"Can you see the big picture?"
Well, it depends on what we mean by it. The very tops of "40 indications" approved or the entire mountain slopes from top to bottom and bottom to top this company will have to climb for those approvals. To give one example, someone mentioned Madrigal Pharmaceutical (MDGL) as the current leader in the race for NASH. To get a sense of what it takes to do Phase 3 in NASH, I suggest reading the last SA article and comments to it. Madrigal has $300 million in cash reserve and has been doing Phase 3 non-invasive imaging and biomarker study, MAESTRO-NAFLD-1 with 100 mg per day of resmetirom for up to 52 weeks.
NB: "Their 2018 phase 2 biopsy-measured trial, there was a two-point reduction in NAS (NAFLD activity score), high NASH and fibrosis resolution in patients. That data catapulted the stock to all-time highs and made Madrigal the leader in the NASH space."
"At the American Association for the Study of Liver Diseases (AASLD) meeting on November 12, they presented previously-released (June) open label data from this trial (Phase 3) which has been pushing the stock up post-market Friday. The data is strongly positive and indicative of what we may see in the blinded study. However, MDGL has a pretty high short interest so we want to figure out why there's a group of people who think MDGL may not do so well."
Here is some comments from investors.
___________________________
No excitement in any NASH drugs coming out of the AASLD meetings
Need combination therapies. Sadly, another 3-5 years will be wasted because no one will take charge and make it happen.
_____________________________
The big risk with the Phase 3 trial is the end-point of NASH reduction. At some point, the inflammatory process has a life of its own so reducing the underlying cause may not modify the disease process enough to reach a positive outcome for the trial. I am long MDGL but have not bet my entire retirement on it.
______________________________
I am confused by the number of patients who had advanced fibrosis as characterized by an ELF score greater than 9.8
Doesn’t seem to do much in that group
Can you shed some light on the N of that subset?
Appears to have potential for early stage NASH, but given the high placebo response rate in NASH trials we need control data
Nevertheless, this drug just might make a dent in the disease, but I still think it’s fibrosis, not fat that matters.
Given the graveyard of drugs that we have gone through over the last 7 years in NASH, I don’t think there is any true cure for NASH- certainly not one drug—drug combinations are needed as well as mitigation of NASH cirrhosis end stage consequences (GALT)
_______________________
And on and in the same vein. No certainty! This is a "big picture." And we are talking about a well-financed company with years of NASH research and trials, including a very promising biopsy-measured Phase 2! So how long and stony our road will be to let say only two indications out of 40, NASH and triple-negative MBC? How high have we climbed already? I am not sure even about one inch. Some time ago I posted a question about our tnMBC results used for the BTD request. I couldn't figure out how was it possible that even with 3600% improvement on SOC our OVERALL AVERAGE in this trial was no higher. I have similar question about our open NASH trial results reported yesterday. Why no OVERALL data was included? Yet this data is absolutely essential for charting how to proceed further or deciding not to proceed at all. Reading the last Q10 filing I came to the para explaining the FDA rejection of CD 12 results.
Quote:
__________________________
In response to our review and reports of analysis of data from subgroups from the CD12 trial, FDA stated that subgroup analyses have well-established limitations, especially in the context of a clinical trial that has failed to show a benefit in the overall study population. The agency indicated that data from CD12 illustrated imbalances in mortality among subgroups, some favoring leronlimab and some favoring placebo. The FDA concluded that none of these analyses met statistical significance when using established and reliable analytical methods that correct for multiple comparisons.
__________________________
To the best of my knowledge, the question about the relevance of OVERALL results for our BTD application for tn-MBC was never raised let alone answered in CCs or board discussions. This makes me feel uncertain about its outcome.
Speaking of NASH, Dr. Recknor's brief comment on the NASH results in yesterday's PR was absolutely non-binding in stark contrast to Nader's. The information presented is incomprehensible to an ignorant peasant like myself and NO attempt is made to explain its significance or even why the release talks about only the last 20 patients out of 30 in the open trial. No time for computing 20+10 results? I can only hope that today's CC will shed light on these questions one way or another.
