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Post by agedhippie on Nov 18, 2023 11:29:48 GMT -5
I will also take Aged's stance he/she had with afrezza, Yutrepia's lung safety is not proven. Why would any doctor prescribe a medication which is almost as good but may cause further lung issues when there is a safe, proven alternative from an established company? Liquidia who? The issue for some endos in the early days was insulin in the lungs based on from what they thought they were starting to see with Exubera. The carrier, Technosphere, was never a concern. I doubt anyone is going to have safety concerns with Yutrepia since Tyvaso has been inhaled for years. If you are counting on lung concerns being an issue I think you will be disappointed.
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Post by agedhippie on Nov 17, 2023 14:00:03 GMT -5
Aged has 66% more posts than me. I am going to need to really step it up. I have been here longer Although not 66%....
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Post by agedhippie on Nov 16, 2023 18:23:34 GMT -5
... No feedback on the advantages MNKD is discovering with their Technosphere platform? That is, they're finding pharmacokinetic advantages with Technosphere during dose escalation studies. Less drugs, less toxicity, better tolerance. ... I think there are a lot of benefits to Technosphere in cases where you want to get the drug into the bloodstream for immediate effect. Some drugs either cannot be taken orally because the stomach destroys them, insulin being a prime example, or the side effects are so nasty you can only use the drug in extremis although you want to use it far more often. There is a whole market sitting there waiting.
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Post by agedhippie on Nov 16, 2023 17:41:26 GMT -5
I'll take you at your word...your first word. It was after all simple yes or no question. If this is how you support the company (MNKD), and you claim to support Liquidia in it's David and Goliath battle, why aren't you on the Liquidia board bashing their product to support it? Or is their product perfect? There is a Liquidia board?
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Post by agedhippie on Nov 16, 2023 14:22:15 GMT -5
In the area you work, you admittedly see the patent system wielded as a club or barrier to entry. Have you posted for years to right that wrong? Do you also see IP stolen from one company to the next? Do you see the likes of a Law firm (Lassman) creating a barrier to entry, which adversely affected every MNKD shareholder? When a known nefarious party enters into the picture who rightfully served his sentence (Skrelli) backing the company in question, no red flags? I have to question your "White Knight" standing for supporting the downtrodden little guy after the years of beating down the downtrodden little guy. So, back to my original question? Will you be bashing Mannkinds next product as well? Yes. I think the patent system is fundamentally broken. It incentivizes companies to build portfolios out dubious patents purely so they ammunition to use against competitors. This is before we get to patent trolls which is an extension of the same problem taken to it's logical conclusion. Patents cease to be about protecting innovation and become a way of preventing it. I often get involved in IP theft investigation which is why I think UTHR's case is particularly weak. There are a set of hurdles you have to clear to win one of these cases and I strongly suspect UTHR are not going to make it over some of them. Really this case is simply about trying to shake investors. You see people use the legal system all the time to create barriers to entry. UTHR is doing it at the moment. And no, I don't approve of either case. Companies cannot pick who supports them. To the best of my knowledge he isn't employed in any role by LQDA. I can live without being awarded White Knight status. With Afrezza I have pointed out over the years that without decent sized trials nothing will change. Do the trials and get the label and PR changed, it's simple. I don't bash MNKD's products. I say why I wouldn't use Afrezza, but that's not a reason why others should use it. Nor have I criticized others for doing so. My view is that every diabetic is entitle to deal with their diabetes how they want. As to Tyvaso-DPI, I don't think I have ever bashed it, it's not an area I know enough about. Likewise I doubt I would bash any other MNKD drug unless there was something particularly egregious. At this point I think I have exhausted the topic. People who think (incorrectly) that I am here to bash MNKD are going to think that regardless of what I say so it rapidly becomes pretty pointless as a discussion.
