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Humanigen sent out a press release today announcing the Wainwright Presentation. It says, "In his presentation Dr. Durrant will provide an update on progress towards release of topline data for ACTIV-5/BET-B and the company’s plans and goals for the remainder of 2022."
https://ir.humanigen.com/English/news/news-details/2022/Humanigen-Announces-Participation-and-Presentation-at-H.C.-Wainwright-Global-Investment-Conference/default.aspx
New slides released for the Wainwright presentation
https://s28.q4cdn.com/539885110/files/doc_presentations/2022/HGEN-H.C.-Wainwright-May-24-2022.pdf
I'm excited about tomorrow and this week. HGEN's share price has the potential to go north of $4.00 this week.
1. Dale's buys might spur others to buy like his buys did in March.
2. Dale might keep buying (most likely starting Tue or Wed and lasting 3 days).
3. Hospitalizations are rising quickly further proving the long term need for lenzilumab.
4. Tim Morris' tweet from May 12th saying things will look up after Memorial Day caused impatient investors to flee so it should bring some of the same investors back this week in anticipation.
@EricTopol
Hard to get to a 2nd booster when you're ranked 62nd in the world for the 1st booster
https://ig.ft.com/coronavirus-vaccine-tracker/?areas=gbr&areas=isr&areas=usa&areas=eue&areas=are&areas=chn&areas=chl&cumulative=1&doses=total&populationAdjusted=1
@EricTopol
The @CDCgov changes its 2nd booster tune from "option" to "urge" for people age 50+
https://nytimes.com/2022/05/20/us/politics/cdc-second-booster.html by @SharonLNYT
“a steep and substantial increase in hospitalizations for older Americans”
Dale bought a million shares over the last 3 days. Looks like he might have also raised the share price to exactly $2.50 in afterhours trading so that he could exercise his calls. Things could get interesting if he continues to buy next week.
https://d18rn0p25nwr6d.cloudfront.net/CIK-0001293310/a080025c-f69e-4b1d-8e7f-5a8627f18620.pdf
Is isn't completely counterintuitive that HGEN could be green on a day that the market as a whole is extremely red. HGEN is a safe haven of sorts. People exiting the rocky seas of market in general can come to HGEN and know that TLD is coming at any moment. HGEN could have a +1,000% day while the market as a whole is collapsing.
The new May presentation is posted on Humanigen's site. Take a look at slide 15. In the group that had a CRP<150mg/L + <85yo + remdesivir, the mortality rate in the placebo arm was 17.3% and the mortality rate in the lenz arm was 7.5%. That is the exact group that is now the primary endpoint population of the ACTIV trial. That is bonkers mortality efficacy! Stat sig on mortality is possible or even likely in the ACTIV trial. Stat sig on mortality could push HGEN's share price north of $30!
https://s28.q4cdn.com/539885110/files/doc_presentations/2022/LSX-World-Congress-May-10-2022.pdf
Humanigen: A ‘Transformative Year’ Awaits, Says Analyst
https://www.tipranks.com/news/article/humanigen-a-transformative-year-awaits-says-analyst/
Accounting for many stocks losing a huge chunk of their valuations in 2022’s inhospitable stock market, analysts have been busy slashing estimates and price targets this year.
However, for H.C. Wainwright analyst Joseph Pantginis, there has been no such change of heart when considering the prospects of biotech company Humanigen (HGEN). Even in the face of FDA rejection and a stock which is down 89% over the past year, Pantginis remains undeterred.
The analyst reiterated a Buy rating for HGEN stock, backed by a $28 price target. If Pantginis is correct in his prognosis, investors will be sitting on gains of a barely believable 1455% in a year’s time.
This latest endorsement comes off the back of Humanigen’s Q1 results. Being a clinical stage biotech, the company has no product to sell, and the quarterly update revolved around the health of its finances and the pipeline’s progress. On the former, HGEN saw out the quarter with $69 million in cash and following the quarter’s end, raised around $18 million via its existing equity facility.
The latter, though, provides the basis for Pantginis’ optimistic outlook and is based around the potential of lenzilumab, indicated for the treatment of cytokine release syndrome related to Covid-19, CAR-T therapy, and allogeneic hematopoietic stem cell therapy.
