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Post by prcgorman2 on Oct 31, 2023 7:23:26 GMT -5
Bet the farm? Or is this personal? Based on LQDA advocate claiming they could gobble up fully 10% of the market, I have to wonder if they were way underselling the threat of Yutrepia, or whether Martine had such a falling out with Roger Jeffs that this is less about the money and more about the win.
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Post by agedhippie on Oct 31, 2023 8:21:01 GMT -5
Bet the farm? Or is this personal? Based on LQDA advocate claiming they could gobble up fully 10% of the market, I have to wonder if they were way underselling the threat of Yutrepia, or whether Martine had such a falling out with Roger Jeffs that this is less about the money and more about the win. I think the market share is dependent on the pricing. Yutrepia can go to higher doses than Tyvaso-DPI, but UTHR is the incumbent so I think it's a wash there. I am not sure that there is active ill-will between them. I think it's more probable that Martine knows Jeffs has built this business before when he was at UTHR and expects he can do it again and that's the concern. |
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Post by mango on Oct 31, 2023 11:10:57 GMT -5
Yutrepia requires more dry powder to achieve a similar clinical response whereas Tyvaso DPI is able to use less dry powder to achieve a similar clinical response simply because of the superior inhaler (and possible dry powder technology) MannKind uses. The PK/PD data and clinical trials data all prove this. It’s also something Martine and Mike have mentioned before in calls.
Yutrepia must use significantly more dry powder because a lot of it impacts the upper airway and doesn’t penetrate the deep lungs like Tyvaso DPI does. So it is also misleading to claim Yutrepia doses higher when in fact the higher dose is needed because not much powder reaches the deep lungs in the first place.
I thought everyone knew about Martine squashing this nonsense when she spoke about it and showed the slides with the data proving it.
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Post by agedhippie on Oct 31, 2023 12:34:23 GMT -5
Yutrepia requires more dry powder to achieve a similar clinical response whereas Tyvaso DPI is able to use less dry powder to achieve a similar clinical response simply because of the superior inhaler (and possible dry powder technology) MannKind uses. The PK/PD data and clinical trials data all prove this. It’s also something Martine and Mike have mentioned before in calls. Yutrepia must use significantly more dry powder because a lot of it impacts the upper airway and doesn’t penetrate the deep lungs like Tyvaso DPI does. So it is also misleading to claim Yutrepia doses higher when in fact the higher dose is needed because not much powder reaches the deep lungs in the first place. I thought everyone knew about Martine squashing this nonsense when she spoke about it and showed the slides with the data proving it. If Yutrepia is garbage Martine is sure spending a lot of time and money on trying to prevent something from coming the market that isn't a threat! You are confusing API quantity with therapeutic breaths (the equivalent of breaths of nebulized Tyvaso - it seems to be what they use in the same way that insulin uses units). Think of it like Afrezza - about 40% makes it through to the blood stream with the resting, being swallowed, not being properly inhaled, passing through unaltered, etc. This is used by certain people (LFD *cough*) to say that Afrezza is ineffective, but that is not the case - you simply use more of the active component. The amount of active drug used is irrelevant, it's the therapeutic effect that matters as Afrezza proves. OK - so how do they compare? They are pretty much the same. In the INSPIRE study the all patient group 6MWD increased by 12.6 meters, the Tyvaso DPI HCP site claims 11.5 meters. That's close enough that in real life I expect there to be no difference. This is hardly surprising since the since the API is the same in both cases. "It doesn't penetrate deep into the lungs" is a claim you see a lot from Technosphere supporters. That's wrong. There is more than one way to skin a cat and MNKD and LQDA illustrate that. The LQDA delivery system, PRINT, does it by printing out specifically shaped micro-particles (hence the name) and using a low resistance device. The shaped particles use the aerodynamics produced by inhalation to penetrate deep into the lungs. If anyone can prove this is untrue I would love to see the evidence. Yutrepia can go as high as the equivalent of 27 breaths of the nebulized Tyvaso which I believe is considerably higher than Tyvaso DPI has achieved. If Martine has data and slides to prove this is nonsense I would love to see them because I haven't found any comparisons. Both sides seem to be tiptoeing around each other with DPI. |
