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Post by sayhey24 on Jul 9, 2023 15:32:42 GMT -5
OK - do you have a link to the study results or any additional information? You seem to know a bit about this study. Based on your response I am assuming they did not load Bydureon on TS. I am also assuming they did not load Victoza on TS. Peppy - Mr. Google shows MKC-180 in this 10k filing along with MKC253. investors.mannkindcorp.com/node/11476/htmlThat's pretty much what I know. For the benefit of others here is the relevant section from the 10K filing Sayhey found. A year later this was was abandoned. (My emphasis on the most interesting sections) We conducted a second Phase 1 trial to assess the effect of MKC253 on post-meal glucose excursions in patients with type 2 diabetes. A total of 15 subjects were each given MKC253, placebo or exenatide on different days and followed for a four-hour period after each administration. In both fasted and fed subjects, inhalation of MKC253 produced a rise in insulin levels that peaked within 10 — 15 minutes. In fasted subjects, this increase in insulin led to a rapid decrease in blood glucose concentrations within 30 minutes, with a slower decline over the next 3.5 hours. Subjects who were fed and given MKC253 displayed a blunting of the initial post-meal glucose excursion for approximately 30-50 minutes, depending on the dose. In the same subjects, exenatide stimulated insulin release but produced much lower peak levels than those produced by MKC253 in either the fed or fasted state. Nonetheless, over the four-hour study period, exenatide also produced mean decreases in blood glucose concentrations. This observation may be due to the fact that exenatide had a profound effect on gastric emptying, with approximately 90% of the meal retained in the stomach at four hours after meal ingestion. In contrast, MKC253 did not have any overall effect on gastric emptying. Until we have conducted a full program of clinical trials, we will not be able to reach definitive conclusions about the potential safety or efficacy of MKC253.The first highlighted part were the drugs involved; MKC253 (GLP-1 on TS), placebo (probably pure TS), and exenatide (Byetta as Bydureon wasn't released for another 7 years.) The second highlight is why GLP-1 on TS will never be used - it doesn't slow gastric emptying. That's game over. A year later from the 2011 10k it does not say MKC253 nor MKC180 were abandoned. What is says is they were halted. MNKD had no money. From the 2011 10k "In February 2011, we implemented a restructuring to streamline our operations, reduce our operating expenses, extend our cash runway and focus our resources on securing the approval of the new drug application, or NDA, for AFREZZA by the United States Food and Drug Administration, or FDA. In connection with this restructuring, we reduced our total workforce by approximately 41 percent and halted activity in certain development programs" From what you copied from the 2010 10k but did not highlight "Until we have conducted a full program of clinical trials, we will not be able to reach definitive conclusions about the potential safety or efficacy of MKC253." I can not find the word you used "That's game over" Lets also remember this was as a T2 medication not obesity. The conclusion am taking is MKC180 was halted and never restarted because of money. Its possible the team working on this got laid off. It sure looks like they never loaded liraglutide on TS. Its also not clear what MKC180 was. To me this is getting more interesting. Back in 2009 they thought they had something for both T2 use and obesity use. In 2010 they ran out of money and they never did the studies. At this point what we know is MKC253 displayed a blunting of the initial post-meal glucose excursion for approximately 30-50 minutes, depending on the dose. In the same subjects, exenatide stimulated insulin release but produced much lower peak levels than those produced by MKC253. We know nothing about MKC180 nor what TS liraglutide would do for obesity. My take away is we need to review all the results from 15 years ago and restart some trials for obesity. Maybe native glp1 on TS; liraglutide on TS; and subq liraglutide. |
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Post by sayhey24 on Jul 9, 2023 16:33:48 GMT -5
From Andrea Leone-Bay - "A product called MKC-180 is a formulation of Technosphere and a natural hormone that controls appetite and that is under investigation as a therapy for obesity with pulmonary administration. “In non-clinical studies we found observed reduction markers in food intake”, affirmed Dr. Leone-Bay. www.anad.org.br/wp-content/uploads/2015/05/13Revistas_URL1.pdfIDK but that sounds pretty good to me. |
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Post by agedhippie on Jul 9, 2023 18:18:48 GMT -5
