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Post by agedhippie on Jun 9, 2023 12:00:32 GMT -5
The most common side effects of Victoza® may include nausea, diarrhea, vomiting, decreased appetite, indigestion, and constipation. Talk to your health care provider about any side effect that bothers you or does not go away. These are not all the possible side effects of Victoza®. Does having to take it daily become more of a burden ? Those side effects are no different from every other GLP-1 analog. That is why I am skeptical that a TS delivered analog will be any different. The test MNKD did predated the availability of GLP-1 analogs and was only a single dose using GLP-1 rather than an analog. |
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Post by sayhey24 on Jun 9, 2023 12:36:52 GMT -5
If MNKD actually want to produce an inhaled GLP-1 then they can do it now. The patent on liraglutide (Victoza) expires this year and a generic is expected next year (at least two pharmas are lining up for this.) That will provide MNKD with a source of the API which they can then load onto TS. Of course they will still need to prove that you can take it more than once and still have no side effects, and compare effectiveness to one of the GLP-1 analog with Victoza as the likely candidate. Then there is question of funding, nobody is going to touch it this side of the data from that phase 2 trial, and then the time to market because you don't want to launch and be a couple of generations behind the market (try selling human insulin today, it sells on price but it's a fraction of the RAA market) The first issue is Mike does not have $1B. As I said before he spent his money on V-Go and he has put it in the sales reps bags. The second issue is I don't think until very recently Mike was thinking about TS GLP1 for the diet market. If I were to guess. Albert's $90B diet market prediction was a stunner for Mike. I think Mike was thinking TS GLP1 would have little or no advantage over a once a week shot for A1c control and spending $1B on it would be ridicules. I agree with that opinion as nothing beats afrezza for mealtime glucose control and we need to get the afrezza/glp1 trial which includes Mounjaro asap. The third is the MNKD model which is to license the platform and manufacture the product. MNKD needs a serious partner for this who want to be in the game. Lenny pointed to Pfizer and I think they are an excellent choice. If Albert is not interested maybe Doug Langa is. The article also says Novo is trying to develop an oral diet product. I am sure there are others too. Whats Merck doing? All three are in driving distance on Danbury. I think the big question is, is the market as big as Albert thinks and do the other BPs think Albert is correct? If so there should be multiple partnering opportunities and what prompted me to start this thread and start the conversation in public. Sports and Mango weighed in and don't like the entire thought of a diet drug. Lenny quickly pointed to Pfizer and their interest in the diet space. You have raised all kinds of objections which are extremely valuable in the discussion. Then again you first pointed out Mounjaro's true value over a year ago and that was its weight loss results. The reality is Pfizer's oral glp-1r development has a real issue. In their latest results they saw a 34% drop out at the higher levels which they need for the big weight reduction. MNKD has a serious potential solution which is FDA approved. That sounds like the perfect marriage. This product's potential dwarfs Tyvaso DPI or any other candidate MNKD is currently looking at. I even think its market potential is bigger than afrezza. jamanetwork.com/journals/jamanetworkopen/fullarticle/2805054?resultClick=1 |
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Post by agedhippie on Jun 9, 2023 15:34:59 GMT -5
... The third is the MNKD model which is to license the platform and manufacture the product. MNKD needs a serious partner for this who want to be in the game. Lenny pointed to Pfizer and I think they are an excellent choice. If Albert is not interested maybe Doug Langa is. The article also says Novo is trying to develop an oral diet product. I am sure there are others too. Whats Merck doing? All three are in driving distance on Danbury. ... The reality is Pfizer's oral glp-1r development has a real issue. In their latest results they saw a 34% drop out at the higher levels which they need for the big weight reduction. MNKD has a serious potential solution which is FDA approved... Novo already has a GLP-1 pill, Rybelsus, that had a TRx last month of 266k so it's safe to say they have got beyond trying to develop a pill  Pfizer has danuglipron, a pill, that has just finished Phase 2 trials. Lilly has a pill in phase 2 right now. My bet is that Pfizer drops danuglipron and goes with a second GLP-1 that they have ready for phase 2. These pharmas are all chasing the oral med market and you are extremely unlikely to pull them away to an inhaled version without compelling data which does not currently exist. MNKD does not have an FDA approved solution. You cannot put an existing GLP-1 on TS and carry over the approval because you have changed the delivery method so it becomes a new drug. If you could do that the approval of Afrezza would have been a lot faster and easier. Tyvaso could do this because it was already an inhaled drug. |
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Post by sayhey24 on Jun 9, 2023 17:58:12 GMT -5
