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Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Form 10-Q - Quarterly report [Sections 13 or 15(d)]

Form 8-K - Current report

Fate Therapeutics Reports Third Quarter 2024 Financial Results and Business Updates

Initial Clinical Data from Phase 1 Autoimmunity Study of FT819 1XX CAR T-cell Product Candidate to be Presented...

Fate Therapeutics Highlights Cancer-selective, HER2-Targeting Profile of FT825 / ONO-8250 CAR T-cell Product Candidate for Treatment of Advanced Solid Tumors at 2024 SITC Annual Meeting

Novel H2CasMab-2 Antigen Binding Domain Shown to Preferentially Target HER2 Expressed on Tumor Cells in...

Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Fate Therapeutics Presents Pan-tumor Targeting Preclinical Data for FT836 MICA/B-targeted CAR T-cell Product Candidate at 2024 SITC Annual Meeting

Multiplexed-engineered, iPSC-derived CAR T Cell Targets Proteins Expressed on Cancer Cells in Response to...

Fate Therapeutics Reports New Employee Inducement Award Under Nasdaq Listing Rule 5635(c)(4)

SAN DIEGO, Nov. 04, 2024 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage...

Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Fate Therapeutics Reports New Employee Inducement Awards Under Nasdaq Listing Rule 5635(c)(4)

SAN DIEGO, Oct. 02, 2024 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage...

Fate Therapeutics to Present at 2024 Cantor Global Healthcare Conference

SAN DIEGO, Sept. 12, 2024 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage...

Form 8-K - Current report

Form 3 - Initial statement of beneficial ownership of securities

NY1972 9 hours ago

Transgene copies at 100M. Looks like 1B will be req'd for mono.
https://x.com/search?q=%24fate&src=typeahead_click&f=top

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jondoeuk 10 hours ago

It could be the cut-off date and wanting to report at least some data at the right conference.

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jondoeuk 16 hours ago

It has been https://www.nature.com/articles/s41577-024-01022-8

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NY1972 1 day ago

ADR not mentioned here.
https://www.nature.com/articles/s41587-024-02446-2.epdf?sharing_token=KklFSSP3p53mf0xPLDQRxdRgN0jAjWel9jnR3ZoTv0NdPHcP7SRuyRglh7NHotfV7BOOCAzc5VDgmfzhtTWkIm07b4aMqRkQn3HTeBwkGpYwc2cH81TsBxXxM6IPCow57SLxzS1GOe-HCo_6SwpyaR2dQyt99EM61q_QsC-r6nc%3D

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NY1972 1 day ago

Why they want to present data from 1 SLE patient? 2 more 20 days later?
The Company plans to present clinical and translational data from the first patient at the American College of Rheumatology (ACR) Convergence being held in Washington, D.C. on November 16-19.
The Company plans to present clinical and translational data from the first three patients at the American Society of Hematology (ASH) Annual Meeting being held in San Diego, CA on December 7-10

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NY1972 1 day ago

Why are they presenting initial clinical and translational data from the Phase 1 BCL study at ACR Convergence, not ASH?

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jondoeuk 2 days ago

Q3 financial results and business updates https://www.globenewswire.com/news-release/2024/11/12/2979634/0/en/Fate-Therapeutics-Reports-Third-Quarter-2024-Financial-Results-and-Business-Updates.html

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jondoeuk 2 days ago

The ADR selective targets 4-1BB+ alloreactive immune cells, but it's possible that there are other alloreactive immune cells that don't express 4-1BB, so the additional KOs would allow for passive evasion (by blocking host immune cell detection and interaction).

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NY1972 5 days ago

ADR targets Treg and mAb targets NK and macrophages. Interesting to me ADR working like LD to create endogenous space. Now I understand why chemo + PD1 has higher ORR than PD1 alone in NSCLC. Also explains why less toxic ADC beats ADC with more toxic payload.

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NY1972 5 days ago

If ADR is working without additional KO in CARNK, there is no need to further edits. Cells can't form synapses with no adhesion.

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jondoeuk 6 days ago

I will wait to see if they add the slides and posters. If not, will email them.

I was expecting quad KO (CD54/CD58/B2M/CIITA (plus the ADR)) to overcome rejection https://www.biorxiv.org/content/10.1101/2023.10.09.557143v1.full

Even without that, I think they should look to add a safety switch https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)30275-1

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jondoeuk 6 days ago

I wasn't expecting activity* from DL1, but hopefully there will be starting at the next dose level.

