Lyell Immunopharma Inc (LYEL)

It will be interesting to see GILD's KITE-753 clinical data. The only difference between it (and KITE-363) is a reduced production time.

However, based on preclinical data, KITE-753 exhibited higher expression of both CARs and increased proportion of CCR7+/CD45RA+ T-cells* compared to the KITE-363 benchmark.

Also, KITE-753 exhibited enhanced cytokine production, enhanced proliferation, increased peripheral peak expansion, and superior antitumour efficacy compared to the KITE-363 benchmark.

* CCR7+/CD45RA+CD4+ of ~60% vs ~5%, and CCR7+/CD45RA+CD8+ of ~80% vs ~15%.

High circulating CCR7+ populations positively correlate with antitumour response https://www.nature.com/articles/s41591-020-1061-7

An update https://www.oncologypipeline.com/apexonco/lyell-takes-jj-and-gilead

An update on prizlon-cel

An update on CRGX https://www.fiercebiotech.com/biotech/cargo-jettisons-remaining-assets-and-90-workforce-it-looks-reverse-merger

LYEL..................................https://stockcharts.com/h-sc/ui?s=LYEL&p=W&b=5&g=0&id=p86431144783

https://ih.advfn.com/stock-market/NASDAQ/lyell-immunopharma-LYEL/stock-news/95521325/form-4-statement-of-changes-in-beneficial-owners

Yup...LYEL...🥳...Moving up nicely...

$LYEL .7486

LYEL...7008...Off the .56 Alert...🥳

georgie18

Member Level
Re: georgie18 post# 32376

Friday, February 21, 2025 9:40:49 AM

Post#
32428
of 32525
LYEL...6868...🥳...Trying for Double Top Breakout here...Off the .56 Alert...

georgie18

Member Level
Re: georgie18 post# 674836

Thursday, February 20, 2025 2:04:23 PM

Post#
674950
of 675048
LYEL...66...HOD...🥳

georgie18

Member Level
Re: georgie18 post# 32041

Wednesday, February 19, 2025 3:48:52 PM

Post#
32270
of 32375
LYEL...6145...Bullish Engulfing Reversal Candle...🥳

LYEL...639...🥳...Looking for $1 plus here...

georgie18

Member Level
Re: None

Thursday, February 13, 2025 4:20:43 PM

Post#
32007
of 32040
LYEL...56...🥳... https://schrts.co/XneECpDw...https://finance.yahoo.com/news/lyell-immunopharma-lyel-upgraded-strong-170012527.html

This is a Rigatoni Play ...one of the best Traders I have had the pleasure of knowing for many years...

LYEL...6868...🥳...Trying for Double Top Breakout here...Off the .56 Alert...

georgie18

Member Level
Re: georgie18 post# 674836

Thursday, February 20, 2025 2:04:23 PM

Post#
674950
of 675048
LYEL...66...HOD...🥳

georgie18

Member Level
Re: georgie18 post# 32041

Wednesday, February 19, 2025 3:48:52 PM

Post#
32270
of 32375
LYEL...6145...Bullish Engulfing Reversal Candle...🥳

LYEL...639...🥳...Looking for $1 plus here...

georgie18

Member Level
Re: None

Thursday, February 13, 2025 4:20:43 PM

Post#
32007
of 32040
LYEL...56...🥳... https://schrts.co/XneECpDw...https://finance.yahoo.com/news/lyell-immunopharma-lyel-upgraded-strong-170012527.html

This is a Rigatoni Play ...one of the best Traders I have had the pleasure of knowing for many years...

LYEL...66...HOD...🥳

georgie18

Member Level
Re: georgie18 post# 32041

Wednesday, February 19, 2025 3:48:52 PM

Post#
32270
of 32375
LYEL...6145...Bullish Engulfing Reversal Candle...🥳

LYEL...639...🥳...Looking for $1 plus here...

georgie18

Member Level
Re: None

Thursday, February 13, 2025 4:20:43 PM

Post#
32007
of 32040
LYEL...56...🥳... https://schrts.co/XneECpDw...https://finance.yahoo.com/news/lyell-immunopharma-lyel-upgraded-strong-170012527.html

This is a Rigatoni Play ...one of the best Traders I have had the pleasure of knowing for many years...