That's pretty much what I know. For the benefit of others here is the relevant section from the 10K filing Sayhey found. A year later this was was abandoned. (My emphasis on the most interesting sections) We conducted a second Phase 1 trial to assess the effect of MKC253 on post-meal glucose excursions in patients with type 2 diabetes. A total of 15 subjects were each given MKC253, placebo or exenatide on different days and followed for a four-hour period after each administration. In both fasted and fed subjects, inhalation of MKC253 produced a rise in insulin levels that peaked within 10 — 15 minutes. In fasted subjects, this increase in insulin led to a rapid decrease in blood glucose concentrations within 30 minutes, with a slower decline over the next 3.5 hours. Subjects who were fed and given MKC253 displayed a blunting of the initial post-meal glucose excursion for approximately 30-50 minutes, depending on the dose. In the same subjects, exenatide stimulated insulin release but produced much lower peak levels than those produced by MKC253 in either the fed or fasted state. Nonetheless, over the four-hour study period, exenatide also produced mean decreases in blood glucose concentrations. This observation may be due to the fact that exenatide had a profound effect on gastric emptying, with approximately 90% of the meal retained in the stomach at four hours after meal ingestion. In contrast, MKC253 did not have any overall effect on gastric emptying. Until we have conducted a full program of clinical trials, we will not be able to reach definitive conclusions about the potential safety or efficacy of MKC253.The first highlighted part were the drugs involved; MKC253 (GLP-1 on TS), placebo (probably pure TS), and exenatide (Byetta as Bydureon wasn't released for another 7 years.) The second highlight is why GLP-1 on TS will never be used - it doesn't slow gastric emptying. That's game over. ... I can not find the word you used "That's game over" Lets also remember this was as a T2 medication not obesity.... Let me help your reading comprehension. "That's game over" was not italicized and was in my commentary so why do you think you can find it in the 10K? The key finding is that gastric emptying was unchanged, that is why it's game over for GLP-1 on TS. Now they could move to GLP-1 analogs, but those are different molecules so the side effects findings for GLP-1 becomes irrelevant and they are back to square one. |
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Post by sayhey24 on Jul 10, 2023 9:49:07 GMT -5
I am ok starting at square one when we are talking about a $90B market and Pfizer is seeing a 34% drop out rate trying to crack the oral market. I would ask the question is it really square "1"? It seems a great deal of work was done and MNKD was taking this very serious before the money ran out.
While my reading comprehension is not great what you said was "That's game over" and MNKD for MKC253 said "Until we have conducted a full program of clinical trials, we will not be able to reach definitive conclusions about the potential safety or efficacy of MKC253." IDK, that seems pretty different to me. They were also looking at the T2 market for this not obesity.
All I have for MKC180 is Andrea saying “In non-clinical studies we found observed reduction markers in food intake”. It seems no trials were ever done but they must have been seeing something pretty positive to talk about it. I find it interesting you don't think this is not worth taking another look and would rather have this entire idea - just go away.
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Post by agedhippie on Jul 10, 2023 10:25:08 GMT -5
It's not that I would rather it just go away, it's more that I don't think it's a good candidate. We already know that GLP-1 doesn't change gastric emptying, and that it clears very rapidly. That alone is likely to be the reason why there are no side effects (no drug = no side effects or benefits.) This will not be quick, look at the development work for Tyvaso, and the issue with this is that the market is rapidly evolving (GLP-1 -> GLP-1 + GIP -> GLP-1 + GIP + Glucagon -> ? ). There is a serious risk that the result is redundant by the time it's produced.
More to the point I feel that the MNKD approach right now is to go for drugs where there is minimal competition which makes sense for a company the size of MNKD.
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Post by sayhey24 on Jul 10, 2023 14:03:36 GMT -5
I guess that's where we differ. I am not really interested in another V-Go to put in the sales reps bags. If all MNKD wants to do is dumpster dive for scraps when they are sitting on the greatest advance in diabetes care and a deliver system which can alter how the body reacts to many other compounds I would say we need new leadership.
