$25M CMC bonus to be announced any day now. Nice Xmas gift !!
Founded 17, sold 11. AM won't deviate from the norm. Mnkd is the one he held on the longest. A BP did offer, AM's asking price was too high, heard $70/sh. You can say he was too greedy. He has many companies. Eyes is the latest. At 89, he can't keep up with many cos any more. He wants Afrezza to become a blockbuster for better price. They likely spin off the Technology first, then sell the Afrezza biz later.
This story appears in the December 29, 2014 issue of Forbes. Top Pick: MNKD.
Trading Biotechs From His Bedroom Nate Pile Beats The Street
This story appears in the December 29, 2014 issue of Forbes.
Trading Biotechs From His Bedroom Nate Pile Beats The Street
For the rest of the Forbes 2015 Investment Guide, click here.
Nate Pile, 45
Day Job: Newsletter Editor, Stay-At-Home Dad
Strategy: Technology and Biotech Investing
Ten-Year Average Return: 17.6%
Top Pick: MannKind
As a math major at UC Berkeley in the 1980s Nate Pile’s awakening to the stock market came quite literally every morning at 6:30 a.m., when his college roommate, an active trader, got a call from his broker at the market open in New York City. The bull market of the 1980s hooked Pile, who landed a part-time job stuffing envelopes at one of the top-performing investment newsletters of the day, Jim McCamant’s Medical Technology Stock Letter.
Pile launched his own investment newsletter, Nate’s Notes, in 1995 from his bedroom, but for eight years he needed to teach junior high school math during the day to pay bills. Today Pile’s newsletter, focused on biotech and technology, is still headquartered in his home, in part because he is caregiver for his two daughters, but it is also one of the top-performing of its type, according to Hulbert Financial Digest. Ten-bagger recommendations of biotech giant Celgene and Apple have given a big boost to Pile’s returns.
Strategy: Pile pays attention to traditional fundamentals and technicals, but because some of his picks are biotechs he doesn’t fixate on traditional metrics. To understand the “story” of a stock, he drills down into the minute details found in the financial statements of the companies he is following. His portfolio tends to be concentrated, holding only 20 stocks. According to Pile, the key factors in his decision to invest are whether the company has a game-changing product that has the potential for huge growth and whether he would be happy to own the company even if the stock market didn’t exist.
Best Idea: Pile likes biopharmaceutical MannKind of Valencia, Calif., trading $3 below the level at which he first recommended it. In June the company finally received FDA approval for an inhaled diabetes treatment called Afrezza, but the stock is still down 60% from its 2004 IPO. Pile says many investors lost hope after Pfizer pulled a similar drug from pharmacies because of weak sales. Yet he points to two crucial differences: Pfizer’s product was the size of a liter bottle and MannKind’s the size of a lifeguard’s whistle. More important, Afrezza works faster, thus giving patients more control.
In 1991, Dr. Solomon Steiner founded Pharmaceutical Discovery Corporation ("PDC"), a biopharmaceutical corporation and is an inventor of its Technosphere™ Technology and MedTone™ Inhaler. Dr. Steiner served as PDC’s Chief Executive Officer and Chairman of the board of directors from its inception until December 2001, when PDC was merged with two other companies to form MannKind Corporation. From December 2001 to February 2003, Dr. Steiner served on MannKind’s board of directors and as a Corporate Vice President and Chief Scientific Officer. Many PDC's patents now belong to Mnkd.
©Sanofi US. All rights reserved
AFREZZA is a registered trademark of MannKind Corporation.
Dated Nov 4, 2014 (French style).
Prescribing Information Including Boxed Warning Medication Guide
AFREZZA REMS (Risk Evaluation and Mitigation Strategy)
What is the AFREZZA REMS?
A REMS (Risk Evaluation and Mitigation Strategy) is a program required by the Food and Drug Administration (FDA) to manage known or potential serious risks associated with a drug product.