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Post by agedhippie on Nov 16, 2023 11:25:05 GMT -5
I'm curious, when Mannkind launches their next product, either alone or in partnership, will the same party here that has soft bashed both Afrezza and Tyvaso attempt to undermine that product as well? If so, at some point you have to ask why? Why argue against our science in support of our competition? Why (for years) undermine every attempt at success for Mannkind and it's investors? You admittedly are not an investor in Mannkind, or an end user of our products? To what end? It used to be your interest in diabetes, did you suddenly contract PAH as well? As a MNKD investor it is certainly frustrating, so mission accomplished I suppose. It's a moderated board, as long as they appreciate the content so be it. I sort of feel that was aimed at me, and usually I don't answer these but since you asked reasonably... Beyond Afrezza (which I absolutely do not want to see discontinued BTW) I don't really have a dog in this race. I don't think I have ever argued against the science, but I have argued against what I see as either incomplete or misleading information. With Afrezza a lot of what I saw was non-insulin users telling me, as an insulin user, what I felt and wanted - you hate needles, the spike is the be all and end all, it's impossible to get better outcomes, that sort of thing. None of this is what insulin users care about which is primarily, where is my HbA1c going, and for the more pro-active what is my TIR. Everything else is fluff for the majority (ok - fluff may be a bit strong, but definitely secondary.) I feel that I advocate for an approach that would make MNKD, and Afrezza specifically, more successful. That is large scale clinical trials because those are what drive change. People kept on seeing small studies and expecting those to change things which was never going to happen because statistically they are to small to extract a good outcomes picture. Things like the pump trial are more relevant because are large enough and will start to get endos attention. TBH I don't need to cheer on every success, we have a board full of people who will do that. But a one sided conversation is not going to let you make an informed decision. Happily I haven't contracted PAH. And I have always said that I think Tyvaso-DPI will take the bulk of the market. What I intensely dislike though is when I think companies are abusing the patent system to compete in the medical field. This is partially down to the area I work in which sees a lot of this sort of thing, although it's not in the medical area, and partly down to a sense of fair play. That inspires me to go and dig into Yutrepia to find out why it has UTHR so badly scared (curiosity helps ) What I find is that a lot of things get said that are based on incomplete information, some of the legal stuff in particular, or that I know professionally are unlikely to go anywhere like the trade secret case (I have been wrong before though). The material is all out there, but most people never dig for it which I entirely understand!
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Post by agedhippie on Nov 16, 2023 10:16:39 GMT -5
1. ...I think is Mike just let the cat out of the bag that they don't want to be dependent upon revenue coming only from royalty streams, rather they go find a drug that was once considered too toxic, horrible side effects, etc, convert the old versions into DPI (if possible), clinically test in animals and humans and market them alone. ... 3. ...I guess it doesn't matter that high flow delivery deposits the drug into the oropharynx so long as the outcome is improved patient health. Again, I don't disagree, as there is always some trade off with drugs so long as it is not or does not become a SAE in the future. Mike spelt out the strategy in the Morgan Stanly conference. He will take royalty work, but he sees it as unreliable since it's dependent on the drug owner coming to you as it's hard to sell the migration of a successful drug, and low margin. Owning the drug from end to end gives far more stability. The question then is where to look and for a small company like MNKD it makes sense to go after the orphan drug sector an look for lucrative niches. Someone like Pfizer or Lilly isn't interested in small volume drugs, they are built for those so a whole class of competitor is removed. As much as anything the depth a particle travels to is a function of particle size. For deep lung penetration from what I have read about 1.5um is about the maximum size (take that with caution - I am not certain). Larger particles don't get as far. As an example diesel emissions are >1.0um which is why they are so dangerous as they deposit cancer-causing organic substances deep into the lungs. Ultimately with all drugs what the medical world is looking for is outcomes. How that effect is achieved is not really of interest beyond whether it impacts patient compliance. As an example nebulized Tyvaso is awkward to use so people don't use it as often as they should. Tyvaso-DPI on the other hand is easy to use so patient compliance is a lot higher meaning you get better outcomes. The fact that one is DPI and one is nebulized is irrelevant to the decision to prescribe - it's the outcomes that drive doctors to DPI.
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Post by agedhippie on Nov 15, 2023 18:31:52 GMT -5
Another advantage to low flow vs high flow, that Mike has been saying for sometime: [paraphrase} DPI doesn't require high .mcg dosages because of the dynamics low flow has over high flow...less dose, less toxicity, equal or better outcomes. There is no evidence of toxicity (this has been through all three phases of FDA trials). The API quantity argument is the same one that LFD has been used against Afrezza in the past and has the same flaw, it goes Afrezza takes more insulin than RAA to get the same effect so therefore Afrezza is bad. That is flatly wrong since what matters is the outcome and not the quantity of API used as Afrezza shows. Liquidia print specifically sized and shaped particles to act as carriers so they get deep lung reach via that route rather than the inhaler. In some ways Liquidia is not unlike Mannkind in that with Print they have come up with a carrier mechanism to deliver drugs deep into the lung. Their first drug is Tyvaso though rather than insulin.
