Gregg Masters 00:08
This is PopHealth Week on health care now Radio. I’m Gregg Masters Managing Director of Health Innovation Media and the executive producer and co-host of the show. Joining me in the virtual studio is co-founder and principal co-host Fred Goldstein, president of Accountable Health LLC. Connect with us via www. popupstudio.productions or direct message me on Twitter @GreggMastersMPH and that’s Gregg with two G’s. On today’s show. Our guest is Dr. Sean Gregory, Vice President Health Economics and market access for Cognito therapeutics, a company developing a novel device-based approach to treating Alzheimer’s disease. According to their website Cognito Therapeutics. the investigational medical device delivers non-invasive neuromodulation with the potential to improve outcomes in a range of neurodegenerative diseases including Alzheimer’s disease and is personalized based on individual brain responses. Do follow their work at Cognito therapeutics via www.Cognitotx.com. And on Twitter via @CognitoTX and with that introduction, Fred, over to you.
Fred Goldstein 01:28
Thanks so much, Gregg and Sean, welcome to PopHealth Week.
Sean Gregory 01:31
Great to be here, Fred. Thanks.
Fred Goldstein 01:33
Yeah, it’s a pleasure to have you interesting area we’re going to discuss today a little bit of digital therapeutics, etc. So why don’t you start by giving our audience a sense of your background and the company?
Sean Gregory 01:42
Sure. Delighted to be here with you, Fred, Sean Gregory, Vice President of Health, Econ, and Market Access for Cognito therapeutics. Here at Cognito Therapeutics, we’re a phase three clinical medical device company focused on a novel neuromodulation mechanism for the treatment of Alzheimer’s disease, and potentially mild cognitive impairment, which is a little upstream in the etiology for Alzheimer’s disease.
Fred Goldstein 02:10
So Alzheimer’s is obviously a big issue. How large is that problem in the United States, now?
Sean Gregory 02:15
We know Fred, there’s about 6 million prevalent cases by the latest CDC standards. And the real interesting component is as aging population increases, that’s that figures supposed to go to about 8.6 million by 2030. So we’ve still got a pretty steep rise in the incident cases. And are we coming on board here over the next decade?
Fred Goldstein 02:38
I know, you know, I know, in our family, I know of some individuals, friends, relatives, etc, who are living with Alzheimer’s, really difficult situation for them and their families, obviously a huge impact on people. So as you’re looking at this from a digital therapeutics approach, what sort of are you focusing on and what does the product do?
Sean Gregory 02:57
Well, we have a novel mechanism, mechanism of action that’s focused on neuromodulation. And specifically, we have some observed technology observed research in the gamma frequency modulation space. And what we’ve observed in particularly in cognition among individuals with Alzheimer’s disease is a lack of or a lower rate of 40 hertz gamma stimulation across the hippocampus where we know much of the cognition action happens. And so we have a novel therapeutic. And that the form factor is a wraparound set of sunglasses, inside of which have 30 hertz, excuse me, 40 hertz, LEDs, and a wraparound earphones, during which we have an auditory stimulation of 40 hertz as well. And by being exposed to that an hour a day, we’ve been able to demonstrate some disease-modifying effects for Alzheimer’s patients mild to moderate Alzheimer’s patients in our phase two data, and are about ready to go with our first patient in for our phase three study for mild to moderate Alzheimer’s,
Fred Goldstein 04:09
and when So what sort of improvements do you have you seen in the studies?
Sean Gregory 04:13
Well, it’s this is where it gets really exciting. We’ve got sort of three buckets, if you will, of outcomes that we’ve been looking at our primary endpoints are around cognition. But we also have included IADLs or activities of daily living to really understand the day-to-day improvements and functionality that might be resulting. And then there’s some very specific neuroanatomy results, as well as some specific results on sleep as a particular symptom of also have mild to moderate Alzheimer’s. And so we’re trying to do is have primary endpoints that are meaningful, scientifically to gain approval, the FDA, but then also the types of endpoints that can kind of contextualize for payers as well as patients and fuzzy missions? What are the what are the meaningful outcomes of this therapeutic?
