Cancer is one of the most important health problems facing the world. It is the second leading cause of death and most costly illness in the United States.1

Biosplice’s goal in oncology is to broadly impact cancer therapy through pharmacological modulation of corrupted proteomes at the level of RNA-recoding.

Our scientific platform is rooted in the biological systems that govern alternative splicing. Endowing the human genome with enormous protein coding potential, alternative splicing can also commonly be “hijacked” by cancers to enable their growth, survival, dissemination throughout the body, and evasion of current standard-of-care therapies. Biosplice Therapeutics has designed small molecules that inhibit CLK/DYRK family kinases to selectively disrupt alternative splicing in a manner that is tuned to disease and tissue context. This can be lethal to cancer cells that rely on dysregulation of alternative splicing for survival, and lead to reversal of drug tolerance mechanisms, and loss of oncogene pathway activation.

A monumental challenge facing durable cancer therapy is the extreme mechanistic diversity and adaptive capacity of tumors within and among cancer patients. For any given drug, benefit is increasingly limited by the subtype of disease and by rapid emergence of drug resistance. Our goal is to deliver broadly active and durable therapy by exploiting alternative splicing as a common cancer vulnerability within the ocean of confounding diversity.


    1. American Cancer Society. Cancer Facts &Figures 2021. Atlanta: American Cancer Society; 2021.

Cirtuvivint (SM08502)


Biosplice Therapeutics has developed a suite of small molecule oral inhibitors of the CDC2-like kinase (CLK) and dual-specificity tyrosine regulated kinase (DYRK) family. These kinases, relatively unexplored for drug development, govern the efficiency and specificity of alternative splicing by directly phosphorylating serine/arginine-rich splicing factors (SRSFs) and thereby influencing pre-mRNA splice junction selection.

The program’s lead clinical asset is cirtuvivint, a first-in-class pan-CLK inhibitor which is in Phase 1 with enrichment ongoing in specific solid-tumor types.


Mechanism of Action

Dysregulation of alternative pre-mRNA splicing has been identified as a common mechanistic driver of tumor initiation, disease progression, and emergence of therapy resistance. An iterative screening and design optimization campaign developed cirtuvivint, a potent pan-inhibitor of CLK/DYRK kinases which are known to regulate alternative splicing.

By inhibiting CLK and DYRK activity, cirtuvivint can control the activity states of these proteins, without halting the majority of constitutive spliceosome activity. Upon cirtuvivint exposure, tumor-selective changes in alternative splicing events are observed, with minimal changes in healthy cells and tissues. Drug-dependent reduction in aberrant splicing activity leads to reduced expression of oncogenic proteins and reduced activity of key tumorigenic regulatory systems.



AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics | October 07 - 10, 2021

AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics | October 07 - 10, 2021

AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics | October 07 - 10, 2021

Cancer Letters | September 24, 2019

  • The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models

    Cancer Letters. doi:10.1016/j.canlet.2019.09.009

    Betty Y.Tam, Kevin Chiu, Heekyung Chung, Carine Bossard, John Duc Nguyen, Emily Creger, Brian W. Eastman, Chi Ching Mak, Maureen Ibanez, Abdullah Ghias, Joseph Cahiwat, Long Do, Shawn Cho, Jackie Nguyen, Vishal Deshmukh, Josh Stewart, Chiao-wen Chen, Charlene Barroga, Luis Dellamary, Sunil K. KC, Timothy J. Phalen, John Hood, Steven Cha, Yusuf Yazici