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Post by dreamboatcruise on Feb 23, 2018 14:52:34 GMT -5
I am very hopeful, as I cannot remember the last time Mannkind put out an announcement during market hours! The announcement will be at 5 p.m. so after market hours. I suggest that anyone that wants more shares... to buy it on the 27th or sooner. We all know what the earnings will be like, but the "company developments" must be really great to give us a chance to buy shares on the last day of the month. Think about it ... The date is very meaningful. 7 represents good fortune and putting a 2 in front of it is like doubling that. Clearly they are trying to send a signal to us. This is about as strong of a buy signal as I've ever seen for a stock. We've been foolish in the past to think that each conference call was going to be the one... but this time it just feels different... well, actually the same, but it's a good feeling so let's run with it for the weekend. Of course load up on those Mar 2nd call options... and/or lotto tickets.
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Post by dreamboatcruise on Feb 23, 2018 14:38:09 GMT -5
OMG, let's not read more into this than is in the release. It will be interesting to hear David Kendal for the first time as a MNKD employee - I look forward to that. As for the rest of it, please be prepared for ho-hum. If it's better, great, but experience should have taught us all otherwise. But the fact that it is happening on a day ending in "y" to me means it really has to be something good.
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Post by dreamboatcruise on Feb 23, 2018 14:34:24 GMT -5
So...three business days from now.... I’m trying to keep my expectations low, but it’s pretty hard when we know they’re in active partnership negotiations and announce a meeting of this importance in the same amount of time that would be needed to disclose material events!!!! They've been in partnership talks for two years now. Though I guess annual earnings call is important... only happens once a year.
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Post by dreamboatcruise on Feb 23, 2018 1:11:15 GMT -5
We know insulin resistance is not the cause because you can take that same early stage T2 put then on insulin, keep non-diabetic TIR and see not only progression stopped but beta cell regeneration. The insulin resistance requires a greater demand on the pancreas but a healthy pancreas will adapt and generate large clumps of beta cells. We see this when you autopsy an obese insulin resistant non-diabetic. If you sprain your ankle running a marathon is not a good idea. If you have lost some beta cell function and are now asking the remaining beta cells to work harder and that obese person needs a lot of insulin things are not going to work out too well unless you can allow the pancreas to rest. Get the PWD to a fasting state asap, allow the pancreas to rest and good things will happen. I think your analogies are wrong. This paper is the best explanation for how beta cells work in Type 2 ( β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes). It's the paper that is usually cited by (3,732) academic papers talking about this topic, including the AACE consensus statement on Type 2 management where it is given as the mechanism by which Type 2 occurs. Anything by Butler or Bonner-Weir is worth reading in my opinion. For those who don't want to read the whole thing; this is the paper that documented the mechanism by which Type 2 diabetics lose beta cells, and why they don't get replaced. Basically there is a genetic flaw that means the body miscalculates and thinks it has built more beta cells than it has, and because beta cells are naturally continually dying and being replaced this error accumulates until the body has a lot less beta cells than it thinks it does. You cannot regenerate beta cells because the body thinks it has the right number. Don't have time to read right now. At the risk of being a plot spoiler... is it a single gene... what percent of the population has the flaw? [Edit] Actually I just quickly read through the discussion at the end. Are you sure this is the paper you were intending to provide a link to. It doesn't seem to suggest what you are saying in the second paragraph. Such as... "One very positive implication from the present studies is that the rate of new islet formation is sustained in patients with longstanding diabetes. In fact, there was no difference in the rate of new islet formation versus age in patients with or without type 2 diabetes. These data imply that if the increased rate of apoptosis present in type 2 diabetes (vida infra) could be inhibited, it should be possible to restore β-cell mass in these patients." This seems to be saying that if cell death were halted the pancreas would happily produce enough beta cells to rebuild itself. Or am I misreading something... I could be, as it's late and that is fairly dense reading.
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Post by dreamboatcruise on Feb 23, 2018 1:05:02 GMT -5
My two cents... Do a series of testimonials from real users each one extrolling one of the main benefits... PWD speaking to PWD T1 and T2. The FDA greatly restricts what a "real user" can say. They can't give anecdotal clinical results... e.g. someone could not say "My A1c went from 9 to 6.5". Having real patients does not allow them to say anything MNKD couldn't already say with actors, text or a voice over.
