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.

picture 1

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.

picture 1

Release Details

Studies Show No Increased Risk of Cardiac Events in Diabetes Patients Treated with AFREZZA(R)

06/24/11
PDF Version
Studies Show No Increased Risk of Cardiac Events in Diabetes Patients Treated with AFREZZA(R)

SAN DIEGO, Jun 24, 2011 (BUSINESS WIRE) -- The findings of two separate studies further substantiate that treatment with the investigational ultra rapid acting mealtime insulin AFREZZA® (insulin human [rDNA origin]) Inhalation Powder does not result in excess cardiovascular events in type 1 or type 2 diabetes patients. Furthermore, results demonstrate that inhaled AFREZZA did not produce clinically significant effects on heart rate, PR and QRS interval duration, or cardiac morphology. The data are being presented at the American Diabetes Association's 71st Scientific Sessions®.

AFREZZA® is a novel, ultra rapid-acting mealtime insulin therapy in late stage clinical investigation for the treatment of adult patients with type 1 and type 2 diabetes mellitus for the control of hyperglycemia. Two phase 3, multicenter clinical trials are currently underway to evaluate the efficacy and safety of AFREZZA using MannKind Corporation's next generation inhalation device.

"In response to the recent concern over the cardiovascular risk of diabetes therapies, it is important to carefully analyze all trials and maintain an ongoing program of safety surveillance," said Anders H. Boss, M.D., M.F.P.M., Senior Vice President and Chief Medical Officer at MannKind Corporation. "These most recent safety findings add to the growing body of evidence that AFREZZA may be a promising new therapy for patients with type 1 and type 2 diabetes, without the concern of increased risk for cardiovascular events."

"Overall Cardio" Study Design and Key Findings

To evaluate whether excess cardiovascular events occurred in patients treated with AFREZZA versus current antidiabetic therapies, cardiovascular adverse events, pooled from nine phase 2/3 clinical trials consisting of 4,467 patients treated for periods from three months to two years, were reviewed. The prevalence of prior cardiovascular disease, such as myocardial infarction, coronary artery disease or stroke, was less than 10 percent in patients with type 1 diabetes but approached 40 percent in patients with type 2 diabetes.

In controlled trials, the incidence of cardiovascular events did not show increased risk with AFREZZA use in type 1 (31 vs. 35, 0.85 relative risk), type 2 (167 vs. 136, 1.02 relative risk) or the combined type 1 plus type 2 (198 vs. 171, 1.01 relative risk) diabetes populations. The number of patients with ischemic events was low and similar between treatment groups. Cerebrovascular events and other cardiovascular events, such as coronary artery disease, and arrhythmic events were also similar between treatment groups.

"QTc" Study Design and Key Findings

In a randomized, 4-period crossover, double-blind, double-dummy, placebo- and active-controlled cardiac safety study, healthy men (n=26) and women (n=22) were dosed with inhaled 40 mg Technosphere® particles, 20 mg Technosphere particles, or placebo, and oral 400 mg moxifloxacin was used as the positive control. ECGs were obtained digitally at regular time intervals before and after each dose and independently evaluated. Safety was monitored through evaluation of adverse events, clinical laboratory values, physical exams, vital signs, and pulmonary function tests.

Time-averaged analysis of the placebo-corrected mean QTcI change from baseline for Technosphere particles showed no significant effect on QTc at all times (0.5 ms and 0.3 ms for the 20- and 40-mg Technosphere particles doses, respectively), with the upper 1- sided 95% confidence bound well below the 10 ms threshold. The placebo-corrected mean QTcI change from baseline for moxifloxacin was +5.5 ms, demonstrating the study sensitivity, and the mean change from baseline for placebo was -2.2 ms. The most commonly observed adverse event was cough (54%), which was highest in the Technosphere particles groups.

About Diabetes

Diabetes, which affects 23.6 million people in the U.S., is characterized by the body's inability to properly regulate levels of blood glucose, or blood sugar. Insulin, a hormone produced by the pancreas, normally regulates the body's glucose levels, but in people with diabetes insufficient levels of insulin are produced or the body fails to respond adequately to the insulin it produces. Historically, mealtime insulin therapy regimens have had a number of limitations, including the risk of severe hypoglycemia, the likelihood of weight gain, inadequate post-meal glucose control, the need for complex titration of insulin doses in connection with meals and the need for injections. Additionally, these therapies have not mimicked the natural time-action profile of insulin normally seen in healthy individuals and presented challenges in maintaining compliance.

About AFREZZA®

AFREZZA® is a novel, ultra rapid acting mealtime insulin therapy being developed by MannKind Corporation for the treatment of adult patients with type 1 or type 2 diabetes for the control of hyperglycemia. It is a drug-device combination product, consisting of AFREZZA Inhalation Powder pre-metered into single use dose cartridges and the light, discreet and easy- to-use AFREZZA Inhaler. Administered at the start of a meal, AFREZZA dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Peak insulin levels are achieved within 12 to 14 minutes of administration, mimicking the release of meal-time insulin observed in healthy individuals. To date, the AFREZZA clinical program has involved 56 different studies and over 5,300 adult patients.

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 lead product candidate, AFREZZA®, is in late stage clinical investigation for the treatment of adults with type 1 or type 2 diabetes for the control of hyperglycemia. 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

Investors:
MannKind Corporation
Matthew Pfeffer, Chief Financial Officer
(661) 775-5300
mpfeffer@mannkindcorp.com
or
Media:
MCS Healthcare Public Relations
Laura de Zutter, (908) 234-9900
laurad@mcspr.com