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Article posted in Cytodyn website:
https://d1io3yog0oux5.cloudfront.net/cytodyn/files/pages/cytodyn/db/256/content/bmj_Edison_Long+COVID%5B5%5D.pdf
Just 2 references to Leronlimab (ctrl+f). Interestingly the article states "Leronlimab is a monoclonal antibody that blocks the function of CCL-5. It has been found to be effective and safe in HIV."
Reference to 2018 published article of Dhody, NP, Kazempour. We know the basis for this is the ph 3 trial where PE was met. Yet SEC has objected to Cytodyn making such claim. Is there a general standard in writing journal articles that we cannot say a drug has been shown to be "effective and safe" unless and until FDA actually has approved the drug? Or is it not unusual (or "illegal") for such a claim to be made based on success in ph 3 trials?
Actually that 8-k is comparing our data against a trial for another drug "SG". We do very well against SOC of that trial but comparably (in subgroups) against their main drug SG. But we don't know how their trial filtered for their patients. Also, Merck updated that Keytruda has passed PE for mTNBC. See their recent news.
Some chance then that it will be countered by a positive PR news, ideally of Brazil trials.
Saw that the main news of questions from FDA came out on the 20th. That's when the price took its big hit. However after today's final CRL, company showing some spine in its response is good to see. Market seems to agree.
ARDX - CRL from FDA and pushback from management. Not into the "Oh GOD FDA said it. All bow and surrender."
Note Stock's price action in the first 10 min after release.
https://finance.yahoo.com/news/ardelyx-receives-complete-response-letter-200100531.html
That matters especially for those still holding to their shares in the company. We are directly invested in the immediate success and goals. If we sell, our mentality willl change; we don't want our reasons for selling falsified. So we start rooting for events that validate our decision to sell and look for ways to win back in and justify our original investment. Sort of Revenge trading.
Can we list where all Nader or management made false statements about the results of their trials?
The only questionable case that comes to my mind is the claim that NEWS2 was SS in cd10. FDA in stating (that's how I read their letter) that cd10 had no SS results seemed to directly contradict the PR that NEWS2 was SS.
I don't recall anywhere else where their statements can be regarded as anything more than forward-looking. With NEWS2, that was a definite mess-up either from management or from FDA. I was upset with the management that they never explained this directly. Either they lied about it to shareholders or were (understandably) afraid to poke the bear any further.
Also anyone know the date of the cc when Nader guaranteed Revenue within a week from Philippines? I want to listen to him again. In my common sense I took that as forward looking right when I heard. Like I do any statement about Brazil trial being very close or "any day now", or likely having first patient soon. We know that it is dependent on other factors coming together beyond the control of management, and till it happens, all such statements must be taken as FLS. Shareholders need to accept what that means and how to sift it from verified written information.
But does that mean they should not point out subgroup analyses that show LL's potential? NO, not for me as a shareholder. Not unless FDA directly makes a rule that defines the limits in no uncertain terms, where we can show Nader's statements as having crossed the boundaries of FLS. Otherwise I certainly want to know all that they can figure out from the data that shows promise. When the trials are low-powered, we have to try and glean the possibilities if the data can show them somehow. Doesn't mean we claim it will come through in a bigger trial. If people think it is all a hoax by Nader and co. to project such info, then they should accept the thesis that LL is just saline and just stay with that. Otherwise of course it matters all that they found and advertised about the subgroup results in cd12, etc. We are in Brazil still not because Nader wants to keep the ball rolling, but because we still believe that past results show great possibility that LL works in Covid.
Is this Keytruda a direct competitor?
https://www.merck.com/news/merck-announces-phase-3-keynote-355-trial-met-primary-endpoint-of-overall-survival-os-in-patients-with-metastatic-triple-negative-breast-cancer-whose-tumors-expressed-pd-l1-cps-≥10/
The pr says they already had interim results that showed significant increase in pfs over chemo alone. Now also for OS. What does this mean for hopes for Leronlimab in this indication?
Credits to Cytodyn Management (on the science front) in past year.
1. cd10 completed.
2. cd12 completed.
3. LH Ph2 completed.
4. Data collected and analyzed for 30 mTNBC patients.
5. Good efforts to initiate opportunities for Covid in Philippines and India.
6. Initiating trials for Covid in Brazil, building off cd12 data. Management has done its job here; it is up to ANVISA at this stage to have the trials go forward.
