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Post by rrtzmd on Dec 8, 2015 23:12:33 GMT -5
1. Afrezza maybe the best mealtime insulin, however its not on the label so SNY and MNKD can't say that to healthcare professionals, patients in advertising and insurance companies. So a mute point at this stage. I'm waiting for superiority studies and see none. Maybe they will come in the future some day. Who knows. 2. I don't disagree that al mann will likely step in to finance mnkd should it come to this. I don't see this as a material factor to an investing decision. Mnkd will be funded, it's just a matter of price (and thus the amount of dilution). 3. I don't buy the technosphere dream. They've been in business for many years and have shown nothing to demonstrate there is any interest or value in TS. 4. The T2 market is big but its going to be an uphill battle. Changing the standard of care will be difficult. This market has many products and cost is an issue. SNY has significantly decreased its outlook. I place a lot of weight on that. Their statements, lack of statements and actions point to niche market or losing patience with afrezza. That's concerning. Discounting all of this, mnkd probably worth about a $1 a share. If SNY bails, mnkd equity is worth nominal value. I don't any compelling reason to buy at this point given SNY's actions. If Al Mann had any interest in putting more money into Mannkind, I think he would have done so before now. Even a minimal investment by him back in August could have sent the stock soaring and relieved the pressure and negative publicity of the debt settlement. Even a minimal investment by him ahead of the TASE listing would have generated positive publicity and likely would have improved the reception the Israeli investors gave MNKD. Even a minimal investment now would send the stock soaring up and away from its 52 week lows. I think somewhere along the way Al decided it was time for Al "junior" to stand and walk on his own without any more help from "papa."
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Post by rrtzmd on Dec 8, 2015 22:58:22 GMT -5
compound26 ... that ATM isn't worth that much at these prices. @davinci ... number 1 and 2 would be key for me. Then I'd try to scrape together some more money to help average down. #3... check out my new avatar. Is that classy enough? The ATM is worth 37 million at any share price. That's one of the reasons I abhor ATMs. Mannkind could be selling shares hand over fist right now and they wouldn't be required to reveal it until the next 10-Q. And the only limit on how many shares they sell is the number authorized in the incorporation document. I still do not understand how the SEC could have approved ATMs without mandating disclosure at the time the ATM is used.
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Post by rrtzmd on Dec 8, 2015 13:27:51 GMT -5
Shareholders have less right to complain than warrant holders. I just noticed the warrants were down 77% today to 2 cents a share.
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Post by rrtzmd on Dec 6, 2015 23:59:15 GMT -5
In reply to your assessment -- the part shown in red on my screen -- the first thing you should try and suppose is an explanation as to why the PD graph shown on the insert looks the way it does. That graph suggests that afrezza's time of onset and effect on glucose lowering is virtually the same as lispro for about the first 60 minutes. One of the trials just completed could indicate that the insert graph may, in fact, be spurious, but, of course, only SNY knows that data at present. However, if the graph turns out accurate, that means the only real differences from lispro is that afrezza can be inhaled and that it is removed from a diabetic's system more rapidly. While the first is a clear advantage, the second remains debatable. As I recall, the trials found no significant difference between the incidence of serious hypoglycemia between afrezza and lispro, and, as has been pointed out elsewhere, the rapid drop in the insulin levels may leave the diabetic exposed to later hyperglycemia from late digesting carbs. Next, if SNY does indeed know the data, you have to try and suppose what their course of action will be given the results. Will they decide it's worthwhile pursuing the kind of large real life trial needed to demonstrate something more than "non-inferiority" that is needed to improve chances for third party reimbursement? rrtzmd, post all graphs including lispro PD graph. The clamp study will produce them as well.
The Clamp Study Single Dose Clamp Study to Evaluate Concentration-time Profile and Metabolic Activity of 3 Dose Levels of Afrezza and 3 Dose Levels of Insulin Lispro in Patients With Type 1 Diabetes Mellitus www.clinicaltrials.gov/ct2/show/NCT02470637
quote: if SNY does indeed know the data, you have to try and suppose what their course of action will be given the results reply: why don't you play suppose. that is the thread.
"post all the graphs..." Are you asking me to post the graphs? If so, this is the best I can do: afrezza insertThe relevant graph is shown on page 15 of the insert. As far as my own supposing, if the trial data matches the insert graph, then I suppose SNY will have make up their mind whether to do a real life study to demonstrate that afrezza is more effective at treating diabetes, since the graph suggests the only material difference in effect is the more rapid decline in insulin effect. That kind of data would suggest a large number of patients might be necessary to detect a difference and, given that SNY might also get the same 'non-inferior" results as well, I suppose they might not find it worth the risk. On the other hand, if the data does show a difference -- i.e. a significant earlier effect on glucose concentration than lispro -- I suppose they would still have to do some sort of real life trial to demonstrate cost effectiveness, but they might at least have an argument to convince third party payors to loosen the purse strings until the study is done.