Fred Goldstein 05:05
And so when you talk about some of those outcomes and changes, I assume that the changes, you’re seeing changes in the anatomy you talked about of the brain. So they’re actually changes that can be measured in an individual’s brain who’s undergone this approach?
Sean Gregory 05:20
Yeah, absolutely. And this is where we’ve had some exciting results that were just announced a couple of weeks back at AIC, in San Diego, we’ve been able to demonstrate that we are preservation of brain volume, whole brain volume, and particularly white matter, again, in the hippocampus, where we know the cognition action is happening. And if you if just to sort of put it in perspective, a normal aging adult over 65, loses about a half a percent of brain volume a year, and Alzheimer’s patient would lose about two and a half percent. And in this phase two data we see, after the use of the device on device for 12 months, we see these amount of moderate Alzheimer’s patients losing about point 6% of blank brain volume, so just a little more than average aging, but certainly not the two and a half percent that you’d see in an Alzheimer’s patient based on today’s therapies.
Fred Goldstein 06:20
And then that’s associated with I would assume differences in cognitive cognition testing or of their functioning.
Sean Gregory 06:26
Yes, absolutely. And that gets back to the primary endpoints where you’re testing for cognition using a variety of instruments MMSE, or MOCA in some cases, and then using the IADLs, which actually are abroad, well used in new neurodegenerative disease, activities of daily living that talk about and rate, if you will, or scale for individuals, their ability to attend to those activities of daily living that are that are meaningful to them. And I think it really helps contextualize the benefit for patients. And then there’s some very specific things that I mentioned, like sleep improvement, we’ve got actigraphy built into our studies, and we’re looking at really market improvements in sleep, which we know have lots of downstream effects on not just cognition, but you know, mood and irritability and nutrition, etc.
Fred Goldstein 07:22
Right, some of our audience is not quite as exposed to some of these terms, et cetera, you know, we’ve obviously got a population health focus group, and you’re very sure, neurologically and science or you define some of the terms like MOCA, et cetera.
Sean Gregory 07:33
Sure, there’s a variety of neuropsychological batteries that rate cognition or decline in cognition for individuals. And in fact, Fred, we had talked recently about the Mini-Cog Assessment, which is a brief assessment that’s part of the annual Medicare exam for individuals on Medicare, which speaking of population health is is almost like a broad-based population health screening. In fact, individuals over 65 and on Medicare, get that screening every year. And I think there’s some data that shows that maybe less than one in five, receive that assessment. And that’s really the first potential screening to indicate problems with cognition that might lead to mild cognitive impairment, any kind of dementia, and then Alzheimer’s as a special case of dementia. And as you move along from normal screening to more disease-specific measures, there are a variety of neuro-psych measures in a normal workup, neurological workup or neurological battery that help measure changes in cognition and then isolate those changes to very specific components of cognition like this is a motor issue, or this is an executive functioning issue. This is more attuned to decision-making. And so that helps a clinician be able to make a diagnosis. But then as we tried to apply a treatment, allows us to basically measure if you will, and I think of it kind of as the equivalent of going to get a lipid panel after you’ve initiated a statin therapy, you know, what is your LDL going to be over time, and many of these measures of the way that we would look for kind of measurement based care outcomes for neurologic disease.
Fred Goldstein 09:24
And you talked about this being specifically for people with mild to moderate cognitive impairment. And so that tells me that as I’m not I’m not a physician, but as a as a physician, or if you’re in a population health program, you want to identify those individuals as early as possible. So I assume the way to do that is to ensure that the primary care doctor or the internal medicine physician, or whoever’s doing that annual wellness visit is actually doing that Mini-Cog, and and taking that data versus having to go see a neurologist, as a way to get the identification.
