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Post by stevil on Aug 30, 2019 19:35:09 GMT -5
I would approach GSK with a proposal to develop Imitrex(TS). They are in the same situation with their migraine drug as United Therapeutics is with PAH. With competition from generics and patent life issues, a rapid-acting inhaled TS-Sumatriptan would breathe new life into their portfolio. I don't see a whole lot of opportunity there. The 5-HT agonists are pretty crowded. I'd prefer they go after the new CGRP class like Aimovig. Those need to be injected IM, like epipens. There is a far greater market for these, especially because they are new. I think a yearly supply runs close to $5k per patient. But insurance companies are happy to pay for it because it keeps migraine sufferers out of the ED. There is also research going on that show IV CGRP's can safely abort status migrainosus, or intractable migraines. Previously they required other neurological medications that typically took a couple days to break the headache. So there will be opportunity for a long time with these medications. The only side effect with them so far has been injection site reactions, meaning they are extremely safe and have essentially no side effects other than what's caused by the needle. Truly, this is one market I hope MC is targeting. MNKD should have a legitimate shot at landing a good partner.
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Post by stevil on Aug 8, 2019 8:41:40 GMT -5
I used to play the part of aged until I realized I'd rather spend time on school than waste it trying to convince people that could not be swayed in their thinking. I actually found it to be counterproductive because it just made people more staunch in their views against me. Anyone is free to go back through my hundreds of posts and see that I called many of the negative events- maybe not called, but explained why negative things were and were going to continually happen and people hated me for it.
I have seen aged say it before and I appreciated his sentiment when he said he doesn't need to highlight the positives all the time, or even with any normal frequency at all. There are plenty here whose hope forever springs eternal and they cannot see the other side. When you have those people already on the board, you don't need to waste time reinforcing it. I would often play devil's advocate to those people, trying to convince myself in the process that they were right. I never could and it's why I haven't been long this stock since I got in and realized all the issues it would have once Sanofi dropped us. I stick around because I am now a doctor (PGY1) and am interested in the healthcare aspect of Afrezza as well as seeing how the story continues to unfold. As long as people are here presenting facts or logical conclusions according to the facts, their motives should not be questioned. It's probably just my personality, but for people who represent "the other side" to my line of thinking, I often look forward to reading their thoughts to challenge my own. I never get upset at them, but really appreciate their work because they expose any blindspots I have. I wish the board would do the same with the understanding that facts are facts and opinions are opinions. Pay attention to the facts and take the opinions always with a grain of salt.
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Post by stevil on Aug 6, 2019 19:01:24 GMT -5
Stevil, Thank you.. it seems like we need a grant and a partner. Big money..and BP You're welcome, sports. I didn't necessarily mean to ask me... So many on here cannot fathom why doctors won't prescribe Afrezza, but like matt said in his post today, can you really blame them when Afrezza statistically isn't as good as RAA by the current metrics used to measure effectiveness of insulin? The problem isn't with doctors or "the system". The problem is with the data. That falls squarely on MNKD's shoulders and no one else's.