The purpose of the AFREZZA REMS is to inform healthcare providers about the following risks of AFREZZA:
Risk of acute bronchospasm in patients with chronic lung disease
Contraindicated in patients with chronic lung disease such as asthma or COPD
Need to evaluate all patients for lung disease before starting AFREZZA
Before initiating AFREZZA, perform
a detailed medical history
physical examination, and
A non-promotional factsheet, reviewed by the FDA, with more detailed safety information on these risks is available in the box to the right
First Website for Afrezza with large Sanofi logo. No Mannkind logo nor Mannkind mentioning at all. We are ready for takeoffs folks!
Sanofi offers glimpse of next-gen. insulin strategy
November 20, 2014
Sanofi hosted a seminar Thursday morning to discuss its late-stage R&D pipeline, saying it's currently projecting the launch of 18 new drugs between 2014 and 2020. These could generate over #$%$30 billion of cumulative sales in their first five years.
The news comes after the Paris-based drugmaker took investors by surprise in late October when it said its diabetes sales would be flat in 2015, a revelation that coincided with the ouster of former CEO Chris Viehbacher.
The company was characteristically tight-lipped on its access and pricing strategy for future medicines. Executives, however, did treat analysts to a preview of strategy for future diabetes products Toujeo (U300) insulin glargine, which is undergoing FDA review, and Afrezza inhaled insulin, which was approved earlier this year but has yet to launch.
Sanofi sees US uptake for Toujeo, its basal insulin which is viewed as an heir to best-selling Lantis, as coming from two groups. The first group is the 5 million existing patients currently on Lantus and Novo Nordisk's Levemir, who Sanofi hopes will switch to the next-gen. insulin. The second group is the newly diagnosed, from which the drugmaker hopes to expand its patient base by a million new patients per year. The drugmaker expects a decision from FDA on Toujeo in the first quarter of 2015.
Andrew Purcell, VP, commercial business unit for US diabetes at Sanofi, told investors the firm hopes to reach that total addressable market of 6 million patients through the drug's own value proposition: targeting frustrated and challenged type 1 and type 2 diabetes patients with uncontrolled HbA1C levels, as well as providing customized patient support.
Toujeo, Sanofi hopes, will prove to be a compelling insulin to endocrinologists due to its lower risk of hypoglycemia and the fact that subjects taking it showed more consistent glucose levels over a 24-hour period than those on Lantus. Purcell noted that 52% of US endocrinologists are aware of the drug, and another 77% say they're willing to prescribe Toujeo, according to Sanofi's own market research conducted in August 2014.
Purcell, citing a Sanofi-conducted segmentation survey, said he sees 29% of those 5 million switchers coming from frustrated and challenged type 2 diabetes patients and another 6% from type 1 patients who are also unsatisfied with their current treatment as “natural switchers.”
He called patient support for Toujeo a “huge opportunity to do a better job of understanding the basal patient journey, doing the one-on-one coaching and support,” so patients can have a successful patient experience.
Riccardo Perfetti, senior medical officer, diabetes for Sanofi briefed analysts on launch plans for inhalable insulin Afrezza, saying Sanofi hopes to target diabetic patients resistant to starting insulin therapy and patients already on a basal insulin who require another mealtime insulin (but are concerned with adding another daily injection to their regimen). MannKind, which developed Afrezza, named Sanofi as its global commercial marketing partner in August.
Perfetti presented market research from Nielsen, which observed that 39% of 77 patients polled—who were on two or more oral diabetes treatments—were resistant to starting insulin therapy because of injections. That same research also found that 60% of patients prefer Afrezza to an insulin pen device, and 57% prefer to add Afrezza to their daily routine rather than injectable mealtime insulins.
Perfetti said other trials are set to begin next year evaluating other dosing regimens for Afrezza to see if other options affect efficacy.
MannKind's Afrezza Manufacturing Facility, California, United States of America
MannKind Corporation is a bio-pharmaceutical firm located in the city of Santa Clarita, California, in the US. It works on the discovery, development and commercialisation of drugs used to treat diseases such as diabetes and cancer.
Afrezza, a rapid-acting insulin therapy being developed for the control of hyperglycemia in adults with type one or type two diabetes, is the company's lead product candidate. MKC1106 and MKC204 are two other products being developed for the treatment of different types of cancer.
Afrezza requires unique a formulation and drug delivery system. The production process is so specialised that no existing manufacturing facility was capable of producing it. The company designed and built its own manufacturing facility in Danbury, Connecticut, for commercialisation of Afrezza.
