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Post by lakon on May 22, 2021 9:55:45 GMT -5
What's a girl to do? BUY, BUY, BUY!
Seriously? Here's my take in the realm of wild speculation about a good fit for a partnership.
FTA: "Clofazimine broadly inhibits coronaviruses including SARS-CoV-2. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and—possibly more importantly—in dealing with coronavirus diseases that may emerge in the future."
FTA: "As of 2017, Gilead's challenge is to develop or acquire new blockbuster drugs before its current revenue-producers wane or their patent protection expires. Gilead has $32 billion in cash, but $27.4 billion is outside the U.S. and is unavailable for acquisitions unless Gilead pays U.S. tax on it, though it could borrow against it."
Currently, Remdesivir is a small molecule API administered by intravenous injection in a hospital setting. Imagine a self-administered Remdesivir DPI formulation in combination with Clofazimine DPI, and the possibilities become intriguing. Similarly to the partnership with United Therapeutics (UTHR), I think a partnership between MannKind Corporation (MNKD) and Gilead Sciences (GILD) makes a lot of sense.
While a vaccine under the MNKD pipeline would be nice to show breadth and depth of Technosphere potential markets, a more valuable approach is creating a treatment regimen for various coronavirus diseases and other viruses as well as potential applications for treating cancers. Vaccines are not 100% effective, and rolling them out globally will take years. Meanwhile coronaviruses are highly mutagenic, and new strains are bound to confound us again. The trend is every 8-9 years. A sensible approach is to expand our treatment options for infected patients while mass vaccination programs help to eradicate particular strains over time.
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Post by peppy on May 27, 2021 16:03:36 GMT -5
What's a girl to do? BUY, BUY, BUY!
Seriously? Here's my take in the realm of wild speculation about a good fit for a partnership.
FTA: "Clofazimine broadly inhibits coronaviruses including SARS-CoV-2. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and—possibly more importantly—in dealing with coronavirus diseases that may emerge in the future."
FTA: "As of 2017, Gilead's challenge is to develop or acquire new blockbuster drugs before its current revenue-producers wane or their patent protection expires. Gilead has $32 billion in cash, but $27.4 billion is outside the U.S. and is unavailable for acquisitions unless Gilead pays U.S. tax on it, though it could borrow against it."
Currently, Remdesivir is a small molecule API administered by intravenous injection in a hospital setting. Imagine a self-administered Remdesivir DPI formulation in combination with Clofazimine DPI, and the possibilities become intriguing. Similarly to the partnership with United Therapeutics (UTHR), I think a partnership between MannKind Corporation (MNKD) and Gilead Sciences (GILD) makes a lot of sense.
While a vaccine under the MNKD pipeline would be nice to show breadth and depth of Technosphere potential markets, a more valuable approach is creating a treatment regimen for various coronavirus diseases and other viruses as well as potential applications for treating cancers. Vaccines are not 100% effective, and rolling them out globally will take years. Meanwhile coronaviruses are highly mutagenic, and new strains are bound to confound us again. The trend is every 8-9 years. A sensible approach is to expand our treatment options for infected patients while mass vaccination programs help to eradicate particular strains over time.
Lakon, did you get a penile implant? (What is this bigger, longer, harder?) Listening to the physicians, remdesivir a disappointment. The real prize for the first week of illness are the monoclonal antibodies. That was GILD< correct? Dr. Griffin said at the end of the pandemic in New York, the monoclonal antibodies are given the first week and they have been/were giving them in peoples homes. Home health nurses. One more thing, the in vitro studies, many times do not play out in real life, this tidbit from This week in virology. They do watch it happen in the dish though. Anyway, keep it down.  |
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Post by lakon on May 28, 2021 1:26:29 GMT -5
What's a girl to do? BUY, BUY, BUY!
Seriously? Here's my take in the realm of wild speculation about a good fit for a partnership.
FTA: "Clofazimine broadly inhibits coronaviruses including SARS-CoV-2. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and—possibly more importantly—in dealing with coronavirus diseases that may emerge in the future."