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Post by stevil on Aug 5, 2019 21:21:32 GMT -5
If you want to know why a doctor doesn't prescribe, ask a doctor. There are many on here with loud voices that have no knowledge of what they speak or live in an alternate reality to the one I live in. Be careful whose voice you listen to. Really, it's not that hard to understand... Just open your ears to the ones who know what they're talking about. It will make much more sense. So what are the reasons and what can be done about them? Sorry I’m sure you’ve told us before. I'm not sure you want to ask me what can be done about them because I don't think many on here will like my answer. It will take creativity beyond what I possess to make Afrezza the blockbuster so many expect. MNKD is between a rock and a hard place because they must prove superiority if they hope to claim it. That will be very expensive. I don't foresee Afrezza overcoming this barrier without a large scale trial or the passing of several years with favorable results on CGM. Until then, they'll just be a niche product for the few whose insurances cover it and can afford to pay the premium. (as a whole) Doctors overlooking Afrezza has nothing to do with collusion or "the good ol boys" club. It has nothing to do with laziness on the part of doctors. While some may call it either of these, that is not the heart of the issue and it is my opinion that they are not just slightly wrong, but wrong by a very wide margin. The heart of the issue is multifold. RAAs have been proven. They have been tested, retested, and then tested again. This is particularly important regarding dosing instructions. RAAs have a known profile while it seems Afrezza's is still being discovered. That uncertainty alone is enough to put doctors off. Not because they're lazy or stupid, but because they're not going to use their patients as guinea pigs when they have a tool they know and trust already that has been, up to this point, been proven to be just as good. The same goes for metformin. Contrary to the opinion of some, the medical community loves metformin and has produced countless studies outlining its numerous benefits. Cost is a huge issue in healthcare, especially in a system as broken as ours (although cost reducing measures would be even greater in a single payer system). Metformin will forever be the first line therapy because it is $4-$8 a month, depending on dosage and where you fill your rx. I'm not sure any evidence will ever surface to justify the order of treatment being different. People can (and do) go decades on metformin without much more than neuropathy and probably a slightly increased chance of coronary artery disease and stroke. It seems there is a huge disconnect between the people of this board and people with diabetes as it pertains to the impact medication cost has on a system. The highest incidence of diabetes is with African Americans, particularly those with lower incomes who usually make poor food choices. Healthy food requires more time, effort, and money than cheap and easy junk food. This means there are literally millions of people who cannot even afford to pay for any insulin, let alone the massive premium Afrezza requires. I have made this point before to the chagrin of so many on the board- metformin and sulfonylureas are a godsend to these people as they would probably die decades sooner without them. The cost burden is only getting exacerbated as younger and younger children are now getting diagnosed with type 2 diabetes, meaning the number of years per person requiring treatment is also increasing as people are getting diagnosed younger and living longer. As far as insulin goes, Afrezza has only proven to be "non-inferior" to RAAs. In a doctor's mind, that means inferior since you have to pay a premium for the same results. Therefore, by default, it gets categorized as a niche product- only those who fear needles and are willing to pay a premium to avoid said needles will get a script. Even beyond this, doctors think in terms of risks and benefits. What is the risk associated with a medication compared to the benefit it provides? So far, the risk with Afrezza is unknown. What is known is that it contains a black box warning and had a spirometry requirement. There was also a link to lung cancer with Exubera (another member in its class, right or wrong) that Afrezza may or may not be able to overcome. The benefits are inhaling vs injecting, which for most people with diabetes I have talked to isn't much of an issue at all. Thus, you have potentially a ton of risk without much proven benefit. The STAT trial was a start, but it proved that Afrezza still caused hypoglycemic episodes, just like every other insulin- only the time spent in hypoglycemia was shorter. While that is meaningful, it will still make it "less safe" than metformin, since metformin does not have any effect on insulin secretion, only increasing sensitivity to insulin. In other words, it cannot induce hypoglycemia. As I have said before, there are thousands of medications on the market that are FDA approved. It is not laziness on the part of doctors if they are not familiar with all of them. It's simply not possible to know every medication through and through. Not even pharmacists know every medication on the market thoroughly and their scope is much narrower and focused solely on medications. The best way to learn medications is to clump them into classes. SSRIs, beta blockers, ace inhibitors, cephalosporins, fluoroquinolones, etc... One learns the class and then learns what differentiates one drug vs another member from its class. Most docs pick one or two medications from each class that they will prescribe. It simplifies things. It allows them to learn the characteristics of the one medication and appreciate the nuances of one medication rather than multiple others that ultimately do the same thing. There are guidelines and trials that would suggest the use of one drug over another member in its class for certain uses, if needed. Otherwise, they are all the same for all intents and purposes. In case I have lost you by now, I'll try to simplify it as it pertains to Afrezza. Afrezza has been characterized as either a RAA or ultra-rapid insulin. The way for Afrezza to differentiate itself from other insulins in its class is to have trial data that proves its