Louise Chen: Congratulations on all the progress this quarter. I wanted to ask you a little bit more on the Phase 3 VERSATILE-003 study and see if you could provide some more details, maybe broadly speaking how you wanted to design that study versus the VERSATILE-002? And then how did the results of 002 inform your thinking on the Phase 3 design for 003? Secondly, are you expecting to present any new data at major medical oncology conferences or even from your virus €“ your Infectimune platform this year? And if so, where would you be presenting those and what venues? Lastly, just thinking about OpEx for 2023, is the fourth quarter of 2022 a good starting point for thinking about how to build things? And you’re starting a major study, so curious how you think about the cadence of R&D expense in 2023.
Frank Bedu-Addo: I’ll start and then hand over to Lauren to finish up. But in terms in terms of the Phase 3 trial, you are correct. We are looking to get as much information as possible from the VERSATILE-002 trial. As I mentioned, overall survival is what we believe will be the key parameter that the FDA would want us to power the trial to really understand. But also what we want to do as we design the trial is also take information from VERSATILE-002. For example, what do our PFS numbers look like? Does increase in PFS in VERSATILE-002 correlate with increase in overall survival, for example. And those were some of the key parameters that we needed to get insight into because, if that’s the case, then we can design that with certain interim data points that may allow us to get data that we could then start discussing with the FDA sooner than later regarding a potential approval.
So, right now, for example, there has been recent guidance from the FDA in terms of how they would look at accelerated approvals and how they would look at single control trials for accelerated and final approval. Right? So, with all that information, part of the key things that we would want to do, as we finalize this design, get input from the other countries into the design, finalize the numbers, but also give ourselves the opportunity to see data sooner than later. And if it’s positive, be able to start having discussions with the regulatory agency. So, that’s one of the key reasons why we needed to really understand how our PFS numbers were beginning to look as well as overall survival and see if there was improvement over published KEYTRUDA monotherapy data in terms of improvement in both sets of parameters.
I’ll hand over to Lauren to address the additional questions.
Lauren Wood: In follow up to Frank’s comments, our intention, Louise, is to present updated data from VERSATILE-002 at scientific meetings. We are targeting to present data potentially either at ASCO, ESMO, and also potentially SITC related not only to the updated clinical outcomes in the ICI naïve population as it relates to PFS and overall survival, which, again, Frank noted, will inform our design of VERSATILE-003, but also confirmation and examination of the immunogenicity parameters that we are seeing in VERSATILE-002. I think one of the most important things to come out last year was the demonstration that we see in patients, even in heavily treatment experienced patients, the induction of these HPV 16 specific multifunctional potent CD8 killer T cells in patients.
And we’re looking to present that data from VERSATILE-002 as well during the course of 2022. So, yes, we will be presenting that data. I can’t really comment regarding Infectimune presentations. The Viruses publications were very, very impressive for us in terms of the ability to demonstrate broad antigen specific CD4s and CD8 cells that are indeed protected from lethal influenza challenge. And I think any scientific presentations during the rest of this year will be guided by additional preclinical studies that we may be pursuing with the goal of progressing our Infectimune based platform to human clinical trials. And there was a third question that you had. Could you just repeat that?
Louise Chen: Yeah, it was a financial question. So I wanted to ask you about OpEx for 2023. Is fourth quarter 2022 a good base to build off of? And then with the start of this VERSATILE-003 by fourth quarter 2023, how should we think about the cadence of R&D expense this coming year?
Matthew Hill: I think in looking at Q4, you’re starting to see the step up and increase in associated costs related to our trials, and that’s going to continue into 2024. But I think if you take €“ obviously, in the fourth quarter numbers, we’ve got the $10 million that we spent with Merck KGaA. So after eliminating that, that’s a good way to think about it. And also, obviously, we’re going to have some additional R&D expenditures as well €“ I’m sorry, general and administrative expenses as well.
Operator: Next question is coming from Kalpit Patel from B. Riley.
Andrew Fleszar: This is Andy Fleszar on for Kalpit. Congratulations on the progress. We know that you had a successful initial meeting with the FDA for the doublet. But is the agency requiring any more data to be submitted along with the final trial protocol? And when should we expect this protocol to be submitted?
Frank Bedu-Addo: I think with the triple, as we mentioned, we are looking to get some additional data. Hopefully, that will inform how we design the statistical portion of that program. And also, one of the key things that we would want to do €“ that the FDA would want to see is €“ I think one of the key things we mentioned a number of times is the contribution of agents. We talked about that quite a bit. Right? And so, pending what that information provides to us, we may be able to go in in terms of looking at PDS0101 and PDS0301 in addition to the triple combination. We anticipate that that may be possible. But again, that’s something that we would have to discuss with the FDA. That’s also important for us because, if you recall, with the triple combination trial, there are two of the three agents which has been found to be critical in the clinical outcomes €“ PDS0101 and PDS0301.
Right? Both of those were found to be critical for those outcomes. And so, part of what we may potentially do is two stage where we look at a small number of patients as a medium to their bigger registrational trial. But again, those are things that we are waiting for information for to finalize that design. We think based on what we know today, we think it’s going to be a smaller design than the VERSATILE-003. But until we have all the information to design that trial, I probably wouldn’t be able to provide too much detail into what you’re asking. But these are some of the key things that we’re looking at to come up with the most efficient design possible.
Andrew Fleszar: Sorry if I misspoke, but I was actually questioning the doublet study.
