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Post by agedhippie on Nov 6, 2023 17:51:01 GMT -5
The AID is part of the study but the AID can not beat afrezza for post prandial glucose control. That is why Aged wants to down play this and wants to point at TIR. With TIR you are no longer looking just at post prandial control but you are adding in the basal's fasting so you can "blur" just how good afrezza is. ... There has been a ton of data over the years showing that Afrezza has a faster onset and where exactly has that got us? Nobody cares, why do you think it will be different this time? Treating diabetes is about the outcome and that's where Afrezza needs to show it can work as a component in the treatment hence the primary outcome in this trial is the HbA1c, and everything else is (literally and figuratively) a secondary outcome. Say what you like, but HbA1c and TIR are the two metrics the endos will be looking at. Blur is a nice way of saying you want to avoid an inconvenient truth - outcomes matter, not features.
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Post by agedhippie on Nov 6, 2023 17:18:30 GMT -5
Did this trial preclude an AID pump or are they not available yet? The trial is made up of 1/3 Afrezza + Tresiba, 1/3 dumb pumps, 1/3 AID pumps. At the end of the 17 week trial everyone gets switched to Afrezza + Tresiba for a 13 week extension to the trial. The AID pumps have been out for three years or so now.
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Post by agedhippie on Nov 6, 2023 8:31:33 GMT -5
I think this trial is Afrezza's best chance of changing the story. The design is interesting and I thought having the dumb pump arm was a mistake, but I suspect it's about saying you don't have to move to an AID pump and that Afrezza is an option. Those dumb pumps are aging out and their users are going to have to switch to something else.
Some of the endpoints are not going to matter - the standardized meal test being the poster child. That purely comes down to the type of insulin used and was has been shown before Afrezza will win by a mile. The issue is that it's not going to change anything since that behavior has already been shown with zero impact (but it will let them write a PR early in the trial.) The 13 week extension when everyone is switched to Afrezza will be interesting as it should show change nicely.
Which outcomes matter? Only two; HbA1c and TIR. Keep focused on outcomes and not features because the endos will.
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Post by agedhippie on Nov 4, 2023 17:43:02 GMT -5
Just read the transcript. He lays out the options they considered, why the arrived at the strategy they have, and what they intend to do. It's all about orphan lung drugs, and GLP-1 is mentioned only as being irrelevant to MNKD since he says, "There's always these weight loss crazes that happen, and eventually they die down." Does that make his view on GLP-1 clear enough? There is a strategy, GLP-1 is not part of it, no he cannot arbitrarily add GLP-1 as companies don't work like that (especially listed companies). Yes. I will be saving this post. I find it amazing how sure you are. I am not sure what is amazing. Did you read the transcript?
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Post by agedhippie on Nov 4, 2023 11:28:09 GMT -5
Not going to happen. Mike is very clear that the focus is orphan lung drugs which definitely does not describe GLP-1. Reread the transcript from the Morgan Stanley call, it's all in there. Should we be calling you Mike and not Aged? Or does Mike have to check in with you before he can add new items to the potential pipeline? Just read the transcript. He lays out the options they considered, why the arrived at the strategy they have, and what they intend to do. It's all about orphan lung drugs, and GLP-1 is mentioned only as being irrelevant to MNKD since he says, "There's always these weight loss crazes that happen, and eventually they die down." Does that make his view on GLP-1 clear enough? There is a strategy, GLP-1 is not part of it, no he cannot arbitrarily add GLP-1 as companies don't work like that (especially listed companies).
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Post by agedhippie on Nov 3, 2023 18:19:47 GMT -5
Victoza patent expiration is next year. I wonder how liraglutide would fly on Technosphere? No shots in the diet market IMO is a blockbuster. Maybe we can sell V-Go and use the money for a pilot study. Not going to happen. Mike is very clear that the focus is orphan lung drugs which definitely does not describe GLP-1. Reread the transcript from the Morgan Stanley call, it's all in there.
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Post by agedhippie on Nov 3, 2023 12:48:45 GMT -5
Mike talked about the strategy in the Morgan Stanley call. He wants to get away from royalty deals like UTHR because they are low margin and unreliable (your fate is in someone else's hands and interests may diverge). His strategy to to own the drug lifecycle from inception to customer without involving partners. This has not worked out well with Afrezza though hence the follow up which is to go for orphan drugs as there is little competition.
