Stemline Therapeutics has licensed the global rights to a preclinical RET inhibitor. The drug, SL-1001, was designed to improve outcomes in RET-dependent tumors by more selectively hitting the target.
Approved multikinase inhibitors such as Eisai’s Lenvima, Exelixis’ Cabometyx and Sanofi’s Caprelsa hit RET but have achieved modest outcomes in patients with the biomarker. The problem may stem from interactions between the drugs and other targets, such as KDR, resulting in dose-limiting toxicities that stop them being administered at the levels needed to deliver optimal outcomes in RET patients.
That hypothesis spurred work at the Cancer Research UK Manchester Institute Drug Discovery Unit in the U.K. In recent years, researchers at the site have published papers on their use of structure-based design to improve on Caprelsa and secure cash from the Cancer Research Technology Pioneer Fund.
At one stage, the U.K. researchers looked set to take the candidate into phase 1 themselves before seeking an industry partner for further development. Now, though, Stemline has licensed the drug from the pioneer fund that bankrolled its early advance, setting the stage for a clinical trial to start next year.
The deal for the drug, the terms of which were not disclosed, comes months after the FDA approved Stemline’s Elzonris for the treatment of blastic plasmacytoid dendritic cell neoplasm, a rare blood disease.
Stemline brought Elzonris to market on the strength of a single-arm trial that enrolled 28 patients and thinks SL-1001 may also offer streamlined development opportunities. RET mutations are found in around 2% of non-small cell lung cancers (NSCLC) and up to 20% of papillary thyroid cancers, suggesting relatively small, highly targeted studies may be possible.
Other biotechs have recognized the same opportunity. Blueprint Medicines and Loxo Oncology have selective RET inhibitors in the clinic and have begun to generate encouraging data, such as the 50% response rate among RET-fusion NSCLC patients who received Blueprint’s BLU-667.