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Post by rrtzmd on Oct 27, 2015 23:39:56 GMT -5
Does it really matter whether Sanofi walks away or not? At present, either way looks rather dark. Consider that, as it stands now, while granting they may be doing something behind the "curtain," publicly SNY appears to be putting little effort into doing the sorts of things that afrezza needs to attract more customers. In particular, Sanofi has yet to announce any trials that might demonstrate afrezza is better than its current "non-inferior" designation. Until that happens, significant reimbursement at a price providing a worthwhile profit margin is highly unlikely. This then translates into perhaps years of losses for MNKD and increasing debt as it utilizes the Sanofi loan facility. Milestone payments ostensibly are out there somewhere, but investors aren't allowed to see them. Nevertheless, we can make some inferences. According to the last 10-Q, MNKD said in reference to Deerfield milestone payments: "In the first quarter of 2015, the Company determined that it was probable that the first commercial sales related milestone would be achieved within the next twelve months." Per the Deerfield agreement: Deerfield agreement...that next milestone was $50,000,000 in afrezza revenues. In other words, MNKD expected to see 50 million in afrezza revenues within the first 12 months of introduction. If that was the case, then one might reasonably assume that the Sanofi milestones were determined along similar lines. Obviously, at its current rate -- using the symphony numbers provided in the "afrezza script counts" section -- it appears revenues likely won't reach 50 million for at least a couple of more years. If the inference is correct, logically Sanofi should not walk away. The debt is secured by literally everything MNKD owns. SNY controls sales and marketing, but doesn't "need" afrezza and it is wealthy enough that it can simply wait. It shares profits but since there aren't any, that's no loss. It shares expenses, but since it controls those, it can be as tight fisted as it desires. If afrezza sales suddenly "explode," SNY does fine. If they don't, MNKD "withers" away until SNY decides it wants to package MNKD's assets for shipment back to France. It will certainly be very interesting to see how MNKD management responds to events over the next year. |
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Post by rrtzmd on Oct 27, 2015 11:44:07 GMT -5
I believe the reason they chose afrezza is because praluent itself is injected and they likely don't want any skin reactions that might arise from injected insulin to be blamed on praluent: "The most common side effects of Praluent include itching, swelling, pain, or bruising where injection is given..." Furthermore, you seem to have a knack for completely disregarding positive or possibly positive factors that might not suit your personal interpretation of the story. ...and, if I might add, a faulty logic, as your statement and quotation clearly demonstrate. I'm afraid I don't see where the logic is faulty. In a trial, all adverse events are recorded under a single heading such as "skin and subcutaneous tissue disorders." The etiology of the adverse event is not assessed nor recorded, just the numbers that occur. Adverse events can affect payor reimbursement decisions. Hence, SNY wants to avoid as many as they can. Praluent itself is already known to produce skin reactions. Insulin injections are also know to produce skin reactions. Eliminating injected insulin from the protocol eliminates one source of skin reactions -- simple as that. |
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Post by rrtzmd on Oct 27, 2015 11:31:36 GMT -5
I cannot agree given the objectives: "To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in patients with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy. To evaluate the safety and tolerability of alirocumab in patients with diabetes treated with insulin." Whatever the results, praluent will get the limelight for anything positive. Sanofi may even resort to blaming afrezza for any bad results. I believe the reason they chose afrezza is because praluent itself is injected and they likely don't want any skin reactions that might arise from injected insulin to be blamed on praluent: "The most common side effects of Praluent include itching, swelling, pain, or bruising where injection is given..." Afrezza will be blamed? What are you talking about again? This