MannKind Corporation
Encyclopedia
MannKind Corporation based in Valencia, California
, is a biopharmaceutical company focusing on the discovery, development, and commercialization of therapeutic products for diseases such as diabetes and cancer
. The company, while technically founded in February 1991, took its present form in 2003 as a merger of three companies owned by Alfred E. Mann
, named after its founder in an attempt at humor. One of the former companies, Pharmaceutical Discovery, was purchased in 2001 from Solomon Steiner; with that purchase MannKind acquired the Technosphere molecule and Medtone Inhaler, upon which was developed its lead product, Afrezza (inhalable insulin
), which was under FDA review. Alfred Mann is chairman of the board and chief executive officer. Mann has invested approximately $900 million in his company.
. In March 2009, MannKind signed a purchase agreement with Pfizer
for its insulin manufacturing facility in Frankfurt, Germany; however, the purchase was subject to Sanofi-Aventis
' right of refusal within 60 days' notification and approval of Infraserv, the corporate park operator. Infraserv gave its consent; however, Sanofi-Aventis exercised its right to refuse, purchasing the facility. MannKind acquired eight tons of insulin for use in manufacture of a pulmonary product, an option to purchase an undisclosed amount of additional insulin at a specified price, and the license to the manufacturing process. MannKind was relieved of ownership of the manufacturing facility.
peaking 12 to 15 minutes following inhalation. More importantly, Afrezza leaves no persistent "tail." After a few hours, it is gone from the system, while injectable insulins typically persist. This leads to the hypothesis that Afrezza may mimic the kinetic synchronization of the hepatic (liver
) system, restoring more natural hepatic function by reducing the excess gluconeogenesis
. The evidence supporting this hypothesis offered by the company is marked and very significant reduction in post-meal glucose excursions and significant improvements in overall glucose control, as measured by decreases in glycosylated hemoglobin
(A1C) levels, without the weight gain typically associated with insulin therapy. However, the investment community, and the pharmaceutical industry, haunted by the failures of Pfizer's Exubera, remain unconvinced that there is any meaningful market for inhalable insulins, including Afrezza, and have ceased research and funding in this area.
MannKind's oncology drug candidates, MKC1106-PP for prostate and MKC1106-MT for advanced stage melanoma (in phase II study), use the body's immune system (immunotherapy
) to target specific melanoma
antigen (PRAME) and prostate specific membrane antigen (PSMA).
MannKind introduced its next generation inhalation technology, a miniature, breath-powered inhaler used in combination with single-use cartridges containing pre-metered doses. The sleek inhaler fits within the palm of the hand and is ready to use with a quick and intuitive cartridge load mechanism. These attributes result in an easy-to-use, elegant delivery system providing optimal discretion during use. Initial pharmacokinetic studies were followed by studies of safety and efficiency involving technosphere formulations of different therapeutic proteins.
with an entity controlled by Alfred Mann, who more recently agreed to swap debt for equity in 700,000-share increments over several months for $7.15 per share.
No revenue was expected until Afrezza is approved by the FDA and marketed. The FDA approval PDUFA date was January 16, 2010; however, on March 12, 2010 (almost one year after the drug application was submitted) the FDA issued a Complete Response Letter indicating that it required additional information. On June 9, the company met with FDA officials to determine FDA requirements. Based on these discussions, MannKind resubmitted its NDA on June 29, 2010. The PDUFA date for the resubmission was December 29, 2010. On January 19, 2011 MannKind Corporation announced that the FDA rejected Afrezza and asked for two more clinical trials.
Valencia, California
Valencia is an affluent planned community located in the City of Santa Clarita, California and Los Angeles County, California, U.S. in the northwestern corner of the Santa Clarita Valley, adjacent to Interstate 5. In 1987, it was one of the four unincorporated communities that merged to create the...
, is a biopharmaceutical company focusing on the discovery, development, and commercialization of therapeutic products for diseases such as diabetes and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. The company, while technically founded in February 1991, took its present form in 2003 as a merger of three companies owned by Alfred E. Mann
Alfred E. Mann
Alfred E. Mann , who is also known as Al Mann, is an American entrepreneur and philanthropist. According to Forbes magazine, his estimated net worth exceeded $2.2 billion as of 2007, ranking him the 204th richest man in America and the 390th richest man in the world.Born and raised in Portland, his...