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Post by rrtzmd on Dec 6, 2015 23:41:14 GMT -5
In reply to your assessment -- the part shown in red on my screen -- the first thing you should try and suppose is an explanation as to why the PD graph shown on the insert looks the way it does. That graph suggests that afrezza's time of onset and effect on glucose lowering is virtually the same as lispro for about the first 60 minutes. One of the trials just completed could indicate that the insert graph may, in fact, be spurious, but, of course, only SNY knows that data at present. However, if the graph turns out accurate, that means the only real differences from lispro is that afrezza can be inhaled and that it is removed from a diabetic's system more rapidly. While the first is a clear advantage, the second remains debatable. As I recall, the trials found no significant difference between the incidence of serious hypoglycemia between afrezza and lispro, and, as has been pointed out elsewhere, the rapid drop in the insulin levels may leave the diabetic exposed to later hyperglycemia from late digesting carbs. Next, if SNY does indeed know the data, you have to try and suppose what their course of action will be given the results. Will they decide it's worthwhile pursuing the kind of large real life trial needed to demonstrate something more than "non-inferiority" that is needed to improve chances for third party reimbursement? With the results seen by some of the early adopters (assuming that data is reliable), I'd question some of your assumptions. It certainly seems that people can push A1c significantly lower on Afrezza without hypo problems than with traditional RAA. The earlier trials were not designed to show this. Further, if the people we've seen reporting results are at all indicative of what can be achieved by most, it doesn't seem like it would have to be an overly large trial to be statistically meaningful. The safety study needs to be very large/long by its very nature to capture the possible unlikely outcomes. If one needed thousands of patients to show better A1c/hypo results with statistical significance it would be results that would be uncommon enough that it wouldn't have financial significance to those deciding to pay for Afrezza. If a majority of users could safely achieve an A1c at least half percent lower with Afrezza than with trad RAA... wouldn't it be possible to have a meaningful study with 50-100 people? Though a counter argument to what I've stated would be... so why hasn't SNY started such a trial if it's not a huge cost? "With the results seen by some of the early adopters..." There is a reason why anecdotal evidence doesn't count in the eyes of insurers -- individual patients are notoriously unreliable sources of info. Although it might seem off-topic, this article about the reliability of eyewitnesses could apply to individual patient reports as well: reliability of individual testimonySimilarly, there are psychological elements in treating illness. People want to get better. They want a drug to work better. In their own minds they might highlight positive events, while finding excuses for instances where the drug didn't perform as well as expected. However, even objective measures like A1C, for example, can be affected by a variety of variables independent of afrezza. Perhaps the patient altered their lifestyle when they started afrezza -- began to exercise more, began to watch their diet more carefully, began to monitor their glucose more closely, began to be more proactive in terms of attending to hyperglycemic episodes, etc. All of that is the reason insurers rank blinded, controlled studies so highly as the gold standard. Indeed, why hasn't SNY announced a "real life" study similar to the ones it's doing for toujeo and praluent? The toujeo one is 3,200 patients, but the praluent one is only 500.
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Post by rrtzmd on Dec 6, 2015 23:16:53 GMT -5
Practically any drug can be fashioned to be inhalable in some fashion or another. It comes down to delivering an accurate does in a cost-effective manner. HGH requires only subcutaneous injection per week. It's very expensive and given the wastage associated with inhaling -- e.g. afrezza where only 40% of what is inhaled actually reaches a spot where the insulin can be absorbed -- it's not likely to be considered a good candidate for inhalation.
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Post by rrtzmd on Dec 6, 2015 11:15:23 GMT -5
In reply to the topic, let's suppose. -Let's suppose the results from the clamp studies are known by sanofi. www.clinicaltrials.gov/ct2/show/study/NCT02470637
-let's suppose the type 1 user's meeting with Sanofi is true. -let's suppose the first of the pediatric study is known. Detailed Description: The patients are expected to participate in the study for approximately 6 to 8 weeks from Screening to final follow-up visit. Patients who completed 4 weeks of Afrezza treatment and have shown to be safe and well controlled with Afrezza + basal insulin will have the option to continue the extension treatment up to 1 year. www.clinicaltrials.gov/ct2/show/NCT02527265?term=diabetes&lup_s=08/04/2015&lup_d=14&show_rss=Y&sel_rss=mod14 -let's suppose the pediatric population all 46 of them like afrezza : Estimated Enrollment: 46 Study Start Date: September 2015
-Matt: *(1 phase insulin response of a non diabetic is the natural signal to the liver to stop releasing glucose for about 90 mins. This prevents blood glucose from rising while eating) afrezza prevents blood glucose from rising in the first place, where injectable insulin blood glucoses rise and then are lowered by the insulin. The first phase begins immediately but it doesn’t lower blood glucose, instead it temporarily stops it rising. This effect seems to be responsible for all the weird and wonderful properties of Afrezza, the first phase does not happen with previous insulins. screencast.com/t/YPzBxxXElA The second phase, however, works like a small dose of injectable insulin. It lowers blood glucose, and takes longer to start working. This is the only phase of Humalog or Apidra..................