LYEL...6145...Bullish Engulfing Reversal Candle...🥳

LYEL...639...🥳...Looking for $1 plus here...

georgie18

Member Level
Re: None

Thursday, February 13, 2025 4:20:43 PM

Post#
32007
of 32040
LYEL...56...🥳... https://schrts.co/XneECpDw...https://finance.yahoo.com/news/lyell-immunopharma-lyel-upgraded-strong-170012527.html

This is a Rigatoni Play ...one of the best Traders I have had the pleasure of knowing for many years...

LYEL...639...🥳...Looking for $1 plus here...

georgie18

Member Level
Re: None

Thursday, February 13, 2025 4:20:43 PM

Post#
32007
of 32040
LYEL...56...🥳... https://schrts.co/XneECpDw...https://finance.yahoo.com/news/lyell-immunopharma-lyel-upgraded-strong-170012527.html

This is a Rigatoni Play ...one of the best Traders I have had the pleasure of knowing for many years...

LYEL...56...🥳... https://schrts.co/XneECpDw...https://finance.yahoo.com/news/lyell-immunopharma-lyel-upgraded-strong-170012527.html

This is a Rigatoni Play ...one of the best Traders I have had the pleasure of knowing for many years...

There are other bi-specific CARs, including two by GILD's Kite, and at least one tri-specific in development as well.

CRGX's CRG-023 (IND cleared, PhI mid-year) is the first tri-specific CAR-T to express three independent CARs from a single vector, with each CAR having a distinct co-stim domain. One co-stim domain incorporates CD2 signaling, which has been designed to overcome immune-evasion mediated by the loss of CD58 https://ashpublications.org/blood/article/136/Supplement%201/53/470303/CD58-Aberrations-Limit-Durable-Responses-to-CD19

Novel CD19 and CD20 scFvs were selected for enhanced CAR performance and combined with the existing CD22 scFv used in firi-cel. These new binders are fully human to limit host-mediated rejection. The iterative engineering allowed for the selection of the optimal costimulatory domain configuration and optimal assemblage in the lentiviral vector used https://www.sciencedirect.com/science/article/pii/S0006497124047827

What they don't say is equally as important as what they do say.

Prizlon-cel, is a novel CD19/CD20 bispecific CAR-T. Of the 48 patients infused, 44 had LBCL. No patient experienced a DLT. CRS occurred in 93.8% of patients, with only one case of grade 3. ICANS occurred in 6.3% of patients, with no grade 3 or higher events. The ORR and complete response (CR) rates in all patients were 91.5% and 85.1%, respectively, and in LBCL patients, ORR was 90.7% with 86.0% CR. With median follow up of 30.0 months, median DOR, PFS, and OS were all not reached. The Kaplan-Meier estimate of 2-year DOR, PFS and OS rates were 66.0%, 62.6%, and 76.5%, respectively. https://ashpublications.org/blood/article/doi/10.1182/blood.2024026401/535112/A-phase-1-trial-of-prizloncabtagene-autoleucel-a

The company behind it has signed deals with both AstraZeneca and Janssen. The latter includes this CAR (and another targeting just CD20), which has been granted Regenerative Medicine Advanced Therapy and Fast Track designations by the FDA for the treatment of patients with R/R DLBCL. Now a PhI/II trial is ongoing https://clinicaltrials.gov/study/NCT05800977

An update https://www.biospace.com/press-releases/lyell-to-highlight-vision-for-its-next-generation-car-t-cell-therapy-pipeline-at-43rd-annual-jp-morgan-healthcare-conference

See slide 10 https://ir.lyell.com/static-files/96379999-4d8e-466b-a5d5-44f5f6f88583

