2023-10-31 02:17:12 ET
Summary
- I will recap the eleven partnership deals MannKind has been involved in over its operation as a corporation.
- I will share my opinion as it relates to the current status of these eleven partnerships.
- I will discuss why it is my opinion that MannKind's marketing of Afrezza is not and will not be sufficient for creating a sustainable revenue stream justifying its manufacturing and marketing costs.
- MannKind apparently does not have a minimum purchase agreement for Tyvaso-DPI and with United owning this drug, United holds a royal flush hand if they decide to manufacture the drug sans using MannKind.
- December 4, 2023 is the date that United could show their hand to MannKind.
Prologue: I shared my first SA article about MannKind (MNKD)on June 8, 2008. In the interim, I shared many more articles about MannKind. In each of my articles, I tried to give external links that support my thesis about MannKind and the fallacy of their Technosphere System being a viable drug delivery system. Afrezza is a dry powder insulin with a newly developed binding excipient fumaryl diketopiperazine (FDKP) and a simple inhaler. Apparently, due to the uniqueness of the insulin molecule, it can’t be successfully dosed orally. Apparently, MannKind needed FDKP to make their inhaled system work—even then it couldn’t deliver more than 39% of every dose. MannKind owns the rights to FDKP. However, MannKind has never shown one penny of revenue from another drug maker using it for their inhaled product---no company wants the extra expense because of the myriad of other excipients that are cheaper and work well for manufacturing oral medications –pill or liquid doses.
The binary of big-time binary events (12/4/2023) is approaching for MannKind and its partnership with United Therapeutics. One should remember that a fox can creep into one's hen house and steal your “nest egg’. This article is lengthy, but I’ve reviewed every partnership MannKind has ever formed. It really isn’t a pretty picture for those who have owned this stock.
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There should be no dispute about Al Mann (1925-2016) being a highly intelligent and brilliant inventor of medical devices for the good of all mankind. The two best examples would be the rechargeable batteries for the heart pacemaker and the insulin pump for delivering insulin into a diabetic’s body. However, he had at least three faults—one being foolish enough to put his name on one of his companies, believing that the Technosphere system would be a viable product, and finally having so much money that he didn’t mind wasting it on Afrezza. After nearly 32 years (February 1991) as a corporation and trying to create value for MannKind’s ( MNKD ) shareholders, it is proving out as I indicated exactly nine years (October 2, 2014) ago when I wrote my first article about MannKind – MannKind: Reality Check.
In my article’s summary comments, I stated, “True reality is always in the details.” The first detail I might cite for my readers is that after my initial article about MannKind, and based on trading in recent days and factoring in that the stock underwent a 1:5 reverse split, the stock price is trading for less than $1.00 a share. This reflects that those holding the shares in the interim period have seen over 90% of their investment dollars disappear.
MannKind needs a new business model . Based on the historical record compiled in nine years of effort to market Afrezza, the growing undeniable monetary results indicate that Afrezza has never earned one penny of actual profit from the revenue generated. MannKind executives need to cut their losses by doing what Pfizer ( PFE ), Sanofi ( SNY ), Lilly ( LLY ), Novo Nordisk ( NVO ), and other smaller insulin marketers have done—giving up inhaled insulin as a viable product that will generate a profit.
A Historical Journey Recapping MannKind’s Failed Efforts
The first SA article dedicated to MannKind was posted on June 8, 2008. From this starting point and ending on June 22, 2008, a contributor, Ahithophel Weissberger, shared a Part I -VI series of articles— Overlooked Biotech With Excellent Prospects(Part I) . These six articles were well-written and made a compelling case for the MannKind story. I mentioned that Pfizer’s inhaled Exubera had failed miserably in the market. He also admits that Novo Nordisk, Lilly, and other drug companies had stopped their efforts to develop an inhaled insulin product. I stated that what MannKind was offering was different; they would only need another significant drug company partnering with them to market the drug. This initial SA contributor has never published another article here on SA.
I should have mentioned the complex manufacturing process to create Afrezza was very expensive compared to making an injectable insulin product. This resulted in a massive cost of the product versus injectable insulin being used. The writer never mentioned the issue of insurance providers not being compelled to cover this additional cost of insulin. Insurance companies are in the business where their top priority is profit-making. After spending nearly $3 billion in creating Afrezza, all the compiled clinical data on thousands of trial patients never showed Afrezza beating the results of injectable insulin in reducing A1c levels, the SOC goals for diabetic treatment. MannKind investors can ignore this issue, but insurance companies don’t overlook the fact with every prescription filled by a pharmacist, they insert a Prescribing Information Document where they provide information for the patient about their drug.
The Afrezza insert ( Page 6: 5.4 Decline in Pulmonary Function) tells the user that the drug adversely impacts their pulmonary function. MannKind even tells the user when they should discontinue Afrezza when their lung function declines to a certain point.
As for the ongoing claim by MannKind, telling investors their inhaler delivers their drug deep into the user's lungs and is the best inhaler on the market, yet they share the following on their insert:
11.2 AFREZZA Inhale: The AFREZZA Inhaler is breath-powered by the patient. When the patient inhales through the device, the powder is aerosolized and delivered to the lungs. The amount of AFREZZA delivered to the lung will depend on individual patient factors.
On page 14, they share 12.3 – Pharmacokinetic Carrier Particles :
“Carrier Particles Clinical pharmacology studies showed that carrier particles [see Description (11.1)] are not metabolized and are eliminated unchanged in the urine following the lung absorption. Following oral inhalation of AFREZZA, a mean of 39% of the inhaled dose of carrier particles was distributed to the lungs, and a mean of 7% of the dose was swallowed. The swallowed fraction was not absorbed from the GI tract and was eliminated unchanged in the feces.”
