Ryan Richardson: Yeah. And I think so what you’re hearing from us, Akash is, in the very short term, we do think that the COVID combination vaccine with flu, if successful, the profitability is going to be dependent in part on COVID vaccination rates. And that’s one of the near-term drivers that has the potential to bring those rates up.
Operator: Thank you. We will now go to your next question. And your next question comes from the line Jessica Fye from JP Morgan. Please go ahead.
Jessica Fye: Hey, there. Thanks for taking my questions. Coming back to BNT311 and the ASCO update, which regimen would you focus us on? And what element of the profile do you expect to best showcase the product’s efficacy? And related to that, what’s the right benchmark to compare that efficacy metric to? Thank you.
Ozlem Tureci: So the regimen we will be presenting will be a combination of BNT311 with pembrolizumab in second line on small cell lung cancers and the post-CPI population to which you would then need to compare this regimen.
Jessica Fye: Okay. Maybe I’ll just throw in one more. Can you recap a hypothetical list of what the 10 potentially registrational trials running by year end might be? I imagine you’ve contemplated a few scenarios here, but maybe you could throw out an example or two.
Ozlem Tureci: Probably 10 trials we are trying to activate or do you want examples? Is this the question? So we have several of them activated. One example is the BNT316 trial. Our cooperation with OncoC4, an entire CTLA-4 which is in non-small cell lung cancer in PD-1, PDL-1 experienced in Phase 3. Another trial, which is potentially registrational is our breast cancer trial in HER2 low breast cancer with BNT323. Also phase III which has started early this year, then in this priority asset list we have trials with autogene cevumeran, the individualized vaccine we are co-developing with Genentech Roche. One example is our colorectal cancer trial, which will read out in — around 2026. Another example is our adjuvant pancreatic cancer trial.
Additionally, we will activate trials with BNT327. So the PD-L1 VEGF compound, we have talked about earlier. So these are several of the examples of potentially registrational trials we would like to activate by end of this year. One very exciting one I should also list here, which is our trial with our CAR-T cell, Claudin-6 CAR-T cell in testicular cancer.
Operator: Thank you. We will now go to the next question. And your next question comes from the line of Yaron Werber from TD Cowen. Please go ahead.
Brendan Smith: Hi, great. This is Brendan on for Yaron. Thanks for taking the questions. Just a quick one from us actually on the infectious disease pipeline. It looks like we’re going to have a Phase 1 update from the shingles vaccine sometime this year. But wanted to also see where you’re at with enrollment and potential timing to data for maybe malaria HSV and TB programs and kind of if there’s any notable updates on how you’re prioritizing this part of the pipeline. Thanks very much.
Ugur Sahin: Yeah. We will provide data updates actually on the HSV 2 trial, on the TB trial and the malaria trial, which created safety and immunogenicity data in Phase 1 and are proceeding now into Phase 2 settings. And the data will come at various events until the end of this year.
Operator: Thank you. We will now go to the next question. And your next question comes from the line of Etzer Darout from BMO Capital Markets. Please go ahead.
Etzer Darout: Great. Thanks for taking the question. Just another bigger picture strategy question around oncology. Looks like the early combination approaches rely on external molecules. But just curious about the strategy for moving combinations of internal assets, particularly combinations of immunotherapy and targeted therapy assets, moving those into proof of concept studies, and when we could start maybe seeing some of those sort of emerge. Thank you.
Ugur Sahin: Yeah. Excellent question. This is actually one of the strengths that we would like now to activate. So the first type of combination trails with internal assets is Claudin-6 CAR-T cell therapy with RNA vaccine. And we have recently reported data shown in Dieter (ph) synergy between the two of the combination increasing the persistence of T-cells. We will see start — end of this year, the first combination trials of our ADC compounds with our IO portfolio. And actually 2025 will be an intense year where we will do multiple combination trails dedicated to contribution of component trails and safety assessments to bring us into the position to go into first registrational trails in our combos in the second half of 2025.
Etzer Darout: Great. Thank you.
Operator: Thank you. We will now go to the next question. And your next question comes from the line of Terence Flynn from Morgan Stanley. Please go ahead.
Terence Flynn: Great. Thanks for taking the question. For BNT122, it sounds like it was on your list of registrational trials. So just wondering for the data next year from that Phase 2 CRC trial what you’d need to show on an efficacy basis to consider filing for an accelerated approval. And then, again, I noticed you had an ASCO presentation on some epidemiologic data here. Again, just what are you expecting to show there at ASCO or what would be the key learnings? Thank you.
Ugur Sahin: Yeah. So this study is a sufficiently powered Phase 2 study. It is in a patient population of colorectal cancer patients who are ctDNA positive. Multiple epidemiological studies have shown that this patient population have a very poor prognosis. Actually — and PFS in this patient population after surgery is around 12 months, after chemotherapy is around seven months. So this is actually a metastatic — early metastatic patient population. And the clinical trial compares a standard of care, which is adjuvant chemotherapy, in this patient population versus standard of care, followed by the personalized vaccine. The clinical trial endpoint is disease-free survival. And we expect the endpoint analysis for this trial in the second half of 2025. The trial is enrolling, as expected at the moment. And, of course, this is all what we can say everything else will depend on the totality of the data.
Ryan Richardson: And do you want to say a few words about the epidemiological study at ASCO?
Ozlem Tureci: Yeah, I can do that. So what we will present at ASCO is an epidemiological study. So it’s not a treatment study. And we have conducted this epidemiological study in order to better understand the prognosis of those patient populations. We have in our ongoing clinical trial with BNT122 in particular, also of subpopulations which are ctDNA positive because that further informs our ongoing clinical trial. In addition, this epidemiological trial is a pre-screening trial to identify patients to recruit into our investigational trial. So you will get, in particular, epidemiological data of ctDNA positivity rates in high-risk populations in colorectal cancer and the disease-free survivors which are seen in these subpopulations.
