Despite considerable progress in supportive care, life prolongation, and prevention of life-threatening complications, current therapeutic strategies suffer from the common neuralgic point of side effects and adverse events, often stemming from the promiscuity of therapeutic agents.

The long-lasting stagnation in overcoming this issue is most perceptible in anticancer therapies, which have failed to eliminate this phenomenon for decades. Given the global cancer burden of 18 million new cases annually, a progressive treatment solution addressing the promiscuity of therapeutics, such as ESiNAR-X®, may have an impact on millions of human lives.

Chronic myelogenous leukemia

CML is a clonal hematopoietic stem cell disorder characterized by an increase in myeloid lineage cells at all differentiation stages.

BCR-ABL1 oncoprotein
-driver of leukemogenesis

-encoding the BCR-ABL1 oncoprotein

Rapid progress in understanding the molecular basis of CML allowed for the development of tyrosine kinase inhibitors (TKI) which have revolutionized the management of CML, with the disease now having a five-year survival rate over 80%.

The evolution of these drugs to treat CML has been quite remarkable in a continuous fight against resistance. Nonetheless, despite the massive improvement in CML treatment over the last years, an important minority of patients (20–30%) display intrinsic or acquired resistance to treatment during the disease course.

The current strategies for addressing TKI resistance have mainly focused on improving the potency and specificity of the drugs and on overcoming the resistance driven by mutations in the BCR-ABL1 oncogene. Alternative approaches addressing current treatment challenges may be necessary for patients who fail to respond to TKIs and novel therapeutic modalities capable of targeting leukemic clones escaping TKI therapy could be game changers in the professional management of these patients.

Current oligonucleotides

Issues to be addressed


Therapeutic lead
  • Promiscuity

    inhibition of homologous off-targets

  • Recognizes exclusively the target RNA

    does not interact with native off-targets

  • Poor cellular uptake

    high doses needed to achieve the therapeutic effect

  • Exhibits spontaneous delivery to cells

    more than 500 million molecules per cell

  • Drug toxicity

    originating from chemistry and promiscuity

  • Shows no toxicity even at extreme concentrations

    healthy cell viability more than 98%

  • Limited efficacy

    only partial suppression of target RNA

  • Remarkable efficacy in target suppression

    reduces BCR-ABL1 RNA levels in mice by 99% in 10 days

  • Non-selective therapeutic action

    the cause of treatment side effects

  • Highly specific towards leukemic cells

    reduces leukemic cell burden in mice by 50% in 10 days

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