Sean Gregory 09:57
Certainly, I mean, I think we’re very advantaged. Certainly in over 65, Medicare beneficiaries to have population-based screening and so how do we raise the awareness and you wonder if something like cognition becomes a new vital sign or so or at least something that is maybe elevated a little on the radar, they’re gonna there’s a more, there’s probably more density of individuals entering that morbidity as we have an aging population and with so how do we kind of elevate the public health messaging there? So I think that that’s really important. And it absolutely is an intervene early type of strategy.
Fred Goldstein 10:35
And is this? Is this something where based on the data, I haven’t looked at it, that we’re possibly missing people and identifying them late?
Sean Gregory 10:43
I think so. And I think that the if you look at kind of the profiles of sort of severity upon presentation or severity upon diagnosis, we do tend to see folks being diagnosed later in disease. And I think that that is, I mean, if you really start to think about it from this public health perspective, how would you set that up, if you’re going to try to intervene earlier in the etiology try to figure out, I think, where the most sort of effective screening intercepts might be. And I think that raising the awareness of this, at a primary care level would probably be important. There’s probably not enough neurologists to do all the screening we would need. So having the primary care opportunity, I think, would be key.
Fred Goldstein 11:28
And you may not have this information, but I would assume just based on everything else, we know that we see disparities in terms of this issue as well amongst people of color and, and other groups.
Sean Gregory 11:43
Certainly, and I might think of it as you know, on on two dimensions there, there are some interesting genetic predispositions. We know concentrations of individuals, let’s say carry the APoE 4 genetic variant. There is an early onset cohort among Latina populations and culture, it’s known as the Columbian cohort. But I think there’s also the vector of social determinants of health, that have that show up in terms of these disparities. So we know that there’s a kind of a rural-urban break, particularly in outcomes, post-diagnosis, and might have some access to care issues associated with it. And certainly, there are some communities of color that have some over representations of disease and and I think, would follow kind of the same disparities you might see in other kind of broad-based disease screening programs.
Fred Goldstein 12:47
So I would assume as you move into phase three trials, and this, you look for as broad a population as you can get to demonstrate efficacy.
Sean Gregory 12:55
Absolutely. And we’ll have two phase three events going on. One is our Hope trial, and that is for mild to moderate Alzheimer’s, that’s our large trial that follows on our Overture, which was our phase two trial. That will be a large, multicenter trial. And I think it does have the geographic, but also the ethnicity variation that we will be looking for to try to make sure it’s it’s, it has the proper representation. And that’s, that’s the kind of the fun and the advantage of having a multi-site type of design. We’ll also have a phase three in mild cognitive impairment, which will have a little bit more of a real-world design. And both both of these have been announced previously, but what we’re excited about doing this on the heels of mild to moderate Alzheimer’s set of results to be able to show again, kind of earlier in the etiology, an indication for a mild cognitive impairment as well.
Fred Goldstein 13:58
Well, it’s you know, it’s fascinating, you raised that I just read a, I didn’t read the study yet, but I’ve seen the abstract on it regarding a study of cognitive impairment later in life associated with the experience of racism.
Sean Gregory 14:11
Interesting,
Fred Goldstein 14:12
which would just be fascinating to see,
Sean Gregory 14:14
sure
Fred Goldstein 14:14
obviously, a major, major issue, but something that perhaps has some relevance here as well.
Sean Gregory 14:21
Sure. I mean, I think that we there’s there’s some interesting evidence in behavioral health that the sort of long-term exposure to traumatic events like one your suggesting there would have some real impacts on not just personality, but certainly cognition and just kind of general outlooks. I imagine there’d be some interesting data there. I’ve not seen anything in that space either. But there’s, this is the kind of fascinating time for neuromodulation as a modality, but also kind of neuroscience in general, where we’re bringing some of these really amazing translations. You know, hopefully To market, certainly to trial and hopefully to market. And that’s sort of the, you know, how our trajectory as a company has been, which is really exciting to see.
