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Post by stevil on Oct 2, 2022 20:44:19 GMT -5
stevil ... I have a question for you.. I respect your point of view.. and what you are adding to the conversation.. So you say you have more shares in Mnkd than you should.. So why do you continue to hold those shares? What are the positives... are you still invested because of technosphere and future molecules? I have been buying (what I consider to be) pretty heavily over the past few years. I think it's a little tacky to post how many shares I own publicly, but if you're curious, I have no problem answering in a message. I have been buying because I think MNKD is undervalued at these levels and comes with the added bonus of being a growth company as well. So I should, in theory, make a decent return over the next few years while I re-evaluate what the future looks like after I've hopefully made at least 2-3x over that time. Right now I'm holding because I have faith in UTHR and Tyvaso DPI and MNKD has some potentially lucrative prospects waiting in the wings that I want to see if anything materializes... Namely the clofazamine treatment. If it ends up being what they think it will, I think that has the potential to be a multi hundred million dollar molecule that MNKD hopefully gets to keep the vast majority.
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Post by stevil on Sept 29, 2022 22:17:43 GMT -5
Thank you Stevil. I wish you wouldn't wait so long between posts.
Mango said something that I think should resonate with you, but wanted to ask if it does.
"Afrezza will ultimately receive the recognition it deserves and rightful place as the Gold Standard of mealtime insulin within the Standards of Care." 100% can stand behind that comment. But I think more still needs to be done due to lack of awareness and familiarity. To piggy back off of Bill’s comment about hypos being nearly non-existent- they need to do better than TIR and actually focus on reportable events from hypoglycemia. This will be challenging because it’s unethical to try to induce hypoglycemia and there isn’t a very large sample size to begin with. But it is a more powerful statistic to me to have fewer hospitalizations/deaths with improved A1c (current measuring stick) than it is to have better TIR because at that point you’re measuring hypoglycemia in a measurement of time when it may be an insignificant consequence if it doesn’t lead to mortality. In other words, who cares if you spend 5% more time in hypoglycemia if there are no consequences from it? I’d love to see MNKD dose more aggressively to prove Bill’s assertion in a respected journal. hypoglycemia is by far the #1 fear when treating people with diabetes. Proving the safety of Afrezza would make it the standard of care for insulin and nearly entirely eliminate basal insulin except for functionally type 1 type 2s.
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Post by stevil on Sept 29, 2022 10:50:52 GMT -5
Hyperinsulinemia and insulin resistance are conditions caused by a diet that elevates blood sugar all day long or is highly inflammatory. Try testing someone that is about to be diagnosed with metabolic syndrome or pre diabetes , that is NOT on any treatment yet... and you will see these markers are most likely are out of control in those patients. These conditions have nothing to do with treating high blood sugar with insulin. The treatment using insulin comes after the T2D diagnosis, and yes, introducing more insulin into the treatment of someone that continues to sabotage their own body with food and drink, that caused the problem in the first place, is an uphill battle. Educate the patients about the root cause of Hyperinsulinemia, metabolic syndrome , insulin resistance and type 2 diabetes. Reversing these conditions is as simple as eliminating the root cause. The data from randomized clinical trials in humans is out there. www.bmj.com/content/bmj/372/bmj.m4743.full.pdfNow you're confusing me. Is the proper treatment then a low carb diet or Afrezza? I'm not taking offense to everyone who is trying to educate me but I do find it to be amusing. Do you all not realize I have spent the last 8 years of my life studying this stuff? While I didn't get my PhD honing in on specifics, my medical degree is no slouch, either. By all means please keep sharing information as I never want to get too smart to learn but the hubris of this board is sometimes appalling. It gets frustrating trying to share medical consensus when you're met at every turn with resistance and people who suffer from the Dunning-Kruger effect because they've read books or online articles. Look, Afrezza is amazing. It is truly a medical breakthrough when it comes to insulin. It's the closest humans will ever get to a physiologic insulin. The problem with diabetes is that it's not just a disease of insulin. I'm not saying that I have all the answers. I'm saying quite the opposite. I don't have the answers, which is why studies and trials are so important. The scientific method uses observation over time to complete. Thus far, Afrezza is in a courtroom with both prosecution and defense holding a substantial case. There does not yet exist enough evidence, either way to form a verdict and it's going to be stuck in court for many years until one can be reached. That's all I'm saying. I can see the benefits of early use of Afrezza from a theoretical perspective. But those who want to change the standard of care based off theory alone reveal their ignorance with how good science works. And to make things worse, I try to help people understand how doctors think so they can be patient with the process and understand doctors aren't (all) imbeciles and there are actually legitimate reasons why Afrezza has not been a success thus far- and why it probably won't significantly change unless the peds trial is a success. I'm happy to keep posting to help those who want to understand and learn, but you all make this exhausting sometimes.
