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Post by sayhey24 on Feb 20, 2023 14:32:39 GMT -5
We don’t need a Aspart Technosphere. What makes it Aspart, or now Fiasp rather, is the fact it’s not even insulin. It’s an altered foreign protein. Fiasp is a hexameric insulin analog with an altered amino acid sequence, proline by aspartic acid in position B28, and is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae (baker's yeast). Right away we know we aren’t dealing with real human insulin anymore. But wait, it get worse… Fiasp also contains: niacinamide, arginine, USP, glycerin, phenol, metacresol, zinc, disodium hydrogen phosphate dihydrate, sodium chloride, water, hydrochloric acid and/or sodium hydroxide. Insulin aspart has the empirical formula C256H381N65079S6 and a molecular weight of 5825.8 daltons. Afrezza consists of human insulin (produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli), FDKP and polysorbate 80. Chemically, human insulin has the empirical formula C257H383N65O77S6 and a molecular weight of 5808. As you can see, only one of the above is real, human insulin while the other is “something else” that attempts (rather poorly) to mimic the real thing. Mango - I hear you but afrezza is not selling. Don't you agree??? I just keep trying to figure out things which might work with little development. TS GLP1 is one and after me whining and being told by MNKD it was no good they file for the patent which you showed us. Are they doing anything with it now, IDK but I have hope. Back in 2007 NVO was pretty excited about their AERx inhaler but then came afrezza and they shut the program down in 2008. Up until last year they were having a field day with Ozempic but then came Mounjaro which showed better numbers. Now they have icodec and Mike seems very excited about it. The fact of the matter is the body sees C256H381N65079S6 almost the same as C257H383N65O77S6. The reality is the best we had before recombinant DNA technology was C257H387N65O76S6 and the human body said OK. If NVO said - hey Mike lets do a deal but we want to frame it like UTHR did. We want to own the patent and we want to call it Novolog DPI. We also want to sell it as our "inhaled" ultra rapid insulin and we know we can sell it with icodec and as an adder to Ozempic. Hey Mike - we think we should be able to do at least $4B, MNKD manufactures and we give you a 22% royalty. Mango - would you not be OK with NVO realizing the market where to-date MNKD has not and does not have the resources to do all the big studies? The pps at $5.63 is a lot better than $1.06 but the right deal with NVO could easily take this to $20+. In the end if they want to sell both insulin human and aspart, I would be OK with that. I just don't know if they would want to sell V-Go, but I would offer it. |
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Post by mango on Feb 20, 2023 15:00:16 GMT -5
We don’t need a Aspart Technosphere. What makes it Aspart, or now Fiasp rather, is the fact it’s not even insulin. It’s an altered foreign protein. Fiasp is a hexameric insulin analog with an altered amino acid sequence, proline by aspartic acid in position B28, and is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae (baker's yeast). Right away we know we aren’t dealing with real human insulin anymore. But wait, it get worse… Fiasp also contains: niacinamide, arginine, USP, glycerin, phenol, metacresol, zinc, disodium hydrogen phosphate dihydrate, sodium chloride, water, hydrochloric acid and/or sodium hydroxide. Insulin aspart has the empirical formula C256H381N65079S6 and a molecular weight of 5825.8 daltons. Afrezza consists of human insulin (produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli), FDKP and polysorbate 80. Chemically, human insulin has the empirical formula C257H383N65O77S6 and a molecular weight of 5808. As you can see, only one of the above is real, human insulin while the other is “something else” that attempts (rather poorly) to mimic the real thing. Mango - I hear you but afrezza is not selling. Don't you agree??? I just keep trying to figure out things which might work with little development. TS GLP1 is one and after me whining and being told by MNKD it was no good they file for the patent which you showed us. Are they doing anything with it now, IDK but I have hope. Back in 2007 NVO was pretty excited about their AERx inhaler but then came afrezza and they shut the program down in 2008. Up until last year they were having a field day with Ozempic but then came Mounjaro which showed