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@humanigen
Data issued today from South Africa show, in contrast to the Beta and #Delta, the #Omicron variant shows substantial evidence for evasion of immunity from prior infection. Highlights the critical need for effective therapies that are #variantagnostic. https://t.co/SHQiF1noTg
— Humanigen, Inc. (@humanigen) December 3, 2021
Here are some lenzilumab science-related articles for those wanting to do some due diligence. Lenzilumab is a GM-CSF inhibitor. The "M" in GM-CSF is macrophage.
Covid
https://www.bbc.com/news/health-56352128
https://immunology.sciencemag.org/content/6/57/eabg9873
https://directorsblog.nih.gov/2021/04/13/mapping-severe-covid-19-in-the-lungs-at-single-cell-resolution/
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30267-8/fulltext
https://www.nature.com/articles/s41586-021-03569-1
https://www.pharmaceutical-technology.com/news/humanigen-lenzilumab-improves-survival/
CAR-T
https://www.nature.com/articles/s41408-021-00459-7
https://www.nature.com/articles/s41421-021-00255-4
https://www.targetedonc.com/view/lenzilumab-plus-axi-cel-achieves-responses-in-100-of-patients-with-dlbcl-with-limited-toxicity-in-small-study
https://www.healio.com/news/hematology-oncology/20210422/lenzilumab-before-cart-induces-high-response-rates-without-severe-toxicities
LENZILUMAB - Calming COVID Cytokine Storm
Stimulating severe COVID-19: the potential role of GM-CSF antagonism
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00539-7/fulltext
Over the past 20 months of the COVID-19 pandemic, a great deal has been crystallised about the ideal therapeutic targets for infected patients. For very sick patients who require hospitalisation, we now know that targeting the dysregulated host response is of greater value than targeting the virus. Through steroids, interleukin(IL)-6 blockade, IL-1 blockade, tyrosine kinase inhibition, or Janus kinase inhibition, we have a breadth of clinical trials that show the possible mortality benefits of both broad and focused immunomodulation in severely ill patients with COVID-19. As the pandemic continues, there is a need to understand whether combinations or different agents that target alternative pathways would continue to improve clinical outcomes, or whether there are ways of identifying specific patients with a higher likelihood of benefit from specific therapies.
One of the key components of the detrimental hyperinflammatory response in COVID-19 is granulocyte-macrophage colony-stimulating factor (GM-CSF), which is an immunomodulatory cytokine that might help to clear respiratory microbes by stimulating alveolar macrophages, but when in excess can cause damage. Its concentrations are low or undetectable in healthy individuals, yet many conditions can cause a rapid increase its concentration.1 Increased circulating concentrations of GM-CSF have been described in patients with COVID-19 compared with healthy controls.2 In the later stages of lung disease in COVID-19, excessive GM-CSF production can contribute to the dysregulated immune response in severe COVID-19,3 in which, upstream of IL-1 and IL-6, activated T cells target neutrophils and macrophages.4 Agents that interfere with its actions have high plausibility for benefit, not just in COVID-19, but in other acute inflammatory conditions, such as acute respiratory distress syndrome or sepsis.5
In The Lancet Respiratory Medicine, Zelalem Temesgen and colleagues6 report on a multicentre, placebo-controlled clinical trial of hospitalised patients with COVID-19, showing that lenzilumab, a neutralising monoclonal antibody against GM-CSF, is associated with improved survival without invasive mechanical ventilation at 28 days. Lenzilumab is a monoclonal antibody that directly binds GM-CSF and is being tested for conditions such as chronic myelomonocytic leukaemia and B-cell lymphoma.
Of 520 randomly assigned patients who were hypoxic or who required oxygen, but who did not require invasive mechanical ventilation, 479 patients were included in the modified intention-to-treat analysis. Patients in the lenzilumab group showed a 6% absolute increase in survival without ventilation at 28 days compared with the placebo group (198 [84%] of 236 patients vs 190 [78%] of 243 patients; hazard ratio [HR] 1·54 [95% CI 1·02–2·32], p=0·040). This difference on the outcome of survival without ventilation was primarily driven by more patients in the placebo group requiring invasive ventilation (49 [20%] patients) than those in the lenzilumab group (26 [11%] patients; HR 0·52 [0·32–0·82], p=0·0059). Key secondary outcomes, such as mortality, ventilator-free days, intensive care unit days, or recovery time, along with adverse events were not significantly different between the two groups.