superiority and demands its use. Otherwise, it will get lost in the crowd if the trial data says it is only as good as other insulins in its class. Insurance companies generally don't care if you're afraid of needles. Comfort will not determine standard of care. Results and cost will. They are in the business of making money and only care about the bottom line. Again, I have seen this mentioned here before. It is the way it is and it will not change unless a single payer system overhauls our current one. For those wishing for this to happen, it would likely eliminate all hope for Afrezza outside of proven long term benefits that reduce later costs associated with comorbidities (heart disease, stroke, neuropathy, etc). I have seen aged talk endlessly about people with diabetes not wanting to think about their disease. He/she is right. Believe it or not, another trial would need to be done, or a meta analysis of a huge conglomeration of data points to prove increased adherence- more people take their insulin and have proven better results in an entire population vs just a single trial- before Afrezza would become standard of care. In other words, this will not happen quickly, even if everything aligns perfectly. As dumb as it sounds, trial data not only needs to support that something is possible, but that it actually does happen as well. For instance, those who only take 1 dose of Afrezza may not have better results compared to one dose RAA'ers. If the increased dosing burden is too high amongst an entire population so much so that the population has worse results with a superior product, it will still not be recommended as standard of care. It would be best for MNKD to find a way to prove superiority with just a single dose rather than a second, extra dose as this will not only increase cost burden, but also the added burden of an extra dose with every meal. While I will not claim infinite knowledge to say the "insulin cartel" does not have political power to ensure their dominance in the industry, I will say that I feel very strongly that this is not the case. Is capitalism to blame and might that be the culprit? I would say this is the case a hundredfold more so than under the table dealing. The way insurances work is that manufacturers make contracts with PBMs and offer discounts to gain exclusivity. This makes it extremely difficult for a new medication to penetrate the market. The best way for MNKD to overcome this is to design a trial that beyond a shadow of a doubt proves its superiority in A1c reduction and increased TIR. Then, after that has been done, to price Afrezza according to other RAAs, unless they can prove with data that their increased cost is justified. Theoretical ideas hold little to no merit. I have a feeling that even if Afrezza does gain superiority, RAAs will drop their price and make it harder to justify using an insulin that is much more expensive. The problem is, no matter how much better Afrezza can be than RAAs, it will be very difficult to justify its use if it is so much more expensive. There is something called "number needed to treat" that is a metric researchers use in order to justify the use of medications amongst a population. If that number is too high, meaning it would take thousands of people to only have a few live better lives, the end may not justify the means. In other words, it doesn't make sense to place an additional strain on the market for a marginally better drug when spending millions extra would rob far more of basic care. For example, $1 million would allow 250,000 people to take metformin monthly vs about 10,000 on Afrezza. The numbers have to justify the cost burden. Right now, they do not. I don't foresee MNKD ever doing so, but will be pleasantly surprised if it can ever be proven. The numbers above assume $1000 monthly for Afrezza vs $4 monthly for metformin. I think the average humalog/novolog monthly rx costs between $250-500 for reference. So in summary, it's: 1. There is not enough compelling data right now to support use of Afrezza vs other RAAs 2. The risk hasn't proven to outweigh the benefit 3. The cost hasn't proven to outweigh the burden 4. Even if 1, 2, and 3 are proven, the vast majority of people would either still not have access to or be able to afford Afrezza How to fix: 1. Fund an expensive well-designed clinical trial to prove superiority as well as small number needed to treat for cost burden purposes 2. Wait several years for the cream to rise to the top and for all the data to eventually find its way (assuming favorable results with Afrezza usage)
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Post by stevil on Aug 5, 2019 19:03:43 GMT -5
Aged - I think you are absolutely correct and we are in violent agreement. They make the rules. If MNKD continues to play by the rules afrezza script growth will be a slow slog. I am hoping today's announcement with One Drop is a step forward in changing the paradigm in how afrezza will be sold going forward. Direct to PWD clinics with 24/7 connected care is the fastest way to increase sales and by-pass the rules which are holding back afrezza sales. Hopefully they will announce a clinic partner soon and get 'er done. If by playing by the rules you mean that Afrezza has to prove itself in the same way everyone else does, you are correct. Science is science. Hypotheses are just theory until you can prove them with reproducible data. Like it or not, these rules are rules for a reason. The board has hashed, rehashed, and then hashed again over a thousand times. It is the way it is and is the way it should be. Good medicine is not guesswork. As long as and until MC decides to make Afrezza more affordable, this will continue to be an issue. I'm not him, so I won't pretend to understand the rationale behind why he has set the price as high as he has. I'm sure he has good reason for it. But if you have to take twice as many doses as other prandial insulins, it will be cost-prohibitive for Afrezza to become the SOC. Cost is a real determining factor in the practice of medicine. The gold standard isn't always the standard of care if it is too expensive for all to have. There are other examples where cheaper tests/medications are given that are not as good of quality because it would help a broader amount of people to give the cheaper alternative vs the minuscule benefit of the best given to the few.
