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

Colby and MannKind Sign License and Joint Development Agreement to Develop and Commercialize Cancer Immunotherapy Products

11/13/12
PDF Version
Colby and MannKind Sign License and Joint Development Agreement to Develop and Commercialize Cancer Immunotherapy Products

SAN JOSE, Calif. & VALENCIA, Calif.--(BUSINESS WIRE)--Nov. 13, 2012-- Colby Pharmaceutical Company and MannKind Corporation (Nasdaq: MNKD) today announced a license agreement granting Colby exclusive worldwide rights to develop and commercialize disease-specific antigen compounds and intra-lymph node delivery technologies from MannKind’s novel MKC1106 active immunotherapy programs, which are currently being developed for the treatment of melanoma, prostate, hematological disorders and other human cancers.

Intra-lymph node injections (ILNI, vaccine inoculation directly into the normal lymph node with ultrasound image guided standard syringes) of cancer vaccine antigens have been reproducibly shown to generate much more potent therapeutic T-cell responses, when compared to cancer vaccine antigen immunizations using traditional intra-muscular or sub-cutaneous injections of the same cancer vaccine antigens in animals. In a Phase 1 human melanoma study of MKC1106-MT, the most advanced ILNI regimen from this program, repeat intra-lymph nodal injection for administration of the therapeutic antigens was well-tolerated and generated strong immune responses, clearly meeting the primary endpoints.

Under the terms of the agreement, Colby will pay MannKind upfront and milestone payments linked to the development, approval and commercialization of products, with upfront and potential milestone payments of approximately $140 million total. MannKind will also receive tiered royalties on sales of products.

“We are very keen on this opportunity and in continuing to work with the experienced drug development team at MannKind,” said David Zarling, Ph.D., MBA, Chief Executive Officer of Colby. “MannKind has amassed an extensive and thorough active immunotherapy patent portfolio. We fully appreciate and understand that ILNI generates remarkably superior immune responses that also can be adjuvanted, and our organizations share a passion to advance the current MKC1106 clinical melanoma, prostate and other programs. We will also evaluate ILNI for potential synergy with our lead adjuvant, JVRS-100, a cationic lipid-based immune activator of both innate and adaptive immunity. ILNI and JVRS-100 both represent compelling new therapeutic approaches. We have good reason to believe that our collaboration will uncover other more optimal cancer vaccine modalities and synergies with novel adjuvants not yet realized by others working on cancer vaccines and immune activation. We believe that MannKind’s ILNI and our new immune activators, like JVRS-100 or JVRS-200, or other adjuvants, will prove to be important for rational cancer immunotherapies.”

About Colby Pharmaceutical Company

Colby is a privately held company located at 5941 Optical Court, San Jose, CA 95138. Colby is developing new oral small molecule signal transduction modulator drugs and immune modulator biopharmaceuticals for cancer, chronic inflammation, pain, infectious diseases, and neurodegenerative or metabolic diseases. Colby is going after the indications for the very sick patients for which there are such poor alternatives – i.e., melanoma, acute myelogenous leukemia, cancer radio-chemo-mitigation or mucositis, and cancer patient vaccination by ILNI. Colby's lead small molecule and biologic drug candidates are new molecular entities which have unique mechanisms of action and are in newly discovered pathways for molecular targeted therapies to treat or cure patients with hard to treat infections, inflammation, malignancies and pain, with minimal toxicities and side effects. The company encourages inquiries to dzarling@colbypharmaceuticals.com regarding potential investment, partnering, and/or licensing opportunities

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, AFREZZA®, 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 http://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.

This press release contains forward-looking statements, including statements regarding our expectations and beliefs regarding the license agreement with Colby, which 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 our current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks regarding reliance on Colby to develop and commercialize immunotherapy products, including risks that Colby may not devote sufficient efforts to those activities, whether due to lack adequate financial or other resources, a strategic decision to focus on other initiatives or otherwise, and risks that the agreement with Colby may be terminated, as well as risks associated with the progress, timing and results of clinical trials, difficulties or delays in seeking or obtaining regulatory approval, competition from other pharmaceutical or biotechnology companies, and other risks detailed in our filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2011. 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 we undertake no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release.

Source: MannKind Corporation

For Colby Pharmaceuticals:
David Zarling
Chief Executive Officer
(650) 333-3150
dzarling@colbypharmaceuticals.com
or
For MannKind Corporation:
Matthew Pfeffer
Chief Financial Officer
(661) 775-5300
mpfeffer@mannkindcorp.com