Specifically CD8 T cells boost effect. And this is what we introduced in our initial primate study. And this is what we added to the protocol of Go-10. So, yes, after kicking the CD8 T cells up to be high titers with the second administration of the chat.
Mayank Mamtani: Understood. Thank you. And then on the regulatory scenarios that could exist after achieving this data in 4Q, could you could you maybe comment on, is there anything that you’re specifically looking to learn from the Moderna Merck situation? Given that you will have the control data, you will have a number of these translation markers, correlating with survival metrics, could you just kind of higher level sort of commentary on how you’re thinking about engaging with the FDA after fourth quarter?
Andrew Allen: Mayank, the donor, obviously, is potentially useful. We, they haven’t published anything on their personalized cancer vaccine program. There have been a few poster presentations at various meetings. So we don’t really know anything about the key attributes, how do they do new action selection, that quantifying the strength of the T cell response for diversity, the phenotype of those cells, the numbers of new antigens being recognized pre and post vaccination. So any of that information would obviously be helpful, and we’ll see whether that’s disclosed. So simple answer is we don’t know much about the data. And we want, we are kind of just waiting like everybody else to see what’s published and presented, hopefully, in short, in short order.
In terms of the agency, obviously, we will have the collective goal of trying to improve outcomes for patients with metastatic colorectal cancer, which remain dismal, the median survival of no more than two years for a typical newly diagnosed patient. And as we all know, no, no real benefit from immunotherapy. And so we’ve had a constructive dialogue with the agency through the development of this program. We started talking to them way back, before we were in the clinic around things like sequencing approaches and how that would be regulated, we solicited their input to the design of our bio manufacturing facility. So we’ve had a good good relay political relationship with the agency. And when we spoke to them last on this topic, which was in the summer of 2021, we aligned on the design of this phase 2/3 program.
And it’s sort of traditional programming that there is a phase 2, randomized phase 2, and we will learn a lot and we will use the insights from those from the phase 2, to inform the design at the phase 3. And the key issue on the table will be what’s the primary efficacy endpoint for phase 3. And that conversation we anticipate will happen in the first half of 2024. And the obvious endpoint is overall survival. It’s unambiguous, it’s internationally accepted and of course, it’s the one that counts. And in terms of timing, unfortunately, this is a disease where you don’t have to wait that long to obtain survival data. As I say median survival is around two years. Whereas a PFS study would be around one year median, PFS 11 months or 12 months, something like that.
So it’s not a big difference between a surrogate endpoint like PFS and the hard clinical endpoint of overall survival. The OS is I think the default. Now it’s possible that a form of PFS might be a good surrogate. But we don’t really know that today and with our kind of immunotherapy, as I’ve mentioned previously, their major concern is pseudo progression, that we drive T cells into lesions which get bigger for a good reason, which is the T cells are proliferating. The assumption of the recessed rules is that lesions getting bigger is bad because it’s T — it’s tumor cell proliferation. And that, obviously, is an assumption that was developed when research was developed for cytotoxic chemotherapy, and it worked for targeted therapeutics, but obviously has just theoretical challenges.
