Tolero and MannKind Sign Collaboration and License Agreement to Develop and Commercialize Novel BTK Inhibitors for Malignancies and Inflammatory Diseases.
Tolero Pharmaceuticals, a biopharmaceutical company focused on the discovery and development of novel therapeutics to treat cancer and other serious human diseases, and MannKind Corporation (Nasdaq: MNKD), focused on discovering, developing and commercializing therapeutic products for diabetes and cancer, today announced a license agreement granting Tolero exclusive worldwide rights to develop and commercialize compounds from MannKind's novel BTK (Bruton's tyrosine kinase) program, which are currently being developed for the treatment of hematological malignancies and inflammatory diseases.
I came across this company that MannKind made a License agreement on some cancer drugs. This is the first time I have seen this bit it shows that there are other potential drugs int the pipeline not even tied to Technosphere. Has anybody ever heard of this company Tolero Pharmaceutical.
NEW YORK (AP) — Diabetes drug developer MannKind Corp. said Monday that it is licensing a group of experimental drugs to Tolero Pharmaceuticals Inc. in a deal that could be worth more than $130 million.
MannKind said the drug candidates are being studied as treatments for blood cancers and inflammatory diseases. Tolero will have worldwide rights to develop the drugs. Tolero will pay MannKind as the drugs advance through clinical development and regulatory review and reach sales targets if they are approved. MannKind said it will also receive licensing payments and royalties on any sales.
The Valencia, Calif., company will have the right to require the drugs after early-stage clinical testing is complete.
Tolero is based in Salt Lake City, and it develops treatments for cancer and other diseases.
The insulin market is highly consolidated and dominated by select players operating on a global level such as Novo Nordisk A/S, Eli Lilly and Company, and Sanofi. In China, local and regional players such as Shanghai Fosun Pharmaceuticals Pvt. Ltd. and Tonghua Dongbao also contribute to the insulin market.
in 2012. Other segments such as premixed, intermediate-acting and short-acting insulin derivatives are expected to lose market share during the forecast period. This is mainly due to low patient preference and lack of R&D in these segments. Pharmaceutical companies have concentrated their R&D strategies towards long-acting and rapid-acting derivatives development, which would boost market growth
The rapid-acting, long-acting and premixed derivatives segments are the most important segments in China. Growth in these segments is mainly attributed to rising population of type-1 diabetes and growing tendency of type-2 diabetes patients to use insulin as a therapeutic agent.
The insulin market in China is expected to grow steadily due to extensive R&D activities for the development of new insulin analogs and formulations that can be administered via different routes. Various products such as LY2605541 (Eli Lilly and Company), MK-1293 (Merck & Co., Inc.), NN1218 (Novo Nordisk A/S) and Afrezza (MannKind Corporation) are under pipeline studies and are expected to enter the market during the forecast period. Due to these new formulations, the market is likely to grow steadily during the forecast period.
Albany, New York (PRWEB) September 11, 2014
According to a new market report published by Transparency Market Research "Global and China Insulin Market (Rapid-Acting, Short-Acting, Intermediate-Acting, Long-Acting, Premixed, Modern and Human Insulin) - Industry Analysis, Size, Share, Growth, Trends and Forecast (Value and Volume), 2013 - 2019", the global insulin market was valued at USD 19.99 billion in 2012 and is expected to grow at a CAGR of 6.1% from 2013 to 2019 to reach USD 32.24 billion in 2019.
Rising prevalence of diabetes is one of the serious healthcare concerns on a global level. Insulin is a hormone secreted by pancreas to absorb the blood sugar. However, in diabetes, it is either not possible for the body to secrete insulin (type-1) or to utilize secreted insulin to metabolize glucose (type-2). Insulin deficiency in diabetic patients is the most important factor driving the insulin market globally. Rising prevalence of diabetes and extensive R&D activities are the other key factors boosting growth in the insulin market. No permanent cure has been invented for diabetes, thus the evolution of insulin therapy has emerged as an indispensible treatment therapy for type-1 diabetes patients.