, named after its founder in an attempt at humor. One of the former companies, Pharmaceutical Discovery, was purchased in 2001 from Solomon Steiner; with that purchase MannKind acquired the Technosphere molecule and Medtone Inhaler, upon which was developed its lead product, Afrezza (inhalable insulin
Inhalable insulin
Inhalable insulin was available from September 2006 to October 2007 in the United States as a new method of delivering insulin, a drug used in the treatment of diabetes, to the body...
), which was under FDA review. Alfred Mann is chairman of the board and chief executive officer. Mann has invested approximately $900 million in his company.
Facilities
MannKind's corporate headquarters are in Valencia, California. The Afrezza manufacturing facility is in Danbury, ConnecticutDanbury, Connecticut
Danbury is a city in northern Fairfield County, Connecticut, United States. It had population at the 2010 census of 80,893. Danbury is the fourth largest city in Fairfield County and is the seventh largest city in Connecticut....
. In March 2009, MannKind signed a purchase agreement with Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
for its insulin manufacturing facility in Frankfurt, Germany; however, the purchase was subject to Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
' right of refusal within 60 days' notification and approval of Infraserv, the corporate park operator. Infraserv gave its consent; however, Sanofi-Aventis exercised its right to refuse, purchasing the facility. MannKind acquired eight tons of insulin for use in manufacture of a pulmonary product, an option to purchase an undisclosed amount of additional insulin at a specified price, and the license to the manufacturing process. MannKind was relieved of ownership of the manufacturing facility.
Product candidates
Afrezza (as is claimed by MannKind and supported by company-funded research and trials) is an ultra-rapid-acting insulinInsulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
peaking 12 to 15 minutes following inhalation. More importantly, Afrezza leaves no persistent "tail." After a few hours, it is gone from the system, while injectable insulins typically persist. This leads to the hypothesis that Afrezza may mimic the kinetic synchronization of the hepatic (liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
) system, restoring more natural hepatic function by reducing the excess gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
. The evidence supporting this hypothesis offered by the company is marked and very significant reduction in post-meal glucose excursions and significant improvements in overall glucose control, as measured by decreases in glycosylated hemoglobin
Glycosylated hemoglobin
Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose...
(A1C) levels, without the weight gain typically associated with insulin therapy. However, the investment community, and the pharmaceutical industry, haunted by the failures of Pfizer's Exubera, remain unconvinced that there is any meaningful market for inhalable insulins, including Afrezza, and have ceased research and funding in this area.
MannKind's oncology drug candidates, MKC1106-PP for prostate and MKC1106-MT for advanced stage melanoma (in phase II study), use the body's immune system (immunotherapy
Immunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
) to target specific melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
antigen (PRAME) and prostate specific membrane antigen (PSMA).
MannKind introduced its next generation inhalation technology, a miniature, breath-powered inhaler used in combination with single-use cartridges containing pre-metered doses. The sleek inhaler fits within the palm of the hand and is ready to use with a quick and intuitive cartridge load mechanism. These attributes result in an easy-to-use, elegant delivery system providing optimal discretion during use. Initial pharmacokinetic studies were followed by studies of safety and efficiency involving technosphere formulations of different therapeutic proteins.
Finances and future of Afrezza
MannKind had approximately $20 million cash, while spending approximately $15 million monthly. It had approximately $188 million of available borrowings under the loan agreementLoan agreement
A loan agreement is a contract entered into between which regulates the terms of a loan. Loan agreements usually relate to loans of cash, but market specific contracts are also used to regulate securities lending....
with an entity controlled by Alfred Mann, who more recently agreed to swap debt for equity in 700,000-share increments over several months for $7.15 per share.
No revenue was expected until Afrezza is approved by the FDA and marketed. The FDA approval PDUFA date was January 16, 2010; however, on March 12, 2010 (almost one year after the drug application was submitted) the FDA issued a Complete Response Letter indicating that it required additional information. On June 9, the company met with FDA officials to determine FDA requirements. Based on these discussions, MannKind resubmitted its NDA on June 29, 2010. The PDUFA date for the resubmission was December 29, 2010. On January 19, 2011 MannKind Corporation announced that the FDA rejected Afrezza and asked for two more clinical trials.