7. HIV BLA (second round) draft of dose justification submitted.
8. NASH enrollment 60 patients completed.
9. Communicates with shareholders promptly any relevant news through PR, proactive interviews, cc.
Current works and Projected goals for this year
1. HIV BLA timelines well-defined with final submission in October. (Being done following Communications/Guidance for FDA.)
2. Communications with FDA regarding LH & mTNBC results. (Depending on FDA response, potential LH trial later this year.)
3. BTD or Ph 3 in LH and Cancer.
4. Brazil trials, which will definitively answer our potential in Covid.
5. NASH results (possibly delayed here if we follow Dr. Recknor's desire for more patients and further bio-marker analysis.)
Discredits to Management
1. HIV BLA submission (first time) botched
2. cd10 trial. NEWS2 said to be secondary endpoint that was met. FDA in its letter flatly negated any such thing. Management refused to explain to its shareholders.
3. Management decision to not have interim look by DSMC at 75% enrollment cd12. Management decision to not take penalty for look at data. In retrospect only, this can be argued as foolhardy.
4. cd12 design could have been better, again only in retrospect. Fact is cd12 turned out to give more info regarding fine-tuning trial design for Brazil. So it was a stepping stone.
Current Management is doing good at this moment. No wish to ruin the potential. Yes we need results. Brazil can help the cause by approving the trial. Then HIV BLA, that is on management to make happen.
If the 13D wins, how will our present goals become disrupted? What will happen to Brazil, LH, BLA, NASH, cancer at whatever stage they are at? Will they simply transition over and continue to completion, and if not how will the timelines change? Will some get dropped or indefinitely postponed? All this present data from mTNBC, LH, research on them, FDA communications regarding them, what happens to all that?
Shareholders will want to see such questions answered in their plan. Especially if they have not already sold out their shares since they are invested in these current immediate goals coming to fruition.
No way for vacations at this time. Yes they are under a heap of pressure. But they should be checking emails regularly. I sent some Qs last week and got a standard reply on Saturday (from Dr. Kelly) that they have legal constraints in answering such in non-public mails.
Best scenario: Just happens to be a busy morning and they cannot give time for this request just yet.
Worst scenario: They are having new doubts about efficacy of LL for cancer, based on recent data; or about the patient population for which it works best - hence hesitant to give eINDs arbitrarily.
Most likely, we hope, the best. Unfortunately even a Compassionate use request and its outcome are not private and we all know about everything through word of mouth. We assume HH is telling the truth from his side. So, now, a mini-session of speculation and paranoia unfolds.
Strange to think. The activists must be hoping against hope that Cytodyn not come out successful in any of their immediate goals and share price keeps struggling so that they get the vote to take over. Will they be happy if Brazil trials get approved next week? Or if FDA comments positively on LH or Cancer results and gives green light for next stage? And share price jumps back over $3 or 4 in the coming month or two?
Dr. Been has done a recent YouTube video on Maraviroc, lot of info on CCR5 in there. Not too much on LH connection but more on HIV. Goes along with his talk on LL MOA last year.
Type your info here and it should work.
https://78449.themediaframe.com/dataconf/productusers/cydy/mediaframe/46064/indexl.html
Ok just noted that 3x post on outstanding shares. Not sure how that will affect the equation, but nothing to act sure about a 7.68% ownership either.
If I own 1000 shares and vote yes, and a group of 100 shareholders have 11 shares each and vote NO, I am thinking the NO wins.
The CNBC article says the activist group has 7.68% ownership. Suppose them and their supporters own 35%, and the owners of the remaining 65% all vote for current management, then in my logic, the latter should win since all together they own more of the company. Prorating should not make a 35% ownership somehow win the vote.
Brazil is up front, HIV BLA is on timeline, initial trials complete for mTNBC and LH and next steps for communicating with FDA for ph 3 or BTD, all on target. Not lost at all and doing a fantastic job presently.
NASH if it is being put on back burner or suspended, I wanted to know whether Nader gave any reason.
Did Nader explain why they may stop the NASH trial? Is it strictly a matter of wanting more patients to increase power of trial, or does it have anything to do with LL not working for the indication or the competition of other companies?
Can you explain this? Is there some weighing of votes based on how many shares each investor has?