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Post by stevil on Aug 5, 2019 18:58:54 GMT -5
If you want to know why a doctor doesn't prescribe, ask a doctor. There are many on here with loud voices that have no knowledge of what they speak or live in an alternate reality to the one I live in. Be careful whose voice you listen to. Really, it's not that hard to understand... Just open your ears to the ones who know what they're talking about. It will make much more sense.
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Dosing
Jul 14, 2019 16:13:54 GMT -5
Post by stevil on Jul 14, 2019 16:13:54 GMT -5
antibiotics these days have a short life span. They need to get going while resistance is low.
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Post by stevil on Jul 14, 2019 16:06:29 GMT -5
Can antibiotics be administered with Technosphere. ? Pc in NYT’s that infections are becoming more resistant to medications even requiring intravenous.... antibiotics bid market... This could be a potentially huge market as patients are sometimes required to stay in the hospital for several extra days even after they are stable for continued IV therapy. Sometimes they're sent home with PICC lines for the treatments that require multiple weeks of IV therapy. But they come with an increased risk of infections themselves. So there is great value to inhaled antibiotics. If I were Mannkind, I'd think about the most common ones, like Vancomycin (although that usually requires a trough to ensure proper blood levels), Zosyn and others.
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Post by stevil on Jul 12, 2019 15:13:27 GMT -5
The study for this would not be inducing anaphylaxis. Rather, it would occur in an ER. Patients coming in with anaphylaxis would be randomly assigned to either the EpiPen group or the inhaled epi group. Should any treatment fail, you have the full capacity of the ER to follow up with other means of resuscitation. I thought I read that they don’t study these types of drugs in the midst of an event, but rather measure serum levels for drug concentrations in healthy patients, given the drug is already well understood. That’s why the insulin testing the FDA dragged Mannkind through for the change in inhalers was so ridiculous. This would be impossible to test without knowing how much of the medication reaches the bloodstream when an airway is closing or closed. The only way to do that would be to test it under conditions of anaphylaxis. In other words, it's not the efficacy of the compound they'd be testing, it'd be the route of administration. They already know what certain blood levels of epinephrine will accomplish. They don't know how much an obstructed airway would affect the ability of the epinephrine to get to its target without conducting real world scenario tests.
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Post by stevil on Jul 12, 2019 15:12:23 GMT -5
I won't pretend to play expert here because I am not.
However, a few things that immediately jump out to me.
1. They'd have to get patient consent. I'm not sure taking the time to explain the differences between the two as well as the risks involved, then get a signature would be a good use of time in this kind of scenario. I did have an EM rotation at one of the busiest emergency centers in the nation so maybe my understanding of the process is jaded, but stuff did not get done that quickly. The staff certainly would not take the time to do this, but maybe it would work at slower centers. Then again, how much anaphylaxis would they see at a slower center?
2. It's likely that they'll already have a needle stick for IV access by the paramedics. At that point, what's the benefit to the patient to receive the medication orally? Especially when it's not proven? I wouldn't choose to participate in that study nor would I encourage a loved one or friend to.
3. I'm sure you're well aware there are varying degrees of anaphylaxis ranging from mild to shock. How do you tease those out? Can you reliably say that taken within x amount of minutes that it would be just as effective as injected? Different people have different immune systems and have more severe reactions than others. You obviously cannot give it to patients with severe reactions if they have to wait that long to get it (as they will be unconscious), so the results will be skewed. So maybe you could make the case for mild anaphylaxis, but then that leaves the door open to litigation because it's a subjective call based on potentially immeasurable quantities (unless they get lucky enough to have as good of results if they can still reliably inhale and that be the proper metric for indication). However, I wouldn't even want to put myself in that position as a patient or physician of having to distinguish when I can or when I can't when I already have an option I know I can reliably trust regardless.
Maybe that's what the BluHale is for. Maybe it will come in the box with the epinephrine and will tell if it's appropriate to inhale. If they can inhale at a certain force that they'd have enough ability to get it into their lungs... just a thought....