The Afrezza manufacturing facility required an investment of $163m. It was dedicated in September 2008.
In January 2010, the plant won two Facility of the Year Awards (FOYA), one for Process Innovation and another for Equipment Innovation. FOYA is sponsored by the International Society for Pharmaceutical Engineering (ISPE), INTERPHEX and Pharmaceutical Processing Magazine. It is given each year to honour and recognise the best of pharmaceutical manufacturing facilities in seven different categories.
Connecticut's Danbury Afrezza manufacturing plant construction
"Afrezza, a rapid-acting insulin therapy being developed for the control of hyperglycemia in adults with type one or type two diabetes, is the company's lead product candidate."
The Danbury project broke ground in early 2007 and was completed in the second half of 2008. The plant has a total floor space of around 23,400 square metres.
The project was part renovation and part new construction. Approximately 20% of the facility is apportioned to facilitate future expansion, which can be undertaken to increase production of insulin therapy or start production of new Technosphere-based products.
Renovations were undertaken within the same building as the company's ongoing clinical manufacturing suite. New manufacturing operations were accommodated by renovating about 6,503 square metres of the existing space and an attached central utility plant was also upgraded.
New construction work involved the addition of 16,723 square metres to the plant. This phase of work involved installation of two fill and two packaging suites with associated support rooms. Each of these suites can accommodate three fill / packaging lines.
The new building houses 882 square metres of material and product storage space, most of which is refrigerated. The total area of the second floor of the new building is outfitted for operations such as offices, meeting, dining and support.
Unique manufacturing processes for MannKind's rapid-acting insulin therapy
MannKind's Afrezza production plant has an advanced, custom manufacturing process line from beginning to end.
The first stage in the process is the creation of the Technosphere(R) particle. The particle is mixed with insulin in a specialty mixer, after which the mixture is frozen to separate the powder. The dried powder is shifted to fillers, where it is then filled into capsules and packaged.
Features and facilities of the award-winning insulin production facility
In order to meet the unique production needs, new technology was designed and innovative adaptations were applied to the existing technology.
"The Afrezza manufacturing facility required an investment of $163m. It was dedicated in September 2008."
One such innovative adaptation was made to specialty reactor which is used to blend Technosphere particles with insulin.
The plant has a high speed filling system and applies a cost-effective mode of moving bulk powder from the lyophilizer to the filler.
A recognising feature of the facility is the first-ever pharmaceutical adaptation of a cryopelletizer in solid-dosage form. The modified cryopelletiser produces uniform pellets. During the bulk lyophilisation process, water from the uniform pellets can be removed quickly in a systematic manner.
Central utilities comprise a steam boiler system. There is also a chill plant with a primary / secondary pumping system.
In order to support the Central Utility Building and keep the facility working, even during a power failure, the plant is equipped with a new 2,500kW substation and emergency generator.
Key contractors and suppliers involved with MannKind's Afrezza plant
Philadelphia-based KlingStubbins was the architect of the inhalable dosage manufacturing facility. Clark, Richardson & Biskup Consulting Engineers (CRB) of Plymouth Meeting, Pennsylvania, was the prime consultant for architectural and engineering design. Construction manager for the plant was Torcon, a construction management and general contracting services provider based in New Jersey.
Automated Control Concepts (New Jersey), Dynamic Systems (North Carolina), Cryogenic Equipment Systems (Belgium), Integrated Process Technologies (Massachusetts), Serail (France) and Siemens Building Technologies (New Jersey) were some of the major suppliers.
PTH is produced by the parathyroid glands and is a hormone that increases calcium levels in the blood and promotes bone growth. A modified form of PTH is sold by Eli Lilly (NYSE:LLY) under the name Forteo and is used to treat some forms of osteoporosis (where bones become weak due to lack of calcium), and is also used off-label (meaning it's unapproved to do the following) to speed up the healing process for bone fractures. Forteo is taken once a day by injection in the thigh or abdomen. Eli Lilly reported that sales of Forteo for full-year 2013 were $1.24 billion, an 8% increase year-over-year. This indicates a sizable market where an inhaled PTH therapy using Technosphere technology could potentially overtake LLY's injected treatment and generate revenue for MNKD.
