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Post by agedhippie on Aug 14, 2023 9:58:05 GMT -5
One thing I don't understand about this thread and similar threads. I'm just making up numbers to make a point. If a one time spend of $30M for clinical studies will lead to making $2B per year, why hasn't it been done yet? If you had a spare $1.5B, would you buy mnkd and do it yourself? Because there will be a team whose role is to pick where to invest their limited funds. This track doesn't look like a winner simply because of how GLP-1 analogs work, and the delivery isn't going to affect that. Contrast that with nintedanib where the byproduct of the breakdown of the drug in the gut causes side effects which an inhaled version would avoid and it's clear why that is in the pipeline and GLP-1 isn't.
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Post by agedhippie on Aug 14, 2023 9:47:04 GMT -5
... Mike has already told us the preliminary numbers from India are in the 1.5 - 2% A1c reduction range. If true he should have some ammo for the T2 SoC and should be able to enlist the CGM vendors for support. I can't do Mike's job for him. Step 1 is getting the pre auths for 2024 removed. Step 2 is leveraging the India results to justify T2 SoC changes. Step 3 is doing the glp1/afrezza study to provide a transition path. OK - now you say Mike can't make a phone call. Al has an issue. Mike may have a solution. Problem solved - I dropped Al a note so he is expecting Mike's call. Mike needs to stop wasting time and see if Victoza DPI works. Maybe Al has an interest in putting his molecules on TA, maybe not. If Victoza DPI works as you predict, "Touchdown". The issue is that if the HbA1c reduction is 1.5-2.0% then Mounjaro already exceeds that. Consequently the ADA will see an India result like the one mentioned as confirmation of their current strategy and the SoC will remain unchanged. I would be very surprised if the CGM makers got involved, they are not about to burn political capital on a lost cause - even after India there is not enough supporting data to get a change. Of course Mike can make a phone call, anyone can make a phone call. Your note never made it to Bourla (unless it was hand delivered). The best case is that the people handling his mail will have routed it to someone in the GLP-1 team, but more likely it was just dumped with the hundreds of similar items they get daily. So when Mike phones his call will get handled exactly like all the other cold sales calls. Let us be clear on this - my expectation is that Victoza on TS will have exactly the same side effects as subq Victoza. Victoza is not GLP-1, it's GLP-1 analog with the side effects that come with that regardless of if it's inhaled, swallowed, or injected. By all means spend the money finding that out, but my suspicion is that Mike already knows this from his background.
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Post by agedhippie on Aug 13, 2023 13:02:36 GMT -5
... Essentially, they are saying that the drug is already being used in a wide array of other diseases, likely to bypass more regulatory hoops as in when patents are being applied brand new molecules. As I believe, MNKD is likely still only going after NTM but, it's interesting that the same drug is used for other viral infections that impact the lungs and respiratory system. The patent process in these sorts of patents isn't about winning, it's about slowing down a competitor (eg. UTHR vs. LQDA) by getting your patent into the Orange book and forcing the new entrant to get your patent revoked. With that in mind you claim for absolutely everything because the aim isn't to win but rather to delay. In this case since the Chinese have already put and antibiotic on FDKP there is a lot of scope for prior art challenges. This is what I dislike about the patent system and companies who use patents like that. It creates a slanted playing field and favors larger companies (again UTHR vs. LQDA) although I entirely understand why companies do it. This also why I don't take big pharma conspiracies against Mannkind seriously, they would have simply gone for Mannkind in court using their patents whereas messing with the stock market is illegal and an unnecessary risk.
