Jake2212 does't post a lot but when he does it is always worth a read:
Posted By: Jake2212
Is Gilead seriously in play to invest in LL for breast cancer? Some may recall my post shortly after last Monday's TNBC PR in which I opined that Dr Jay clearly has a good reason to invest the time and money to conduct another preclinical study for LL in mTNBC, this time with SMC Labs. I assumed then that CYDY's main focus would be on the Keytruda arm, but noted parenthetically that, because we don't know what we don't know, perhaps the Trodelvy arm might actually be the main focus.
Well, faced with the necessity to muddle through another weekend without football games to watch, I revisited the March, 2023, BioSpace article in which Cyrus had waxed eloquent about the ongoing MD Anderson mouse study involving LL and Keytruda, with his expectation of synergistic results. But no results were ever announced. Unless the study was never completed, I would think that both CYDY and MRK were furnished with the results, suggesting to me that either CYDY or MRK may have invoked a NDA to bury the results. That outcome would have been consistent with ohm's prediction that Keytruda would add nothing to LL. Therefore, no synergistic effect.
So why repeat the LL/Keytruda mouse study 2 years later? Well. unless CYDY believes that the SMC Labs mice are considerably more humanized than the MD Anderson mice, the reason escapes me.
On the other hand, Gilead's Trodelvy, the other leading FDA approved treatment for mTNBC, wasn't involved in the aforementioned MD Anderson study, but was the drug that the FDA cited to deny LL breakthrough designation status when CYDY announced LL's mTNBC phase 2 clinical trial results in August and November, 2021. Back then, LL produced a OS (overall survival) endpoint that although only slightly better than Trodelvy's, was still ongoing because more than half of the 26 women from the trial were still alive.
From last Monday's PR we now know that LL's OS was ultimately many months beyond Trodelvy's. The exact difference will undoubtedly be announced at or before the upcoming conference in Munich. Also, bear in mind that 9 of the 26 women in the trial received only 350 mg doses of LL, and only 3 received the maximum 700 mg doses. Given that the 350 mg doses would not have fully covered the CCR5 cells (thank you ohm), it may well be that the final Leronlimab OS data for the other 17 women (if over half are now deceased) will be particularly provocative compared to Trodelvy.
As I now ponder the above info, it seems much more reasonable to intuit that the LL/Trodelvy arm will be the main focus of attention for both CYDY and Gilead. According to Gilead's recently released annual report, Trodelvy produced revenue of 1.3B in 2024, all of it treating breast cancer. In Merck's annual report, I was not able to isolate Keytruda's breast cancer revenue, but I believe it would compare favorably to or exceed Trodelvy's.
MRK's sp has declined about 30% in the last 12 months, while GILD's sp has increased 70% since last June. GILD had 10B in cash at the end of 2024. And ohm has stated in a recent post that he would not be surprised if LL and Trodelvy were to produce a synergistic effect. If that proves to be true, or even if it doesn't, obtaining the use or ownership of a breast cancer drug arguably far superior to Keytruda or Trodelvy would likely translate to billions in new revenues for GILD, and that's without considering the rest of ohm's list.
Admittedly, however, MRK should also be actively engaged with CYDY concerning LL. With a faltering sp, stagnant revenues, and a Keytruda patent cliff now 2 years closer, MRK has good reason to reconsider LL in light of the newly revised Leronlimab OS that has probably already been communicated to MRK by CYDY. Because, if MRK is no longer interested in CYDY/LL, why is Keytruda still being included in the current mouse trial? And what could be better than 2 BP heavyweights being focused on the major impact that using or owning LL could have for them.
Seems very interesting to me. But bear in mind that I don't know what I don't know. And that's always problematic.
MGK_2 responded:
MGK_2
Re: Jake2212 #150709
I put together this analysis on the human mTNBC trial as depicted in this
CytoDyn Announces Preliminary Results from 30 mTNBC Patients Treated with Leronlimab. Decreases in CAMLs after 4 Doses of Leronlimab were Identified in Over 70% of Patients and were Associated with a 450% Significant Increase in Overall Survival at 12-Month Analysis
I go into an analysis of it In Preparation for the Coming Results on mTNBC
Improved Comparison of the previous PR on 7/19 and The Compassionate Use Study of LL in BC
Here is an excerpt:
Quote:
"In standard of care, the majority of TNBC patients do not make it beyond 6-7 months. In the 7/19 PR, all 21 out of the 29 patients who actually responded to the Leronlimab treatment as seen by increases in CAML and / or CTC, remained alive at the 12 month point of analysis. 21 of 29 remained alive at 12 months with a series of (4) 700mg Leronlimab injections with carboplatin, where if they were to have received Standard of Care, they would have died by the 6-7 months point. In the latest PR on Compassionate Use Study of LL in BC, the numbers, claimed are 570-980% increase in Overall Survivability, (OS); this translates into 34 to 59 months of life with scheduled, continuous weekly 350mg Leronlimab injections. That's 3 to 5 years of life with continuous weekly Leronlimab injections."
I put together this post at about that time to determine how they extrapolated to get 4 year OS
Example using Spreadsheet to Estimate Overall Survivability using available Trial Data for future prediction
Here is an excerpt:
Quote:
The Press Release gave a range from 34-59 months as Overall Survivability. The mid point of that is at 48 months or at 4 years. On my hypothetical data example of this study, we have at 48 months: the likelihood of surviving is 46.2%. But 95% confidence interval requires adding and subtracting 17.37% which gives us a Range of 28.83 - 63.57%. 50% is within this Range. So this data set could qualify to be comparable with the actual since this Range include 50% at the same 3 month time interval of 48 months.
Now, in my hypothetical data set presented here, the Overall Survivability occurs at the 3 month time interval of 42 months, since Survivability is 49.6%, (closest to 50%). Here the 95% Confidence Intervals are: 17.5% giving a range of likely survivorship from 32.1 - 67.1%. Since 67% occurs at 24 months and since 32% occurs at nearly 57 months, we have a Range of 24 - 57 months, which is somewhat similar to the results of the Press Release, (34-59) months .
Lastly, previously put together thoughts on BTD
BTD for LL on mTNBC
Here is an excerpt:
Quote:
In contrast, our Compassionate Use Study reveals an overall survivability of 34-59 months, or 3-5 years . This was determined by use of statistical analysis and extrapolating a death rate to determine time at which 50% of original 30 patients would likely be dead by, and that came out to time range.
The FDA recommended withdrawal due to the current landscape of medications for treating mTNBC. Certainly, the FDA is aware of this most recent LL study and how it utterly blows the doors off the outcome from Atezolizumab with Paclitaxel. We just may have been the reason why the FDA made this recommendation.
With regard to BTD, break through therapy designation, I believe Leronlimab is the best drug for mTNBC out there right now. No one can touch our PFS or OS. We double the stand alone Standard of Care Paclitaxel for PD-L1 BC in PFS and OS. We have no side effects stand alone , but in this Compassionate Use Study of Leronlimab in Breast Cancer, LL was combined according to each Treating Physician's Choice with any one single-agent chemotherapy drug administrated according to local practice: eribulin, gemcitabine, capecitabine, paclitaxel, nab-paclitaxel, vinorelbine, ixabepilone, or carboplatin. Side effects of chemotherapy produce considerable morbidity.
AI
