Nkarta Inc (NKTX)

[jondoeuk]

(OT) ONK Therapeutics

The company has a three-candidate pipeline led by a dual-targeted NK cell therapy that has a CD19 CAR and membrane-bound TNF-related apoptosis inducing ligand variant. This targets the death receptor 5 pathway [1]. Previously the death receptor 4 pathway, and both were going to be targeted for certain types.

The second candidate is an anti-CD38 CAR and will be given with a systemic anti-IL-6(R) mAb [2].

The third targets MUC-1 and there may be knock-out of genes encoding PD-1 [3], TIGIT [4], CD96 [5] and/or Siglec-7 [6]. Doing the same with a few others, such as CBL-B [7], IL-1R8 [8], and these [9] would help improve efficacy.

All allo (healthy donor) products will use a CD28 co-stim and soluble IL-15 (similar to this [10,11]). Also, they plan to increase trafficking to sites of disease [12-14].

However, cancer cells can develop resistance to the death receptor pathway(s) being targeted [15]. But there could be ways to overcome that [16].

Refs:
1 https://journals.lww.com/immunotherapy-journal/Abstract/2013/06000/Membrane_bound_TRAIL_Supplements_Natural_Killer.4.aspx
2 https://www.frontiersin.org/articles/10.3389/fendo.2018.00788/full
3 https://www.jacionline.org/article/S0091-6749(16)30360-8/fulltext
4 https://www.nature.com/articles/s41590-018-0132-0
5 https://www.nature.com/articles/nri3799
6 https://onlinelibrary.wiley.com/doi/full/10.1111/sji.12455
7 https://www.nature.com/articles/nature12998
8 https://www.nature.com/articles/nature24293
9 https://cancerres.aacrjournals.org/content/80/16_Supplement/891
10 https://www.nature.com/articles/leu2017226
11 https://www.nejm.org/doi/full/10.1056/NEJMoa1910607
12 https://ashpublications.org/blood/article/132/Supplement%201/4547/275557/Providing-a-Homing-Receptor-for-CAR-Engineered-NK
13 https://link.springer.com/article/10.1007%2Fs00262-014-1629-5
14 https://link.springer.com/protocol/10.1007%2F978-1-4939-3684-7_19
15 https://www.nature.com/articles/onc2012164
16 https://ashpublications.org/blood/article/135/9/597/429647/Integrated-drug-profiling-and-CRISPR-screening