CervoMed Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Very good. Thank you to everyone for either being here or listening in. I'm John Alam. I'm the CEO at CervoMed. My background is in R&D in various companies over the last few years. I'm a physician by background. I was at Biogen most of the '90s as a lead physician for AVONEX, their first drug in multiple sclerosis. 11 years at Vertex Pharmaceuticals as head of clinical and then chief medical officer. 4 years at Sanofi, based in France, heading an R&D group in disease of aging, but in particular all their CNS activities. Alzheimer's, Parkinson's, Stroke were in that group. For the last decade, a little bit more, building out the clinical program that we'll be talking about around neflamapimod, originally in the early days in Alzheimer's disease, but really focused now in dementia with Lewy bodies.

Originally a private company that 3 years ago, we merged in with a public company and renamed ourselves as CervoMed, CRVO. Neflamapimod with DLB is very much the leader in developing a specific therapy in dementia with Lewy bodies. We're the only ones with positive phase II data, which I know we will be talking about. We have an agreed upon, with multiple regulatory authorities, both FDA and global regulatory authorities, clear registration path on a phase III program that would support approval, again, as a first drug that would be a specific treatment for dementia with Lewy bodies. We have, over the last year or so, also expanded the program into additional indications, in particular in non-fluent primary progressive aphasia, which is a subtype of frontotemporal dementia.

We are, again, at the forefront in developing a therapy there that's very good science, which I hope we can touch on a little bit as well. Very excited by how that we have a phase IIa trial that has progressed actually much more quickly than we had originally thought. We will be presenting the first data out of that study in October of this year at an international FTD meeting. Another milestone that is really quite near-term is that we will be working with a U.K. academic group, starting a study in ALS, amyotrophic lateral sclerosis, near the end of this year. Again, like PPA, primary progressive aphasia, really very good science. We're targeting very specific molecular mechanisms associated with ALS, which is the reason why that group had approached us. We're excited by that as well.

But mostly, we will be talking about dementia with Lewy bodies, which is, I think you all know, is a big disease. It is a bad disease. There is a lot of medical need there. Our drug and mechanism is really very specific now, targeted therapy targeting, again, the specific neuroinflammation pathways that we today know are what drives and what is dementia with Lewy bodies from a pathogenesis standpoint.

Lewy bodies is the pathology that you see under the microscope associated with the clinical syndrome of dementia with Lewy bodies. But it is, I think, the easiest way to think about it is what amyloid plaque and tau and neurofibrillary tangles, which you all know about, I think, for Alzheimer's disease. For dementia with Lewy bodies, that is the pathology that you see is the Lewy bodies. It is made up of a protein called alpha-synuclein. Which is, again, as much as amyloid beta is to Alzheimer's disease, alpha-synuclein you can think about in dementia with Lewy bodies. Lewy bodies and alpha-synuclein are the same pathology in Parkinson's disease, but it happens in a different part of the brain.

The pathology that with DLB and Lewy bodies, what matters is in the upper parts of the cortex and what it does in terms of a very specific part of the brain called the basal forebrain cholinergic system, or the cholinergic neurons of Parkinson's, is in dopaminergic neurons. So that is pathology. Clinically, again, it is very specific. It is a dementia, so the primary symptom is major cognitive decline that affects day-to-day living.

It is different than Alzheimer's because in its purest form, it is not memory, it is executive function, judgment, reasoning, and attention. Then there are some very specific associated symptoms. Fluctuations, hallucinations, sleep disorder, Parkinsonism, some of the symptoms of Parkinson's disease that go along with it. It is a constellation of symptoms that makes it substantively more impactful on day-to-day living, quality of life, and caregiver burden than Alzheimer's disease if you match to a given stage. It also moves clinically faster than does DLB, which is, on one level, of course, all of that is terrible for patients. From a drug development standpoint, there are actually some, especially clinical development, which is where I have been, you actually get more clinical signal to work against on the trials. It is the reason why For DLB, you are talking about for DLB.

Okay. Which is what allows you to do as we are doing.

You can pick up efficacy signals, you can demonstrate clinical activity in 3 to 6-month trials, and you can go, as we are, in a phase III trial and potentially get approval with a 32-week study rather than what you hear about in Alzheimer's disease of 18 months, maybe longer. It also substantially decreases the size of the clinical trials that you need to do to get definitive evidence of clinical efficacy.

What I said in terms of the symptoms, et cetera, again, is patients who have pure dementia with Lewy bodies, that they have dementia with Lewy bodies, but they do not have Alzheimer's disease and the Alzheimer's disease pathology on top of it. That represents about half the patients who would carry, who would eventually, you would say, have dementia with Lewy bodies at autopsy. Those are the people who have the specific symptoms that I talked about.

Less memory deficit. From a drug development standpoint, what is critical about that is those patients have fundamentally less neuronal loss and neurodegeneration than Alzheimer's disease patients or patients who have DLB with Alzheimer's disease pathology. Their disease is more one of a functional deficit. The nerve cells in that part of the brain, the basal forebrain, they are sick. They are not dead. Other parts of the brain and perhaps more importantly, they also have less neuronal lesson damage. In particular in the hippocampus, that is a memory part of the brain where the disease is in Alzheimer's disease. An Alzheimer's disease patient inherently will have significant neuronal death and loss in that part of the brain. It is a more advanced disease form. If you have DLB plus AD, you have more neurodegeneration, fixed deficit, tougher nut to crack.