Really there isn't a lot of choice. Drug delivery is a low volume low margin business and MNKD is not broadly competitive (the UTHR deal was announced five years ago and the sales pipeline looks pretty empty). Afrezza will probably get a one time bump next year when it becomes available for kids, but growth will remain sluggish as there is nothing to change the narrative on outcomes. That leaves the drug pipeline as the only option by a process of elimination.
The interesting question is whether MNKD call sell the drugs. To date sales results have been rather anemic to be polite with campaigns like flying burgers and melting ice cream, and no evidence for why endos should prescribe. That problem is alleviated with orphan drugs because there is little or no competition so the sales organization becomes less about sales and marketing, and more about order taking. If your organization can't sell then pick an area where they don't need to.
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Post by agedhippie on Nov 2, 2023 12:11:59 GMT -5
Anybody have a theory why UTHR decided this quarter to reveal exactly the percent Mannkind makes? Low double digits, HA as Mannkind as shown several times they like to massage the truth. The LOWEST double digit looks to be the answer. There was a limit to how long UTHR could get away without revealing the royalty rate. It was nothing to do with MNKD and everything to do with pressure from the analysts covering UTHR. The analysts need to be able to model the revenue stream and without the numbers it was harder than necessary, and no company wants to upset the analysts covering them. Regardless, there comes a point where you can work out the numbers reasonably accurately anyway with a bit of work (something the analysts like to avoid) so the secrecy had run it's course.
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Post by agedhippie on Nov 2, 2023 8:05:28 GMT -5
... the fact that our production is at capacity I struggle to find a negative with...I agree clofazamine is in the future, it has to be, we are at capacity for now, later will come. Or not. What an exciting few quarters Mannkind investors have to look forward to! All good. This is why I don't see an issue with UTHR taking over manufacturing. In the Morgan Stanley call Mike talks about what he wants for MNKD and it's to become a biotech pharmaceutical company rather than rely on partnering and royalties. With that in mind recovering the manufacturing capacity is important as it allows this to happen. This part of the transcript is where he outlines his plan; We went through our growing pains and saying, what are we? Are we a platform company? Are we a licensing company? Are we just going to develop products and formulate and sell them off? And I think the way you really create value is to become a self-sustaining biotech pharmaceutical company.
And you look at the margins, and you look at the, while we can get royalties, that's great. At the end of the day, if you're a CMO, you're stuck in a very low-margin business, and you're on high-risk failure, and assets don't come along fast enough to sustain your company when you see these models. And so we really did pivot in 2019 to say, we are going to be fully focused on orphan lung, leverage our technology, help those patients.
That is better news for the future of Afrezza than the alternative (a royalty focus) as Afrezza now fits that model of owning the product from design to sales. It also sets the table for for going it alone with clofazamine and not using partners. The aim becomes to identify orphans where there little or no competition so the revenue stream is solid. This is also why GLP-1 would be a bad choice for MNKD, it's a heavily contested market and the domain of the big boys.
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Post by agedhippie on Nov 1, 2023 7:40:40 GMT -5
Thanks, that was exactly what I was looking for.
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Post by agedhippie on Oct 31, 2023 19:45:33 GMT -5
just a few risks from liquida's recent 10Q The following is a summary of the principal risk factors described in this section: ... Lol. Actually that's quite short. The UTHR one is much longer. Those sections are always long because if you don't disclose a risk there it can get you into a shareholder lawsuit, or possible prosecution by the SEC. Consequently they read like War and Peace and everyone skips them.
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Post by agedhippie on Oct 31, 2023 17:56:07 GMT -5
Do they really believe LQDA is much competition or was it more personal? Didn't one of Martine's trusted guys leave and go to Liquidia taking a bunch of trade secrets? Who was it Roscigno? If he did this to me I would sue them too. Serious question - does LQDA have any money to even try and compete? IDK I don't give them much of a chance. Back in the day when UTHR was considering them prior to MNKD sure but I don't give them much chance with "broadly comparable" trials. For whatever reason when UTHR compared them to Technosphere, they lost. It's not personal it's business, Roscigno left LQDA three years ago. I don't think the trade secret case is serious. Roscigno left UTHR in 2007 for a healthcare company where he worked for another 6 years before joining LQDA. Given the interval between his leaving UTHR and joining LQDA proving a trade secret breach of significance is going to be hard. Besides, Roger Jeffs had still been working at UTHR then so if LQDA wanted data Jeffs knowledge was far more current. LQDA is actually quite well off and can get past launch without needing cash. The odds are that they do a raise before launch though because why not? My bet is that UTHR got a far better deal out of MNKD than they could have got out of LQDA. At that point MNKD really needed the deal, but LQDA had the resources to wait and try for the whole enchilada rather than just royalties.
