ASCO thoughts

For the first time, a team of researchers have shown that the “coldness” of a tumour correlates with the amount of ENOX2 present; and that inhibition of the ENOX2 (the principal target of Veyonda) converts the tumour from COLD to HOT.

The ASCO data for Veyonda and Nasopharyngeal carcinoma (see https://meetings.asco.org/abstracts-presentations/212713) showed that the addition of Veyonda plus Cisplatin allowed 67% more immune cells to infiltrate the tumour, compared to the control group, turning it from COLD to HOT. This is a significant finding for Nasopharyngeal cancer, but also provides support for the use of Veyonda with check-point inhibitors like Opdivo.

COLD tumours do not respond to immunotherapy. The Nasopharyngeal data shows that inhibition of ENOX2 converts tumours from Cold to Hot, thus increasing the likelihood of a positive reaction to IONIC treatment.

The fly in the ointment is Cisplatin, which is not used in the IONIC trial. I note that Veyonda is administered for seven days in each 14-day cycle, providing a high level of exposure to ENOX2 on an ongoing basis. Whether the results in IONIC would be better if Cisplatin was included remains to be seen, but it seems to me that dose-dense Veyonda will have the ability to knock out ENOX2 and thus reverse resistance to Opdivo.

Graham Kelly has long believed that cancer cells switch from ENOX1 to the harder-working ENOX2, which results in higher levels of sphingosine-1-phosphate in the cancer which in turn creates an S-1-P gradient (high in the cancer, lower in blood) that drives immune cells out of the tumour. The ASCO abstract shows that he was right; and that inhibition of ENOX2 can reverse this process.

This is huge news. My prediction is that Veyonda will prove to be synergistic with Opdivo.