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【新藥案源媒合】In vivo model proven protein phosphatase modulators for the treatment of cancer

刊登日期:Nov-15-2016  |  瀏覽:295  |  資料來源:
 

In vivo model proven protein phosphatase modulators for the treatment of cancer
SupremeCure Pharma Inc.
Oncology
#Si2C1601
 
 
Hepatocellular carcinoma (HCC) represents about 90% of primary liver cancers and ranks as the third cause of cancer-associated death globally. There are about 780,000 new HCC cases per year worldwide, and the 5 year survival rate of HCC patients is around 12 percent. Sorafenib (Nexavar), which is an antiangiogenic multikinase inhibitor, is the first and currently the only approved medication for the treatment of advanced HCC. However, sorafenib only provides marginal benefits, as unsatisfactorily low tumor regression (around 2 to 3 percent) and median overall survival (usually less than one year) have been observed. We have identified that Signal transducer and activator of transcription 3 (STAT3) is a major kinase-independent target of sorafenib in HCC, and sorafenib abolishes p-STAT3 signals by enhancing Src homology region 2 domain-containing phosphatase-1 (SHP-1) phosphatase activity. We thus derived a series of first-in-class SHP-1 agonists, which reduces p-STAT3 signals, for the treatment of HCC. SC-43, a potent SHP-1 agonist which exhibits strong anti-HCC activity, was then selected as the candidate.
 
SC-43, a SHP-1 phosphatase agonist, abolishes p-STAT3 signals for the treatment of cancer
 
SC-43, is a SHP-1 phosphatase agonist (orally administrated small molecule) that abolishes p-STAT3 signals. SC-43 enhances SHP-1 activity by switching SHP-1 conformation from auto-inhibitory (closed) to active (open). The anti-tumor activity of SC-43 has been observed in HCC, colorectal cancer, breast cancer, and cholangiocarcinoma animal models. Furthermore, the “SC-43 plus” regime by applying SC-43 to eliminate STAT3-related pro-survival signals could be combined with sorafenib, immunotherapy, biologics, or other small molecules to combat cancer. Our recent proof-of concept animal studies also demonstrated that SC-43 exhibited anti-fibrosis activity. The CMC (cGMP) and toxicology studies (GLP) have been completed and we will submit IND application in 2017. The plan is to initiates our phase I trial in Taiwan and then includes some sites in China and other Asia-Pacific region for phase II trial. We are currently seeking US$ 5 million in series A to initiate our phase I study and advance our proprietary phosphatase-targeting technology.
 
Lead Inventor:
Founder of SupremeCure Pharma Inc.
Associate Professor/Attending physician, National Taiwan University Hospital
 
Co-founder of SupremeCure Pharma Inc.
Professor, National Yang-Ming University
 
Applications:
  • Treatment of hepatocellular carcinoma
  • Treatment of colorectal cancer
  • Treatment of fibrosis
  • Treatment of breast cancer
  • Treatment of cholangiocarcinoma
  • Treatment of diffuse large B-cell lymphoma (DLBCL)
 
Advantages:
  • Reduced tumor growth by targeting protein phosphatases.
  • Manageable toxicity.
  • Abolished p-STAT3 signals; in great position for combination trials with sorafenib, immune-therapy, biologics, or other small molecules.
  • Cost-effective.
 
Patent Information:
Related patents have been filed in 23 regions (including EU). As of 10/2016, patents have been issued in USA, China, Taiwan, Korea, Canada, Australia, New Zealand, South Africa, Russia, and Singapore. We expect more coming up soon.
 
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