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They're probably done recruiting and are now waiting for time-based endpoints to read out.
that's a good point about prophylaxis.
I actually stumbled across hgen when looking for anti-gmcsf mabs because I thought they might have monotherapy activity against solid tumors. Not sure anyone would ever test this b/c the mechanism isn't straightforward enough to test w/o combining with SOC (I think - not a clinician, lol). But I'm still speculating that it'll have more synergies with CAR T and potentially other immunotherapies beyond controlling CRS via myeloid suppression.
Let's be realistic, there is no way lenz is going to outsell even Humira in the next 5y. If we're lucky, lenz will hit peak year sales for its first indication in 5 years. Humira has like a dozen... I agree this looks like a great drug with a unique value prop, but it will take time and resources to realize meaningful benefit. Drugs like Humira have entire organizations dedicated to selling/dtc advertising, payer mgmt, hcp education...
To be honest given its likely broad spectrum potential the best owners would be players with significant development infrastructure for immuno assets (not just CAR T players imo). Notching this first (maybe even second) indication will be a big regulatory derisk and signal to buy
does anyone have the ISCGT data they presented on hand?
Sorry, let me clarify the CAR T bit - I agree hitting GM-CSF is very promising when it comes to curtailing rampant inflammation caused by CAR T. However, it will not prevent CAR T cells from killing non-cancerous B cells that also express CD19 or BCMA. B cell aplasia is serious but can be managed. CRS/hyperinflammation, life-threatening and only kind of manageable with anti-IL6R. The takeaway is that while lenz could mitigate one of the most serious side effects of CAR T, it leaves a number of other safety concerns on the table (which is totally fine, but we shouldn't construe it as a panacea for CAR T side effects).
However, I 100% agree with you about immunotherapy, which is a massive market beyond CAR T. Inflammation there is generally less life-threatening but still quite common. If lenz can be shown to help that setting, then there is a huge door of opportunity to be opened...
Pharma is dumb money. Don't conflate steady overall cash flows with competence in a specific area. Brand names mean jack in science, and I promise big companies know less about a specific indication than a biotech developing a product for it. To be fair, they don't have to. Their expertise is in product launch, regulatory relations, and payer negotiations (esp. countries w/ single payer systems).
That being said, CAR T is not that lucrative at present, as even products in more mature phases of their sales cycle pull < $1B p.a.; more importantly, CRS is NOT the only adverse effect. It would be great if lenz could solve CRS, but it does nothing for on-target off-tumor toxicity, such as B cell depletion and neurotoxicity (some papers show CD19 expression in brain). 4/4 approved CAR Ts hit B cell targets, 3/4 hit CD19.
New products are coming, some of which have safety engineered in and some of which don't; I'll reserve speculation regarding these. If mgmt has a clear forecast for what the CAR T space is going to look like in 2-3 years - and I venture that Dale does - I think it's totally plausible that Hgen backed out to prevent a premature marriage to GILD. I reckon it has to do with optimism: should we take a small win now and shut the door on future opportunities?
conference abstract tomorrow
I think from phase I so probably just safety data? Someone correct me if i'm wrong
short-term I think you're right, long-term I see this as building momentum toward other myeloid inflammation indications
the powers that be don't want to hear about Brazil!! What a remarkable time to have technical difficulties, lol.
investor asks about exploring OS as lenzilumab endpoint. Dale estimates they'd need ~1800 patients to give 80% power at their expected effect size.
Also, no data yet on T cell recovery - very high interest from all parties, pending deeper data analysis
I'm not a fan of the stockpiling angle, tbh. If the EU/AstraZeneca debacle has shown us anything, it's that govt buyers will bust the private sector's balls when it comes to setting a price point. Whether that's good or bad is a matter of personal opinion, but I'm not sure it's a major plus just yet
tough but very important set of questions from an investor right now: separation of primary endpoint curve early in Km plot, but narrowing later - what's happening to those patients? Any notes on secondary endpts?
Cameron/Dale on separation of curves: See mayo clinic article, where ARDS was shown to resolve extremely rapidly after lenz. However, sustained benefit not expected after lenzilumab clears from site of action (lung); single dose + relative difficulty of getting drug into lung drives this.
Cameron on secondary endpts: secondary endpts are still being mapped out, we are eager to share in a publication. There is a trend in OS, one of the secondary endpts.
hey, looks like they're playing up the myeloid-driven hyperinflammation tagline. Nice.
is anyone else unable to see the slides?
jesus christ, finally!
glad Dale mentioned the MDSC bit, that's why I bought in the first place >1y ago
proxalutamide readout has me very, very nervous.
Cameron posted this article on LinkedIn today. Independent scientific study out of UK published in Science Immunology highlighting the central role of GM-CSF and IL-6 in COVID-related immunopathology.
https://immunology.sciencemag.org/content/6/57/eabg9873
I'm here to put a damper on CAR T hype. Don't get me wrong, I'm team HGEN, but I would refrain from overestimating the CAR T market for now... even the earliest approved CAR Ts are still swinging < $500M global sales. It would be interesting how that'd be expanded by having lenz as a tox-controlling adjuvant, but it's hard to say. The main issues with mass use of CAR T (in my layman eyes) are a) the variable source material, and b) its highly technical manufacturing requirements. Until we get to allogeneic/off-the-shelf cell therapy, sales will be limited to larger, well-resourced hospitals.
