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

United Therapeutics and MannKind Announce Collaboration for Pulmonary Hypertension Products

09/04/18
PDF Version

Exclusive license agreement for Treprostinil Technosphere®; $95 million in upfront and milestone payments

Research agreement for additional products for additional $10 million

SILVER SPRING, Md. and WESTLAKE VILLAGE, Calif., Sept. 04, 2018 (GLOBE NEWSWIRE) -- United Therapeutics Corporation (Nasdaq: UTHR) and MannKind Corporation (Nasdaq: MNKD) today announced that they have entered into a worldwide exclusive licensing and collaboration agreement for the development and commercialization of a dry powder formulation of treprostinil, an investigational product currently being evaluated in clinical trials for the treatment of pulmonary arterial hypertension.

Under the agreement, United Therapeutics will be responsible for global development, regulatory and commercial activities.  MannKind will manufacture clinical supplies and initial commercial supplies of the product at its manufacturing facility in Danbury, Connecticut. Long-term commercial supplies will be manufactured by United Therapeutics. 

Under the terms of the agreement, MannKind Corporation will receive an upfront payment of $45 million and potential milestone payments of up to $50 million, dependent upon the achievement of specific development targets.  MannKind will also be entitled to receive low double-digit royalties on net sales of the product.  In addition, MannKind granted United Therapeutics an option to expand the license to include other active ingredients for the treatment of pulmonary hypertension.  Each optioned product would be subject to the payment to MannKind of up to $40 million in additional option exercise and development milestone payments as well as a low double-digit royalty on net sales of any such product. 

The effectiveness of the licensing and collaboration agreement is conditioned on expiration or termination of the required waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

The parties also entered into a research agreement for the conduct of research by MannKind on behalf of United Therapeutics for products outside the scope of the licensing and collaboration agreement.  MannKind will receive an immediate payment of $10 million in consideration for its performance under the research agreement. 

“We are excited to partner with United Therapeutics, a company that shares our passionate focus on changing patients’ lives,” stated Michael Castagna, Pharm.D., Chief Executive Officer of MannKind. “We are pleased with this new opportunity to demonstrate the value of our drug and device combination platform for delivering therapeutic products.  We believe this collaboration will have the potential to significantly improve the lives of people living with pulmonary arterial hypertension.”

“On the very same day 21 years ago, we enabled the development of treprostinil into a practical treatment thanks to an invention of the late Al Mann – the discrete, ambulatory, programmable, parenteral infusion pump called the MiniMed 407c,” said Martine Rothblatt, Ph.D., Chairman and Chief Executive Officer of United Therapeutics.  “By marrying our molecule and MiniMed’s device, Remodulin® was born. As we now move into the second generation of United Therapeutics products, we are proud to once again team with Al Mann’s brilliance, this time with his Dreamboat®, Bluhale® and Cricket® devices for inhalation.  I believe these revolutionary new inhalation devices will accomplish for Tyvaso® what our recently-approved Implantable System for Remodulin, pending RemUnity™ system and recently-acquired Trevyent® product represent for Remodulin – a further step toward a next generation of treprostinil drug-device systems that enhance options for patients, their families and their prescribers.”

Conference Call

MannKind will host a conference call today at 4:00 p.m. Eastern Time. To listen to the conference call webcast live via the Internet, visit the Company's website at www.mannkindcorp.com and click on the link in the Webcasts section of News & Events.  To participate in the live call by telephone, please dial (800) 289-0438 toll-free or (323) 794-2423 toll/international and use the conference passcode: 6006518.

A telephone replay of the call will be accessible for approximately 14 days following completion of the call by dialing (844) 512-2921 toll-free or (412) 317-6671 toll/international and use the replay passcode: 6006518.  A replay will also be available on MannKind's website for 14 days.

About MannKind Corporation

MannKind Corporation (NASDAQ: MNKD) focuses on the development and commercialization of inhaled therapeutic products for patients with diseases such as diabetes and pulmonary arterial hypertension.  MannKind is currently commercializing Afrezza® (insulin human) Inhalation Powder, the Company's first FDA-approved product and the only inhaled rapid-acting mealtime insulin in the United States, where it is available by prescription from pharmacies nationwide. MannKind is headquartered in Westlake Village, California, and has a state-of-the art manufacturing facility in Danbury, Connecticut. The Company also employs field sales and medical representatives across the U.S. For further information, visit www.mannkindcorp.com.

About United Therapeutics

United Therapeutics is a biotechnology company focused on the development and commercialization of innovative products to address the unmet medical needs of patients with chronic and life-threatening conditions. [uthr-g]

Forward-looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although United Therapeutics’ and MannKind’s management teams believe that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of United Therapeutics and MannKind, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA, regarding whether and when to approve any drug or device application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the absence of any guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives as well as those discussed or identified in the public filings with the Securities and Exchange Commission made by United Therapeutics and MannKind, including those risks and uncertainties listed in United Therapeutics’ and MannKind’s annual reports on Form 10-K for the year ended December 31, 2017, and listed or described in subsequent reports filed by United Therapeutics and MannKind with the Securities and Exchange Commission. We are providing this information as of September 4, 2018, and neither United Therapeutics nor MannKind undertake any obligation to update or revise the information contained in this press release whether as a result of new information, future events or any other reason.

REMODULIN and TYVASO are registered trademarks of Untied Therapeutics Corporation. REMUNITY is a trademark of United Therapeutics Corporation. TREVYENT is a registered trademark of SteadyMed Therapeutics, Inc. DREAMBOAT, AFREZZA, BLUHALE, CRICKET and TECHNOSPHERE are registered trademarks of MannKind Corporation.

Contacts:

United Therapeutics
James Edgemond
Phone: (301) 608-9292
E-mail: jedgemond@unither.com

MannKind Corporation
Rose Alinaya
SVP, Investor Relations
818-661-5000
ir@mannkindcorp.com

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Source: MannKind