* All three were heavily pre-treated patients, all of whom were previously treated with at least five prior lines of therapy, including HER2-targeted therapy.

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jondoeuk 6 days ago

The PRs https://www.globenewswire.com/news-release/2024/11/09/2977966/0/en/Fate-Therapeutics-Highlights-Cancer-selective-HER2-Targeting-Profile-of-FT825-ONO-8250-CAR-T-cell-Product-Candidate-for-Treatment-of-Advanced-Solid-Tumors-at-2024-SITC-Annual-Meeti.html

https://www.globenewswire.com/news-release/2024/11/08/2977858/24675/en/Fate-Therapeutics-Presents-Pan-tumor-Targeting-Preclinical-Data-for-FT836-MICA-B-targeted-CAR-T-cell-Product-Candidate-at-2024-SITC-Annual-Meeting.html

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NY1972 6 days ago

In an ongoing Phase 1 study in advanced solid tumors, three patients were treated with FT825 / ONO-8250 in the first low-dose cohort as monotherapy, and no dose-limiting toxicities (DLTs) and no events of any grade of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD) were observed.

https://finance.yahoo.com/news/fate-therapeutics-highlights-cancer-selective-183000221.html

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NY1972 1 week ago

No PR for 10Q and SITC? Strange Mgt has become speechless.

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NY1972 1 week ago

Sounds promising and first in class.

Additionally, we have verified that H2CasMab-2, unlike trastuzumab, uniquely recognizes carboxyl-terminal HER2 fragments (p95), where p95 detection has been observed in up to 30% of patients previously treated with trastuzumab and is considered a predictive marker of resistance to trastuzumab-based therapies.

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NY1972 1 week ago

No IL7RF?

iPSCs were engineered to express 3MICA/B CAR and other novel synthetic receptors, including an allo-defense receptor, a TGFß-signal redirection receptor, a high-affinity, non-cleavable CD16a (hnCD16), and a CXCR2 receptor, and to knock-out CD38, CD58, and T-cell receptor alpha. Engineered iPSCs were differentiated into a uniform population of CD8+ alpha-beta T cells (iT) cells, uniformly expressing all engineered elements.

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jondoeuk 1 week ago

The abstracts

https://jitc.bmj.com/content/12/Suppl_2/A302

https://jitc.bmj.com/content/12/Suppl_2/A310

https://jitc.bmj.com/content/12/Suppl_2/A355

https://jitc.bmj.com/content/12/Suppl_2/A388

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jondoeuk 1 week ago

They knockout SOCS1, CISH, BIM and FAS. Nothing about the proprietary signal converter or design of the CAR. As for HLA-E, it makes little sense to me as 50-90% of the human population are CMV+ (NKG2C+ adaptive NKs target HLA-E+ cells) https://onlinelibrary.wiley.com/doi/10.1002/rmv.2034

Also, work on iPSC-derived ab T-cells is ongoing.

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jondoeuk 1 week ago

Next-Generation Off-the-Shelf CAR T-Cell Therapy Developed to Eliminate a Broad Spectrum of Pathogenic Cells in Hematological Diseases in the Absence of Conditioning Chemotherapy https://ash.confex.com/ash/2024/webprogram/Paper209465.html

Alloimmune Defense Receptor Combined with Genetic Ablation of Adhesion Ligand CD58 Is a Comprehensive Approach to Promote Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy https://ash.confex.com/ash/2024/webprogram/Paper210846.html

Development of Induced Pluripotent Stem Cell-Derived T Cells Exhibiting Phenotypic and Functional Attributes of Primary CAR T Cells https://ash.confex.com/ash/2024/webprogram/Paper210786.html

Notch will present at ASH

A Regulated Cytokine Engineering Strategy to Augment in Vitro and In Vivo persistence of Allogeneic iPSC Derived CD8 T-Cells https://ash.confex.com/ash/2024/webprogram/Paper211835.html

A Layered Cloaking Strategy to Generate Allogeneic iPSC-Derived CD8 T-Cells That Evade NK Clearance https://ash.confex.com/ash/2024/webprogram/Paper210003.html

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jondoeuk 1 week ago

BGNE are now developing their own*.