This is the sequence in which MannKind shares information on the Afrezza insert for every prescription:
- The patient’s Pulmonary Function can be impacted by using Afrezza, and they admit it does affect the user’s lungs.
- The amount of Afrezza delivered to the lung depends on individual patient factors—mainly being able to breathe deeply and correctly.
- Then, the insert admits the mean delivery of each dose of Afrezza getting into the users’ lungs is 39%, meaning 61% of each dosage is wasted.
After these open admissions by MannKind some investors thought Pfizer, Lilly, Sanofi, and Novo Nordisk didn’t understand the merits of inhaled insulin. Still, some thought it would be a profit center for Mannkind. In 1921, under the leadership of Fredrick Banting, Charles Best, and JJR Macleod, working in a laboratory at the University of Toronto, they identified insulin and its impact on treating diabetes. Within two years, scientists in Germany began to search for a way to deliver insulin other than by injection. At the time, medical research on a worldwide basis was led by German scientists, with Bayer being the most significant drug company in the world. 102 years later, there has never been a successful method for delivering insulin into a human’s body other than by injecting insulin. Currently, there are no new clinical trials involving inhaled insulin being conducted. Mankind spent over $3 Billion dollars in developing Afrezza, and now we can see billions of dollars have not been worth the effort.
Let’s Look at the Numbers
#1 Partnership – Sanofi ( SNY )
Sanofi launched Afrezza into the market in January 2015, soon to be ten calendar years ago. With no base drug users and no doctors currently prescribing the drug, by Week 43, the Sanofi sales team reached 424 patients who had their Afrezza prescription filled by a pharmacy. And Sanofi then opted to cancel its partnership with MannKind. Sanofi reached this decision when they found the unenthusiastic response from the medical professionals, the lack of uptake by those suffering from diabetes, and the staggering number of initial users refusing to get their prescription refilled and opting to restart using their injectable insulin. With nearly 75% of initial users dropping out of using Afrezza, Sanofi could easily see that the future was bleak for them to be successful in the marketplace. They made a prudent business decision and canceled the MannKind partnership.
MannKind decided to relaunch Afrezza into the marketplace with the insistence that they could prove Sanofi was wrong and accomplish this feat by spending less money than Sanofi spent on their marketing effort. Then, on the week of December 9, 2022, 368 weeks later than when Pfizer achieved the 400+ new weakly high-water mark, MannKind broke the 400 level with 419 NRxs for Afrezza. Now that we are well into 2023, we find the last time MannKind achieved the weekly 400 number of NRxs was week 433 data, May 12, 2023, showing 424 prescriptions. In the ensuing 23 weeks (nearly six months) since this May event, MannKind has seen a 200+ week and the other 22 weeks in the 300 level of NRxs. With 455 weeks (8.75 years) of Afrezza weekly prescriptions in 41 of the 52 weeks in 2023, the weekly average for new prescriptions is 370. More telling is that in these 8.75 years of prescription data, the refills have been at most three digits, with 589 being the highest for this number. This data supports the fact that initial users refuse to refill their prescriptions.
Now, into what will soon be the tenth calendar year that Afrezza has been available for diabetics, we have seen a discernable plateau for Afrezza NRxs. Over a year ago (September 16, 2022—week 399), we saw refills breaking the 500 level. Since refills are roll-over numbers from NRxs, investors should see the refills well into the six-digit level, but after 456 weeks of effort, this number has never broken above the 500 level.
Nearly into the ninth year of marketing, Afrezza's weekly prescription data tells the tale---MannKind has had ample time to turn Afrezza into a profit-making product. Yet, it isn’t even close to profiting from Afrezza's revenue. Under the current structure, Afrezza will never generate a profit stream for MannKind.
Status: Sanofi canceled their partnership deal within a few months of launching Afrezza. Now, eight years later, MannKind is achieving fewer weekly NRx than Sanofi.
#2 Partnership - Cipla:
On May 9, 2018, MannKind partnered with the India-based pharmaceutical company Cipla.
The following is from their press release, and it highlights the critical components of this partnership deal:
“ Our partnership agreement with Cipla for Afrezza provides us with a long-term partner with a wealth of knowledge and experience in diabetes. Cipla is a leader across therapies in India with an established sales, marketing, and distribution network. With this partnership, Cipla will leverage its strength in inhalation and extend it to diabetes therapy/portfolio,” stated Michael Castagna, Chief Executive Officer of MannKind. “The International Diabetes Federation estimates that 425 million people are currently living with diabetes worldwide, including 73 million in India. This agreement with Cipla, our second international partnership agreement for Afrezza, extends the potential opportunity for approximately 1 out of 4 people of the worldwide population with diabetes to manage their disease with our novel mealtime insulin, when combined with our earlier agreement in Brazil and our efforts in the United States.”
“Cipla is committed to providing access to innovative medicines and newer drug delivery systems to the patients. Afrezza, an inhaled insulin, is a cutting-edge product which will increase patient convenience,” said Umang Vohra, MD & Global CEO, Cipla Ltd. “The innovative drug delivery system will revolutionize the diabetic care in India. This partnership with MannKind is another step from Cipla to cater to the unmet needs of the patients.”
Under the terms of the agreement, Cipla will be responsible for obtaining regulatory approvals to distribute Afrezza® in India, including approval from the Drug Controller General of India. Cipla will also be responsible for all marketing and sales activities of Afrezza in India. MannKind is responsible for supplying Afrezza to Cipla.
MannKind will receive a $2.2 million upfront payment from Cipla within 30 days of entering the agreement, with the potential to receive additional regulatory milestone payments, minimum purchase commitment revenue , and royalties on Afrezza sales in India. “
For $2.2 million dollars, MannKind has given the country with the second largest population the right to market Afrezza to their citizens. More important is the fact that in their partnership deal, MannKind got a minimum purchase commitment –so kudos go to MannKind for seeking this MPC arrangement. Still, investors should keep this factoid in their memory reserve for later in this SA article.