FTA: "As of 2017, Gilead's challenge is to develop or acquire new blockbuster drugs before its current revenue-producers wane or their patent protection expires. Gilead has $32 billion in cash, but $27.4 billion is outside the U.S. and is unavailable for acquisitions unless Gilead pays U.S. tax on it, though it could borrow against it."
Currently, Remdesivir is a small molecule API administered by intravenous injection in a hospital setting. Imagine a self-administered Remdesivir DPI formulation in combination with Clofazimine DPI, and the possibilities become intriguing. Similarly to the partnership with United Therapeutics (UTHR), I think a partnership between MannKind Corporation (MNKD) and Gilead Sciences (GILD) makes a lot of sense.
While a vaccine under the MNKD pipeline would be nice to show breadth and depth of Technosphere potential markets, a more valuable approach is creating a treatment regimen for various coronavirus diseases and other viruses as well as potential applications for treating cancers. Vaccines are not 100% effective, and rolling them out globally will take years. Meanwhile coronaviruses are highly mutagenic, and new strains are bound to confound us again. The trend is every 8-9 years. A sensible approach is to expand our treatment options for infected patients while mass vaccination programs help to eradicate particular strains over time.
Lakon, did you get a penile implant? (What is this bigger, longer, harder?) Listening to the physicians, remdesivir a disappointment. The real prize for the first week of illness are the monoclonal antibodies. That was GILD< correct? Dr. Griffin said at the end of the pandemic in New York, the monoclonal antibodies are given the first week and they have been/were giving them in peoples homes. Home health nurses. One more thing, the in vitro studies, many times do not play out in real life, this tidbit from This week in virology. They do watch it happen in the dish though. Anyway, keep it down. "...remdesivir exhibited antiviral synergy in vitro and in vivo..."
I understand systemic effects could play a role, but I expect the Physics to Trump the system when observing the direct treatment of the lungs by physical contact with the medicine as though the lungs were a giant Petri dish holding viruses or bacteria or fungi...
That said MNKD has patents regarding monoclonal antibodies on Technosphere so YES! Thanks for playing.
HODL a BIGGER position for LONGER than expected and apparently HARDER to profit, but I'm STICKING with it until it goes WAY UP! No, I will not keep it down. 
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Post by peppy on May 28, 2021 5:58:15 GMT -5
Lakon, did you get a penile implant? (What is this bigger, longer, harder?) Listening to the physicians, remdesivir a disappointment. The real prize for the first week of illness are the monoclonal antibodies. That was GILD< correct? Dr. Griffin said at the end of the pandemic in New York, the monoclonal antibodies are given the first week and they have been/were giving them in peoples homes. Home health nurses. One more thing, the in vitro studies, many times do not play out in real life, this tidbit from This week in virology. They do watch it happen in the dish though. Anyway, keep it down. "...remdesivir exhibited antiviral synergy in vitro and in vivo..."
I understand systemic effects could play a role, but I expect the Physics to Trump the system when observing the direct treatment of the lungs by physical contact with the medicine as though the lungs were a giant Petri dish holding viruses or bacteria or fungi...
That said MNKD has patents regarding monoclonal antibodies on Technosphere so YES! Thanks for playing.
HODL a BIGGER position for LONGER than expected and apparently HARDER to profit, but I'm STICKING with it until it goes WAY UP! No, I will not keep it down.
"That said MNKD has patents regarding monoclonal antibodies on Technosphere so YES!" Right there with you. What a great delivery system. regarding monoclonal therapies, therapies, I am getting information from Dr. Daniel Griffin and TWIV, they go over the scientific papers. Phase 3 Data Presented at ATS 2021 Show REGEN-COV™ (casirivimab with imdevimab) Reduced Risk of Hospitalization or Death by 70% in Non-hospitalized COVID-19 Patients www.prnewswire.com/news-releases/phase-3-data-presented-at-ats-2021-show-regen-cov-casirivimab-with-imdevimab-reduced-risk-of-hospitalization-or-death-by-70-in-non-hospitalized-covid-19-patients-301292557.htmlAnyway, Daniel saids monoclonal antibodies the first week. Additionally, listening to Dr. Daniel Griffins weekly podcast, There is now a standards of care for COVID19.
