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Post by hellodolly on Nov 16, 2023 6:48:32 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. Correct, but what I was speaking to was in the context of the MNKD products that Mike has addressed or has been published in journals, a news release, and currently medically proven with Afrezza, TYVASO, DPI and most recently MNKD-101. I think a pattern is developing whereby Technosphere can become a platform for the repurposing of many drugs once used orally, subcutaneously, nebulized and other methods of administration into low dose administration that is safe and efficacious. Problem 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. Below is a PR of a couple of quotes form a recent journal publication: investors.mannkindcorp.com/news-releases/news-release-details/mannkinds-inhaled-clofazimine-will-advance-adaptive-phase-23 "Direct delivery of clofazimine to the lungs may provide a treatment option for nontuberculous mycobacterial (NTM) lung disease that potentially overcomes systemic toxicity and lessens side effects.""Additionally, a paper has been published in the American Society for Microbiology journal Antimicrobial Agents and Chemotherapy examining the potential for treatment of nontuberculous mycobacterial (NTM) infection through direct delivery of inhaled clofazimine to the lungs, overcoming the systemic toxicity witnessed in oral treatments."
2. Don't argue with your thoughts on LFD. 3. 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... Here the interesting point you make is this is the same argument regarding LFD's flawed argument, "... what matters is the outcome and not the quantity..." concerning LFD and his history making false points about Afrezza. Personally, myself...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. |
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Post by longliner on Nov 16, 2023 10:03:11 GMT -5
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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 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 longliner on Nov 16, 2023 12:29:25 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?
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Post by thekid2499 on Nov 16, 2023 12:51:06 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 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? Bingo! When we are on the short end of that stick, the debbie downer crew will say that's just business and any reasonable company would do it. But when MNKD is better positioned to take advantage, the same crew is inspired and compelled to trumpet this other company's drug and spend lots of time and effort digging into it and posting how great it is even though they have no investment and don't have the disease. But it's all good, opposing points of view are great as long as you contextualize them. And be happy you live in a more positive existence. |
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Post by cretin11 on Nov 16, 2023 13:46:01 GMT -5
I suppose we could have a rule that only cheerleading posts are allowed on this forum. People would be confused why our share price has floundered for a decade, but perhaps comforted by the echo chamber assuring them massive success for Afrezza (and everything else MNKD touches) is just around the corner.
The mods can decide that. In the meantime, thanks aged and others who have shared their honest opinions, even if not exactly what we want to hear. I hope you’ll continue to post. It turns out aged has been about the most accurate one here at predicting Afrezza’s path. Doesn’t mean it’ll hold true for his predictions on Tyvaso, Yutrepia or anything else. Longliner you say aged’s posts are frustrating, my suggestion is don’t let it get to you, consider taking a breath and realizing each post by aged is a new opportunity for learning something.
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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 longliner on Nov 16, 2023 15:56:58 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?  |
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Post by harryx1 on Nov 16, 2023 16:10:12 GMT -5
" 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." agedhippie - The USA was built on the patent system and has been the heart of innovation since it was created. Just as you have your opinion that it's broken due to patent trolls, it's equally broken due to large companies stealing legitimate patents, reaping billions and never paying a dime to the inventor or company that patented the idea/process. Very rich and powerful people/groups have convinced Congress to create the PTAB (patent death squad) for their benefit, so they can make millions if not billions off of innovations others have created. "The Origins of Patent and Copyright Law Our nation's founders recognized the value of intellectual property, and in the U.S. Constitution, they granted Congress the power to protect it. From the beginning of our nation, Congress has enacted patent and copyright laws to protect the works of creative people and to encourage others to be creative." In my opinion, you & cretin speak in a way that takes your opinion and subtly suggest it as fact in many cases. I debated on whether to even respond and waste my time and energy so this is far as I'll go. Some Important Historical U.S. Patents  |
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Post by hellodolly on Nov 16, 2023 16:19:18 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. Thanks, as I mentioned and you confirmed for me, Mike made the comment (I had forgotten which conference) about not favoring "royalties" as a business strategy, so we agree on that when I noted, "... they don't want to be dependent upon revenue coming only from royalty streams...". Glad LLY and PFE are not built around the same business strategy as MNKD. While we have our own competition in the industry, I'm happy to see MNKD Board steering Mike towards their strategy of organic growth. He hinted a few times that if the right deal came along, they would take a look. 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. Only time can tell if they can score more drugs that have been shelved, or re-puropse others. I posted this in the thread Clofazimine Patent Issued: In some embodiments, clofazimine inhalable compositions, including CIS and dry powders can be used for the treatment of other diseases, including, of leprosy and other bacterial infections, including, in the treatment of nontuberculous mycobacterial diseases. In treatment of bacterial infection using clofazimine capsules, the drug is relatively well tolerated, with the main side effects including yellow skin discoloration and gastrointestinal issues at least in half the patients. Preclinical studies have evaluated CIS for the treatment of NTM-PD and TB, and a series of toxicology studies have been performed, which have shown that CIS is safe and well tolerated at doses up to ˜3.0 mg/kg (reaching lung levels of ˜10 μg clofazimine/g). Patent publication date 8/10/2023I'm satisfied with the direction the board is taking however, I'm not so sure they're on track to have one FDA approved product in the pipeline each year. That is a lofty goal Mike mentioned. Finally, the irony many MNKD investors find with your last observation. You correctly observed and noted, " 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." Damn if I wasn't first drawn to MNKD by the fact that I thought the delivery of insulin via an inhaler over needles wouldn't matter, given exactly what you said. Thanks for the civil dialogue and discussions. I've learned a lot from you. I don't always agree but, they are duly noted. when I'm out of my lane, I don't try and jump into the discussion aka Aged v Sayhey. |
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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 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 sayhey24 on Nov 16, 2023 18:44:18 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. Aged - did you listen to the interview Mike did the other week? You might want to augment what he said at Morgan Stanley with that additional info. The bottom line is it all depends on the deal and with who. Granted MNKD did not bring any leverage to the UTHR deal but it kept the "Out of Business" off the front door and now its paying the bills. To date the only other deal I think Mike negotiated was V-Go. Hopefully he has better negotiation skills than demonstrated on these first 2 deals. If so and the deal make sense and Mike can negotiated a good deal, I doubt Mike will look a gift horse in the mouth. Then again he already has a gift horse sitting at his front door and its called Saxenda DPI. |
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Post by sayhey24 on Nov 16, 2023 19:02:50 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. Aged - do you think it has gone through all the studies Al Mann did prior to afrezza/Technosphere product approval? I doubt it. He did a ton of safety studies before he spent that $1B. Yet for years and years you told us it was going to cause serious lung damage. Why would you not take the same position with LQDA that you did with afrezza? Thats kind of a head scratcher to me. Great - it went through three FDA trials and how many separate safety trials? What did it take, 5 years after approval for your endos to give the thumbs up that they were wrong on afrezza lung safety? For Tyvaso DPI, Technosphere was a time proven safe product. This one, at this point is a wildcard. |
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) 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!
