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Fate Therapeutics Inc

Fate Therapeutics Inc (FATE)

3.01
-0.06
(-1.95%)
Closed October 09 4:00PM
3.01
0.00
( 0.00% )
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FATE Discussion

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NY1972 NY1972 11 hours ago
Do you think It will be trimodal? FATE is turning NK and T cells into swiss army knife. Fate has become a light house in the ocean of ADCs.
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jondoeuk jondoeuk 13 hours ago
No, as the only milestones for the platform this year are to disclose new target(s) and product configurations for at least two next-generation cell product candidates, one being FT836.
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NY1972 NY1972 17 hours ago
Do you think FT836 is ready for IND in 2024?
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jondoeuk jondoeuk 5 days ago
There have been a number of papers (preclinical) showing that ''avidity enhancement'' (increasing cell-cell binding) can lead to better efficacy. Here is one https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00157-X
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jondoeuk jondoeuk 6 days ago
SITC titles

Abstract Number 264: Development of an Off-the-shelf, MICA/B-targeted CAR T cell to Overcome a Pan-tumor Escape Mechanism for Solid Tumors

Abstract Number 269: Preferential targeting of HER2-expressing cancer cells by FT825/ONO-8250, an off-the-shelf iPSC-derived CAR-T cell incorporating novel synthetic mechanisms for enhanced solid tumor activity

Abstract Number 308: A novel Avidity-enhancing Receptor (AvER) for superior CAR-dependent specificity and activity against tumor cells

Abstract Number 336: Alloimmune Defense Receptor with Genetic Ablation of Adhesion Ligand CD58 Promotes Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy
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jondoeuk jondoeuk 2 weeks ago
There is a collaboration with EdiGene to explore novel mechanisms and potential targets to be edited https://www.businesswire.com/news/home/20220209005463/en/EdiGene-and-Neukio-Enter-Collaboration-to-Develop-Next-Generation-Immune-Cell-Therapies
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jondoeuk jondoeuk 3 weeks ago
They initiated the first clinical trial (ITT) back in May. Also, are working on CAR-NKs for autoimmune diseases as well.
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jondoeuk jondoeuk 3 weeks ago
Preclinical data (could be licensed to the company) https://news.yale.edu/2024/06/25/boosting-natural-killer-cell-activity-could-improve-cancer-therapy
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Monksdream Monksdream 1 month ago
FATE under $4
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jondoeuk jondoeuk 2 months ago
While ICEs could help reduce antigen escape, TGFb signaling limits tumour immunosurveillance by converting NKs into (intermediate) type 1 innate lymphoid cells https://www.nature.com/articles/ni.3800

Engineering the NKs with a dnTGFb receptor not only protects the cells from TGFb induced dysfunction, but also locally reduces TGFb signaling to other cells within the tumour microenvironment. This could elicit more durable responses.
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jondoeuk jondoeuk 2 months ago
iPSC-derived NK cells expressing high-affinity IgG Fc receptor fusion CD64/16A to mediate flexible, multi-tumor antigen targeting for lymphoma https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1407567/full

Based on this and other (preclinical) data, I don't think it's unreasonable to assume that the next-gen iNKs FATE is working on will have this receptor. One question is are they able to further optimise the function of it with different transmembrane regions and signaling/co-signaling domain(s).
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jondoeuk jondoeuk 2 months ago
A thread Happy to share the final work from my post-doc with @MalmbergLab published in @CellStemCell today https://t.co/ZcC8Q32kts
extensive 15-post-🧡 below pic.twitter.com/jlTbeASoVJ— Quirin Hammer (@QuirinHammer) July 8, 2024
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jondoeuk jondoeuk 2 months ago
Q2 results https://www.nasdaq.com/press-release/fate-therapeutics-reports-second-quarter-2024-financial-results-and-business-updates
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Monksdream Monksdream 2 months ago
FATE under $6
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NY1972 NY1972 3 months ago
CART or CARNK need ICEs to engage endogenous NK and macrophages to combat MRD.
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jondoeuk jondoeuk 3 months ago
The study showed that blocking TGF-B signalling is necessary for the effective treatment of hepatocellular carcinoma (and likely other solid tumours that have high TGF-B levels) with iPSC-derived NK cells https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00217-0