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Post by agedhippie on Nov 14, 2023 9:28:24 GMT -5
I know this doesn't belong here but I can't find an appropriate thread. What's up with Futures this morning? Is this a head fake or are the markets looking to JUMP? According to Bloomberg; the report Peppy mentioned reinforced the view that interest rates had peaked and the Fed would have room to ease policy next year.
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Post by agedhippie on Nov 13, 2023 17:20:33 GMT -5
Hey Aged, you wrote "it is possible to put it into remission (the Newcastle diet does this very effectively) for a period given time it will always return, hence remission rather than cure." I disagree, but I suppose it's only semantics. I corresponded with Dr. Lim back in 2011 when his study (the basis for the Newcastle diet) published. I was fascinated, and impressed, that he was the one who figured out that there was nothing magical about gastric bypass surgery reversing Type 2 - it was instead the severe caloric deprivation that these patients undergo from the surgery. I have helped two people reverse their diabetes and another drastically reduce the medications she needed to manage the disease using the teachings of Dr. Lim and others. In my limited experience, it is merely the bad diet (and lifestyle) that goes into remission. Once the former T2 resumes the bad diet, gains back the weight, and doesn't exercise, indeed the T2 will eventually return. Btw, I am very grateful for your informative posts and learn a lot from you. You obviously are very educated in diabetes care. I am only posting this because I want T2's reading this to know that, whether you call it remission or a cure, many can reverse their T2 indefinitely. The Newcastle diet works. But once the severe calorie restriction phase of the diet is over, they must maintain a healthy lifestyle of proper diet and exercise, and keep the weight off. You are right about the lifestyle change. and the ability to reverse T2 indefinitely. Sadly, also that a lot of people revert to their old lifestyle and the diabetes returns. It's particularly interesting in that it takes a relatively small weight loss to put diabetes into remission, that was a big surprise to me. The Newcastle diet has now been adopted by the UK National Health System as a standard treatment for T2 and is used throughout most of the UK.
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Post by agedhippie on Nov 13, 2023 16:56:09 GMT -5
... Many years ago Aged told us the reason he would not use afrezza is that it will cause severe lung damage over time. Its been 10 years since the 171/175 trials and 9 years since approval. Lung function is being reported to be no worse than what would be expected but in some cases its better. What do these expert endos say now? The answer I get is go read a text book. ... Again, you are remembering incorrectly. What the endos said was that it is possible it may cause IPF based on what they thought they had seen with Exubera. At no point did any endo I had say it will cause IPF over time - that's you. The last time I heard this discussed was six years ago when they didn't see it as an issue. You don't listen to what I say so suggesting you read a text book on the topic to get some knowledge seems like the best idea, it's what I do in that position.
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Post by agedhippie on Nov 12, 2023 10:24:43 GMT -5
I’ve assumed insulin resistance is attributable to a diet too rich in sugar. The digestive system dutifully absorbs it and causes blood sugar to increase, and the pancreas does its insulin thing. But perhaps the body’s ability to absorb the sugar (either burning it or turning it into fat) is limited meaning a greater amount of sugar remains in the blood than would otherwise be there. We know high blood glucose over extended periods of time damages organs and nerves. I don’t assume the pancreas is immune from high blood sugar just because it secretes insulin. Our bodies don’t work as well when we’re older. I don’t know how much of that is attributable to imperfect copies of cells or extended periods of high blood sugar, but it doesn’t surprise me that older folks tend to be T2 more often than younger folks. You are not far of the mark with some of this. Primarily though T2 is genetic. You can see this in families, but also because the obesity rate far outpaces the T2 diabetes rate which would not be what you expected if obesity was the root cause (you can see this through the HANES studies and CDC data). The cycle you are describe is thought to be part of the cause, although it should be carbohydrates in general rather than just sugar. The insulin receptors become less responsive for a variety of reasons, one of which is reduced sensitivity due to the amount of circulating insulin which leads to the requirement for more insulin. Your body becomes used to a higher level and tries to maintain it. The aim with treatment is to get that baseline back nearer normal so you aren't fighting your body, and then maintaining it. Despite what people say T2 is a progressive disease although it is possible to put it into remission (the Newcastle diet does this very effectively) for a period given time it will always return, hence remission rather than cure. This was the point Mike was making about the impact of GLP-1 buying time but essentially being overcome leading to the need for insulin. Insulin is the end state because it always works provided you take enough - essentially T2 creates a relative deficiency and external insulin makes up that shortfall. In older people insulin production slows down just like everything else. This tends to expose the borderline groups who were ok, but now are not. It is quite possible to have all the conditions of T2, but the progression is so slow that you die of old age before it ever shows. One of the problems with diabetes in general, and Type 2 in particular, is that it comes in a lot of different shapes and sizes because it's genetically diverse. At the last count there are over 120 genes associated with Type 2 and most Type 2 diabetics only have around five. It's why I think we see a cure for Type 1 before we see a cure for Type 2.