* iPSC-Derived CAR-Gamma Delta T with Novel Combinatorial KO Demonstrated Extended Longevity and Profound Anti-Tumor Efficacy without Cytokine Support in Preclinical Studies https://ash.confex.com/ash/2024/webprogram/Paper205086.html

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NY1972 2 weeks ago

B7-H3 is a tumour associated antigen. It reminds me of the famous PSMA in the last few decades.

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jondoeuk 2 weeks ago

A few years ago they had two therapies* targeting B7-H3**. So one of the first next gen iTs could be targeting it. All we know now is that the next gen iTs will have the ADR and secrete immune modulators.

* They first identified a novel camelid nanobody and then created CAR motifs for NKs and T-cells. For the latter, delivered a single tricistronic cassette encoding the nanobody (fused to a CD28-CD3z-1XX signaling domain), an IL-7 receptor fusion protein, and a high affinity non-cleavable CD16 receptor into the TRAC locus. They also knocked out CD38.

** B7-H3 is a tumour associated antigen, found on numerous solid tumours including, NSCLC, SCLC, RCC, prostate, and breast cancers. It contributes to immune evasion, metastasis and is associated with disease progression, recurrence, poor prognosis, and drug resistance. Furthermore, is minimally expressed on normal tissue, making it an ideal target for broad treatment.

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NY1972 2 weeks ago

FRa next?
A recent study has shown that immunotherapy can overcome this problem by targeting folate acid receptor-a. Gene-modified ?dT cells express the FRa-CAR and secrete IL-7 and CCL19 (7 × 19 CAR-?dT). The 7 × 19 CAR-?dT cells show anti-tumor activity in vitro, and are more beneficial to the growth of TNBC xenograft mouse models than CAR-?dT.

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NY1972 2 weeks ago

Looking at AFMD ICE + CBNK trial, resetting the endogeneous immune cells is the key for long term remission. Getting T, B, APC involved to eradicate the tumor is the key. I don't think you need perfect CAR T cells with many edits to do the job.

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NY1972 2 weeks ago

Adding cetuximab can flip the innate cells so 825 will have less hostile TME to deal with resulting in longer CAR T persistence and higher ORR.

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jondoeuk 2 weeks ago

Neukio is now using multiple gene editing strategies and screening, as well as working on fully closed and automated production. The pipeline has grown to nine products (all undisclosed), with a number of candidates at the preclinical stage, and they plan to advance some of these into the clinic next year.

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jondoeuk 2 weeks ago

Yes, and while FT819 exhibited similar expansion to auto CAR-T's cells, had shortened persistence. Adding the ADR (+/- additional KOs, such as CD54/58) should help overcome the latter, but I still think they need to improve differentiation protocols, engineering, selection, CAR constructs, expansion, and formulation (high Tscm (+/- Tcm) phenotype(s)). The goal should be best-in-class products.

Long-term, look to add CD4+ https://ashpublications.org/blood/article/134/Supplement_1/1937/428148/Guided-Polarization-of-iPSC-Derived-CD4SP-Helper-T

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jondoeuk 2 weeks ago

Yes. Here is some preclinical data for FT819 https://aacrjournals.org/cancerres/article/78/13_Supplement/LB-108/541582/Abstract-LB-108-Generation-of-off-the-shelf-TCR

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NY1972 2 weeks ago

FT825 should work in EBV related cancers

Both EBV and HPV manipulate chemokine profiles to enhance viral survival:

EBV-infected cells tend to increase pro-inflammatory chemokines, potentially leading to immune cell recruitment but also immune exhaustion.

HPV-infected cells often suppress chemokine responses to avoid detection, with selective increases in chemokines like IL-8 in tumor stages to create a supportive environment for cancer progression.
This alteration of chemokine profiles helps both viruses persist and, in some cases, contributes to the development of virus-associated cancers.

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NY1972 2 weeks ago

aßT cells according to
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY

iPSC-derived aßT, NK, and iNKT cells are currently being tested in phase I clinical trials. The ability to perform (multiplexed) gene editing at the iPSC level and subsequent differentiation into effector populations not only expands the arsenal of ACT but allows for development of ACT utilizing cell types which cannot be efficiently obtained from peripheral blood or engineered and expanded in vitro.

https://www.sciencedirect.com/science/article/abs/pii/S0301472X24005137

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NY1972 2 weeks ago

Do FT819 and FT825 secret IFN gamma?

