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Dang! Forgot about it. Can you re-post link? Thx.
Still, there is a clear difference in tone between "this clearly says leronlimab should be studied" and "this in no way proves leronlimab cures COVID."
The difference in tone could be the difference between getting published or not. I'm wondering if this article and the eIND paper might end up being published as a package.
These were some reviewer's objections. It was like the reviewer didn't get that an MOA piece was appropriately separate from (and prior to) an outcomes piece, which is to come based on the group of 49 eIND patients.
Does it imply a rejection, or at least delay? I don't know.
Before the trial results, I'm interested in the promised "outcomes" paper on the first 49 eIND patients, with 14-28 day followup. NP said it was just a week or two behind Patterson. Who is the lead author? Yang has half the patients.
Thx. Will be there.
Time?
Crossing 500m as we speak. There were 175m warrants out end of Feb quarter. Most people assume this is headed sufficiently skyward to treat it as 650-700 m diluted shares but with exercises yielding at least a couple quarters of cash.
Aha! So, you can get a 96-well plate RANTES ELISA assay for only $575. Won't break you.
But what is really exciting on their price list is that there is a special on the bulk size of RANTES!
"Recombinant Human RANTES (CCL5) 1.0 mg
Regular Price: $2,720.00
Special Price: $2,220.00"
Probably a big seller!
BTW, FBAG, was the second paragraph yours or theirs? I didn't spot it on their website.
Second paper re: outcomes of 49 EIND patients. NP said it would follow Patterson paper shortly. Any news? Any ideas as to when it will be submitted or even who are the primary authors? Yang at UCLA has most patients.
Did the FDA say it, or did Targeted Oncology say the FDA said it? I don't think that's totally clear. Targeted Oncology could have heard it from another party.
Do others think this is clear?
Thanks Blane and Rockleo - I have wondered for a while whether that was a significant impediment to adoption. There are other oddball filters out there - e.g. exosomes. Glad to know that isn't operationally difficult to implement.
Thanks, I don't know this stuff at all. Please give me a description & how big an issue it is in a COVID ward.
KC, I hadn't realized how much CTSO is being managed towards being a high quality, cash-flow positive, SMALL medical device company. Not a lot of urgency in Chan's capacity comments:
"[We] have ramped production to near-full capacity with the ability and flexibility to go up or down with the current situation."
Still, with a new CMO and an EUA for COVID-19?
With limited volume, they could be some help in showing that cytokine-related treatments are the way to go.
Agree - unlimited upside is why I consolidated into CYDY. Still, we should keep in mind many solutions may split the pie. At least the CTSO filter has a good safety record. Any doctors in here who know how much of a pain it is to put in a dialysis line?
Add the CytoSorb blood filter from CytoSorbents to the list of cytokine treatments. This snaps in to a dialysis machine - been used 80k times in Europe/Asia in surgeries likely to trigger a storm - does what it says. Here are their COVID comments from their earnings call:
"and in the first quarter, we treated the first 70 COVID-19 patients, including the very first patients treated in China with partner China Medical Systems Holding Limited of now more than 750 patients treated, including 25 under the US FDA Emergency Use Authorization."
The stock dipped as low as $4 late March, now $10.40 - up 40% since I took profits to put all my bets on CYDY.
All endpoints in mild/moderate trial are at 14 days - wow. I had forgotten that.
The primary endpoint is "Clinical Improvement as assessed by change in total symptom score," the secondary ones include time to resolution and a 7 point scale ranging from death thru hospitalization with various levels of oxygen support thru home and happy.
Today's trading - the sound of all CYDY traders (on both sides) collectively holding their breath. The silence is getting louder.
Not to be confused with lack of interest.
I would guess it's just a copy writer's error, but note the past tense:
"A total of 54 patients were treated with leronlimab in that phase."
...
"A Phase 2 trial is designed to evaluate the drug’s effectiveness in people with the disease or condition being studied, and to determine the common short-term adverse effects and risks associated with the drug. A total of 54 patients were treated with leronlimab in that phase."
Holzer doesn't answer their phone? Coronavirus stay-at-home order? Not thoughtful enough to change the answering machine message before leaving?
Oh, wait, didn't Georgia open up? OK, where are they?
Thanks for highlighting this OUTSTANDING news from the FDA.
It says they have finished their first look at the filing (which was made when stated), and that all they need are a few database adjustments, expected in under a week, after which it will be considered not only FILED, but COMPLETE!
The FDA could have (and often does) say a filing is inadequate and ask for more studies.
With the promised PDUFA, they should give us a DATE for an advisory meeting and for APPROVAL.
Again, thanks for highlighting the OUTSTANDING news.
Outstanding quote from Novant's Chief Medical Officer - expanding to severe/critical trial after early experience with mild/moderate.
As "manufacturing, manufacturing, manufacturing" becomes "enrollment, enrollment, enrollment" this is exactly what we need.
"Encouraged by early reports ... in critically ill patients ... under EIND." Sounds like he's responding to Patterson's paper.
Not sure how to think about 400 being screened for the Phase II but only "a number" admitted. Thoughts?
So the info is known internally.
Do you think it's reasonable to get NP to agree to release that publicly on a scheduled basis, say once a week? Not just transparency, but assurance of future transparency.