Looking more carefully at page 17, the last chart comparing Rantes for LL and placebo,
the distribution for both seem mostly clustered near each other, the mean or median being slightly less for placebo than for LL. I doubt we can say placebo patients had significantly less Rantes in the system than LL. Both groups had slightly decreased Rantes overall at week 4 compared to baseline, with placebo for whatever reason reducing a bit more.
My logic however for LL was that since it blocks CCR5 in lungs etc., the organs should not attract CCL5 in the LL patients as much as it would in placebo patients, and therefore we should find a significantly greater % reduction of CCL5 in LL patients than in placebo patients. This clearly is not the case.
The conclusion from this may only be that Rantes may not be the key problem for LH patients unlike for the critical covid patients. The MOA of LL (if it works for LH) for LH patients is not about its blocking of ccr5 or reducing the presence of ccl5. Likely something else.
Pg 16 shows biomarkers for which LL seems to have higher and positive % change than the placebo. These may be more relevant for LH than change in ccl5.
???
I see kgro's maxing off my post on twitter
Excepted the study doesn’t “show” it and Leronlimab has been pumped up by illegal stock promoters - welcome to their team$CYDY : IT’S ALL FAKE https://t.co/cZkOWl4dpJ
— kgromax (@kgromax) July 23, 2021
$CYDY baggies discovering that Loserlimab is no better than saline and maybe worse - this is a giant IQ test and the results are not pretty pic.twitter.com/8qgFWQOrkc
— kgromax (@kgromax) July 23, 2021
Questions sent to IR
Quote
In the 8-k, there were two charts that were confusing and concerning.
For the cancer trial, we are getting better data for patients having < 50% CCR5 expression. But don’t we expect our drug to stand out more in helping those with higher CCR5?
Secondly, in the LH data chart for CCL5/RANTES, the placebo is showing lower levels of RANTES. Shouldn’t LL treated patients have lesser RANTES since the drug blocks CCR5 and hence does not attract RANTES into lungs etc.?
Can you explain?
Unquote
I wish they had done these labs on cd12 or eINDs where cytokine storm is the main issue. Still this is a bit discomforting. Wonder if management can give a viable explanation; the entire premise of LL is that it is CCR5 antagonist.
That’s what it seemed like in the article as well. It may get classified later as another “chemo” drug, whatever that means.
The article cited by daemon has this in the abstract:
The graphs are very interesting; some analysis of what I am presently understanding.
Comparison with SOC and SG from SG trial.
They have compared the results of LL against both SOC (chemo) and another drug's trial (Sacitizumab Govitecan). Most likely Cytodyn has used the SOC data from that trial. So that would be a firm reference point for our study, and not some adhoc numbers pulled out of a hat.
LL has done much better than SOC but either similar to or slightly better than SG (at least in certain identified subgroups)
Graph on Pg 6:
This shows the mPFS and mOS graph for SOC (the left column) and the SOC vs SG on the right column. (So the left column just separates out the SOC data in the right column and presents it separately).
SOC: mPFS = 2.3 months. (i.e. half of patients in the control SOC group of the SG trial had PFS <= 2.3 months (disease became worse within 2.3 mo) and half had > 2.3 (disease became worse only after 2.3 mo))
SOC: mOS = 6.6 months (half of the control group of SOC-only patients in the SG trial died within 6.6 months)
SG: mPFS = 5.6 mo. (half of SG patients in the SG trial had disease progression within 5.6 mo and half had only after 5.6 mo)
SG: mOS = 12.1 mo (half of SG patients in the SG trial survived over 12.1 mo and half died within ~ 1 year)
In the Summary Page 11,
the goals stated are that we want LL patients to have mPFS > 2.3 mo of the SOC or >5.6 of the SG trial; likewise goal of mOS>6.7 of SOC or >12.1 of SG.
Clearly we would like to be above the benchmarks of SG. If the SG trial leads to approval and it becomes the new SOC, then we would have to outperform it. However for now, at the least we need to do better than SOC.
However the purpose of our "trials" is first of all to figure out the ideal patient population on which LL will work best on. This is VERY important. Our 29 or 30 patients is a whole mix of unfiltered patients including both Compassionate eINDs and the phase 1b group. The SG trial would have been much more honed in on the group for whom they decided from their early phase trials their drug will work optimally. We are trying to do this now.
