Nkarta Inc (NKTX)

[jondoeuk]

Updated

[NY1972]

With all the edits, CAR NK is more like ADC, not NK cells that have also been described as ‘immune-regulatory’ because of their ability to produce an array of cytokines and chemokines, through which they help shape B cell and T cell responses, and impact the function of DC, macrophages and neutrophils

[jondoeuk]

More from

$NKTX hopes to avoid the fate of $FATE, via @evaluatevantage -> https://t.co/1SOK7gOAbS

— Jacob Plieth (@JacobPlieth) June 27, 2023

[jondoeuk]

PR https://finance.yahoo.com/news/nkarta-updates-clinical-progress-car-110100481.html

Slides https://ir.nkartatx.com/static-files/681c0391-4a87-453b-91a5-2af3e6d3f477

[jondoeuk]

The update will be today at 8:00 a.m. ET https://nkx101-clinical-update-conference-call.open-exchange.net/registration

[jondoeuk]

PR https://www.globenewswire.com/news-release/2023/04/17/2648511/0/en/Nkarta-Presents-Preclinical-Data-Exploring-Gene-Knockout-Strategies-and-Combination-Agents-with-NK-Cell-Based-Therapies-at-the-2023-AACR-Annual-Meeting.html

Posters https://www.nkartatx.com/file.cfm/75/docs/nkarta_aacr2023_poster%20890_adam17%20ko%20of%20nk%20cells.pdf https://www.nkartatx.com/file.cfm/75/docs/nkarta_aacr2023_poster%203183_nkx101%20and%20cetuximab%20combo.pdf

[jondoeuk]

Yes, it could have been primary resistance due to low MICA/B (or other NKG2DLs) expression, but without any translational data from the company there is no way of knowing.

[NY1972]

Disfunctional NKs have a few more mutations than dysfunctional NKs.

[NY1972]

My point was MDS patients has disfunctional NK cells which cause the cancer to slow down on MICA expression. With lowered MICA expression, NKTX cells don't work. I doubt MDS TME is more suppressive than AML.

[jondoeuk]

In patient's there is immune cell dysfunction, but using off-the-shelf should be able to overcome some of that. As for primary, adaptive and/or acquired resistance, only translational data will be able to give insights as to what strategies could combat that.

[jondoeuk]

Yes, just a shame about the target.

[NY1972]

It will be interesting to see how this DT HER2 x NKG2D x CD16A engager works since it won't be impacted by the # of ligands on cancer cells.

[NY1972]

Cancer is adapting. Why bother expressing ligands if the NK cells are not working anyway.

NKG2D surface down-modulation in freshly isolated NK cells from MDS patients may be a clinically useful “biomarker” of suppressed NK function.

[jondoeuk]

Without any translational data it is hard to say why. I know in one paper the authors reported that just 30% of MDS blasts expressed the NKG2D ligands MICA/B https://ashpublications.org/blood/article/109/11/4816/23111/Reduced-natural-killer-NK-function-associated-with

That was confirmed by another group, showing a low expression of NKG2D ligands https://www.nature.com/articles/leu2010149

There are plenty of other mechanisms, including Tregs, either via cell-to-cell interactions of soluble factors, such as TGF-B https://rupress.org/jem/article-lookup/doi/10.1084/jem.20051511

[NY1972]

This one is puzzling. Four patients with MDS were treated, with no response observed.

[jondoeuk]

The update is expected to include longer-term follow up from patients who were in response as of the previous April '22 data cut-off; clinical data from at least ten new R/R AML patients treated at 1.5B (x3); clinical data from patients who received one or more additional three-dose cycles; and clinical data from a new cohort of patients who received lymphodepletion with cytarabine and fludarabine.

[jondoeuk]

Speaking of expansion. From this: ''We apply a human B-lymphoblastoid cell-line 721.221 (hereinafter, 221)-based artificial feeder cell system with membrane-bound interleukin 21 (mIL 21) to propagate NK and CAR-NK cells. The expansion capability, purity, and cytotoxicity of NK cells expanded with 221-mIL-21 feeder cells are superior to that of conventional K562-mIL-21 feeder cells. RNA sequencing (RNA-seq) data show that 221-mIL-21 feeder cell-expanded NK cells display a less differentiated, non-exhausted, limited fratricidal, memory-like phenotype correlated with enriched metabolic pathways, which explains underlying mechanisms.'' https://www.cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(20)30138-8

Also, additional ways that could improve it https://ashpublications.org/blood/article/118/21/4035/68863/Nicotinamide-a-Form-of-Vitamin-B3-Promotes https://aacrjournals.org/cancerres/article/77/20/5664/623001/GSK3-Inhibition-Drives-Maturation-of-NK-Cells-and https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00130-3

[jondoeuk]

Some more info. Pre-activation is IL-12/15/18 and expansion with uAPCs (engineered K562 feeder cells expressing mbIL-21 and 4-1BBL) plus IL-2, transduction with a retroviral vector, before another round of expansion. From two cord blood units, 250 doses have been manufactured with a (CAR) transduction efficiency of 60%. Six dose levels will be tested, with DL1 completed. Also, over 90 cryopreservation protocols were tested, with MDACC outperforming standard frozen.

[jondoeuk]

Turns out the trial in solid tumours (ccRCC, mesothelioma, or osteosarcoma) is open. However, there are a number of differences, including design of the CAR (which has constitutive IL-15), ex vivo expansion, and they are using CB-derived NKs.