The global and China insulin market is segmented based on source and mode of action. The insulin market by source is categorized as modern insulin and human insulin. The modern insulin segment is expected to grow at the fastest rate during the forecast period from 2013 to 2019, globally as well as in China. The insulin market by mode of action is segmented into rapid-acting, short-acting, intermediate-acting, long-acting and premixed insulin derivatives. Due to advantages over other derivatives, the long-acting derivatives segment is expected to grow rapidly during the forecast period. The segment held the largest share of 42.77% of the total market in 2012. It is expected to be the largest segment by the end of 2019. Rapid-acting insulin was the second largest segment
sale between $250M, $350M, Mnkd gets $250M bonus.
sale between $350M, $500M, Mnkd gets $350M bonus.
sale between $500M, $750M, Mnkd gets $500M bonus.
sale more than $750M, Mnkd gets $650M bonus ($925M - $150M - $75M - $50M)
$50M in 10-Q is for EU and Japan approval. Matt will disclose the $250M target. How will mkt react ?
Only intelligent response is solicited.
In a private phone call, Matt said that $250M sale is easily achievable. It's a multi-tier sale target. For instance,
Here is one short term catalyst.
Last year’s meeting in San Francisco, California, brought together over 450 clinicians and scientists from 24 countries to focus on applying science and technology to fight diabetes.
This year’s Diabetes Technology Meeting will include sessions on: (1) Wearable Devices for Diabetes; (2) Big Data for Diabetes Management; (3) Performance of Cleared Blood Glucose Monitors – What is Needed?; (4) Controversies in Developing the Artificial Pancreas; (5) Novel Treatments & New Technology for Insulin Delivery; (6) Is Diabetes Technology Better in the US or Europe?; (7) Role of mHealth in Managing Diabetes; and (8) New Technology in CGM
On Thursday, November 6, Diabetes Technology Society will present 4 optional pre-meeting workshops.
Concurrent morning workshops are:
•Workshop A: Reimbursement for Diabetes Technology
•Workshop B: Technology for Detection and Prevention of Hypoglycemia
Concurrent afternoon sessions are:
•Workshop C: Regulatory Science; New Performance Guidances & a New Surveillance Error Grid
•Workshop D: Improving Adherence to Diabetes Technology Devices
•Afrezza is administered through MannKind’s proprietary Technosphere technology, which resembles the size of an inhaler and makes insulin delivery easy and fast.
•MannKind has a partnership with Sanofi (SNY), which will use its resources and marketing power to give Afrezza meaningful distribution potential.
•After the FDA approved Afrezza in June, MNKD stock peaked at $11.48 per share.
•The MNKD stock price today hovers around the $5.50 level.
Having followed MNKD stock closely for more than two years, I’ve noticed that institutional money tends to flow in and out of the stock fairly quickly. It flows in before a major catalyst, and it flows out after a major catalyst.
Afrezza hitting the market in early 2015 is a major catalyst. And if you’re comfortable with a make-or-break short-term play like MNKD in your portfolio, you’d be hard-pressed to find a more attractive risk-reward profile than MannKind stock. It’s not often that the individual investor gets a chance to front-run Wall Street, which is why I’m not letting this opportunity slip away.
Playing a run-up in MannKind is a risky, short-term move with tremendous possible upside
Oct 23, 2014, 12:42 pm EDT | By John Divine, InvestorPlace Assistant Editor
To anyone who argues that markets are perfectly efficient, allow me to introduce you to a little biotech stock called MannKind (MNKD). For those unfamiliar with the company, it has a potentially revolutionary FDA-approved diabetes drug called Afrezza hitting the shelves in early 2015.
Here are some quick facts about diabetes that should give you some context about the scope of the problem that MNKD’s inhaled insulin product, Afrezza, will address:
•As of October 2013, the WHO estimated that about 350 million people worldwide are afflicted with diabetes.
•2012 CDC estimates suggest nearly 30 million U.S. adults over the age of 20 have diabetes
•The number of Americans with diabetes rose by about 13% between 2010 and 2012, according to the American Diabetes Association.
•The WHO estimates that total deaths attributable to diabetes will rise by upwards of 50% in the next decade alone.
You get it. Those are some daunting, ugly statistics. Diabetes is a massive problem that needs to be addressed immediately.
In light of these facts, what makes the biotech stock such a special opportunity?
Quick Facts on MannKind, MNKD stock, and Afrezza
MannKind’s CEO is Alfred Mann, a billionaire entrepreneur and biophysicist who has “founded or largely funded” 17 companies in his lifetime. More than half of those were eventually acquired for a sum total of roughly $8 billion. Most of Alfred Mann’s net worth is tied up in MannKind. The point: Mann knows business.
