Towards Breakthrough Therapeutics In Oncology
Beactica is using its proprietary and world-leading drug discovery platform to build a pipeline of novel and mechanistically defined small molecule therapeutics to address unmet medical needs.
Lysine-specific demethylase 1 (LSD1/KDM1A) is bi-functional epigenetic protein that regulates the expression of disease-associated proteins. On one hand, its enzymatic function removes methyl groups from mono- and dimethylated Lys4 of histone H3, thereby changing the chromatin configuration that governs regulation of DNA transcription. On the other hand, LSD1 is a structural protein with a scaffolding function to support the formation of larger epigenetic protein complexes.
Significant research shows that modulation of LSD1 is relevant for the treatment of several common cancers and also impacts the immune system's ability to fight cancer. However, the catalytic LSD1 inhibitors currently in clinical trials have a limitation in their anti-cancer effect as compared to genetic knockdown of LSD1. It is therefore of vital importance to develop alternative modulators that target LSD1 in novel ways.
Beactica is developing first-in-class small molecule allosteric modulators of LSD1 (KDM1A) with a mechanism of action that is fundamentally different from catalytic inhibitors currently in clinical development. The compounds have an attractive PK profile and exhibit in vivo efficacy in a clinically relevant glioblastoma animal model, and indication of efficacy also in other animal cancer models.
Beactica’s LSD1 programme has been supported by the Swedish Governmental Agency for Innovation Systems (Vinnova) with three grants of SEK 3.0 million (2015), SEK 2.0 million (2017) and SEK 2.8 million (2019).
- Sheng et al. (2018) LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell, 174:1–15. doi:10.1016/j.cell.2018.05.052.
- Qin et al. (2018) Inhibition of histone lysine-specific demethylase 1 elicits breast tumor immunity and enhances antitumor efficacy of immune checkpoint blockade. Oncogene, 38:390-405. doi: 10.1038/s41388-018-0451-5.
- Sehrawat et al. (2018) LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. PNAS, 115:E4179-E4188. doi: 10.1073/pnas.1719168115.
- Segerman et al. (2016) Clonal variation in drug and radiation response among glioma-initiating cells is linked to proneural-mesenchymal transition. Cell Rep, 17:2994-3009. doi: 10.1016/j.celrep.2016.11.056.
- Suva et al. (2014) Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell, 157:580-94. doi: 10.1016/j.cell.2014.02.030.
Information on partnered programmes can be found under Drug Discovery Partnerships.
Beactica is continually evaluating new targets with therapeutic breakthrough potential to add to its pipeline.