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Post by dreamboatcruise on Feb 22, 2018 22:00:22 GMT -5
What the data is actually starting to show is ALL beta cell loss is initially caused by an underlying attack on the beta cells. As we test more and more T2s and earlier we have been seeing and will continue to see more who test positive for the current anti body tests. As testing gets better additional ones will probably also be found. We know insulin resistance is not the cause because you can take that same early stage T2 put then on insulin, keep non-diabetic TIR and see not only progression stopped but beta cell regeneration. The insulin resistance requires a greater demand on the pancreas but a healthy pancreas will adapt and generate large clumps of beta cells. We see this when you autopsy an obese insulin resistant non-diabetic. If you sprain your ankle running a marathon is not a good idea. If you have lost some beta cell function and are now asking the remaining beta cells to work harder and that obese person needs a lot of insulin things are not going to work out too well unless you can allow the pancreas to rest. Get the PWD to a fasting state asap, allow the pancreas to rest and good things will happen. Genetics fits into the equation as it opens up certain groups to a greater risk of infection and it can also effects how fast a person's beta cells can regeneration. Its like hair, some people have good hair and others don't and some people's hair grows faster. My hair is not so great. However, the Qatar study is showing with pretty much certainty almost all will regenerate beta cells to some degree. We also know its not just genetics because identical twins will not always both get diabetes. If it was simply genetics they both would always get it. As far as Al's assertion about basal vs prandial there is no question he is right. Prandial in T2s should be first line treatment. That is a main pillar in the Al Mann Dogma. It is the medically correct way to treat T2s. It also seems to be the direction David Kendall is taking. It seems finally, someone has read Al's 50+ studies. We have clinical studies from the 1950's on early insulin intervention. However the key with afrezza is its ability to restore hepatic function and achieve greater time in range. To see beta cell regeneration you need to keep the time in range near non-diabetic. DeFronzo is doing this in Qatar with his Actos/Byetta cocktail. I don't recommend this approach but he is achieving near non-diabetic TIR by removing the after meal spike and increasing insulin sensitivity. You can not so this with a basal. After meal the T2 will spike 200, 250, 300+ then take the next 4 hours to bring it down with the on board basal only to see it spike again after lunch and diner. At the same time the liver is dumping glucose adding to the mess and the pancreas never ever gets to a fasting state. That actually isn't what the bulk of literature says, such as the paper that I provided link, which itself was looking at a lot of literature. Not saying there couldn't be some paper that says that, but I'd be interested in their methodology and how many subjects were involved. A bulk of diabetics do not test positive for antibodies. And immune disorders don't work where you can have undetectable levels of antibodies and yet have a clinically significant immune response. It's actually quite the opposite, where modern tests for antibodies can pick up levels well below when there is any meaningful immune response... such as the cases in Afrezza trials where insulin antibodies were detected in the lungs, but no immune response effects. The notion that all diabetes is an auto-immune disease is way, way off from what the medical profession believes. I'm curious if you know of a single scientist that has stated that all diabetes is immunological. As for Al Mann dogma... part of Albert Einstein's dogma was that quantum mechanics had to be bogus. Scientists rightly realize that accepting dogma from smart men isn't part of the scientific process. I personally believe Al Mann, but the scientific method requires evidence in the form of clinical trials. As for your statement about beta cell growth from insulin resistance that is totally consistent with what the mainstream lit says. Here is a paragraph from the paper I provided a link for on T2 progression. "Thus, in type 2 adipogenic diabetes, excessive carbohydrate and fat intake causes hyperinsulinemia in association with increased hepatic lipoprotein secretion, adipose tissue growth, and increased free fatty acid levels in genetically susceptible individuals. Together with episodes of postprandial hyperglycemia, elevated free fatty acid levels cause muscle and liver insulin resistance and increase hepatic glucose production. The same stimuli also facilitate β-cell compensation by promoting insulin secretion and biosynthesis as well as β-cell growth. In late stages, however, the progressive rise in insulin resistance, combined with alterations in β-cell gene expression and signaling induced by rising levels of free fatty acids, cause β-cell failure. Overt diabetes occurs as a result of this β-cell decompensation, with altered insulin secretion and apoptosis as possible contributing factors." It is recognized that insulin resistance first causes beta cell growth... but in many it will then progress to beta cell failure. As I stated in my prior post, it is also recognized that some have genetics that seem to have burn out proof beta cells, so they can have significant insulin resistance and their pancreas successfully adjusts. Other phenotype pancreases have limits to how much they can adjust.
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Post by dreamboatcruise on Feb 22, 2018 20:11:49 GMT -5
I hate to see where the green line goes to in 2019 Well, look at it this way. Think if that line had been drawn in May of 2016. We've done way better than where that would have gone... it would have hit $0 long ago.