Status:
This partnership has been well over five years, and there has yet to be one update. Five years is exceptionally long for clinical trials when the FDA has approved the drug. With a cursory search of the internet and Cipla documents and company reports, I didn’t find one mention by Cipla related to their MannKind partnership. At the time, worldwide, there has been a concerted effort for drug companies to find ways to lower the price of the insulin products they sell. Cipla was founded and has prospered by developing generic and now biosimilar drugs. Cipla has contracts with Lilly and Novartis to market their diabetes drugs in India. The blockbuster insulin products developed earlier by Novo Nordisk, Lilly, and Sanofi are now going off-patent. There are now companies feverishly working to create cheaper biosimilar products. These new drugs can be sold for much cheaper prices to consumers. We have seen that in the United States, Afrezza has failed to achieve sustainable levels of users to support the cost of manufacturing and marketing for Afrezza. Why should one think that one of the more impoverished nations wants to buy the most expensive insulin product in the marketplace?
As for the MannKind claim related to this partnership, their CEO envisioned they could obtain 25% of the worldwide diabetic patients. In the real world, they have garnered about 1% of the United States market in nine years. If American citizens are not willing to pay for Afrezza, why would anyone expect India's citizens to be willing to pay the exorbitant price for Afrezza?
At this point, with no evidence to the contrary, it appears Cipla’s partnership has failed.
#3 Partnership - Receptor Life Sciences
On January 21, 2016, MannKind issued a press release about their partnership with this Seattle company whose principal management executive was a critical former employee of MannKind. After more than seven years of waiting for this partnership to show data for any product in development, MannKind no longer mentions them in their list of partnerships. Should anyone check the home page of the Receptor Life Science website, they will find no news entry since 2022. Mark Theeuwes is shown as being their CEO. By checking the LinkedIn website for the name—Mark Theeuwes, you will find that Mark Theeuwes is the COO for a Philadelphia, PA, area biotech named Reunion Neurosciences, and he has worked there for about two years.
STATUS: This makes just another MannKind partnership that fails to deliver any revenue. And they quietly fade away into the out basket for MannKind’s investors.
#4 Partnership - Biomm SA :
On May 31, 2017, MannKind issued a press release that features these comments from MannKind and the CEO of Biomm-Brazil:
"We are pleased to partner with Biomm to bring Afrezza to the Brazilian diabetes market," said Michael Castagna, Chief Executive Officer of MannKind Corporation. "Our founder, Alfred Mann, had a vision to reduce the global burden of diabetes through novel technologies. In 2015, more than 14 million people were estimated to have diabetes in Brazil. Given Biomm's presence and knowledge of the diabetes market in Brazil, we believe that Biomm is the ideal partner to reach healthcare providers and patients with the message that there is another potential option in their fight against diabetes."
"As a pioneering biotechnology company in Brazil, we believe that we can leverage our current portfolio of diabetes products to offer another option to the significant and growing numbers of patients with diabetes," said Heraldo Marchezini, Diretor Presidente/CEO of Biomm SA. "We are proud to be the first company to bring inhaled mealtime insulin to the Brazilian market.”
After this announcement, in 2017, BIOMM purchased an initial supply of Afrezza—about $500,000.00. What MannKind now fails to mention about their current inclusion of BIOMM, as being in partnership with MannKind, BIOMM has not ordered any more Afrezza other than this initial 2017 purchase.
STATUS: Another Failed Partnership. Waiting six years for BIOMM SA to reorder a supply of Afrezza indicates that the Brazilian market is not a worthwhile user of Afrezza. So now we have Pfizer, Cipla, Receptor Life Science, and BIOMM partnership not being a viable revenue source for MannKind. We are now seeing a major pattern for how MannKind's partnerships failed to deliver.
#5 Partnership - Thirona Bio, Inc.
On June 10, 2021, MannKind issued a press release about their latest partnership where they commented:
“Mannkind and Thirona agreed to evaluate the therapeutic potential of Thirona’s locally acting TGF-inhibitor, FBM5712, for treating pulmonary fibrosis. MannKind is developing MNKD-501, a dry powder inhaled formulation of FBM5712. If initial studies are promising, MannKind can exercise certain rights to seek a full license for the compound for clinical development and commercialization for pulmonary fibrosis.”
Point #1 - Thirona lists an address for where they are located—3570 Carmel Mountain Road, Suite 200, San Diego, CA.
Point #2 —Thirona lists no phone number for them being contacted.
Point #3 -The principals of Thirona are Gordon Foulkes, CEO, and David Bullough.
Point #4 – Not only did MannKind agree to a partnership deal, but they also invested MannKind’s limited amount of cash into this company.
Point #5 - Michael Castagna, CEO of MannKind, becomes a member of Thirona’s board of directors. Was this a case of someone buying their board of directors’ position? I don’t know the answer! But such a position does look good for one’s resume.
Point #6- Two months after MannKind invested in Thirona, another biotech company, created a convertible promissory note arrangement with Thirona, giving them the same rights MannKind got--a partnership for their pulmonary fibrosis drug.
EnZen Therapeutics :
SAN DIEGO, Aug. 30, 2021 /PRNewswire/ — EnZen Therapeutics, Inc. (“EnZen”) and Thirona Bio, Inc. (“Thirona”) today announced that EnZen has invested in Thirona under a convertible promissory note arrangement. Proceeds from the investment will support the development of Thirona’s novel compound, FBM5712, which is intended for the prevention or reduction of fibrosis.
