|
|
Post by hellodolly on Jan 20, 2023 6:48:35 GMT -5
Actually yes  It's section 5.2 in the contract. Mannkind agree to help them set up manufacturing: 5.2c) ...The Manufacturing Information will be of sufficient detail to enable a reasonably experienced manufacturer to manufacture, assemble, test, operate, and service the Initial Product.
And agree that UTHR can buy the raw materials directly from the manufacturer to produce the drug: 5.2d) The Parties agree that United Therapeutics has the right under Section 2.2 to source all raw materials for the manufacture of Product from the suppliers of its choice...
(Section 2.2 allows UTHR to grant sub-licenses. That allows UTHR to have someone else manufacture all or part of the drug. It's also multi-tiered so they can grant sub-licenses below the sub-licensee) It's worth remembering that the expectation back when this started was that beyond the initial batch UTHR would manufacture the drug and Mannkind would get a royalty. In the interval UTHR sub-contracted manufacture to Mannkind on a longer basis which made sense for UTHR because it reduced their risk if something went wrong - they didn't want to be landed with a manufacturing plant for a poorly selling drug. This is why I think it is good that they are starting to exercise their options - they are now convinced it will be successful to the point where it makes sense to incur the cost of a manufacturing plant. It only gives them "the right" under 2.2 but it doesn't mean they will exercise that right. Certainly could be an offer from MNKD, in the future now that everyone sees the success of the launch and uptake by patients converting to the new formulation, to counter the agreement to amend it to more favorable terms for UTHR yet, still allow MNKD to manufacture the powders. "That allows UTHR to have someone else manufacture all or part of the drug."Under 2.2 it gives UTHR the right to have someone else become involved but again, see above. Say UTHR/MNKDs next collaboration is for CF. Also, during this period when UTHR could exercise these manufacturing rights, the PHII/III of clofazimine is potentially approved by the FDA. Add the possibility that the PHIII trials in India and PHIII Peds trials are complete. Now the decision becomes tricky and the question becomes more problematic (in a good sense). Does MNKD need to continue the manufacturing of Tyvaso? Can they continue? I believe the contract was written to benefit both parties in that nobody knew with 100% certainty how the future of MNKD, (TI) and UTHR (Tyvaso) would play out. Nothing more. nothing less. It's all about the lungs: Now that the picture is becoming more clear, UTHR might just out right buy MNKD as MNKD fits into the over all "orphan lung disease" treatment and therapeutic space...alongside UTHR. Not only do they fit in that same capacity, MNKD drugs are all manufactured, developed, tested, administered and marketed to be inhaled to where else...into the lungs. V-Go being the exception, that can be sold off if profitable. |
|
|
|
Post by sayhey24 on Jan 20, 2023 11:23:42 GMT -5
Dolly - If UTHR bought MNKD what would happen to our MNKD ProBoards? Could UTHR "buy" MNKD maybe. The time would be now but I know the one thing Mike struggles with is returning the $3B investment which has been made in afrezza. He knows he is sitting on something which has the potential of being really big "at some point".
MNKD now has some time and is now in a position where Tyvaso DPI will pay the bills and all MNKD needs to do is make product. Sales and growth are on UTHR. This was the exact "model" Al envisioned for MNKD and what Sanofi was suppose to do with afrezza. My expectation for India is low and their trial is a "re-do" of the Affinity 2 trial which showed superiority. The kids data is not being submitted to the FDA for at least another year. If UTHR/MNKD collaborate on CF we are 2 or 3 years away from an approved drug.
It seems pretty clear for 2023 Tyvaso DPI should have a breakout year. For disaster recovery UTHR needs at least 2 manufacturing sites. On a regular basis I doubt both sites will be fully operational. They should be able to produce more than enough powder out of Danbury and I think they also have filling capacity. Can UTHR save money by doing the manufacturing themselves IDK but why break what's not broken.
For 2023 Mike needs to figure out what he is doing with afrezza. Based on last weeks presentation it looked like no big plans for 2023. What they are expecting to take to ADA2023 is a question. They could take Longline's afrezza rescue tool and submit a paper on it. They should have enough data so no studies would be needed to coble something together and lay the framework for a change to the SoC by positioning afrezza as the standard of care in addressing those out of control highs and not chasing with their RAA. I think this would be very doable and should not cost very much but clearly not associated with "orphan lung" and outside of current UTHR interests. Could it be a big deal for the T1 SoC, I think so. It could potentially have every T1 getting prescribed afrezza and keeping it in their "tool bag" for those occasions when they have these highs.