GLP-1 is an incretin, which is a family of hormones that reduce blood glucose levels. Currently, treatments using GLP-1 include Novo Nordisk's (NYSE:NVO) Victoza and Eli Lilly's Trulicity, which are both injected and used to treat diabetes mellitus type 2. Victoza achieved annual 2013 sales of about $1.9 billion, while achieving a growth rate of about an average of 8% every quarter for the past five quarters, and Trulicity, which was just approved this September, is predicted to achieve sales of $1.4 billion by 2020. These numbers indicate a huge market for GLP-1 treatments, and MNKD has the means to gain some, if not most, of the market share by developing an inhaled GLP-1 treatment using Technosphere technology.
Now some of you might be thinking that MNKD already has a product approved to treat type 2 diabetes so why is GLP-1 important. Most importantly, GLP-1 stimulates the release of insulin and inhibits the release of glucagon (which raises blood sugar levels) directly based on the glucose level in the blood. Meaning treatments involving GLP-1 mimic the body's natural response to blood sugar changes better than treatments just involving insulin. GLP-1 treatments only trigger insulin secretion when blood sugar levels rise to a certain degree, while rapid-acting insulin treatments like Afrezza must be taken before meal times because the response is absolute. It is for this reason that GLP-1 treatments have a lower risk of causing hypoglycemia. If MNKD were to develop an inhaled GLP-1 therapy with Technosphere technology, then type 2 diabetes patients would never have to take an injected treatment, even if products like oral insulin and Afrezza failed to control blood sugar levels properly.
Dry powder, device and advanced development technologies are uniquely integrated at MannKind to enable real world translational medicine. We strive to get medicinal concepts rapidly progressed into sensible, patient-friendly treatment solutions.
Inhaled drug delivery provides many benefits, including:
Rapid onset of action
Avoidance of first pass metabolism
Needle-free administration for systemic or local drug effect
These are important differentiators within the growing market of self-administered medicines. Application for our MannKind technologies exists in many areas, and we are seeking collaborative interest from the medical industry to create new opportunities for treatment of:
Migraine [to be partnered with GSK since IMITREX patent expired]
Anti-nausea [to be partnered with GSK since ZOFRAN patent expired]
Anti-obesity [Andrea is featured speaker at 4/2015 7th Diabetes Conf]
Pulmonary arterial hypertension
Humira is made by the pharmaceuticals giant AbbVie (NYSE:ABBV) and is approved for the treatment of, among other diseases, rheumatoid arthritis. The drug was made to inhibit production of TNF, or tumor necrosis factor, because TNF can cause severe inflammation and can impair the mobility of limbs and joints. Sales of Humira for full-year 2013 totaled a whopping $5.2 billion in the U.S. alone, a sales increase of nearly 18% year-over-year. The drug is taken by injection either by syringe or by injection pen usually weekly or biweekly in a new injection site every time.
Create a formulation with Technosphere particles and monoclonal antibodies that bind to and inhibit the TNF protein, and get FDA approval, or license to others.
Mannkind Technologies Corp. will be formed and split off from Mannkind Corp with Technosphere and the pipelines. Shares will be issued to Mannkind original shareholders for the Technologies Co., so now we will own a piece of two companies. If this scenario plays out, it will be very exciting, and the shorts are so screwed. Mannkind/Afrezza stand alone and partnered, and the other company with Technosphere and pipelines also partnering with other approved drugs, to improve delivery to the patient by advance inhalation using Technosphere. Absolutely HUGE markets.
The following is from the Annual Meeting Q & A
Question #3 from Attendee
"What are the other applications of the Technosphere platform, and what is Al's vision?"
In a very upbeat manner, Al Mann quickly stated, "The process offers a very very powerful way to deliver a drug very quickly into the blood and stabilize drugs that are not stable enough to deliver through many other technologies. A drug delivered for migraine headache now takes about an hour for a person to become comfortable. Imagine being able to deliver it (pain management medication) in 2 to 3 to 4 minutes and having freedom from a migraine. Wouldn't that be a big improvement? There are a lot of opportunities… But we have to concentrate first on getting Afrezza to market." President and COO Hakan Edstrom went on further to say, "We are looking at all organizations to get Afrezza to market on a global basis, and our vision is to create a MannKind Development Corp. as well, which would exploit the platform to other applications. There are a number of opportunities."