Enrollment for the Phase 2/3 ACTIV-5/BET-B study evaluating lenzilumab as a treatment for Covid-19 patients has been completed with top-line data anticipated this quarter. Following which, Humanigen will file its amended EUA with the FDA. Recall, last September, the FDA rejected lenzilumab, citing the need for more data before moving ahead. The company met with the FDA during the quarter and said talks were “productive” and that they have “gained alignment with the agency on the data and statistical analysis to support the amendment.”
Additionally, the protocol for the upcoming registrational Phase 3 SHIELD study of lenzilumab for the prevention of CAR-T therapy associated toxicities has also been agreed upon with the regulatory body and the first patient should be enrolled this quarter too. Lastly, enrollment in the Phase 2/3 PREACH-M study of lenzilumab in chronic myelomonocytic leukemia is also ongoing.
All the above are “catalysts” which could propel the stock forward, in what Pantginis believes could be a “transformative year.” “As we await updates from the ACTIV-5/BET-B study and the initiation of new trials, we are encouraged by the company’s efforts to move lenzilumab rapidly to commercialization stages, while increasing the asset’s footprint in numerous therapeutic contexts,” the analyst summed up.
Pantginis might have high expectations, but his take is no anomaly. All 4 analyst reviews on record are positive, providing the stock with a Strong Buy consensus rating. Moreover, while the average target is lower than Pantginis’s, at $21.75, the figure is still set to generate one-year returns of a huge 1108%.
XBI hit a new 5-year low today. It has to be close to rebounding. When it does, it will be wind beneath HGEN's wings.
We're back at $1.80. It held last week. I think it'll hold again.
Looks like Dale isn't buying. I'm going to look at this optimistically and hope that he isn't allowed to buy in because data is locked and TLD is coming soon.
There are no big buys, yet. It is possible that data has locked and insiders are precluded from buying. That would be good news in my opinion. The other possibility is that Cameron or Adrian made a small purchase today. Dale always lets the other small insiders buy first. Dale's buys might come tomorrow or Thursday. We should know by Thursday night if there were insider buys this week.
Tomorrow should be the day that insiders start buying if it is going to happen. I've heard it put forth elsewhere that insider buys have normally started at 10:30am or 11:00am EST in the past. If insider buys happen tomorrow, we should hear about it Thursday afternoon/night.
Humanigen's year-end financial report was released at 1:05pm on Feb 28th. That day opened at $2.08, had a price range of $1.97-$2.08, and closed at $2.03. The next day opened at $2.04, had a high of $2.44, and closed at $2.32. HGEN then steadily rose over the next 20 days until it had a share price of $4.11 on March 21st. No one bought HGEN afterhours last night, or in premarket today, or in the first 30 minutes of trading this morning. So both situations are similar in that the buying wasn't immediate following the financial report. Let's hope we continue to have a similar experience as March and reach $4.11 this month.
May is looking like it might be a repeat of March.
Let's hope we get back to $4.10 again.
And then TLD comes out so we don't lose those gains again.
The 10-Q being released earlier than normal makes me believe that insiders will be buying. Dale bought a million shares at $3.00 on March 11th. Nothing has changed to lower the value of the stock since that time. So his buying plan might keep buying shares until it gets to the $3.00 level. And then he can exercise his May $2.50 calls for more shares. I will be very surprised if the share price doesn't get back to $3.00 in May.
Insider buying can commence 2 trading days after the release of the 10-Q. The buying window lasts 20 days. Since the 10-Q was released afterhours, I'm not sure if today counts as the first trading day. The below citation is from the SEC. It says today would count as the first trading day if the public disclosure happened before the market closes. The PR was released at exactly 4:00pm, does that count? The 10-Q was released at 4:31pm, does being released during afterhours trading count as before the market closes? I'm not sure on either question. So insiders might be able to buy on Monday. If not Monday, then Tuesday.
8-K
https://d18rn0p25nwr6d.cloudfront.net/CIK-0001293310/0edf9b05-002a-4178-b6e3-ca5ba6dd1c72.pdf
Humanigen Reports First Quarter 2022 Financial Results
SHORT HILLS, N.J. May 5, 2022--(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 (LENZ®), today provided a corporate update and reported financial results for the first quarter ended March 31, 2022.