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Post by agedhippie on Aug 13, 2023 9:26:57 GMT -5
... If you have the guys number and you say you know him, give him a call. Whats worst case, his admin blocks Mike. So what, keep trying. When you finally talk with him, maybe he laughs at you but then again maybe not. What I do know is Peter Richardson had some good success with native GLP1 and Martine is having great success with Tyvaso DPI. I think you can put an elevator pitch together around that. As far as the US vs the UK, maybe Mike can just focus on the US Medicare market for now. If he can get 10% of the T2s on Medicare that would be a huge start and he can then build from there. ... So Mike is trying to cold call the CEO of one of the largest pharmas in the world who doesn't know him from a hole in the wall as far as we can tell. I absolutely guarantee he gets blocked and I doubt he even reaches the admin. There will be hundreds of people a day trying to call him and those calls get (politely) dumped. You cannot have a CEO at that level getting off schedule. Right now 28% of Afrezza sales are going to Medicare which equates to the percentage other RAA pharmas see. I expect it to go up a few points from here since Afrezza doesn't currently have a pediatrics market and so it is weighted to the older end, but that sounds like a ceiling. He is not getting 10% of T2 on Medicare, the SoC is in the way of that.
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Post by agedhippie on Aug 12, 2023 9:23:37 GMT -5
OK - just to be clear you are saying GLP1s are designed to only be used for a short period of time. And then what? The PWD gains back the weight and loses BG control and in a year or two goes back on the GLP1? I am not sure that approach is outlined in the T2 SoC. I also bet as soon as they stop using and their food flows normally through the digestive system we will see post meal spiking and that 92% TIR will be in the rear view mirror. I don't consider two years a short period of time although all things are relative. The UK NHS has it's own T2 SoC, as do most countries, so they are likely to differ from the US. You would lose that bet since if that was happening the patient would not be in remission - remission means no symptoms. What is the benefit of combining Afrezza and GLP-1 over just taking either Afrezza or GLP-1? That is what the trial would need to quantify - how the treatment translates into an actual reduction in complications (not it reduces spikes, but how many few CVD cases are there or how much is progression slowed for example.) Is Bourla really a friend or did they just happen to work in the same company of several thousand people at one point? (Genuinely asking as I don't know what the relationship is) If you get the same side effects for inhaled vs. injected GLP-1 analogs (as I expect) then what is the benefit to Pfizer is dumping their pill that they have spent millions on developing and have just about ready to go and delaying entering the GLP-1 market for a couple of years while an inhaled version is developed and trialed?
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Post by agedhippie on Aug 11, 2023 18:26:16 GMT -5
Wow, you have now brought up something I never considered. You said - "Once their HbA1c is in range they can stop and go back on it a year or two later if necessary" I was not aware GLP1s were curing T2 diabetes. I was aware Al Mann had some pilot studies showing afrezza reversed the disease in some cases but I think GLP1s doing this is breaking news. When I googled on it I did find this "The study authors hypothesized that because of its mechanism of action, LIRA “could address the multiple pathogeneses of T2DM,” and therefore, “should bring complete remission of T2DM in newly diagnosed patients.” AACE 2017 Meeting; Drugs Context. 2015; 4: 212283. Published online 2015 Jul 9. doi: 10.7573/dic.212283 Now - this was published 8 years ago. if you have a link showing GLP1s reversing diabetes could you please post it. ... Let's be clear on this. it has never been shown that Type 2 diabetes can be cured, but it can be put into remission. Weight loss reduces insulin resistance and sufficient weight loss can allow people's own insulin to be sufficient for their needs and that is the entire point of the Newcastle protocol that the UK NHS uses. The link to GLP-1 is obvious in this model, it facilitates that weight loss. Again though; Type 2 diabetes can be put into remission but cannot be cured. Reversing is an imprecise term since it can either refer to remission, or cure which are not the same.