Albert Bourla knows he has a problem. He knows he has a 34% drop out rate. I would rather pick up the phone and convince Albert Bourla to give MNKD a few $M to put danuglipron on TS and see what happens. To Albert that's round-off and who knows maybe MNKD was on to something years ago. Maybe TS can actually reduce how sick these people are getting and reduce the amount of danuglipron needed.
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Post by prcgorman2 on Jul 10, 2023 15:34:37 GMT -5
Comparing V-Go to a TS-enabled product is not really an apples-to-apples comparison. V-Go is a device, so the comparison would be V-Go versus Dreamboat which in itself is also not a good comparison because one is an inhaler and the other a manual pump so it would be more appropriate to compare V-Go to a pump, and Dreamboat to a nebulizer (and even that comparison breaks down). I also wouldn't call V-Go "dumpster diving" so much as a flyer.
TS formulations is what you're arguing for, and MannKind does have that in focus in the pipeline although the nearest term candidate in the pipeline is nebulized clofazimine for NTM (and then eventually the TS un-nebulized version), and then TS nintedanib for idiopathic pulmonary fibrosis (IPF). If I had to guess, if approved, TS clofazimine and TS nintedanib might be available for prescription in the same year (2025? 2026?).
MC has emphasized that what is in the pipeline now was identified for development years ago, so even if development and business case for other candidates such as you're interested in are under consideration, it might be some time before we would learn about it. From what I can tell, MannKind (and all other BPs) study all sorts of possibilities, but few candidates drop out of the narrow end of the hopper for full-scale development and marketing, and the process is slow.
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Post by peppy on Jul 10, 2023 15:41:31 GMT -5
I misspelt it. It was MKC180 and the comparator was exenatide. Now you have the right spelling Google should find it! The issue was that GLP-1 did not significantly slow gastric emptying compared to exenatide. That's hardly surprising though as it's a well known problem given the half life of GLP-1. OK - do you have a link to the study results or any additional information? You seem to know a bit about this study. Based on your response I am assuming they did not load Bydureon on TS. I am also assuming they did not load Victoza on TS. Peppy - Mr. Google shows MKC-180 in this 10k filing along with MKC253. investors.mannkindcorp.com/node/11476/htmlMKC 180 obesity compound, that was it...... it sure disappeared from the pipeline page. |
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Post by agedhippie on Jul 10, 2023 15:42:10 GMT -5
The problem is that Pfizer has an agreed strategy which is danuglipron in pill form and that's what they are focused on executing on. There is nothing to show Pfizer except an old experiment with a different molecule. They are not going to buy that. If this is truly a $90B market then Pfizer will be just fine with a 34% drop out rate because the remainder will be huge.
Peter Drucker did an interesting work on the taxonomy of companies where he compared them to the military; start ups were the storm troops, fast moving and nimble but lightly armed and not designed to hold ground, the infantry behind them who take over an hold ground but moving in formations, and finally the bureaucracy (he used the pay corp) which follows on is the infrastructure supporting everything but very slow with huge inertia. Pfizer and Abbott are the last of those; they have huge scale and need multi-year strategies, they do not change direction unless there is a catastrophe. Pfizer has decided pills so pills it will be.
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Post by wyattdog on Jul 11, 2023 15:35:52 GMT -5
Novo Nordisk A/S: European Medicines Agency issues statement on ongoing review of GLP-1 receptor agonists
12:36 PM ET, 07/11/2023 - Briefing.com
EMA's safety committee, the PRAC, is reviewing data on the risk of suicidal thoughts and thoughts of self-harm with medicines known as GLP-1 receptor agonists, including Novo's Ozempic (semaglutide), Saxenda (liraglutide) and Wegovy (semaglutide). These medicines are used for weight loss and for treating type 2 diabetes. The review was triggered by the Icelandic medicines agency following reports of suicidal thoughts and self-injury in people using liraglutide and semaglutide medicines. So far authorities have retrieved and are analysing about 150 reports of possible cases of self-injury and suicidal thoughts. Liraglutide and semaglutide medicines are widely used, with an exposure of over 20 million patient- years2 to date. It is not yet clear whether the reported cases are linked to the medicines themselves or to the patients' underlying conditions or other factors.The review of Ozempic, Saxenda and Wegovy started on 3 July 2023 and has now been extended to include other GLP-1 receptor agonists. This review is expected to conclude in November 2023.Statement (NVO, LLY, PFE, MRK, VKTX, GPCR, ETNB, ALT)
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Post by peppy on Jul 11, 2023 16:07:01 GMT -5
Joy Reid on MSNBC looks to have lost and be losing weight.