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Post by dreamboatcruise on Feb 22, 2018 20:03:08 GMT -5
So many good ideas here....wait, I thought we were all excited when Mike joined Mannkind because he is a marketing guy??? Mike, you're the absolute best person for the job... now let me tell you what you should be doing I kinda assume Mike is going to do the best he can within the confines of FDA demands and restrictions on commercials.
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Post by dreamboatcruise on Feb 22, 2018 19:59:41 GMT -5
Bringing this to the top again - reminder that you may vote daily - I think up to 10 times from a device. The gap has narrowed to 49% for Mike C. and 40% for next closest. Link to vote: joinappa.com/awards/Without getting around cookies (not that I would do that ), it doesn't let me vote even twice, whether multiple days or not. I voted weeks ago and it doesn't show the vote button for that category even now.
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Post by dreamboatcruise on Feb 22, 2018 19:41:03 GMT -5
DBC - I am going to again post what I will refer to as part of the AL Mann Dogma. It is a bit off topic of One Drop but may help with the above discussion. The following are truths about diabetes which are not debatable. In summary there are some baseline facts which need to be understood 1. All diabetics share the fact that they are not making enough insulin for THEIR bodies needs 2. All diabetics first loose their robust first phase insulin release 3. Diabetes is a spectrum of insulin production. Some diabetics produce a good amount of insulin and we term them pre-diabetics. Some produce very little which we term T1s, LADAs, Late Stage T2s and a few more terms. The rest get labelled T2 and their insulin varies on the spectrum. 4. T1's show antibodies and the more we test T2's we find more of the T2's having anti-bodies and rename them LADAs 5. Obesity and being a coach potato is a trait of T2 diabetes and not the cause. The cause is the loss of beta cell function. "When" insulin response is lost, yes it is first phase. Certainly there are people in the medical field that would disagree with other assertions. Many, if not most, would say that obesity and lack of exercise will cause insulin resistance, and that this insulin resistance can lead to beta cell function loss. For some people they don't lose beta cell function even when challenged with by insulin resistance. It seems to be accepted now that there are also T2's that occur because of a genetic predisposition to beta cell failure. Here is a paper I found useful: www.ncbi.nlm.nih.gov/pmc/articles/PMC2811457/So my understanding is: T1 is an autoimmune disorder where your immune system turns on your beta cells, this can occur early in life or later (and kinda irrelevant that it used to get misdiagnosed as T2) T2 in many people is caused by insulin resistance that develops from lifestyle, though with some having better genetic resistance to poor lifestyles than others * T2 in some can be caused by genetic predisposition to beta cell failure even with lifestyle that wouldn't cause problems for most people (whether this is a third class or simply on the spectrum of T2 might be open for debate). I guess the open question there would be whether insulin resistance is necessary as a precursor or whether this subset truly could develop T2 without insulin resistance. * that one sort of seems like smoking. We know smoking causes cancer but we also know some people just have genetics that mean they'll die at 100 from boredom after a life of smoking. And "poor lifestyle" may be a poor choice of wording above. Quite frankly our bodies simply aren't physiologically evolved for the reality of modern life. It takes active fighting against what would come natural to us from evolution to to avoid these "lifestyle" problems. Too bad beta cells aren't like muscles and get stronger the more they are used. As for Al's assertion about basal vs prandial as first line. I think he well may be right, but I'd still want to see some clinical studies to really be convinced. It is not uncommon for something that seems logical in fields such as physiology to turn out to not be true. This is a very complicated subject, and I've yet to hear of anybody developing a computer model of diabetes progression that can accurately predict how it will progress for individuals, based on their treatments and actions. Lacking that level of understanding, we must rely on clinical trials.
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Post by dreamboatcruise on Feb 22, 2018 19:00:19 GMT -5
Before this thread is terminally hijacked, it would be good to hear how others feel about the nature and content of MannKind's advertising for this coming year.... Here would be my general contribution to the discussion. I just went to the old ad to refresh myself on it. I decided to pull out a stopwatch to see what was actual content vs what was the mandatory FDA stuff. Turns out the content out of a 1 minute ad is only 16 seconds. Remember the primary purpose of those funny images is to give you some amusement (and possibly help you remember it) while they rattle off all the things they have to rattle off in the voice over. (and no, the FDA doesn't allow them to speed it up by 500% like they do with financial disclosures on radio ads) So, keep in mind when you're planning an ad for them you've got 16 seconds, unless you want to turn it into a commercial that requires more than 1 minute airtime. The content they managed to hit on in that 16 seconds was: It's a mealtime insulin (ok this probably should have been one extra second counted as mandatory) With injections "when do I prepare, where do I inject" Afrezza is inhaled Afrezza allows you to inhale "when food arrives" (so this is contrasting with the "when do I prepare" for injection) You can be more spontaneous Don't have to rely solely on injections It's not a lot, but 16 seconds isn't a lot of time.
