Delving into the Latest Updates on oNKo-innate Pty Ltd. with Synapse

Overview

Tags

Neoplasms

Fusion protein

CAR-NK

CRISPR/Cas9

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	6

Top 5 Drug Type	Count

Fusion protein	2
CAR-NK	2
Small molecule drug	1
CRISPR/Cas9	1

Top 5 Target	Count

IL-12(Interleukin-12)	2
IL-15(Interleukin-15)	1

Histone methyltransferases (HMTs) are crucial in gene regulation and function, yet their role in natural killer (NK) cell biology within the tumor microenvironment (TME) remains largely unknown. We demonstrate that the HMT DOT1L limits NK cell conversion to CD49a+ CD49b+ intILC1, a subset that can be observed in the TME in response to stimulation with transforming growth factor (TGF)-β and is correlated with impaired tumor control. Deleting Dot1l in NKp46-expressing cells reveals its pivotal role in maintaining NK cell phenotype and function. Loss of DOT1L skews NK cells toward intILC1s even in the absence of TGF-β. Transcriptionally, DOT1L-null NK cells closely resemble intILC1s and ILC1s, correlating with altered NK cell responses and impaired solid tumor control. These findings deepen our understanding of NK cell biology and could inform approaches to prevent NK cell conversion to intILC1s in adoptive NK cell therapies for cancer.

01 Feb 2024·Nature Immunology

IKAROS and AIOLOS directly regulate AP-1 transcriptional complexes and are essential for NK cell development

Article

Author: Scheer, Sebastian ; Shen, Zihan ; Kallies, Axel ; Rautela, Jai ; Nutt, Stephen L ; Andoniou, Christopher E ; Cursons, Joe ; Davis, Melissa J ; Kong, Isabella Y ; Parish, Ian A ; Schuster, Iona S ; Degli-Esposti, Mariapia A ; Hennessey, Robert ; Thiele, Daniel ; Sudholz, Harrison ; Huntington, Nicholas D ; Chopin, Michael ; Pfefferle, Aline ; Beavis, Paul ; Hediyeh-Zadeh, Soroor ; Souza-Fonseca-Guimaraes, Fernando ; Meng, Xiangpeng ; Foroutan, Momeneh ; Goh, Wilford ; Delconte, Rebecca B

Ikaros transcription factors are essential for adaptive lymphocyte function, yet their role in innate lymphopoiesis is unknown. Using conditional genetic inactivation, we show that Ikzf1/Ikaros is essential for normal natural killer (NK) cell lymphopoiesis and IKZF1 directly represses Cish, a negative regulator of interleukin-15 receptor resulting in impaired interleukin-15 receptor signaling. Both Bcl2l11 and BIM levels, and intrinsic apoptosis were increased in Ikzf1-null NK cells, which in part accounts for NK lymphopenia as both were restored to normal levels when Ikzf1 and Bcl2l11 were co-deleted. Ikzf1-null NK cells presented extensive transcriptional alterations with reduced AP-1 transcriptional complex expression and increased expression of Ikzf2/Helios and Ikzf3/Aiolos. IKZF1 and IKZF3 directly bound AP-1 family members and deletion of both Ikzf1 and Ikzf3 in NK cells resulted in further reductions in Jun/Fos expression and complete loss of peripheral NK cells. Collectively, we show that Ikaros family members are important regulators of apoptosis, cytokine responsiveness and AP-1 transcriptional activity.

01 Jan 2024·Immunology & Cell Biology

Small molecule. Big biology. Dual phosphatase inhibitor enters the immunotherapy fray

Article

Author: Huntington, Nicholas D ; Wilson, Nicholas S

AbstractThe advent and clinical success of immune checkpoint inhibitors Ipilimumab, Nivolumab and Pembrolizumab has had a seismic impact on our drug discovery focus and rationale. Novel extrinsic targets that enhance immune responses to cancer are actively being pursued, while tumor intrinsic targets that render cancer cells more sensitive to the immune system have joined traditional intrinsic targets (e.g. directly cytotoxic) in the drug discovery pipeline. The phosphatase PTPN2 (TC‐PTP) and its paralog PTPN1 (PTP‐1B) are negative regulators of several cytokine signaling pathways and T cell receptor (TCR) signaling. In a recent publication, Baumgartner et al. demonstrate the pre‐clinical efficacy of a first‐in‐class dual PTPN1/N2 active site inhibitor (ABBV‐CLS‐484/AC484) in cancer models.

100 Deals associated with oNKo-innate Pty Ltd.

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100 Translational Medicine associated with oNKo-innate Pty Ltd.

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Pipeline

Pipeline Snapshot as of 06 May 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

6

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

oNKo-046	Neoplasms More	Preclinical
oNKo-044 ( IL-12 )	-	Preclinical
oNKo-001 ( IL-12 )	Solid tumor More	Preclinical
oNKo-038	Neoplasms More	Preclinical
oNKo-037 ( IL-15 )	Neoplasms More	Preclinical