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Monksdream Monksdream 3 months ago
FATE under $5
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harry crumb harry crumb 3 months ago
Will it short down to the 2.50 area again, time will tell
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jondoeuk jondoeuk 3 months ago
They will use the standard flu/cy as part of the conditioning regime, but also either cyclophosphamide or bendamustine. They have been testing the integration of the ADR tech in next-gen iPSC-derived CD8+ CAR T-cells, which could allow conditioning-free therapy. Adding additional edits could prevent rejection as well https://www.biorxiv.org/content/10.1101/2023.10.09.557143v1.full
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NY1972 NY1972 4 months ago
Make sense. 100% depletion of B cells probably not ideal outcome anyway.
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jondoeuk jondoeuk 4 months ago
In the second half, they expect to read-out initial PhI data for the first 3-5 patients treated with FT819 for moderate to severe SLE. They seek to administer FT819 without fludarabine and instead with commonly used treatment regimens for autoimmune diseases. They seek to demonstrate the potential of the proprietary ADR tech. Specifically, they expect to read-out 3-5 patients treated with FT522 in the PhI for B-cell lymphoma. They seek to broadly investigate FT522 without conditioning chemo for treatment of various B-cell autoimmune diseases. They seek to establish an initial clinical proof-of-concept with the first 3-5 patients treated with FT825 in the PhI for advanced solid tumours. Also, plan to disclose new target(s) and product configurations for at least two next-gen product candidates.
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jondoeuk jondoeuk 4 months ago
The CEO should follow (or be kicked) given his poor communication and disastrous performance https://ir.fatetherapeutics.com/node/13526/html
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jondoeuk jondoeuk 4 months ago
Shinobi Therapeutics and Anocca will co-develop allogeneic T-cell receptor engineered induced pluripotent stem cells (TCR-iPs-Ts) for solid tumors https://www.bioprocessintl.com/deal-making/shinobi-and-anocca-to-advance-cancer-killing-ips-t-cell-therapies
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jondoeuk jondoeuk 5 months ago
"T cell engagers did not appear to drive deep/durable remissions beyond treatment and as such would require chronic therapy,'' Dr. Schett*

*Cantor Fitzgerald research note April 29, 2024.
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jondoeuk jondoeuk 5 months ago
First Quarter Financial Results and Business Updates https://www.marketscreener.com/quote/stock/FATE-THERAPEUTICS-INC-14297698/news/Fate-Therapeutics-Reports-First-Quarter-2024-Financial-Results-and-Business-Updates-46682981/
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jondoeuk jondoeuk 5 months ago
First Lupus Patient Treated in Phase 1 Autoimmunity Study of Off-the-shelf FT819 CAR T-cell Program https://www.globenewswire.com/news-release/2024/05/09/2878757/24675/en/Fate-Therapeutics-Announces-First-Lupus-Patient-Treated-in-Phase-1-Autoimmunity-Study-of-Off-the-shelf-FT819-CAR-T-cell-Program.html
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jondoeuk jondoeuk 5 months ago
LBA https://www.globenewswire.com/fr/news-release/2024/05/03/2875365/24675/en/Fate-Therapeutics-Announces-Presentation-of-FT522-Preclinical-Data-for-Autoimmune-Diseases-in-Late-breaking-Abstract-at-ASGCT-Annual-Meeting.html
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jondoeuk jondoeuk 5 months ago
Novel a3-MICA/B-specific CAR T-cell immunotherapy demonstrates ubiquitous targeting of cancer cells and resistance to immune-surveillance evasion https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=59250