“A key highlight of the first quarter was the completion of enrollment in the ACTIV-5/BET-B study. We also held a productive Type B pre-EUA meeting with FDA where we gained alignment on the data and statistical analysis plan to be included as part of the amendment to our EUA for LENZ in COVID-19 patients. In concert with the NIH, we anticipate top-line data in the primary analysis population to be reported in the second quarter, with an amendment to our EUA submission planned to follow,” stated Cameron Durrant, Chairman and Chief Executive Officer, Humanigen. “We anticipate hospitalizations from COVID-19 will continue for years to come. Published data on LENZ, confirmed by key opinion leaders and national guideline committees, including NIH, supports treatment guidance based on CRP levels and first-line utilization in hypoxic patients.”
“Hospitalizations from COVID-19 in the US continue to remain steady with a 7-day average of 2,072 new daily hospitalizations. While there have been more than 900,000 people already hospitalized in the US this year to date, synergizing results from multiple forecasting models prepared by leading experts in epidemiology in four different scenarios forecast additional COVID-19 hospitalizations in the United States, to range from approximately 500,000 to 1,200,000 for the remainder of 2022. Variant agnostic treatments for hospitalized patients are still desperately needed,” commented Edward Jordan, Chief Commercial Officer, Humanigen.
“As well as its clinical benefit in reducing invasive mechanical ventilation and death, LENZ could deliver significant economic savings to health care systems. LENZ can be used in combination with remdesivir, which is currently used in 50% of hospitalized COVID-19 patients in the U.S. Sales of the top two hospital treatments for COVID-19 exceeded $7 billion in global revenue in 2021. We believe LENZ is well positioned to participate in this sizable and sustainable market,” he added.
Lenzilumab is an investigational product and is not currently authorized or approved in any country.
First Quarter and Recent Highlights:
Lenzilumab in COVID-19 patients
· Completed enrollment of the Phase 2/3 ACTIV-5/BET-B study, sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and enrolled over 400 patients in the primary analysis population (patients with a C-reactive protein level at baseline of less than 150mg/L).
· Gained alignment with the FDA during a Type B pre-EUA meeting on the data and statistical analysis plan to be included in the amendment to the EUA.
· Announced a peer-reviewed publication in ClinicoEconomics and Outcomes Research outlining the potential clinical and health economic benefits of lenzilumab, if authorized or approved for use in the United Kingdom.
· First subject dosed in the PK study in Korea.
Lenzilumab in Development in Other Therapeutic Areas
· Gained alignment with the FDA on the protocol for the planned registrational Phase 3 SHIELD study of lenzilumab for the prevention of CAR-T therapy related toxicities including Immune Effector Cell-Associated Neurotoxicity (“ICANS”), in which Humanigen intends to enroll the first patient in the second quarter.
· Announced a peer-reviewed publication in Leukemia, a leading oncology and hematology journal, entitled “GM-CSF disruption in CART cells modulates T cell activation and enhances CART cell anti-tumor activity.”
· Notified by the University of Birmingham, UK, that the amended Investigational Medicinal Product Dossier has been accepted by Medicines & Healthcare products Regulatory Agency for the “RATinG” study. Humanigen believes the first patient will be enrolled in this Phase 2/3 potentially registrational trial for lenzilumab to treat patients who have undergone allogeneic hematopoietic stem cell therapy, who are at high and intermediate risk for acute Graft versus Host Disease (“aGvHD”) in the second quarter.
· Continued enrollment in the PREACH-M study of lenzilumab in chronic myelomonocytic leukemia. Study sponsor planning for expansion of clinical
sites.
First Quarter Ended March 31, 2022 Financial Results
Net loss for the quarter ended March 31, 2022 was $21.3 million, or $0.32 per share, as compared to $65.6 million, or $1.25 per share, for the quarter ended
March 31, 2021. The decrease in net loss was due to a decrease in total expenses, mainly Research and Development (“R&D”) expense. R&D expense
decreased $42.7 million from $59.9 million for the three months ended March 31, 2021, to $17.2 million for the three months ended March 31, 2022. The
decrease is primarily due to a decrease of $35.7 million in lenzilumab manufacturing costs.
Cash and Cash Equivalents
Net cash used in operating activities, net of balance sheet changes, was $19.4 million for the quarter ended March 31, 2022. During the first quarter of 2022,
the company sold shares of its common stock under its At-the-Market or “ATM” facility, raising net proceeds of approximately $18 million. As of March 31,
2022, the company had cash and cash equivalents of approximately $69 million.