Another thing which Mike could do for ADA2023 is put a paper together on "Treat to Target" for T2s which could outline a new Standard of Care protocol targeting those T2s >9 A1c which currently get treated with insulin. I don't know if they have enough existing data but they might with the exception of adding GLP1s into this protocol. I think Steve Edelman has some info on "Treat to Target" put together but I don't think it provided an option of adding a GLP1 for weight loss. Adding the GLP1 could be a nice discussion point for ADA2023 if he started a pilot study. The thing is, if he could get some traction and by some miracle got "Treat to Target" added into the T2 section of the SoC, the potential sales are probably bigger than Tyvaso DPI. Selling to UTHR would then make little sense and Mike might be able to return the $3B investment but probably more. Of course there are a lot of "ifs" and "maybes" and a miracle but its a very doable target which we already know afrezza would work great at and its not disrupting the entire $40B market so it has a chance.
|
|
|
|
Post by porkini on Jan 20, 2023 11:57:09 GMT -5
Dolly - If UTHR bought MNKD what would happen to our MNKD ProBoards? Could UTHR "buy" MNKD maybe. The time would be now but I know the one thing Mike struggles with is returning the $3B investment which has been made in afrezza. He knows he is sitting on something which has the potential of being really big "at some point". Maybe become the MUTHR of all Proboards?  |
|
|
|
Post by longliner on Jan 20, 2023 12:02:04 GMT -5
Dolly - If UTHR bought MNKD what would happen to our MNKD ProBoards? Could UTHR "buy" MNKD maybe. The time would be now but I know the one thing Mike struggles with is returning the $3B investment which has been made in afrezza. He knows he is sitting on something which has the potential of being really big "at some point". Maybe become the MUTHR of all Proboards? Watch it Porky, if Martine thinks this band of misfits is part of the package it'll kill the deal for sure.  |
|
|
|
Post by hellodolly on Jan 20, 2023 12:58:44 GMT -5
Dolly - If UTHR bought MNKD what would happen to our MNKD ProBoards? Could UTHR "buy" MNKD maybe. The time would be now but I know the one thing Mike struggles with is returning the $3B investment which has been made in afrezza. He knows he is sitting on something which has the potential of being really big "at some point". MNKD now has some time and is now in a position where Tyvaso DPI will pay the bills and all MNKD needs to do is make product. Sales and growth are on UTHR. This was the exact "model" Al envisioned for MNKD and what Sanofi was suppose to do with afrezza. My expectation for India is low and their trial is a "re-do" of the Affinity 2 trial which showed superiority. The kids data is not being submitted to the FDA for at least another year. If UTHR/MNKD collaborate on CF we are 2 or 3 years away from an approved drug.It seems pretty clear for 2023 Tyvaso DPI should have a breakout year. For disaster recovery UTHR needs at least 2 manufacturing sites. On a regular basis I doubt both sites will be fully operational. They should be able to produce more than enough powder out of Danbury and I think they also have filling capacity. Can UTHR save money by doing the manufacturing themselves IDK but why break what's not broken. For 2023 Mike needs to figure out what he is doing with afrezza. Based on last weeks presentation it looked like no big plans for 2023. What they are expecting to take to ADA2023 is a question. They could take Longline's afrezza rescue tool and submit a paper on it. They should have enough data so no studies would be needed to coble something together and lay the framework for a change to the SoC by positioning afrezza as the standard of care in addressing those out of control highs and not chasing with their RAA. I think this would be very doable and should not cost very much but clearly not associated with "orphan lung" and outside of current UTHR interests. Could it be a big deal for the T1 SoC, I think so. It could potentially have every T1 getting prescribed afrezza and keeping it in their "tool bag" for those occasions when they have these highs. Another thing which Mike could do for ADA2023 is put a paper together on "Treat to Target" for T2s which could outline a new Standard of Care protocol targeting those T2s >9 A1c which currently get treated with insulin. I don't know if they have enough existing data but they might with the exception of adding GLP1s into this protocol. I think Steve Edelman has some info on "Treat to Target" put together but I don't think it provided an option of adding a GLP1 for weight loss. Adding the GLP1 could be