As for Afrezza and the prospects for MNKD stock:
•The future of MannKind hinges directly and solely on the commercial success of Afrezza, MNKD’s rapid-acting inhaled insulin product that is slated to hit the shelves in early 2015.
•Afrezza treats both type 1 and type 2 diabetes.
•Afrezza is administered through MannKind’s proprietary Technosphe
Barriers to the use of prandial insulin regimens include inadequate synchronization of insulin action to
postprandial plasma glucose excursions as well as a significant risk of hypoglycemia and weight gain.
Technosphere® insulin (TI) is an inhaled ultra-rapid-acting human insulin that is quickly absorbed in the
alveoli. With a time to maximum plasma drug concentration of approximately 14 min and a time to maximum
effect of 35 to 40 min, TI more closely matches the postprandial insulin concentrations seen in nondiabetic
individuals. Studies have shown that long-term administration of prandial TI in combination with long-acting
basal insulin results in reductions in hemoglobin A1c comparable to conventional subcutaneously injected
prandial insulins but with improved control of early postprandial BG. Furthermore, TI has been associated
with less weight gain and a lower incidence of hypoglycemia, which may enhance patient satisfaction and
acceptability of insulin therapy. This review discusses the clinical properties of TI and proposes strategies for
Currently available, subcutaneously delivered RAAs have
PK/PD profiles that are still poorly synchronized with
PPG excursions. Ultra-rapid-acting insulins, such as inhaled
TI, result in better control of early PPG with less weight
gain and less frequent hypoglycemia, but control of late
PPG remains suboptimal. Preliminary evidence suggests
that, when needed, a second dose of ultra-rapid-acting
insulin may result in more prolonged control of late PPG
without further adverse effects.
Anders H. Boss and Richard Petrucci are employees of and hold
stock in MannKind Corporation. Daniel Lorber is a prior advisor
to MannKind Corporation; he has received research support from
MannKind Corporation, Novo Nordisk, Merck & Co., Johnson &
Johnson, and Boehringer Ingelheim and was on a speaker panel for
think a lot of that, the success in that area is driven by peoples reluctance to start taking insulin and that’s why starting gradually with the basal insulin, that’s a nice way to go, but adding AFREZZA is a natural add-on, I think.
And then the big market after that and they’ve talked about this a lot too. We certainly have as well, because we view this sort of the big part all at the end of the rainbow, will be those diabetics who are not yet on in insulin, because we know people, we just heavily going on insulin, it’s kind of treatment of last resort for most of them, there is lot of stigma associated with it and it’s hard to get them do at all, when they do it, it’s hard to get them to stay on it.
Offering an attractive alternative in a non-injected insulin form with some daily advantage is the half, I think, this would have a lot of benefits to people generally. We now going on insulin earlier for better outcomes for patients and helps them avoid some of the long-term complications of diabetes.
So if we can get any piece of that market, I think, it will not only beneficial for us from sale perspective obviously, but it will really have a lot of benefits for the population as a whole and we do see those very difficult outcomes.
And so that last group by the way is much larger than either of the other two groups, so wouldn’t take very much, so that’s have a pretty significant amount of sales. There is somewhere around about 4.5 million in the first group the current prandial insulin users and a couple of million in the basal-only group, but the last group in excess of 15 million and this is just in the U.S. So it’s a huge market opportunity.
break the market into three buckets that we view as obvious candidates for this product. The one most people think of but it’s not necessarily when we think of first is people that are currently on the prandial insulin.
It’s well known that’s a group that has subject to a lot of issues with compliance. They don’t take it as they should and when they should, and giving them an alternative that might be more attractive to them might help in that group. But lot of the focus we have seen and certainly in the public comments that Sanofi has made recently. They have echoed this.
Then other two buckets are in many ways even more attractive and potentially a greater faster penetration and first of those will be those diabetics who are currently only on a basal insulin, especially in Sanofi’s case, where they own that market essentially. They have a huge installed base of people taking [man test] and ultimately and potentially (indiscernible).
I think it’s safe to say that essentially all those people would benefit from the addition of prandial insulin as well and they all – they certainly know who those people are and I would be very surprised to say that we go after those folks very aggressively, offering them something they would find attractive as an add-on and that would,
obviously obviously, be AFREZZA.
November 20, 2014
Sanofi will hold an IR Thematic Seminar on New Medicines at the Genzyme Headquarters in Cambridge, MA.
