Cognition Therapeutics, led by CEO Lisa Ricciardi, is on a mission to change the course of neurodegenerative diseases. With a focus on Alzheimer’s disease and Dementia with Lewy bodies (DLB), the company is working to help patients maintain healthier lives longer while easing the burden on caregivers. Ricciardi underscores the urgency of this work, pointing to the scale of Alzheimer’s and the severe underdiagnosis and lack of investment in DLB, which leaves patients with few meaningful treatment options.
At the center of Cognition’s approach is zervimesine, an investigational, once-daily, oral therapy designed to target toxic oligomers at the synapse before irreversible neuronal loss occurs. Unlike more complex treatment regimens, this ORAL approach aims for simplicity, scalability and earlier intervention. In clinical studies, zervimesine demonstrated the ability to significantly slow disease progression in Alzheimer’s disease and deliver substantial reductions in neuropsychiatric symptoms in patients with DLB, including particularly strong effects in psychosis, known delusions and hallucinations.
Ricciardi also discusses Cognition’s close collaboration with the FDA and the importance of generating real-world evidence to support how therapies are ultimately used in practice. For patients and caregivers facing devastating, fast-moving diseases with few approved options—particularly in DLB—Cognition’s work represents a meaningful step toward slowing progression and preserving quality of life.
Irena Luo:
Hi, I'm Irena Luo, conference producer at Fierce, and I'm sitting down today with Lisa Ricciardi, president and CEO of Cognition Therapeutics. Cognition Therapeutics is a clinical stage neuroscience company working in the area of neurogenerative diseases. Lisa, can you share more on Cognition's mission and why does it matters now?
Lisa Ricciardi:
Yeah, thank you. Thanks for having me. I'm delighted to talk about the work we do at Cognition, Irena. I would say the words are easy and the task is very big. Our mission is simple. What we think about is for patients with Alzheimer's disease and Lewy body dementia, maintaining their lives as healthy as possible longer, and relieving the burden on the caregivers, these are really difficult conditions.
So I like to think of it as changing the course of health where we can and relieving the burden of illness in these very important neurodegenerative conditions. If I may, Alzheimer's is enormous, right? Everyone knows people with Alzheimer's at six million patients. It will grow to 30. DLB, not so much. It's a smaller condition. All the resources to date have gone into Alzheimer's disease, and while there've been lots of trial failures, there's a great deal of science to be learned on the AD side.
When we think about Lewy body dementia, we think about, I call it a do loop, not studied, not recognized, not invested in. You go all the round, all over again. Doctors have nothing to treat, so they don't typically identify the patients. The patients don't know to ask for what they need. It's just a very, very challenging condition as well as a situation for the patients and developers like us, for investors. So we are quite focused on DLB.
We have an Alzheimer's trial running. Our focus right now is on Lewy body dementia. And if I may, I'd like to just characterize it a little. We found that most people don't understand what the disease is. There's five buckets, maybe more, of symptoms. The first is, of course, dementia and cognition, as the name implies. Neuropsychiatric problems are huge for patients with DLB.
In our trial, we measured 12 of them. Depression, anxiety, agitation, hallucinations, REM sleep disorders. I used to be able to name all of them and I can't. They're very, very disturbing for the patient. And in fact, the reason patients often get taken out of their homes to institutional settings is because of psychosis, which is hallucinations and delusions. The other conditions are fluctuations. I have heard patients say, "Lisa, I keep a walker by my bed because when I wake up in the morning, I don't know whether I'll have the wherewithal to walk properly or need a walker."
And the cognitive fluctuations, I have heard spouses say, "I took my husband to the doctor and boy, he was totally on and articulate." And the doctor's like, "There's no problem here." And meanwhile, the caregiver's ready to strangle that person because she experiences them much more in that fluctuating situation. These patients fall a lot. It's a Parkinsonian condition, so they're in the ER. And this disease, in fact, is more expensive to treat than Alzheimer's disease, if you can believe it.
And the last thing I'd say is what these patients go through to get diagnosed. If you boil down the experience of everyone, a year and a half, three different specialists, seven doctor's appointments. I was just with patients two weeks ago at a conference. They were talking about months to get to the first doctor and months to get to the first test. There aren't enough neurologists to go around. So back to our mission and why we think it matters, big patient population, big burden for everybody and no drugs here at all.
Irena Luo:
I can imagine DLB being extremely underdiagnosed due to the similarities it has with the psychiatric symptoms that you mentioned with hallucination, with Parkinson being more of the movement symptoms that we see in DLB patients. We know there's no cure for DLB or Alzheimer's. Can you share your science and approach and why it's so unique?
Lisa Ricciardi:
What we're aiming to do with our therapy, it's called Zervimesine. And the goal of using this treatment is to get to the synapses before there's irreversible neuronal loss. So here's how I like to think about it. You have toxic oligomers in your brain. You may say, "What's an oligomer?" I go back to when our kids were building snowmen and you roll up a smaller and a larger and a larger snowball, right? Monomers, dimers, trimers. These toxic oligomers aggregate.