In reply to your assessment -- the part shown in red on my screen -- the first thing you should try and suppose is an explanation as to why the PD graph shown on the insert looks the way it does. That graph suggests that afrezza's time of onset and effect on glucose lowering is virtually the same as lispro for about the first 60 minutes. One of the trials just completed could indicate that the insert graph may, in fact, be spurious, but, of course, only SNY knows that data at present. However, if the graph turns out accurate, that means the only real differences from lispro is that afrezza can be inhaled and that it is removed from a diabetic's system more rapidly. While the first is a clear advantage, the second remains debatable. As I recall, the trials found no significant difference between the incidence of serious hypoglycemia between afrezza and lispro, and, as has been pointed out elsewhere, the rapid drop in the insulin levels may leave the diabetic exposed to later hyperglycemia from late digesting carbs. Next, if SNY does indeed know the data, you have to try and suppose what their course of action will be given the results. Will they decide it's worthwhile pursuing the kind of large real life trial needed to demonstrate something more than "non-inferiority" that is needed to improve chances for third party reimbursement?
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Post by rrtzmd on Dec 4, 2015 13:05:16 GMT -5
I got 100 Jan 2017 3 calls. And 50 2017 2.50 Consider the 2018 $5 calls; last traded for 45 cents. I saw the warrants were trading at $0.08.
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Post by rrtzmd on Dec 4, 2015 13:02:44 GMT -5
rvc ... if your comment was in reply to mine... oooo, sorry, didn't AT ALL mean to imply SNY was going to be communicative about their plans, just that as the plans play out eventually there will be evidence that becomes visible. Heavens no I wasn't implying we'd be told anything... that be crazy talk. rrtzmd ... even if we make the leap to say this is the first sign of a SNY strategy to put in place a plan to prove superiority (not the most unequivocal statement I've ever made), it may be a situation of necessary but not sufficient regarding share price. There is still the issue of liquidity and potential dilution. Unless there is some TS deal that materializes and with better terms than many would suspect, MNKD will need to raise capital before any of what SNY is discussing in SD will result in a positive cash flow. "...what SNY is discussing in SD will result in a positive cash flow." The thing is that I don't believe there is any meeting in San Diego -- at least not between anyone related to afrezza or MNKD and SNY. No credible evidence has been offered that I have seen. It reminds me of that alleged Las Vegas meeting where hundreds of afrezza reps were meeting for some grand afrezza purpose to do something or another. It allegedly came, it allegedly went, and not one thing happened afterwards that remotely hinted that any such event actually took place. Now there are 11 pages of comments speculating on this new rumor -- to what end?
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Post by rrtzmd on Dec 4, 2015 12:20:45 GMT -5
Here is what my father, a retired orthopedic surgeon and very heavily invested MNKD long, discovered from speaking with his friend, a local pharmacist: The relative wholesale cost of pen injected Humalog vs. Afrezza (which the pharmacist had never even heard of) was $1.12 for Humalog and $2.50 for Afrezza, comparing 4 units of each. Has anyone on this board investigated this issue? If the reported information is correct, is there any wonder why Afrezza is not being covered by insurance and why it isn't selling as we expected? We were told by MNKD's management that Afrezza was to be priced competitively with insulin pens. Why would they say that if they knew that Sanofi was intending to make it more than twice as expensive? Is Sanofi breaching its contractual obligation with MNKD by pricing Afrezza so high? I'm not looking for any speculation here, but if someone knows something relevant to this issue, I'd love to hear it. Have you tried searching the board? I believe the topic has been thrashed a number of times.
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Post by rrtzmd on Dec 4, 2015 12:17:20 GMT -5
No one should be questioning whether this meeting is taking place or not, I think it has been very well comfirmed at this point. The questions we should be asking is whether this meeting will be a non-material event as all the others have OR will it be some turning point? This is what I would like to know. Looking at MNKD's stock chart since the rumor started, I'd say it's about as non-material as anything could possibly be.
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Post by rrtzmd on Dec 3, 2015 22:37:47 GMT -5
"'I don't think I've heard any negative feedback from patients that have started it and that were able to successfully go on it with their insurance company approving it,' she said." Of course, it would have been more informative if she had actually provided the number of those patients.