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Post by stevil on Jul 12, 2019 14:25:03 GMT -5
Is there as effective an alternate rescue medication available for ashtma in this case? If there is no other good option, you have to use what is available. plytle , I saw your post just after I posted above - the point is spot on.
mnkdfann , the point was not whether there were options available, but rather rtmd implied it would be a malpractice risk to prescribe an inhaled medication for "an ailment whose hallmarks are airway constriction and difficulty breathing." Care guidelines for asthma illustrate the silliness of that claim. Litigation is chock-full of silly claims. If I would ever consider prescribing inhaled epinephrine, I would only do so with an accompanying epipen script. It's up to the patient at that point which or both they want to fill, but at least I'll be able to document to cover myself that I offered an injected version to my patients. You have to remember that judges do not have medical knowledge and lawyers are able to exploit any loophole and make it look like a highway tunnel. All I will add to this is be careful about how much of a "no brainer" this is. I think it was mentioned before, the same was thought of Afrezza. I would also want to see that outcomes were as good or better than an injected epinephrine before considering a script. I'm not sure inducing anaphylaxis would be ethical, although I'm not an expert. I am way more weary of prescribing epinephrine than I would be for insulin because the margin for error is much wider with a chronic disease than one that can kill you within minutes. Just my opinion. Take it for what it's worth. Edit: To illustrate my point of how silly lawsuits can be, I'll share a story from a GI doctor I rotated with. He was treating a woman with diabetes who had gastroparesis. There aren't a lot of good options for it. About the only thing that is FDA approved is Reglan. So he prescribed her Reglan. A serious side effect of Reglan is tardive dyskinesia. It can be reversible if you stop Reglan soon after initial symptoms present themselves. He told her to stop taking the medication. He even documented that he told her to stop taking it. The problem was that he gave her a year's prescription of it right before she started showing signs of TD, and she kept taking it. The story doesn't make a lot of sense to me when you consider why she waited 10 years after he saw her to sue him, but that's supposedly what happened. Well, you're allowed to shred medical records after 6 years and that's what he did. So there went his proof that he told her to stop taking her medication and he ended up losing the case. So she developed a well-known side effect from the drug but the doctor lost a lawsuit because it's our responsibility to make sure the drug isn't harming our patients. There was proof that his treatment plan harmed her and no proof that he did his job to protect her. No patient's convenience is worth a lost lawsuit.
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Post by stevil on Jun 2, 2019 11:55:21 GMT -5
My guess for why Afrezza isn’t used exclusively is one of at least 3 things.
1. The longer tail leads to a greater reduction in A1c without follow up dosing
2. It’s more burdensome to constantly need to dose more than once per food intake
3.Repetitive multiple doses leads to a much higher cost than combining the two.
I’m not in the camp that says MC should be fired, all 3 should be able to be fixed by him and his crew. Studies showing proper dosing leads to better A1c reduction, fewer repetitive dosages, and overall reduced cost (although Without the benefit of time it’s harder to prove this one...) at this point it makes sense to commit heavy resources to fewer interested docs because conversion rates thus far have been abysmal. They need to identify doctors that are open minded and flood them with attention and resources to convert.
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Post by stevil on May 25, 2019 22:22:29 GMT -5
If a doctor contacts a rep to work with a patient, or a rep contacts a doctor to offer assistance with any patients having trouble, or a patient contacts a doctor and asks the doc to set up a meeting with a rep, or a patient contacts a rep and asks they both meet with the doctor, those are all special cases. In all of those I can see how a rep would learn the patient's identity. I don't know the details of laborer's situation. Could it be one of those? But if a random patient fills a prescription does the pharmacy really relay that information to the local rep? Or do doctors automatically inform reps every time they prescribe that rep's product? Those are the cases I was wondering about. Reps have access to exactly how many scripts a doctor writes. I don't know exactly how it works, but I think it's probably a doctor's NPI number gets attached to the script and the data can be mined by the manufacturer. There is no violation of HIPAA since no patient info is given in the data... just which doctor prescribes how many scripts. Which begs the question, why can't MNKD have a correctly updated prescriber list?