FT819-102: Clinical Translation of Off-the-Shelf TCR-Less CD8ab+ Anti-CD19 CAR-T Cells for the Treatment of B Cell-Mediated Autoimmune Disorders https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=60404
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jondoeuk jondoeuk 5 months ago
Depends if the companies are holding on to autoimmune diseases as their last straw. If so, it could be the end of them.
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NY1972 NY1972 5 months ago
What is CARNK bios going to do if T cell engagers eat the autoimmune pie?
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jondoeuk jondoeuk 5 months ago
A case report https://www.ejcancer.com/article/S0959-8049(24)00727-5/fulltext
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Monksdream Monksdream 5 months ago
FATE under $5
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harry crumb harry crumb 5 months ago
Entry at 3.50’s coming again
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jondoeuk jondoeuk 5 months ago
Found this https://www.nature.com/articles/s41591-024-02964-1

They used two cycles of low-dose blinatumomab in refractory rheumatoid arthritis (N=6). There was robust B-cell depletion with a 50% reduction in relevant auto-antibodies. Some minor fevers. However, most patients were then put on maintenance abatacept, so little insight into durability.
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harry crumb harry crumb 6 months ago
4 area is loading zone again, over an over my friends
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jondoeuk jondoeuk 6 months ago
(OT) Shinobi announced their $51M Series A funding https://www.prnewswire.com/news-releases/shinobi-therapeutics-launches-with-completion-of-51m-series-a-to-advance-hypoimmune-ips-t-cell-therapy-platform-302012188.html

Targeting tech https://www.cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(23)00148-1

Immune evasion tech https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00365-X
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jondoeuk jondoeuk 6 months ago
From last year https://finance.yahoo.com/news/cellorigin-announced-treatment-first-patient-170000142.html
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jondoeuk jondoeuk 6 months ago
DNA has acquired Modulus Therapeutics' cell therapy platform assets, including their CAR and switch receptor libraries https://www.prnewswire.com/news-releases/ginkgo-bioworks-acquires-modulus-therapeutics-cell-therapy-assets-to-strengthen-next-gen-car-designs-302105056.html
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jondoeuk jondoeuk 7 months ago
From this paper https://www.nature.com/articles/s41540-024-00355-3




Adoptive T-cell therapy also benefits from the combined activity of CD4+ and CD8+ T-cells, but FT819 is a CD8+ only T-cell therapy https://www.nature.com/articles/s41417-020-0183-x https://www.sciencedirect.com/science/article/pii/S0952791521001230 https://www.sciencedirect.com/science/article/pii/S0304419X2030158X https://www.science.org/doi/10.1126/science.1251102 https://www.nejm.org/doi/10.1056/NEJMoa0800251 https://www.science.org/doi/full/10.1126/sciadv.abe3348 https://www.science.org/doi/full/10.1126/sciadv.aba7443
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jondoeuk jondoeuk 7 months ago
1338 / 21 - Novel activation domains coupled to chimeric ILT receptors (CIR) enhance NK cell targeting of HLA-G+leukemic and solid tumor cells https://www.abstractsonline.com/pp8/#!/20272/presentation/6031
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jondoeuk jondoeuk 7 months ago
AACR abstracts

3618 / 24 - High-avidity BCMA CAR and high-affinity, non-cleavable CD16 Fc receptor incorporated in off-the-shelf CAR T cells promote multi-antigen targeting and durable anti-tumor cytotoxicity in the treatment of multiple myeloma https://www.abstractsonline.com/pp8/#!/20272/presentation/7153

3995 / 4 - A novel chimeric Fas signal redirect receptor enhances the durability of anti-tumor activity and serial killing potential of CAR T cells https://www.abstractsonline.com/pp8/#!/20272/presentation/6132

5240 / 15 - Novel CD3-Fusion Receptor enables combination of T-cell engagers and allogeneic CAR T cells to promote enhanced antitumor activity and overcome antigen escape https://www.abstractsonline.com/pp8/#!/20272/presentation/6056
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jondoeuk jondoeuk 7 months ago
Not many are in development. I know the PI of the trial in Germany said one of the chemo drugs used for lymphodepletion is (likely) playing a role as well.
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harry crumb harry crumb 7 months ago
Fate always makes money again $$$$
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NY1972 NY1972 7 months ago
No place to hide for many CARNK, CART bios