better numbers. Now they have icodec and Mike seems very excited about it. The fact of the matter is the body sees C256H381N65079S6 almost the same as C257H383N65O77S6. The reality is the best we had before recombinant DNA technology was C257H387N65O76S6 and the human body said OK. If NVO said - hey Mike lets do a deal but we want to frame it like UTHR did. We want to own the patent and we want to call it Novolog DPI. We also want to sell it as our "inhaled" ultra rapid insulin and we know we can sell it with icodec and as an adder to Ozempic. Hey Mike - we think we should be able to do at least $4B, MNKD manufactures and we give you a 22% royalty. Mango - would you not be OK with NVO realizing the market where to-date MNKD has not and does not have the resources to do all the big studies? The pps at $5.63 is a lot better than $1.06 but the right deal with NVO could easily take this to $20+. In the end if they want to sell both insulin human and aspart, I would be OK with that. I just don't know if they would want to sell V-Go, but I would offer it. I don’t see any need for a “Novolog DPI” when there is already Afrezza. I don’t think it would work as well either because those analogs are in hexameric form and have a ton of additives, including zinc, which is what the insulin molecules need to be held together. The absorption would be much too slow and I think with all the other stuff there would be some serious side effects. I think if Novo approached MannKind and just wanted to make a Fiasp DPI, MannKind would be better served to counter offer for Novo’s Icodec or strike a partnership to promote Afrezza + Icodec. |
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Post by sayhey24 on Feb 20, 2023 16:48:43 GMT -5
Mango - C256H381N65079S6 is bundled as a hexamer to stabilize it the same as C257H383N65O77S6 was a hexamer until it was put on Technosphere as a monomer.
Once C256H381N65079S6 is put on TS it would need the same additives as afrezza. All that stuff in Fiasp would go poof. Its mostly there to try and speed up absorption.
The absorption for insulin aspart as a monomer on TS should be about the same as insulin human on TS and it should get to the deep lung just like afrezza.
I am not understanding "MannKind would be better served to counter offer for Novo’s Icodec". I think Mike is trying to do something now with afrezza and icodec but I don't know how interested NVO is in working with MNKD. To do the proper trials requires money which MNKD may not have or want to spend. The best case is NVO is interested in afrezza but I doubt it but I hope I am wrong.
If I am right and I was Mike, I would pitch putting aspart on TS an follow the UTHR model.
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Post by lennymnkd on Feb 20, 2023 17:10:54 GMT -5
Icodec Afrezza, and let’s not forget the CGM.
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Post by mango on Feb 20, 2023 18:01:04 GMT -5
Mango - C256H381N65079S6 is bundled as a hexamer to stabilize it the same as C257H383N65O77S6 was a hexamer until it was put on Technosphere as a monomer. Once C256H381N65079S6 is put on TS it would need the same additives as afrezza. All that stuff in Fiasp would go poof. Its mostly there to try and speed up absorption. The absorption for insulin aspart as a monomer on TS should be about the same as insulin human on TS and it should get to the deep lung just like afrezza. I am not understanding "MannKind would be better served to counter offer for Novo’s Icodec". I think Mike is trying to do something now with afrezza and icodec but I don't know how interested NVO is in working with MNKD. To do the proper trials requires money which MNKD may not have or want to spend. The best case is NVO is interested in afrezza but I doubt it but I hope I am wrong. If I am right and I was Mike, I would pitch putting aspart on TS an follow the UTHR model. MannKind buying the rights for the basal. Maybe one day… I just don’t see the point in wasting time and resources on an Aspart DPI when there’s already Afrezza. |
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Post by agedhippie on Feb 25, 2023 14:11:37 GMT -5