This study population had lower baseline C-reactive protein (CRP) concentrations than the cohorts in RECOVERY and REMAP-CAP—trials where IL-6-targeted therapy has shown the largest benefit.7, 8 Exploratory sensitivity analyses suggested greater benefit of lenzilumab in patients with CRP concentrations less than the median value of 79 mg/L; further study of a CRP-guided approach, possibly targeting patients with lower CRP concentrations, earlier in their disease course, or of a different disease phenotype, could therefore be warranted. Whether biomarker-driven immunotherapy with stratification of patients can guide individualised use of immunomodulatory treatments in COVID-19 needs to be explored.
Studies of other agents acting to block GM-CSF in COVID-19 are also starting to report results. Otilimab (another GM-CSF inhibitor) is being studied in an older cohort of patients, aged more than 70 years, after some encouraging results in a subgroup of an initial study.9 Small studies of mavrilimumab (a GM-CSF receptor inhibitor) have shown no benefit,10 although larger studies are also underway. For lenzilumab, further study is happening through the ACTIV-5 platform, given the encouraging results from this trial.
As background standard of care for severe COVID-19 rapidly evolves, doing clinical trials of targeted immunomodulators becomes increasingly difficult. This trial, which enrolled patients between May, 2020, and January, 2021, did not allow administration of other immunomodulators, such as tocilizumab or baricitinib, during the acute stay, and was done before these medications became more routinely used in clinical practice. Without knowledge of the added benefit or the added risk of different, concurrently used immunomodulators, trials that do not integrate available standards of care are difficult to interpret. Hence, the specific value of GM-CSF blockade, in the absence of comparative or additive data with other targeted immunomodulators, is impossible to evaluate. As treatment regimens for COVID-19 constantly change and become more complex, evaluation of interactions must be the goal, and probably requires coordination across clinical trials, industry sponsors, and the involvement of large platform trials.
Buy quickly cause the share price is going to rise fast!
Someone bought almost exactly $1 million worth of HGEN at 4:30pm EST in After-Hours trading. Total After-Hours volume is 229,052
XBI hit its 52 week low at 12:15pm EST and ascended the rest of the day.
HGEN hit its 52 week low at 12:16pm EST and ascended the rest of the day.
But then some crazy high volume came into HGEN the last 10 minutes of market hours. Someone bought a ton of shares.
XBI plummeting and taking HGEN down with it. Hopefully, XBI is near rock bottom and a rebound will happen soon.
Humanigen Resumes Clinical Trials for Antibody Treatment Targeting Cytokine Storm
https://www.benzinga.com/general/biotech/21/11/24323400/these-biotech-companies-are-attempting-to-use-improved-antibody-technology-in-the-fight-to-eradic#/.YaUWzGg4a9I.twitter
One of the major risk factors in COVID-19 patients is the threat of cytokine storm, an inflammatory condition that occurs when an overworked immune system starts attacking its own body as it tries to fight the virus.
Humanigen Inc. HGEN -1.64% has been working hard to develop an antibody treatment that could prevent cytokine storms from happening or minimize the damage when they do. It does this by targeting the cytokines themselves.
While the FDA rejected Humanigen’s request for emergency use authorization last month, it invited the company to apply again when it had more clinical data available. Despite the setback, ongoing trials continue to study the potential benefits of the antibody treatment, and the company is working to get authorization in the United Kingdom and elsewhere.
The share price not increasing yesterday was frustrating. But the new variant news did come out on Tuesday and the share price went up nicely on Wednesday. It still would have been nice to get back to $7 yesterday. But buyers will come in over the next weeks when they research Omicron and seek variant agnostic therapeutics to invest in. Variant agnostic therapeutics will be here as long as Covid evolves which might be forever.
The US FDA and MHRA are well aware that lenz is variant agnostic. The Omicron variant definitely improves lenz's chances at getting an authorization in both countries. The US FDA took over 100 days to decide on lenz's original EUA application. They were likely on the fence. Hard to imagine that they don't give the EUA soon if they were indeed on the fence in September.
@ItsVeryJerry
$HGEN Recent study has identified features linked to severe COVID-19.
— Jerry Q*👁️🗨️ (@swandivr) November 26, 2021
High amounts of viral RNA (vRNA) in plasma, which has been associated with greater severity and worst outcome
Several cytokines were positively correlat... https://t.co/T2SBXhDYLw pic.twitter.com/0D9GNWGITr
HGEN is being pulled down by XBI this morning. $6.30 is an excellent time to buy. People are going to buy HGEN as the day goes along.