And here's the thing, these oligomers are not visible. Plaque is visible. The toxic damage comes when these oligomers sit in a synapse pocket and kill off the neurons. And so our goal is to prevent the binding in the synapse and therefore not harm the neurons, if you will. The oligomers that are bound are released and cleared through the cerebral spinal fluid. So we believe it's a very elegant solution to a problem and it allows us to get in as early as possible for these patients.
Another really important thing about our therapy is we have an oral once a day drug. So there are two monoclonals for Alzheimer's disease, which is a huge accomplishment. These patients need imaging, they need diagnostic imaging, they go to infusion centers, they need surveillance for ARIA. And if you think about that, you will hear people talk about, "Wow, there is an access for everyone." That's true. How can people adhere to therapy when it's that complicated? And that's true. And some people move to, "Well, that's not public health equity."
No one is aiming to leave people out of a good healthcare solution, but the infrastructure isn't there. And I tell investors all the time, can you imagine an oral once a day drug? It can be distributed to any market in the world and people can take it. I honestly tell our team sometimes, "Irena, we could change the world." Can you imagine having a treatment that was simple, can be scaled up and distributed?
And for Lewy body dementia patients, they have exactly nothing for treatment. Drugs are borrowed for their symptoms from other conditions, and often these drugs make their symptoms worse or they're contraindicated. So if you want to put your effort into something important and hard, come join us. This is it.
Irena Luo:
No, I love that. I think as you mentioned, the only available treatment is really the management of those symptoms with the DLB. So it's not even attacking the disease itself. It's just how can we help these patients really maintain their daily living without being in pain and even helping the caregivers as well. And accessibility, I think that's a huge thing when it comes to medication adherence. Once daily, that's such an easy thing for caregivers to be able to do for their loved ones. You shared a lot about the unique mechanism of action of Zervimesine. What is the potential for this treatment and how can it really compliment the other existing treatments?
Lisa Ricciardi:
Great question. So I'll start with Alzheimer's disease because that trial read out first. We refer to this as our SHINE trial. And when this read out in July of '24, what we saw is that we slowed the progression of disease. That's what we're measuring, slowing damage. No one is becoming a chess player, right? We're not adding capabilities here. And the monoclonals were 25, 35% reduction in progression, and we were more like 35, 38.
We also treated a sicker group of patients, mild to moderate, not early stage. The great thing was, Irena, we had pre-planned an analysis of patients that had a lower level of pTau. I'll just explain. Everybody with Alzheimer's disease has elevated pTau. So if you take zero to 100 in the trial, we took the 50 and below. These patients had a 95% slowing of the progression of disease. And again, I always say to investors, "Can you imagine if you could take the person you love and you're worried about and freeze them?"
The trial was only six months long, but for six months, they don't get worse. They can maintain their quality of life, interact with their families, et cetera, et cetera. So in our next AD trial, which we haven't determined when that'll start, we're going to pre-screen for those patients who appear to benefit the most. Now, on the Lewy body dementia side, wow, we had phenomenal results in a trial called SHIMMER.
Looking at those neuropsych symptoms, as I said, there were 12 of them. The best results were in psychosis, but overall agitation, depression, et cetera, 86% reduction in symptoms. So again, when you look at the data, you go, "Gosh, on the day these people started and the day the trial was over, their disease barely progressed in this manner." On CDR, looking at memory and cognition, 85% slowing of disease fluctuations. This really bothers the patients.
When they wake up and they just don't know how they're going to be able to comport themselves through their day, 91% reduction in the progression of disease. Also, movement disorders, activities of daily living. Can you get up and bathe and dress and leave your house and come home? Every category we studied for these patients showed an important from smaller to larger positive results. And by positive results, again, I mean slowing of the progression. No one's curing this disease or turning it around. So we are extremely happy with that.
I will tell you, we have another trial running right now. It's called START. 550 patients funded by a grant of over $80 million. And these are early mild cognitive impairment, early patients. We're following them for 18 months. And so we'll have data just about a year from now. The last patient will finish and a couple months later we'll have data. So that's a pretty big deal for us and frankly for the industry. And one other trial that's running is our EAP, Expanded Access Program. I'll touch on that in a moment.
To answer your question directly about use, so far what we've seen is a drug that can be safely used once a day. It's oral. With regard to concomitant use, in our START trial, the big one, 550 patients, the decision makers who run our trial all agreed, we need standard of care. Well, Biogen got approved, Kisunla got approved, Leqembi got approved. And so the decision was made, let patients on the monoclonal antibodies come into our trial. And so about 20% of our patients have concomitant therapy.