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Post by rrtzmd on Dec 3, 2015 22:33:56 GMT -5
I doubt SNY will drop afrezza. However, I suspect all they will do is use it to promote Wirt's "listen to the patient" hype, and then push all their other diabetic drugs past it. That said, I don't see much of a future for MNKD unless SNY declares its intention to pursue a trial to demonstrate that afrezza is better than "non-inferior." That act would indicate that SNY sees something worth pursuing aggressively and that trial is what is necessary to get decent third party payor reimbursement -- as well as convince docs that afrezza is worth the effort required to use it. As for technospheres, I have to score that a zero until MNKD gets past the "promises" and the "hope" and actually comes up with someone with some cash who wants to use it.
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Post by rrtzmd on Dec 3, 2015 11:04:50 GMT -5
Hakan Edstrom referred to the above referenced studies at the beginning of his 11/9/15 conference call. He stated that for the first study the treatment of subjects had been completed and the "data analysis and clinical study report is tracking ahead of FDA-assigned due date." For the second study, the subjects will have completed dosing by early December. These studies deal with the "effectiveness" of Afrezza in terms of PK and PD. While the PK (absorption of insulin by time) has been publicized and charted by Mannkind 10k's and Afrezzauser.com (Blog, week 15), the PD (glucose infusion rate) has been questioned. (www.acessdata.fda.gov "Afrezza pharmacokinetic study" pages 15-16.) My understanding of the biochemical processes and of clinical trial reporting procedures are both nil and I could be missing important aspects of both. But I see the above as leading -- hopefully very quickly -- to selling Afrezza on its effectiveness in blood sugar control, not just its "convenience" and needle avoidance. Does someone have insight regarding: 1) When the results of the above studies will be available to the public? 2) If the Afrezza PD mimics the Afrezza PK which mimics the effects of a healthy pancreas, could these studies result in the ability of Sanofi to immediately promote Afrezza on its effectiveness in blood sugar control? Thanks. "When the results of the above studies will be available to the public? " Whenever SNY decides to release them. The results belong to them and it's up to them to release the results. SNY does not have a good history of releasing results. "...could these studies result in the ability of Sanofi to immediately promote Afrezza on its effectiveness in blood sugar control?" No. The two studies were mandated by the FDA to clarify dose/response issues. For example, when MNKD did the PK/PD studies they compared 4U and other doses of afrezza to just a 8 or 10U dose of lispro. So one of the new studies will now compare equivalent doses -- 4U afrezza versus 4U lispro, etc. The other study is to assess "Within-Subject Variability of a Single Dose of Afrezza." If you look at the PK graph shown in the afrezza insert, you can see that the insulin concentration after dosing shows a wide range of variability as compared to lispro. Why is that? What is even more odd is that the PD graph implies that there is no difference in the time of onset of effect or in the the glucose lowering effect for about the first hour between afrezza and lispro. As I recall, SNY even included a comment on the graph or just below it noting that oddity. Why doesn't afrezza's PD graph reflect its PK graph more than it does? In any case, to truly prove afrezza is more than non-inferior will likely require a large, "real life" trial like the one SNY is doing for toujeo.
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Post by rrtzmd on Dec 3, 2015 10:40:58 GMT -5
I don't agree with biotec that the unfounded cancer scare is likely the biggest roadblock, but I'm sure it plays a role. It certainly got raised as an issue with Exubera. If everyone in the medical community believed there was no possibility of a risk, MNKD would not have spent the significant resources on doing those trials specifically to prove it isn't a problem. Like it or not, the FDA has specified long term safety studies... those that are ultra cautious may well think it safest to wait until those are done. biotec may simply have a different risk profile than others here and thus, even if not believing this specific unfounded risk, believe the concern occurs more in others than we do. Personally, here is how I imagine it might be most harming Afrezza. You've got some overworked doc. He's heard about Afrezza but just to the extent it's non-inferior and doesn't require needle. He vaguely remembers something about safety concerns with Exubera... perhaps even mistakenly thinking that the concerns had to do with its withdrawal from the market. Says to himself... eh, doesn't seem compelling if it's just a patient convenience thing, maybe I'll wait for more safety data. "You've got some overworked doc." Most likely. As far as the rest, think more in terms of the doc having lispro/lantus protocols memorized inside/outside/and all around the town. He/she has honed their dosing skills to a fine enough edge so that if awakened at 3 am about some problem, little more than instinct is needed to give out instructions that at least won't kill whoever is on the other end before office hours. The doc can then roll over and go back to a peaceful sleep. Here comes the Sanofi rep touting afrezza. What? More rapidly absorbed? More rapidly eliminated? 4U, 8U, 12U cartridges? 4U for 1, 2, 3, or 4U of lispro? Get away from me already!
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