It is designed to be variant agnostic. It's a nucleoside analog that disrupts viral replication. The RNA polymerase recognizes it, incorporates it, and this causes a disruption of the RNA replication and a mess of downstream errors that prevents successful replication (I'm not super well versed in it's mechanism but I believe this is the gist).

It's possible for a strain to mutate and develop ways to evade this drug I'm sure but this will have good, broad coverage of all COVID strains.

The delta variant replicates much faster and viral loads are much greater compared to wild type strain, though, so that might change how effective MRK's drug is. I'm interested to see the complete data from the study

Complete game changer? 50% relative reduction in unvaccinated patients w/ an absurdly high placebo rate (14%). Trial size only a couple hundred patients larger than LIVE air and this is for outpatient.

Will it provide benefite? Sure, definitely. The game changer that people are hyping it up to be? Doesn't seem like it.

Also, it might be mutagenic to mammalian cells.

I imaging the FDA will have no "concerns" with their safety data though and a prompt EUA will be issued :D

Yes - critical is described in page 18 in that same document. Critical is defined as a pt w/ shock, multi organ failure, or Vent/ECMO/HFNC/NIPPV.

LIVE-AIR included HFNC/NIPPV, so there is some overlap (I didn't think those were included as criteria but clearly misremembered haha).

I believe the 60 day guidance was focused on hospitalized patients on mech. ventilation. While still hospitalized, LIVE-AIR's population isn't quite as severe. Overall I agree though, 60 day data is important and surprised the FDA didn't have it for EUA decision

Dale wasn't really attending anything post-P3 data release. Only thing we saw him in was the leaked video with the LIVE-AIR investigators. Dale is busy behind the scenes

1. good question about peer review. They do take a while, and humanigen being a small company doesn't help. I would expect it pretty soon. If it drags into december/2022 then I'd be pretty concerned. not worried right now.

2. Age <85, CRP <150 is a significant subset and was about 75% of patients in LIVE-AIR. This group will cover most COVID patients presenting to hospital. Currently, there aren't any great treatments for early hospitalization. Toci/Bari are more for later in disease course. Lenz can fill in the gaps perfectly and be used for patients upon presentation to hospital.

3. a)SWOV I believe is a good endpoint. Mortality is the most important of course, but preventing ventilation is very important. The long term morbidity of COVID, especially if you get sick enough where you require intubation, is substantial. Also, hospital costs of patients in the ICU/on ventilation is substantial. Preventing ventilation is important.
b) Yes mortality will be studied in the BET trial. LIVE-AIR hit statistical significance in mortality reduction in the <85, CRP<150 sub group and that was only on 330 patients (pretty incredible to achieve stat sig in mortality on such small n). The BET trial should have no trouble having great results and meeting statistical significance with 500 patients in this optimal subgroup.
-> Lenz will save lives, prevent ventilation (reducing morbidity), reduce ICU burden, and will be cost effective

4. CAR-T trial will take a long time. I believe latest guidance is starting their trial in 2022 and that will take 1-2years or so I believe. CMML and GvHD trials should be starting soon but will also take a long time. I believe this company is worth much more than the current 400m M and these indications are a big reason for that - but will take a lot of time for CMML/GvHD/CAR-T indications to come to fruition.

nice find. Really interesting and the inclusion of 12-18 year olds is very exciting. Placeholder text or not, for them to add that makes me think good things

It hit stat sig on mortality with 230ish patients in LIVE-AIR. Dale’s comment about sample size doesn’t really apply to this specific population

Yes the NIH doesn't include KNSA's recent P2 with Mav (which showed favourable results) in their summary of GM-CSF targetting. If their Phase 3 trial can show similar efficacy it will provide more evidence in validating GM-CSF blocking as an effective covid therapeutic

W/r/t the 60 day endpoint, I believe that is more for critically ill. From my understanding, the FDA told RLFTF to extend to 60 days because:

"28-day endpoint adopted in the 1990s for trials in Acute Respiratory Distress Syndrome is not appropriate for critically ill patients with Covid-19, who are frequently maintained in the ICU with advanced technologies well beyond this time point"

Source: https://www.prnewswire.com/news-releases/neurorx-announces-that-zyesami-aviptadil-has-successfully-demonstrated-10-day-accelerated-recovery-from-respiratory-failure-in-critically-ill-patients-with-covid-19-treated-with-high-flow-nasal-oxygen-at-28-day-interim-endpoint-301233805.html

I believe the 28 day primary endpoint for our population is adequate but agree with what you're saying in general.

the 2021 preliminary additions in the link I gave shows humanigen.

https://www.ftserussell.com/resources/russell-reconstitution

reconstitution takes place June 25 after market (guessing they put 28th since June 25 is a friday)

Bari, dex, and rem too I believe all continued getting placebo trials after EUA. this just isn’t how it works imo and not a concern. They’ve always needed more double blinded RCT data vs placebo for full BLA. P3 is sufficient for EUA.

