So, one of the things that we identified was that we very clearly saw on-target activity from performing RNA-seq on our pre- and post-treatment samples and the responders and non-responders. We did see that decreases in E2F pathway scores, where E2F is a transcription factor that’s bound by RB, which is downstream of CDK4 and CDK6-induced phosphorylation of RB. So we found that there was a significant decrease in E2F pathway activity score, and that was a predictor of response to abemaciclib...
So, one of the things that we identified was that we very clearly saw on-target activity from performing RNA-seq on our pre- and post-treatment samples and the responders and non-responders. We did see that decreases in E2F pathway scores, where E2F is a transcription factor that’s bound by RB, which is downstream of CDK4 and CDK6-induced phosphorylation of RB. So we found that there was a significant decrease in E2F pathway activity score, and that was a predictor of response to abemaciclib. Interestingly, we also found that abemaciclib downregulates critical proteins involved in homologous recombination repair of double-stranded DNA breaks. And we are proposing, based on data from this clinical trial and also from our laboratory, that sequential abemaciclib can enhance the efficacy of DNA-damaging agents, including antibody drug conjugates, such as enfortumab vedotin, which is currently being tested as a next generation of neoadjuvant chemotherapies in combination with immune checkpoint inhibition with pembrolizumab. So we think that this paradigm of EP-Pembro followed by abemaciclib in the neoadjuvant setting, but also in the metastatic and the advanced setting is going to lead to improved efficacy. And that is where we think clinical trials need to go.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