We believe that FBM5712 is a promising preclinical asset,” said Dr. Dominic King-Smith, Chief Executive Officer of EnZen. “Inhibition of TGF-? is a well-validated target, and Thirona’s focus on local treatments for scleroderma, keloids, and cancer is closely aligned with EnZen’s focus on the development of topical therapies for less common dermatology conditions.”
FBM5712 is a novel small molecule inhibitor of the ALK-5 kinase (TGF-? receptor kinase), which is being developed by Thirona as a topical product targeting indications such as scleroderma, keloid scars and certain cancers where there are no effective therapies. The drug has been designed to minimize the potential safety issues associated with systemic inhibition of the TGF-? pathway. As part of the arrangement, the parties will also discuss entering into an agreement whereby EnZen’s parent, Encube Ethicals, would manufacture cGMP drug product on behalf of Thirona to support future clinical trials.
“EnZen’s investment will support and accelerate Thirona’s development of FBM5712,” stated Dr. Gordon Foulkes, Co-Founder and CEO of Thirona Bio. “ Our team has enjoyed a close collaboration with scientists in the Encube Ethicals group, and we look forward to deepening the relationship through the current transaction.”
Point #7 - This is where things get interesting. Go back and make note of Point#1, Point#2, and Point#3. For each of these points—address, no phone number, and same principal management officers as listed, they have another biotech firm located in the same exact address location—Lipido Pharmaceutical.
Point #8 – On June 10, 2021, MannKind’s CEO announced a partnership deal with Thirona, where they supposedly obtained the option for their potential fibrosis drug. Then, on August 30, 2021, EnZen’s CEO announced a partnership with Thirona related to the same fibrosis drug that MannKind claims they have the option for developing the drug. If MannKind’s CEO is on the board of directors for Thirona, why would he allow a competitor to sign on with Thirona and cut MannKind from developing their fibrosis drug candidate?
These are links to both Thirona and Lipido .
With the Thirona partnership being agreed to more than two years ago, reviewing their corporate website, you will not find one entry that shares ANY achievement on what should be the clinical development of a viable drug that will generate revenue. The only thing management appears to be accomplishing is getting MannKind’s cash and giving out board of directors’ positions. Then they give another company potential rights to the same drug. The lack of clinical development also applies to Lipido--- there is nothing of substance on their news front about any development of a drug candidate.
Status : Who knows! Appears from the limited information on their websites there are two biotechs in San Diego selling imaginary drug candidates and director’s positions—being my guess. If they have a viable drug candidate, they hide it from public disclosures. MannKind continues to associate with dubious operations and give them their limited corporate cash. This is not a sustainable business model. At this point, I would place the Thirona partnership in the failed category as it doesn't have the potential to benefit from the drug Thirona "could" develop.
#6 Partnership - NRx Pharmaceuticals
NRx was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for ZYESAMI™ (aviptadil) for the treatment of Critical COVID-19 with respiratory failure; currently in clinical trials.
WESTLAKE VILLAGE, Calif., Aug. 4, 2021 /PRNewswire/ -- MannKind Corporation (Nasdaq: MNKD) has partnered with NRx Pharmaceuticals (Nasdaq: NRXP) (NRx) to evaluate the feasibility of formulating a dry powder formulation of ZYESAMI™ (aviptadil), a synthetic form of human Vasoactive Intestinal Peptide (VIP) – an endogenous substance produced by the body that helps protect cells against inflammatory conditions. An intravenous formulation of ZYESAMI is currently in clinical trials, having been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of Critical COVID-19 with Respiratory Failure
Status : No mention by MannKind in any recently filed SEC documents, so it can be assumed that this effort is not being pursued by either party. Chalk up another failed effort. But for those interested, they can load up on ( NRXP ) stock for $0.28 a share---much cheaper than back in the days of touting their shares.
#7 Partnership - Vertice Pharma
WESTLAKE VILLAGE, Calif. and NEW PROVIDENCE, N.J., Dec. 17, 2020 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD) and Vertice Pharma today announced that they have entered into a co-promotion agreement for Thyquidity™ (levothyroxine sodium) oral solution through MannKind’s specialty sales force. THYQUIDITY is indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. THYQUIDITY is not indicated for suppressing benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients or hypothyroidism during the recovery phase of subacute thyroiditis.
Under the terms of the agreement, MannKind’s sales force will promote Thyquidity to adult endocrinologists, pediatric endocrinologists and other US healthcare providers who treat hypothyroidism. Vertice will make a specified quarterly payment to MannKind to defray the costs of the additional promotional activity and will pay MannKind royalties on gross profit resulting from all sales of Thyquidity.
Status: The partnership dissolved in a few months due to a lack of sales. MannKind racks up another failed deal.
#8 Partnership - Qrum Pharma Inc.
WESTLAKE VILLAGE, Calif., Dec. 07, 2020 (GLOBE NEWSWIRE)- MannKind(Nasdaq: MNKD) toda y announced that it has acquired Qrum Pharma, Inc ., a privately held pharmaceutical company developing inhalation treatments for severe chronic and recurrent pulmonary infections, including Nontuberculous Mycobacterial (NTM) lung disease.
“We have focused on building a stronger pipeline to treat unmet needs for orphan lung diseases, an area where we can leverage our experience and technology to create differentiated therapeutic products,” said Michael Castagna, Chief Executive Officer of MannKind. “This acquisition brings us a lead program that is expected to enter Phase 1 in late 2021. In addition, our combined capabilities have the potential to create a dry powder formulation that will enable patients suffering from NTM to have a much more positive treatment experience. We are also very excited to add the Qrum Pharma development team to our roster of talent, with their deep expertise of inhaled drug delivery.”
“My team and I are thrilled to be joining forces with the MannKind development team,” said Dr. Thomas Hofmann. “I look forward to leveraging MannKind’s best-in-class technology to bring new therapies to patients with orphan lung diseases.”
