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Fate Therapeutics to Present at Upcoming Investor Conferences

SAN DIEGO, Feb. 14, 2025 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage...

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

SAN DIEGO, Feb. 04, 2025 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage...

Form 4 - Statement of changes in beneficial ownership of securities

Form 144 - Report of proposed sale of securities

Form 8-K - Current report

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

SAN DIEGO, Jan. 03, 2025 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage...

Fate Therapeutics Presents New Phase 1 Clinical Data of FT819 Off-the-shelf, CAR T-cell Product Candidate for Systemic Lupus Erythematosus

All Three Patients Treated in First Dose Cohort Administered Fludarabine-free Conditioning and Show Rapid...

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

SAN DIEGO, Dec. 03, 2024 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage...

NY1972 15 hours ago

This is why 1xx CAR matters. CD19 donor dose effective at 26 mil per MSK trial
$FATE 1xx: recommended phase 2 dose (RP2D) was 1 × 106 CAR T cells/kg.
$ALLO 120× 106 CAR T cells

https://ashpublications.org/blood/article/142/Supplement%201/892/502952/A-Phase-I-Study-of-CD19-Targeted-19-T2-28z1xx-CAR

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jondoeuk 1 day ago

For in vivo, I know a number are using either viral vectors or LNPs to target certain populations, such as CD7+ T and NK cells.

As for the TME, CAR-T can actually make it worse. In this paper (looking a B-ALL), MDSCs expand, hypoxia increases, and T-cells (both CAR and endogenous) exhibit severe exhaustion. So multiplex gene editing (including designing local secretion of certain ''payloads'') and combinations will likely be needed https://www.biorxiv.org/content/10.1101/2024.12.20.629119v1.full

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jondoeuk 1 day ago

For cancer, I hope they open dose expansion cohorts testing FT836 with (low dose) radiotherapy [1], (low dose) chemo [2], or panobinostat [3]. Also, test multiple infusions.

Refs:
1 https://aacrjournals.org/cancerres/article/81/13_Supplement/1591/667388/Abstract-1591-FT536-Preclinical-development-of-a
2 https://jitc.bmj.com/content/10/Suppl_2/A291
3 https://pmc.ncbi.nlm.nih.gov/articles/PMC7269842/

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NY1972 2 days ago

Holy grail: pan cancer, off the shelf, no chemo T cells. all that for a donut.
How many bio investors can read?

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NY1972 2 days ago

Revealing .. T-Dxd and EGFR mut, KRAS ....

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NY1972 3 days ago

There is a lot to be digested in the new deck. The tumors targeted are reviewing.

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glenn1919 6 days ago

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

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glenn1919 2 weeks ago

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

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NY1972 2 weeks ago

ADR works like CD16a/ADCC but targets exhausted T cells 4-1BB+ instead. Invivo has plenty of issues uptake, off target...... Effective ACT needs to keep TME from resurgence after LD. FT525 have a good chance of doing it with 3 doses.

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jondoeuk 2 weeks ago

New deck https://ir.fatetherapeutics.com/static-files/1cac8c4b-ac0b-42cf-bc22-80acbc38405b

FT829 (anti-CD19/CD38) is new and will be tested in autoimmune diseases. CD38 is involved in many, including lupus https://www.sciencedirect.com/science/article/abs/pii/S156899722300023X

I hope the anti-CD19/BCMA candidate is not far behind and they will take at least another forward (anti-CD19/CD20).

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jondoeuk 2 weeks ago

A lot rests on the ADR tech.

I should also say that in vivo cell therapies are moving into the clinic (some are not giving any LD chemo). Pretty early data from one trial https://jitc.bmj.com/content/12/Suppl_3/A1712

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NY1972 2 weeks ago

FT829, FT836 no LD req'd. FT525 DBLCL no LD req'd. CEO is sending a message but few can hear.

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NY1972 4 weeks ago

Would be clear if they stratified by NLR. Gastric have higher NLR where the Ab failed for good. It seems to work when NLR is low (before VEGF) with high CD8 clones in CRC.

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NY1972 4 weeks ago

Many failed attempts 4-1BB (26 clinical prgms - 0 approved), these T cells must be passively protecting the cancer cells. Also Circulating aged neutrophils (e.g., those undergoing senescence or prolonged circulation due to impaired clearance) have been reported to express higher levels of 4-1BB compared to younger neutrophils.
We will see if high dose 522 + Rituximab can result in CR without LD in DBLCL patients.

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jondoeuk 4 weeks ago

The PR is an utter mess! The ORR across subgroups is higher, but the (m)PFS isn't that great.