Here are some lenzilumab science-related articles for those wanting to do some due diligence. Lenzilumab is a GM-CSF inhibitor. The "M" in GM-CSF is macrophage.
Covid
https://www.bbc.com/news/health-56352128
https://immunology.sciencemag.org/content/6/57/eabg9873
https://directorsblog.nih.gov/2021/04/13/mapping-severe-covid-19-in-the-lungs-at-single-cell-resolution/
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30267-8/fulltext
https://www.nature.com/articles/s41586-021-03569-1
https://www.pharmaceutical-technology.com/news/humanigen-lenzilumab-improves-survival/
CAR-T
https://www.nature.com/articles/s41408-021-00459-7
https://www.nature.com/articles/s41421-021-00255-4
https://www.targetedonc.com/view/lenzilumab-plus-axi-cel-achieves-responses-in-100-of-patients-with-dlbcl-with-limited-toxicity-in-small-study
https://www.healio.com/news/hematology-oncology/20210422/lenzilumab-before-cart-induces-high-response-rates-without-severe-toxicities
Nasty new Covid variant newly discovered in South Africa. It could escape vaccines and antiviral mAbs entirely. Lenz is variant agnostic because it isn't an antiviral. Lenz is an immunomodulator that only dampens the body's immune response preventing the body from attacking itself. Lenz will work equally well on this and all future variants. Since Covid is looking like it could be endemic, lenz might be used for decades. GM-CSF is the key to stopping the cytokine storm.
HGEN is tracking XBI extremely closely again today. On low volume and/or no news days, HGEN's share price moves more from the XBI-related trading than HGEN-related trading. The good news is that the XBI hit its 52 week low today so there is reason to believe a rebound is imminent. Also, any HGEN lows caused by XBI lows are HGEN buying opportunities.
https://www.cnbc.com/quotes/HGEN
https://www.cnbc.com/quotes/XBI
For those wondering why the XBI going up and down causes buying and selling of HGEN, the below link explains arbitrage:
https://stockmarketmba.com/ETFmechanics.php
Arbitrage is a common investing term for the practice of taking advantage of a price differential between two or more markets. An arbitrage opportunity is inherent in the ETF structure. The authorized participants can make money trading the ETF shares, and in doing so, they benefit everyone by keeping the market price of the ETF close to the NAV of the ETF.
Here is how it works. At any time, the authorized participants can buy the shares of the securities included in the ETF's creation basket, and give them to the ETF in exchange for shares of the ETF priced at the ETF's NAV. The authorized participants can then sell those ETF shares on the open market. Even though the authorized participants pay a small transaction fee for this exchange, they can make money on the exchange if the ETF's shares are trading at a premium to the ETF's NAV. The expected result of the arbitrage activity is that the market value of the ETF moves back in line with the ETF’s NAV per share , as more shares of the ETF are now available to be bought and sold.
For U.S. stocks that are highly liquid, the arbitrage by the authorized participants is highly effective. The authorized participants, who are sophisticated traders, can easily execute these creation basket exchanges, even if the margins at first blush seem pretty small. The process is not quite as effective for other securities that are not as liquid, such as bonds or global equities, as it is more difficult for the authorized participants to easily and cheaply accumulate the securities in the creation basket. The arbitrage process isn't perfect, but it does generally work. You can visit the website of an ETF to compare at any time the market price of the ETF to the ETF's NAV.
By way of comparison, closed-end investment funds, which are also traded on an exchange, do not have the authorized participant and arbitrage setup of an ETF. They are called "closed-end" funds because they do not issue or redeem shares in response to market trading.
The FDA could grant an EUA at any time. When the FDA wants to work quickly, they can do things in less than a week's time. They have already done an in depth analysis of our original application. They were likely on the fence with giving the EUA in September. They now have the 60 day data and the CRP data. It won't be at all surprising if they decide to now give the EUA to lenz to combat what is certainly going to be a horrible winter wave.
Nothing is any different than 3 weeks ago when we were $8+. Peer review is still coming and a decision from the UK could come at any time. There is still no good drug available for newly hospitalized patients. Lenz has 154% efficacy for patients with a CRP<150mg/L. That is a game changer. No other drug at any stage has that efficacy. Our time will come.
