Synergistic combinations with allosteric LSD1 modulators for the treatment of glioblastoma
| Reference number | |
| Coordinator | Beactica Therapeutics AB |
| Funding from Vinnova | SEK 2 820 116 |
| Project duration | May 2019 - April 2021 |
| Status | Completed |
| Venture | Swelife and Medtech4Health - Collaborative Projects for Improved Health |
Important results from the project
Combination therapy is becoming increasingly common in treating cancer. The goal of this project was to identify specific treatments that when combined with Beactica LSD1 Allosteric Modulators (LAMs) synergize to increase their efficacy. Synergy with several classes of compounds could be shown, including positive results in syngeneic animal models of glioblastoma and colon cancer in combination with checkpoint inhibitor drugs approved for cancer treatment.
Expected long term effects
Beactica has identified a novel series of LSD1 Allosteric Modulators (LAMs) which have displayed promising antitumor effects. While LAMs display little standalone activity in PDX models of cancer, it was found that LAMs synergize with checkpoint inhibitors to activate the immune system to clear cancer. Furthermore, standard-of-care (SoC) for glioblastoma (temozolomide + radiation) works in part by activation of the immune system, but the response is not durable. It was found that when SoC is combined with LAMs, the duration of the response is significantly prolonged.
Approach and implementation
To identify synergetic companion drugs that might increase the effectiveness of the LAMs, we performed screens of a broad panel of co-administered drugs. Several classes of drugs were found to synergize with LAMs. We then explored the possibility that LAMs could synergize with cancer immunotherapies, and in particular checkpoint inhibitors which are approved for a broad range of cancers and the current standard-of-care for glioblastoma.