Dr. Hofmann was touting the best-in-class technology to bring new therapies to patients with orphan lung diseases. So much for best-in-class technology being used to create new therapies, MannKind uses a centuries-old technology to deliver the drug to patients—a nebulizer. Once again, it is a classic example of a ‘spin story’ for gullible investors.
STATUS : There is so much to say about this fantastic and expensive use for the limited cash position that MannKind has on hand. They buy a company where the principal and many other scientists worldwide have attempted to recycle a drug discovered more than 70 years ago. After sacrificing a few canines(dogs), they promoted the planned start of clinical trials using human subjects.
On September 6, 2022, MannKind issued a press release discussing the Phase I results for the humans in their clinical trial—40 healthy individuals without lung disease. The maximum dosing duration was daily dosing for seven days for one cohort of patients and a single dose for the other cohort, where they were confined for five days for daily assessment.
“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.”
It was September of 2022 when MannKind released this press release—more than a year ago. On June 20, 2023, Mannkind published in the Journal of Infectious Diseases & Therapy an article—" Inhaled, Nebulized Clofazimine for the Treatment of Pulmonary Nontuberculous Mycobacteria Disease Offers the Prospect of Convenient Dosing and Prolonged Activity.”
However, in the initial abstract discussion for this article, they state very clearly:
“However, systemic administration of clofazimine can lead to drug accumulation in extrapulmonary tissues and clinically significant adverse reactions in non-target organs such as gastrointestinal side effects, QT prolongation, and skin discoloration. To overcome these limitations, an inhaled formulation has been developed and tested “preclinically and in healthy volunteers----.”
For better clarification, one should reference the previous page and understand the preclinical data was obtained from dogs, and then the minuscule number of Phase I patients were healthy patients with no lung condition disease. The actual exposure time to the clofazimine dosage was a matter of a few days. For patients suffering from Pulmonary Nontuberculous Mycobacteria , the dosing regimen will take months to achieve the desired results. Novartis, the patent holder for clofazimine, knows that prolonged drug use creates horrible adverse events, which is why they no longer actively market the drug. Plus, you will read later in this article about Novartis having an FDA-approved clinical using clofazimine for the same medical condition MannKind was working---and now it appears Novartis has canceled their trial efforts.
What has happened is that MannKind met with the FDA in December to discuss moving their clofazimine trials into a normal Phase II clinical trial with very finely honed goals they hope to achieve in the clinical data generated from such an FDA-approved trial. Instead, they opted to kick the can down the road.'
On January 23, 2023, they issued a press release outlining that MannKind would now undertake an Adaptive Clinical trial using clofazimine instead of starting a Phase I Clinical Trial . So now the clock has been reset, and we have waited and waited on the protocol requirement that MannKind still needs to submit to the FDA. A complete detailed plan for the protocols they would use in conducting this Adaptive Clinical Trial. But then, on June 26, 2023, MannKind issued a Form-K stating that a fire had damaged the German manufacturing facility where they were making the supply of clofazimine, and it would be months before they were back up and running.
MannKind must submit a formal plan to the FDA concerning the protocols for their adaptive trials. MannKind should have already done this required submission so that when the mystery German facility reopens MannKind would be ready to start the required clinical trials. Then there is the fact that there is a manufacturing company in India that is the largest manufacturer of clofazimine. MannKind could have already obtained clofazimine from this company, and the trial would be underway.
Soon, we will be in the fifth calendar year since MannKind purchased this product that had been under development for several years before MannKind came into the picture. Since MannKind gave no details about who and where the German manufacturer is domiciled, verifying that a German company is involved in this continuing delay tactic, it has been hard to confirm that this ongoing delay is based on a fire. But we do know that Novartis, the drug company that holds the patent for clofazimine, had started an FDA-approved clinical trial with the drug for treating (NTM), a lung disease. The same condition that MannKind is using the drug. However, if one checks the FDA website, Novartis has not updated the FDA for what will soon be two years—two years of silence. If Novartis, the owner of this drug, has stopped its clinical trial effort, it appears the fire delay is just another tactic from MannKind to delay any clinical trial. Will a tornado or hurricane be next, hitting the German manufacturing facility?
Status : Who knows? We know MannKind isn’t sharing any information on the issue. MannKind has a long history of promising a drug being taken through FDA-approved clinical trials, examples being an inhaled migraine drug and an inhaled replacement for the EPI-Pen replacement. After touting them for years, each of these drugs were never taken into clinical trials. My prediction --Clofazimine as an inhaled product will never be approved by the FDA. The horrible history of this drug and the devasting side effects should be heeded. Novartis has!
#9 Partnership - One Drop
“WESTLAKE VILLAGE, Calif., Aug. 05, 2019 (GLOBE NEWSWIRE) -- MannKind Corporation (NASDAQ: MNKD) and One Drop today announced that they have signed a collaborative agreement that is intended to integrate MannKind’s BluHale® accessory device into the One Drop platform. BluHale is a Bluetooth-connected accessory that attaches to the Afrezza® inhaler and is designed to convey real-time information about inhalation effort and insulin dose. The goal of this collaboration is to provide a seamless experience for Afrezza patients, including automatic tracking of their insulin doses as well as other important health information on the One Drop platform. The agreement is expected to bring One Drop’s award-winning user experience to Afrezza users, empowering them with AI-enabled glucose forecasts, predictive insights, and the opportunity to connect one-on-one with One Drop’s certified diabetes educators, an educational service that has been recognized by the American Diabetes Association.”
It will soon be the sixth calendar year, what has MannKind accomplished with this promise of producing a Bluhale accessory device that will track and report patient’s insulin doses and other important health information on the One Drop platform? The corporate website shows a clunky and ugly whistle-looking gizmo for teaching Afrezza users how to inhale their insulin. It appears that One Drop is not promoting any product from MannKind, and there appears to be no promotion by MannKind for the One Drop platform.