Humanigen Announces Abstracts Accepted for the British Thoracic Society Winter Meeting 2021
https://ir.humanigen.com/English/news/news-details/2021/Humanigen-Announces-Abstracts-Accepted-for-the-British-Thoracic-Society-Winter-Meeting-2021/default.aspx
***Abstract #S48 describes top-line results from the Humanigen Phase 3 LIVE-AIR study in hospitalized COVID-19 patients, which reveal a 54% relative improvement in the likelihood of survival without invasive mechanical ventilation (“SWOV”) in lenzilumab-treated patients compared to those treated with standard of care plus placebo
Abstract #S49 describes an exploratory analysis from LIVE-AIR demonstrating a 3-fold improvement in SWOV in hospitalized COVID-19 patients less than 85 years with baseline CRP<150 mg/L treated with lenzilumab compared to those treated with standard of care plus placebo
Abstract #S51 describes an analysis from the literature related to several in-hospital COVID-19 treatments, which shows the number of patients needed to be treated to prevent a single death in the subsequent 28-day period was 22.7 for lenzilumab, 26.3 for remdesivir, and 37.0 for baricitinib
BURLINGAME, Calif.--(BUSINESS WIRE)-- Humanigen, Inc. (Nasdaq: HGEN) (“Humanigen”), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab, today announced three abstracts pertaining to the potential use of lenzilumab in hospitalized COVID-19 patients will be presented at the British Thoracic Society Winter 2021 Meeting taking place Nov. 24-26, 2021. The society counts more than 4,000 members comprised of doctors, nurses, respiratory physiotherapists, scientists, and other professionals with a respiratory interest.
“We are pleased to have the opportunity to share the results of our Phase 3 study of lenzilumab in hospitalized COVID-19 patients with our medical and scientific colleagues in the United Kingdom,” said Cameron Durrant, MD, Chairman & CEO, Humanigen. “We believe the analysis of our LIVE-AIR data using baseline C-reactive protein (CRP) levels is important because it identifies a subset of patients, approximately 75% of the study population, for which lenzilumab treatment appears to show the greatest benefit. This is particularly relevant in the United Kingdom, where the government funded the formation of the International Severe Acute Respiratory Infection Consortium (ISARIC), a UK-wide consortium of doctors and scientists, that developed the 4C Mortality Score, which utilizes CRP levels as the only biomarker marker used to calculate the score. By focusing on patients most likely to benefit from treatment with lenzilumab, analysis shows the number needed to be treated to potentially prevent a death over a subsequent 28-day period may be reduced from 22.7 to 13.9.”
Lenzilumab is not authorized, or approved, in any country.
Abstract #S48
Lenzilumab Efficacy and Safety in Newly Hospitalized Covid-19 Subjects: Results from the LIVE-AIR Phase 3 Randomized Double-Blind Placebo-Controlled Trial
Summary: The abstract describes top-line results from Humanigen’s LIVE-AIR Phase 3 study, which reveal a 54% improvement (HR: 1.54; p=0.0403) in SWOV in lenzilumab-treated patients hospitalized with COVID-19 compared to those treated with standard of care plus placebo. The study also demonstrated significant improvement in SWOV for the predefined subgroup of subjects who received both corticosteroids and remdesivir (HR: 1.92; nominal p=0.0067). The incidence of treatment-emergent serious adverse events was similar across treatment groups. Treatment with lenzilumab resulted in no serious infusion-related reactions, no increase in the incidence of secondary infections and no attributable serious adverse events, including, hematologic or liver enzyme abnormalities. In addition, no cases of pulmonary alveolar proteinosis were reported.
Abstract #S49
C-Reactive Protein as a Biomarker for Improved Efficacy of Lenzilumab in Covid-19 Patients: Results from the LIVE-AIR Trial
Summary: The abstract describes an exploratory analysis of LIVE-AIR data, from the Phase 3 study of lenzilumab in patients hospitalized with COVID-19, based upon an assessment of baseline CRP measurements, a biomarker that is commonly used to assess the body’s inflammatory response. The analysis shows those patients in the LIVE-AIR clinical trial with baseline CRP<150 mg/L and age <85 who were treated with lenzilumab benefited from a 3-fold improvement in SWOV (HR: 3.04; nominal p=0.0003) compared to those treated with standard of care plus placebo. The analysis led to the conclusion that inhibition of GM-CSF, an orchestrator of cytokine storm, by lenzilumab early in the hyperinflammatory response improves outcomes in COVID-19.
Abstract #S51
Evaluation of Treatment Approaches for Hospitalized COVID-19 Patients
Summary: The abstract describes an analysis from literature of several in-hospital COVID-19 treatments, which showed the number patients needed to be treated (NNT) to prevent a single death in a subsequent 28-day period were 22.7 for lenzilumab, 26.3 for remdesivir, and 37.0 for baricitinib. The NNT for lenzilumab improved with refinement of concomitant medications and patient phenotype. The NNT to prevent a single death in a subsequent 28-day period is reduced to 13.9 in patients age less than 85 years with a CRP<150 mg/L.