LYEL.................................https://stockcharts.com/h-sc/ui?s=LYEL&p=W&b=5&g=0&id=p86431144783

lyel..............................https://stockcharts.com/h-sc/ui?s=LYEL&p=W&b=5&g=0&id=p86431144783

LYEL................................https://stockcharts.com/h-sc/ui?s=LYEL&p=W&b=5&g=0&id=p86431144783

As a reminder, the ORR was ~12.5% for LYL797. BMY's JCAR024 had an ORR of 5-6%, but was discontinued, while a Fred Hutch construct showed no responses.

An update https://www.globenewswire.com/news-release/2024/10/24/2969054/0/en/Lyell-Immunopharma-to-Acquire-ImmPACT-Bio-and-Prioritizes-its-Pipeline-to-Focus-on-Next-Generation-CAR-T-cell-Therapies.html

The webcast https://lyell-company-update-2024.open-exchange.net/registration

Slides https://ir.lyell.com/static-files/40d6bd34-9ad0-49dd-b816-4bda3bd53eb0

LYEL..........................https://stockcharts.com/h-sc/ui?s=LYEL&p=W&b=5&g=0&id=p86431144783

Preclinical data (Stim-R tech) https://www.nature.com/articles/s41598-024-72392-1

LYEL..................................https://stockcharts.com/h-sc/ui?s=LYEL&p=W&b=5&g=0&id=p86431144783

(OT) Dr Restifo is Co-founder and Chief Scientist at Marble Therapeutics. From this: ''At Marble Therapeutics, he is working to figure out how to rewind the epigenetic clock on these cells, using any means possible. The company started out with a focus on skin rejuvenation, adds CEO Denitsa Milanova, but expanded to also work on adoptive cell therapy to prove their platform works.'' https://web.archive.org/web/20231218233715/https://www.nature.com/articles/d41573-023-00206-6

They have a license for TIL plus a neoantigen vaccine https://www.federalregister.gov/documents/2024/02/07/2024-02491/prospective-grant-of-an-exclusive-patent-license-vaccine-augmented-adoptive-cell-therapy-for-the

Preclinical data on the vaccine https://jitc.bmj.com/content/11/Suppl_1/A418

LYEL.....................................https://stockcharts.com/h-sc/ui?s=LYEL&p=W&b=5&g=0&id=p86431144783

LYEL active in the Gaucho session

Tempting but I will remain on the sidelines.

LYEL under $3

LYEL..................................https://stockcharts.com/h-sc/ui?s=LYEL&p=W&b=5&g=0&id=p86431144783

They could be working on this https://ash.confex.com/ash/2023/webprogram/Paper182417.html

Upcoming https://www.globenewswire.com/news-release/2023/09/27/2750444/0/en/Lyell-Immunopharma-Announces-the-Acceptance-of-Six-Abstracts-for-Presentation-at-2023-Society-for-Immunotherapy-of-Cancer-SITC-Annual-Meeting.html

LYEL new 52 week low

LYL119 https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=13739

Preclinical data from another group (LYL119 will be NR4A3-deficient) https://www.biorxiv.org/content/10.1101/2023.04.21.537841v1.full

LYEL..........................https://stockcharts.com/h-sc/ui?s=LYEL&p=W&b=5&g=0&id=p86431144783

The FDA has cleared an IND for LYL845. The PhI trial will initially enroll patients with relapsed and/or refractory metastatic or locally advanced melanoma and subsequently expand into NSCLC and CRC. Initial data presentation is expected in 2024.

