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 (AS). Endowing the human genome with enormous protein coding potential, AS can also commonly be “highjacked” by cancers to enable their growth, survival, dissemination throughout the body, and evasion of current standard-of-care therapies. Biosplice 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 AS 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 AS 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 has developed a suite of small molecule 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 RNA 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 (SM08502), a first-in-class pan-CLK inhibitor which has completed dose-escalation in Phase 1 with subject 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 (SM08502), 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.


Expanded Access

Biosplice is committed to developing safe and effective medical solutions to help patients. Biosplice may, in the future, provide access to its investigational drug products for expanded access, sometimes called “compassionate use,” if and when there is sufficient scientific evidence to support an expectation of net benefit to the specific patient and where such use would not unduly jeopardize the investigational product’s potential to benefit a larger patient population.

Biosplice is not offering expanded access for any investigational drug product at this time.


American Society of Clinical Oncology (ASCO) | June 02 - 06, 2023

Cancer Cell, | January 09, 2023

  • Modulation of RNA splicing enhances response to BCL2 inhibition in leukemia

    Cancer Cell. doi:10.1016/j.ccell.2022.12.002

    Eric Wang, Jose Mario Bello Pineda, Won Jun Kim, Sisi Chen, Jessie Bourcier, Maximilian Stahl, Simon J. Hogg, Jan Phillipp Bewersdorf, Cuijuan Han, Michael E. Singer, Daniel Cui, Caroline E. Erickson, Steven M. Tittley, Alexander V. Penson, Katherine Knorr, Robert F. Stanley, Jahan Rahman, Gnana Krishnamoorthy, James A. Fagin, Emily Creger, Elizabeth McMillan, Chi-Ching Mak, Matthew Jarvis, Carine Bossard, Darrin M. Beaupre, Robert K. Bradley, and Omar Abdel-Wahab.

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