Mango - C256H381N65079S6 is bundled as a hexamer to stabilize it the same as C257H383N65O77S6 was a hexamer until it was put on Technosphere as a monomer. Once C256H381N65079S6 is put on TS it would need the same additives as afrezza. All that stuff in Fiasp would go poof. Its mostly there to try and speed up absorption. The absorption for insulin aspart as a monomer on TS should be about the same as insulin human on TS and it should get to the deep lung just like afrezza. I am not understanding "MannKind would be better served to counter offer for Novo’s Icodec". I think Mike is trying to do something now with afrezza and icodec but I don't know how interested NVO is in working with MNKD. To do the proper trials requires money which MNKD may not have or want to spend. The best case is NVO is interested in afrezza but I doubt it but I hope I am wrong. If I am right and I was Mike, I would pitch putting aspart on TS an follow the UTHR model. Hexamers are only a problem until they hit the bloodstream as it converts in seconds. The problem is the movement of the hexamers through the subq layer and TS bypasses that (as do embedded pumps but they are very rare.) You can happily use RAA in an IV with exactly the same outcome as human insulin (I have seen it done - long story.) There is also a mechanic where you inject into a muscle and then it's fast (not as fast as IV, but only a few minutes) and it hurts a lot! The upshot of that is that you could add RAA to TS, but it's pretty pointless since the outcome would be the same. The part of the insulin molecule that has been modified was changed to accelerate passage through the sunq layer - and if you add RAA to TS that becomes redundant. In other words there is no reason for NVO to put aspart on TS, they may as well use Novolin R (human insulin) as it's a lot cheaper. At that point you are better off just selling Afrezza since that is Afrezza (TS + human insulin) to NVO which would be nice, but isn't going to happen. |
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Post by agedhippie on Feb 25, 2023 14:18:01 GMT -5
... I think if Novo approached MannKind and just wanted to make a Fiasp DPI, MannKind would be better served to counter offer for Novo’s Icodec or strike a partnership to promote Afrezza + Icodec. I assume you mean to make an Icodec DPI since there is no way Mannkind could afford to buy Icodec. Making Icodec DPI is a non-starter since the mechanism that makes icodec last a week (or Tresiba last a day) breaks down in the blood hence the administration restrictions on the Tresiba label. |
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Post by mango on Feb 25, 2023 21:48:11 GMT -5
... I think if Novo approached MannKind and just wanted to make a Fiasp DPI, MannKind would be better served to counter offer for Novo’s Icodec or strike a partnership to promote Afrezza + Icodec. I assume you mean to make an Icodec DPI since there is no way Mannkind could afford to buy Icodec. Making Icodec DPI is a non-starter since the mechanism that makes icodec last a week (or Tresiba last a day) breaks down in the blood hence the administration restrictions on the Tresiba label. I meant MannKind buy Icodec. How much would thatcost them? |
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Post by agedhippie on Feb 25, 2023 22:14:15 GMT -5
I assume you mean to make an Icodec DPI since there is no way Mannkind could afford to buy Icodec. ... I meant MannKind buy Icodec. How much would that cost them? I don't really know, but given that it's a replacement for Tresiba and the first weekly basal into the market I would think we are comfortably into the billions. Realistically they would not sell because it currently looks like their strongest seller and the basis of other products like Icodec and GLP-1 (in trials, but some way out) At this point their play book is going to be the same as Sanofi with Toujeo and Lantus - replace the older insulin with the newer one at the same price to maintain their edge. There is a Lilly weekly insulin in phase 3 trials at the moment I believe so NVO cannot afford to concede this territory. |
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Post by neil36 on Mar 23, 2023 13:33:44 GMT -5
Since MNKD attends these conferences and SVB Leerink (Securities) has one of the analysts who covers us, I was curious if the investment bank would stay in business. Impossible to know, but I was curious if the SVB collapse was triggering the liquidation of one of more large investments somewhere. A quick Google search returned this:
Is SVB Leerink part of Silicon Valley Bank?
In 2022, SVB acquired media and telecom research company MoffettNathanson. Further, SVB Leerink was rebranded as SVB Securities LLC. Following the collapse of Silicon Valley Bank in March 2023, the management of SVB Securities planned to buy back their firm from the parent group.
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