Oncolytics Biotech Inc T.ONC

Companies now seek to moderate TME to expand PD-(L)1 effect

[Noteable]

October 19, 2022 - "PD-L1 expression, while still an important biomarker, is not the static, “yes/no” predictor of tumor response for which researchers hoped. 

The challenge for PD-1/PD-L1 checkpoint inhibitors is the tumor microenvironment (TME). It is such a complicated mass of cells and proteins that no single therapy is likely to cure all or even many types of cancers in all patients. 

Now companies are pursuing other targets, often as adjuvants to moderate the TME and thus expand the efficacy of anti-PD-1/anti-PD-L1 therapies.

[ONCY's pelareorep is one such target that has already demonstrated that it is able to moderate/remodel the TME to expand the efficacy of anti-PD-(L)1 immune checkpoint inhibitor therapies by also employing innovative predictive biomarkers that are able to identify which patients will positively respond to the pelareorep + ICI immuno-oncology combination before and then throughout the course of treatment ]

https://www.biospace.com/article/beyond-anti-pd-1-pd-li-3-companies-swing-for-the-fences-with-new-targets-/

[jimsenior]

A  very interesting article admtting that PD-1/PD-L1 is not enough. CD8 is mentioned on slide 25 of the current presentation, and also in Preinduced reovirus-specific T-cell immunity enhances the anticancer efficacy of reovirus, and elsewhere I am sure. I do not really know what it means, and have come to the conclusion that this whole subject is too complex for most. Conclusion: this is so

[Noteable]

This may not take as long as you might expect, given that ONCY has demonstrated (Aware-1 study) which predictive biomarkers can be used to determine which breast cancer patients and now which GI cancer patients can benefit from the I/O combination of pelareorep + PD-(L)1 through the current Bracelet-1 and Goblet Phase 2 studies. This has been explained throughout the clinical development process

[jimsenior]

Yes. You are right. Just for fun (and sometimes just searching words brings some clarity) I searched: PDAC CD8 GOBLET and pelareorep. The results were interesting. No question Roche placed this trial in very good hands indeed. I am still debating whether or not to add a few shares (my position is small beer compared to most) and I must be careful. As someone said the other day pela looks to be

[jimsenior]

One last question to myself. As a biomarker in PDAC I think a low expression of CEACAM6 is indicated. If so, if CEACAM6 can be downregulated,  I think that is the correct term, would not said biomarker have a dual purpose. Those who would likely benefit, and those who might benefit if the expression could be lowered. Please advise if you know if CEACAM6 expression can be lowered. TIA

[Noteable]

Yes - over expression of CEACAM6 negatively modulates the TME in pancreatic cancer. In order to avoid the immune response, tumor cells can change the degree of expression of specific antigens on the cell surface with the main objective to repress the activation of immune cells that would otherwise recognize and attack the transformed cells.   One of those membrane proteins is

[Noteable]

Tinurilimab (Bay 1834942) is an anti-CEACAM6 monoclonal antibody and was demonstrated to be equally efficacious compared to blockade of PD-L1, (which was not enhanced by ONCY's pelareorep) and the anti-CEACAM6 mab showed an additive efficacy when combined with anti-PD-1 or anti-TIM-3 antibodies, suggesting an efficacy independent of the PD-1/PD-L1 axis, in contrast to ONCY's