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Post by agedhippie on Oct 31, 2023 12:49:08 GMT -5
... Yutrepia can go as high as the equivalent of 27 breaths of the nebulized Tyvaso which I believe is considerably higher than Tyvaso DPI has achieved. If Martine has data and slides to prove this is nonsense I would love to see them because I haven't found any comparisons. Both sides seem to be tiptoeing around each other with DPI. I don't usually comment on my own posts  I was curious about the dosing so I checked. The label for Tyvaso DPI has a maximum dose as 11 - 12 breaths of nebulized Tyvaso. The maximum dose for Yutrepia is 27 breaths from trials and calls. Not everyone needs that, but as this is a progressive illness there will come a point where patients will have to roll off as their needs exceed the maximum dose and with Yutrepia that comes later. |
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Post by cretin11 on Oct 31, 2023 13:17:08 GMT -5
Yutrepia must use significantly more dry powder because a lot of it impacts the upper airway and doesn’t penetrate the deep lungs like Tyvaso DPI does. So it is also misleading to claim Yutrepia doses higher when in fact the higher dose is needed because not much powder reaches the deep lungs in the first place. Gotta be careful cherry picking facts like this, as the same critique can be made regarding Afrezza. It really doesn’t matter for Afrezza or Yutrepia, the dosage can be adjusted accordingly for both of them. |
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Post by akemp3000 on Oct 31, 2023 15:00:56 GMT -5
What's most important is UTHR is the big dog in this fight, if a fight even happens one day!
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Post by mango on Oct 31, 2023 15:12:21 GMT -5
Yutrepia requires more dry powder to achieve a similar clinical response whereas Tyvaso DPI is able to use less dry powder to achieve a similar clinical response simply because of the superior inhaler (and possible dry powder technology) MannKind uses. The PK/PD data and clinical trials data all prove this. It’s also something Martine and Mike have mentioned before in calls. Yutrepia must use significantly more dry powder because a lot of it impacts the upper airway and doesn’t penetrate the deep lungs like Tyvaso DPI does. So it is also misleading to claim Yutrepia doses higher when in fact the higher dose is needed because not much powder reaches the deep lungs in the first place. I thought everyone knew about Martine squashing this nonsense when she spoke about it and showed the slides with the data proving it. If Yutrepia is garbage Martine is sure spending a lot of time and money on trying to prevent something from coming the market that isn't a threat! You are confusing API quantity with therapeutic breaths (the equivalent of breaths of nebulized Tyvaso - it seems to be what they use in the same way that insulin uses units). Think of it like Afrezza - about 40% makes it through to the blood stream with the resting, being swallowed, not being properly inhaled, passing through unaltered, etc. This is used by certain people (LFD *cough*) to say that Afrezza is ineffective, but that is not the case - you simply use more of the active component. The amount of active drug used is irrelevant, it's the therapeutic effect that matters as Afrezza proves. OK - so how do they compare? They are pretty much the same. In the INSPIRE study the all patient group 6MWD increased by 12.6 meters, the Tyvaso DPI HCP site claims 11.5 meters. That's close enough that in real life I expect there to be no difference. This is hardly surprising since the since the API is the same in both cases. "It doesn't penetrate deep into the lungs" is a claim you see a lot from Technosphere supporters. That's wrong. There is more than one way to skin a cat and MNKD and LQDA illustrate that. The LQDA delivery system, PRINT, does it by printing out specifically shaped micro-particles (hence the name) and using a low resistance device. The shaped particles use the aerodynamics produced by inhalation to penetrate deep into the lungs. If anyone can prove this is untrue I would love to see the evidence. Yutrepia can go as high as the equivalent of 27 breaths of the nebulized Tyvaso which I believe is considerably higher than Tyvaso DPI has achieved. If Martine has data and slides to prove this is nonsense I would love to see them because I haven't found any comparisons. Both sides seem to be tiptoeing around each other with DPI. You mean 70%. MannKind’s technology delivers ~70% of the dry powder to the deep lungs. As for the slides, Martine presented a handful of data slides illustrating Tyvaso DPI’s superiority over Yutrepia. I’m surprised you didn’t see them, they were being posted and discussed for a while. |