CCR5
Page 7 shows:
Among the patients (18 out of 29) who had CCR5 < 50% in tissue samples, Leronlimab+Carboplatin showed similar mPFS as SG. However for the 11 patients who had CCR5>= 50%, LL showed worse mPFS than SG. (It is not clear if the CCR5 % noted here is what is recorded before the treatment starts; after treatment starts, LL may impact the expression (?))
Their conclusion in the Summary Pg 11:
This correlation between LL efficacy in mPFS and the CCR5 expression suggests that LL works better on patients who initially had < 50% CCR5 expression.
However when it comes to mOS, there is no specific correlation with CCR5 expression that our data shows. Leronlimab seems to generally have mOS similar to SG.
The CAML data
In our trial 18 of 25 patients (72%) showed decrease in CAML after 1 cycle of LL treatment and 7 of 25 showed increase in CAML after 1 cycle.
Interestingly they found excellent improvement in both mPFS and mOS in the subgroup of patients who had CAML decrease after 1 cycle. That's where the 300% and 450% showed up; probably in comparison with SOC but from page 9 graphs, the OS for this subgroup is superior to SG as well. We may guess that in this group, many are surviving well past 12 months.
(Pg 9 graphs seems to suggest that patients having small CAMLs tend to do better with LL (and comparably with SG) than patients with large CAMLs. But I don't follow what that means. Is that an earlier stage of the cancer?)
All this information tells us the possibility that LL may prove to be best drug for patients who had CCR5 < 50% and who showed decrease in CAML after 1 month 1 cycle treatment with LL. Hopefully the FDA will look at this wealth of data and conclude that indeed we should do further trials and let us move forward in that direction.
If not for SG, our data would already be extremely compelling against the SOC that the SG trial was comparing its data against. "Unfortunately" for us, the bar seems to be set very high by SG though we may still have a subgroup of mTNBC patients for whom LL will work best. More importantly, if we can build off these initial results and show that LL is indeed a cancer fighter, then it also bodes well for our chances for the many other solid tumors that we hope our MOA works on.
8-k out
Probably you already sent to ir@cytodyn.com skelly@cytodyn.com Nader email in (https://www.cytodyn.com/contact). Otherwise you can do so.
I am a committed long hoping for the company and drug to succeed. But if they are real (or more importantly Leronlimab is real), they have to be able to answer the critics properly and not make mistakes in their PRs that give space for criticisms that they cannot candidly defend against.
We will see; I am hoping that the management tackles today some of these questions and criticisms of their latest PR, or at least makes a proper case that the results indeed are significant no matter how shorts and skeptics try to invalidate them.
Not true. Brazil update is expected in the cc, if anything. Same for LH. But it is not something we can be asking new questions about at this point. I had asked them recently on Brazil; if others have something specific on Covid or HIV, they should send the questions. Are you a long with money invested? Then send the questions on cd12, Brazil, HIV to ir without showing animosity; I think they read it out more or less in order and we can see how Dr. Recknor, SK and NP answer them.
Shorts will love this thread:
Cytodyn ($CYDY) has put out yet another press release touting "strong results" from their triple negative breast cancer (TNBC) Leronlimab research and their intent to "evolve into an oncology-focused company. As a TNBC patient & advocate (NOT an investor), I have some questions. pic.twitter.com/CogRkPjwtF
— Quidama (@IamBreastCancer) July 20, 2021
Sent to IR:
Quote
The clinical trial website shows that these trials were single arm studies. Without a placebo arm, how have you come up with formal numbers like 300% increase in mPFS and 450% increase in mOS? Even Daniel Adams in the PR only stated that typical mPFS is 2 months while we had 6 months - which is only 200% increase and not 300. And people in stock forums claim that literature shows that Cytodyn’s median (mean?) values are no better than the typical numbers unlike what Adams claims.
Let us know how exactly you got 300 and 450; FDA will surely expect a rigorous justification based on available literature and “typical values” largely accepted in the medical community. Tell us what that is.
Unquote
This is not phase 3. At this point if the results are as positive as Cytodyn is presenting, then we have a compelling case for conducting phase 3 or getting BTD. Suppose a drug is given to 10 cancer patients and all are cured, do we look at it as potentially being a cure and justifying further study or simply act like it’s completely meaningless and start bashing? The former.