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Post by stevil on Sept 28, 2022 15:05:40 GMT -5
There has to be a benefit for any major shift in prescribing habits. Metformin is first step because it is cheap, safe, and effective. Sulfonylureas used to be second step but fell out of favor, despite being cheap, due to poor side effect profile, lack of cardiovascular/renal benefit, and hastening the progression of disease. The only reason the newer/more expensive medications jumped the older/cheaper medications is because they showed better long term outcomes. Mannkind needs to pick some quantifiable and significant metric to target for their trials. I don't know where some on here get their information from because I don't think this would be that easy of a feat from the data I've reviewed. The bigger problem for mannkind is that any study of this type will take years- up to a decade or longer- to reap the rewards. Currently, time in range hasn't shown a significant benefit to those not already on insulin. Hard sell there, although some extrapolations could be piggybacked off of other's work in the space since it is a popular new topic that is being studied. I don't really see how Afrezza will lead to an improvement in cardiovascular and renal outcomes based off the data I have already reviewed. Everything I have read says otherwise - increased amounts of insulin actually increase both cardiovascular and renal disease since insulin is thought to increase inflammation and worsen coronary artery disease and it can be damaging to the kidneys as well, hastening renal disease. This information is based on previous studies of other insulins. However, since this data already exists, it will take more work to undo it for Afrezza, since it too is insulin. The biggest problem Afrezza has is there isn't really any indication for early use unless someone's A1c is over 12 and that's only because you can then make the case for early intensive insulin treatment. But then you're right back into the standard of care once their A1c is controlled. With SGLT-2s and GLP-1s, you've got cardiovascular and renal benefits as well as weight loss on your side. Afrezza maybe will cause some weight loss, but for most will be weight neutral at best. Any benefit you'll get from Afrezza won't be realized for over a decade and the clock hasn't even started on collecting that data. I'm ambivalent to Mike. I don't know enough to know whether he is brilliant or rotten at his job. I do, however, see how difficult it is to navigate Afrezza through the mess of healthcare. As much as I hate the idea of sitting back and doing nothing, it's really the only option the company has right now as long as it will require a substantial investment that won't realize a return for many years down the line. Their best hope is that time in range studies will be completed by CGMs and prove to be significant. Afrezza will likely never be first step in any standard of care. By the time they would be, there will probably be a cure or a near cure that will restore beta function. I say this as someone that definitely has more shares than I should in the company. I gave up on Afrezza a long time ago. It's going to be the rest of the pipeline that carries the company going forward. Afrezza will continue to grow slowly over time and remain a niche product for the reasons I mentioned above. I don't expect it to be a popular opinion, but I believe it's one that is pretty sound according to the data that is widely available from respectable sources. Stevil - I mean no disrespect, but I do not agree with the implication that Afrezza may/will "increase inflammation and worsen coronary artery disease and it can be damaging to the kidneys as well". While it could be possible that injectable insulin may have those effects, we must keep in mind that those products are in the hexameric form, so are fundamentally different from (monomeric) Afrezza which structurally and functionally closely mirrors the natural insulin produced by our bodies. Therefore, if Afrezza were to cause the negative effects you mentioned, then that is tantamount to saying that non-diabetics are being damaged by the natural insulin produced by their own bodies, which of course is not true. Except it is true. It's exactly their own insulin that is believed to cause the inflammation and increased risk of heart attack and stroke from diabetes. Despite what has been said here, there