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jondoeuk 4 weeks ago

We won't know until it is tested, but from this: ''We found activated CD19 CAR.ADR T cells have lower levels of detectable 4-1BB on their surface compared to CD19 CAR T cells, suggesting partial downregulation or masking of 4-1BB upon ADR expression (Supplementary Fig. 9a). Indeed, expression of a truncated non-signaling ADR on activated T cells protected them from cytotoxicity by ADR T cells (Supplementary Fig. 9b-d) so that cis-masking of 4-1BB by ADR likely contributes to fratricide resistance of activated ADR T cells.'' https://pmc.ncbi.nlm.nih.gov/articles/PMC7854790/

FATE has its own data (that they still won't share!)

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NY1972 4 weeks ago

Hidden message from LPTX on CRC
No prior anti-VEGF therapy: Patients in the Experimental Arm (n=49) had an ORR of 51%, compared to 29% ORR in the Control Arm (n=45)
Prior anti-EGFR therapy: Patients in the Experimental Arm (n=28) had an ORR of 54%, compared to 27% ORR in the Control Arm (n=22)

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NY1972 4 weeks ago

To be deleted by ADR?
Exhausted T cells, typically arising from chronic antigen stimulation in the tumor microenvironment (TME), may express activation-induced costimulatory receptors like 4-1BB alongside inhibitory receptors
exhausted T cells are not actively immunosuppressive like Tregs. Their role is more of a failure to sustain effective anti-tumor responses rather than actively suppressing other immune cells. However, their presence in large numbers can create a functionally "tolerant" immune environment that indirectly benefits the tumor.

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NY1972 1 month ago

The key to success is CXCR2 and 1xx for FATE CART. MSK 1xx CD19 auto trial showed ORR at 25M cells dose, so trogocytosis, persistence and proliferation must be optimal to be effective.

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jondoeuk 1 month ago

One of the potential downsides of inhibiting (CD16(a)) shedding is that it could slow NK detachment and reduce serial killing https://rupress.org/jcb/article/217/9/3267/120862/Shedding-of-CD16-disassembles-the-NK-cell-immune

It was shown some years ago that CD64 binds to the same IgGs, but with at least 2-3 orders of magnitude higher affinity than CD16(a). Based on that data, I think they should switch to using it and look to add additional modifications https://jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01455-z

They (and others) need to learn from the (early) mistakes of FATE.

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jondoeuk 1 month ago

Trogocytosis can impact both CAR-T, as well as CAR-NK therapies. Strategies to overcome trogocytosis-induced antigen loss, fratricide and/or cell exhaustion include, pharmacological targeting, modulating CAR affinity, ''armouring,'' modulating the signalling domain(s), or using a dual CAR strategy. Some preclinical data on the latter https://www.nature.com/articles/s41591-022-02003-x

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NY1972 1 month ago

The functional effects of trogocytosis remain to be elucidated, however, it has been shown to interfere with successful CAR-mediated antitumor responses as it promotes tumor antigen escape as well as CAR T cell dysfunction due to fratricide killing
https://jitc.bmj.com/content/11/2/e005691

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NY1972 1 month ago

This study was done without ADCC.

expression of CXCR2 in CAR-T cells can significantly improve these T cell migrating to the tumor microenvironment of hepatocellular carcinoma, which provides the strong evidence to support that CXCR2 is of great potential to be utilized in CAR-T cell therapies for various solid tumors.

https://onlinelibrary.wiley.com/doi/full/10.1002/eji.201948457?utm_source=chatgpt.com

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jondoeuk 1 month ago

Both follow LD chemo in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment (in Cycle 1), participants may be considered for an additional treatment cycle (Cycle 2 retreatment).

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jondoeuk 1 month ago

NEUK201-00* is being tested in advanced/metastatic solid tumours at a single site.

* It could be an iNK with just a high-affinity non-cleavable CD16(a) receptor, but this comes from a Chinese site that has undergone translation. The IL-2 dose is intermediate.

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NY1972 1 month ago

ADCC will lead to higher expression of CXCL8 by innate cells which will lead to more FT825 into TME. The combo trial will be a game changer. What is the dosing schedule for cetuximab?

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jondoeuk 1 month ago

Translational data from the PhI B-cell lymphomas trial demonstrated primary, secondary and tertiary tissue trafficking and clearance of CD19+ cells. That should help enable an immune reset in autoimmune diseases.

The next-gen CAR-T's will incorporate a suite of novel synthetic edits that are designed to enhance homing and biodistribution to secondary and tertiary tissues.