www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html
www.covid19treatmentguidelines.nih.gov
Coronavirus Disease 2019 (COVID-19)
Treatment Guidelines
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Post by lakon on May 30, 2021 4:51:14 GMT -5
Monoclonal antibodies are used to treat cancer and COVID-19. MannKind [MNKD] might be starting out with coronaviruses via another route ( Clofazimine), but I expect them to return full circle to cancer treatments, like part of the business that was sold off years ago. There are just too many opportunities for Technosphere, and yet, they are only on the cusp of a sustainable business. After Tyvaso DPI, additional lung treatments make significant strategic sense to expand and grow marketable DPI's. Long-term treatment options to combat novel coronaviruses are a good start. Cancer treatments could follow from there, preferably in partnerships, such as with GILD. Continuing forward with additional treatments for PAH and lung diseases paves the way for regulatory easing towards other areas. After additional lung treatments, the next logical step for UTHR is to partner with MNKD for anti-rejection drugs as part of their long-term goal to create sustainable organ replacements. The regulators and medical community seem fearful of hormones, but hormones are the ticket to long-term innovation and success. Eventually Afrezza will succeed. After becoming a blockbuster, it will bust open the opportunities for other hormones, such as Melatonin, Oxytocin, and PTH. Cannabinoids are another significant market opening and dominating opportunity. The opportunities are endless, an embarrassment of riches to come. Right now, a partnership with GILD would put MNKD and GILD years ahead of everyone else, and GILD would maintain a tight grip on an endless supply of patented therapies around their core competencies with huge growth potential surrounding the treatment of novel coronaviruses.
In the United States, clofazimine is considered an orphan drug, and it is unavailable in pharmacies. (In other words, the price is the price, and the government helps support the cost.)
Just like MannKind's [MNKD] initial work with Treprostinil led to a strong partnership with United Therapeutics [UTHR], I think there is a strong case for a path forward in partnership with Gilead Sciences Inc [GILD]. The path is slightly different; however, it makes a lot of sense to select an orphan drug as a path towards a strategic partnership with a company making complementary medicines that work in combination. The pattern of creating opportunities fits with MannKind's recent co-promotion agreement with Vertice to promote Thyquidity. Under the terms of the agreement, MannKind’s sales force will promote Thyquidity to adult endocrinologists, pediatric endocrinologists and other US healthcare providers who treat hypothyroidism. There is clear synergy with this co-promotion because of Afrezza promotion to endocrinologists. Note that the less obvious partnership potential between MannKind and Vertice would be a Technosphere PTH DPI, which MannKind already tested years ago. The marketed brand could be Thyquidity DPI. THYQUIDITY is indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. Notice the primary, secondary, and tertiary. Similarly Gilead has many ways to leverage Technosphere into highly profitable self-administered DPI versions of their scientific discoveries. There have been a lot of complaints about MannKind's CEO Mr. Michael Castagna on this board, but from where I sit, he seems to have a grasp of long-term strategy. He just needs to continue executing a sound strategy, like I see. Eventually MannKind will get there.
Hyperglycemia - significant market with blockbuster potential [Afrezza]
Hypothyroidism - significant market with blockbuster potential [Thyquidity] PAH - significant market with blockbuster potential [Tyvaso DPI]
In general and theoretically, hormone replacement therapies represent large markets with blockbuster potentials. [MannKind, Vertice]
In general and theoretically, treating novel coronaviruses (as well as common cold viruses) and cancers represent large markets with blockbuster potentials. [MannKind, Gilead]
In general and theoretically, organ replacements represent large markets with blockbuster potentials. [MannKind, United Therapeutics]
www.mdanderson.org/cancerwise/monoclonal-antibodies-and-cancer-treatment--what-to-know.h00-159386679.htmlwww.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art-20047808www.ncbi.nlm.nih.gov/pmc/articles/PMC7551545/www.cancer.gov/about-cancer/treatment/types/immunotherapy/monoclonal-antibodies |
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Post by sportsrancho on May 30, 2021 8:50:57 GMT -5
Great post and a way to promote positivity, instead of bitching about negativity👍🏻 Lots of food for thought!
