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 Successfully Completes Phase 1 Trial of Treprostinil Technosphere for Pulmonary Arterial Hypertension Advancing Development to Next Phase

06/07/18
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  • Study achieved primary endpoint of safety and tolerability
  • Progressive dosing of Treprostinil Technosphere (TreT) significantly exceeded the corresponding peak plasma and exposure levels of the maximum recommended dose of Tyvaso® Inhalation Solution
  • Achieved a maximum tolerated dose with no serious adverse events reported

             
WESTLAKE VILLAGE, Calif., June 07, 2018 (GLOBE NEWSWIRE) -- MannKind Corporation(Nasdaq:MNKD) today announced that it has completed a Phase 1 clinical study of Treprostinil Technosphere (TreT) under an Investigational New Drug application filed with the Food and Drug Administration.

The key highlights of this study are:

  • Ability to deliver TreT within 1-2 inhalations in <10 seconds
  • Maximum tolerated dose is expected to be able to deliver higher plasma concentrations above the reported data for the current commercially available inhaled treprostinil
  • Based on these data, MannKind is preparing the next phase of development to evaluate the safety and tolerability of TreT in patients with PAH
  • Data will be submitted to be presented at an upcoming conference

“We are pleased to have completed the TreT Phase 1 trial, which met the study’s safety, tolerability and pharmacokinetics objectives,” stated David Kendall, Chief Medical Officer of MannKind. “We are excited to utilize our existing technology platform and device capabilities to create an easy-to-use and tolerable formulation of treprostinil to help unmet patient needs in a serious chronic disease such as PAH.”

TreT is proposed as a drug-device combination product for the treatment of patients with pulmonary arterial hypertension (PAH), utilizing a small, portable, breath-powered inhaler that is intended to simplify drug dosing. The regulatory and development pathway is expected to be capital efficient, using existing safety data of the component API to reduce Phase 3 requirements to a pivotal safety and efficacy trial and a pivotal bioequivalency trial.  The regulatory submission in the United States is expected to utilize the 505(b)(2) pathway.

“People living with PAH need more convenient and tolerable treprostinil treatment options to help them live a less intrusive lifestyle. I am excited to see that MannKind was safely able to achieve higher plasma levels than reported for the current standard of care using Technosphere-based treprostinil,” stated Lewis Rubin, MD, Emeritus Professor of Medicine at the University of California, San Diego School of Medicine.

This was a single site study with 48 healthy, normal subjects enrolled in 8 cohorts of 6 subjects each. The treatments were intended to establish the maximum tolerated dose, starting at 30 mcg. Each subject received one dose of TreT by oral inhalation during the treatment period. A total of 12 pharmacokinetic blood samples were collected from each subject. Plasma pharmacokinetic samples were analyzed for treprostinil.

The primary objective of the Phase 1 clinical study was to investigate the safety, tolerability, and pharmacokinetics of TreT in healthy volunteers after dosing by oral inhalation.  Secondary endpoints include the evaluation of systemic exposure and pharmacokinetics of TreT, including dose proportionality. For more information about the study, please visit www.ClinicalTrials.gov.  

About Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension (PAH) is a chronic, progressive disease characterized by abnormally high blood pressure in the pulmonary arteries between the heart and lungs of an affected individual.  Over time, this can cause increased strain on the heart, leading to right-heart failure. Symptoms of PAH include shortness of breath, dizziness and fatigue, which grow more severe as the disease progresses. PAH represents Group I within the Pulmonary Hypertension WHO clinical classification system and is one of five such groups.

About MannKind
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.

Forward-Looking Statements
Statements contained in this press release that are not strictly historical in nature are forward-looking statements that involve risks and uncertainties.  These statements include, without limitation, statements regarding MannKind's anticipated use of the proceeds from the offering. Words such as "believes," "anticipates," "plans," "expects," "intends," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon MannKind's current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation, the risks detailed in MannKind's filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2017. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and MannKind undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release.

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

 

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Source: MannKind