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Post by agedhippie on Nov 12, 2023 10:02:40 GMT -5
Exploding lungs is entirely your fantasy, you really out to get over it. The rest of your argument is incoherent. It runs counter to what Afrezza users say (take Afrezza during the meal, by which time your pancreas is happily engaged and there is no wait), and the idea that human insulin from the pancreas is different from human insulin from Afrezza - I honestly don't know what to say. I think at this point you are chasing a ton of squirrels and confusing fact with conjecture. You need to stop, find an endocrine textbook, and educate yourself. Google - Exploding Lung Syndrome and what do you get - pneumothorax. Isn't that what your endo said was going to happen over time taking afrezza? I believe it was and why you told us years ago you would not try afrezza. Isn't that correct? I believe so. All I want to know is have they said they were wrong? ... Seriously? You do know the difference between a collapsed lung and pulmonary fibrosis (PH-IPF) don't you? If you don't I really don't know what to say. Endos haven't been bothered about fibrosis for years as I said repeatedly, but you ignored. These days I don't usually even bother to comment when you bring it up because you will just ignore it again. I feel like you make stuff up, announce it as fact, and then disregard anything that contradicts it. And no, I am not going to teach you diabetology because I am a diabetic and not an endocrinology professor. If you want to that (which I would applaud) then do real courses at a real institute. The idea that human insulin delivered by inhaling is different from human insulin the body produces, or even is injected is just bizarre.
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Post by agedhippie on Nov 11, 2023 18:39:22 GMT -5
This is pure fantasy and medically groundless. Hey - I think thats what they told Al when he was first talking about afrezza and its near normal control - fantasy and groundless. How about ELS (exploding lung syndrome)? Wasn't that the great hope for deep sixing afrezza? It seems not so much. Answer me this - why is it if we give the afrezza at the start of the meal and stop the spike we need half the insulin than if we wait until the pancreas releases its insulin and the BG spikes. We then need 2X or 3X the afrezza after the spike. That ain't no fantasy - its reality and can be demonstrated over and over. We would think if we just need to "top off the tank" of insulin as you say, after the pancreas releases its insulin, we would need less, a lot less afrezza. Thats not how it works. Go - your turn. And, let us know about your endo's update on ELS. Exploding lungs is entirely your fantasy, you really out to get over it. The rest of your argument is incoherent. It runs counter to what Afrezza users say (take Afrezza during the meal, by which time your pancreas is happily engaged and there is no wait), and the idea that human insulin from the pancreas is different from human insulin from Afrezza - I honestly don't know what to say. I think at this point you are chasing a ton of squirrels and confusing fact with conjecture. You need to stop, find an endocrine textbook, and educate yourself.
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Post by agedhippie on Nov 11, 2023 12:14:24 GMT -5
I stopped buying calls in Mannkind years ago for exactly this reason. There are too many traders selling calls with the ability to manipulate the market. Having expiration come on an earnings week was a dinner bell for them. I don't know why I didn't think of that, but actually yes you could be right about the dinner bell although not for the reasons you think! I traded this myself from time to time. As earnings approach the implied volatility spikes because of the uncertainty and then after the call when the uncertainty is gone the spike collapses really fast. The nice thing about the IV Crush trade is that it's almost entirely independent of stock price movement.
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