a nice discussion point for ADA2023 if he started a pilot study. The thing is, if he could get some traction and by some miracle got "Treat to Target" added into the T2 section of the SoC, the potential sales are probably bigger than Tyvaso DPI. Selling to UTHR would then make little sense and Mike might be able to return the $3B investment but probably more. Of course there are a lot of "ifs" and "maybes" and a miracle but its a very doable target which we already know afrezza would work great at and its not disrupting the entire $40B market so it has a chance. Sayhey - The remaining terms are until 2031 so, I'm feeling more and more confident that MNKD will be standing on their own two feet and probably off and running by then with Clofazimine, CF, kids Afrezza and India/Brazil, not to mention something with RLS in either epilepsy and/or anxiety disorders. The 2031 date was the impetus for the ramble this morning. I too liked the idea of Afrezza becoming some sort of "rescue tool" for those pesky excursions or, even for the sudden urge to eat a pint of ice cream just knowing I got my Afrezza in my pocket. Then it dawned on me that the cabal would peg Afrezza deeper into the "niche" category but, I hadn't thought of MC laying the framework to change the ADA SoC to include Afrezza as an RI rather than patients using their RAAs. In fact, the epiphany for me came when I realized (after reading your comments) that MNKD could do an "end around" the slow uptake using the current business model by dramatically increasing users (Rx) if there was a change in the SoC and Afrezza became a RI first...then, convince patients they can use Afrezza for all their meals. At that point, selling to UTHR becomes a barrier because MNKD won't be affordable. |
|
|
|
Post by sayhey24 on Jan 20, 2023 13:53:33 GMT -5
Dolly - my thoughts exactly. I could see two new products with at least one being bigger than Tyvaso DPI.
Afrezza-R which is sold in a new box with some mix of small and medium cartridges and a label targeting bringing down the high. This product should be in every T1s tool kit including Ages. A focused, targeted effort in getting this in the SoC should be doable near term. They have all the info and data its a matter of putting the study paper together, presenting at ADA2023 and lobbying the ADA. I think they can get this one by BP as its as you say a niche use. Of course the implications are now every T1 has afrezza and every endo has now prescribed afrezza. Who knows maybe they start using it as they main prandial insulin and avoid the out of control high to start with.
Afrezza-T3 (Treat to Target) would take a bit more work but is very doable as its hitting the T2s who are being put on insulin day 1 anyway and not the antiglycemics. If they can have this added as a new "protocol" in the T2 SoC we now have a homerun. It would also get the support of our CGM friends who can now get medicare to cover most of the cost of their CGM as the protocol would require CGM use. It would target a specific BG number and then keep the T2 there for a period of time - a couple of weeks, a month, etc. as their doctor best thinks best based on their starting BG and overall health. For example if they are at 400, you target 350 and keep them there for a month and then lower to 300, 250, etc. down to 100. Add in the GLP1 and we have the support of Nova and Lilly.
If Mike could make that happen, at that point it may make more sense for Mike to buy UTHR. He is going to need another manufacturing facility.
|
|
|
|
Post by agedhippie on Jan 20, 2023 16:40:03 GMT -5
There are two issues with the rescue inhaler idea.
The first is that there is no trial data to quantify the benefit - yes it will drop your level quickly, but in the grand scheme of things how much does it matter? Benefits not features - you have to be able to show the benefit. And no, saying but its obvious that it's better because it gets you to baseline faster doesn't does not quantify the benefit. Will people use it when they should, what is the reduction in complications, what does compliance look like, those sort of questions.
The second issue is that Type 1 diabetics are being pushed to use hybrid loop pumps these days. External insulin sources do not play nice with these since the pump algorithm assumes that the pump is the sole source of insulin so it's still going to try and correct the level, and suddenly you have an excess of insulin flying around... This isn't a problem with the old style pumps, or with pens, but those aren't were everyone is going.
|
|
|
|
Post by lennymnkd on Jan 20, 2023 18:24:21 GMT -5
Why would the pump produce more insulin, when affrezza provided the adequate amount..