A live video webcast of the seminar will be available at
2:30 pm CET / 1:30 pm GMT / 8:30 am EST.
The event will be the first in a new series of events focusing on late-stage pipeline assets.
The agenda will consist of several deep dive sessions on new medicines and vaccines that we expect to launch in 2015, such as alirocumab, Dengue vaccine, Toujeo® and Afrezza®. A high level update on the next wave of innovative medicines and vaccines will also be provided.
The presentations will be followed by a Q&A session.
“Inhaled Powder” Vaccines
“Shelf-Stable, Self-Inhaled, Powderized” VLP Vaccines.
TechnoVax and MannKind Corp. have combined their respective technologies to create a Powder Formulation of VLP Influenza Vaccine for Intrapulmonary Self-Delivery by Inhalation.
No refrigeration is required, and because it is potentially self-administered public exposure is limited. In the event of an emerging pandemic the vaccine could be easily distributed to the population, greatly reducing the spread of the virus!
■Extended Shelf Life and Elimination of Cold Chain results in improved distribution costs and inventory management.
■Best Route of Immunization (mucosal surface – respiratory tract)
■Increased Patient Acceptance (inhaled vs. injection)
VLP’s are combined with FPDK Excipient Particles for optimized airflow delivery using the Cricket Inhalation Device.
Flu - Inhaled Powder
RSV - Inhaled Powder
Respiratory Syncytial Virus (RSV) is the most important cause of lower respiratory tract infection (LRI) in infants, children and the elderly worldwide: RSV affects 64 million people and claims the lives of 160,000 yearly. In the USA only, RSV is responsible for about 100,000 infant and 175,000 elderly hospitalizations leading to the death of 14,000 elderly patients. There is no vaccine currently available.
"We believe that MKC253 represents a novel approach to the use of GLP-1 as a prandial therapy for diabetes either alone, or in combination with prandial insulin. In addition, if we are able to demonstrate the same weight reduction or satiety effects seen with long-acting analogues of native GLP, MKC253 may have therapeutic potential in obesity. At present, this indication for GLP-1 is currently limited by the need to administer peptide hormones by injection. The results of this trial, although preliminary, indicate once again that utilizing the Technosphere platform to deliver a metabolically important peptide in a manner that produces a unique time-action profile can potentially transform the
2Q14 10-Q, pg 43"Under the terms of the Sanofi License Agreement, we granted to Sanofi a right of first negotiation in the event we propose to grant to any third party a license to develop or exploit an inhaled glucagon-like peptide-1 agonist. In addition, if our board of directors determines to pursue a change of control of MannKind, we will be required notify Sanofi of such determination within a certain period of time so that Sanofi may, at is discretion, negotiate with us for a potential acquisition of MannKind by Sanofi"
Mannkind's Inhaled GLP-1 could be quickly licensed out in a deal that brings double digit royalty arrangement along with milestone payments. Mannkind may wait for Afrezza to to gain market acceptance to negotiate a better deal that could be part of a Sanofi buyout, Sanofi partnership or licensed out to another company.
"Our hypothesis at present is that delivery of active GLP-1 to the arterial circulation via the lung avoids much of the degradation by dipeptidyl peptidase-4 that occurs prior to the compound reaching the primary site of endocrine action. Thus, we may be able to achieve a different response profile with pulmonary MCK253 than that seen with subcutaneous or intravenous administration of GLP-1. Moreover, the pulsatile administration of MKC253 achieved with our proprietary Technosphere delivery technology appears to avoid the dose-limiting vomiting characteristically associated with GLP-1 and replaces a physiological response lost in patients with diabetes that cannot be replicated by other forms of GLP-1," said Dr. Peter Richardson, Corporate Vice President and Chief Scientific Officer. "As well, with pulsatile delivery, we may potentially avoid unusual adverse effects such as the acute pancreatitis that has been described with presently marketed GLP analogues."
