Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Sent to IR
Quote
Please let us know if we have missed our opening in Brazil to do the Covid trials due to their situation having improved dramatically in the past few weeks. Or are we stagnated due to other reasons and we still expect these trials to happen? What does your silence mean; we were all so hyped for Brazil opportunity and now fear it has been lost.
Unquote
Another Data website for Covid:
https://ourworldindata.org/coronavirus#coronavirus-country-profiles
Check the metrics for vaccinations. (Compare US vs Brazil etc.)
Brazil and US both have ~ 60% vaccinated at least partially. A month back (July 27) US had 54% vaccinated at least partially and Brazil had only 34%. That means they have vaccinated (at least partially) another quarter of their population in the last month.
The rapid increase in vaccination may explain why the rate of new hospitalizations and critical cases may be going down. Good for them but it also means it will only become more difficult to recruit patients as time goes on.
Other stats:
US has by now ~ 50% fully vaccinated whereas Brazil has 26% fully vaccinated.
Brazil has a much higher case-fatality rate but much lower Delta-variant share.
Take back this post of mine.
I know shorts are having a field day with this point, but I am just as nervous about our trials not starting even 3 weeks after ANVISA approving cd17. It doesn't look normal to me.
Different reasons possible or talked about:
1. Not enough cash to run trials
2. BIOMM is waiting for final notes from ANVISA
3. BIOMM is waiting for LL to be imported (*Just saw that Nader is pointing to this reason as the primary difficulty, which has been overcome now. But not clear what other hurdles they face.)
4. Covid situation is improving fast in Brazil, so new severe/critical patients not coming in large numbers and opting to participate in our trials. Lost time is lost opportunity for this indication.
Cytodyn and others have done too much work to get this far and not have the trials go on and give LL a final chance to prove itself in Covid. At this point am mainly looking for updates on this. Good to know cancer, HIV etc. but time for Covid is NOW.
This matters for our trials since one of our requirements is that the patients are recently hospitalized and needing supplemental/high-flow/non-invasive O2, or for critical, recently got on ECMO (within past 72 hours). So even though Brazil has over 8000 serious/critical patients, only those who came into our category recently (i.e. ~ newly hospitalized, or newly on ECMO) will be candidates for our study. Adding overall new cases slowly means even smaller increments to these severe/critical categories.
That said, it doesn't explain fully why we have no recruits yet. Unless they are stalling in order to assess whether the trial will be completed given how things are seeming to get better and patients may get recruited too slowly. Bad scenario, hopefully none of this and we get started soon.
What do you mean "Brazil has kicked up the program" and therefore numbers going down? Do you think we will find it harder to have people to sign up for the trial since Brazil is already getting out of covid either naturally or due to higher vaccinations?
We thought US was out of the pandemic and Brazil & India were still struggling. Now Brazil is doing better and US seems to be shifting back a bit.
Quoting from my post 163447 where I did some number analysis on pre 14 and post 14 days data for LL+SOC vs SOC alone.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=163593995
(Note I may have got the hard numbers by my own calculations at that time; so there is some difference (in SOC arm) from what was published - check. But they are close enough and the same analysis should apply.)
14-day mortality for the 62 critical patients
LL+SOC: 2 deaths out of 43 patients (4.65%)
SOC only: 5 deaths out of 19 patients (26.32%)
Mortality between Day 15 and 28
LL+SOC: 10 deaths out of remaining 41 patients. (24.39%)
SOC: 2 deaths out of remaining 14 patients (14.29%)
Leaving aside the question of insufficient trial size for the subgroup and looking just at the numbers:
Shorts: LL-arm fared worse after 14 days because it is no better than saline if not worse.
Long argument: LL's presence in body reduced and the treatment effectively became equivalent to SOC after day 14. Thus we find ~ 24% mortality in the second 14-day period when many of the patients who might have already died in the first 14-days if given only SOC ended up relapsing and dying during the second 14-day period after the effect of LL tapered off.
Recap:
SOC: Days 1-14: ~25% of critical patients died; Days 15-28: ~15% of patients still alive at start of Day 15 died by Day 28.
LL+SOC: Days 1-14: ~5% died. Days 15-28 (when effect was closer to just SOC): ~25% of remaining patients died by Day 28.
So apart from the 5% of patients, LL had arguably shifted the starting point for others by 14 days - after which they followed the SOC pattern. This shift may have been sufficient for some; but for the majority (of those for whom LL could have made the difference) not enough. Had the patients been given 2 more doses, they could perhaps have gained another 14 days to avoid lasting damage on the organs from the cytokine storm and for the body immune system to recover its balance.
Is there a link where Biomm has indicated this is the reason for delay?