A summary of key financial highlights as of and for the three months ended March 31, 2022 and 2021 is as follows ($ in thousands):
In CAR-T, lenzilumab successfully achieved the pre-specified primary endpoint at the recommended dose in a Phase 1b study with Yescarta® in which the overall response rate was 100% and no patient experienced severe cytokine release syndrome or severe neurotoxicity. Based on these results, Humanigen plans to test lenzilumab in a randomized, multicenter, potentially registrational, Phase 3 SHIELD study to evaluate its efficacy and safety when combined with Yescarta and Tecartus® CAR-T therapies in non-Hodgkin lymphoma. Lenzilumab will also be tested to assess its ability to prevent and/or treat aGvHD in patients undergoing allogeneic hematopoietic stem cell transplantation.
A study of lenzilumab is also underway for patients with chronic myelomonocytic leukemia exhibiting RAS pathway mutations. This study builds on evidence from a Phase 1 study, conducted by Humanigen, that showed RAS mutations are associated with hyper-proliferative features, which may be sensitive to GMCSF neutralization.
Yeah, the wait on data has been brutal. Let's pray that Dale knew what he was doing when he bought those May calls and we get data before May 20th. But I'm not too stressed. The share price isn't going to go much lower regardless of how long data takes.
I think $1.80 is going to hold. A nice time for an entry.
Israeli researchers warn of new international COVID wave, driven by Delta comeback
Omicron didn’t wipe out the previous variant, which is super-resilient and could reemerge with a vengeance, according to peer-reviewed study based on cutting-edge sewage monitoring
https://www.timesofisrael.com/israeli-researchers-warn-of-new-international-covid-wave-driven-by-delta-comeback/amp/
There is a real danger of another international COVID wave this summer, with the Delta variant possibly poised to make a comeback, new Israeli research suggests.
The peer-reviewed study is based on cutting-edge Israeli monitoring of sewage, which reveals not only the prevalence of coronavirus cases, but also their variant.
It showed that even at the height of the Omicron wave, the previous Delta variant hadn’t been wiped out, even though it was expected to be based on the dynamics of previous waves.
After monitoring the patterns of the two variants, the researchers concluded that Omicron and its subvariants are likely to disappear soon, but Delta has shown such strong resilience that it could well reemerge.
“Our findings highlight that the pandemic is not over and suggest that sooner or later there will be another wave, potentially in the summer or at the end of the summer,” Prof. Ariel Kushmaro, who runs the Ben-Gurion University of the Negev wastewater lab that conducted the research, told The Times of Israel.
He said that the significance extends far beyond Israel, and indicated that internationally, Delta still poses a larger threat than widely assumed. Delta could reemerge in its existing form, or could spread in the form of a new subvariant, he predicted.
Some COVID experts say that the study gives a clear basis in data for a warning they have been giving for weeks.
“The pandemic isn’t over, and this great piece of research provides clear findings that emphasize this and help us to understand the situation,” immunologist Dr. Yariv Wine, a Tel Aviv University academic who wasn’t involved in theBen-Gurion research, told The Times of Israel.
Kushmaro said that Delta’s resilience surprised his team. “In the past, we saw that when one variant rises, others disappear; but this just doesn’t seem to have happened with Delta, which seems to have a certain ability to survive,” he said.
“In this study, we identified that even when Omicron was at its very highest in the wastewater, Delta was still circulating,” he added. “The patterns we see indicate that Omicron is in demise, but Delta has survived and is positioned to possibly reemerge.”
Kushmaro and his colleagues, including Dr. Karin Yaniv, wrote that according to their analysis model Delta is expected to continue to circulate largely undetected — what they call cryptic circulation — until it causes a wave. They published their findings in the journal Science of the Total Environment.
“According to the developed model, it can be expected that the Omicron levels will decrease until eliminated, while Delta variant will maintain its cryptic circulation,” they wrote. “If this comes to pass, the mentioned cryptic circulation may result in the reemergence of a Delta morbidity wave or in the possible generation of a new threatening variant.”
Thanks!
There are two potential positive catalysts to look forward to in the next few weeks.