Well, it depends on what we mean by it. The very tops of "40 indications" approved or the entire mountain slopes from top to bottom and bottom to top this company will have to climb for those approvals. To give one example, someone mentioned Madrigal Pharmaceutical (MDGL) as the current leader in the race for NASH. To get a sense of what it takes to do Phase 3 in NASH, I suggest reading the last SA article and comments to it. Madrigal has $300 million in cash reserve and has been doing Phase 3 non-invasive imaging and biomarker study, MAESTRO-NAFLD-1 with 100 mg per day of resmetirom for up to 52 weeks.
NB: "Their 2018 phase 2 biopsy-measured trial, there was a two-point reduction in NAS (NAFLD activity score), high NASH and fibrosis resolution in patients. That data catapulted the stock to all-time highs and made Madrigal the leader in the NASH space."
"At the American Association for the Study of Liver Diseases (AASLD) meeting on November 12, they presented previously-released (June) open label data from this trial (Phase 3) which has been pushing the stock up post-market Friday. The data is strongly positive and indicative of what we may see in the blinded study. However, MDGL has a pretty high short interest so we want to figure out why there's a group of people who think MDGL may not do so well."
Here is some comments from investors.
___________________________
No excitement in any NASH drugs coming out of the AASLD meetings
Need combination therapies. Sadly, another 3-5 years will be wasted because no one will take charge and make it happen.
_____________________________
The big risk with the Phase 3 trial is the end-point of NASH reduction. At some point, the inflammatory process has a life of its own so reducing the underlying cause may not modify the disease process enough to reach a positive outcome for the trial. I am long MDGL but have not bet my entire retirement on it.
______________________________
I am confused by the number of patients who had advanced fibrosis as characterized by an ELF score greater than 9.8
Doesn’t seem to do much in that group
Can you shed some light on the N of that subset?
Appears to have potential for early stage NASH, but given the high placebo response rate in NASH trials we need control data
Nevertheless, this drug just might make a dent in the disease, but I still think it’s fibrosis, not fat that matters.
Given the graveyard of drugs that we have gone through over the last 7 years in NASH, I don’t think there is any true cure for NASH- certainly not one drug—drug combinations are needed as well as mitigation of NASH cirrhosis end stage consequences (GALT)
_______________________
And on and in the same vein. No certainty! This is a "big picture." And we are talking about a well-financed company with years of NASH research and trials, including a very promising biopsy-measured Phase 2! So how long and stony our road will be to let say only two indications out of 40, NASH and triple-negative MBC? How high have we climbed already? I am not sure even about one inch. Some time ago I posted a question about our tnMBC results used for the BTD request. I couldn't figure out how was it possible that even with 3600% improvement on SOC our OVERALL AVERAGE in this trial was no higher. I have similar question about our open NASH trial results reported yesterday. Why no OVERALL data was included? Yet this data is absolutely essential for charting how to proceed further or deciding not to proceed at all. Reading the last Q10 filing I came to the para explaining the FDA rejection of CD 12 results.
Quote:
__________________________
In response to our review and reports of analysis of data from subgroups from the CD12 trial, FDA stated that subgroup analyses have well-established limitations, especially in the context of a clinical trial that has failed to show a benefit in the overall study population. The agency indicated that data from CD12 illustrated imbalances in mortality among subgroups, some favoring leronlimab and some favoring placebo. The FDA concluded that none of these analyses met statistical significance when using established and reliable analytical methods that correct for multiple comparisons.
__________________________
To the best of my knowledge, the question about the relevance of OVERALL results for our BTD application for tn-MBC was never raised let alone answered in CCs or board discussions. This makes me feel uncertain about its outcome.
Speaking of NASH, Dr. Recknor's brief comment on the NASH results in yesterday's PR was absolutely non-binding in stark contrast to Nader's. The information presented is incomprehensible to an ignorant peasant like myself and NO attempt is made to explain its significance or even why the release talks about only the last 20 patients out of 30 in the open trial. No time for computing 20+10 results? I can only hope that today's CC will shed light on these questions one way or another.
2
CytoDyn Inc (CYDY) Stock Research Links
Whatever happens, we have got
Le-Ron-Li-Mab, and they have not.
Le-Ron-Li-Mab, and they have not.