Is there evidence that you can point to, that establishes beyond doubt that AF knew of the FDA letter before it was posted to the public?
Yes it does not seem like something they would specially care to upload for ordinary retail. It does send a positive confidence message to the investor, showing clear summary of past results and the goals/program for the remaining year. But why? We already know most of it.
It would make more sense if they had to make a new presentation to potential big-shot investors or potential BP partner behind the scenes, so prepared this, polished and professional. If that is the case, the presentation then should have been before Friday and they uploaded the file on the website on Friday.
What amazes me is the attempt to create a false equivalence of some plan though not complete to our knowledge and no plan. Brazil trials are plan in action, credit management for that. For other indications as well, we know what we did so far, what we are trying to do next and where we seek to direct our energies.
It is not that the bar is low but to keep hammering such a ridiculous point that any semblance of a plan from 13d can be touted as something much bigger. And if it never comes, stay with the inane argument that present management also has no plan. Whatever.
Refer to my post 179516
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=165495852
If someone talks of severe or critical, we have to find out the inclusion-exclusion criteria in their trials and approvals, then compare with what we are seeking to treat.
Your reasoning makes sense. I was not here at that time but it has been truly tragic to this company’s success if the FDA indeed made us unnecessarily run on a wild goose chase even while approving drugs showing much lower efficacy. Now we are facing the loss of our main indication due to competition catching up.
I mentioned in post 179516 that our “moderately ill” in Brazil includes a large subgroup of those considered Critical in cd12. Only ECMO level patients fall in Critical category in Brazil.
If that is correct, then yes from the standpoint of LL, the distinctions we presently have for these categories apply at a later stage of the disease, and it will not be appropriate to conflate our “moderately ill” with what others consider severe.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=165495852
If your children just were diagnosed, it is probably too soon to think directly of LL. But good that you are planning ahead and will know exactly when and how to set the process of getting LL into motion. Good luck.
Misiu, this is a gem of a post, simple wisdom. This is NOT the time for this charade. And I am not even thinking of the incelldx connection and what they would do. I am thinking of ongoing effects on stock price, when we need cash and funds, when we are trying to run key Covid trials; the Time getting diverted and lost, when we need focus and attention to complete the BLA correctly on time. They are truly putting our interests, our investment in jeopardy right now, willing to and quite likely wanting to see us fail on these two major goals this year, in order to make Nader and co look bad. I strongly feel if not for their game now the stock price would be going up and not down based on recent news, and the company would start moving from strength to strength.
Anyone who thinks Covid is a real potential win for Leronlimab I think should be aghast and hurt by what this 13d is doing AT THIS TIME. Just step back and come again next year. That should have been obvious if they were really more interested in us shareholders. But for what they are doing now, I really cannot see them as anything noble. They are causing a mountain of hurdles to our succeeding in goals this year. At this point I cannot honestly hold Nader singularly accountable even if the BLA is not completed by October. And I don’t want to imagine not completing Brazil because of the ill effects on our SP and ability to raise cash. People can decry him all they want, but I see what is happening now. Like you are working to lead a group project to complete in a week and a section of your group unhappy with your leadership in the first go-around does everything to sabotage your time and resources and ensure failure now, so that you garner more blame and they can replace you as leaders. No, what this group is doing at this crucial time, jeopardizing our chances, tells enough of their leadership that will follow.
Question: How does the SP manipulation happen? Who sells?
13D puts out news before market close and independent gangs of shorts pounce on it and short,
Or 13D itself (and their supporters) conspires and coordinates a news+dump strategy in order to pull down the share price?
These are supposed to be our saviors?
That is ok. We can agree to disagree on some of these points.
I came in during the covid hype, and I am seeing a lot of things accomplished in a very short time by an OTC company. Most number of eINDs, two completed trials, at the same time going after LH, Cancer, Nash, HIV. Going after opportunities in multiple other countries, getting set in Brazil for a final and decisive push for Covid.
This is doggedness that I appreciate, if not marvel when I think back. Did the efforts come out successful in a binary scale? Not yet, but good intent + determination + hard work will add up. There are some intangibles that cannot be replaced easily; we either sense and value or not. What we call incompetence is part of the growing pains. Big Companies have it and more so the little ones. Which of the approved drugs (Remdesivir, Tocilizumab etc.) just got perfect results in every trial? cd12 is a stepping stone; Brazil is the completion.
Fine if some want to put the management on watch due to their past failures. Sometimes however the method of "watching" becomes a hindrance to the work at hand. Every minute spent in dealing with these threats and manipulations and their effects on SP etc, is a minute lost for working to get LL to succeed. That minute lost cannot be directly blamed on present incompetence of management but rather on the shareholders who employ the tactics based on what they see as incompetence of the past. But the goal of the detractors being the removal of the management, for the supporters of the management, the opposition efforts are directly against their immediate interests. For their focus is on the work that the management is trying to do right now and they have conviction that the management is already on the right trajectory.