[jondoeuk]

(OT) Dr. Rezvani presented some early, but impressive data showing activity with an CD70-targeted CAR-NK cell therapy in a patient with R/R cHL, from a basket trial for R/R haematological malignancies. A trial in solid tumours should be starting soon.

[jondoeuk]

Updated results from the ongoing trial of NKX101 should be presented this quarter.

[jondoeuk]

ADAM17 knockout NK or CAR NK cells augment antibody dependent cellular cytotoxicity (ADCC) and anti-tumor activity https://www.abstractsonline.com/pp8/#!/10828/presentation/3022

Combination of anti-EGFR antibody cetuximab with NKX101, an allogeneic NKG2D-L targeting NK cell therapy, enhances potency and in vitro cytotoxicity against solid tumors https://www.abstractsonline.com/pp8/#!/10828/presentation/3049

[jondoeuk]

Watching from the sidelines, but the NKX101 delayed data readout is a worry.

[jondoeuk]

NKX019 update https://www.globenewswire.com/news-release/2022/12/05/2567250/0/en/Nkarta-Announces-Updated-Clinical-Data-on-Anti-CD19-Allogeneic-CAR-NK-Cell-Therapy-NKX019-for-Patients-with-Relapsed-or-Refractory-Non-Hodgkin-Lymphoma.html

Slides https://ir.nkartatx.com/static-files/9cb11d46-a4aa-49a3-baca-dc1a36e5aa60

Webcast https://nkarta-nkx019-clinical-update-conference-call.open-exchange.net/registration

[jondoeuk]

Posters

https://www.nkartatx.com/file.cfm/75/docs/nkarta_sitc_2022_poster_381_nk_cell_expansion.pdf

https://www.nkartatx.com/file.cfm/75/docs/nkarta_sitc_2022_poster_902_nkx019_cd20_mab_combo.pdf

[jondoeuk]

SITC titles

Large-scale expansion and engineering of human NK cells sourced from peripheral blood versus umbilical cord blood

NKX019, an Off-the-Shelf CD19 CAR-NK Cell, mediates improved anti-tumor activity and persistence in combination with CD20-directed therapeutic mAbs

[jondoeuk]

Additional NKX101 and NKX019 clinical data expected by year-end. The data is expected to include safety and activity data for newly enrolled patients at higher dose monotherapy regimen and extended durability follow-up for previously reported patient responses. Also, in June, the company filed a protocol amendment with the FDA for 019 to optimise the trial's design as they prepare for potential dose expansion cohorts. The amended protocol, now in effect, allows for an increased dose of cyclophosphamide with lymphodepletion, in line with 101, and various expansion cohorts evaluating it in combination with rituximab.

[jondoeuk]

Cowen 3rd Annual Oncology Innovation Summit webcast https://wsw.com/webcast/cowen115/nktx/2047935

[crudeoil24]

Time for some momo/fomo to kick in. Let's go NKTX!

[crudeoil24]

Offering is now closed Company raised over $200M within a few sessions. Let's see if tutes accumulate NKTX shares today. Possibly 20.00+ today!

[stock1ace1]

20$

[crudeoil24]

NKTX is a great $$$$$ opportunity.

[crudeoil24]

Not a p&d. Some folks need to learn how to read a corporate balance sheet / and SEC filings.

[crudeoil24]

18.93 > > Looks like NKTX shelf placement is completed. Looks like another $200M in the kitty.

[Saving Grace]

Front Loaded Pump and Dump, They are trying to promote this to death before the Med Beds that cure anything and everything come out.

Japan is already using the Med Beds with indisputable results

Caveat Emptor! with this horseshit scam.

[JamBop]

That would be if the number 15 was the actual value. But why offer an actual value to someone as a valuable transaction?
Makes more sense that 15 is a discount.

[Gator44]

Shouldn't this open at $15 when the market opens for trading ?

[rynlrt]

Price target is 109. Wouldnt consider 18 high

[TheFinalCD]

thats assuming a high price of 18

Message in reply to:
That's only about 10M shares if @ 18.00 price NKTX could absorb that in one session. Could close shelf placement this week + have plenty of cash for their operations & expenses.

[crudeoil24]

That's only about 10M shares if @ 18.00 price NKTX could absorb that in one session. Could close shelf placement this week + have plenty of cash for their operations & expenses.

[crudeoil24]

Turn your monitor upside down! lol

[TheFinalCD]

UP ON OFFERING NEWS

HAVE SEEN IT ALL NOW!!!

[crudeoil24]

I see > NKTX @ 19.84 now. Probably most traders are clueless. Maybe the upcoming big volume days will absorb the $150M shelf placement by April 30.

[TheFinalCD]

$NKTX Nkarta Announces Proposed Public Offering of Common Stock

$150M

[crudeoil24]

Thank you ! I wish Elon Musk buy 50 million shares! lol

NKTX

[TheFinalCD]

18.94 CONGRAT$

[crudeoil24]

PT > 109.00 > Mizuho Maintain Buys On Nkarta, Raises Price Target To $109

[crudeoil24]

NKTX > PHI SLAMMA JAMA!

[crudeoil24]

NKTX > 17.94

[jondoeuk]

Another group plans to test an anti-CD70 CAR-NK (with IL-15) in GBM. Knockout of NR3C1 (steroid receptor pathway) allows for the concurrent use of steroids without negating activity of the therapy