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Katsuaki Maehara: Therapeutic development of 4th generation TKIs is active for acquired resistance to osimelnitinib for C797
Dec 23, 2023, 03:25

Katsuaki Maehara: Therapeutic development of 4th generation TKIs is active for acquired resistance to osimelnitinib for C797

Katsuaki Maehara, Director of Medical Education Colleagues, recently shared the following on X/Twitter:

“Therapeutic development of 4th generation TKIs is active for acquired resistance to osimelnitinib for C797.

Part 2 from the previous issue summarizes the resistance mechanisms and the efficacy of preclinical but therapeutic agents.

Katsuaki Maehara: Therapeutic development of 4th generation TKIs is active for acquired resistance to osimelnitinib for C797

Osimelninib enters the ATP of the EGFR TK domain and covalently binds to residue C797. Therefore, it acquires resistance to C797.

Preclinical but 4th generation TKIs have shown efficacy and safety, especially against coexistence on the same side of the DNA double-strand (in-cis).

Katsuaki Maehara: Therapeutic development of 4th generation TKIs is active for acquired resistance to osimelnitinib for C797

The first of the therapeutic agents does not act on the ATP pocket but binds to allosteric sites.

Unfortunately, allosteric inhibitors alone do not show efficacy and are effective in combination with EGFR inhibitors.

Katsuaki Maehara: Therapeutic development of 4th generation TKIs is active for acquired resistance to osimelnitinib for C797

The second class of therapeutic agents are tyrosine kinase inhibitors that bind to ATP sites. We have selected two of the many candidates and summarized their efficacy and safety data.

– BBT-176 – Bridge Biotherapeutics, Inc.
– BLU-945 – Blueprintmedicines corporation.

Katsuaki Maehara: Therapeutic development of 4th generation TKIs is active for acquired resistance to osimelnitinib for C797

Finally, I summarized the SHYPHONY study of BLU-945 presented at ASCO 2023 with slides divided into safety and efficacy.”

Katsuaki Maehara: Therapeutic development of 4th generation TKIs is active for acquired resistance to osimelnitinib for C797

Source: Katsuaki Maehara/X