On January 15, 2019 Kitov Pharma (NASDAQ/TASE: KTOV), an innovative pharmaceutical company, reported new findings from its ongoing collaboration with researchers from the Hebrew University of Jerusalem (Press release, Kitov Pharmaceuticals , JAN 15, 2019, View Source [SID1234532669]). The data reveal NT219’s high affinity and selective binding to its target proteins.
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Hadas Reuveni, Ph.D., Chief Technology Officer at Kitov’s subsidiary, TyrNovo Ltd., in collaboration with Dr. Galia Blum and Dr. Ofra Moshel from the Hebrew University demonstrated that NT219 binds directly to Insulin Receptor Substrates (IRS) 1/2 and to the Signal Transducer and Activator of Transcription 3 (STAT3), both known modulators of tumor survival, metastasis and drug resistance. Data showed that a short exposure of cancerous cells to NT219 was sufficient to trigger irreversible shutdown of these pathways, resulting in a long-term anti-cancer effect.
Based on these latest findings, Kitov and Yissum, the Technology Transfer company of the Hebrew University of Jerusalem, have extended their collaboration agreement in order to deepen the understanding of NT219’s efficacy in overcoming tumors’ resistance to immunotherapy.
As previously reported (Reuveni et al, Cancer Research, 2013) upon binding to IRS1/2 a three-step mechanism is activated. IRS1/2 dissociates from the cell membrane, undergoes serine phosphorylation which prevents rebinding to the receptor, and is finally degraded by the proteasome. This sequence of events leads to the blockage of AKT – a major cancer cell survival pathway.
"We are excited about the new data which demonstrate NT219’s unique mechanism of action. NT219, a new and promising concept in cancer therapy, is designed to prevent, reverse, and delay resistance to anti-cancer drugs. We are developing NT219 as a drug to be used in combination with other therapies that has a potential to overcome cancer drug resistance and to boost the efficacy of numerous oncology drugs on the market today," stated Kitov CEO, Isaac Israel.
About NT219
NT219 is a small molecule that presents a new concept in cancer therapy by promoting the degradation and inhibiting the phosphorylation of two oncology-related signal transducers, Insulin Receptor Substrates (IRS) 1/2 and signal transducer and activator of transcription 3 (STAT3), respectively. While targeted anti-cancer drugs inhibit the "ON" signal, NT219 activates the "OFF" switch, extensively blocking major oncogenic pathways. In pre-clinical trials, NT219, in combination with several approved cancer drugs, displayed potent anti-tumor effects and increased survival in various cancers, including sarcoma, melanoma, pancreatic, lung, head & neck, prostate and colon cancers, by preventing the tumors from developing drug resistance and reversing resistance after it had been acquired. NT219 is licensed from Yissum, the technology transfer company of the Hebrew University of Jerusalem