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Post by dreamboatcruise on Feb 22, 2018 18:49:00 GMT -5
I never liked the commercial for Afrezza. It seemed like a fairytale / cartoon with burgers coming down on parachutes. I would focus on the speed of action in and out and why that’s so important. I would also focus on the ease of use, compliance and why time in range is so important. I would focus on how unique Afrezza is compared to all other mealtime insulins. I would focus on Afrezza being human insulin as compared to all non insulin concoctions that could be harmful and eventually lead you down the path to Insulin anyway. I would focus on all the negative complications that come from uncontrolled BG levels. Education in very simple terms would get me to listen to the message. The "why is it so important" might run into restrictions of what FDA would allow. Interesting idea on talking about the non-insulin treatments. Would be interesting whether any other drug company has used that tactic, and how it might be looked at by FDA. As for educating, remember there isn't a lot of time that is really available in a commercial.
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Post by dreamboatcruise on Feb 22, 2018 18:13:53 GMT -5
1 month update: Lucky me, my insurance covers this meter including a mere $10 copay for 90 day supply of sensors. The sensors are easy to apply and do not sting at all. Removal is like taking off an Elastoplast bandage. A little more tenacious than a normal band-aid. I started using the meter a month ago due to my A1c stalling at about 8, yet my finger stick readings looked good. Either I was lying to myself or I was missing some key data. The meter helped me find out. Turns out: 1. The breakfast cereal I was eating was amping my BG, and coming back down by the time I took my mid-morning reading. It was totally hidden from me since I wasn't testing continuously. 2. I eat too much at supper, and was indeed fooling myself. 3. I needed more basal to keep me in control at night. I would say that I'm 2/3 there now on the way to having tight control again. I'll grab some screen shots and post them soon. What a great tool. That's great on the co-pay, and sounds like it has already paid for itself to your insurance multiple times over. Is that private insurance or the National system? Do you think you'll want to keep using it in the long run, or do you think you'll learn what you need to know and then not want to have it attached? Hopefully private insurance here in US will start covering these for any PWD that want them... hopefully even on a temporary basis for those with "pre-diabetes". Perhaps I'm dreaming on the latter.
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Post by dreamboatcruise on Feb 22, 2018 18:00:15 GMT -5
If you're yelling about a disease that is very poorly treated in the US... where our healthcare system is failing patients... then by all means, no need to even ask for forgiveness, it will take some yelling to change things. If you're yelling at me about it, you are simply lashing out in bizarre emotional ways. Over and over again here on proboards I've expressed my belief in Afrezza as a major breakthrough, my profound disappointment with insurance companies blocking payment for it. Just today in a thread with some actual useful discussion (no I don't really think the two of you venting that you think I'm a bad person is useful), I was discussing the science of why I thought Afrezza should precede basal insulin in treatment progression. I've actually spent countless hours educating myself on diabetes... way beyond what I'd do if I were only interested in this as an investment. I may not know everything, but I have contributed a lot of information to this board including giving links to scientific articles so people here could understand the disease better. Not only advocating Afrezza, here on proboards I've expressed my outrage over insurance companies limiting the number of test strips and insulin for patients. I've told of my personal experience with a loved one that died in assisted living from outrageously poor diabetes treatment, who's life probably could have been greatly extended if Medicare had only covered Dexcom a few years earlier... advocating that anyone with a family member in similar circumstances not take their proper care for granted, and get a Dexcom if at all possible. So how dare you accuse me of not being concerned, and expressing it, for those suffering with this dreaded disease. Really... childish is you insisting that everyone needs to celebrate with you. That this should be a party for you. If I've somehow crushed your "hopes and dreams"... they were pretty fragile, and don't blame me for that. I think you've just illustrated my earlier point. I appear to have way more conviction than you do about Afrezza if my discussions about finances, here on a forum about investing, has done that to you. The finances of MNKD are actually a crucial aspect of getting Afrezza to patients. If you really care about the disease and patients dealing with it, then you to should actually be concerned about MNKD's finances, not wishing to sweep them under the rug and celebrate. And thank you for the end of the conversation, as when your true feelings eventually come out they are pretty offensive. I would appreciate no further personal comments. I will do the same. DBC, Thanks for you common sense here. I want to hear both the good and the bad, so long as both are relevant to the dialogue and not a lame argument, illogical fallacies, red herrings and the typical BS you read at SA. Nothing wrong with civil discourse. I'm getting educated about diabetes along the way. Besides, you and I both know that the BOD at MNKD look at both the threats and the opportunities. If they didn't, they wouldn't be making the kind of positive steps they have, i.e.; Dr K, authorization for more shares, testing ad markets, studies, etc. to address the threats. I'ms are there is a vision and timeline Mike has shared with his staff and they are either "on the bus or off the bus". Best regards - Thanks I also suspect Mike is the type leader that can hold things together and keep the team focused when the plan and timeline have unexpected twists and setbacks, as almost always happens. I've only once worked in a company as large as MNKD, but I think they have recently been facing challenges similar to a startup company. From this distance at least, to me it seems Mike has the qualities of the successful entrepreneur CEOs I've known. Though on a couple of occasions I might have questioned his actions, I'm certainly glad he's on board. Still think the road ahead might be rocky one, likely both for company and for shareholders. Hope for the best, prepare for being tested.
