Andrew Allen: So we don’t know. We did not anticipate that. Obviously, we wouldn’t have set the endpoint the way we did. So clearly we had a failure of the endpoint in the study. That’s an important distinction that I think has been lost on a lot of people. You can have an endpoint fail or a product fail or both. In this case, the endpoint failed because we saw ctDNA dropping in the control group just for the first three to four weeks after the completion of induction chemo. And so that’s presumably telling us that there is some delayed or persistent effect of the induction chemotherapy. We had no data to guide us before we designed the study. So this was a new observation, and obviously it’s one that tripped us up, but at some level not that important, because obviously what matters A, is that PFS is delivering clear signals here and is a more relevant regulatory endpoint, as we discussed in this call.
And secondly, the long-term ctDNA analysis is highly consistent with the PFS signal. In other words, patients on vaccine do better. ctDNA is controlled for longer, and that certainly is what you would expect from an active therapy in this disease setting. Now, moving forward in this disease, we will not be worried about ctDNA because we’re now potentially entering Phase 3, and we’ll be using traditional endpoints, PFS or OS. And obviously, that’s something we’ll be discussing with the agency at the end of Phase 2 meeting. And as you know, PFS has been used for approval in this first line disease setting. So that’s what we’ll be doing in metastatic colorectal cancer. However, we obviously, if all goes well, we’ll be developing the program in other settings, and particularly in earlier stage trials, especially if single arm ctDNA outcomes are potentially very important as an early efficacy metric before you get to big randomized studies.
And therefore, it is important that we understand how to interrogate ctDNA in a way that renders it a useful surrogate for clinical endpoints such as PFS and OS. Today, I can’t give you the answer because we don’t have the mature PFS and OS data, but of course, the data we’re generating will be an invaluable resource to enable us to figure out a way to use ctDNA that adeptly captures long term clinical benefit and can then be deployed in single arm smaller trials in other indications.
Chengxiang Liu: All right, thank you so much.
Andrew Allen: Thank you.
Operator: The next question comes from Mayank Mamtani with B. Riley Securities. Please proceed.
Unidentified Analyst: Hey, guys, Madison here on for Mayank. Thanks for taking our question. So, wondering, what do you guys anticipate the touch points will be with the FDA whenever you meet to discuss Phase 3? And also curious how those patients could look relative to what we’ve seen in GRANITE. After 75% liver met 50% KRAS, if that’s just kind of representative of the population. And then lastly, the fact we didn’t see any pseudo progression, do you expect that would hold in a Phase 3, or is that something that you’ll attempt to address in the design in the event there is pseudo progression? I appreciate it, guys. Thanks.
Andrew Allen: Yes, thanks, Madison. Good question. So, in a slightly different order, in which you ask the questions by design, this was a very straightforward frontline study across the United States in a variety of centers with very straightforward inclusion and exclusion criteria, very standard. And that’s good, of course, because it means there’s not much opportunity for patient selection. You’re just taking the patients that come through the door, and there aren’t that many trials in frontline colorectal cancer. So, most people who were clinical trial eligible and at a site where our trial was operating, would have been offered our study, which is why it enrolled very swiftly, particularly in the first half of 2023. So there is unmet need there the trial is very straightforward and recruits patients without any special selection.
We don’t anticipate changing that for Phase 3. Why would you? You want a representative population, so that’s good news. And obviously, we would anticipate that the degree of liver metastases and KRAS mutations will be constant in the Phase 3, because, of course, your dream is to run a Phase 3 that is basically unchanged from your Phase 2. That reduces the chance that something new, you’ve made some new assumption, or something else is happening that’s altering the outcome. You want that so called sleep easy Phase 3. So our incentive is to change as little as possible. And obviously, we’ll go to the FDA, and the traditional forum is an end of Phase 2 meeting, which we’d anticipate towards the end of this year, taking to them the data from this study, which, of course, we’ll have in hand in Q3.
And then we’ll be discussing, among other things, the Phase 3 primary efficacy endpoint. And that is likely to be a choice between PFS and OS. We also, of course, need to align with the FDA on manufacturing because these are complex products. We’ve obviously been in lockstep with the FDA from the very get going fact we first spoke to the FDA about manufacturing before we were in the clinic, when we were literally designing the layout of our biomanufacturing facility. So we held a Type C meeting back then just to solicit FDA’s input to make sure that we were on the right track in terms of the way we make these products. There’s obviously a step up in regulatory quality as you move to Phase 3 and commercial, and we need to make sure that we’re aligned with the agency.
That’s also part of the end of Phase 2 meeting alongside the clinical endpoint discussions.
Unidentified Analyst: Got it. Thank you.
Operator: The next question comes from Kaveri Pohlman with BTIG. Please proceed.
Unidentified Analyst: Hi, this is Christian. I’m on for Kaveri today. My first question is, I would like an update on the CORAL program. I saw that you guys presented positive data recently on the CORAL study on South African patients, and there was positive data in the three vaccine candidates. So is there any development there? Are you guys planning to which candidate are you guys planning to move forward?
Andrew Allen: The. Obviously, if successful with our BARDA study, we’ll be moving forward another candidate because, of course, we’re expecting there to be an update of the strain that is required for the fall season of 2024. As you’re aware, WHO and the EU have issued guidance to use the JN.1 variant, if you remember, obviously, last year, it was the XBB.1.5 variant. So there will be a strain change. We’ve not disclosed the exact nature of the T cell component that we’ll include in the vaccine, but that will be included. That’s part of our chimeric vaccine design, intended to induce protective antibodies as well as those protective T cell responses against conserved antigens. So that’s the expectation going forward, and that’s the primary focus of the CORAL program right now.
Unidentified Analyst: Okay, thank you. And regarding the BARDA study, I just noticed in the press release that it says the company will be initiating that as soon as they can. Should we still expect that in fall 2024 or is that being reevaluated?
