Fate Therapeutics Inc (FATE) Quote

FATE under $4

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.

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).

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

Q2 results https://www.nasdaq.com/press-release/fate-therapeutics-reports-second-quarter-2024-financial-results-and-business-updates

FATE under $6

CART or CARNK need ICEs to engage endogenous NK and macrophages to combat MRD.

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

FATE under $5

Will it short down to the 2.50 area again, time will tell

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

Make sense. 100% depletion of B cells probably not ideal outcome anyway.

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.

The CEO should follow (or be kicked) given his poor communication and disastrous performance https://ir.fatetherapeutics.com/node/13526/html

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

"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.

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/

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

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

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

Depends if the companies are holding on to autoimmune diseases as their last straw. If so, it could be the end of them.

What is CARNK bios going to do if T cell engagers eat the autoimmune pie?

A case report https://www.ejcancer.com/article/S0959-8049(24)00727-5/fulltext

FATE under $5

Entry at 3.50’s coming again

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.

4 area is loading zone again, over an over my friends

(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

From last year https://finance.yahoo.com/news/cellorigin-announced-treatment-first-patient-170000142.html

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

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

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

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

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.

Fate always makes money again $$$$

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

FATE new 52 week high

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?

Far more are going under quietly and unnoticed https://www.fiercebiotech.com/biotech/catamaran-sends-out-life-raft-financing-challenges-claim-another-biotech

Got back in a few months ago. Can we see another run to $120 like back in 2020-21 please??

Very nice run to 6 again

(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

From last year (presented at SITC) https://jitc.bmj.com/content/11/Suppl_2/A1763

(OT) oNKo-innate is a discovery-stage biotech company dedicated to target identification and preclinical IO (drug) development.

In this, the functional genomics and target discovery team have used their platform to perform enrichment screens in primary human NK cells, identifying novel IL-15 axis regulators that contribute to survival and persistence. Phenotypic screens similarly revealed regulators of NK cell cytotoxicity and interferon gamma production. By validating these targets, the team has demonstrated that they are able to regulate various aspects of NK and CAR-NK cell function.

FT825/ONO-8250 update https://finance.yahoo.com/news/fate-therapeutics-announces-initiation-phase-130000499.html

Took my chips off the table and cashed out. $fate has worked in my favor I beat the street. In sub $2 out @ $4.50.

Thank you to the posters here I enjoyed the scientific discourse even if it was way over my head

Looks like the inducement grant was for Dr. Cooley's replacement. Given the company's history, I was hoping that there would be a new CEO.

Took my profits, playing with house money riding freebies.

Using CRISPR screening of metabolic genes, they found that KEAP1 played an important role in the pro-inflammatory activity of macrophages through inhibiting the production of itaconate. As ACOD1 is the sole enzyme to generate itaconate, ACOD1 knockout promoted pro-inflammatory activity of macrophages and enhanced the function of CAR-Ms derived from iPSCs https://www.nature.com/articles/s41467-023-41470-9

Preprint https://www.biorxiv.org/content/10.1101/2023.12.10.570687v1