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Post by agedhippie on Oct 31, 2023 15:54:15 GMT -5
You mean 70%. MannKind’s technology delivers ~70% of the dry powder to the deep lungs. As for the slides, Martine presented a handful of data slides illustrating Tyvaso DPI’s superiority over Yutrepia. I’m surprised you didn’t see them, they were being posted and discussed for a while. You may be correct, as checking that 40%- it's for the Medtone inhaler and the Dreamboat is more efficient. I cannot find any data on the Dreamboat though (the Medtone data was from a MNKD paper). To be clear though, the point was that the amount making it through is unimportant in the overall scheme provided enough can get through to work - with Afrezza 30% doesn't make it through, but it still works just fine. If I had seen the slides I wouldn't be asking for a link
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Post by agedhippie on Oct 31, 2023 12:49:08 GMT -5
... Yutrepia can go as high as the equivalent of 27 breaths of the nebulized Tyvaso which I believe is considerably higher than Tyvaso DPI has achieved. If Martine has data and slides to prove this is nonsense I would love to see them because I haven't found any comparisons. Both sides seem to be tiptoeing around each other with DPI. I don't usually comment on my own posts I was curious about the dosing so I checked. The label for Tyvaso DPI has a maximum dose as 11 - 12 breaths of nebulized Tyvaso. The maximum dose for Yutrepia is 27 breaths from trials and calls. Not everyone needs that, but as this is a progressive illness there will come a point where patients will have to roll off as their needs exceed the maximum dose and with Yutrepia that comes later.
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Post by agedhippie on Oct 31, 2023 12:34:23 GMT -5
Yutrepia requires more dry powder to achieve a similar clinical response whereas Tyvaso DPI is able to use less dry powder to achieve a similar clinical response simply because of the superior inhaler (and possible dry powder technology) MannKind uses. The PK/PD data and clinical trials data all prove this. It’s also something Martine and Mike have mentioned before in calls. Yutrepia must use significantly more dry powder because a lot of it impacts the upper airway and doesn’t penetrate the deep lungs like Tyvaso DPI does. So it is also misleading to claim Yutrepia doses higher when in fact the higher dose is needed because not much powder reaches the deep lungs in the first place. I thought everyone knew about Martine squashing this nonsense when she spoke about it and showed the slides with the data proving it. If Yutrepia is garbage Martine is sure spending a lot of time and money on trying to prevent something from coming the market that isn't a threat! You are confusing API quantity with therapeutic breaths (the equivalent of breaths of nebulized Tyvaso - it seems to be what they use in the same way that insulin uses units). Think of it like Afrezza - about 40% makes it through to the blood stream with the resting, being swallowed, not being properly inhaled, passing through unaltered, etc. This is used by certain people (LFD *cough*) to say that Afrezza is ineffective, but that is not the case - you simply use more of the active component. The amount of active drug used is irrelevant, it's the therapeutic effect that matters as Afrezza proves. OK - so how do they compare? They are pretty much the same. In the INSPIRE study the all patient group 6MWD increased by 12.6 meters, the Tyvaso DPI HCP site claims 11.5 meters. That's close enough that in real life I expect there to be no difference. This is hardly surprising since the since the API is the same in both cases. "It doesn't penetrate deep into the lungs" is a claim you see a lot from Technosphere supporters. That's wrong. There is more than one way to skin a cat and MNKD and LQDA illustrate that. The LQDA delivery system, PRINT, does it by printing out specifically shaped micro-particles (hence the name) and using a low resistance device. The shaped particles use the aerodynamics produced by inhalation to penetrate deep into the lungs. If anyone can prove this is untrue I would love to see the evidence. Yutrepia can go as high as the equivalent of 27 breaths of the nebulized Tyvaso which I believe is considerably higher than Tyvaso DPI has achieved. If Martine has data and slides to prove this is nonsense I would love to see them because I haven't found any comparisons. Both sides seem to be tiptoeing around each other with DPI.
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