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jondoeuk 1 month ago

I hope they will pick up the pace with enrolment. It can't be as slow as last year.

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jondoeuk 1 month ago

Shoreline has let go of an undisclosed number of employees tied to a cell therapy project with GILD's Kite Pharma, Endpoints News reported. Shoreline CEO declined to disclose the number of workers that were laid off and said the future of the collaboration is still ''to be determined.''

The two had agreed to change the focus of their partnership. Instead of developing a CAR-iNK cell therapy for B-cell lymphomas (either CD19-targeted or CD19/CD20-targeted), they switched to autoimmune diseases. Shoreline already had a pre-IND meeting with the FDA and was recruiting US and international clinical trial sites for a PhI trial in autoimmune diseases. They were going to enter the clinic in the coming months and planned to give Kite the possibility of opting in after concluding the trial.

As Kite went through leadership changes in recent years, Shoreline's CEO said the two had a ''wonderful collaboration,'' including being aligned with the new [autoimmune] focus for that therapy. They agreed on ''90%'' of the terms in an adjusted deal, including another potential equity investment from GILD, but they couldn't come to an agreement on any ''back-end economics.'' Shoreline believed it deserved a ''larger portion on [the] upside.''

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NY1972 2 months ago

Pipe valued at 10% of paid in capital. A CART that follows the chemotactic gradient to TME is free today.

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NY1972 2 months ago

Ft825 - 4 more sites added

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NY1972 2 months ago

FT819 can act as a ligand sink and change DC/CD8, NLR ratios in 2nd lymphoid and inflammed tissues. Creating a new Bronx so to speak.

CXCR4 is critical for the organization of secondary lymphoid tissues, such as lymph nodes and spleen, where immune responses are initiated.
Dysregulation of CXCR4 signaling may contribute to abnormal germinal center reactions and the development of autoreactive immune cells.

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jondoeuk 2 months ago

Maybe they thought that better penetration into the bone marrow could allow for greater effectiveness in targeting certain types, such as B-ALL. CXCR4 is critical for bone marrow homing of T-cells https://onlinelibrary.wiley.com/doi/10.1002/eji.201747438 https://journals.aai.org/jimmunol/article/193/3/1013/108777/Cutting-Edge-CXCR4-Is-Critical-for-CD8-Memory-T

I know they have a patent for hematopoietic stem or progenitor cells being contacted with an agent that increases CXCR4 gene expression in the cells.

However, the iTs (that are either contacted with that agent or not) express high levels of Fas https://www.jci.org/articles/view/121491 https://www.nature.com/articles/s41467-017-00784-1 https://www.nature.com/articles/nm.3541

To overcome it, this was created https://aacrjournals.org/cancerres/article/84/6_Supplement/3995/740628/Abstract-3995-A-novel-chimeric-Fas-signal-redirect

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NY1972 2 months ago

Why FT819 has high CXCR4 expression?

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NY1972 2 months ago

Rearranging the deck.
Follicular structures were disrupted and FDCs were depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX
Let see if FT825 can do the same with LD and Cetuximab.
https://ard.bmj.com/content/annrheumdis/early/2024/09/11/ard-2024-226142.full.pdf

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NY1972 2 months ago

The key is in CART and neutrophil interactions within the draining lymph nodes. Neutrophils build TME and suppress CD8+ /NK via Treg. For the primary tumor, CART will need mAb to deal with antigen escape.

https://aacrjournals.org/cancerrescommun/article/4/2/588/734969/Characterizing-Neutrophil-Subtypes-in-Cancer-Using

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jondoeuk 2 months ago

I want to say one of two, but can't remember off the top of my head.

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jondoeuk 2 months ago

Metastatic cancer cells can develop multiple (suppressive) mechanisms that enable the evasion of NKs, such as this https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01206-3

In one patent the same group goes on to show that EP2/EP4 KO enables the NKs to secrete chemokines, such as XCL1 that recruit key immune cell populations required for T-cell mediated tumour immunity https://www.cell.com/cell/fulltext/S0092-8674(18)30039-4

In another paper, a different group identifies IGSF8 as a new immune checkpoint that suppresses NKs (and dendritic cells) in antigen presentation deficient cancer cells https://www.cell.com/cell/abstract/S0092-8674(24)00355-6

So I think the right combination of edits will be needed to overcome trafficking, infiltration, potency, expansion, persistence, while also preventing exhaustion/dysfunction, suppression, tackle antigen heterogeneity and evasion.