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Post by cretin11 on Oct 31, 2023 15:42:36 GMT -5
What's most important is UTHR is the big dog in this fight, if a fight even happens one day! It's nice to be on that side of the equation for a change. |
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Post by agedhippie on Oct 31, 2023 15:54:15 GMT -5
You mean 70%. MannKind’s technology delivers ~70% of the dry powder to the deep lungs. As for the slides, Martine presented a handful of data slides illustrating Tyvaso DPI’s superiority over Yutrepia. I’m surprised you didn’t see them, they were being posted and discussed for a while. You may be correct, as checking that 40%- it's for the Medtone inhaler and the Dreamboat is more efficient. I cannot find any data on the Dreamboat though (the Medtone data was from a MNKD paper). To be clear though, the point was that the amount making it through is unimportant in the overall scheme provided enough can get through to work - with Afrezza 30% doesn't make it through, but it still works just fine. If I had seen the slides I wouldn't be asking for a link  |
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Post by sayhey24 on Oct 31, 2023 17:27:40 GMT -5
Why do you think LQDA will be much competition for UTHR? Do you think they have a better mouse trap or salesforce? The last I checked it did not seem their solution had the same deep lung penetration as technosphere. If they weren't a threat UTHR would not have spent the amount of time, money, and effort trying to stop them as they have and instead would have just rolled right over them. So are they competition? UTHR appears to think so, but the question is how big. I think that UTHR still gets the majority of the market by virtue of it's salesforce. Deep lung penetration (or not) is irrelevant. What matters is the outcomes and from the trials those are broadly comparable. Don't fixate on the technology at the expense of the outcomes, the outcomes are what doctors care about. There is still UTHR's appeal against the PTAB. If UTHR win that then superiority, sales, and everything else won't matter. Do they really believe LQDA is much competition or was it more personal? Didn't one of Martine's trusted guys leave and go to Liquidia taking a bunch of trade secrets? Who was it Roscigno? If he did this to me I would sue them too. Serious question - does LQDA have any money to even try and compete? IDK I don't give them much of a chance. Back in the day when UTHR was considering them prior to MNKD sure but I don't give them much chance with "broadly comparable" trials. For whatever reason when UTHR compared them to Technosphere, they lost. |
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Post by agedhippie on Oct 31, 2023 17:56:07 GMT -5
Do they really believe LQDA is much competition or was it more personal? Didn't one of Martine's trusted guys leave and go to Liquidia taking a bunch of trade secrets? Who was it Roscigno? If he did this to me I would sue them too. Serious question - does LQDA have any money to even try and compete? IDK I don't give them much of a chance. Back in the day when UTHR was considering them prior to MNKD sure but I don't give them much chance with "broadly comparable" trials. For whatever reason when UTHR compared them to Technosphere, they lost. It's not personal it's business, Roscigno left LQDA three years ago. I don't think the trade secret case is serious. Roscigno left UTHR in 2007 for a healthcare company where he worked for another 6 years before joining LQDA. Given the interval between his leaving UTHR and joining LQDA proving a trade secret breach of significance is going to be hard. Besides, Roger Jeffs had still been working at UTHR then so if LQDA wanted data Jeffs knowledge was far more current. LQDA is actually quite well off and can get past launch without needing cash. The odds are that they do a raise before launch though because why not? My bet is that UTHR got a far better deal out of MNKD than they could have got out of LQDA. At that point MNKD really needed the deal, but LQDA had the resources to wait and try for the whole enchilada rather than just royalties. |
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Post by wyattdog on Oct 31, 2023 18:33:50 GMT -5
just a few risks from liquida's recent 10Q The following is a summary of the principal risk factors described in this section:
● We expect to incur significant expenses and operating losses for the foreseeable future as we advance our product candidates through clinical trials, seek regulatory approval and pursue commercialization of any approved product candidates. The future viability of our company may depend on our ability to raise additional capital to finance our future operations.