About ISARIC Coronavirus Clinical Characterisation Consortium (4C) Mortality Score
The UK government funded the formation of ISARIC 4C (Coronavirus Clinical Characterisation Consortium), a consortium of doctors and scientists across the UK that gathered and analyzed samples from COVID-19 patients.1 Using data from 57,824 patients, ISARIC developed the 4-C Mortality Score.2 This risk-stratification tool outperformed existing risk-stratification tools and has been extensively validated in independent studies in other countries across the world, including France, The Netherlands, Italy, Pakistan, Turkey, and Canada.3 Use of the assessment tool results in a 4C Mortality Score that can range from 0-21 with direct correlation between a higher score and higher mortality rate. For example, a score of 1 equates to a mortality rate of 0.3%, while a score of 10 equates to 22.9% mortality rate, and a score of 21 is associated with an 87.5% mortality rate.4 CRP levels are one of the eight variables and the only biomarker utilized in this scoring system to arrive at the 4C Mortality Score and increasing CRP levels lead to higher scores (e.g., CRP<50 mg/L = +0, CRP 50-99 mg/L = +1, CRP≥ 100 mg/L = +2)4.
Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies
https://jeccr.biomedcentral.com/articles/10.1186/s13046-021-02148-6
Targeting GM-CSF
GM-CSF is also an important cytokine associated with CAR T-cell-related adverse events, especially ICANS [89, 91]. Lenzilumab, a monoclonal antibody against GM-CSF, can resolve ICANS and CRS induced by CAR T-cells in mouse models by inhibiting myeloid cells and T cells entering the CNS [91]. Intriguingly, instead of dampening CAR T-cell expansion, lenzilumab even enhanced its antitumor effect [91]. The ZUMA-19 trial (NCT04314843) preliminarily showed the efficacy and safety of lenzilumab and Axi-Cel (an FDA-approved CD19 CAR T-cell product) in treating patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). It was observed that lenzilumab could induce a lower risk of severe CRS and ICANS and reduce inflammatory markers, such as IL-6, CRP, ferritin, MCP-1, IL-8, and IP-10 [168].
(link from Rush12 on ST)
Today has been all XBI caused movement. Our charts are nearly identical.
@EricTopol
This isn't good, folks, and tells where we're headed
— Eric Topol (@EricTopol) November 18, 2021
—USA new cases today 115,000, 7-day average up to ~88,000, a 14% increase in a week
—Hospitalizations are on the rise again, 850 more today, to ~48,000
—Over 1,700 deathshttps://t.co/xStmHRzwg2
Below are some quotes from the paper. We already knew GM-CSF inhibition was the key to stopping severe Covid and Covid death but it seems GM-CSF inhibition is also the key to preventing Long Covid as well. Tomorrow is going to be very green!
full pdf of paper
Eric Topol quoting a new paper stating that Long Covid is caused a triad of cytokines which are activated by macrophages in the lungs during initial infection which turns into a feedback loop. This is huge!
Here are some lenzilumab science-related articles for those wanting to do some due diligence. Lenzilumab is a GM-CSF inhibitor. The "M" in GM-CSF is macrophage.
Covid
https://www.bbc.com/news/health-56352128
https://immunology.sciencemag.org/content/6/57/eabg9873
https://directorsblog.nih.gov/2021/04/13/mapping-severe-covid-19-in-the-lungs-at-single-cell-resolution/
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30267-8/fulltext
https://www.nature.com/articles/s41586-021-03569-1
https://www.pharmaceutical-technology.com/news/humanigen-lenzilumab-improves-survival/
CAR-T
https://www.nature.com/articles/s41408-021-00459-7
https://www.nature.com/articles/s41421-021-00255-4
https://www.targetedonc.com/view/lenzilumab-plus-axi-cel-achieves-responses-in-100-of-patients-with-dlbcl-with-limited-toxicity-in-small-study
https://www.healio.com/news/hematology-oncology/20210422/lenzilumab-before-cart-induces-high-response-rates-without-severe-toxicities
The US has had rising cases for 9 straight days and the UK has had rising cases for 5 straight days. The winter wave is officially here. Let's pray that the US and the UK choose lenz to help alleviate what will certainly be a brutal Covid season.