seems like another attempt to diffuse a good news story? You seem to have a glass empty type of view of all things Afrezza... No, I'm merely assessing the possibilities. Praluent is already approved, so Sanofi, with this study, is most likely looking for justification to move up the "tier" ladder in order to improve reimbursement from third party payors. In that aspect, this trial is similar to the large "real life" trial they are doing for toujeo. Like I said, SNY likely wanted to avoid injected insulin in order to prevent praluent getting the blame for any skin reactions caused by insulin injections, hence avoiding "adverse reactions" that insurance companies can hold against the drug. Now, the thing is, if the trial is successful and praluent works, it will be given all the credit since it is a "big ticket" item with all of the profit going to SNY. On the other hand, if it doesn't work out in praluent's favor, it wouldn't surprise me if SNY went looking for something to blame it on -- that happens frequently after failed trials -- hence the possibility that afrezza may find itself being the one getting blamed. |
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Post by rrtzmd on Oct 27, 2015 9:59:05 GMT -5
If the Proluent/Afrezza combination is the one that proves superior than any other Proluent combination, then its not Proluent that will be in the spotlight, it will be Afrezza. I cannot agree given the objectives: "To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in patients with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy. To evaluate the safety and tolerability of alirocumab in patients with diabetes treated with insulin." Whatever the results, praluent will get the limelight for anything positive. Sanofi may even resort to blaming afrezza for any bad results. I believe the reason they chose afrezza is because praluent itself is injected and they likely don't want any skin reactions that might arise from injected insulin to be blamed on praluent: "The most common side effects of Praluent include itching, swelling, pain, or bruising where injection is given..." |
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Post by rrtzmd on Oct 26, 2015 22:18:23 GMT -5
I'm disappointed that they didn't provide more details as to how the debt itself was finally resolved. Investors are still left hanging a few more days until the 10-Q comes out. Sorry you are disappointed, we know a fair bit about how it was resolved. I personal think it was a prefect announcement, just my humble opinion. I can't agree. The "perfect" announcement would have been one back in early August that the debt was settled as planned per MNKD's declaration on July 29 to the effect that $28 million would be rolled over into new, 2018 debt; that $57 million would be converted into MannKind equity; and that $15 million would be repaid with company cash. Instead, what investors got was an announcement two days before the debt was due that the refinancing was delayed, which, in turn, led to Goldman Sachs issuing a "note" that the delay was due to how slowly the Afrezza sales launch was "ramping." Then came plan "B" with the delay announcement on August 13: "$28 million rolled over into new, 2018 debt (done); 2. $8 million converted into MannKind equity (done); 3. $32 million converted into MannKind equity (ongoing); and 4. $32 million repaid with company cash (ongoing).They then said that $32 million of that was extended to Sept. 30. At that time, MannKind will attempt to exchange it for equity." That was followed a few days later by the headline, "MannKind Financial Woes Escalate on Failed Debt Settlement." And when September 30 rolled around, did MNKD issue a PR reassuring everyone that the debt issue was resolved? No, instead investors were treated to a newspaper story to the effect that MNKD had laid off a third of its employees as a consequence of slow afrezza sales. Indeed, no point could I find anywhere that the 9 million shares were ever an issue for MNKD's management, so why did they bother with a press release for them now? Instead, everyone is stuck waiting to see how Plan "B" worked out and its effects until the 10-Q. I still think a PR detailing how they managed Plan "B" would have been more useful. |
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Post by rrtzmd on Oct 26, 2015 10:19:54 GMT -5
Will someone please google, phase III trials afrezza uk. It appears there is more information if you have access to this site. Thank you, Perry.
