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 Unveils Proposed Trade Name at Dedication of Danbury Manufacturing Facility

09/17/08
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MannKind Unveils Proposed Trade Name at Dedication of Danbury Manufacturing FacilityDANBURY, Conn., Sept. 17 /PRNewswire-FirstCall/ -- MannKind Corporation (Nasdaq: MNKD) today announced that it has proposed to the United States Food and Drug Administration to use AFRESA as the trade name for its Technosphere Insulin System.

AFRESA (pronounced uh-FRESS-uh) was unveiled today by Alfred Mann, Chairman and Chief Executive Officer of MannKind, during a ceremony at the company's Danbury, Conn., location that marked the completion and dedication of a new facility for the commercial manufacture of the product.

The events in Danbury included a building dedication, a luncheon, and tours of the 263,900 sq. ft. production facility for invitees, who included investors, medical and industry professionals, scientists, employees, and government officials. The completion of the building phase of this project brings MannKind's investment in plant and equipment at the Danbury site to almost $200 million. The facility is now in the process of being qualified and readied for preapproval inspection by the FDA.

Featuring state-of-the-art equipment and processes and redundant utilities, the new facility includes expansion space that will allow production capacity to be increased to meet expected demand over the next few years. The architect for the project was Kling Stubbins. The engineering firm was Clark Richardson Biskup and the construction manager was Torcon.

MannKind is proud to note that its facility expansion received the 2008 Bronze Vision Award in the Corporate Owner: Industrial/Manufacturing category at the Ninth Annual Constructech Vision Award ceremony, held in Chicago on August 21, 2008. The Constructech Vision Awards honor construction and engineering projects that have solved critical business issues through the use of innovative technology solutions. The award was presented to MannKind by Mike Carrozzo, chief editor of Constructech Magazine and accepted by Abigail Smith, MannKind's Vice President of Engineering, and Stephen Hall, MannKind's Senior Director of Engineering.

"Today's event is a milestone in the history of MannKind," Mr. Mann said. "We are preparing to manufacture a unique and differentiated therapy for the treatment of diabetes on a commercial scale. This has been a busy week for MannKind. Yesterday, we announced a collaboration with Pfizer that will allow certain Exubera patients with an urgent medical need for inhaled insulin to transition to AFRESA on a compassionate use basis. In addition, we released some top-line results from the first of our three completed pivotal Phase 3 clinical studies. In this trial of 565 patients with type 1 diabetes, we established that AFRESA is non-inferior in A1C and superior in other objectives compared to today's standard of care for prandial insulin needs, a rapid acting insulin analog. Later this Fall, we will report the results from our other two pivotal studies of AFRESA before we enter the final stretch of our effort to submit a new drug application by year-end or shortly thereafter."

About AFRESA

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. As described in publications in the Journal of Diabetes Science and Technology, MannKind's AFRESA 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. In a one-year Phase 3 clinical study of patients with type 1 diabetes, the meal-time use of AFRESA (in combination with an injected long-acting insulin) was associated with a statistically significant reduction of fasting blood glucose levels compared to the meal-time use of an injected rapid-acting insulin (also in combination with an injected long-acting insulin).

Additional Phase 3 data for AFRESA is scheduled to be disclosed later this year.

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. For more information on MannKind Corporation and its technology, visit http://www.mannkindcorp.com.

AFRESA and TECHNOSPHERE are trademarks of MannKind Corporation.

SOURCE MannKind Corporation

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

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