MNKD Investors

Technosphere®

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.

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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.”

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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 Reports Top-Line Results from Two Pivotal Phase 3 Clinical Studies in Type 1 and Type 2 Diabetes

12/18/08
MannKind Reports Top-Line Results from Two Pivotal Phase 3 Clinical Studies in Type 1 and Type 2 Diabetes

VALENCIA, Calif., Dec. 18 /PRNewswire-FirstCall/ -- MannKind Corporation (Nasdaq: MNKD) today released preliminary top-line results from two pivotal Phase 3 clinical studies of AFRESA™, the company's ultra rapid acting insulin product (Studies 102 and 030). The protocols for these studies were reviewed and prospectively approved by the FDA under its special protocol assessment (SPA) procedure. As previously announced, both studies achieved their primary endpoints.

Study 102 - comparable decreases in A1C levels

Study 102 compared the efficacy of meal-time AFRESA in combination with a long-acting basal insulin versus twice daily injections of pre-mixed insulin (a mixture of rapid-acting insulin and intermediate-acting insulin) in patients with type 2 diabetes. A total of 323 patients were randomized to the AFRESA group and 331 patients were randomized to the pre-mix group.

Over the 52-week period of this study, A1C levels decreased comparably in the two treatment groups, 0.59 in the AFRESA group and 0.71 in the pre-mix group. The 95% confidence interval (0.29%) of the between-group difference did not exceed the predetermined threshold of 0.40%, thereby establishing non- inferiority between AFRESA and pre-mixed insulin.

Other study highlights:

-- A comparable percentage of patients reached A1C target levels in each treatment group.

-- There was a significantly greater decrease in fasting blood glucose levels in the AFRESA group compared to pre-mixed insulin.

-- Patients in the AFRESA group gained significantly less weight than did patients in the pre-mix group.

-- Severe hypoglycemic events were significantly less common in the AFRESA group than in the pre-mix group

-- There were no between-group differences in pulmonary function measures, including FEV1 (forced expiratory volume in one second), FVC (forced vital capacity), DLCo (carbon monoxide diffusing capacity) and TLC (total lung capacity).

-- These preliminary results are subject to further statistical analysis.

Study 030 - no adverse effect on lung function

Study 030 compared the pulmonary safety of meal-time inhalation of AFRESA versus usual care (the comparator group). A total of 938 patients with type 1 and type 2 diabetes were randomized to the AFRESA group; 951 patients were randomized to the comparator group. An additional 164 subjects without diabetes were enrolled into a third arm in order to assess the effect of diabetes on pulmonary function.

The primary endpoint of Study 030 was pre-specified with the FDA as a between-group difference (AFRESA-treated vs. comparator group) of less than 50 mL per year in the decline from baseline measures of FEV1 over the entire study period. After two years of treatment, the difference between mean FEV1 values for the two treatment groups was 37 mL (95% CI: 14-60 mL) -- well within the 100 mL pre-defined limit. Non-inferior results were also observed in secondary measures of lung function, including FVC, TLC and DLCo.

Other study highlights:

-- On average, patients in the AFRESA group gained less weight than did patients in the comparator group or subjects without diabetes.

-- Comparable decreases were observed in A1C levels between the AFRESA- treated group and the comparator group

-- Severe hypoglycemic events were significantly less common in the AFRESA group compared to the comparator group.

These preliminary results are subject to further statistical analysis.

Dr. Peter Richardson, MannKind's Chief Scientific Officer, commented, "We are continuing to analyze the results of our pivotal Phase 3 clinical studies, and plan to share more data at upcoming investor presentations and the American Diabetes Association scientific meeting in June. In addition, we anticipate shortly the completion of the bioequivalency study that compares the clinical version of our inhaler to the more rugged and less costly commercial version. With this gating item behind us, we are now focusing on readying our new drug application for AFRESA for submission to the FDA early in the new year."

About AFRESA

AFRESA is an ultra rapid acting insulin product that has completed Phase 3 trials. The pharmacokinetic profile of AFRESA sets it apart from all other insulin products. The large surface area of the lung provides unique access to the circulatory system. The pH-sensitive AFRESA particles immediately dissolve upon contact with the lung surface, releasing insulin monomers that rapidly enter the bloodstream. It achieves peak insulin levels within 12-14 minutes of administration, effectively mimicking the release of meal-time insulin observed in healthy individuals, but which is absent from patients with diabetes.

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 pipeline includes AFRESA, which has completed Phase 3 clinical trials, and MKC253, which is currently in phase 1 clinical trials. Both of these investigational products are being evaluated for their safety and efficacy in the treatment of diabetes. MannKind maintains a website at http://www.mannkindcorp.com to which MannKind regularly posts copies of its press release as well as additional information about MannKind. Interested persons can subscribe on the MannKind website to email alerts that are sent automatically when MannKind issues press releases, files its reports with the SEC or posts certain other information to the website.

Forward-Looking Statements

This press release contains forward-looking statements, including statements related to the promise for AFRESA, next steps in the Company's clinical trial program, plans and timing for the submission of a new drug application and expectations regarding potential position and use of AFRESA in the market. 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, difficulties or delays in seeking or obtaining regulatory approval, MannKind's ability to enter into any collaborations or strategic partnerships, MannKind's ability to raise additional financing 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 news release.

SOURCE MannKind Corporation

CONTACT:
Peter Richardson,
Chief Scientific Officer
of MannKind Corporation,
+1-201-983-5064,
prichardson@mannkindcorp.com

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