Fate Therapeutics Inc (FATE) Options

AUTL just presented preliminary data from an initial six patient cohort treated in a PhI trial in systemic lupus erythematosus, which supports them progressing obe-cel into a planned PhII pivotal trial (N=30) in severe refractory lupus nephritis. The first patient is expected to be dosed by the end of the year. The primary endpoint will be complete renal response at 6 months. The key secondary endpoint will be DORIS at 6 months.

They have a development path in MS as well.

NKX019 has shown in responses in patients with R/R NHLs despite (widespread) malignant B-cell in the blood, bone marrow, lymph nodes, secondary lymphoid tissue, and/or extra-nodal sites.

NEUK200-13 (an anti-DLL3 CAR-NK) is already in the clinic. It is being advanced SCLC.

The first patients received the planned four doses (once a week) at DL1. During the DLT observation period, there were no DLTs, no SAEs occurred, and the AEs were all grade 1 and 2. Now they are planning to test DL2. If the maximum tolerated dose is still not reached, the dosing regimen can be adjusted to once every three days according to the safety/tolerability data.

FATE, under $2

True. CARNK issue with AID will be chemotaxis primarily. Like the auto/allo CART, they infiltrate inflammed tissues, not BM. Persistence secondary.

Apples to pears, but I think NKX019 needs to show better efficacy than KN5501. I know the former has a more optimised CAR (for NKs), IL-15 and is being given more proximal to LD. The PK data for NKX019 in NHL showed extended overall exposure and sequentially increased Cmax levels with the dosing they are using for AIDs.

Yes, but a (near-term) lifeline (£££) has been cut forcing them to review strategic alternatives. From this: ''With the focus on future EBVALLO value paramount, the Company has made the difficult decision to pause development of its allogeneic CAR-T cell programs and to discontinue all CAR-T operations including terminating the clinical trials evaluating ATA3219. The Company’s strategic review is ongoing.'' https://www.businesswire.com/news/home/20250307401908/en/Atara-Biotherapeutics-Announces-Fourth-Quarter-and-Full-Year-2024-Financial-Results-and-Operational-Progress

Did you check out ATRA posters? They were planning on mono CART with 1XX also. No LD based on comparable cytokine expressions of EBVALLO

Just nabbed FDA RMAT Designation as well https://www.globenewswire.com/news-release/2025/04/14/3060843/0/en/Fate-Therapeutics-Receives-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-from-FDA-for-FT819-to-Treat-Moderate-to-Severe-Systemic-Lupus-Erythematosus-SLE.html

Depends on the data. I think we could see oral presentations at either ACR Convergence and/or ASH. I think there were some presented at the former last year.

As for dosing regimens, a number have already been tested in hematological malignancies, so that (as well as preclinical data) will give them guidance.

$FATE has is setting a new bar for AUTO, ALLO, CARNK

MONO 819

Experimental: Regimen B1 (Single-dose without AMP, background therapy temporarily suspended)

Combining CARTs targeting uPAR and HER2 + cetuximab. Interesting

Problem with CARNK, AUTO and ALLO is reduced FLU dose has shown subpar result in clearing long lived B cells in BM. NKTX is not looking for DORIS remission as goal. They are skipping FLU because rheumatologists don't want it. They know ALLO will be the better option if CARNK requires the same preconditioning.

CRSP's CEO is pretty bullish. He said top-line data will be at a company event and additional data will be shared at a conference later in the year. Also that they may explore different LD.

NKTX is not using Flu.