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Post by agedhippie on Aug 11, 2023 13:56:07 GMT -5
I have always been clear on that. I need the share price to get above $5 and stay there for a decent length of time. I got out all those years ago just before the reverse split and I need the share price to return to that point. Right now I don't think Mannkind knows how to sell Afrezza (not saying that I do, but then I am not paid to know), and UTHR looks like a nice cashflow but also a high concentration risk. What I would like to see is at least two other big, not necessarily huge, pharmas like UTHR using TS. My view is that selling access to TS is where the money is.Ditto. MRK LLY REGN PFE GSK etc. Plenty of medications. I always felt that TS was where the money was and that Afrezza was intended as a demonstration (look what we have done to the insulin market, sign up for us to help you as well...) That's probably not a popular view though
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Post by agedhippie on Aug 11, 2023 13:44:32 GMT -5
Why do you think you failed finding AGPs for GLP1 users? I sound like a broken record on this. Mike needs to do the study and then you will be able to find them. He said a few calls back they were going to start the pilot. One arm is suppose to be adding afrezza to the GLP1. The thing is, it doesn't really matter short term which one wins. Long term the PWDs stop using the GLP1s. My point is Mike needs to be positioned to fill that gap. If he can show adding afrezza to the Medicare GLP1 users they can also get an almost free CGM. He also needs to do the Victoza DPI pilot and prove this will never work for the diet market. But then again, maybe it will. On Monday he did say they have bandwidth to run some pilot studies. Because an APG is meaningless in a clinical trial - they are individually tailored. Notice that there are no Afrezza APGs either? You keep saying that diabetics quit GLP-1 in the long term, but you are failing to account for that being by design (protocol). Once their HbA1c is in range they can stop and go back on it a year or two later if necessary - that a cycle that is being used in Europe and probably in the US. The idea that on top of everything else you have to worry about a CGM is not a great sales pitch. People want a magic bullet which is why Ozempic is such a huge seller for weight loss and diabetes. Mike is not going to seriously follow up on GLP-1 because the science says it is very unlikely that you get a different result from injected GLP-1 analogs at which point a daily Victoza loses to a weekly Ozempic. He knows that so other than PR he isn't going down that path.
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Post by agedhippie on Aug 11, 2023 12:35:15 GMT -5
So..Aged…About at what point are you going to wet your “beak”, and invest back into Mannkind? I have always been clear on that. I need the share price to get above $5 and stay there for a decent length of time. I got out all those years ago just before the reverse split and I need the share price to return to that point. Right now I don't think Mannkind knows how to sell Afrezza (not saying that I do, but then I am not paid to know), and UTHR looks like a nice cashflow but also a high concentration risk. What I would like to see is at least two other big, not necessarily huge, pharmas like UTHR using TS. My view is that selling access to TS is where the money is.
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Post by agedhippie on Aug 11, 2023 10:29:28 GMT -5
Given UTHR's rosy outlook for Tyvaso DPI that just keeps getting rosier, I've no problem with LQDA getting to wet their beak. I'm not concerned that there may be some dramatic improved patient experience with LQDA's product compared to Tyvaso DPI and thereby prove a substantial threat to the domination being achieved by UTHR and Tyvaso DPI. I am somewhat amused that UTHR filed a new patent as yet another legal stumbling block for LQDA. UTHR's strategy for maintaining market share has been brilliant. Acquire one potential competitor, sue another, partner with the 3rd (MNKD). Dr. Rothblatt is a shrewd businessperson. I think she rightly recognized the value of an improved inhalable version of treprostinil. I assume both LQDA's and MNKD's products were under consideration, and I remember reading on ProBoards that apparently LQDA was also approached about a buyout but it fell through for whatever reasons. The result? Tyvaso DPI. Dare I say it? The MannKind story is edging toward "epic". I think there was a question in one LQDA transcript about market share with respect to UTHR and Merck (Sotatercept) to which the response was that the market was big enough to support everyone. It's why I am not stressed about competition here.
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Post by agedhippie on Aug 11, 2023 10:04:12 GMT -5
What? GLP1s are not competing against afrezza today in the Medicare market. Nearly all pre auths for afrezza are for T1s. It will not be until afrezza is available without pre auths does the game begin. This is why I sound like a broken record about Mike needing to get pre auths removed for 2024. Once that is accomplished afrezza is in a brand new world. ... As I said earlier, insurers decide where pre-auth applies, not Medicare, so there is nothing Mike can do here. The largest two Medicare insurer in the US, UHC and Humana, do not even have Afrezza in their formulary so pre-auth is irrelevant in that case for over 50% of the US Medicare patients.