... The third is the MNKD model which is to license the platform and manufacture the product. MNKD needs a serious partner for this who want to be in the game. Lenny pointed to Pfizer and I think they are an excellent choice. If Albert is not interested maybe Doug Langa is. The article also says Novo is trying to develop an oral diet product. I am sure there are others too. Whats Merck doing? All three are in driving distance on Danbury. ... The reality is Pfizer's oral glp-1r development has a real issue. In their latest results they saw a 34% drop out at the higher levels which they need for the big weight reduction. MNKD has a serious potential solution which is FDA approved... Novo already has a GLP-1 pill, Rybelsus, that had a TRx last month of 266k so it's safe to say they have got beyond trying to develop a pill Pfizer has danuglipron, a pill, that has just finished Phase 2 trials. Lilly has a pill in phase 2 right now. My bet is that Pfizer drops danuglipron and goes with a second GLP-1 that they have ready for phase 2. These pharmas are all chasing the oral med market and you are extremely unlikely to pull them away to an inhaled version without compelling data which does not currently exist. MNKD does not have an FDA approved solution. You cannot put an existing GLP-1 on TS and carry over the approval because you have changed the delivery method so it becomes a new drug. If you could do that the approval of Afrezza would have been a lot faster and easier. Tyvaso could do this because it was already an inhaled drug. We are talking weight loss. Rybelsus doesn't seal the deal. Novo has been working on a 4x supped up version. They announced last month that obese or overweight adults who took a once-daily 50 milligram dose of oral semaglutide for 68 weeks lost 15% of their body weight. The findings are based on results from a phase 3 study that involved 667 people. Of course there was a lot of vomiting. Its also not as good as Pfizer's glp-1r results. $10M is also round off for Doug Langa to do a proof of concept. Selling technosphere as an oral alternative I think is very doable. Albert wants "oral". He doesn't want the needle. I think with the proper marketing campaign, inhaling vs taking a pill can be very appealing. "Diet Pills" have always had a bad name. Putting the TS GLP1r in a pretty box, some great TikToc videos and inhaling is sexy. Additionally you a not vomiting like with the pill. And, think of the swag market for carrying cases, inhaler decorations, etc. As far as technosphere goes its a proven platform for two FDA approved drugs which are drug/device combos. Assuming Albert only considers me a little crazy and not a full on lunatic and he thinks $10M is worth a proof of concept and it pans outs, yes - Pfizers's new blockbuster drug will need to go through trials. A Pfizer TS GLP1r drug is years away but in the mean time Mike can work on selling afrezza to the kids and to the seniors. I will say IMO the Pfizer TS GLP1r drug would have a shorter development/approval time than what Albert is currently doing because the GI tract is not Alberts friend. If he wants to come to market with the pill first, OK. UTHR came to market with Tyvaso first and now look at what Tyvaso DPI is doing. Don't even get me started on afrezza approval. Technosphere was never the issue. In fact all Al was asking for was human insulin to be approved for human use. In Al's mind it was a slam dunk. The first CRL was about the cartridge packaging and the cleaning of the medtronic inhaler. It was a staling tactic. Al comes back with the Gen 2 inhaler and Pharma Bro shows up on Christmas with the Hamburgler's husband running Renaissance Technologies. Even the Chinese chemist thought afrezza approval was a done deal and he was never wrong. Then we had the hallway discussions during the Adcom that I just happened to overhear. Thank heavens Al pushed for the Adcom and we got the 13-1 & 14-0 votes to approve. |
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Post by agedhippie on Jun 9, 2023 18:36:05 GMT -5
... A Pfizer TS GLP1r drug is years away but in the mean time Mike can work on selling afrezza to the kids and to the seniors. I will say IMO the Pfizer TS GLP1r drug would have a shorter development/approval time than what Albert is currently doing because the GI tract is not Alberts friend..... There is no way that Pfizer is going to take an inhaled GLP-1 drug all the way through development and trials, as you point out, taking several years when they have two pill options on the ramps. Nobody know if TS GLP would have a better GI profile because it has never been studied so it's a gamble. The killer though is that timeline; by the time they got to market things will have moved on to GLP-1/GIP and possibly beyond (Lilly are already trialing a GLP-1/GIP/Glucagon triple therapy.) Nobody will want to roll that dice. As I said before if MNKD wants to do this then their best bet is to use a Victoza generic as the API since it's about to come off patent and take it through phase 2. I can't see that happening though because of the cost, time, and development cycle of the competitors (LILY vs. MNKD is not a fair fight) involved. I expect some nibbling around the edges for PR purposes. |
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Post by sayhey24 on Jun 10, 2023 7:31:19 GMT -5