They are working on both next-gen iTs and iNKs that target senescent cells. In the context of pancreatic cancer, uPAR is strongly implicated in progression and OS https://www.mdpi.com/2218-273X/12/2/152

A quick search brings back these (uPAR is (broadly) expressed on a number of different types) https://www.biospace.com/press-releases/monopar-initiates-clinical-trial-of-novel-upar-targeted-radiopharmaceutical-therapy-in-advanced-cancers https://www.prnewswire.com/news-releases/adcendo-announces-us-fda-clearance-of-ind-application-for-phase-iii-first-in-human-adcelerate-01-trial-of-adce-d01-uparap-receptor-targeting-adc-trial-in-patients-with-metastatic-andor-unresectable-soft-tissue-sarcoma-sts-302268929.html

As for fibrotic disease https://www.mdpi.com/1422-0067/24/2/1796

In pancreatic cancer, uPAR (urokinase-type plasminogen activator receptor) is a protein that promotes tumor growth and spread. It's often overexpressed in pancreatic cancer compared to healthy tissue. Targeting uPAR with drugs, like antibody-drug conjugates (ADCs), can suppress tumor growth and reshape the immune system in pancreatic cancer models.

I did not find any EULAR oral on T cell engagers. Wonder why? How they decide when to stop the treatment or just cycles like treating cancer?

A non-proliferative CART has low cytokine need, no LD req'd and acts like CARNK
1/ Cartesian’s CAR-T for MG: Strong Signals…BUT nobody cares, Why?$RNAC just shared 12-month Phase 2b data for Descartes-08 in myasthenia gravis.

Durable responses.
No lymphodepletion.
Outpatient.
So…why doesn’t Wall Street care?

Let’s dig in. pic.twitter.com/lIQEL1xzDL— BowTiedBiotech 🧪🔬🧬 (@BowTiedBiotech) April 8, 2025

The Mkt can't tell CARNK from CART. Many PhDs on X think TCE will take the AID pie. Few left buying FATE are traders. I prefer LD because it creates a vacuum and deepened chemotaxis gradient for CXCR2+ CART to migrate to TME. We will see what 825+ cetuximab can do.

Upcoming at ASGCT

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.

Targeting UPAR With Multiplexed-Engineered iPSC-Derived CAR T Cells to Reverse Age- and Insult-Related Fibrotic Disease.

FT836, a Novel MICA/B-targeting CAR T-cell Therapy Engineered to Eliminate the Need for Conditioning Chemotherapy with Broad Activity Across Solid Tumor Indications.

Next-Generation Off-the-Shelf CAR T-Cell Therapies for Conditioning-Free Treatment of a Broad Spectrum of Autoimmune Diseases and Hematologic Malignancies.

Phase 1 Translational Assessment of an Off-The-Shelf CAR NK Cell Armed with Alloimmune Defense Technology for Conditioning-free Therapy.

Oral is good.

Let's hope the market sees it that way.

Poster probably on 522.. I think 819 can do without LD anyway.

CAR-iT's. FT829 is ahead and they plan to finalise the product configuration, and complete IND-enabling activities this year.

CRSP and NKTX may as well halt the trials and see what 819 is capable of doing without FLU and without LD in stable SLE. The big issue for CARNK and allo CART is whether they work without depleting the existing activated T cells.

Where is CARNK

Either an LBA or at least a few should present data sometime in 2H.

and CTX112?

Updates (in oncology and autoimmune diseases) are expected mid-year.

Immunocleansing-Associated Toxicity Syndrome (ICATS) in CAR T-cell treated patients with autoimmune disease

Altered gut microbiota composition in autoimmune disease patients undergoing CD19-CAR T-cell therapy

825 seems to be progressing too. NIH has none to update the web site to show the latest changes, The combo is intriguing, FIC.

NK cells don't work well under chronic inflammation or suppression. Look at the results from AFMD NK engagers trials, only one that worked is CD30 combined with CBNK and LD. I listened to NKTX Leerink presentation, the reason they are skipping FLU is because the Rheumatologists don't want it. Their end game is renal function improvement not Doris remission.

We will see as NKTX plans to present data from the Ntrust-1 (lupus nephritis) and Ntrust-2 (systemic sclerosis, idiopathic inflammatory myopathy and ANCA-associated vasculitis) trials in the second half of the year.