And what I think about, Irena, is when we launch this drug, doctors will have real world evidence, "How do I use these drugs in combination?" I think that's such a plus for the prescribing community and for the patient community. So we're optimistic about the profile of the drug and how we think it will be used on top of with existing treatments.
Irena Luo:
Yeah. I think you hit on that and that idea that any way that we could slow the progression of this disease can make huge impact in not just the individual and the patient, but also in the families who are caring for their loved ones and seeing the disease. It's a heartbreaking disease because you see it and you don't know when it's going to happen sometimes because some days are good and some days they're not.
Lisa Ricciardi:
Exactly right. I will tell you, Lewy body patients tend to progress a lot faster, four to seven years from diagnosis till they pass away. Alzheimer's disease, I don't know if this is good or bad, 10 to 15 years. We're taking huge averages here, but the Lewy body patients, to your point, you don't know from day to day. All you know is it's moving fast.
Irena Luo:
So you share a lot of the results. Can you share more about the progress that you have made clinically?
Lisa Ricciardi:
We have completed our proof of concept studies in both Alzheimer's disease and in Lewy body dementia. Those were both in mild to moderate patients. The START trial is early Alzheimer's, and we sort of look at that and go, "My God, if it hits early, mild, moderate," that's going to answer a lot of questions. The SHIMMER trial has been completed and a patient from the Shimmer trial came to me and said, "Gosh, I really want my spouse to stay on this. Can I give you money?" Because we didn't have enough money to do it.
And so we've created an expanded access program. So that gives us additional safety data. Patients who wish to stay on longer have been able to stay on longer. And this comes from patients experience, and we have other people wanting to provide economic support to us to run those programs. It's very expensive. So that's our progress.
For us, the next steps involve the FDA. We went to the FDA at the end of the summer to talk about Alzheimer's disease and found them to be so collaborative and helpful. We had a conversation. We said we're going to have 100 milligram dose, these kind of endpoints. The patients with low pTau will target enrollment. It was phenomenal. As a small company, we said, "Okay, we have the roadmap for Alzheimer's disease. What about Lewy body dementia?" Applied for another meeting, sat down in January.
And once again, I give a lot of credit to the agency. I like to think of it as engagement, collaboration, and a roadmap. Same division we worked with for years. And when we talked to them, they said, "Your strongest data is in psychosis. You as a management team should go over here to the Division of Psychiatry within the FDA and get them to look at your program for behavioral psychiatric drugs." And so now we will be sitting down with that group to look at what do we study to have a registrational program in DLB?
Then we'll share that information with our advisors, opinion leaders, families, investors. We will, of course, be able to say, "We need this many patients for this period of time." We feel like this is a really important set of conversations coming up right now. So we've had a lot of clinical progress and we've made the decision where we want to go in the clinic, and that is with DLB.
And we think our partnership with the FDA has been an underpinned for why we've made so much progress. They get a real bad rap in the press all the time. And all I can say is these are incredibly hardworking people, and you know what? They want success for these patients just as much as we do.
Irena Luo:
Yeah. With the leading neurodegenerative disease being Alzheimer's, and second to that is dementia with Lewy body. We need more resources to pour into that in order to bring these treatments for these patients. So adding to what you just shared with the strong results from SHIMMER in advancing in DLB, what could this treatment really mean to patients and caregivers?
Lisa Ricciardi:
We have in our conference room a big poster, and it says on there, "We are the beginning of the end of neurodegenerative diseases." Now, when you're small like us, you got a punch above your weight, that's a great thing to think about. Could we be that for these patients? Could there finally be a drug to treat Lewy body dementia and eventually Alzheimer's disease? That is what we aspire to, to eradicate the understudied, underrecognized, undertreated condition and to take our science, which built on all the science that came before us through the clinic and provide that to patients. Patients want better options. We think we could be a linchpin of that for them.
Irena Luo:
Absolutely. And I think if anything else, there's that hope that you're providing for these patients with 30 million plus people worldwide who has Alzheimer's. And even more for those who are underdiagnosed or misdiagnosed, Cognition Therapeutics is really trying to help provide that treatment for the patient's individuals and the caregivers as well.
Lisa Ricciardi:
Yeah. Your focus on the caregivers is particularly noteworthy. It's absolutely critical. It is the most burdensome job. The person with Alzheimer's disease isn't necessarily aware of ... There's everything, right? That's the problem with the condition. Those around them are very aware, and it's extremely hard and DLB is worse yet. So you're right, part of these treatments change the burden for the caregiver, and we hope to be a part of that, to lead the way, in fact, for DLB.
Irena Luo:
I love that. Well, thank you so much, Lisa, for joining and having this conversation with me. I look forward to seeing more from Cognition Therapeutics and the work that you're doing in neurodegenerative diseases.
Lisa Ricciardi:
Thank you. I really appreciate the chance to speak with you. Thank you, Irena.