Is there any of the biomarkers that we’re looking at?
Thomas Heineman: Well, we — so we are looking at a variety of different markers. But I think to date, as you pointed out, Matt, the TIL expansion is the one that seems to be the most — it has the best correlation with response and is also consistent with the prior literature. So I think that’s probably the most interesting one that we’ve identified so far.
Matt Coffey: There’s some additional work being done with If you’re familiar with the literature Dr. Anne Noonan at OSU has demonstrated that the patients with better outcomes have lower CEACAM6 levels. That was in the NCI study looking at this. So we are verifying that result as well because that could be a selection criteria based not post-treatment but pretreatment. So we’ll have additional information for you there in that area as well.
Soumit Roy: Nothing you’ve seen on KRAS due to demutation or DNA damage response [indiscernible] mutations?
Thomas Heineman: Well, just — so in pancreatic cancer, the large majority of patients, somewhere in the 80-plus percent will have a KRAS mutation. So that is unlikely to be discriminatory in that particular patient population.
Soumit Roy: All right. Thank you so much.
Thomas Heineman: Thanks, Soumit.
Operator: [Operator Instructions] Our next question comes from the line of Jason McCarthy from Maxim Group. Please go ahead.
Unidentified Participant: Hi, guys. This is Chad on for Jason. Thanks for taking the questions. So I was just wondering, 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 Coffey: 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.
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. And then the question is reimbursement. A tele combination will be priced like other — any other immunological therapy. If we add a checkpoint inhibitor, that will double that number again.
So the question is how much benefit do we have to see to ensure reimbursement of a drug combination that could be looking between $300,000 and $400,000 conservatively. So it is a question we have to answer, but it will be answered as we’re running the Phase III program so that we can say, okay, let’s get the approval. Here’s the next steps, but I agree with you wholeheartedly. Avelumab, unfortunately, was a poor choice and I don’t think it’s reflective of the underlying synergy we see with other checkpoint inhibitors, and it is something we can study. And it was interesting, we just had a Board meeting yesterday, and the clinical component of our discussions were as we’re running the Phase III, where can we get other studies with cooperative groups like PanCAN, EORTC, NCI, NCIC to really start bolstering studies into other pivotal indications.
And obviously, checkpoint inhibitors is going to figure very largely into that picture.
Unidentified Participant: Great. Yeah. Thanks for the detailed answer there and taking the question and congrats again on all the progress.
Matt Coffey: Thanks, Chad.
Operator: That was just our last question. I’d now like to turn the call back over to Mr. Coffey for any closing remarks.
Matt Coffey: Thank you for that. Thank you to everyone who turned in to hear about our progress. The data presented at ESMO pancreatic and colorectal cancer, in addition to our AWARE-1 abstract data presented at since they reinforce the ability of pela to remodel tumor microenvironments and generate immune responses in patients even in those with immune systems diminished by previous lines of therapy. The data also adds to the portfolio of evidence that pela synergizes with checkpoint inhibitors like atezolizumab. We’ll continue to advance towards licensure-enabling studies in breast and pancreatic cancer and provide additional update on our progress. With that, I wish everyone a wonderful rest of your day. Thanks again, everyone. I appreciate it.
Operator: Thank you, sir. Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines. Have a lovely day.