Two other ISTs are listed as well. Dosing of the first patient for the treatment of systemic lupus erythematosus led by researchers at the Columbia University Irving Medical Center was reported in Nov 2024. Clearance of the IND for the second for the treatment of myasthenia gravis led by researchers at the University of California, Irvine and the University of Kansas Medical Center was reported in Dec 2024.

The dosing schedule was harmonised across all four. Patients receive NKX019 (anti-CD19 CAR-NK) on Days 0, 3 and 7 following single-agent lymphodepletion with cyclophosphamide.

Interesting they pick 819 for CART and beyond session. Where is CARNK and CTX112?
To understand the potential of allogeneic CAR cell therapy in rheumatology;

Thanks. Oral is good. Dr. Vaneet Sandhu gave a talk 4 months ago.


Poster probably on 522.. I think 819 can do without LD anyway. SLE pts have problem with 'SELF'

I found two

Treatment of Refractory Systemic Lupus Erythematosus with Off-the-Shelf iPSC-derived Anti-CD19 CAR T-cell Therapy https://apps-congress.eular.org/eular25/en-GB/pag/presentation/20190

Next-Generation Off-the-Shelf CAR T Cells: A Novel Platform to Enable Comprehensive Elimination of Aberrant Effector Cells for the Treatment of Autoimmune Diseases in the Absence of Conditioning Chemotherapy https://apps-congress.eular.org/eular25/en-GB/pag/presentation/20837

The problem with NK is it needs FLU to ablate the B cells in BM to get 50% DORIS remission. Not some super safe if LD is req'd for stable SLE. 90% Doris for FT819 without Flu. Which is the winner is obvious.

In haematological malignancies, they are at the final dose level (flat dose of 4 billion).




Also, have been working on a single (CISH KO) and dual (CISH/TGFBR2 KO) edited version.

Both non-CRISPR edited (CD70- and TROP2-targeting) CAR-NKs are in the clinic. The former is being tested in at least two separate PhI/II trials (advanced RCC, mesothelioma and osteosarcoma, or R/R haematological malignancies), while the latter in a single PhI/II (delivered intraperitoneally for platinum resistant ovarian, mesonephric-like adenocarcinoma, and pancreatic cancers).

I don't think CARNK will work in SLE.

From one company in China (non-optimised CAR and no additional modifications) https://www.healio.com/news/rheumatology/20241212/carnk-cell-approach-achieves-efficacy-persistence-and-super-safety-in-lupus

CART has a mix of Tcm, Teff cells with different CXCR2/cxcr4 expressions for migration to lymphoid organs and inflammed tissue. 819 is high on cxcr4 compared to AUTO CART, great for depleting B cells in BM. That also explains why FLU is not need for preconditioning.

I think (the current) CAR-T's will show better efficacy over CAR-NK's.

I don't think CARNK will work in SLE. CART has a mix of Tcm, Teff cells with different CXCR2/cxcr4 expressions for migration to lymphoid organs and inflammed tissue. 819 is high on cxcr4 compared to AUTO CART, great for depleting B cells in BM. That also explains why FLU is not need for preconditioning.

A regulatory checkpoint (of CAR and IL-15 signaling): ''Further experiments demonstrated that IL-15 induced CREM in a dose-dependent manner, with CREM expression abolished upon IL-15 blockade. The combination of CAR signaling and IL-15 stimulation synergistically enhanced CREM expression, highlighting the interplay between these pathways.