... A Pfizer TS GLP1r drug is years away but in the mean time Mike can work on selling afrezza to the kids and to the seniors. I will say IMO the Pfizer TS GLP1r drug would have a shorter development/approval time than what Albert is currently doing because the GI tract is not Alberts friend..... There is no way that Pfizer is going to take an inhaled GLP-1 drug all the way through development and trials, as you point out, taking several years when they have two pill options on the ramps. Nobody know if TS GLP would have a better GI profile because it has never been studied so it's a gamble. The killer though is that timeline; by the time they got to market things will have moved on to GLP-1/GIP and possibly beyond (Lilly are already trialing a GLP-1/GIP/Glucagon triple therapy.) Nobody will want to roll that dice. As I said before if MNKD wants to do this then their best bet is to use a Victoza generic as the API since it's about to come off patent and take it through phase 2. I can't see that happening though because of the cost, time, and development cycle of the competitors (LILY vs. MNKD is not a fair fight) involved. I expect some nibbling around the edges for PR purposes. Wow - thanks for setting me straight "Nobody will want to roll that dice". I guess the entire idea of technosphere is ridiculous. What was Martine thinking? Its a good thing Mike bought V-Go so we can get out of the TS business. We have a $90B market opportunity and a phase 1 which showed no one died nor got a belly ache. We also have a bunch of BPs trying to get away from the shot for the diet market and all facing the same issue, their pills when loaded up with enough glp1 for weight loss cause a big belly ache. If its so ridiculous why should MNKD go it alone? As you say "I can't see that happening". I would think its ridiculous for Mike not to pick up his phone and try to partner. To date I am pretty sure Mike never considered the $90B market and we know he was not even aware of Peters work until last year. Then again how does Mike tell the board MNKD has been sitting on this and he was not aware and has not done anything? If he was not aware of it then it would not have been in any plans he presented to the board for the 2023 pipeline. Right now he has 6 months to make V-Go breakeven per the board mandate. I will admit, I am a bit crazy. I just remember Peter and Al discussing their TS GLP1 work and how excited both of them were. At the time I really did not appreciated it and never cared about glp-1s for diabetes because afrezza is better. But you got my interest up with Mounjaro's weight loss and then came TikToc and now 2.5M Ozempic scripts last month. Its hard to say its not a real market and we know the industry is scrambling for an oral solution. I don't think I am going to give up on this. I should have been more aggressive last year but its not too late. IMO its better money spent on this ridiculous idea with a $90B market potential than putting any more V-Gos in the sales reps bags. I also think your idea of Victoza is a good one as a fall back or to get the ball rolling for partnership discussions. Whats clear is in current form Victoza will not make the cut for weight loss. Victoza's typical dosages are 0.6 milligrams (mg), 1.2 mg, or 1.8 mg per day. In studies, people who took 1.2 mg of Victoza per day lost an average 2.1 kilograms (kg), or about 4.6 pounds (lbs.), after a year of treatment. People who took Victoza 1.8 mg per day lost an average of 2.5 kg (about 5.5 lbs.). Peter loaded 100mg of his glp-1 and said they did not have the nausea. I wonder what 100mg of Victoza on TS would do for weight loss? |
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Post by agedhippie on Jun 10, 2023 9:40:17 GMT -5
Wow - thanks for setting me straight "Nobody will want to roll that dice". I guess the entire idea of technosphere is ridiculous. What was Martine thinking? Its a good thing Mike bought V-Go so we can get out of the TS business. We have a $90B market opportunity and a phase 1 which showed no one died nor got a belly ache. We also have a bunch of BPs trying to get away from the shot for the diet market and all facing the same issue, their pills when loaded up with enough glp1 for weight loss cause a big belly ache. ... No, the idea that Technosphere is suitable for all drugs is what is ridiculous. Technosphere is suitable for some drugs hence Martine using it for Tyvaso (inhaled to inhaled). You seem to be falling into the trap where if all you have is a hammer, everything looks like a nail. Some drugs just aren't candidates. Nobody will bite based on that trial because: - It's a different drug, GLP-1 vs. GLP-1 analog (think human insulin vs. RAA) so it has different behavior - It was only taken once in a form that cleared rapidly (GLP-1) rather than building and maintaining a constant serum level (which requires an analog because of the half life of GLP-1) - Because it was only a single shot we can make no statement at all about the degree of associated weight loss, is it good or bad? - Taken once with fast clearance there were no side effects. Unsurprising if it is hardly in your system for long enough to modify your gut behavior. - Time to market. Putting this all the way through FDA approvals mean it will be a generation late Nobody will want to roll that dice. If MNKD want to develop this they will have to do the work themselves and I don't think they are that stupid. I will check back in a year to see who was right. |
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Post by prcgorman2 on Jun 10, 2023 10:22:39 GMT -5
You both seem to agree a TS GLP-1 is technically possible. One of you thinks it is worth pursuing with a partner. The other seems to think a partner is impossible. The idea that the ship has sailed for GLP-1 as an inhaled weight loss drug is not entirely persuasive because I can’t tell that Mounjaro changes the equation enough to be entirely dismissive of TS GLP-1 as an inhaled weight loss drug. I don’t see anything wrong with exploring the topic with potential partners if for no other reason than to remind potential partners about the value proposition of TechnoSphere as an inert carrier molecule permitting interesting forms of new or existing drugs such as GLP-1. I’m not pushing for TS-GLP-1, but I’m also not against it if a partner wants to take a flyer on a non-nauseating non-injection form to get some piece of a $90B market (or whatever huge market it’s looking to be).