exists a state of hyperinsulinemia (in the monomeric form, mind you) due to believed insulin resistance. This is the part that is so hard to explain to people that haven't been educated to see the big picture and thus thinks the solution is much simpler than it actually is. Diabetes (type 2) is not simply a disease of insulin deficiency. There are so many other known mechanisms that are impaired that affect the release and absorption of insulin. The body's natural response, when beta cell function is still intact, is to do just what you all are recommending - increasing serum insulin. This is known to cause albuminuria, which then increases kidney disease. An increase in insulin is also believed to cause inflammation of arteries (along with AGEs), which would then lead to cholesterol formation and plaque deposition= stenosis. Again, this is current theory of insulin and why I believe it is going to be an incredibly challenging uphill battle for Afrezza to have a significant role in early type 2 treatment outside of early intensive treatment. I have been following VDex's work closely because while I want desperately for the thoughts and opinions on this board to be true, the data has not born out the same conclusions... Yet. It's going to take a tremendous amount of work to reverse what is already believed to be known if indeed different outcomes are achieved with Afrezza. Sweedee is correct, I am not all of your enemies. The answer just isn't as simple as it appears to be. Until different data appears that conflicts with what is already known, Afrezza will remain one of the last steps of treatment in the standard of care. Not even I (as a self-proclaimed Afrezza enthusiast) am convinced it should be otherwise, which is why I remain so interested in VDex's work. I'm hopeful that their patients do have better long-term outcomes and that they're able to publish those results for us all to see.
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Post by stevil on Sept 28, 2022 10:49:11 GMT -5
And what did he accomplish after saying those words? That, to me, is more interesting. Switching the topic doesn't discredit his accomplishment in becoming the Chief Scientific Officer of the American Diabetes Association. He has credibility. I wasn't changing the topic. I was supporting my assertion that nothing is going to change in the type 2 space regarding Afrezza. Kendall wasn't able to get anything done despite his thoughts and convictions about how great Afrezza is.
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Post by stevil on Sept 28, 2022 0:18:12 GMT -5
And what did he accomplish after saying those words? That, to me, is more interesting.
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Post by stevil on Sept 27, 2022 22:42:35 GMT -5
There has to be a benefit for any major shift in prescribing habits.
Metformin is first step because it is cheap, safe, and effective.
Sulfonylureas used to be second step but fell out of favor, despite being cheap, due to poor side effect profile, lack of cardiovascular/renal benefit, and hastening the progression of disease.
The only reason the newer/more expensive medications jumped the older/cheaper medications is because they showed better long term outcomes. Mannkind needs to pick some quantifiable and significant metric to target for their trials. I don't know where some on here get their information from because I don't think this would be that easy of a feat from the data I've reviewed. The bigger problem for mannkind is that any study of this type will take years- up to a decade or longer- to reap the rewards.
Currently, time in range hasn't shown a significant benefit to those not already on insulin. Hard sell there, although some extrapolations could be piggybacked off of other's work in the space since it is a popular new topic that is being studied.
I don't really see how Afrezza will lead to an improvement in cardiovascular and renal outcomes based off the data I have already reviewed. Everything I have read says otherwise - increased amounts of insulin actually increase both cardiovascular and renal disease since insulin is thought to increase inflammation and worsen coronary artery disease and it can be damaging to the kidneys as well, hastening renal disease. This information is based on previous studies of other insulins. However, since this data already exists, it will take more work to undo it for Afrezza, since it too is insulin.
