On December 1, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported results from a preclinical in vivo study for its highly selective CDK9 inhibitor, GFH009, that demonstrate robust inhibition of tumor growth in a mouse xenograft model of small cell lung cancer (SCLC) (Press release, Sellas Life Sciences, DEC 1, 2022, View Source [SID1234624703]).
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GFH009 was tested against NCI-H209 SCL xenografts in athymic nude mice in four treatment groups of eight mice each (n=32) consisting of GFH009 alone, olaparib (a PARP inhibitor) alone, a combined regimen of GFH009 and olaparib, and a vehicle control. Treatments were initiated after tumor xenograft volumes exceeded 120 mm3 in each animal group and mice were subsequently sacrificed after mean tumor volume exceeded 1,500 mm3 in the control group.
GFH009 treated mice exhibited a 40.4% decrease in mean tumor growth compared to the control group in this very aggressive cancer model which had a tenfold increase in average tumor volume over 20 days. Strongest effects were observed with GFH009 in combination with olaparib, with mean tumor growth decreased by 72.3%. Treatment with olaparib alone resulted in a 30.2% mean decrease in tumor growth. No significant toxicity or safety concerns were observed in any of the treatment groups.
"We are looking forward to expanding use of GFH009 into solid cancers and these results indicate CDK9 can be an actionable target not only in the apoptotic pathway but also the DNA damage response pathway," said Dragan Cicic, MD, Senior Vice President, Clinical Development, of SELLAS. "This opens up additional avenues for the use of GFH009 in an expanding array of difficult to treat cancers based on their genomic and proteomic traits, moving another step towards truly personalized medicine."
Olaparib is a commercially available targeted oncology drug that acts as a PARP inhibitor and induces synthetic lethality in BRCA mutated cancer cells via DNA damage and response (DDR) pathways. Recently published clinical trials have demonstrated early signals of efficacy for olaparib both as a single agent and in combination with agents targeting DDR, specifically ATR pathways in refractory SCLC patients. CDK9 is known to bind with cyclin K, forming a complex that plays a key role in the DDR pathway which could enhance synthetic lethality of olaparib.