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Post by dreamboatcruise on Feb 22, 2018 13:40:46 GMT -5
That probably depends on how early in the progression of T2 one is started on basal. We know eventually in the progression basal alone is not enough. The open question would be whether starting on basal or starting on prandial (Afrezza) would give better results... short term and perhaps slowing progression. Aged has presented reasoning behind why basal might be better, and I believe with Afrezza the reasoning is linked to whether restoring/enhancing the first phase spike has a feedback effect with the liver. Another argument for Afrezza first is that if there is meaningfully less chance of hypos, which is the main cause of delaying introduction of insulin, that could enable starting insulin sooner. Seems to me there will be no answers until very large clinical trials are run, ideally looking at when in progression insulin is introduced and what type. It might even be complicated by the fact that an individual's dietary habits might play a role in whether basal or prandial would be better to start on. I personally have bought into the idea that Afrezza would be the ideal early treatment, if not before metformin at least right after, but I'm objective enough to realize that since I started studying all of this after becoming a MNKD investor, I may not be fully objective. It doesn't seem like the algorithm in the ADA standard of care is going to change anytime soon without clinical trials. In the meantime hopefully MNKD can start at least winning the battle against RAA where they are currently placed in the standard of care (after basal)... with some practitioners such as VDEX trying a different approach and hopefully leading eventually to a reassessment of the standard of care. dreamboatcruise - Perhaps I'm oversimplifying, but how could having T2's start with insulin (basil + Afrezza) be a bad thing as long as the basal dose is mild enough to avoid hypos and Afrezza is used after proper titration. Seems like the primary reason insulin has been avoided is because of hypo risks. With Afrezza in the mix, that issue mostly goes away, doesn't it? If Afrezza alone, or basal + Afrezza gives superior results, then the last question is at what point do the higher costs of Afrezza (with or without Basil) for T2's result in lower healthcare costs for the individual, e.g., halting progression of the disease and/or reduced medical expenses in the out years? My wild guess would be less than 5 years since it doesn't take more than a few severe hypos to offset Afrezza's annual costs. Even with PWDs moving among insurance carriers, so one carrier may not see the out-year benefits from their coverage, common sense would suggest that every departing PWD using Afrezza would be offset by an entering PWD using Afrezza--zero sum situation. If you're asking which would be best, starting with just Afrezza or Afrezza and basal, then I certainly wouldn't know, and in reality I'm pretty sure no one does. I don't think the physiology and especially the progression of the disease are understood well enough. Bear in mind that exogenous augmentation of hormones can lead to changes in the natural production... e.g. men taking testosterone supplements leads to their body producing less. Is it better to use maximum safe levels of exogenous insulin immediately, or not? There are some studies showing the first phase insulin response is first to go in T2... is it better to simply replace that at a minimum level to keep post meal BG within range and let the body continue to play more of role? So, what exogenous insulin regime would best slow/halt the progression of beta cell "burnout" seems to me quite complicated. I can throw out different arguments of what "might" happen... but (a) this isn't actually my field and (b) I don't even think those in the field know all the answers. I think clinical trials are needed. I think Afrezza is a big advance because the combination of basal and RAA has certainly proven to have risks, and patient acceptance barriers, that has lead to it being considered an inappropriate early treatment. If only Al Mann were still around and had another half billion to throw at this problem.
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