Status : Under the Partnership section of MannKind’s corporate website, One Drop is not listed as being in a partnership arrangement with MannKind. It should be assumed this is another failed effort by MannKind.
#10 Partnership - AMSL
WESTLAKE VILLAGE, Calif., May 16, 2019 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD) today announced that it has entered into an exclusive marketing and distribution agreement with the AMSL Diabetes division of Australasian Medical & Scientific Ltd. for the commercialization of Afrezza® (insulin human) Inhalation Powder in Australia.
"We are excited to partner with AMSL Diabetes to accelerate patients’ access to Afrezza in Australia," said Michael Castagna, Chief Executive Officer of MannKind Corporation. “This agreement with AMSL, our third international partnership for Afrezza, aligns us with a partner with a strong presence and knowledge of the diabetes market in Australia, giving us an opportunity to provide more healthcare providers and patients with a new option in their fight against diabetes."
“Adding Afrezza to our portfolio is a significant step towards addressing the needs of Australian patients with diabetes who are looking for a mealtime insulin with a unique time-action profile,” said Richard Plowright, Managing Director of AMSL. “Through our exclusive partnership with MannKind, we can bring the benefits of inhalable insulin to patients across Australia.”
Under the terms of the agreement, AMSL Diabetes will be responsible for obtaining regulatory and reimbursement approvals to distribute Afrezza in Australia. AMSL Diabetes will also be responsible for sales, marketing, and customer support, and distribution activities. MannKind will retain responsibility for the supply and manufacturing of Afrezza.”
What will soon be six calendar years since this partnership announcement, ASML has never generated one penny from marketing Afrezza. Not one further comment from MannKind about this partnership since the MannKind CEO stated—
“our third international partnership for Afrezza, aligns us with a partner with a strong presence and knowledge of the diabetes market in Australia"
Status: Just another failed venture from MannKind’s growing list of partnerships and failure to deliver any results. MannKind does not show on its corporation website that they have an ongoing partnership.
#11 Partnership - United Therapeutics Corporation
Is United a friend or a foe? That is the question, so let us look at the potential answer to the query.
“SILVER SPRING, Md. and WESTLAKE VILLAGE, Calif., Sept. 4, 2018 /PRNewswire/ -- United Therapeutics Corporation (Nasdaq: ( UTHR ) and MannKind Corporation (Nasdaq: MNKD) today announced that they have entered into a worldwide exclusive licensing and collaboration agreement for the development and commercialization of a dry powder formulation of treprostinil, an investigational product currently being evaluated in clinical trials for the treatment of pulmonary arterial hypertension.
Under the agreement, United Therapeutics will be responsible for global development, regulatory and commercial activities. MannKind will manufacture clinical supplies and initial commercial supplies of the product at its manufacturing facility in Danbury, Connecticut. Long-term commercial supplies will be manufactured by United Therapeutics.
Under the terms of the agreement, MannKind Corporation will receive an upfront payment of $45 million and potential milestone payments of up to $50 million, dependent upon the achievement of specific development targets. MannKind will also be entitled to receive low double-digit royalties on net sales of the product. In addition, MannKind granted United Therapeutics an option to expand the license to include other active ingredients for the treatment of pulmonary hypertension. Each optioned product would be subject to the payment to MannKind of up to $40 million in additional option exercise and development milestone payments and a low double-digit royalty on net sales of any such product.”
The effectiveness of the licensing and collaboration agreement is conditioned on the expiration or termination of the required waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.
The parties also entered into a research agreement for the conduct of research by MannKind on behalf of United Therapeutics for products outside the scope of the licensing and collaboration agreement. MannKind will receive an immediate payment of $10 million in consideration for its performance under the research agreement.
We are excited to partner with United Therapeutics, a company that shares our passionate focus on changing patients' lives," stated Michael Castagna, Pharm.D., Chief Executive Officer of MannKind. "We are pleased with this new opportunity to demonstrate the value of our drug and device combination platform for delivering therapeutic products. We believe this collaboration will have the potential to significantly improve the lives of people living with pulmonary arterial hypertension."
MannKind’s CEO stated he was “excited to partner with United Therapeutics, a company that shares our passionate focus on changing patients’ lives.” With this enthusiasm by the MannKind CEO, investors should have read closely what a shrewd and savvy deal United's CEO foisted off on MannKind’s CEO.
United knew MannKind was dealing with a weak hand and desperately needed such a deal with them. But United also had issues where they needed a quick solution and maybe a temporary solution for their need.
The following is a brief chronology of United Therapeutics:
United Therapeutics:
- In 1996, United Therapeutics was created for the noblest of all causes when Martine Rothbatt opted to find a cure for her daughter's life-threatening condition—pulmonary arterial hypertension.
- Also, in 1996, United Therapeutics went public with an IPO priced at $12.00 per share.
- In 1997, the company acquired the rights for Treprostinil from Glaxo Wellcome, Inc.
- It was 2001 when United received approval from the FDA for its first drug, Remodulin, delivered by subcutaneous infusion.
- Next was in 2008, when United received FDA approval for Tyvaso, a nebulizer-delivered Treprostinil drug for treating PAH.
- United’s human organ transplant program is years away from being a source of revenue.
- Merck ( MRK ) has on-track approval for a breakthrough designated new PAH treatment—sotatercept, pending an FDA decision on March 22, 2024.