● We have a history of losses and our future profitability remains uncertain. Our net losses and significant cash used in operating activities have raised substantial doubt regarding our ability to continue as a going concern.
● We are primarily dependent on the success of our product candidates, YUTREPIA and L606, and these product candidates may fail to receive final marketing approval (in a timely manner or at all) or may not be commercialized successfully.
● United Therapeutics has initiated a lawsuit against us in which it has claimed that YUTREPIA is infringing three of its patents and a separate lawsuit against us that we and a former United Therapeutics employee, who later joined us as an employee, conspired to misappropriate certain trade secrets of United Therapeutics and engaged in unfair or deceptive trade practices. The judge in the patent lawsuit entered a final judgment finding that one of the three asserted United Therapeutics’ patents is both valid and infringed and ordering that the effective date of any final approval by the FDA of YUTREPIA shall be a date which is not earlier than the expiration date of the infringed patent, which will be in 2027. While the PTAB found that this same patent was unpatentable, the PTAB’s decision with respect to the patent will not override the court’s order unless and until the decision of the PTAB is affirmed on appeal. These lawsuits may result in our company being delayed in its efforts to commercialize YUTREPIA.
● Liquidia PAH does not hold the FDA regulatory approval for Treprostinil Injection, the RG Cartridge or pumps used to administer Treprostinil Injection and is dependent on Sandoz, Chengdu and the pump manufacturers to manufacture and supply Treprostinil Injection, the RG Cartridge and pumps used to administer Treprostinil Injection, respectively, in compliance with FDA requirements, and is more broadly dependent on their FDA and healthcare compliance relative to Treprostinil Injection, the RG Cartridge and the pumps used to administer Treprostinil Injection, respectively.
● Treprostinil Injection is presently administered subcutaneously via Smiths Medical’s CADD-MS 3 infusion pump. Smiths Medical no longer manufactures the CADD-MS 3 infusion pump and has no obligation to service or maintain CADD-MS 3 infusion pumps after January 1, 2025. Should components of the CADD-MS 3 pump become unavailable, Smiths Medical’s ability to service and maintain such pumps may terminate earlier than anticipated. For instance, during 2022 we became aware of a potential shortage of a critical component of the CADD-MS 3 infusion pump that may cause the number of CADD-MS 3 infusion pumps available for the administration of Treprostinil Injection to be depleted prior to January 1, 2025. In the event the specialty pharmacies are unable to access sufficient quantities of operable pumps or in the event we are unable to identify or develop a new pump prior to the current pumps becoming unavailable, the commercial success of Treprostinil Injection may be adversely affected.
● Sales of Treprostinil Injection are dependent on market acceptance of generic treprostinil for parenteral administration and the medical devices used for administration of Treprostinil Injection, including the Smiths Medical infusion pumps, any future pumps that we develop, and the RG Cartridge, by patients, health care providers and by third-party payors, while interactions with these persons and entities are subject to compliance requirements. The commercial success of Treprostinil Injection may also be impacted by increasing generic competition which may result in declining prices for Treprostinil Injection.
● We expect that we will need further financing for our existing business and future growth, which may not be available on acceptable terms, if at all. Failure to obtain funding on acceptable terms and on a timely basis may require us to curtail, delay or discontinue our product development efforts or other operations. The failure to obtain further financing may also prevent us from capitalizing on other potential product
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candidates or indications which may be more profitable than YUTREPIA and/or L606 or for which there may be a greater likelihood of success.
