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

New Findings Show Bioequivalence, Ease-of-Use and Efficiency of MannKind's Drug Delivery Platform

11/15/10
PDF Version
New Findings Show Bioequivalence, Ease-of-Use and Efficiency of MannKind's Drug Delivery Platform

VALENCIA, Calif., Nov 15, 2010 (BUSINESS WIRE) -- MannKind Corporation (Nasdaq: MNKD) unveiled new data on its drug delivery, device and particle technologies demonstrating the bioequivalence, ease of use and efficiency of the company's novel platform. The proprietary technology, founded on the company's expertise in inhaled drug development, device engineering and powder formulation performance, was evaluated in four separate studies presented at the 10th annual meeting of the Diabetes Technology Society in Bethesda, Maryland, November 12-13. The first application of this technology, the novel, ultra rapid-acting insulin AFREZZA® (insulin human [rDNA origin]), is currently under review by the U.S. Food and Drug Administration (FDA) and has a PDUFA date of December 29, 2010.

"We are excited about the progress of AFREZZA, our first program to utilize this technology, and we look forward to applying the platform to other products where there is a medical benefit," said Dr. Peter Richardson, MRCP, corporate vice president and chief scientific officer for MannKind Corporation.

Findings of the studies are as follows:

  • Bioequivalence of the inhaler used in the Phase 3 clinical trials for AFREZZA (MedTone® ) and the next-generation delivery system planned to be marketed with AFREZZA (Gen2) was demonstrated using two separate methods of analysis (Roche ECLIA and RIA) with all parameters and dose groups passing the bioequivalence criteria.
  • An additional study also demonstrated the bioequivalence of the Gen2 device and the clinical inhaler. Based on the results, insulin exposures when using either system to administer AFREZZA insulin were bioequivalent while dose-equivalence between two 10 U cartridges and one 20 U cartridge of AFREZZA inhalation powder was also achieved.
  • A third trial, designed to evaluate the bioavailability of insulin delivered using the two inhalers and the acute effects on lung functions immediately after inhalation, found no clinically meaningful acute FEV1 changes observed from pre- to post-inhalation over a two-hour period. With the Gen2 delivery system, acute FEV1 changes after the administration of AFREZZA were minimal and consistently smaller than those observed with the MedTone inhaler.
  • Additional data showed that children as young as 4 years of age can successfully handle, assemble and operate the Gen2 device.

All presented posters are available on the MannKind website (www.mannkindcorp.com):

  • Acute Pulmonary Effects of Technosphere® Insulin Inhalation Powder Administered Using a Gen2B Inhaler Compared to a MedTone® C Inhaler
  • Bioequivalence and Dose Proportionality of AFREZZA® Inhalation Powder Administered Using a Gen2 Inhaler Compared to the MedTone® Inhaler
  • The Relationship Between Two Insulin Assays Used to Determine Bioequivalence and Dose Proportionality of AFREZZA® Insulin Administered Using a Gen2 Inhaler Compared to a MedTone® Inhaler: Simulation of Clinical Trials and Actual Trials
  • Handleability and Characterization of Inhalation Profiles Using the Gen2 Delivery System in a Pediatric Population

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® and MKC253. MKC253 is currently in phase 1 clinical trials. In March 2009, MannKind submitted a 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. In March 2010, MannKind received a Complete Response letter to this NDA from the FDA, requesting additional information. In July 2010, the FDA accepted MannKind's reply to the Complete Response letter and set a PDUFA action date of December 29, 2010. Other products in MannKind's pipeline include the cancer immunotherapy platform MKC1106, which is currently in phase 2 clinical trials. MannKind maintains a website at 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