The dream would be off-the-shelf cells with modular CARs, where we can swap out CAR constructs on a whim. There are a number of players in this field, so I'm sure we'll get there eventually...
some may have seem ACTIV-3 (Vir/GSK) virus-neutralizing mab failure. I'll refer you to this post as to why this isn't a cause for concern:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=159226393
Here's a reputable source regarding the role anti-immune drugs can play in hospitalized settings, summarized in layman's terms:
https://www.nytimes.com/interactive/2020/10/05/science/charting-a-covid-immune-response.html
agreed - Dale has about as relevant of a scientific background as you can get, not to mention deep experience with institutional capital.
What I do worry about, given the small size of their team, is how they keep up with advances in the field.
They addressed the pseudo-scientific questions I threw in the pot pretty well. They also mentioned potentially generating ifabotuzumab-based ADCs and CAR constructs, which would be very interesting. I need to read more about the target.
IP wise, they painted a strong picture with 100+ patents pending, issued, or licensed.
strong data mining capabilities, with segmentation and targeting of buyers by geography. Durrant suggests they have the ability to forecast case density 4 wks prior - if true, that would be astounding. Personally I'm a tad skeptical without seeing methodology
Cameron making a stark departure from his optimistic yet reserved tone of the past - now, stating "we have executed, and intend to continue executing at a furious pace" (paraphrasing)
LOL, Chappell going straight in on GSK. 90 mg for GM-CSF neutralization too low, over an order of magnitude lower than lenzilumab dose. Looks like the previous poster speculating about lenz safety studies in other indications was spot-on - Humanigen quite confident in high-dose lenz.
Fair point about the otilimab ventilator population, I missed that. Willing to bet effect size was squashed by dex in the SOC arm.
Too bad about the breaking OncoImmmune news, I quite like that company...
Most important news today, I think. Same target and similar pt population - unclear why results were poor. Does anyone know the dosing regimen they used?
this is exactly the issue, which I'd like to emphasize. Hospital-restricted mAbs for mild COVID are inherently limited because nobody in their right mind wants to be near the ICU unless the benefit outweights the risk (e.g., they're severely ill). And as we all know, antiviral mAbs aren't effective in the severe setting because viral titers have already declined, whereas the myeloid system will continue to crescendo.
The other important note that has only come up in the more recent investor presentations is the effect on T cell immunity. Will definitely be looking for that when mgmt decides to release trial data.
likewise. Well, I also bought the majority of my shares at $5 pre-RS so it'd be painful to do anything other than hold and trust the team
great to see HGEN will be at JPM. I'm fast approaching the one year mark since my first few shares. Crazy ride
great interim news from pfizer. Remember that the vaccine's cold chain requirements will require pts. to go the point of use twice - mass vaccination is a ways off. We still need Tx to bridge the gap.
hope the 75% analysis (and possible early stoppage for 'overwhelming efficacy, p<0.019) bears out in a few weeks after this election mess is settled. Maybe there'll be some bandwidth on mainstream media for us.
Cameron!! Continuing his habit of dumping on other immune modulators. LMAO. RIP canakinumab and novartis
In my opinion these data are very, very good, but not overwhelmingly amazing and mind-blowing (HR < 1.5 and trial expansion requested). I have a hard time believing they didn't expect to benchmark to SOC (rem/steroids) when designing the trial for 300 patients while aiming for HR 1.5. I forget the exact timeline for rem and dex trial data release, though, so it's possible the endpoints were designed before those pieces of evidence.
That being said, Dale did a nice job explaining why think the company is still (rightfully) excited about these outcomes. I expect EUA and BLA based on efficacy in the near term, maybe H1 2021. Definitely going to be an important boost to SOC as covid isn't going anywhere soon...
discharge or improvement by a certain # of points on a clinical scale, I believe
edit:
"Time to Recovery [ Time Frame: Up to 28 days ]
Time to recovery is defined as the first day on which a subject satisfies one of the following 3 categories from the 8-point ordinal scale (Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities)."
dale giving us a biostats lesson, haha. love it.
fingers crossed for good news, though I think we'll probably have to wait til next week at least. The US election will probably dominate news cycles this week...
the whole reason dexamethasone works in severe covid is because it's an immunosuppressant. Dex does nothing for viral load, period. You might even postulate it increases viral load because it's impairing your immune compartment and reducing its ability to clear viruses. Clearly, in severe covid viral load is not the problem.
I think of lenz as a more discriminate dex that doesn't come packaged with a bunch of side effects.
antiviral mabs are not the same as immunomodulating mabs. Antiviral mabs help early in infection when they bind to and prevent viruses from entering cells. They don't help in severe covid because the viral replication cycles have ALREADY HAPPENED; viral load has already been reduced by recruited immune cells and the issue is the huge number of innate immune cells they've attracted. These things are hyperactivated and dump inflammatory cytokines all over your respiratory epithelium. Hence ARDS.
Comparing lilly and regeneron mabs to humanigen's anti-gmcsf ab is stupid. They don't have the same moa and, as a result, of course they work in different points in time over the course of an infection. It's like comparing the throw distance of a football and a basketball because they're both balls. apples and oranges.