● We face significant competition from large pharmaceutical companies, among others, in developing our products and in gaining regulatory approval to bring them to market in time to achieve commercial success, and our operating results will suffer if we are unable to compete effectively, including if one or more such products have a superior product profile to YUTREPIA and/or L606.
● Our financing facility with HCR requires mutual agreement of both HCR and us in order to draw down on the facility. HCR may not agree to make additional advances pursuant to the facility. Failure to receive further funding from HCR may result in our having insufficient financing for our existing business plan. Our financing facility with HCR also contains operating and financial covenants that restrict our business and financing activities, and is subject to acceleration in specified circumstances, which may result in HCR taking possession and disposing of any collateral.
● Our products may not achieve market acceptance.
● Our product candidates are based on proprietary, novel technology, which have not been used to manufacture any products that have been previously approved by the FDA, making it difficult to predict the time and cost of development and of subsequently obtaining final regulatory approval.
● Our business and operations may be adversely affected by the effects of health epidemics, including the COVID-19 pandemic.
● We may not be able to build a commercial operation, including establishing and maintaining marketing and sales capabilities or entering into agreements with third parties to market and sell our drug products.
● We depend on third parties for clinical and commercial supplies, including single suppliers for the active ingredient, the device, encapsulation and packaging of YUTREPIA and single suppliers for the drug product and device for L606. In the event of any disruption in these supplies, our ability to develop and commercialize, and the timeline for commercialization of, YUTREPIA and/or L606 may be adversely affected.
● We rely on third parties to conduct our preclinical studies and clinical trials.
● We may become involved in litigation to protect our intellectual property, to enforce our intellectual property rights or to defend against claims of intellectual property infringement by third parties, which could be expensive, time-consuming and may not be successful.
● We depend on skilled labor, and our business and prospects may be adversely affected if we lose the services of our skilled personnel, including those in senior management, or are unable to attract new skilled personnel.
● We expect that the market price of our common stock may be volatile, and you may lose all or part of your investment.
● As a public company, we are obligated to develop and maintain proper and effective internal control over financial reporting and any failure to do so may adversely affect investor confidence in us and, as a result, the trading price of our shares.
Risks Related to our Financial Position and Need for Additional Capital
We expect to incur significant expenses and operating losses for the foreseeable future as we advance our product candidates through clinical trials, seek regulatory approval and pursue commercialization of any approved product candidates. The future viability of our company may depend on our ability to raise additional capital to finance our future operations.
We are subject to risks and uncertainties common to early-stage companies in the biotechnology industry, including, but not limited to, development by competitors of new technological innovations, dependence on key personnel, protection of proprietary technology, compliance with government regulations, the impact of the COVID-19 pandemic, and the ability to secure additional capital to fund operations. We expect to incur significant expenses and may incur significant operating losses for the foreseeable future as we advance product candidates through clinical trials, seek regulatory approval and pursue commercialization of any approved product candidates. In addition, if we obtain
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marketing approval for any of our product candidates, we would incur significant commercialization expenses related to product manufacturing, marketing, sales and distribution. These efforts require significant amounts of capital, adequate personnel and infrastructure, and extensive compliance-reporting capabilities. Even if our development efforts are successful, it is uncertain when, if ever, we will realize significant revenue from product sales. The future viability of our company may depend on our ability to raise additional capital to finance our future operations. We may seek additional funding through public or private financings, debt financing or collaboration. Our inability to obtain funding, if and when needed, would have a negative impact on our financial condition and ability to pursue our business strategies.
We have a history of losses and our future profitability remains uncertain. Our net losses and significant cash used in operating activities have raised substantial doubt regarding our ability to continue as a going concern.
We have incurred net losses of $35.3 million during the six months ended June 30, 2023 and $41.0 million and $34.6 million during the years ended December 31, 2022 and 2021, respectively. We also had negative operating cash flows for each of these periods. As of June 30, 2023, we had an accumulated deficit of $385.9 million.
