CervoMed Inc. Common Stock Canaccord Genuity's 46th Annual Growth Conference

Thank you, Srimant. Somehow this conference ends up being an incredibly fortuitous time every year, and it's always nice to have a conference here in our hometown. We are Boston-based. I do have a few slides because I do want to catch up people a little bit. This year, already to this point, the first half of this year, we have actually for, I think, the size of company that we are, have made as much progress as anyone in this whole sector. We have a Phase III-ready drug in dementia with Lewy bodies, which is a major indication, and this is as well having progressed into another significant indication, and with a subtype of frontotemporal dementia.

I'm not going to go through all of this, but if you look at this in every aspect in terms of clinical data, in terms of financing, in terms of non-clinical data, regulatory progress, across the board, significant progress in a very short period of time. Everything is really coming together. That's why I say it's a perfect time to be coming and speaking with you, and Srimant has teed up, I think, a great set of questions for us to go about. But I did want to focus on three very specific things that I think many in the investment community have, given all this progress, have yet to fully catch up on. I just want to highlight a few things around that. One is in terms of the biology of dementia with Lewy bodies and why we call this a targeted therapy for dementia with Lewy bodies.

In the end, there is a tremendous amount of science that is developed externally that really now defines what is the underlying disease process in dementia with Lewy bodies, which is about neuroinflammation and the interplay between that and alpha-synuclein and how it impacts a very specific part of the brain, the basal forebrain cholinergic system. I am not going to walk you through the science, but it is all referenced down below, mainly last 2 years set of papers that goes to this is what dementia with Lewy bodies is.

Probably an exclamation mark on that is a paper published in Neuron, which is the major neuroscience journal, July 15th this summer, a month ago, that says that the biggest study ever done across neurodegenerative diseases in terms of proteomics, that the key mechanism for dementia with Lewy bodies that leads to symptoms and disease progression is at the end, interleukin-6 and interleukin-1 beta signaling. That is at the heart of, that is the mechanism of attraction of our drug. It is blocking interleukin-1 beta signaling and impacting interleukin-6 production and other cytokines and other downstream effectors.

But this is the science meets what is then otherwise what we actually. This is data we presented for the first time at ADPD, in the ADPD conference in April, of we are a very potent blocker of interleukin-1 beta signaling on the left that translates directly into reducing interleukin-6 levels in the spinal fluid. So puts the whole mechanism together towards targeting specific disease mechanism in dementia with Lewy bodies, all vary both from the science standpoint and what we have now understood of what our potency and activity of our drug is, all very recent news that comes together.

The second point is around the Phase IIb clinical trial results, where I think those who have been following the story that much of it in the past year has been comparing 2 different drug batches, one at higher blood levels versus one that at lower blood levels and the effects during the extension period. Data we presented at ADPD, then at further at Alzheimer's Association International Conference last month, is that within the placebo control period, even with the batch of capsules that had lower blood levels, if we look at what is now the standard cutoff, which is 21 picogram per mil for whether a patient has Alzheimer's disease in addition to DLB and identify the pure DLB population.

On here, there is a 0.7 point improvement in CDR Sum of Boxes, which is greater than the 0.5 considered clinically meaningful with that lower blood concentration level Batch A of capsules in the placebo control period. 45, 46, 48 number of patients gets you to a P value of 0.054, which is consistent with this is actually the magnitude effect we were looking for in the study to begin with. We were powered for a significant effect with 80 patients per arm. We come up there, but there's a clear signal. More importantly, perhaps, there is a significant effect if you look at the upper half, that in terms of blood concentrations and above the median, there's flat.

Again, the drug effect that we were looking for all in the placebo control period goes to then you should really be looking at then at higher blood concentrations, and that's when then the Batch B results all makes sense. Indeed, when you have higher blood concentration, higher drug effect. This is then in the end, what one I'm sorry. Let me go back. Should on the right-hand side effect in our Phase III trial, lowest cutoff level with Batch B blood concentrations, flat in terms of drug effect, and a big difference to placebo, more than a one-point improvement. Again, all data that we presented more recently and puts the whole story together. Batch A does work, lower blood concentrations, but you do even better when you go to the Batch B.

This is then showing you what the full potential of the drug is in dementia with Lewy bodies. Then the other one, which is, again, I would say that people haven't fully caught up to is really what is, in my mind, really very remarkable data in terms of MRI within the study, the Phase IIb study. On the left-hand side, this was only a sub-study. Only patients in the U.K. and the Netherlands received MRIs in the study. So it's a small number, but it's very compelling data. Neflamapimod, this is placebo control period. Eight patients +3.5%, actually a small increase in the volume. The more, the better. You actually have a clear structural effect, while placebo goes down as it does in every clinical trial or longitudinal study in dementia with Lewy.

It's this progressive loss of volume in the basal forebrain that is the disease of pure dementia with Lewy bodies. With 16 weeks of treatment, you get full stabilization, if not a slight improvement. Significant P value with only 18 patients because of the magnitude of the drug effect. Then that's further supported, and I think it becomes even more interesting. Those placebo patients who are going down here, and you can see them here, here. When they go onto neflamapimod at week 16, when they go into the extension, they actually turn. Stabilization, stabilization, and these three actually improve. Really direct pharmacology and biology in terms of the drug effect. Then it is where all of this data that I just talked about is actually what we put into what's called the ILAP process, Innovative Licensing and Access Pathway.

This is the first time, in particular, the placebo-controlled data with Batch A, that a regulatory agency has seen that data because we didn't have that analysis until very recently. We submitted that in April, and it's part of the reason why, in my view, why we received that designation, which is a regulatory agency validation of the data that we have in DLB to this point. I'm going to stop there. I know that was probably a little bit longer than you wanted me to go, and I apologize for that. It really has been a terrific first half of the year. Everything has come together very nicely. The last point maybe to make is, this was in our announcement yesterday. Maybe go back to I'll actually just go to here. Finish with this one. This is just the overall DLB.

I think we have a very uniquely positioned drug in a major disease indication. I would ask you to. All around this is about there is history to this company. I know many of you followed it. We've had our ups and downs. I acknowledge it. The ask is look at us now with what all the data that's come together. I think it's a very compelling story in DLB. What is also added to that is the non-fluent variant primary progressive aphasia. 15,000 patients in the U.S. Significant rare neurologic disorder. It's a subtype of frontotemporal dementia. It is what Bruce Willis and Wendy Williams have. Bad disease. No treatments available. We have great scientific rationale. Validation of that. Despite the numbers, we actually over-enrolled and enrolled much more rapidly than we thought.