SLS009 (formerly, GFH009 is a next generation highly selective cyclin-dependent kinase 9, or CDK9, inhibitor which we in-licensed from GenFleet Therapeutics (Shanghai), Inc. in March 2022. We have worldwide development and commercialization rights, except for Greater China.

In general, CDKs are a family of protein kinases which are important in regulating cell cycles. Deregulation of CDKs is associated with many cancers. CDK9 is one transcriptional subfamily and is a major cancer target whose activity has been shown to correlate negatively with overall survival in several cancer types, including hematologic cancers, such as acute myeloid leukemia and lymphomas, as well as solid cancers, such as pediatric soft tissue sarcomas and ovarian. CDK9, together with cyclin T1, forms positive transcription elongation factor b, or P-TEFb, which plays an important role in allowing long RNA strands to be quickly transcribed[SY1] from DNA. P-TEFb is crucial for the synthesis of some of the key proteins, namely MYC, a key anti-apoptotic, and MCL-1, an oncogene, that drive division of cancer cells and protect them from programmed cancer cell death. Inhibition of CDK9 can decrease the levels of MCL-1 and c-MYC which can result in apoptosis and cell cycle arrest.

It is important that other kinases are not inhibited along with CDK9. First generation CDK9 inhibitors worked across many CDK targets in addition to CDK9 and therefore had significant toxicity due to their low selectivity. Next generation CDK9 inhibitors, including SLS009, have the potential for higher specificity, potentially resulting in less toxicity and more consistent clinical activity.

As almost all AML patients have heterogenous cancer cells, some cells will depend mostly on BCL2 and will be killed by venetoclax, a BCL2 inhibitor, while some will depend on MCL1 and will potentially be killed by SLS009. When patients respond to venetoclax, one of the primary drivers of their resistance is that the cells are no longer dependent on BCL2, but use other antiapoptotic methods to survive. MCL1 is a dominant mechanism of survival in patients that either don’t respond to a venetoclax-based regimen or respond then subsequently relapse. By harnessing an effect against MCL1 with SLS009, the main driver of cancer survival after venetoclax, SELLAS believes SLS009 could potentially be used synergistically with venetoclax to block the antiapoptotic effects of both MCL1 and BCL2.

For more information on our development of SLS009, visit our pipeline.