnership for the commercialization of Technosphere® Insulin. Words such as "believes", "anticipates", "plans", "expects", "intend", "will", "goal", "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon MannKind's current expectations and involve risks and uncertainties. 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 related to the progress, timing and results of clinical trials, whether results of further clinical trials of Technosphere® Insulin will reveal safety concerns, whether the clinical data regarding Technosphere® Insulin will support regulatory approval, difficulties or delays in seeking or obtaining regulatory approval, whether MannKind will be able to enter into and maintain a collaboration with a pharmaceutical partner for commercialization of Technosphere® Insulin and its other peptide hormone drug candidates on attractive terms for MannKind if at all, and other risks detailed in MannKind's filings with the Securities and Exchange Commission, including the Annual Report on Form 10-K for the year ended December 31, 2007 and periodic reports on Form 10-Q and Form 8-K. 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 MannKind undertakes 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

CONTACT: Hakan Edstrom, President and Chief Operating Officer, +1-661-775-5300, hedstrom@mannkindcorp.com

Web site: http://www.mannkindcorp.com