This is perspective. I am fine with NP/SK credibility, as are Misiu, learning, Monroe and a few others. Things are not perfect, management I believe is improving, and retrospective criticism is at all time high. But they are presently doing good, have their heart and mind in the right place. Brazil is in front of us due to the unrelenting efforts of this management; hopefully the trials will proceed normally.
Of course, I want the same order as with cd17. Biomm first and then the PR from management. Good that ANVISA has approved but something not sitting well about Biomm and Cytodyn not already announcing it. Apparently they have 4 days to do so, tomorrow is fourth. And we need that "Not yet recruiting" to change.
I will relax a bit only after we get the PR that Critical is approved AND that Recruiting has started and moving smoothly.
Anyone know whether there is a difference between the event "first patient dosed" and the announcement "Recruiting has started"? Seems to me they are two different things, since recruiting now does not necessary imply someone recruited already. What exactly does it take to start the recruiting process officially and make a formal announcement of it? I thought this would be immediate after approval.
See also this one
Wow misiu what you said of your son’s second dose reaction matches perfectly with what Melon Toy said, about how fatigue persisted after the first dose but vanished after the second. It made her feel strongly “It has to be the drug” and not placebo. This raises my confidence that Brazil will succeed (if only we start recruiting!).
Jaylimab, looking at the clinical trials pages,
1. Brazil trials consider people requiring non-invasive ventilation or high flow oxygen as "moderately ill". And only those who are on ECMO are critical.
2. Where did cd12 put people requiring non-invasive ventilation? It clubbed them in the same group as Critical. The severe in that trial required that patient should NOT have "ECMO, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations"
So what does this mean? What we call "moderately ill" includes a major sub-group of those who were considered Critical in cd12.
The Need for Oxygen is the key indication. We are isolating that criterion into lesser and greater categories, i.e those who are a. hospitalized and requiring supplemental oxygen or high flow, non-invasive ventilation, or b. on ECMO.
In cd12, most of both these categories were considered part of Critical. In Brazil, we are focusing on this group primarily but splitting it up into two.
That also means that we are not focusing on the many other cd12 type "severe" patients who are neither here nor there and may be severe for reasons not related to what we think is Leronlimab's MOA. The Brazil trials have refined criteria that tries to weed them out. For example, we want patients who entered the "moderately ill" or the "Critical" phases within 72 hours prior to LL treatment and who have low probability of dying within 48 hours of study inclusion. So a patient may be suffering for a while, with some serious organ failure, doctors know there is little to no chance; yet cd12 may have considered that patient as eligible. In Brazil, we would be saying "NO" to including such a patient.
So, we got not so good results for "severe" in cd12 possibly because the patients were too broadly selected, and now we have refined the selection process. And in fact, the refinement is really focused on the "critical" of cd12 where we got the good results.
A couple of other references to some related issues:
In this tweet of Dr. Patterson,
he says that the dosage he used in the eINDs was 3-4. I don't know the number of such patients but lot of the early enthusiasm for LL in Covid came from his positive comments which were based on his observations of anecdotal eINDs for critical patients. One assumes this data was part of Cytodyn's cd12 proposal to the FDA.I used 3-4 doses on EIND patients so I was not the one choosing 2! https://t.co/R5WzOtVOeg
— Bruce K. Patterson MD (@brucep13) July 5, 2021
Longs, what explains why we are not recruiting in cd17 yet? Is this normal?
Also, we were saying on Saturday based on a webpage that ANVISA has already approved the critical. Is this a settled thing already, or could that have been a premature entry? For cd17, the news came out of Biomm first and then Cytodyn posted it in their webpage and issued a PR the following day. For the critical, there is no way for the Company to be silent on it today if ANVISA had approved by Saturday. ??
Yes, he made his statements with conviction in that audio and is willing to publicly confirm them again. Glad he was not silent and decided to reply to my message.
I sent a mail to Dr. Lalezari yesterday, basically telling that his audio is being referenced by Longs and asking whether he will stand by what he said if the powers-that-be challenge him. (Email sent through his quest-clinical website).
His Response 4:34 PM today:
From what I read and others also mentioned, "moderately ill" is our "severe".
cd10 "moderate" inclusion criteria:
The FDA letter said this:
But I will add frankly: I am not happy that Cytodyn said NEWS2 was a SE that was met in cd10, but never came back to defend or explain after FDA letter negated that cd10 met any SE. Cytodyn owes the shareholder an explanation, but can see they were caught between a rock and a hard place.