The biggest problem Afrezza has is there isn't really any indication for early use unless someone's A1c is over 12 and that's only because you can then make the case for early intensive insulin treatment. But then you're right back into the standard of care once their A1c is controlled. With SGLT-2s and GLP-1s, you've got cardiovascular and renal benefits as well as weight loss on your side. Afrezza maybe will cause some weight loss, but for most will be weight neutral at best. Any benefit you'll get from Afrezza won't be realized for over a decade and the clock hasn't even started on collecting that data.
I'm ambivalent to Mike. I don't know enough to know whether he is brilliant or rotten at his job. I do, however, see how difficult it is to navigate Afrezza through the mess of healthcare. As much as I hate the idea of sitting back and doing nothing, it's really the only option the company has right now as long as it will require a substantial investment that won't realize a return for many years down the line. Their best hope is that time in range studies will be completed by CGMs and prove to be significant.
Afrezza will likely never be first step in any standard of care. By the time they would be, there will probably be a cure or a near cure that will restore beta function. I say this as someone that definitely has more shares than I should in the company. I gave up on Afrezza a long time ago. It's going to be the rest of the pipeline that carries the company going forward. Afrezza will continue to grow slowly over time and remain a niche product for the reasons I mentioned above. I don't expect it to be a popular opinion, but I believe it's one that is pretty sound according to the data that is widely available from respectable sources.
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Post by stevil on Jun 29, 2022 14:19:18 GMT -5
Just a hunch... if the changes in body habitus were caused by medications, it's likely due to high dose steroids. Antiepileptics don't normally cause changes like that. In fact, most of them decrease appetite and lead to weight loss. Topamax is often used for this purpose.
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Post by stevil on Jun 29, 2022 14:07:30 GMT -5
LFD left out the important fact that Tyvaso and Tyvaso DPI are approved for PH-ILD and that's where growth is anticipated. Liq861 is not approved for PH-ILD and there is nothing in clinicaltrials.gov about Liquidia trials for PH-ILD. This doesn't always matter. If UTHR does the heavy lifting and gets those indications approved, doctors would be able to prescribe off-label without much issue. It's not uncommon for other products to get "grandfathered" in for indications. It's essentially a waste of resources to redo trials if one product displays efficacy and there is little variation between compounds.
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Post by stevil on Jun 15, 2022 14:01:03 GMT -5
I bought some August 4 1/2 calls yesterday at $.30. It exercises a week or so after earnings. Felt the need to do something at these prices. not sure why we are getting thrashed even on days like today. Market sell off. Many people think cash is the safest place for asset protection until the dust settles. Bonds are getting killed alongside equities.
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Post by stevil on Jun 10, 2022 12:16:26 GMT -5
My pleasure, Sweedee. I don't really get offended easily or tend to care too much about what others think of me... I try to do what is right regardless of whether it will be popular or not. That sometimes gets me in trouble with people, so I'm sorry if I come across too strong to anyone here. It's not my intention to belittle anyone or make anyone feel small. I'm motivated by truth and getting things right, not to harm anyone.
I know people used to question my motives when I first got here. Most of those people seemed to have moved on, or at least don't post as much as they used to. Hopefully I've won over the rest as I haven't been called out as a paid short in quite some time.
I often wonder if the investment of my time is worthwhile to the board, so it's nice to hear someone appreciates it from time to time. I try to lurk as much as possible just because I don't like the headache of conflict or the amount of time it takes to go back and forth. If some things need to be straightened out, I'll keep doing it as long as others appreciate it.
