FTS for the treatment of cancer

THE TECHNOLOGY and NEED
K-Ras is a highly prevalent oncogene that plays a key role along with the EGFR gene in the pathways regulating other proteins associated with tumor survival, angiogenesis, proliferation and metastasis. The change of a single base in the DNA that encodes for K-Ras is associated with primary resistance to EGFR inhibitors. In tumors with K-Ras mutations, K-Rasmut is constitutively active and will continuously code for tumor growth without regulation. Mutant versions of Ras are found in approximately 70-90% of pancreatic cancers, 25% of non-small cell lung cancers and 30-40% of colorectal cancer.
Salirasib is the first-in-class “rasib” and is not a farnesyltransferase inhibitor (FTI) or Epidermal Growth Factor Receptor (EGFR) antagonist. Unlike FTIs and EGFRs, salirasib has a much broader ability to inhibit Ras signaling by dislodging all isoforms of Ras from membrane binding sites. Among other trials, the Phase 1 and proof-of-concept clinical study program included:
• Successful completion of a Phase I program in both solid tumors and hematologic
• Successful completion of a Phase I/II study in newly diagnosed stage IV pancreatic cancer patients of dose escalating salirasib with standard doses of gemcitabine.
RESULTS
• The combination of salirasib (400-600 mg b.id.) and gemcitabine resulted in a median survival time of 21.6 months. These results compare favorably to standard therapeutic benchmarks in similar patient populations, including gemcitabine monotherapy.
• The combination of Gem + salirasib appears safe with no PK interactions
POTENTIAL APPLICATIONS
• Part of the standard of care, in combination with chemotherapy, in pancreatic, non-small cell and colorectal cancer for patients who harbor K-Ras mutations.
ADVANTAGES
• Favorable safety profile
• Positive results in Pancreatic Cancer (synergy with standard Chemo to reach disease stabilization and extended survival – up to 2 years)
• Clear go/no go clinical trial (a controlled pivotal study with the effective dose )
• Strong IP on oral formulation
• Unique MOA.
PATENTS
US Patents for the Treatment of Cancer and oral formulation

Project manager

Elisha Natan
Director BD

Project researchers

Yoel Kloog
T.A.U Tel Aviv University, Life Sciences
Neurobiology