Ronna McDaniels looks to have lost weight.
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Post by lennymnkd on Jul 11, 2023 16:31:11 GMT -5
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Post by sayhey24 on Jul 11, 2023 16:57:55 GMT -5
The problem is that Pfizer has an agreed strategy which is danuglipron in pill form and that's what they are focused on executing on. There is nothing to show Pfizer except an old experiment with a different molecule. They are not going to buy that. If this is truly a $90B market then Pfizer will be just fine with a 34% drop out rate because the remainder will be huge. Peter Drucker did an interesting work on the taxonomy of companies where he compared them to the military; start ups were the storm troops, fast moving and nimble but lightly armed and not designed to hold ground, the infantry behind them who take over an hold ground but moving in formations, and finally the bureaucracy (he used the pay corp) which follows on is the infrastructure supporting everything but very slow with huge inertia. Pfizer and Abbott are the last of those; they have huge scale and need multi-year strategies, they do not change direction unless there is a catastrophe. Pfizer has decided pills so pills it will be. Have you ever talked with Robert Ford or Albert Bourla? I can guarantee you their Admins will protect them like crazy from letting anyone get to them. The thing is if you have had the chance to talk with them, they are just guys. The thing is both have a similar problem, with covid over, sales for the vaccine and test kits have dropped like lead balloons. Robert thinks he can sell a boat load of CGMs to the T2 Medicare crowd and needs a better way to do that. Albert Bourla has a 34% drop out rate for his glp1 pill. Maybe not a catastrophe but if you can have a direct discussion and provide a few alternative ideas which their huge staffs have not, you may very well be surprised how they can turn the Titanic on a dime. Here is the bottom line - "If there was a drug like Wegovy without the nausea side effects, I would love to take it," Vogt said. This article just bumped up Bourla's $90B to $100B and you would still rather dumpster dive? Sure, lets go put some V-Gos in the sales reps bags, NOT! In this article is a list of companies Mike should be calling tomorrow if he is not too busy selling MNKD stock. TS should be able to help at least one of them, including Pfizer. www.reuters.com/business/healthcare-pharmaceuticals/biotech-firms-target-weight-loss-drugs-without-wegovys-side-effects-2023-07-07/ |
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Post by sayhey24 on Jul 11, 2023 17:01:10 GMT -5
Exactly - this is why Mike needs to get the afrezza/glp1 study going ASAP. The 1 year drop out rate is huge and by year 2 its about 80%. Could you imagine how much afrezza would be sold if it only got 50% of the glp1 drop-outs. Did I also mention afrezza stops the post meal spike and glp1s not so much. |
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Post by agedhippie on Jul 11, 2023 18:26:39 GMT -5
... Peter Drucker did an interesting work on the taxonomy of companies where he compared them to the military; start ups were the storm troops, fast moving and nimble but lightly armed and not designed to hold ground, the infantry behind them who take over an hold ground but moving in formations, and finally the bureaucracy (he used the pay corp) which follows on is the infrastructure supporting everything but very slow with huge inertia. Pfizer and Abbott are the last of those; they have huge scale and need multi-year strategies, they do not change direction unless there is a catastrophe. Pfizer has decided pills so pills it will be. ... Albert Bourla has a 34% drop out rate for his glp1 pill. Maybe not a catastrophe but if you can have a direct discussion and provide a few alternative ideas which their huge staffs have not, you may very well be surprised how they can turn the Titanic on a dime. ... You are confusing startups with major enterprises. Enterprises do not turn on a dime, and that's by design. They have a strategy and that is what they are executing on. There is nothing to show these firms beyond a decade old trial with a different molecule that failed to show delayed gastric emptying and a request for money. With that story you would be lucky to even get to their admins, never mind a CEO. The first gatekeeper will kill this. |
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