A new Website, mannkindtechnologiesDOTcom
"So turning a little bit more towards commercialization. Obviously with the kind of market we are talking about, it's important to address where we are going to make this stuff and we happily have a very nice data facility located in Danbury, Connecticut that has been our commercial facility for some time.
We didn’t fully build it out because it's quite expensive to do so pre-approval, but the facility is scaled to do up to two billion cartridges per year fully built out and by that, we're really talking about filing the rooms with the equipment that they are sitting there waiting to have installed.
So the primary bottleneck facility has mostly the fill finish machines. You can probably imaging two billion cartridges is a lot of cartridges and you need a lot of equipment to fill those, almost no matter how fast you do it.
At launch, we expect to have three of those finish lines in place, which should give us a $375 million per year capacity, that's a quarter of the total capacity of the facility to some of the layer once it have a little higher than if you are doing the math and it doesn’t quite work.
You have to trust me on this, but it can go up to two billion cartridges a year at full capacity and we can add the capacity in a very nice relatively rapid modular way, which is one of the advantages of having built this very nice expensive facility with all the clean rooms and things in place, just waiting to drop the machines in."
is source for "$25M bonus/line, $75M/3 lines. $25M paid 1Q, $50M paid in 2Q15. 3 lines support $850M. 12 lines cap."
Expect $25M bonus in a few weeks. Another $50M bonus announcement in 2Q15. Hakan, 3Q14 CC:
"Most of the supply chain and manufacturing PV activities have successfully concluded, so I am pleased to announce that we have begun commercial production and we are confident than [rebate] of the supply of Sanofi, the launch inventory necessary for a successful launch.
As a result we’re also closed to triggering payment of the first of two milestone payments associated with manufacturing and supply considerations.
Not only are we in commercial production as we speak but we are also well underway in expanding cost building capacity in [inaudible].
During the first half of 2015, we will have added two additional filling lines to make sure our capacity can meet currents and anticipate the demand growth.
In Sanofi internationally represents a major longer term opportunity for AFREZZA. We know already from having being approached by companies and governments from the Middle East, China and Japan that AFREZZA could fit very well into their treatment and cultural pattern.
Representatives from the US, France, Germany are participating in the launch preparation, the clinical development programs, the regulatory preparations and the commercial manufacturing startup activity."
Matt: “We didn’t fully build [Danbury] out because it's quite expensive to do so, pre-approval, but the facility is scaled to do up to two billion cartridges per year fully built out,” he said at the Jefferies Global Healthcare Conference earlier this month. However, the biggest bottleneck to scale-up is fill finish capacity, he added.
“At launch, we expect to have three of those fill finish lines in place, which should give us about 375 million per year capacity.”
He continued: “We can add capacity in a very nice relatively rapid modular way, which is one of the advantages of having built this very nice expensive facility with all the clean rooms and things in place, just waiting to drop the machines in.”
Afrezza is based on Mannkind's Technosphere technology, which uses the excipient fumaryl diketopiperazine (FDKP) as the particle matrix to carry recombinant human insulin to the lungs. The product is inhaled from the cartridge using a device described by Pfeffer as looking a "little bit like a whistle in use," powered by inhalation alone.
Wells Fargo Healthcare Conference Call
June 17, 2014 10:00 AM ET
Matt Pfeffer - Chief Financial Officer
Slide about commercialization, needless to say, we do expect to commercialize this product with product manufactured by us out of a facility we've already built in Danbury, Connecticut. It’s not fully built out yet, there is a lot of room sitting vacant waiting for a fulfill and finish equipment being put in; what we expect to launch was about a quarter ultimate capacity, some 375 million to 400 million cartridges, that capacity increases as you added the newer machines, but we expect ultimately that that facility was designed and scaled to accommodate 12 fill and finish lines so we'll launch will 3 and we’ll install the other ones as needed but it was designed [inaudible] fairly quickly as the demand goes up. But ultimately we can do 2 billion cartridges a year out of that facility, which is pretty good number"