First off, Dale and other insiders will likely have another window of opportunity to buy more shares 2 days after the Q1 quarterly report is released as long as they are still not in possession of non-disclosed material information. Last year's Q1 quarterly report happened on May 12th but they might rush this year's release date to increase the chances of getting their buys in before TLD is released. This year's annual report was released on Feb 28th whereas it was released on March 10th the year before. So the Q1 quarterly report could conceivably come out as soon as tomorrow and insider buys could happen as soon as Wednesday. In March, Dale bought one million shares and a bunch of calls but his buying plan might have bought significantly more shares if the share price had been lower. The share price was exactly $2.00 when Dale set up his buying plan. It is anyone's guess the number of shares that Dale's buying plan would have bought if the share price had stayed at $3.00 or below. There were 11 days left in his buying window after his purchase of 1,000,000 shares at $3.00.
Another event that might help the share price is the May 20th options expiration. Max pain is $2.50. So the sellers of puts have incentive to increase the share price to $2.50 by May 20th and there is zero disincentive to raising the share price to $2.50 for the sellers of calls. The share price closing at exactly $2.50 on May 20th wouldn't be surprising. Although, there is a 20 day buying window for insider's share buys so let's hope Dale's buys push the share price significantly higher than $2.50 on May 20th and beyond. He felt that it was worth buying a million shares at $3.00 in March so let's hope his buying plan keeps buying until it reaches that level.
HGEN Q1 quarterly report dates according to Investing.com
May 16, 2017
May 15, 2018
May 9, 2019
May 7, 2020
May 12, 2021
2/
— Chris Turnbull (@EnemyInAState) April 28, 2022
Nearly 30% of sequences are coming back as BA4: looks like it has some sort of growth advantage pic.twitter.com/HcoV8y7et6
A new fast growing Omicron variant that has the severity of Delta is very bad news. Hospitalizations will skyrocket if this variant becomes dominant which it looks poised to do.
1/ UHOH: cases in South Africa DOUBLING IN A WEEK starting to hit exponential rise with BA4 variant quickly dominating: BA4 is a recombinant of BA1 + BA2 & contains the deadly L452R Delta spike mutation: it's a Deltacron on steroids and climbing fast. pic.twitter.com/r4pXWZezJa
— Chris Turnbull (@EnemyInAState) April 28, 2022
The wait for data is brutal. But it will be worth it. The primary endpoint population of the ACTIV trial had 243% efficacy in the LIVE-AIR trial. No other Covid treatment at any stage comes close to that efficacy. And there is still no good treatment for newly hospitalized patients which is obviously a very important stage to treat. Lenzilumab is coming soon to a hospital near you.
https://www.bioworld.com/articles/518108-other-news-to-note-for-april-21-2022
Humanigen Inc., of Burlingame, Calif., published results of GM-CSF disruption in CAR T cells in the journal Leukemia. Data showed CRISPR/Cas9-mediated GM-CSF knockout in CAR T cells, enhanced CAR T-cell proliferation, reduced activation-induced cell death and enhanced antitumor activity in a xenograft model.
Immune Signature of COVID-19: In-Depth Reasons and Consequences of the Cytokine Storm
https://www.mdpi.com/1422-0067/23/9/4545
"Lenzilumab, a recombinant monoclonal antibody against human GM-CSF, also has the potential to be used to treat COVID-19. Patients who received intravenous lenzilumab treatment had reduced progression to ARDS and reduced inflammatory markers"
(from LPF_91 on Stocktwits)
GM-CSF Knock-out CAR-T Study Published in Peer-Reviewed Journal Leukemia
https://ir.humanigen.com/English/news/news-details/2022/GM-CSF-Knock-out-CAR-T-Study-Published-in-Peer-Reviewed-Journal-Leukemia/default.aspx
-CRISPR/Cas9-Mediated GM-CSF knock-out (GM-CSFko) CAR-T cells demonstrate reduced apoptosis and enhanced in vivo anti-tumor activity in preclinical models
-Phase 3 SHIELD study utilizing lenzilumab to prophylactically neutralize GM-CSF in CAR-T to begin 1H22
SHORT HILLS, N.J.--(BUSINESS WIRE)--Humanigen, Inc. (Nasdaq: HGEN) (“Humanigen”), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm,’ announced today a peer-reviewed publication in Leukemia, a leading oncology and hematology journal, entitled “GM-CSF disruption in CART cells modulates T cell activation and enhances CART cell anti-tumor activity.”