There are no phase 3 trials currently using afrezza. The website you refer to, and which someone else has provided a link to, only indicates the stage at which afrezza currently exists in the UK. In other words, it hasn't been approved and they are waiting for submission of the phase 3 data there. Once Sanofi applies for approval by the EMA, the phase 3 data will be submitted to the "Committee for Medicinal Products for Human Use," which will evaluate the data and make recommendations to the EMA. Once that has happened, it will be published by the EMA here: pending EC decisions |
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Post by rrtzmd on Oct 26, 2015 8:54:38 GMT -5
MannKind Announces Termination of Stock Lending Agreement VALENCIA, Calif., Oct. 26, 2015 (GLOBE NEWSWIRE) -- MannKind Corporation (NASDAQ:MNKD) today announced the return of 9,000,000 shares of its common stock that were loaned to Bank of America, N.A. pursuant to a stock lending agreement dated August 18, 2010. The stock lending agreement was entered into to facilitate the establishment of hedge positions by investors in MannKind's offering Senior Convertible Notes due 2015, which closed on August 24, 2010. The stock lending agreement terminated a specified number of days following the date as of which the entire principal amount of Senior Convertible Notes due 2015 ceased to be outstanding and MannKind had settled all payments and deliveries in respect of such convertible notes, which occurred on August 17, 2015. About MannKind Corporation MannKind Corporation (Nasdaq:MNKD) focuses on the discovery and development of therapeutic products for patients with diseases such as diabetes. MannKind maintains a website at www.mannkindcorp.com to which MannKind regularly posts copies of its press releases as well as additional information about MannKind. Interested persons can subscribe on the MannKind website to e-mail alerts that are sent automatically when MannKind issues press releases, files its reports with the Securities and Exchange Commission or posts certain other information to the website. I'm disappointed that they didn't provide more details as to how the debt itself was finally resolved. Investors are still left hanging a few more days until the 10-Q comes out. |
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Post by rrtzmd on Oct 25, 2015 19:17:17 GMT -5
Maybe someone is interested: - NAVB made the dual listing with TASE last month (September 8, 2015). - NAVB is highly shorted. I think the chart is very interesting. Well, I looked at the three month chart on NAVB: three month NAvB chartUp to August 24, it was trading about $1.60. It then began a steady and somewhat suspicious -- under the circumstances -- rise to about $2.00 when the Tel Aviv listing was announced 9/2. NAVB actually started trading in Tel Aviv on September 8. It closed at $2.28 that day. The highest it got was $2.41 on 9/18. And since the beginning of October, it has "dribbled" down to its closing price on Friday of $1.91. So the impact -- at least short term -- of actual trading in Tel Aviv doesn't appear too dramatic. |
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Post by rrtzmd on Oct 25, 2015 19:03:00 GMT -5
After Sanofi, is Teva our next partner? Mannkind Corp. Technosphere® Technology Pipeline • Leading Target Indications - Pain Management*
- Pulmonary Disease*
- Oncology
- Other
*---Targets Selected for 2015 Teva Acquires Labrys Biologics For Positioning In Pain Market Teva currently has a diverse group of approved treatments and investigational drugs for pain, migraine, and cancer. www.clinicalleader.com/doc/teva-acquires-labrys-biologics-for-positioning-in-pain-market-0001 Why would listing in Tel Aviv have anything to do with Teva? Teva has made deals with and/or bought outright dozens of companies over the years -- have any of them been preceded by listing in Israel before the deal was made? Teva just bought Rimsa for 2 billion, I'm pretty sure Rimsa didn't list in Tel Aviv beforehand. |
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Post by rrtzmd on Oct 22, 2015 13:24:16 GMT -5
rrtzmd you're getting warm, just go a little further and you'll come to the same conclusion that I have. The amphistar deal is going to go down as one of the many big blunders MNKD management has made with this product. They made an obscene commitment when they had no basis for volume and they did this just prior to signing a deal with SNY. I understand the need to make sure they have access to materials for production however all along we've been told they have inventory from the pfizer insulin purchase. Even after making the commitment they didn't address how this commitment would be met while writing the SNY agreement. Again, outstanding product, tremendous potential with incompetent management at the helm. The obligation is only an issue during the slow ramp (2015) and hopefully not a drag once we get going in 2016. And it's not one that will break the bank so long as sales make it onto that ramp within a reasonable time frame. Also, at this stage MNKD does not have FDA permission to use the Pfizer insulin, although they continue to maintain and monitor it for potential submission later as an FDA approved source of supply. I was totally unaware of this: "Also, at this stage MNKD does not have FDA permission to use the Pfizer insulin, although they continue to maintain and monitor it for potential submission later as an FDA approved source of supply." Is that written in any official document or press release? Why hasn't the FDA approved it? Can approval be expected at some point? How old is it now? If they can't use it, can they sell it? |