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Post by Clement on May 30, 2021 9:14:47 GMT -5
What's a girl to do? BUY, BUY, BUY!
Seriously? Here's my take in the realm of wild speculation about a good fit for a partnership.
FTA: "Clofazimine broadly inhibits coronaviruses including SARS-CoV-2. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and—possibly more importantly—in dealing with coronavirus diseases that may emerge in the future."
FTA: "As of 2017, Gilead's challenge is to develop or acquire new blockbuster drugs before its current revenue-producers wane or their patent protection expires. Gilead has $32 billion in cash, but $27.4 billion is outside the U.S. and is unavailable for acquisitions unless Gilead pays U.S. tax on it, though it could borrow against it."
Currently, Remdesivir is a small molecule API administered by intravenous injection in a hospital setting. Imagine a self-administered Remdesivir DPI formulation in combination with Clofazimine DPI, and the possibilities become intriguing. Similarly to the partnership with United Therapeutics (UTHR), I think a partnership between MannKind Corporation (MNKD) and Gilead Sciences (GILD) makes a lot of sense.
While a vaccine under the MNKD pipeline would be nice to show breadth and depth of Technosphere potential markets, a more valuable approach is creating a treatment regimen for various coronavirus diseases and other viruses as well as potential applications for treating cancers. Vaccines are not 100% effective, and rolling them out globally will take years. Meanwhile coronaviruses are highly mutagenic, and new strains are bound to confound us again. The trend is every 8-9 years. A sensible approach is to expand our treatment options for infected patients while mass vaccination programs help to eradicate particular strains over time.
There are a lot of links in this thread. but the most exciting to me is the one Lakon posted from nature.com: Title: "Clofazimine broadly inhibits coronaviruses including SARS-CoV-2" Link: www.nature.com/articles/s41586-021-03431-4.pdf |
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Post by golfeveryday on May 30, 2021 9:51:44 GMT -5
What's a girl to do? BUY, BUY, BUY!
Seriously? Here's my take in the realm of wild speculation about a good fit for a partnership.
FTA: "Clofazimine broadly inhibits coronaviruses including SARS-CoV-2. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and—possibly more importantly—in dealing with coronavirus diseases that may emerge in the future."
FTA: "As of 2017, Gilead's challenge is to develop or acquire new blockbuster drugs before its current revenue-producers wane or their patent protection expires. Gilead has $32 billion in cash, but $27.4 billion is outside the U.S. and is unavailable for acquisitions unless Gilead pays U.S. tax on it, though it could borrow against it."
Currently, Remdesivir is a small molecule API administered by intravenous injection in a hospital setting. Imagine a self-administered Remdesivir DPI formulation in combination with Clofazimine DPI, and the possibilities become intriguing. Similarly to the partnership with United Therapeutics (UTHR), I think a partnership between MannKind Corporation (MNKD) and Gilead Sciences (GILD) makes a lot of sense.
While a vaccine under the MNKD pipeline would be nice to show breadth and depth of Technosphere potential markets, a more valuable approach is creating a treatment regimen for various coronavirus diseases and other viruses as well as potential applications for treating cancers. Vaccines are not 100% effective, and rolling them out globally will take years. Meanwhile coronaviruses are highly mutagenic, and new strains are bound to confound us again. The trend is every 8-9 years. A sensible approach is to expand our treatment options for infected patients while mass vaccination programs help to eradicate particular strains over time.