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NY1972 2 weeks ago

Neutrophils has plenty CXCR2. TAN is major player in TME. Both ADC and PD1 lower NLR for ORR. LD + FT825 seems to lower TAN and up lymphocytes counts at the same time. I think FT825 will be big surprise for many sellers.

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jondoeuk 2 weeks ago

I think that is likely.

On the topic of NKG2DLs, one group engineered an NKG2D CAR-NK cell product (which would target ULBP1-6 as well) that is unaffected by TGFB or soluble NKG2DLs, is able to kill MDSCs and rescue impaired CAR-Ts https://aacrjournals.org/cancerimmunolres/article/7/3/363/469550/NK-Cells-Expressing-a-Chimeric-Activating-Receptor

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jondoeuk 2 weeks ago

It has been disclosed. But CD4+* CAR-T cells play a direct role as well https://www.nature.com/articles/leu2015247

* There are different subsets, including Th1, Th9 and Th17 cells.

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jondoeuk 2 weeks ago

In the context of cancer, different tumour types can vary in their secretion of chemokines, and successful T- (or NK) cell trafficking depends on matching the chemokine with its appropriate chemokine receptor. Chemokines also recruit immunosuppressive cells into the TME.

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NY1972 2 weeks ago

FT836 = FT825 targeting MICA/B + ADR?

Recognition of Stress Molecules: ?d T cells recognize stress-induced molecules, like MICA/B and ULBP, that are commonly upregulated on tumor cells. This recognition is independent of the MHC system, which allows ?d T cells to identify and infiltrate tumor sites without requiring specific antigen presentation, as conventional T cells do.

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NY1972 2 weeks ago

That is the role model for FT825?
Chemokine Receptor Expression: ?d T cells express a range of chemokine receptors, such as CCR5, CCR6, and CXCR3, which can respond to chemokine gradients created by tumor cells and stromal cells. This chemokine-guided migration helps ?d T cells home in on tumor sites and penetrate the solid tumor mass.

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NY1972 2 weeks ago

Did FATE CEO say that? ?d T cells can activate DC and macrophages.
Cytokine Production: ?d T cells produce significant amounts of cytokines like IFN-? and TNF-a, which enhance anti-tumor immunity by promoting other immune cells’ activation and cytotoxicity against tumors.

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jondoeuk 2 weeks ago

Its an alpha beta CD8+ T-cell product.

Type I NKTs have an invariant TCR and the Rezvani Lab (at MD Anderson) is working on an NK product with that (as well a CD16a receptor and CD3 fusion receptor).

The iTCR can directly recognise and kill CD1d-expressing cancer cells https://www.sciencedirect.com/science/article/abs/pii/S1521661613001757

Also, kill certain immunosuppressive cells in the TME https://www.jci.org/articles/view/37869

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jondoeuk 2 weeks ago

First allo (healthy donor) CAR-NK data https://acrabstracts.org/abstract/allogenic-cd19-car-nk-cells-therapy-in-refractory-systemic-lupus-erythematosus-an-open-label-single-arm-prospective-and-interventional-clinical-trial/

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jondoeuk 2 weeks ago

Looking at autoimmune, we are starting to see data on auto dual-targeted CARs (showing long-term medication-free remissions) https://ard.bmj.com/content/83/10/1304

Too early to stay about ICEs, allo CAR-NKs or allo CAR-Ts, but there is some limited data for the latter https://www.cell.com/cell/abstract/S0092-8674(24)00701-3

As for CAR-NKs/Ts (for different cancers), there are ways to activate innate cells in the TME. I know one group showed that IL-18-secreting CAR-Ts could reprogram the myeloma bone marrow microenvironment through type-I/II interferon signaling, and activate macrophages to mediate antimyeloma activity.

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NY1972 2 weeks ago

Is FT825 CAR NKT cells?

Natural Killer T (NKT) Cells: Some NKT cells express CD16a, which can allow them to mediate antibody-dependent cellular cytotoxicity (ADCC) in response to antibody-coated targets, a property more commonly associated with NK cells.