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Post by rrtzmd on Oct 20, 2015 20:20:19 GMT -5
What makes me go "hmmmm' is that screenshots 1 & 2 of peppy's three screenshots for Afrezza and Toujeo both list UK Availability in 2015. I believe this is the most recent document: 2015PrescribingOutlook-NewMedicines-FINALIt says, "UK availability: Uncertain," on page 37. They also add: "Implications: Needle-free insulin will be attractive to patients, especially those with needle phobia or problems injecting. Exubera (an inhaled insulin formulation launched in 2006 but discontinued due to poor sales) was not approved for use by NICE on cost-effectiveness grounds. Financial: Cost of Afrezza in US is $7.54/day (based on 12units/day). In 2006, Exubera cost £1,100 annually." That seems to imply a potential cost barrier to approval. |
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Post by rrtzmd on Oct 20, 2015 11:24:42 GMT -5
"Airways have distinct and very important laminar and turbulent properties."  Yes! To the flow of AIR! I agree entirely! You DO understand that the OP was talking about the specific properties of the afrezza particles and how their shape, etc, made them "non-aerodynamic" and thereby affected distribution? The relatively TINY amount of TINY afrezza particles CANNOT affect the "laminar and turbulent properties" of the AIR FLOW and, therefore, are practically irrelevant to the particles' distribution. You would get about the same distribution if you inhaled smoke or any other fine particulate. "...basis of gas exchange..." No! Gas exchange is determined by the PARTIAL pressures of the gases. Partial pressure is analogous to concentration and has nothing to do with the airway pressure. Oxygen, for example, simply moves down a gradient from an area of higher partial pressure/concentration in the alveolus to an area of lower partial pressure/concentration in the blood. As far as "gibberish," are you referring to this: "The only IMPORTANT place where particle properties matter is in the "de-agglomeration" from inside the cartridge. It's important that afrezza gets broken up as much as possible into the smallest fragments possible in order to assure maximum distribution. Consequently, things like electrostatic attraction, geometry, weight, etc, contribute to how well it "de-agglomerates." But once broken into its smallest fragments and in the air flow, nothing specific to the particles matters much in terms of affecting distribution to the distal lung." That is not "gibberish." "De-agglomeration" is "The process of breaking up or dispersing that which has agglomerated, or aggregated, or clustered together." That is what happens to the afrezza in the cartridge as the Venturi effect produces a vacuum to suck the afrezza up. I would think it would be obvious that the specific properties of the particles could have significant effects on that process. Sorry, but there is no "gibberish" there. |
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Post by rrtzmd on Oct 20, 2015 11:08:50 GMT -5
I am not really sure what the argument is here. Surely rrtzmd is not suggesting that Afrezza does not reach the deep lungs. Is the suggestion that the dreamboat design is somehow inferior and substandard? It is well know that some of the TI powder is left in the mouth and throat, but that is accounted for in the cartridges that do not contain 4 units of insulin, but a 4 unit equivalent, for example. I am not a scientist, but that bong gif did remind me of a certain device made by Nektar Therapeutics. The OP made the assertion, "So if you wanted maximum disbursement of your drug that has to go through a bunch of twists and turns, would you want it shot out of a cannon...or would you want it as slow as possible to get where it needs to go." He further asserted that afrezza had specific qualities that made it "non-aerodynamic" and which resulted in it somehow "slowing down." However, that's simply incorrect. The afrezza particles are TINY relative to the total mass of air. Once they are suspended in the airflow, they move at the same speed as the air! Hand someone a baseball and time a 100 yard dash. Then hand them a football or an egg -- would that affect how fast they ran the 100 yards? The "disbursement" is determined primarily by turbulence at each bifurcation. That's why so much afrezza gets deposited at the back of the throat -- the air flow slamming into the back of the throat not only causes direct impaction of the afrezza particles, but also generates a great deal of turbulence which contributes to the particles getting "tossed out" of the air flow and against the walls of the airway. That's why 60% of the afrezza in each cartrdige NEVER reaches the alveoli. The "energy" of the airflow is dissipated by turbulence at each bifurcation. A "bong" would be more effective than a simple inspiration, because it would generate a larger amount of energy that overcomes the reduction caused by the turbulence. Like I said, the particle's shape, etc, IS important in effective "de-agglomeration" of afrezza while inhaling but otherwise but does little to affect the distribution. |