Notably, CRISPR/Cas9-mediated knockout (KO) of CREM in CAR NK cells significantly enhanced their cytotoxicity, cytokine production, resistance to tumor-induced immunosuppression across hematologic and solid tumor models, including CD70- and TROP2-targeting CAR NK cells. In vivo, CREM KO improved NK cell proliferation, persistence, tumor infiltration, tumor control, and survival of mice in multiple aggressive solid and hematologic tumor models including metastatic breast cancer, orthotopic pancreatic cancer, and Raji Burkitt lymphoma.'' https://www.abstractsonline.com/pp8/#!/20273/presentation/7612

Compared to CAR-NKs, CAR(PDZ)-NKs showed improved efficacy. CAR(PDZ)-Ts also demonstrated improved efficacy relative to CAR-Ts

From another group https://www.abstractsonline.com/pp8/#!/20273/presentation/1853

''Key pathways enriched among the hits included components of the Cul5-RING ubiquitin ligase, the Mediator and the SAGA complexes, as well as genes involved in chromatin remodeling and negative regulation of NF?B. These findings highlight transcriptional reprogramming and post-
translational modification (PTM) components as means to optimize NK cell effector functions for enhanced anticancer immunity.

Targeted ablation of top hits MED12, ARIH2 and CCNC markedly improved the antitumor potency of both non-transduced and CAR/IL-15-engineered NK cells against multiple hard-to-treat cancers using two different IL-15-armored CAR receptors targeting CD70 and TROP2. ARIH2 and CCNC deficient TROP2/IL-15-CAR-NK cells displayed enhanced metabolic fitness and a marked increase in activated/cytotoxic clusters (DNAM-1high, Granzyme Bhigh, Perforinhigh, CD69high), with a concomitant decrease in inhibitory subsets (NKG2Ahigh, Granzyme Blow, CD69low), as shown by mass cytometry.

Multiplexed ARIH2/CCNC editing of TROP2/IL-15-CAR-NK cells significantly increased NK cell expansion, tumor bed infiltration, release of cytotoxic granules and antitumor efficacy in an orthotopic in vivo mouse model of pancreatic cancer. This was accompanied by the induction of cytotoxic (CD16high, Granzyme Bhigh, Perforinhigh) and activated (DNAM-1high, CD69high, NKG2Dhigh) NK cell subsets.

In conclusion, by applying high-content genome-wide CRISPR screening in primary human NK cells, this study revealed novel regulators of NK cell function, including MED12, ARIH2 and CCNC. Targeting these regulators enhances CAR-NK cell metabolic fitness, cytotoxicity and in vivo antitumor efficacy, offering new opportunities for optimizing CAR-NK therapies.''

Hard to say. Without the sword/shield tech some conditioning may be needed to either create space and/or create (greater) access to certain cytokines, as well as delay rejection.

This is Regimen B (no LD chemo) in patients with R/R BCLs. At the first dose level (300 million cells per dose), live cells were detected in the patients' peripheral blood (N=3) through Day 15 (one week post-infusion of the third dose), demonstrating the ability of FT522 to persist in the presence of an unmatched, fully-intact immune system.

FT819 express high CXCR4 and target BM, SLE has low Treg. I think it can do without LD with multi 360M doses

AUTO has CAR and TCR to boost activity on malignant cells. In SLE, that TCR can cause ICANS so hospital stay probably will be req'd. FT819 don't have TCR to deal and no T cell clones to worry about. Seems to be a perfect choice for SLE pts.

I will, but I don't see auto CAR-T's being feasible for the largest and most lucrative parts of the market.

CABA CEO talk at Cowen is worth a listen. ICANS caused by T cell clones, AUTO efficacy, logistics bottleneck .........

Studies suggest that 5-20% of DLBCL cases may have CD19-negative malignant cells at baseline, and CD19 loss can increase due to treatment pressure. That explains why auto CART had higher ORR and PFS. AUTO is TIL with 50% CD19 CAR and 50% without. I think 819 360 M will be good without CY since Treg is lacking in SLE patients who have no malignant cells.

SLE and CART
https://pmc.ncbi.nlm.nih.gov/articles/PMC11694027/#B181

CEO said they have submitted a series of abstracts to EULAR.

I meant 825

819 is turning into mAb conjugated to a mutated T cells. ATC. Muti dose, muti cycles is big deal.

819 did demonstrate durable B-cell depletion for at least one month post treatment (in the presence of flu-free conditioning). They will escalate to DL2 (at 720M cells) as well.