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Post by lennymnkd on Jun 10, 2023 12:39:04 GMT -5
On the basis of current guideline recommendations, SGLT2i and GLP-1 RA with proven cardiovascular benefit are recommended in patients with T2D and ASCVD or those at high risk of cardiovascular events.
Not to mention 🤔
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Post by sayhey24 on Jun 10, 2023 13:12:37 GMT -5
Wow - thanks for setting me straight "Nobody will want to roll that dice". I guess the entire idea of technosphere is ridiculous. What was Martine thinking? Its a good thing Mike bought V-Go so we can get out of the TS business. We have a $90B market opportunity and a phase 1 which showed no one died nor got a belly ache. We also have a bunch of BPs trying to get away from the shot for the diet market and all facing the same issue, their pills when loaded up with enough glp1 for weight loss cause a big belly ache. ... No, the idea that Technosphere is suitable for all drugs is what is ridiculous. Technosphere is suitable for some drugs hence Martine using it for Tyvaso (inhaled to inhaled). You seem to be falling into the trap where if all you have is a hammer, everything looks like a nail. Some drugs just aren't candidates. Nobody will bite based on that trial because: - It's a different drug, GLP-1 vs. GLP-1 analog (think human insulin vs. RAA) so it has different behavior - It was only taken once in a form that cleared rapidly (GLP-1) rather than building and maintaining a constant serum level (which requires an analog because of the half life of GLP-1) - Because it was only a single shot we can make no statement at all about the degree of associated weight loss, is it good or bad? - Taken once with fast clearance there were no side effects. Unsurprising if it is hardly in your system for long enough to modify your gut behavior. - Time to market. Putting this all the way through FDA approvals mean it will be a generation late Nobody will want to roll that dice. If MNKD want to develop this they will have to do the work themselves and I don't think they are that stupid. I will check back in a year to see who was right. Aged - this was done over 15 years ago and its not my hammer. Its Peter Richardson and Al Mann's hammer. I just knew it existed and started asking what happened to it. What I do know is they were able to put it on Technosphere and the results blew them away. Those two being so excited is why I remembered that hammer was some where. I just find it hard to believe both Peter Richardson and Al Mann were ridiculous. Maybe you are right but I kind of remember near everyone thought Al would stop afrezza development after the Exubera cancer scare because afrezza would cause cancer too. Who knows maybe it would even blow up lungs. Can they load lotiglipron on TS. IDK but I bet they could. Can they load tirzepatide on TS. IDK but I bet they could. Would we see weekly results like Mounjaro probably not but I have no idea what we would see. Would we see results with lotiglipron to last the day, maybe. Right now Pfizer would be happy with 2 doses per day with daunuglipron and I bet we could load that on TS. What Peter said is they saw the same appetite suppression without the nausea. Whats interesting is I got some feedback that the big road blocks where the $1B and it may not be any better than Mounjarno at A1c. I did not get the impression that its a technical challenge or the idea is technically ridiculous. Since I don't care about A1c what I care about is the shot and the belly ache I am not yet deterred. The question is how much appetite suppression, over what period of time and what is the dose required. You are also correct it will take awhile. Then again so will all the pill development and a 34% drop out rate is a loser. They may never come to market. If we can get things moving while the pills are pre-Phase 3 even if the TS version comes later it can address that 34% who want to lose the weight but got too sick with the pills. Is it worth the $1B if all the TS GLP1 drug can do is 5% of the $90B market? Was it worth the 3 year development time for Tyvaso DPI? This should not take any longer as we have a bunch of glp1s and we have technosphere. This is not a technical challenge although you seem to imply loading the analogs on TS will not be possible which I doubt. We also have a business model developed with UTHR which should provide a framework for partnering discussions. Maybe you are right and MNKD is not this stupid. Maybe its just me who is. Please do check back in a year. |
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Post by agedhippie on Jun 10, 2023 13:55:11 GMT -5