In our case FooBar has given the trial info that there was no placebo arm. That raises a valid question how they came up with formal numbers like 300% increase in mPFS. Even Dan Adams is only saying typically 2 months while we had 6 months - which is only 200% increase. And for OS, where is 450% coming from? If Cytodyn wants to present such numbers as facts, then they have to be able to give reference in literature of the “typical” values compared to which our numbers are showing such % increase.
Goal for me is to get as much clarity as possible; give management a chance to explain details during the cc. I hope others also send questions with this mindset. If people (longs) doubt the virtue of testing CTCs based on the article of kgromax, ask management to explain. Direct to Dr Recknor if you wish.
I misunderstood OS or mOS. It is also time, for overall survival.
If people feel that the stated mPFS or mOS are no better than typical results elsewhere and that the Director Daniel Adams is giving wrong numbers to favor LL, then you should write out the argument carefully and succinctly with the references openly stated. Then someone can send that as a question to IR and management for clarification during the CC.
Add: If we don't ask the management this question before the CC, then at the CC we can expect these numbers repeated without any pushback. So best to challenge the numbers Adams is putting out there and have them justify in proper manner.
Ok, I missed the "typical" info they have in there. Have to look at it again. But the % data resembles that of a trial where you compare against the control group in the trial.
If Cytodyn says 300% increase in "mean PFS" and 450% increase in overall survival in 12 months, how can we possibly say those survival numbers are not better than typical medians? The PR has not given any information on the actual median PFS in either arm of this study, so how can we compare with some data elsewhere (of "typical medians")?
It would make more sense to understand that when our data for mPFS or OS for the LL arm is compared against the Placebo arm, we find that the mPFS for LL arm is 300% higher than placebo arm (like 4 months vs 1 month) and 450% higher for OS (like 11 patients survived vs 2).
(4-1)/1 = 3 (4 is 300% increase over 1)
(11-2)/2 = 4.5 (11 is 450% increase over 2)
Some shorts in twitter are honing in on Holly Kennedy's death in spite of LL treatment - almost suggesting (in 2nd tweet) as if the deterioration was accelerated because of LL.
This $CYDY pump is particulary disgusting bc it preys on vulnerable women with an aggressive type of breast cancer. CytoDyn doesn’t mention the mTNBC patients like those in Ireland who took leronlimab under compassionate use and died within weeks.
— Adam Feuerstein ✡️ (@adamfeuerstein) July 19, 2021
I don’t care if you donated. They are the FACTS. She did travel to pick up her drugs& note she was well enough to do so, still under care of Irish oncologist. After that the drugs were going to be delivered to Ireland. She dramatically deteriorated once starting Leronlimab FACT
— Eileen OS (@eosull) July 19, 2021
Problem is ANVISA formally says "Review and approval process by ANVISA typically takes 18 weeks."
I had asked a question on this in the June 21 CC. See after 58:30. Nader said they are in touch with the groups there and hopes for July end; and Dr. Recknor pointed out that Covid situation is expedited due to their urgent need right now; "much faster timeline".
But that is all just our hope, perhaps based on what BIOMM and the hospital there are telling us. Once the application goes to ANVISA, we are probably just in waiting mode till they answer. The best scenario is whenever they do respond, they don't reject or call for changes that cause further delays.
https://globalregulatorypartners.com/wp-content/uploads/clinical-trial-brazil-05.30.20.sd_.pdf
Does anyone know if ANVISA tells them thumbs up or down, is Cytodyn obligated to inform the shareholder of the decision within a certain number of days?
That one seems targeted at the investor-activist but that Dr. Lalezari is still favorable about the drug. The others seem to use Dr. L's silence and private communications to undermine management or confidence of LL on covid and other non-HIV indications. He is backing tweets of Dr. Bream in them. Anyway that's part of the campaigning going on.
Dr. Yo is tweeting in subliminal fashion suggesting Dr. Lalezari also has lost confidence with management and is no longer in good terms with them. All these docs have sort of ganged up now, professing pro-LL but "Nader's to blame". Would be nice again if Dr. Lalezari would tweet independently rather than talk with a clearly biased Dr. Yo who then insinuates the Dr. L's changed opinions.
https://twitter.com/YoDoctorYo/status/1415539695744782340
https://twitter.com/YoDoctorYo/status/1414992481083531267
https://twitter.com/YoDoctorYo/status/1413554037182582785