iOmx Therapeutics Announces Discovery of Novel, Druggable Immune-Checkpoint Targets
iOTarg™ Platform Identifies SIK3 Kinase as an Immune Checkpoint in Multiple Solid Tumors and IGSF11 as an Immune Checkpoint in PD-L1 Resistant Tumors
iOmx is Building a Pipeline of Monoclonal Antibodies and Kinase Inhibitors TargetingNovel Checkpoints with Quality of PD-1/PD-L1 Axis
Martinsried / Munich, Germany, September 26, 2019: iOmx Therapeutics AG (iOmx), a biopharmaceutical company developing cancer therapeutics based on novelimmune checkpoint targets, announced today the presentation of two posters at theFifth International Cancer lmmunotherapy Conference (CICON 2019) which showcasesthe company’s proprietary, high-throughput genetic screening platform, iOTarg™.
iOTarg is designed to broadly screen tumor cells for hijacked immune checkpoints, which enable targeting of the tumor´s immune resistance mechanisms.
“iOmx has reached a significant inflection point by demonstrating the ability of itsiOTarg genetic screening platform to successfully identify novel and druggable immune checkpoint targets expressed by cancer cells. As demonstrated in our poster presentations at CICON, our lead antibodies and kinase inhibitors have shown
significant anti-tumor effects and the potential to be first-in-class treatments for cancers that can otherwise not be addressed with conventional immune checkpoint therapies,” said Apollon Papadimitriou, Ph.D., chief executive officer of iOmx Therapeutics.
The first poster, titled, “Salt-inducible kinase 3 facilitates tumor cell resistance against cytotoxic T cell attack by shifting TNF signaling from apoptosis to survival,” reports the identification and validation of SIK3 as a novel tumor-associated immune checkpoint in multiple solid tumors. Based on these findings, iOmx´ researchers developed a novel SIK3 inhibitor, which when tested in a MC38 syngeneic mouse model, demonstrated a significant single-agent anti-tumor immune response. SIK3 was found to render cancer cells resistant to TNF-mediated apoptosis and to promote NFkappaB-mediated transcription of pro-survival genes by inhibiting HDAC4. Inhibition of SIK3 is shown by iOmx to re-sensitize tumors to TNF and T cell attack as a compelling novel strategy for cancer therapy. Pancreatic cancer patients often manifest a high expression of a TNF/SIK3/NFkappaB-dependent gene signature, making this disease a possible indication for a SIK3 inhibitor.
The second poster, titled, “Inhibition of novel immune checkpoint IGSF11 mediates efficient tumor cell killing in vitro and in vivo,” reports the identification by iOTarg of IGSF11 as a tumor-expressed immune checkpoint target in a setting where PD-L1 inhibition is ineffective. Based on this finding, iOmx is developing novel anti-IGSF11 monoclonal antibodies, which when tested in vitro, trigger immune cell-mediated lysis of tumor cells in an epitope-dependent manner. Further, in an MC38 murine colon adenocarcinoma mouse model, CRISPR knockout of IGSF11 resulted in significant retardation of tumor growth in wild-type mice, along with reshaping of the intratumoral immune compartment. On the basis of this target validation, iOmx´ researchers expect that IGSF11 blocking antibodies have the potential as monotherapy in patients with solid tumor indications that are resistant to PD-1/PD-L1 therapies.
Based on these discoveries, iOmx has initiated pre-clinical development activities of proprietary molecules that are designed to target SIK3 and IGSF11. Furthermore, the company continues to investigate new Immuno-oncology targets with its IOTarg platform.
About iOmx Therapeutics
iOmx (www.iomx.com) focuses on the development of first-in-class cancer therapeutics addressing novel immune checkpoints hijacked by cancer cells. The company’s proprietary platform, iOTarg™, systematically screens tumor cells for expression of immune checkpoint modulators, that, when knocked-down, increase T cell immunity against cancer cells. iOmx is building a pipeline of promising cancer immunotherapeutics based on novel, proprietary targets with a known mode of action. Founded in 2016 based on the work of its scientific founders Philipp Beckhove and Nisit Khandelwal conducted at the German Cancer Research Center, the company has been funded by MPM Capital (both its BV2014 and UBS Oncology Impact Funds), Sofinnova Partners, Wellington Partners and Merck Ventures and is based in Martinsried / Munich, Germany.
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