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 Corporation Achieves All Milestones of Research Agreement with Multiple Myeloma Research Foundation to Develop New Therapy

03/29/10
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MannKind Corporation Achieves All Milestones of Research Agreement with Multiple Myeloma Research Foundation to Develop New Therapy

NORWALK, Conn. & VALENCIA, Calif., Mar 29, 2010 (BUSINESS WIRE) --The Multiple Myeloma Research Foundation (MMRF) and MannKind Corporation (Nasdaq:MNKD) today announced that MannKind has successfully achieved all milestones of a research agreement with MMRF to develop a novel, first-in-class inhibitor for the treatment of multiple myeloma. The MMRF awarded MannKind a $1 million grant through its 2007 Biotech Investment Award program, a multi-year, results-driven commitment to fund the development of innovative and effective treatments for multiple myeloma, based on clearly defined milestones.

The final milestone of the research agreement was achieved based on selection of an IRE-1a (inositol-requiring enzyme-1) inhibitor for evaluation in the preclinical studies that are required to file an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration.

Results from nonclinical studies show that the IRE-1a compound inhibits growth of tumor cells by selectively targeting and inhibiting the key signaling process that regulates protein folding and facilitates cell death, known as the IRE-1a and XBP-1 (X-box binding protein-1) pathway. Researchers believe that by restoring normal cell regulation and function, tumor cells no longer continue to multiply, and become more susceptible to common oncology treatments, such as chemotherapy, radiotherapy and other therapies used to prevent the growth of new blood vessels in solid tumors.

"We are very pleased to have met these important milestones and to continue development of a targeted drug therapy that may inhibit the growth of cells in cancers like multiple myeloma," said Peter Richardson, MRCP, Corporate Vice President and Chief Scientific Officer, MannKind Corporation. "I am especially proud of our group's successful work in discovering and optimizing this inhibitor to the point where it is now ready for the preclinical evaluation that is needed before starting human clinical trials. MannKind looks forward to continuing its relationship and collaboration with the MMRF beyond completion of this research agreement, as we too are committed to developing innovative therapies to address the unmet medical need in cancer."

MannKind's IRE-1a program includes a group of novel compounds that have potential applications for the treatment of multiple myeloma as well as breast, prostate, and pancreatic cancers; autoimmune diseases, such as rheumatoid arthritis and lupus; amyotrophic lateral sclerosis (ALS); type 2 diabetes mellitus; Alzheimer's disease, and ischemia-reperfusion, such as heart attack and stroke.

"Our focus at the MMRF is to support research in pursuit of next generation therapies that may help extend the lives of patients and treat multiple myeloma," said Louise M. Perkins, PhD, Chief Scientific Officer of the MMRF. "We are delighted that MannKind has committed to taking its investigational therapy to the next level of development in the hopes of finding more effective treatments that may one day improve the lives of patients."

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer. The five-year relative survival rate for multiple myeloma is approximately 34 percent, one of the lowest of all cancers. In 2009, approximately 20,000 adults in the United States were diagnosed with multiple myeloma and approximately 11,000 people died from the disease.

About the Multiple Myeloma Research Foundation (MMRF)

The Multiple Myeloma Research Foundation (MMRF) was established in 1998 as a 501©3 non-profit organization by twin sisters Karen Andrews and Kathy Giusti, soon after Kathy's diagnosis with multiple myeloma. The mission of the MMRF is to relentlessly pursue innovative means that accelerate the development of next-generation multiple myeloma treatments to extend the lives of patients and lead to a cure. As the world's number-one private funder of multiple myeloma research, the MMRF has raised over $130 million since its inception to fund nearly 120 laboratories worldwide. An outstanding 93 percent of funds raised go toward research and related programming. The MMRF has supported 40 new compounds and approaches in clinical trials and pre-clinical studies and has facilitated 22 clinical trials through its sister organization, the Multiple Myeloma Research Consortium (MMRC). For more information about the MMRF, please visit www.themmrf.org.

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 an 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 to this NDA from the FDA requesting additional information. Currently, AFREZZA remains under regulatory review. Other products in its pipeline include the cancer immunotherapy products MKC1106-PP and MKC1106-MT, which are currently in phase 1 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 

For MannKind Corporation:
Investors:
MannKind Corporation
Matthew Pfeffer, Chief Financial Officer
661-775-5300
mpfeffer@mannkindcorp.com
or
Media:
MCS Healthcare Public Relations
Alanna Jamieson, 908-234-9900
alannaj@mcspr.com
or
For Multiple Myeloma Research Foundation:
Terri Clevenger, 203-227-0209
tclevenger@continuumhealthcom.com