This publication is a significant addition to the findings from a previous article in the leading hematology journal, blood, which demonstrated that neutralization of GM-CSF with lenzilumab (LENZ®) was able to break the efficacy/toxicity linkage by reducing cytokine release syndrome (CRS) and neuroinflammation (ICANS) while enhancing CAR-T function.1 The Leukemia publication demonstrates that CRISPR/Cas9-mediated GM-CSF knockout in CAR-T cells directly ameliorates CAR-T cell early activation, reduces activation-induced cell death, and results in enhanced anti-tumor activity in vivo in a xenograft model.2
Enhancing CAR-T cell in vivo efficacy by using strategies to non-specifically stimulate CAR-T cell proliferation utilizing synthetic biology or combination therapy to edit exhaustion pathways or prevent apoptosis is an important goal and is the subject of substantial ongoing research. However, while this may improve CAR-T efficacy, it is often at the cost of an increase in important toxicities, such as CRS and ICANS. In contrast, these data published in Leukemia indicate that GM-CSko CAR-T cells result in enhanced CAR-T cell proliferation and anti-tumor activity while being associated with a marked reduction in GM-CSF levels, which have been linked to CAR-T associated toxicities.
CAR-T therapies have resulted in significant advances for patients. However, for up to one-third of patients, toxicities such as severe ICANS and CRS occur, and tumor relapse is still a frequent occurrence.3 Currently, the widespread adoption of CAR-T therapy is limited, in part, by the requirement for treatment in centers that are experienced in managing the common toxicities of ICANS and CRS and by the financial and health burden that this creates. “CRS, ICANS, and tumor relapse remain challenges for physicians and patients treated with CAR-T therapy,” said Saad Kenderian, M.B., Ch.B., hematologist at Mayo Clinic Cancer Center, an author of the Leukemia paper and the primary investigator for the SHIELD study (Study on How to Improve Efficacy and toxicity with Lenzilumab in DLBCL and other NHL patients treated with CAR-T therapy). He added, “They result in additional morbidity for patients, as well as significantly increased costs for healthcare providers. Treatments that can prevent ICANS and CRS while potentially improving CAR-T efficacy could address a critical unmet need.”
This publication adds to the body of knowledge of GM-CSF depletion in CAR-T. The upcoming Phase 3 CAR-T study, known as SHIELD, will determine the efficacy and safety of prophylactic lenzilumab on the rates of ICANS, CRS, and CAR-T efficacy. “The SHIELD trial has been designed to build on the positive results from the ZUMA-19 study. The primary endpoint of SHIELD will focus on demonstrating a significant improvement in neurotoxicity associated with both Yescarta® and Tecartus®. We will also seek to explore the beneficial impact that lenzilumab may have CAR-T efficacy,” stated Dale Chappell, M.D., MBA, Chief Scientific Officer, Humanigen.
GM-CSF disruption in CART cells modulates T cell activation and enhances CART cell anti-tumor activity
https://www.nature.com/articles/s41375-022-01572-7
Inhibitory myeloid cells and their cytokines play critical roles in limiting chimeric antigen receptor T (CART) cell therapy by contributing to the development of toxicities and resistance following infusion. We have previously shown that neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF) prevents these toxicities and enhances CART cell functions by inhibiting myeloid cell activation. In this report, we study the direct impact of GM-CSF disruption during the production of CD19-directed CART cells on their effector functions, independent of GM-CSF modulation of myeloid cells. In this study, we show that antigen-specific activation of GM-CSFKO CART19 cells consistently displayed reduced early activation, enhanced proliferation, and improved anti-tumor activity in a xenograft model for relapsed B cell malignancies. Activated CART19 cells significantly upregulate GM-CSF receptors. However, the interaction between GM-CSF and its upregulated receptors on CART cells was not the predominant mechanism of this activation phenotype. GM-CSFKO CART19 cell had reduced BH3 interacting-domain death agonist (Bid), suggesting an interaction between GM-CSF and intrinsic apoptosis pathways. In conclusion, our study demonstrates that CRISPR/Cas9-mediated GM-CSF knockout in CART cells directly ameliorates CART cell early activation and enhances anti-tumor activity in preclinical models.
(from Tumzilla70 on Twitter)