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Post by agedhippie on Aug 11, 2023 9:50:55 GMT -5
LOL, arguing both for and against GLP-1s. For if it’s on TS, against if it’s not. sayhey24, you are to be cherished. You’re a powerhouse. Of course I am because I am looking at it for 2 different markets. When we are talking A1c control they are both about equal short term. For post prandial control afrezza wins hands down. Longer term afrezza will win as GLP1s plateau and afrezza users may see improved beta cell development. Of course Mike needs to do the study to show that. ... Afrezza providing better meal time control is currently unsupported. I have tried to find charts comparing the two and failed so far. Right now the idea goes that Afrezza has a fast action therefore it must hit the spike faster. This overlooks that part of the action of GLP-1 is to make the body's own insulin more effective and therefore you can kill the spike without external insulin. This is a case where YMMV applies heavily. Mike needs to do a study to support that because currently there is no evidence that this scenario plays out. Certainly the idea that Afrezza cause beta cell development is pretty radical.
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Post by agedhippie on Aug 11, 2023 8:03:02 GMT -5
They gave you LQDA’s view. The doctor attorney CEO of United Therapeutics might (would) give a different view. :-) You may well be right about the validity of the patent. I can't see LQDA saying that it all looks good. The eligibility to compete in the PH-ILD market is solid though since that's a defined process and if the steps are followed then the outcome is certain. Once it gets into legal areas like the validity of patents things become a lot more hazy.
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Post by agedhippie on Aug 10, 2023 22:38:37 GMT -5
Here it is in the transcript. Mike said, " There is an IP update from United Therapeutics in their recent quarterly earnings, where we heard the patent for ILD should be issued and give allowance through 2042." It's a little misleading because what the patent will not do is prevent LQDA from selling into the PH-ILD market. LQDA filed the paper work with the FDA before the patent was issued so: " ...there will be no 30-month stay at the FDA that attaches to this new patent. While we expect United may file a lawsuit alleging that a liquidity infringes this new patent, we would not automatically be delayed in our ability to seek final approval for the PH-ILD indication. Instead, the burden would be on United to seek and prevail on obtaining a preliminary injunction. To do so, the burden would be on United to demonstrate among other things that they are substantially likely to prevail on the merits of the case. Historically, the courts have generally declined to grant preliminary injunctions in situations where there are substantial questions as to the validity of the patented issue." (From the LQDA earnings call today) They went on to discuss the problems the patent would have with prior art, not least from UTHR's own '793 patent! In short, this patent may delay other competitors, but not LQDA. I was curious about the impact of that patent.
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Post by agedhippie on Aug 10, 2023 22:14:36 GMT -5
Lilly has trial data for people on Mounjaro with 91.2% TIR, and 72% between 80-140 from the SURPASS-3 trial. Against that getting Afrezza to preempt GLP-1 in the Type 2 SoC is a very hard sell. Add in the cardiovascular study results from Novo Nordisk and I really cannot see it happening, it simply offers much better value. OK, so? In the Medicare market GLP1s can not compete against $35 afrezza. Do you really think these seniors are going to pay $1k+ a month when they can pay $35, get better control and not get sick in the process? Oh. and they get a CGM for a few bucks. Lets see what the India results are and if they are as Mike said they might be maybe Mike can get CMS and CGM vendors to sponsor SOC T2 changes. BTW - have one of these seniors take the "Coke Challenge" and lets see that GLP1 stop the spike. Heck. 91% it should be 100% when these people are hardly eating and what they do does not get digested. ... I don't know about "in the medicare market GLP1s can not compete against $35 afrezza" because GLP-1 is competing today and seems to be doing pretty well. And I guess that gives you your answer on whether seniors will pay for GLP1s - looks like they will. The idea that Mounjaro can hit 91% because people are not eating or digesting food is silly, they hit that number because GLP-1 works. As I said, the Mounjaro low end average was a 2.0 reduction so that's what the India trial needs to beat. Actually I think it's possible to land around there with decent dosing, but the 175 Type 2 trial had an average reduction of 0.82. There are a lot of reasons why GLP-1 get discontinued. In the UK the protocol is to use it for 2 years and then discontinue it because the bodyweight loss means the person is usually in remission. Some insurers are following the same pattern. This is the reason why the GLP-1 makers have been running trials looking for other benefits - they want to stop protocols like that.
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