Fate Therapeutics Inc (FATE) Options

Better than allo, Hipsc

FATE has found all the pieces needed for alloT/NK when investors have abandoned it for dead,

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.

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.

Do you think FT836 is ready for IND in 2024?

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

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

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

They initiated the first clinical trial (ITT) back in May. Also, are working on CAR-NKs for autoimmune diseases as well.

Preclinical data (could be licensed to the company) https://news.yale.edu/2024/06/25/boosting-natural-killer-cell-activity-could-improve-cancer-therapy

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??