I'd be happy with a 2x3 table (#injected,#sites injecting) x (compassionate, mild/moderate, severe/critical).
I defer to your knowledge as to precise content and whether/how to pursue with NP.
Are you saying the data is available, or that it is typically public?
Should we encourage NP to agree to put out a table every Monday updating the number of people injected and sites injecting, broken down by compassionate, mild/moderate, and severe/critical? Transparency...
What resources do you find most valuable?
Thanks, I didn't hang for the Q&A
Yang's brief talk:
3 of 7 slides totally about leronlimab: a) ucla blood work justifying studies (suggestive only), b) MOA - RANTES is a "beacon protein" trafficking too many immune cells into damaged areas; c) summary and positive comments on Patterson paper. No outcome mentions.
On early slide, listed with "IL-6r blockers" as candidate for damage limitation phase. Slide showing list of all UCLA studies showed all three leronlimab open, w/ 25 compassionate use. Only 2 in RCTs but they have only been open 5 days.
Slide on Remdesivir balanced - only relevant in early virus replication phase.
For clarity, this is "Nature Reviews Immunology," a part of the Nature family of journals.
I can't read this dense stuff quickly, but it says macrophages are a problem - a nice set up for Patterson saying we can keep them from aggregating.
Not true in these times, IMO. I've been through the delays you describe (got a JAMA co-authorship myself), but back then reviewing a paper was never anyone's priority.
Today, say Nature called (ha-ha) saying they want you to review a paper that could change COVID-19 treatment. After finishing nature's call, what else besides responding to Nature's call would be more important in your day - 24 hours a day?
Also, (1) these major journals are competing for major COVID scoops - Lancet even bothered to publish negative results on RVD from an underpowered study, and (2) prelim versions of Patterson's paper have been making the rounds in medical circles (again, ha-ha) for weeks.
Here's an alternative, just speculation, about why a Nature paper could take another week. Nature includes opinions and commentary - they could be turning this into a multi-dimensional piece. Again, just could be.
Dr. Yo was clear it was to appear in Nature. He even described the way the materials were organized for submission - in a way that is unique to that journal.
That same interview is where many of us got the impression it would be in the next issue of Nature to come out. Others have said Nature comes out on Thursdays.
ScienceOC - can you verify you have a copy of Nature dated 5/7/20?
Charts (c) and (d) may show absolute, not relative, binding.
On rereading, even though the analysis was done using "competitive flow cytometry assay," I think they are saying that, by day 14, virtually 100% of the CCR5 receptors on the bulk T-cells and monocytes were occupied by a molecularly-labeled leronlimab cooked up by BP.
Nowhere for RANTES/CCL5 to attach.
True for every single patient.
Again, help from any doctors out there. I'm not one.
Thanks, rstar. As a way-back statistician, I so love great graphics. And how they communicate great results.
For the future, right? Interesting "in cell culture."
OK, getting the sense of the other Figure 2 graphs.
(b) and (c) go together - (b) shows CD8 recovery relative to all CD cells "3 or higher" while (c) shows recovery relative specifically to CD4. Both show normalization of the immune system. Both statistically significant.
(d) and (e) go together, telling the story of CCR5 "receptor occupancy" - (c) looks at bulk T-cells and (e) at monocytes. This is a "relative binding" number as I read it. I believe these two charts are where make BP makes his case that leronlimab's preferential binding to CCR5 is the causal factor in improvements. Can someone help here?
Man, I wish Nature could put Figure 2 on the cover.
Figure 2 shows 6 charts, one per blood chemical, each with a line per patient showing levels at days 0, 3, 7 and (sometimes) 14 days.
The ones I understand are Il-6, the CD8/CD4 ratio and viral load (graphs a, c, and f). Because you are measuring change over time, there is an honest-to-goodness p-value calculable: they are p=.037, p=.001 and p=.011 respectively! On just ten patients!
There are also healthy controls on the some graphs (can someone dig in to identify who?): Il-6 was zero, no surprise but good to show. Viral load was zero by def. The distribution of the CD8/CD4 ratio for controls matched the day 14 leronlimab range and did not show a time trend.
I don't know how to copy the graphs here - go to the pre-print site, find "download PDF," open it and see page 22 of 24.
They are beautiful!
Dr. Otto Yang of UCLA Health, who has treated 23 EIND patients and is the PI for both leronlimab RCTs there, is a panelist at a UCLA Clinical Research talk at 3:00 pdt Wednesday. Preview of his input to the outcomes paper?
Mike, you said:
"Some CMO structure their contracts such that payment is due between bulk production and final fill"
The Anjimoto press release says they are providing "fill and finish services." No indication they are actually growing the stuff. Sounds like your concept.
This is for the "fill and finish" of the drug. No reason to think Samsung isn't growing it in a bio-reactor.
Outstanding! The Wednesday briefing from Otto Yang, who is the the P.I. at UCLA Health for both leronlimab RCTs and the "compassionate use" (that's what they call it - I know it's an EIND) program is at 3pm PDT. I hope he will preview his input into the upcoming paper on outcomes.
Absolutely. The good doctor and I are in the weeds discussing whether you need to assume AZT has to be given along with HCQ in considering its side-effect profile.