There are a lot of links in this thread. but the most exciting to me is the one Lakon posted from nature.com: Title: "Clofazimine broadly inhibits coronaviruses including SARS-CoV-2" Link: www.nature.com/articles/s41586-021-03431-4.pdf and this is likely one of the reasons why MC said he was most excited about Clofazamine when asked the other day what he is most excited about. He did not say Tyvaso. |
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Post by peppy on May 30, 2021 10:53:20 GMT -5
There are a lot of links in this thread. but the most exciting to me is the one Lakon posted from nature.com: Title: "Clofazimine broadly inhibits coronaviruses including SARS-CoV-2" Link: www.nature.com/articles/s41586-021-03431-4.pdf and this is likely one of the reasons why MC said he was most excited about Clofazamine when asked the other day what he is most excited about. He did not say Tyvaso. I went hunting for slide decks, something that had Clofazamine listed as a molecule. I didn't find it. www.accessdata.fda.gov/drugsatfda_docs/label/2019/019500s014lbl.pdfLAMPRENE® ( clofazimine) capsules, for oral use Initial U.S. Approval: 1986 --------------------------INDICATIONS AND USAGE---------------------------- LAMPRENE is an antimycobacterial indicated for the treatment of lepromatous leprosy, including dapsone-resistant lepromatous leprosy and lepromatous leprosy complicated by erythema nodosum leprosum. (1.1) 11 DESCRIPTION LAMPRENE (clofazimine) is an antimycobacterial available as soft gelatin capsules for oral administration. Each capsule contains 50 mg of micronized clofazimine suspended in an oil-wax base. Clofazimine is a substituted iminophenazine bright-red dye. Its chemical name is 3-(p-chloroanilino)-10-(p-chlorophenyl)-2, 10-dihydro-2-isopropyliminophenazine, and its structural formula is Clofazimine is a reddish-brown powder. It is readily soluble in benzene; soluble in chloroform; poorly soluble in acetone and in ethyl acetate; sparingly soluble in methanol and in ethanol; and virtually insoluble in water. Its molecular weight is 473.4. Its molecular formula is C27H22Cl2N4. 12.4 Microbiology Mechanism of Action Clofazimine exerts a slow bactericidal effect on Mycobacterium leprae (Hansen’s bacillus). Clofazimine inhibits mycobacterial growth and binds preferentially to mycobacterial DNA. Clofazimine also exerts anti-inflammatory properties in treating erythema nodosum leprosum reactions. However, its precise mechanisms of action are unknown. The mechanism of action for the antimycobacterial activity of clofazimine can be postulated through its membrane- directed activity including the bacterial respiratory chain and ion transporters. Intracellular redox cycling, involving oxidation of reduced clofazimine, leads to the generation of antimicrobial reactive oxygen species (ROS), superoxide hydrogen peroxide (H2O2). Secondly, interaction of clofazimine with membrane phospholipids results in the generation of antimicrobial lysophospholipids, which promote membrane dysfunction, resulting in interference with K+ uptake. Both mechanisms result in interference with cellular energy metabolism by disrupting ATP production. Anti-inflammatory activity of clofazimine is primarily through inhibition of T lymphocyte activation and proliferation. Clofazimine may indirectly interfere with the proliferation of T cells by promoting the release of ROS and E-series prostaglandins (PGs), especially PGE2 from neutrophils and monocytes. =========================================================================================================== Nature Paper. " inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Effects on SARS-CoV-2 life cycle We first evaluated the antiviral activity of clofazimine using a time-of-drug addition assay in a single infectious cycle. Treatment with clofazimine during inoculation strongly inhibited SARS-CoV-2 infec- tion, which indicates that clofazimine inhibits viral entry. Clofazimine also blocked SARS-CoV-2 infection at a post-entry step, as evidenced by an observed reduction in viral replication when clofazimine was added at 5 h after infection (Extended Data Fig. 2a). To further evaluate the effect of clofazimine on viral entry, we used vesicular stomatitis b, Clofazimine inhibits membrane fusion mediated by SARS-CoV-2 S. (Leprosy a chronic infectious disease caused by Mycobacterium leprae.) www.who.int/health-topics/leprosy#tab=tab_1 |
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