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Post by stevil on Jun 9, 2022 18:24:19 GMT -5
Stevil - if you don't want to debate, thats fine. Just don't respond. I am sorry what I am saying is completely uncompelling to you. I am just telling what DeFronzo said about metformin, what Holme said about in the end the T2 will be on insulin anyway and why Al Mann put $1B of his own money into afrezza. I know this is not what you learned in school but its hard to argue with what we are now seeing with CGMs. I wish you the best of luck but when people are saying things which may not make sense listen. When I first met Al Mann he was saying all this stuff which made little sense to me either. One thing it did was challenge me to try and understand what he was saying and why. Maybe in the end Al was wrong. Maybe his understanding of diabetes was way off base. Maybe in the end Al's understanding was so screwed up he just wasted $1B. One suggestion for you is to go back and read Al's old interviews and available interviews. Then ask yourself, why is he saying that. You're probably right, and I'll do that going forward. I actually really admire your persistence, stubbornness, and unwavering self confidence. I'm sure that has led to incredible successes in your life. You just seem to have a lot of opinions and strong beliefs and speak with an authoritative voice. I just wanted to make sure that the readers of the board have the most accurate information from what the great majority of doctors believe. I suppose to each their own who they want to believe and trust. To be clear, I don't think you're wrong about all things. I just don't think you're zooming out far enough to see the whole picture. It's really hard to gauge where people's understanding is. It seems Aged understood what I was saying... it's sometimes hard to know if you're talking past someone or not because a lot of assumptions are built into the discussion. If we don't have the same starting point and general baseline understanding of what we're talking about, it's harder to discuss the finer details and nuances. I find that a lot of people on here think I am in any way diminishing Afrezza and how remarkable of a treatment it is. Far from the truth. It is the best insulin on the market, hands down. Researchers still cannot agree on what causes diabetes, which is, in part, why we're even having this debate. But when we can't agree on general principles we won't agree on the finer details either.
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Post by stevil on Jun 9, 2022 17:17:43 GMT -5
Stevil - my position is pretty simple. Its the same as Ralph DeFronzo's which is that starting T2s on metformin is a waste of time. My position is also the same as Philip Home which is once you give the PWD all this crap in 5-15 years they will be on insulin anyway. diatribe.org/type-2-diabetes-start-early My position is also the same as what Al Mann said and why he invested $1B of his own money into afrezza's development which was put all the T2s on afrezza day 1. I wish someone can find the video of Al going at it with DeFronzo. Right now Mike has a study going on in India. It appears to be a redo of the Affinity2 trial. We already showed a superiority in Affinity2. My position is we need a head to head trial with Mounjaro for A1C and I don't give a crap about weight. I only care about A1C. My last position is we need to fix the ADA's SoC and if we can't just like Dave Kendall couldn't then Mike needs to work with another organization that is willing to do the right thing for T2s. I don't like being a jerk, I just don't really have any interest in debating with you. It's nothing personal... I just don't agree with most of your scientific knowledge and find your arguments to be uncompelling. It would take a long time to read the information you've read and based off our cursory discussion of it, I'm not drawn to learn more about it. It is not consistent with my theoretical understanding of the disease at the molecular level nor does it align with what I see clinically. I won't go so far as to say that you're wrong because I don't possess the knowledge to do so. It has been a while since I dove head deep into the biophysical chemistry of metabolism, but from my undergraduate degree to medical school to now residency, the theory has been consistent. As has current research that our discussions have led me to use to refresh my memory. There's probably a great deal of information that I've learned in my education that will be proven incorrect in the future. I just don't think this topic is one of them...
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Post by stevil on Jun 8, 2022 21:17:30 GMT -5
Maybe the FTC can help determine why PBM's (who are not necessarily, if ever, trained medical professionals) seem to try to make/force medical decisions based on their formularies vs what FDA approved drugs patients request or what is prescribed by doctors on their behalf? Attention on PBM over-influence and over-reach is much overdue, as is inspection of their negotiated discounts, which are really pay to play schemes with little to no benefit passed on to the consumer/patient. I know the AMA is aware of this issue and is trying to fight back politically. They sent me a survey asking me what the most important issues that physicians want them to address and this was one of them. It's getting to the point where their formularies are so restricted that they say "you can prescribe any medication you want as long as it's this one". It's a loophole, but they're essentially turning themselves into the prescriber with these tactics.
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Post by stevil on Jun 8, 2022 21:03:19 GMT -5
I don't think we're getting anywhere as we're both seemingly firmly entrenched in our own sides. I think we may just have to agree to disagree.
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