One can look at this historical list of United’s events and sources of revenue, and it is obvious that their impressive revenue comes from one drug being the active ingredient---Treprostinil. Adding Tyvaso-DPI was the last inclusion, as United saw that competitors like Merck and Liquidia ( LQDA ) were on the verge of entering the PAH market. Liquidia received FDA approval for their Treprostinil PAH drug long before United got FDA approved for their inhaled version. In fact, United's version was first rejected and required additional data collection before the FDA would approve its version.
The launch of Liquidia’s drug has been delayed until the FDA receives confirmation that the patent lawsuit United has against Liquidia is no longer valid. MannKind’s investors should have been watching and paying attention to their and United’s stocks. With the projected growth in Tyvaso-DPI sales being highly favorable, MannKind's stock has fallen below $4.00 a share. But it should be noted that under $5.00 a share, based on the earlier 1-5 reverse split, the stock for the long-term holders, what will soon be in the tenth calendar year, are holding a sub-$1.00 stock.
As for United holding a near monopoly on their revenue-generating drugs and projecting their revenue growth would continue to expand, we have seen over the recent few months that their stock has lost nearly $64.00.00 per share. This represents a loss of $2+ billion in their market capitalization.
The following issues appear to be impacting the potential for United and MannKind’s marketing efforts and what action United has taken to resolve this potential loss of revenue---with MannKind being the odd company out based on shrewd deal-making by United’s CEO.
Factors That Could Impact the MannKind and United Therapeutics Partnership:
Tyvaso-DPI is owned and controlled by United Therapeutics. The initial revenue for sales goes directly to United. Plain and simple—should anything happen to dissolve the partnership—Tyvaso-DPI is owned by United.
Go back to the Cipla part of this article, and let me remind my readers about this part of the Cipla/Mannkind partnership:
“MannKind will receive a $2.2 million upfront payment from Cipla within 30 days of entering the agreement, with the potential to receive additional regulatory milestone payments, minimum purchase commitment revenue , and royalties on Afrezza sales in India “(My bolding of critical words)
Based on this wording outlining the significant considerations of the partnership, MannKind’s CEO is aware of what a ‘minimum purchase commitment revenue’ legally binds the two partners making such a partnership.
When the partnership was created in 2018, the contract did not mention a ‘minimum purchase commitment’ on the part of United. MannKind cannot claim they were unaware of such commitments because they requested an agreement with Cipla.
In an early article I shared here on SA I included the following update about United wanting to alter certain aspects of their partnership. In August 2021 and then two months later, in October 2021, United stipulated changes in their agreement.
In August 2021, something sparked United into wanting to modify the terms of their contract with MannKind. The significant change was that United wanted to turn all product manufacturing over to MannKind. The original contract was that MannKind would only manufacture the product for the clinical trials and the initial launch supply of the DPI product.
After the August 2021 change in the contract, two months later, in October 2021, United came back with a new CSA where, in the first sentence, they stipulate the contract would continue until December 31, 2031 (unless earlier terminated.) Then, in the last sentence of this new CSA we see for the first time –that “each has normal and customary termination rights, including termination for material breach that is not cured within a specific timeframe or in the event of liquidation, bankruptcy, or insolvency of the other party.”
In reviewing public documentation, I can find no binding agreement that involved United being required to buy a minimum amount of Tyvaso-DPI from MannKind. I was able to find this June 2023 announcement from the Durham, North Carolina, Economic Development Organization
PUBLISHED JUNE 30, 2023
“A multibillion-dollar company is growing its footprint in Research Triangle Park with plans for a $500 million manufacturing facility.
United Therapeutics (Nasdaq: UTHR) is building the facility to expand its capacity to produce a drug-device combination product that received approval by the U.S. Food and Drug Administration last year. The product, Tyvaso DPI, is a central part of the company’s growth strategy as it aims to double its revenue in the coming years.”
This is another source for what United will use this massive new manufacturing and distribution facility in North Carolina.
“Alongside ProKidney, United Therapeutics , which has co-headquarters in Silver Springs, Maryland and Research Triangle Park, announced a $500 million investment in a new manufacturing facility in North Carolina. First reported by Triangle Business Review, the new site will allow the company to expand manufacturing of the company’s dry powder inhaler for treatment of pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD). The FDA approved Tyvaso DPI in May 2022. “
Conclusion:
Afrezza has been available for doctors to prescribe the drug for 456 weeks, or 8.75 years. In two months, this availability for Afrezza to be used by diabetics will span ten calendar years. During this time, Sanofi, one of the largest drug companies competing in the diabetes market, signed on in 2014 to market Afrezza. After launching the drug in late January 2015, before the year had ended, Sanofi opted to cancel its partnership with MannKind. Left with no other drug company offering to take Sanofi’s place, it was up to MannKind to undertake the marketing efforts.
Within weeks in 2015, Sanofi, with no foundational basis for marketing Afrezza, achieved weekly prescriptions in the mid-400 level. Now 455 weeks into Afrezza being on the market, MannKind’s sales effort over the last 22 weeks has generated an average of 370 new prescriptions. During these 22 weeks, the weekly total has been less than 400 new prescriptions.
As for refills, with the 456 weeks of new prescriptions rolling over every 90 days to be refilled, the weekly number has never exceeded the 500 level. The lack of initial users having their Afrezza prescription refilled means that somewhere in the order of 75-90% fail to maintain their use of Afrezza. Now, the clamor is that pediatric patients will be the solution for getting and maintaining levels of prescriptions needed to save Mannkind. In my opinion, this happening will be doubtful. In the ten years that Afrezza has been FDA-approved, every doctor who prescribes insulin for their patients has had the opportunity to prescribe it, and they don’t!
Think about the prescription data—after 8.75 years of prescription, the latest weekly data shows (10/13/2023) 362 NRx and 472 Refills. Afrezza is a failed drug! Every major drug company that participates in the diabetes market told those who would listen that inhaled insulin would not be successful. So did I!
