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

Pre-Clinical Data Demonstrates Promising Potential of MannKind’s IRE1α Inhibitor to Treat Multiple Myeloma

05/31/12
Pre-Clinical Data Demonstrates Promising Potential of MannKind’s IRE1α Inhibitor to Treat Multiple Myeloma

VALENCIA, Calif.--(BUSINESS WIRE)--May. 31, 2012-- Results published in Blood, the official journal of the American Society of Hematology, confirm that inhibition of the IRE1α-XBP1 pathway impacts the survival of myeloma cells, suggesting a promising therapeutic option in multiple myeloma. The pre-clinical study, conducted by researchers at Dana-Farber Cancer Institute in collaboration with MannKind Corporation (Nasdaq: MNKD), confirm that blocking the XBP1 arm of the unfolded protein response with MannKind's novel, first-in-class IRE1α RNase domain inhibitor, MKC-3946, alone or in combination with bortezomib or 17AAG, inhibited growth in multiple myeloma cells, while leaving normal cells intact.

"Results from this research study demonstrate that biologically based therapies have great potential to advance the treatment of multiple myeloma and extend the lives of patients with this devastating and deadly disease," said Kenneth C. Anderson, M.D., director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, Kraft Family Professor of Medicine at Harvard Medical School, and corresponding author of the study. "Our findings show that targeting the XBP1 pathway with a selective IRE1α inhibitor, in this case the small molecule inhibitor MKC-3946, is a promising therapeutic strategy, providing the preclinical basis for future trials evaluating the clinical efficacy of this approach to improve patient outcomes in multiple myeloma."

In healthy individuals, a key signaling process, known as the unfolded protein response, regulates protein folding and facilitates cellular homeostasis. In patients with multiple myeloma, this process is not properly regulated, in part because the IRE1α enzyme activates the XBP1 gene, allowing myeloma cells to escape cell death, grow and/or become resistant to chemotherapy, radiotherapy and certain cancer drugs. Researchers believe that by restoring normal cell regulation and function, myeloma tumor cells no longer continue to multiply, and become more susceptible to common oncology treatments.

Findings from this pre-clinical study show that MKC-3946 inhibited the IRE1α-XBP1 pathway of myeloma cells, successfully blocking XBP1 splicing. Results also showed that the study compound:

  • Enhanced cytotoxicity induced by the oncology agents bortezomib or 17AAG, even in the presence of bone marrow stromal cells or exogenous IL-6;
  • Contributed to cell death in combination with these agents and as a single agent with fresh bone marrow aspirates from myeloma patients;
  • Inhibited growth of multiple myeloma cells in vivo alone and in combination with these agents

MannKind's IRE-1α inhibitor MKC-3946 is part of a drug discovery program (MKC204) targeting the key biochemical signaling pathway of unfolded protein response that may play a role in a number of diseases. Through this program, MannKind has identified and optimized several IRE-1α inhibitors as potential investigational agents. In addition to multiple myeloma, IRE-1α inhibitors may have potential applications in other indications where this pathway plays a key role, such as breast, brain and pancreatic cancers as well as autoimmune diseases, neurodegenerative diseases and certain metabolic disorders.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer with a five-year relative survival rate of approximately 41 percent, one of the lowest of all cancers. In 2012, an estimated 21,700 adults in the United States will be diagnosed with multiple myeloma and approximately 10,710 people will die from the disease.

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, AFREZZAR, 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 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