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Post by rrtzmd on Oct 19, 2015 22:47:25 GMT -5
rrtzmd, As for many of the things you say above I respectfully disagree with much of what you are saying. Be it about the 'uninformed' Mannkind expert, the reason for particle aerodynamics mattering in turbulent vs laminar airways (where does this matter and in what part of the airway and you didn't mention electrostatic interactions), the simply very wrong misunderstanding of laminar vs turbulent flow in a respiratory tree (and complete misunderstanding of how air does get to the alveoli. Hint: pressure gradients), explanation for need of aero chamber in many inhalation devices (not relavant to TS) and why the way they use the Ventori effect in the Dreamboat really is very important (as Erzasfund is possibly referring to). Not that I want to be the scientific police (as this has very little bearing on the true prospects of Afrezza which we all know works regardless of how it works) and this may seem harsh but much of what you say sounds more like a scientific 'word cloud' than a scientific explanation. We seem to be having a run on this stuff recently! Airways are neither "turbulent" or "laminar." Air FLOW, on the other hand, is. Laminar air flow is AROUND an object and obviously doesn't apply to the lungs. Turbulent airflow, on the other hand, is important because of the bifurcations as I described. The particles of afrezza within the in the air flow are TINY relative to the total mass of the air flow and CANNOT affect the changes in resistance caused by bifurcations. For example, imagine what would happen if you dumped a bunch of sawdust into the middle of a river. Would the size, shape, interactions, etc, affect the overall movement of the particles within the flow of the river? The only purpose of the Venturi effect is to disperse the afrezza powder. That is simply ALL it can do. The properties of the particles themselves can affect how the powder "de-agglomerates" but the Venturi does NOTHING more than create a vacuum to suck up the particles. And "pressure gradients"? What do you think a pressure gradient does to a tube of air -- "Hint": blow on a straw and feel what comes out the other end. When you inhale, the pressure gradient is produced by expansion of the chest wall lowering the pressure inside the chest cavity and causing air to rush in until there is no longer a gradient. Try for a few minutes to breathe without moving your chest wall and see what happens. The only IMPORTANT place where particle properties matter is in the "de-agglomerization" from inside the cartridge. It's important that afrezza gets broken up as much as possible into the smallest fragments possible in order to assure maximum distribution. Consequently, things like electrostatic attraction, geometry, weight, etc, contribute to how well it "de-agglomerates." But once broken into its smallest fragments and in the air flow, nothing specific to the particles matters much in terms of affecting distribution to the distal lung. |
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Post by rrtzmd on Oct 19, 2015 20:30:39 GMT -5
If you study the deceptively simple looking Dreamboat device you will see how the mouthpiece is flared. This is where the Venturi effect is employed to precisely regulate the speed at which the TI powder enters the lungs. No, that is incorrect. The Venturi effect increases the speed at which the air is moving in the channel but causes a decrease in pressure behind the channel and serves only to facilitate dispersal of the particles from the cartridge. This video illustrates well how it works, except he uses a blower while a patient uses inhalation: how venturi effect is employed to disperse powder
The initial speed of the powder is depends on the rate of airflow with inspiration and the subsequent loss of velocity depends on the increasing turbulence effected by the bifurcations. |
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Yes! To the flow of AIR! I agree entirely! You DO understand that the OP was talking about the specific properties of the afrezza particles and how their shape, etc, made them "non-aerodynamic" and thereby affected distribution? The relatively TINY amount of TINY afrezza particles CANNOT affect the "laminar and turbulent properties" of the AIR FLOW and, therefore, are practically irrelevant to the particles' distribution. You would get about the same distribution if you inhaled smoke or any other fine particulate.