Frank Bedu-Addo: Thank you very much. Yes. So Mayank, I think, you are absolutely right. We have seen highly encouraging survival data with PDS0101, as well as PDS01ADC, as well as extremely encouraging ORR with the PDS01ADC. Now, we have certainly considered the application of the PDS01ADC in the earlier line ICI naive. However, after talking to key opinion leaders in the field, as well as the regulatory experts, it’s evident that the survival and safety data generated with a doublet, presents the most straightforward regulatory pathway, as well as the robust uptake if and when it becomes standard of care, right? With the doublet will also enable a more rapid potential approval path for early, even early use. Now, when we look at the triple in the ICI resistant population, it also presents the quickest path to approval and potentially application in multiple HPV cancer indications, as you mentioned, essentially tumor agnostic.
This triple combination may then also subsequently find its way to an approval for use in ICI naive patients. So, this is something we have actually seriously considered, but after talking to the experts in the field, the two options we are taking now appear to provide the quickest paths to rapid approvals and uptake.
Mayank Mamtani : I understood. Thank you for that clarification. And then maybe drilling down on the doublet trial protocol, are there any details on the SAP that you’re able to share in terms of the target OSS [ph], differential, you’re going for against standard of care? I recognize you are talking about sites, but not specific patient numbers, but just sort of it would be helpful to understand what sort of hazard ratio, what sort of delta on OSS you’re aiming for. And this is related question, your ESMO translational biomarker data was actually quite novel in context of demonstrating CD8 T-cell responses specific to tumor cells. So, I was wondering if there are any implications of that in terms of patient enrichment or response assessment strategies that you could deploy in your late state development.
Frank Bedu-Addo : Mayan a lot of really good questions. So, let me start with the biomarker data. So, with the biomarker data, as you did mention, we are looking at a number of novel approaches to really understanding and documenting how PDS0101 is working and really documenting and clarifying the differentiation of our assets. So, if you look at the data presented at ESMO, for example, looking at the poly functional CDA T-cells, confirming increase in poly functionality was very important. But also understanding the kind of immunological profile that PDS0101 is promoting, for example, going from a TH2 bias to a TH1. TH1 being well documented to be better associated with strong CD8 T-cell responses, right? And also showing that we have potential exit of the CDA T-cells from the blood to the tumor sites, right?
Showing the decline in circulating peripheral blood, um, containing CDA T-cells. So, we have that approach in that study in the PDS0101 KEYTRUDA. Now, when you also look at what’s been done in terms of biomarkers in the Immunotherapies study, right? Very complimentary to what we’ve seen with the PDS0101 KEYTRUDA study. In the IMMUNOCERV study, what MD Anderson was looking at is circulating tumor DNA. Circulating tumor DNA is extremely important for a number of reasons, right? If you look at cancer today, most patients don’t die from the initial tumor or the initial cancer. They often die from micrometastatic cancer that remains after the initial treatment, right? And so being able to essentially eliminate the tumors from the patient’s body becomes extremely important.
And how do you know that your technology or product is actually achieving that? What we have seen now with our circulating tumor, DNA in that study is the strong potential for PDS0101 to actually dramatically eliminate and reduce and eliminate the circulating tumor DNA, right at five weeks, 92% reduction versus 52% reduction with the standard of care. MD Anderson is extremely excited about that because they believe it has direct implications for patient survival and very importantly, recurrence of the cancer, right? So that is — data that we will hopefully be expecting to see coming up in 2024, how that elimination of circulating tumor DNA correlates with recurrence of the cancer and survival of the patients. Now, what they also looked at a very innovative approach using cervical brushing to really quantify and understand the kinds of T-cells that are actually accumulating in the patient’s tumors, right?
So, we talked about the CDA T-cells in the blood and exiting the blood, but it’s also important to understand what’s happening in the tumor. And what they also showed was a really strong correlation between this elimination of circulating tumor DNA and accumulation targeting accumulation of the CDA T-cells within the patient’s tumor, right? So, again, very different to date, most of our peers have looked at T-cells in the circulating blood, looking at things like interferon gamma, but what we are showing here that these T-cells generated by diverse immune technology actually do target and accumulate in the patient’s tumors, right? So again, we have very complimentary studies which are in agreement with each other, which are given us a really good picture of how and why we’ve seen the results we’ve seen in these patients today.