SITC titles

NR4A3 gene editing and c-Jun overexpression synergize to limit exhaustion and enhance functional activity of ROR1 CAR T cells in vitro and in vivo

Engineering potent CAR T-cell therapies by controlling T-cell activation signaling parameters using the Stim-R™ technology, a programmable synthetic cell-signaling platform

The Epi-R™ technology produces a polyclonal TIL product (LYL845) with diverse tumor-reactive clones that have stem-like qualities and anti-tumor function

The Epi-R™ technology produces a polyclonal TIL product (LYL845) with a greater expansion success rate across hot and cold tumors, improved product phenotype, and maintenance of TCR diversity

Increased potency and functional persistence in vitro of a next-generation NY-ESO-1-specific TCR therapy incorporating Gen-R™ genetic reprogramming technology

recent technical advances using culture conditions with IL-7/IL-15 and
the addition of IL-21 may enhance the enrichment for TSCM cells
in the final CART product (74–76), which can be further increased
with the addition of drugs blocking T-cell differentiation, such as
glycogen synthase-3 inhibitors (77). Nevertheless, robust clinical grade protocols for generating TSCM-enriched CART products
have not been developed so far. Recently, a few CART19 clinical
trials for DLBCL have been conducted in which CART products
were manufactured from CD62L+ isolated T cells to generate
cellular products enriched for TCM cells (21, 78); however, due to
prolonged culture conditions, enrichment for TSCM and TCM
subsets in the infused product could not be demonstrated

https://www.frontiersin.org/articles/10.3389/fimmu.2022.904497/full

The AEs from the LD chemo*. I expect more data (dose expansion is ongoing) from them at ASH. As for NVS, a pivotal trial is planned and DL2 (12.5M) is the recommended dose.

* Some very early clinical data testing an anti-GD2 CAR-T with constitutive signaling from an engineered IL-7 receptor

Thanks for the link.
Most commonly reported grade 3/4 AEs were neutrophil count decrease (6/9, 67%), anemia (5/9, 56%), thrombocytopenia (2/9,22%), platelet count decrease (2/9, 22%) and no infection was reported. Complete response rate(CRR) was 78%

Compared to T-Charge
http://www.koreabiomed.com/news/articleView.html?idxno=12767

For Epi-R, they use media with high concentrations of potassium (as well as multiple cytokines). As for that, T-Charge or BE, I think a product with mostly ''stem-like'' cells and additional edits will be needed. But it doesn't have to be the latter, as shRNA can be used. Here are some clinical data on an anti-CD19 CAR-T with knock-down of both PD-1 and TIGIT https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.7522

Which will perform better ? BE with 7,8 edits on many genes, Epi secret sauce
or T-Charge which seems to add a CAR only to starting material in order to retain CD4/CD8 ratio.
YTB323 CAR-T cell products generated via this novel expansionless manufacturing process retained the immunophenotype of the input leukapheresis materia

That depends. Typically, the more the cells expand during manufacturing, the more they differentiate. In the case of ALLO, it seems most are effector memory (manufacturing time is ~19 days and there are a number of steps involved). LYEL refer to this as the expansion/quality paradox. With Epi-R, they have shown they can expand TCR-T cells up to 18 billion by day ten. In addition, these cells are over 94% viable and maintain their ''stem-like'' qualities.

Do you need Epigenetic Reprogramming if pts can be treated with healthy, young donor T cells?

ISSCR poster https://ir.lyell.com/static-files/971404cb-28eb-46fc-839f-b20735899373

Posters https://ir.lyell.com/static-files/d3a3d05c-1b39-4092-bf82-a486933bc268

https://ir.lyell.com/static-files/6014be8d-4e9d-499b-a496-513d2962f3e4

1115: Epigenetic Reprogramming (Epi-R™) Yields T-Cell Receptor Products with Improved Stemness, Metabolic Fitness, and Functional Activity in the Presence of Persistent Antigen Exposure https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=2014

661: Preclinical Development of LYL797, a ROR1-Targeted CAR T-Cell Therapy Enhanced with Genetic and Epigenetic Reprogramming for Solid Tumors https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=1597

GSK has updated the master protocol for their next generation constructs to include a third arm with GSK4427296 https://clinicaltrials.gov/ct2/show/NCT04526509

This uses Epi-R.