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Predicting the Response to Tyrosine Kinase Inhibitors (TKIs)

Prof. Jukka Westermarck, University of Turku; Dr Eleonora Mäkelä, University of Turku

Innovations, Entrepreneurship and Transnational Education, University of Turku


Tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML)

  • TKIs have revolutionized CML treatment 
    • approximately 15% of all global leukemia cases (437,000 CML cases in 2018)
  • TKIs exist in several generations
    • Imatinib - 1st generation TKI drug - the safest and most inexpensive. Average price of generic imatinib in the U.S. is $35,000 per year with a lowest cost of $4,400 annually. 
    • 2nd (e.g. dasatinib) and 3rd (e.g. ponatinib) generation TKI drugs are more potent, but also have more side effects and are costly ($135,000 for dasatinib and $138,000 for ponatinib in 2014 and 2017, respectively)
  • Selecting the most optimal TKI drug can have significant economic consequences and impact on the disease outcome for each patient $8.5M (1st TKIs) vs. $850M (2nd/3rd TKIs) for new CML patients worldwide every year


The NOCIVA solution

A novel companion biomarker for predicting response to TKI treatment

  • NOCIVA (1) is a novel splicing variant of the oncogenic PP2A inhibitor CIP2A (2-4)  
  • The NOCIVA biomarker assay could be utilized for:
    • Selection of individual CML patients to different TKI therapies
    • More precise stratification of patients for clinical TKI trials
  • Clinical proof for the method achieved in two independent CML patient cohorts

1) Mäkelä et al., doi: 
2) Junttila et al., Cell, 2007;
3) Laine et al., Cancer Discovery, 2013;
4) Kauko et al., Science Translational Medicine, 2018

Commercial Opportunity

NOVICA – unique biomarker test for CML

NOCIVA biomarker - no direct competition

  • Previously unidentified CIP2A variant sequence
  • Current CML biomarkers are used for monitoring the treatment response, not for front-line testing for de novo CML patients to select between first-line 1G and 2G TKI therapy
  • Although there is strong clinical utility and medical need for such assay (1), there are no gene expression biomarkers for CML used in the clinic for such purpose as presented here



1) Branford et al., Leukemia (2019) 33:1835–1850

Development Status

NOCIVA test optimizes TKI treatment in CML

  • Simple qPCR or dPCR-based test to detect NOCIVA in peripheral blood of CML patients
  • The detection technology is already commonly used in hospital laboratories
  • Patients with low NOCIVA expression can be treated with 1st generation TKIs
    • 1st generation TKIs significantly more affordable (up to 100x) compared to 2nd/3rd therapies 
       --> Remarkable economical benefits to public healthcare (chronic treatment)
  • Patients with High NOCIVA expression could be allocated to 2nd/3rd generation TKIs directly
    • Obvious interest of pharma companies with 2nd/3rd TKI drug development
    • TKI clinical trials with more precise and characterized patient populations 
       --> Improvements in patient outcomes with more representative clinical trial results

Patent Situation


Applicant (owner) University of Turku, (PCT/FI 2018/050844) filed 20.11.2018)

EPO 18811327.8

USA 16/765,084

Canada 3,082,650

Japan 2020-527797


Applicant (owner) University of Turku, PCT filed 18.4.2019


Further Reading

Discovery of NOvel CIP2A VAriant (NOCIVA) and its clinical relevance in myeloid leukemias

Mäkelä et al., doi:



Predicting the Response to Tyrosine Kinase Inhibitors (TKIs)