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Post by stevil on May 15, 2019 7:58:26 GMT -5
I don’t agree with your negative spin in terms of the “out of their hands”, but I do sense you are correct that they’re saying, “steady as she goes”. They have chosen their course, they don’t have fear of it, and will continue on it. I suppose MNKD has full control over if a doctor prescribes Afrezza. Ha, how is that “negative spin” in any way? I see a lot of chaffing here on this board which is understandable for those who’ve been invested longer than I (2013). But let me ask, did this ASM have the same feeling as when Edstrom and Pfeffer were CEO’s? I see other posts from time to time which say, in effect, that Mannkind is working with a shoestring budget. I couldn’t agree more. Talk of large trials in that environment are wishful thinking. Even maintaining a consistent TV DTC campaign is not sustainable. Large overt efforts to change the Standard Of Care are not possible given the Are we able now to be dismissive of the idea of further dilution? NO! But I’m glad people are finally seeing it as the most likely outcome. Before it was “there’s no way the Mann foundation would let MNKD go bankrupt.” Then there was the hopeful faith that Al’s pals would come to the rescue. Now, people are finally beginning to see and can no longer deny that they’re going to be the ones funding this venture going forward and it will be their backs and feels the weight. How can anyone recommend this stock today knowing that it’ll be worth potentially half as much by the time this all gets fixed? Why would anyone buy now or why would anyone hold when there’s not much reason for the share price to increase with the downward pressure of dilution constantly looming over the stock? You’ll be able to get back in after a couple years, make more money somewhere else, then have more cash to buy more of the company later than you would today. There just isn’t a case to own the stock right now and the more people begin to realize this, the worse the share price gets and the more painful the dilution. Whatever is said in response to the question should be colored by a fixation on the fact that Afrezza IS a superior prandial insulin to all existing RAA insulins which has not sold well yet, but which attracted the talents of Kent Kresa, and Dr’s Castagna and Kendall. TechnoSphere technology IS the basis for Mannkind pipeline development. Afrezza is the first result. The main reason you will find me defensive of our leadership is because I share their fixation on Afrezza and TS technology. I think they’re doing magnificently all things considered. I don’t think people share your sentiment about “all things considered”. That’s a moral victory that I don’t think any honest poster would admit was their expectation when they got into this investment. I’m not making the case that progress isn’t being made. I’m making a case to view this as an investment and to analyze the stock as such. Right now, this is not a good investment, and hasn’t been since its IPO. The potential has always been there. The market now knows MNKD too well. It knows exactly what is coming and will no longer reward moral victories. Only substantial events will improve SP going forward and besides the pain molecule which we don’t know much about.... there’s not really a lot to hang your hat on for the next several years.
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Post by stevil on May 14, 2019 20:36:05 GMT -5
Kevinmik $MNKD What I didn't like at today's meeting was MNKD using a Type I Diabetic & a company Sales Representative as props to tug at the hearts of shareholders and deflect attention away from management strategic shortcomings & under performance. Stories surrounding their experience with Afrezza were compelling, but nothing we don't already know. There are lot's of positive patients testimonials on social media going back many years that are available for viewing and I have no doubt Mannkind has many great line employees in sales, manufacturing & R&D doing a great job, however, today's meeting should have been all about the company's under performing MNKD 2.0 strategy, that's contributed huge shareholder value destruction over the past 3 years. Instead Management & BOD should have presented a plan that navigates MNKD in a new direction to reach a goal of helping more patients targeting more diseases and especially to finally start driving a growing stock price and Shareholder value. I think people are missing what management is saying by having the type 1 diabetic speak at the meeting. When I read this, I read loud and clear that they think they're walking the correct path. They're saying that their plan is working and that people are getting results with Afrezza. It's so great it will catch on... Just give it time. Mike telling the story of minimed taking time... They are, as clearly as they can, trying to tell shareholders that there is nothing to do but wait for things to change and that they aren't going to do anything radically different in the meantime. How else can they justify giving themselves bonuses? They think they've done a great job and have earned it. Marketing- out of their hands Changing SOC- out of their hands Getting doctors to prescribe- out of their hands Need for better trials- we're going with what we've already got Those looking for changes in strategy with Afrezza have gotten their answer. The plan is set, now they're working on execution. In other words, they don't see a problem with their plan. They're sticking to it, for better or worse....
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