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 Study of Inhaled Clofazimine

09/06/22
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  • Study supports the dosing regimen that will be pursued in further clinical programs
  • No serious adverse events or QT prolongation identified
  • Planning underway to discuss results and the ongoing clinical program with the FDA

DANBURY, Conn. and WESTLAKE VILLAGE, Calif., Sept. 06, 2022 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD), a company focused on the development and commercialization of inhaled therapeutic products for patients with endocrine and orphan lung diseases, announced today that it has successfully completed a Phase 1 study of clofazimine inhalation suspension (MNKD 101) and is planning discussions with the U.S. Food and Drug Administration (FDA) regarding results and the ongoing clinical program.

Clofazimine is being developed as an inhalation treatment option for nontuberculous mycobacterial (NTM) lung disease. NTM lung disease is a serious infection that is caused by bacteria common in the environment that can lead to a reduction in lung function, cough, fatigue, and quality of life. It is estimated that approximately 86,000 people in the U.S. are living with NTM lung disease, and it is on the rise growing 8% each year with women, the elderly, and those with underlying lung conditions at greatest risk. MNKD-101 has been designated by the FDA as both an orphan lung and a qualified infectious disease product (QIDP) for the treatment of pulmonary NTM infections.

“There is a high unmet need to develop medicines that are well tolerated and effective in alleviating symptoms for those living with NTM lung disease,” said Michael Castagna, PharmD, Chief Executive Office of MannKind Corporation. “As we continue to expand our orphan lung diseases focus at MannKind, we are encouraged by what we are seeing with inhaled clofazimine and the future potential to help patients.”

Study MKC-CI -001 was a Phase I randomized, double-blind, placebo-controlled, single- (SAD) and multiple-ascending dose (MAD) study to evaluate the safety, tolerability, and pharmacokinetics (PK) of MNKD-101 in healthy volunteers. The key safety findings of the study included:

  • Clofazimine inhalation solution found to be generally well tolerated at daily doses of up to 90 mg over a seven-day period
  • No lab abnormalities, QT prolongation, or serious adverse events identified

“The safety and tolerability results for inhaled clofazimine are encouraging and we look forward to advancing the nebulized formulation of clofazimine to the next phase of development,” said Thomas Hofmann, Chief Scientific Officer of MannKind Corporation. “Clofazimine presented as being very lipophilic and demonstrated the expected therapeutic plasma concentrations we were targeting. In future studies, we plan to evaluate the potential for MNKD-101 to produce drug levels that exceed the minimum inhibitory concentration in the lung beyond the treatment period.”

In the SAD portion of the study, 24 adults were enrolled in one of three cohorts (n = 8 per cohort) that received a single inhaled dose of 30 mg, 60 mg or 90 mg clofazimine, respectively. Participants resided at the clinical research unit until day 5 post-dose, during which time they were evaluated for safety and samples were collected for PK assessment. Participants returned on days 8 and 15 for additional safety assessments and sample collection. During the MAD portion of the study, 16 adults were enrolled in one of two cohorts (n = 8 per cohort) that received a daily inhaled dose of 30 mg or 90 mg clofazimine for a seven-day period. Participants resided at the clinical research unit until day 8 post-dose, during which time they were evaluated for safety and samples were collected for PK assessment. Participants returned on days 15 and 36 for additional safety assessments and sample collection.

Additional data collected during the MKC-CI-001 study is currently undergoing final analysis. Detailed data findings will be presented in upcoming publications and scientific conferences.

About MannKind
MannKind Corporation (Nasdaq: MNKD) focuses on the development and commercialization of innovative therapeutic products and devices to address serious unmet medical needs for those living with endocrine and orphan lung diseases.

We are committed to using our formulation capabilities and device engineering prowess to lessen the burden of diseases such as diabetes, pulmonary arterial hypertension (PAH) and nontuberculous mycobacterial (NTM) lung disease. Our signature technologies – dry-powder formulations and inhalation devices – offer rapid and convenient delivery of medicines to the deep lung where they can exert an effect locally or enter the systemic circulation.

With a passionate team of Mannitarians collaborating nationwide, we are on a mission to give people control of their health and the freedom to live life.

Please visit mannkindcorp.com to learn more, and follow us on LinkedIn, Facebook, Twitter or Instagram.

Forward-looking Statements
This press release contains forward-looking statements about the implications of clinical data that involve risks and uncertainties. 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, which include, without limitation, the risk that continued testing of an investigational drug product may not yield successful results or results that are consistent with earlier testing, and other risks detailed in MannKind’s filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2021 and subsequent periodic reports on Form 10-Q and current reports on Form 8-K. 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 and the MannKind logo are registered trademarks of MannKind Corporation.

For MannKind:
Christie Iacangelo, Corporate Communications
(818) 292-3500
Email: media@mannkindcorp.com

Rose Alinaya, Investor Relations
(818) 661-5000
Email: ir@mannkindcorp.com 


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Source: MannKind