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.

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).

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.

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.

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

Source: Katsuaki Maehara/X