|
|
|
|
Post by longliner on Jan 20, 2023 19:05:29 GMT -5
Why would the pump produce more insulin, when affrezza provided the adequate amount.. Have you ever known agedhippie to put anything forward regarding afrezza that wasn't a roadblock?  |
|
|
|
Post by agedhippie on Jan 20, 2023 19:55:13 GMT -5
Why would the pump produce more insulin, when affrezza provided the adequate amount.. Because the pump doesn't know about the Afrezza so it continues as if that never happened. Suppose you were at 300; the pump decides that you need 10u to get you back to the baseline and starts giving it to you, within about 5 minutes it will have given you most of the dose. At the same time you take Afrezza manually. Now you have a lot more insulin than you need and are almost certainly going to go low. You would have the same problem if you used a pen. If the pump was manual you could offset dose to allow for the Afrezza because you know about it, but the pump is automated... |
|
|
|
Post by agedhippie on Jan 20, 2023 19:56:13 GMT -5
Why would the pump produce more insulin, when affrezza provided the adequate amount.. Have you ever known agedhippie to put anything forward regarding afrezza that wasn't a roadblock? Somebody has to answer the questions |
|
|
|
Post by dh4mizzou on Jan 20, 2023 20:34:35 GMT -5
Why would the pump produce more insulin, when affrezza provided the adequate amount.. If the pump was manual you could offset dose to allow for the Afrezza because you know about it... Aged, Sounds like you're describing the V-Go to me. |
|
|
|
Post by lennymnkd on Jan 21, 2023 7:27:38 GMT -5
Sounds like you need a CGM , Afrezza is all about the CGM .. if the CGM didn’t exist , people would be saying
If we only had a device….CGM …THAT WOULD MONITOR OUR BLOOD SUGAR LEVELS.. then Afrezza would be
Perfect in every scenario… WELL GUESS WHAT ! we have have it . The whole thing is not as frustrating as it is
INSANE .
|
|
|
|
Post by sayhey24 on Jan 21, 2023 7:51:42 GMT -5
There are two issues with the rescue inhaler idea. The first is that there is no trial data to quantify the benefit - yes it will drop your level quickly, but in the grand scheme of things how much does it matter? Benefits not features - you have to be able to show the benefit. And no, saying but its obvious that it's better because it gets you to baseline faster doesn't does not quantify the benefit. Will people use it when they should, what is the reduction in complications, what does compliance look like, those sort of questions. The second issue is that Type 1 diabetics are being pushed to use hybrid loop pumps these days. External insulin sources do not play nice with these since the pump algorithm assumes that the pump is the sole source of insulin so it's still going to try and correct the level, and suddenly you have an excess of insulin flying around... This isn't a problem with the old style pumps, or with pens, but those aren't were everyone is going. I am glad we can start off 2023 as we started off 2022 and agree to disagree. How much does it matter for the T1 to get back into range, IDK but I think a lot. Why else do they currently chase the high giving multiple RAA injections only to go low, then take some sugar, then go high? Steve Edelman has a video on this. I think he called it "Rage Bolusing". I would think the ADA has stats on this MNKD can use for the baseline. I would also hope Mike can put together a paper, a "study" and a "Seeing is Believing" demo for ADA2023. I think I see two questions in this. Can Mike move the SoC to include the T1 rescue protocol? How big is the market? I think even the hybrid loop users may want to keep the afrezza in their "tool bag" even if they never use it. Maybe a friend will. Then again we know the JDRF studied afrezza with the hybrid loop and concluded the best control they got with the hybrid loop was using afrezza at meals. What many have said on social media is after using afrezza they would never go back to a pump. As Mike said last week when he went to the diabetes camp - none of the kids want the pumps. They take them off, put them on, take them off again to go swimming, its a mess. I think once the kids get approved in 2024 the days of kids using pumps will be ending. Mike proposed little on afrezza last week for 2023 at JP Morgan. This is something which should be a doable focused 2023 target and will not bankrupt MNKD. I bet Ginger Vieira would be willing to write another article just on this and MNKD trying to add this protocol to the SoC. She has already discussed its use in other articles and said "I’ve found that I’m also able to correct most high blood sugars within 60 minutes of using it, and it makes it possible for me to correct quickly and land within my target range." beyondtype1.org/inhaled-insulin-diabetes-management/ |
|
|
|
Post by sayhey24 on Jan 21, 2023 8:05:24 GMT -5
|
|