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1335998/full?utm_source=S-TWT&utm_medium=SNET&utm_campaign=ECO_FIMMU_XXXXXXXX_auto-dlvrit
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Monksdream Monksdream 8 months ago
FATE new 52 week high
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NY1972 NY1972 8 months ago
ACTs are turning into migrants armed with a pistol and name looking for a felon. They don't know the hoods and the local sheriffs. How long can they last in the hostile ground?
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jondoeuk jondoeuk 8 months ago
Far more are going under quietly and unnoticed https://www.fiercebiotech.com/biotech/catamaran-sends-out-life-raft-financing-challenges-claim-another-biotech
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jb128 jb128 8 months ago
Got back in a few months ago. Can we see another run to $120 like back in 2020-21 please??
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harry crumb harry crumb 8 months ago
Very nice run to 6 again
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jondoeuk jondoeuk 8 months ago
(OT) Artec Biotech is built upon methods for differentiating iPSCs into NK cells, as well as proprietary modifications. One example is the alteration of checkpoint receptors, such as PD-1 KO, which will be used for ART-002. The lead is ART-001, an unmodified NK product.

Although iPSC-NKs and PB-NKs of the same donor exhibited similar gene expression profiles, analysis revealed notable differences in genes that are important for NK cell function. Some of these genes were highlighted. Given the success of checkpoint inhibition in treating certain types of cancer, they evaluated checkpoint receptor expression in iPSC-NKs compared to PB-NKs. As demonstrated by a recent study, the expression of multiple checkpoint inhibitors was significantly higher in CD73+ cells, and the frequency of CD73+ cells correlated with larger tumour size in breast cancer patients https://www.jci.org/articles/view/128895

In their differentiation system, they produced NKs with down-regulated CD73 expression.

The next gene of interest was PTGER4, which encodes prostaglandin E2 receptor 4 (EP4). In NK cells, the binding of prostaglandin E2 to the receptor can initiate immunosuppression. In contrast, EP4 inhibition has been shown to enhance NK antitumour activity https://www.tandfonline.com/doi/full/10.1080/2162402X.2021.1896643

EP4 was down-regulated.

TIGIT was another gene of focus. Although not expressed in iPSC-NKs, it was highly expressed in PB-NK control. Overall, TIGIT is variably expressed in human NKs. Notably, NKs with lower TIGIT expression have exhibited higher cytokine secretion capability, degranulation activity, and cytotoxic potential https://onlinelibrary.wiley.com/doi/10.1002/eji.201545480

Furthermore, blocking TIGIT expression via monoclonal antibodies alleviated NK exhaustion https://www.nature.com/articles/s41590-018-0132-0

Similar to TIGIT, cytokine-inducible Src homology 2–containing protein (CIS), encoded by the CISH gene, is also involved in cytokine secretion. CIS is a member of the suppressor-of-cytokine signaling family of proteins. CISH deletion in either iPSC-NKs or PB-NKs increases their sensitivity to IL-15 and enhances JAK/STAT and mTORC1 signaling. This leads to increased NK metabolic fitness that contributes to an improved antitumour response https://ashpublications.org/blood/article/137/5/624/463715/Targeting-a-cytokine-checkpoint-enhances-the

Their iPSC-NKs have significantly down-regulated CISH expression compared to PB-NKs.

Aside from direct mechanisms that tumours employ to down-regulate NK function, the tumour microenvironment also impairs NK function by negatively affecting NK metabolism https://www.frontiersin.org/articles/10.3389/fimmu.2019.02278/full

Enhancing NK metabolic functionality is currently being pursued as one of the avenues for increasing NK cell activity against tumours https://www.pnas.org/doi/10.1073/pnas.2107507118

Considering this, they further evaluated the metabolic profile of iPSC-NKs and PB-NKs. The assessment focused on significantly expressed genes, which impact NK metabolic function. The following genes showed up-regulation in iPSC-NKs: Slc2a1 (involved in glucose transport), Slc7a5 (an amino acid transporter), Slc3a2/CD98 (an amino acid transporter), and TFRC/CD71 (involved in receptor-mediated iron uptake). These data yield insight into the efficacy of iPSC-NKs because nutrient transport is essential and increased expression of nutrient transporters promotes an increased metabolic rate, as well as elevated NK activity https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02377-8
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