- R&D Pipeline
- Season 1 (2011-2020)
(KDDF-201111-02) Development of anticancer drug NPS-1034 targeting lung cancer, based on new mechanism which inhibits activity of c-MET/AXL kinase associated with cancer metastasis and growth simultaneously.
Oncology, Chemical
In the treatment of various solid cancers such as lung cancer, EGFR inhibitor antitumor agents such as Tarceva(Erlotinib) and Iressa(Gefitinib) are used. While these are effective in early stage, after an average of six to eight months of treatment most patients acquire a resistance to the antitumor agent, which ultimately leads to a worsening of the cancer and finally death. As the importance of c-MET has been highlighted in the main mechanism of acquiring tolerance, the development of inhibitor medicine has been active. However, recently there have been reports that AXL not only plays an important role in acquired tolerance for EGFR inhibitor but also is related to poor prognosis after treatment has been continued. In terms of the importance of AXL being increased in acquired tolerance, since AXL is overexpressed/overactive in various solid cancers, especially in non-small cell lung cancer, it will effectively obstruct AXL, and c-Met inhibition activation also will contribute to the development of novel anticancer treatments. Therefore, we are planning to develop NPS-1034, which has been developed as a target anticancer medicine in Neopharm, Inc and targets AXL and effectively obstructs c-Met inhibition activation, as a treatment for patients who already have acquired tolerance, and extend period occurring acquired tolerance.
NPS-1034 is targeted at patients who show AXL dependence acquired tolerance by EGFR mutation among EGFR dependence cancer patients or c-Met dependence acquired tolerance. It also is targeted at patients who want to extend the occurrence period of acquired tolerance among patients who do not meditate EGFR inhibitor anticancer drug. Various drugs have been developed to overcome acquired tolerance of EGFR inhibitor, but most have been focused on the development of c-Met inhibitor, so there is no medicine that can effectively obstruct AXL, which plays an important role in acquired tolerance. Accordingly, there may be a huge medical demand for NPS-1034, which can obstruct AXL and c-Met at the same time.
We have completed research involving animal effect test, active mechanism, physical and chemical character research, cardiotoxicity, carcinogenesis genotoxicity, metabolism, medicine type research and crystal form of NPS-1034. Sample for non clinical test (GLP toxicity study) has also been developed in a completed GLP compound by CMO (USA). Beginning at the end of December, 2012, non-clinical tests will be started in an overseas CRO.
We already applied for patent in Korea (2011), Australia (2012) and New Zealand (2012), and are currently applying for patents in 8 main countries (USA, EU, Japan, China, Russia, Canada, Brazil and India).
Firstly, NPS-1034 is a first-in class drug effectively obstructing new target AXL which participates in acquired tolerance of the most widely used EGFR inhibitor anticancer drugs.
Secondly. it not only effectively obstructs c-Met, the 1st signal passing course of acquired tolerance of EGFR inhibitors, but also effectively cuts out the signal passing course of the 2nd tolerance after the 1st tolerance.
Third, in case of c-Met, various mutations occur in most cancers, and it can also effectively obstruct these. NPS-1034 can effectively obstruct not only wild type but also mutant type, meaning that it can be applied to a much wider range of patients.
Fourth, NPS-1034 has good effects on patients with lung cancer, one of the most prevalent types of cancer, and particularly on patients with non-small cell lung cancer.
Fifth, it also is highly effective not only on lung cancer, but also on stomach cancer when c-Met is overexpressed/overactive/mutated when independently injected.
Sixthly, it can enlarge indication for most other solid cancer treatment such as not only non-small cell lung cancer and stomach cancer, but also breast cancer, rectal and colon cancer, Head and neck squamous cell carcinoma, pancreatic cancer, brain cancer and ovarian cancer.
Seventhly, it is a drug for a new target so high treatment effects can be expected through joint injection with existing anticancer drugs.
Eighth, NPS-1034 is a novel lead backbone which has new chemical structure so that it can compound many new derivatives. Currently, it secures two back-up materials.
Ninth, it reacts very peculiarly for AXL, c-Met, but its reaction spectrum with other Receptor tyrosine kinase is low, minimizing side effects.
Tenth, it obstructs specific targets by targeting and doesn't show fatal dose in a high concentration of 2g/kg, so there are little side effects in terms of cell toxicity.
Eleventh, it effectively acts on Erotinib tolerance cancer cells that Pfizer's PHA-665752, a c-Met inhibitor, does not affect, so it is much more excellent than other c-Met inhibitors currently developed.
Twelfth, there are no concerns over accumulation in the body, as it has a short period of stay while having an excellent cancer cell growth restraint effect.
anticancer drug
Apr.01, 2012~ Dec.31, 2012
Neopharm, Inc.
Lead Optimization