Gregory Glenn
Analyst · JPMorgan, Your line is now open
Thanks, Dan. As we gave a detailed review of the data last week, I'm just going to give a high level overview today. So, on slide five, what you can see is that the 2373 is, is a product of a technology platform that uses the insect cell and Matrix‑M adjuvant. So we are able to take a sequence from a virus such as the spike protein sequence from SARS-CoV-2, manufacture this into a nanoparticle that has the full-length protein and combine this with Matrix-M which is a potent Adjuvant, which for which we have a great deal of clinical experience. So let's turn to the trial on slide six. This slide shows the study objectives. The phase will trial, evaluate the safety immunogenicity of the Novavax-CoV2373 protein or [Indiscernible] nanoparticle vaccine with or without Matrix-M Agilent. The primary outcomes were reactogenicity, safety, and lab assessments, and the immunoglobulin G IgG anti-spike protein response in humans. Secondly, secondary outcomes included adverse events, wild type neutralizing antibodies and T-cell responses. So on slide seven, we’ll give some details on the design. It was a randomized, observer-blinded, placebo-controlled trial and was designed to evaluate the immunogenicity and safety of Novavax-CoV2373. Our focus is on the trial, you can see in the red box, so in Group C and D, or we had two doses of our antigen, either five micrograms and 25 micrograms with the Matrix-M. And that was given twice at day zero of 21. We compared that to placebo. We also compare to Group-B which did not have the adjuvant and we compare it to Group-E, which had the adjuvant with our Matrix-M given once, followed by placebo at day 21. So on slide eight, just overall, we summarize the conclusions here. And again, we provide a great deal of detail about this last week. But we did see let's go to the highlights here. The data demonstrated a dose dependent response, sorry, dose independent response, both doses levels induced high and comparable levels of IgG. So, the trial showed a dose effect. The IgG levels compared favorably to those seen in convalescent serum that we obtained from the Baylor College of Medicine and we note a 100% IgG seroconversion rate. There was an Adjuvant required for the optimal immune response which is quite clear. So, demonstration adjuvant effect was an important findings in this trial. With respect to wild type neutralizing antibodies, they appear to be in the two dose groups, numerically superior to what we saw in the Convalescent Sera overall, both dosage levels again induced a high comparable wide wild-type neutralizing antibodies. We saw 100% wild-type neutralization seroconversion rates after the second dose, and the neutralization response was tightly correlated with the IgG response. We also looked for T-cells in the pulmonary way and we saw that we had polyfunctional CD4 T-cells were induced that favored the Th1 phenotype. Overall, the Phase 1 trial did demonstrate a reassuring safety and reactogenicity profile. We saw no serious adverse events. All unsolicited adverse events were mild or moderate and a local systemic, reactogenicity was not dose limiting. So let's just talk to the next slide for briefly look at the some of the highlights of the immunogenicity. We covered this previously, but this is the anti-spike IgG ELISA. You can see that on the Y-axis, it’s on the log scale. You can see on the far length, are the subjects who represent the human convalescence sera. The next row has the placebos. The next row has the 25 microgram dose given that day zero and 21 without Adjuvant. And then the five microgram dose given with Matrix-M adjuvant day zero 21, 25 micrograms a day zero 21 and the 25 micrograms dose given once a day 21 followed by placebo. You can clearly see the difference between the Groups in B, where one of the two doses compared to say Group D, where they had the equivalent antigen dose, you can see the Adjuvant effect was profound. You can also see that there is a great benefit in the second dose, achieving very high levels of anti-spike IgG. You can see some of the details on the far on the right there we have a for Group C, with a second dose we have a 63,160 Eliza and a titer and that compares to the convalescent sera where the titer on the geometric mean basis was 8,344. So robust responses. The overall geometric mean this was approximately seven fold higher than the convalescent sera and a robust response. Go to the next slide. Here we show the wild type neutralization. This is done through collaboration at University of Maryland School of Medicine. And again, you can see the graph is organized in the same way, very similar messages, importance of the adjuvant, importance of second dose and with reference to convalescent sera you're seeing again the vaccine group is an excess of the geometric meet of this, this group from Baylor College of Medicine. We did discuss fairly extensively and note that there is a tiered response based on in the convalescence, sera based on the severity of outcome. And I think our vaccine compares very favorably with the sticker subjects that are in that trial. So, as we mentioned in the results, this, this correlation between the IgG and the micro, it was a very tight correlation. We also saw a strong T-cell response. We won't go into that detail again here. That was a preliminary result. We're going to expand on those results as we go. But it was consistent with what we've seen in our pre-clinical programs in our previous clinical trials, where we see a robust T-cell response, CD4 effective memory cell response, and it's a polyfunctional T-cell that has a Th1 phenotype virus. So overall if you go to the next slide. We're ofcourse, we've been very buoyed by this result. And just want to show how this does fit into our, our pipelines. We are still very committed to our NanoFlu vaccine program, which you see in the second bar there, where we had very good results at all of our eight co-primary endpoints in March, and we expect to continue that development. So with that, I'm going to turn this back over to Stan.