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NY1972 3 weeks ago

In the TME, TANs are often influenced by factors secreted by both cancer and stromal cells, which can polarize them into either pro-tumor or anti-tumor phenotypes. However, their lack of IL-7R expression means they are generally not directly responsive to IL-7 levels, even if IL-7 concentrations are elevated within the TME or systemically due to conditions like lymphodepletion

Pts with CPI-naïve relapsed/refractory (R/R) MSS-CRC and PDAC, and CPI-treated R/R TNBC, NSCLC, and SCLC, were enrolled. NT-I7 (efineptakin alfa) 1200 µg/kg intramuscularly every 6 weeks
A sustained and significant (approximate 3X from baseline) increase of peripheral lymphocytes in all arms was observed as shown in our previous report
https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.2514
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0286834#pone.0286834.ref035
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.747324/full

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jondoeuk 3 weeks ago

FT522 preclinical data https://acrabstracts.org/abstract/development-of-a-multiplexed-engineered-off-the-shelf-car-nk-cell-with-unique-multi-pathogenic-cell-targeting-capacity-for-the-treatment-of-autoimmune-diseases-in-the-absence-of-conditioning-chemothe/

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jondoeuk 3 weeks ago

Yes. The IL7-RF to increase persistence and CD38 KO to enhance metabolic fitness and persistence. The latter also overcomes anti-CD38 mAb-mediated fratricide so allows for targeted conditioning (no cy/flu)*.

There is preclinical data from other groups https://aacrjournals.org/cancerdiscovery/article/7/11/1238/6513/Constitutive-Signaling-from-an-Engineered-IL7 https://www.cell.com/molecular-therapy-family/oncology/fulltext/S2950-3299(24)00061-4

* https://ashpublications.org/blood/article/140/Supplement%201/7388/492103/iPSC-Derived-CD38-Null-NK-Cells-in-Combination

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NY1972 3 weeks ago

wrong question. Since 825 already have 1xx, what benefit do they expect from IL7-RF and CD38KO, lower dose and higher persistence than 819?

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NY1972 3 weeks ago

825 doesn't have 1XX. Are they expecting IL7-RF and CD38KO to get persistence?

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Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Form 10-Q - Quarterly report [Sections 13 or 15(d)]

Form 8-K - Current report

Fate Therapeutics Reports Third Quarter 2024 Financial Results and Business Updates

Fate Therapeutics Highlights Cancer-selective, HER2-Targeting Profile of FT825 / ONO-8250 CAR T-cell Product Candidate for Treatment of Advanced Solid Tumors at 2024 SITC Annual Meeting

Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Fate Therapeutics Presents Pan-tumor Targeting Preclinical Data for FT836 MICA/B-targeted CAR T-cell Product Candidate at 2024 SITC Annual Meeting

Fate Therapeutics Reports New Employee Inducement Award Under Nasdaq Listing Rule 5635(c)(4)

Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Fate Therapeutics Reports New Employee Inducement Awards Under Nasdaq Listing Rule 5635(c)(4)

Fate Therapeutics to Present at 2024 Cantor Global Healthcare Conference

Form 8-K - Current report

Form 3 - Initial statement of beneficial ownership of securities

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Real-time discussions and trading ideas: Trade with confidence with our powerful platform.

FATE News

Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Form 10-Q - Quarterly report [Sections 13 or 15(d)]

Form 8-K - Current report

Fate Therapeutics Reports Third Quarter 2024 Financial Results and Business Updates

Fate Therapeutics Highlights Cancer-selective, HER2-Targeting Profile of FT825 / ONO-8250 CAR T-cell Product Candidate for Treatment of Advanced Solid Tumors at 2024 SITC Annual Meeting

Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Fate Therapeutics Presents Pan-tumor Targeting Preclinical Data for FT836 MICA/B-targeted CAR T-cell Product Candidate at 2024 SITC Annual Meeting

Fate Therapeutics Reports New Employee Inducement Award Under Nasdaq Listing Rule 5635(c)(4)

Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Form SC 13G/A - Statement of Beneficial Ownership by Certain Investors: [Amend]

Fate Therapeutics Reports New Employee Inducement Awards Under Nasdaq Listing Rule 5635(c)(4)

Fate Therapeutics to Present at 2024 Cantor Global Healthcare Conference

Form 8-K - Current report

Form 3 - Initial statement of beneficial ownership of securities

FATE Discussion

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