Oncolytics Biotech Inc T.ONC

Phase III for mBC Trial

[Quentin30]

From the 3Q 2023 Conference Call Transcript - Matt was asked

"In the same way you got the grant from PanCAN to run a different combo in pancreatic. Do you think there would be a similar opportunity in breast cancer, say, evaluating pela with a different checkpoint that was used in BRACELET-1?"

Matt Response
Excellent question, Chad, thanks. Yes, we do believe that -- and again, for people looking at the story, at ESMO, we presented was a tripling of the objective response rate when we added pela to paclitaxel, a 50% increase in the median overall survival, and then we're tracking for overall survival. The hazard ratio is 0.29. So it was really quite a remarkable improvement. When we added avelumab, it eliminated that benefit and what we've found out since and subsequently avelumab is the only approved checkpoint inhibitor with a non-modified Fc portion. So for anyone not familiar, the Fc portion on an antibody. So an antibody basically looks like the letter Y or a ranch.

The part that would engage with is the bolt is the SAB portion. That's the portion that changes and finds the epitope and allows you to have a selective antibody response against a specific epitope. The handle of the ranch interacts with other immune cells through MHC molecules. Every other developer on the planet has silenced that FC portion so that it doesn't engage with macrophage. And the reason for that is it can lead to T cell engulfment or macrophage engulfment of the T cells. So as opposed to expanding a T cell response, it will actually collapse it. And there's actually publications in the literature talking about how avelumab treatment can actually lead to hyper proliferation, just to say it will actually lead tumors grow faster. So it was a poor choice to combine with an agent like ours that relies on a T cell response.

- Basically Matt is admittin ghere that they f^*&cked up with the selection of a CPI - so much for Bracelet-1 shortening timeframes. But I digress... read on...

And you can see this from our two TTR sequencing, the addition of avelumab caused total collapse. When we spoke with partners about this, they said that was an expected outcome based on this non-silence FC Portion. So we still think breast cancer can benefit from the addition of a checkpoint inhibitor and especially something like atezolizumab where it is directed against the PD-L1 MOD rather than PD-1 and that's just to say, for us, it's better because we're getting expression on the tumor cells itself. So we can actually direct where we want to direct. So it should work with durva, atezolizumab, but we've seen synergy with other PD-L1s that have that have non -- half silent Fc Portions like Merck. I'm just -- with the growing body of evidence the atezolizumab is looking really good in terms of the underlying synergies.

Yes, I think we should be looking at this in the breast cancer space. And I think that becomes an important component of our life cycle management. for a couple of reasons. I think we'll be successful with just paclitaxel and pela, two randomized studies, I'm very comfortable, thinking that a third study is going to be as successful as the last two. But the question is can we make it even better? Can we get complete responses, even better survival, more objective response. So I think it makes sense to study that. But the Phase III is not going to look at that. That will be more of a life cycle management aspect.


So, the bit I have highlighted in red is effectively Matt saying that they will be running a two arm Phase III trial and the Type C meeting may "hopefully" be because they now (think) they have adequate biomarker correlation between PFS and OS. Still NOTHING on Accelerated Approval here...

For those who are unfamiliar with the term  "Life Cycle Management", this specifically refers to POST-APPROVAL supplements (changes) to the BLA. Matt here is musing that after getting approval for Pela + Pax, they might explore trying this combo with a different CPI, but not as part of the Phase III... This devalues the proposition for a partner if their CPI can't be used from the get-go... Step up Merck maybe.?

He then went on to talk about reimbursement... ibut for example, f it only costs 50k for Pela + Pax to gain 12 extra months OS, and you can improve it by only say 6 months with a CPI added, is that worth an additional few hundred grand..? So the money opportunity may not even be there.


The reason why I have to keep stating that they will NOT be getting accelerated approval, is because MATT is on record speaking of a regular Phase III... 

[ONCInvestor]

Thanks for all of your work on this Quentin, including your review of the corporate presentation.  Really good work.