Could be, for that indication. I don't recall the details of that trial. It was preliminary and low-powered trial, and for most patients in that phase, the recovery may be natural and so much more difficult to establish that our drug makes a significant difference.
Remember also that LL is expected to make its main impact in the second phase of covid, if the disease progresses beyond the viral phase and into the cytokine storm stage. So even if it is not very effective for mild disease, it could be much more effective for severe/critical.
cd12 was "hypothesis-generating". We have now filtered the 'optimal' indications, trial design, dosage etc. for the Brazil trials based on the knowledge we gained from earlier trials. Things are in the right place and the Brazil trials need to be completed for a final assessment of LL in Covid.
Even if there is confidence based on eIND etc. that a drug on trial can work independently, it is not yet proven. So they can't risk the lives of severe/critical patients by comparing the trial-drug against a strict saline-placebo. The base has to be SOC and the trial drug + SOC has to prove its superiority vs only SOC. In the case of mild disease, they may go with Drug vs Saline.
Wrong
Note how it went from dosage and FDA role to a debate on NP. As if we have to pander to such diversions or get insulted, and of course if longs push back here, you know what happens ...
Well, I don't care for your colorful trip back to 13D salvation; that is not why I replied to your "nonsense" post.
For anyone else thinking "nonsense" about the FDA's role in dosage, that audio is a good reference.
I trust the doctors who have made public statements on this. For instance, between 0:20 and 0:40
http://ohm20.s3.amazonaws.com/CYDY%2010-20-2020%20--%20Dr.JL.mp3
You need not trust him.
FDA rebuke and general statement on trial design, one cannot jump from there to a negation of what the doctors have said with regard to their communications on the question of dosage.
Cytodyn had asked for 4 doses, FDA came back with "2". That is what Doctors involved in the communications said. Unless you know further about what FDA said in those discussions, you are talking nonsense with the assumption that Cytodyn could then have redesigned and started over in a hot-minute and all will be merry well with FDA approving. You know nothing.
We really cannot know this, what proportion of initial discharges will be premature.
Your assumption is that patients may get discharged prematurely and later they die when this could have been avoided with more LL doses. The trial as designed places much greater significance to the first outcome of discharge from hospital (for criticals). If early discharge happens for these patients, that is itself to be marked as a success, as something indicating efficacy of the drug if we get SS on this. If patient relapses later, yes it is bad for that patient and bad for some of the SE; but we cannot take those cases to assume that the discharge was unwarranted in the first place. Discharge with SS is big enough result to conclude LL efficacy.
Let me look at the situation strictly from the standpoint of our trial.
If a patient gets discharged from hospital, then they have effectively met the primary endpoint of the trial. There is no question of going back on that one simply because they later got worse. They have the value 1 or 2 (red below) in the 8-point scale. (3 in bold black is also part of the PE)
Not hospitalized, no limitations on activities
Not hospitalized, limitation on activities and/or requiring home oxygen
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
Hospitalized, requiring supplemental oxygen
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Death
Among the secondary endpoints we have:
Proportion of patients clinically recovered [ Time Frame: At days 14, 28, 42, and 60 ]
Ordinal Scale of 1, 2 or 3
All-cause mortality [ Time Frame: At days 14, 28, 42, and 60 ]
All-cause mortality
Proportion of patients discharged alive [ Time Frame: At days 14, 28, 42, and 60 ]
Ordinal Scale 1 or 2
Clinical Status [ Time Frame: Days 14, 28, 42, and 60 ]
Ordinal Scale
Duration of invasive mechanical ventilation or ECMO [ Time Frame: 28 days ]
Days
Length of hospital stay [ Time Frame: 28 days ]
Days
Length of ICU stay [ Time Frame: 28 days ]
Days
In all the bold SE, we have either met or have a superior outcome if the patient was discharged early.
It is only in all-cause mortality and Clinical status that the evaluations continue potentially well after treatment period, and the situation you envision can actually hurt our trial results. For instance, patient is discharged Day 11, disease relapses and they worsen by Day 28 and possibly die Day 31. Here that patient gives us a bad score in later-days Clinical status and all-cause mortality even though they were not given LL on Day 14 and after. Yes, that would be unfair to us since perhaps more doses of LL would have avoided such result.
However that is why it makes sense to keep these as Secondary Endpoints. It is a worst case scenario but in order for it to happen, that same patient has already given us a positive outcome for all the other endpoints (Bold black) including our PE. So, for the trial, I think this is deemed a sensible trade-off, a compromise we have to make that will not hurt us in the long run - with goal being showing LL succeeds in PE and some SE at least.