... Nobody will bite based on that trial because: ... - Because it was only a single shot we can make no statement at all about the degree of associated weight loss, is it good or bad? ... ... What Peter said is they saw the same appetite suppression without the nausea. Again no. He did not see appetite suppression with or without nausea. What he actually said was; " We believe that MKC253 represents a novel approach to the use of GLP-1 as a prandial therapy for diabetes either alone, or in combination with prandial insulin. In addition, if we are able to demonstrate the same weight reduction or satiety effects seen with long-acting analogues of native GLP-1, MKC253 may have therapeutic potential in obesity."That work was never done so right now nobody knows. That's a showstopper, no partner is going to even look at this until that question can be answered. |
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Post by agedhippie on Jun 10, 2023 14:14:56 GMT -5
On the basis of current guideline recommendations, SGLT2i and GLP-1 RA with proven cardiovascular benefit are recommended in patients with T2D and ASCVD or those at high risk of cardiovascular events. Not to mention 🤔 Definitely. If you say that Trulicity is predominantly Type 2 then their TRx last month was 1.26 million. Looking at the growth charts I would guess (and it's just a guess) that in May Ozempic's sales would have been around 1.5 million. There is a big demand for GLP-1 from diabetics with GLP-1 being inserted into the step two position. Out of idle curiosity I looked at metformin TRx for last month, 7 million! |
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Post by sayhey24 on Jun 10, 2023 17:06:59 GMT -5
... What Peter said is they saw the same appetite suppression without the nausea. Again no. He did not see appetite suppression with or without nausea. What he actually said was; " We believe that MKC253 represents a novel approach to the use of GLP-1 as a prandial therapy for diabetes either alone, or in combination with prandial insulin. In addition, if we are able to demonstrate the same weight reduction or satiety effects seen with long-acting analogues of native GLP-1, MKC253 may have therapeutic potential in obesity."That work was never done so right now nobody knows. That's a showstopper, no partner is going to even look at this until that question can be answered. Aged - on this point I can say with 100% certainty that Peter was very excited about the weight loss possibility. It was not why they were testing glp1 on TS. But what they heard was all these people losing their appetite. The advantage they had was they were dosing up to 100 milligrams and did not get the nausea. I do have a quote from Peter somewhere about this but in the link provided and you posted above Pete mentioned about weight loss and the possibility of this being a weight loss drug. Why would he even bring that up when it was not what the phase 1 was about??? Back in 2007 I don't think many were looking at glp-1s for weight reduction. Something was unique about what Peter was seeing to say this. I know you want to blow it off as "nothing to see here" but I think Peter was confident at that point in time that they would have follow on trials targeting weight loss. The reality is we had the Exubera cancer scare, MNKD cash was running short and Al stopped everything except getting afrezza approved and building out the factory for the anticipated demand. You may be right about "no partner is going to even look at this until that question can be answered" but lets see. Is a $10m bet worth a $90B payoff? When $10M is round off for a BP like Pfizer it most likely is worth the bet. The next step is finding the partner. |
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Post by lennymnkd on Jun 10, 2023 17:19:14 GMT -5
On the basis of current guideline recommendations, SGLT2i and GLP-1 RA with proven cardiovascular benefit are recommended in patients with T2D and ASCVD or those at high risk of cardiovascular events. Not to mention 🤔 Definitely. If you say that Trulicity is predominantly Type 2 then their TRx last month was 1.26 million. Looking at the growth charts I would guess (and it's just a guess) that in May Ozempic's sales would have been around 1.5 million. There is a big demand for GLP-1 from diabetics with GLP-1 being inserted into the step two position. Out of idle curiosity I looked at metformin TRx for last month, 7 million! |
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Post by lennymnkd on Jun 10, 2023 17:19:48 GMT -5
Does metformin improve heart function?
Metformin's benefit on heart diseases was found in the UK Prospective Diabetes Study Group, in which a 39% lower risk of myocardial infarction (MI) was observed in metformin group compared to conventional group.
Not bad ! Any chance of a combo .. with GLP1 On TS … hey wishful thinking
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