Since our incorporation, we have invested heavily in the development of our product candidates and technologies, as well as in recruiting management and scientific personnel. To date, we have not commenced the commercialization of our product candidates and all of our revenue has been derived from up-front fees and milestone payments made to us in connection with licensing and collaboration arrangements we have entered into and the Promotion Agreement, under which we share in the profit derived from the sale of Treprostinil Injection in the United States. These up-front fees and milestone payments have been, and combined with revenue generated from Treprostinil Injection may continue to be, insufficient to match our operating expenses. We expect to continue to devote substantial financial and other resources to the clinical development of our product candidates and, as a result, must generate significant revenue to achieve and maintain profitability or raise additional capital to fund clinical development. We may continue to incur losses and negative cash flow and may never transition to profitability or positive cash flow. These factors raise substantial doubt about our ability to continue as a going concern and to satisfy our estimated liquidity needs for one year from the issuance of the condensed consolidated financial statements.
We expect that we will need further financing for our existing business and future growth, which may not be available on acceptable terms, if at all. Failure to obtain funding on acceptable terms and on a timely basis may require us to curtail, delay or discontinue our product development efforts or other operations. The failure to obtain further financing may also prevent us from capitalizing on other potential product candidates or indications which may be more profitable than YUTREPIA and/or L606 or for which there may be a greater likelihood of success.
We anticipate that we will need to raise additional funds to meet our future funding requirements for the continued research, development and commercialization of our product candidates and technology. In the event that funds generated from our operations are insufficient to fund our future growth, we may raise additional funds through the issuance of equity or debt securities or by borrowing from banks or other financial institutions. We cannot assure you that we will be able to obtain such additional financing on terms that are acceptable to us, or at all. Global and local economic conditions could negatively affect our ability to raise funds. To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted, and the terms of such securities may include liquidation or other preferences that adversely affect your rights as a stockholder. Such financing, even if obtained, may be accompanied by restrictive covenants that may, among others, limit our ability to pay dividends or require us to seek consent for payment of dividends, or restrict our freedom to operate our business by requiring consent for certain actions.
If we conclude that we require additional financing and fail to obtain it on terms that are favorable to us, we will not be able to implement our growth plans, and we may be required to significantly curtail, delay or discontinue one or more of our research, development or manufacturing programs or the commercialization of any approved product. Furthermore, if we fail to obtain additional financing on terms that are acceptable to us, we may forgo or delay the pursuit of opportunities presented by other potential product candidates or indications that may later prove to have greater commercial potential than the product candidates and indications that we have chosen to pursue.
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Post by agedhippie on Oct 31, 2023 19:45:33 GMT -5
just a few risks from liquida's recent 10Q The following is a summary of the principal risk factors described in this section: ... Lol. Actually that's quite short. The UTHR one is much longer. Those sections are always long because if you don't disclose a risk there it can get you into a shareholder lawsuit, or possible prosecution by the SEC. Consequently they read like War and Peace and everyone skips them. |
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Post by anderson on Oct 31, 2023 22:41:30 GMT -5
You mean 70%. MannKind’s technology delivers ~70% of the dry powder to the deep lungs. As for the slides, Martine presented a handful of data slides illustrating Tyvaso DPI’s superiority over Yutrepia. I’m surprised you didn’t see them, they were being posted and discussed for a while. You may be correct, as checking that 40%- it's for the Medtone inhaler and the Dreamboat is more efficient. I cannot find any data on the Dreamboat though (the Medtone data was from a MNKD paper). To be clear though, the point was that the amount making it through is unimportant in the overall scheme provided enough can get through to work - with Afrezza 30% doesn't make it through, but it still works just fine. If I had seen the slides I wouldn't be asking for a link Thank you harryx1 for posting the slides. mnkd.proboards.com/post/247614/thread |
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