I have just shared eleven (11) partnerships that MannKind entered, where BIOMM contributed $500,000.00, and only United Therapeutics has been a fundamental contributor of meaningful revenue flowing to MannKInd. However, what we are seeing currently is that United’s public disclosures are beginning to show that maybe the MannKind-United Therapeutics partnering was a ‘marriage of temporary convenience’ version.
As mentioned earlier in this article, United has the problem of having one drug as the active ingredient for their major revenue stream. United uses Treprostinil as the drug, providing the active ingredient for efficacy for their PAH patients. In 2018, when they formed their partnership, United saw a new competitor on the horizon, a competitor that could drastically impact their revenue. Plus, it would fill the one category where United didn’t have a Treprostinil version available—a dry powder inhaled version.
The CEO of United is a highly capable executive and is also a person willing to play hardball where the use of lawsuits could be deployed because United has the cash to spend and the motive. Plus, there was a personal issue involved.
The United CEO had an issue with the current CEO of the soon-to-be competitor, LIQUIDIA( LQDA ). Dr. Rogers Jeffs was the CO-CEO who led the development of the United Therapeutics products for 16 years. Upon joining Liquidia, he created a company where he developed an injectable form of Treprostinil for PAH patients. Now working with Sandoz ( SDZXF ), the two companies split net profits for their drug. As of the second quarter results, they each made a net profit of nearly $5 Million. But assuming the gross revenue is $5.0 million, this means Liquidia/Sandoz, on an annual basis, is taking $40.0 million of what would have been United Therapeutic revenue.
With Liquidia having an already FDA-approved dry powder inhalation treprostinil product, Yutrepia, they are now awaiting the decision from the proper appeals court. This court will meet on December 4, 2023. Their decision should be rendered shortly after the hearing. In recent months, Liquidia and their sales team have been building inventory for Yutrepia and preparing to launch their product in short order, assuming the court decision is affirmative for Liquidia.
What will be the impact for United if Yutrepia is finally able to be launched in the United States?
We know that United has a contract with MannKind for manufacturing the finished supply of Tyvasso-DPI. We know that MannKind has a contract that will pay them a low double-digit royalty on net sales of Tyvasso-DPI. MannKind will get a low single-digit cost plus payment for manufacturing Tyvasso-DPI. If MannKind gets a 12% royalty on net revenue and 5% for the cost-plus manufacturing, this would mean that if United opted to eliminate MannKind from the picture, United would save 17% of their revenue being paid to MannKind. However, this would require United to absorb the manufacturing process fully.
But MannKind has a signed contract with United---don’t they? The answer is yes, but unlike the Cipla partnership, MannKind’s CEO did not get a minimum purchase agreement from United Therapeutics. Based on the contract that MannKind signed, United could order any small size order and comply with their contract. The only holdup is that the new North Carolina manufacturing and distribution center will not be finished until 2025.
This new facility being built in North Carolina is a state-of-the-art building, and United is spending $500,000,000.00 on the construction and equipping of this manufacturing and distribution center. With United paying this massive cost for this facility, they can’t afford it sitting empty and not generating a source of revenue. But United has already publicly told investors what they will be manufacturing in the facility ---
United Therapeutics (Nasdaq: UTHR) is building the facility to expand its capacity to produce a drug-device combination product that received approval from the U.S. Food and Drug Administration last year. The product, Tyvaso DPI, is a central part of the company’s growth strategy as it aims to double its revenue in the coming years.”
17% of the current revenue going to MannKind could be a significant contributor of funds for United paying for this building.
United notified MannKind with their second revision to the original contract in October 2021.
“After the August 2021 change in the contract, two months later, in October 2021, United came back with a new CSA where, in the first sentence, they stipulate the contract would continue until December 31, 2031 (unless terminated earlier.) Then, in the last sentence of this new CSA we see for the first time –that “each has normal and customary termination rights, including termination for material breach that is not cured within a specific timeframe or in the event of liquidation, bankruptcy, or insolvency of the other party.”
On June 30, 2023, they publicly told investors they would manufacture Tyvaso-DPI in their new North Carolina manufacturing facility.
With Liquidia already taking $40 million of United’s revenue from Remodulin sales, United is well aware of Liquidia's ability to manufacture their products for a lower price and then undercut the price United charges. With a favorable December ruling for the launch of Yutrepia, United could see maybe 50% of its current revenue disappear.
Who would be the odd man out of this triad? Mannkind is trading around $3.90, or $0.78 per share, based on the 1:5 reverse split of their shares post-2015. There is a reason for this disparity between Liquidia's stock price and MannKind’s stock price. There is also a reason why, in recent months, United’s stock has dropped by $64.00 a share—representing a little over $2 billion in market capitalization for them.
As I stated earlier in this article, since May 19th, as reported by the Symphony data reporting service company, the weekly prescription data has been in the 300 level for the ensuing 23 weeks of reporting. As for the first three weeks of the 4thQ, the weekly prescription rate, as compared to the 3rdQ number, is down more than 3%. MannKind can not afford to continue manufacturing and marketing Afrezza. This is my opinion, based on hard data and nearly nine years of such hard data. This opinion and considering what at least United is openly revealing about their Tyvasso-DPI product, for the sake of MannKind, I hope I'm wrong.
As I opined in my October 4, 2014, initial article about MannKind— MannKind: Reality Check , I pointed out, and I quote again— “True reality is always in the details.”
I wish those invested in MannKind’s stock---good luck! It is still my desire that someone, or a company, will always maintain the availability of Afrezza for select patients—after all, it is an insulin product. I’m not suggesting that anyone short or buy MannKind’s stock. As for shorting the stock, this would require you to have a margin account---no one should have a margin account.
For further details see:
MannKind: Are They Working With A Friend Or A Foe?