"UK submission over the next few days" (just went back to watch quickly)

Nov calls intrigue me the most right now. I dabbled in May calls (RIP) but am mostly shares because I am very long with Lenz.

But given the variants, vaccine efficacy waning as people are months out of their 2nd dose, people wanting to live a normal life over the summer, general pandemic fatigue, and of course winter beginning, November calls intrigue me. I think we'll have EUA and hopefully CMA by then and if COVID spikes in the US again for the reasons I mentioned, HGEN will do very very well

Yeah it would be really interesting to see given the half life of lenz. Also, the KM plot in the original mITT population had great separation early but that plateaued and the lenz arm gave up a bit of ground approaching day 28. It's hard to say for sure what it will look like.

It could very well make our already great results look even better

Yeah my impression would be that all 60 day data would be done by around May 1. So maybe they weren't finished running the numbers prior to pre-print, but why not delay a couple days for that? A small part of me worries that 60 day data might look less favorable although that seems unlikely given how great the results were.

I've been wondering about the 60 day secondary end points and why the omission. I guess when the full paper is published that will be included?

little odd close staying so stable around 18.60 compared to usual.

Fintel update showing some significant institutional ownership adds (Fidelity index funds, Schwab ETF's - *effective date Feb. 28) -> https://fintel.io/so/us/hgen

I think it's worth noting the placebo mortality rate (and VFS rate) were incredibly low. I haven't come across placebo rates that low in any study looking at hospitalized COVID patients. I expect both our primary end point and mortality reduction trends would've looked even better if we weren't going up against such strong standard of care

I was thinking similar... wouldn't want a large short position heading into monday AM premarket. We shall find out

New institutional buy today!!... (Gradient Investments, 200 shares XD)

Which explains the termination of agreement. The trial with KITE was running at a snail's pace and opening Lenz up to the broader market makes sense financially and should speed the phase 2 study up imo

What does COVID EUA have to do w/ CAR-T trials?

Why should we be shocked? They finished the 1.b) portion and decided to terminate the agreement and open Lenzilumab up to the broader CAR-T market. Maybe I'm in the wrong but it seems some people are reading into this too much (similar to the mITT/ITT fiasco)

There is precedent for approval after phase 2 in CAR-T. Given the promising results so far with Lenz w/r/t efficacy and, most importantly, safety, I would not be surprised to see an excellent P2 study and approval based on that

I think you might not understand pump and dump scheme's very well. I would suggest you look into "CYDY" to learn more but it seems you frequent that board often!

These are numbers taken straight from our P3 study. Simply put, we have shown that we're the best therapeutic in hospitalized patients right now.

Great points. I was wondering what the implications of this is given the end of April deadline as you mentioned. Did they change the agreement? Is it just application? Are the confident of an april approval given the original agreement as you mentioned?

Given no news re: EUA application, I have a hard time believing we will get approval before May so I'm not sure what to make of it. Very positive news nonetheless

I guess you don't understand the multitude of issues from using outpatient IV Ab treatment in mild patients. That drug is not gonna catch on

Lenzilumab is THE anti-inflammatory drug for COVID right now. I can't think of any competing COVID therapy that fit's what Dr. Gallo is saying better than Lenz... giddy up everybody

Also, the partnership w/ Eversana can be terminated if no EUA by April 30... I think $HGEN is planning for this to be done by then although they'll need to file quickly for that timeline to be realistic

It leaves a bit of a sour taste for sure... thinking about the risk I took pre-P3 release only to see the price where it is today.

But I'm taking full advantage of this opportunity. Sub-20 at this point seems like an incredible discount right now. I've almost doubled my position and expect the price to ramp up quickly once this offering is closed

18.50 minus a $1.11 underwriting discount, per their prospectus: https://sec.report/Document/0001214659-21-003739/#underwritingsuppl

Reloaded at 18.52... Could drop below the offering and I'll be ready to reload some more. These prices seem like a no brainer

Ready to load up heavy if there's a morning dip.

I think I will go to sleep on this note. Beautifully put and what a magnificent day for $HGEN longs

I tried to copy it over, but I'm having some issues with the formatting (particularly the text linked to sources). Sorry about that

Hey all, writer of the reddit post here. Thanks for all the kind words earlier! All credit goes to the smart people on here and twitter!

Very excited (and nervous!) for this week. GL to everyone. Let's go!