"We believe that MKC253 represents a novel approach to the use of GLP-1 as a prandial therapy for diabetes either alon
Treatment or prevention may be by neutralization (i.e., an agent that binds to and neutralizes a nerve gas or toxin or its receptor), for example, an antibody or ligand such as atropine, by treatment of the resulting infection (an antibiotic, an antiviral, antibodies), or by immunize individuals against agents of biological warfare (antigens, adjuvants, immunostimulants such as cytokines). Exemplary biologically active molecules include atropine, antibodies, antigens, and antibiotics.
a. TECHNOSPHERE(tm) Encapsulated Atropine
Atropine is encapsulated and stabilized in the TECHNOSPHEREs™. The rapid absorption of atropine provides an immediate response to nerve gas.
b. TECHNOSPHERE(tm) Encapsulated Antibodies
High affinity, anti-toxin, monoclonal antibodies are encapsulated in TECHNOSPHEREs(tm). The antibodies may bind to toxins produced by organisms such as Anthrax, ricin, botulinus, cholera, tularemia, and bubonic plague.
The use of 100% human antibodies avoids deleterious human-anti-mouse immune responses, enabling multiple administrations and reducing side effects. In the preferred embodiment, the TECHNOSPHEREs(tm) are 2 microns.
Accelerated stability studies were used to test the shelf-life for the compositions. The TECHNOSPHERE(tm) encapsulated atropine has a shelf-life exceeding 2 years.
I see no reason why the CDC wouldn't fast track Technosphere delivery. Injections would be used immediately to stem the outbreak, but a portable Cricket inhaler that delivers an immunization that doesn't require refrigeration? Oh yeah, the CDC would definitely accept that delivery system.
Publication number US6991779 B2
Original assignee Mannkind Corporation
Compositions containing biologically active molecules encapsulated in self-assembling, diketopiperazine microspheres (TECHNOSPHEREs™) and methods for making and administering such compositions are described herein. The compositions can be used to immunize individuals against agents of biological warfare. The biologically active molecules include atropine, antibodies, antigens, and antibiotics. The compositions can be placed in an inhalation device for self-administration.
The present invention is generally in the field of methods and compositions to neutralize or treat biologicals used especially in bioterrorism or biological warfare.
Prevention of death and disease from biological warfare agents is a concern for people serving the military and for civilians. Agents used in biological warfare include nerve gases, anthrax, ricin, botulinus, cholera, tularemia, and bubonic plague.
Atropine is a nerve gas antidote. Presently, it is delivered either by injection or via the pulmonary route employing a pressurized metered dose inhaler (PMDI). Individuals who are not practiced in self-injection frequently show reluctance to self-administer a drug via injection, let alone during times of stress, such as when under attack with a chemical agent. More importantly, pulling such a device out of a pack and moving all of the clothing and other paraphernalia to reach an appropriate site for injection incurs an unacceptable delay in time of treatment.
Biologically active molecules are encapsulated in self-assembling, diketopiperazine microspheres, such as TECHNOSPHEREs(tm). Such molecules include atropine, antibodies, antigens, and antibiotics. In some embodiments, the compositions may contain additional molecules, such as inflammatory cytokines, chemokines and lectins.
B. Biologically Active Agents
powder products. Most recently, Chad has been involved with leveraging MannKind’s expertise in the field of pulmonary drug delivery to create growth opportunity through external collaboration.
Partnerships in Drug Delivery
Save The Date! October 14-15, 2014 Renaissance Boston Waterfront Hotel, Boston, MA
Partnerships in Drug Delivery Speakers
Chad Smutney B&W
Chad C. Smutney
Senior Director, Device Design
Chad began his career at a development stage company named Bio-Plexus, Inc. in 1994. His involvement included the design, development, manufacture and commercialization of medium and high volume class II safety medical devices sold under the PUNCTUR-GUARD® trademark. His work contributed to various public stock offerings, product portfolio growth, intellectual property filings, regulatory approvals, and technology license agreements. Most notably, he led the design and development of the Bard Access Excalibur® PICC Introducer.
In 2001, Chad and three Bio-Plexus principles formed a consultancy firm named aVisionary Company. Here, the entrepreneurially driven development of medical devices learned at Bio-Plexus was extended to companies ranging from Fortune 500 to small start-up. For five years, high end product development, project engineering, and business development services were used to help medical device clients achieve success with their technology development initiatives and endeavors. As a founder/owner, Chad worked to develop aVisionary into a premier service provider for advanced drug delivery devices.
In 2006, Chad joined MannKind Corp. as Director of Device Design and immediately formed a technology development team chartered with advancing the pulmonary delivery of insulin using dry powders that feature Technosphere® technology. His work at MannKind has resulted in the DreamBoatTM and CricketTM inhaler systems as well as several ancillary technologies such as BluHale® designed to ease the development of inhalable dry