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NY1972 2 months ago

Which other bios have CART with CXCR2? That feature is critical after lymphodepletion causing BM suppression for 2 weeks.

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NY1972 2 months ago

Sounds like what one would find in SLE, cancer pts with a reset immune system.

?d T-cell proliferation was dependent upon CD137L expression on aAPC and addition of exogenous IL2 and IL21. Propagated ?d T cells were polyclonal

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jondoeuk 2 months ago

For many, many years the focus was on the Vd2 subset, but recent evidence in multiple tumours showed associations of other subsets (Vd1 and/or Vd3) with increased patient survival and/or clinical benefit https://www.nature.com/articles/s43018-022-00376-z https://www.science.org/doi/10.1126/scitranslmed.aax9364

There is also preclinical data which show that the Vd1 subset has superior cytotoxicity over Vd2 https://aacrjournals.org/clincancerres/article/20/22/5708/117332/Activating-and-Propagating-Polyclonal-Gamma-Delta

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NY1972 2 months ago

NK is fine for SLE since the depletion of the memory B cells is the goal. For solid, creating polyclonal T cells with memory phenotype is the key for OR duration.
From ChatGPT:
Studies with 1XX CAR T cells highlight their enhanced capacity for cytokine production and survival, suggesting a stronger potential for interaction with and modulation of DCs compared to conventional CAR T cells. Dendritic cells in the TME can process these antigens and cross-prime endogenous T cells against TAAs, creating a polyclonal immune response that complements the CAR T-cell activity.

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jondoeuk 2 months ago

They should get a B7-H3 CAR into the clinic https://www.oncologypipeline.com/apexonco/fourth-challenger-dualitybio-and-biontech

Based on preclinical data targeting the IgC domain is more effective https://www.nature.com/articles/s41467-023-41631-w

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jondoeuk 2 months ago

Unlike NKs, the differentiation of T-cells from iPSCs is (far) more complex. Also, the NKs from iPSCs are more comparable functionality to PB/CB NKs, and can kill independent from the CAR.

It would make sense to test the two https://aacrjournals.org/cancerimmunolres/article/7/3/363/469550/NK-Cells-Expressing-a-Chimeric-Activating-Receptor

But there are still hurdlers (for the NKs) to overcome, including persistence and lack of expansion. The use of an IL15-RF may impair NK functions as well https://insight.jci.org/articles/view/96219 https://www.pnas.org/doi/10.1073/pnas.1012128107

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NY1972 2 months ago

1xx, autologous T cells and lactate
https://pmc.ncbi.nlm.nih.gov/articles/PMC11588660/

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NY1972 2 months ago

SP from 100 to 1 while revamped pipeline from 1 to 100

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NY1972 2 months ago

CEO was pretty bullish on 825 + cetuximab. I think Ig1 is as effective as TCE as it activates the innate arm.

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jondoeuk 2 months ago

FT825 would require an additional receptor https://ashpublications.org/blood/article/140/Supplement%201/7429/491146/A-CD3-Fusion-Receptor-CD3-FR-Uniquely-Enables

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NY1972 2 months ago

Failure to revive old cells
https://www.merck.com/news/merck-provides-update-on-keyvibe-and-keyform-clinical-development-programs-evaluating-investigational-vibostolimab-and-favezelimab-fixed-dose-combinations-with-pembrolizumab/

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NY1972 2 months ago

FATE revamped it's cell to deal with TME. Yet the SP is 1.8% of what it used to be. 95% investors were in it for ride because J&J was on board. They had little understanding of science.

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Fate Therapeutics Inc (FATE)

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FATE News

Fate Therapeutics to Present at Upcoming Investor Conferences

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

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 144 - Report of proposed sale of securities

Form 144 - Report of proposed sale of securities

Form 144 - Report of proposed sale of securities

Form 8-K - Current report

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

Fate Therapeutics Presents New Phase 1 Clinical Data of FT819 Off-the-shelf, CAR T-cell Product Candidate for Systemic Lupus Erythematosus

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

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Professional-Grade Tools, for Individual Investors.

FATE News

Fate Therapeutics to Present at Upcoming Investor Conferences

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

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 4 - Statement of changes in beneficial ownership of securities

Form 144 - Report of proposed sale of securities

Form 144 - Report of proposed sale of securities

Form 144 - Report of proposed sale of securities

Form 8-K - Current report

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

Fate Therapeutics Presents New Phase 1 Clinical Data of FT819 Off-the-shelf, CAR T-cell Product Candidate for Systemic Lupus Erythematosus

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

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