Fred Goldstein 15:10
And where did this technology come from?
Sean Gregory 15:12
Well actually six years ago out license from the MIT labs of doctors Ed Boyden and Li-Huei Tsai, brilliant neuroscientists still at MIT. And they were able to come to an agreement to license on their existing and future IP to actually create a real-world trial here and in real-world translation, which is really exciting.
Fred Goldstein 15:42
So what got you excited to get into this area? Or what made you go into this area?
Sean Gregory 15:47
Well, I had, I was in the payer business, and then went to academic medicine for about a decade. And then was, came back to the payer world, to try to think specifically about how to do translation of behavioral health therapeutics, and really to kind of lift the evidence base application of behavioral health. And it has a lot to do with the work I did academically when we were looking at the cost and comparative effectiveness of different behavioral health treatments. And there’s a wide variety of effectiveness, and I guess, a wide variety of cost-effectiveness there. So I guess you’d say there’s lots of heterogeneity and outcome. And I thought it was a really interesting area to focus on. And coming back to the payer space, it was specifically around looking at how to integrate behavioral health into physical medicine and what opportunities there were. And then to get maybe a little bit more narrow, I got introduced to the neuro-modulation modality of treatment and look at looked at that in OCD and depression in some other areas, and just really became enamored with it as a modality. With it has a relatively clean safety profile. It doesn’t have some of the side effects that you see in behavioral health medicine. And it just really appealed to me as certainly potentially a first-line therapy. And then to get to see an application of it like Cognito, that’s focused on not the easiest of diagnoses, but really starting to say, can we solve something really hard with neuromodulation? And then if so, can you cascade down to sort of adjacent or less severe morbidity and I just thought that’s like an amazing moment, to be in neurology and behavioral health and to be in and around this this modality, we’ve got a great team, and I’m really happy to be to be an early part of it.
Gregg Masters 17:45
And if you’re just tuning in, you’re listening to PopHealth Week on health care now radio, our guest is Dr. Sean Gregory, Vice President Health Economics and Market Access for Cognito Therapeutics, a company developing a novel device-based approach to treating Alzheimer’s disease.
Fred Goldstein 18:04
You touched on another issue, and obviously worked with payers. You mentioned already this will have to get FDA approved, should it get through the studies, etc. But there’s been some real hesitancy among payers to pay for digital therapeutics. There are a few FDA approved, not many, I think we’ve discussed some of them on the show. And so how do you plan to try to overcome that? Or how should others in the digital therapeutic space look at that and say, Wait a second?
Sean Gregory 18:32
Yeah, I think there’s I think it’s a really interesting moment. I mean, just to be to be specific, we are taking a medical device through the FDA. And that’s our chosen strategy. And so the the reason why I mentioned that is the device, the you know, the health effect, or the health claim for the device will be based solely on the treatment that the device delivers, and not associated with any digital therapeutic or kind of software around it. And so I think in today’s regulatory environment, you first have to make a decision if you’re a device or if you’re a digital therapeutic, and then within that maybe are your prescription digital therapeutic. But I think therein lies a lot of kind of the heart of the matter. And right now the Digital Therapeutics Alliance, trade industry group, led by Andy Molnar, has some draft legislation that they’re trying to move through the house to authorize CMS or allow CMS to pay for digital therapeutics and I think that that probably is what it would be able to take at a broad base level, to be able to have CMS be able to look at these digital therapeutics and just like they do devices and certainly a little bit similar to how they look at pharmaceutical. So I think that that’s important, but you know, when I put my payer hat back on and reflect on the last several years looking at, you know, 50, 60, 70 different types of digital therapeutic and innovations. I think the reluctance on the payers has a lot to do with what kind of science and what kind of data does the digital therapeutic manufacturer, if you will show up with. And I think that that’s the challenge that we’re trying to overcome. Here, as we introduce a new modality, we feel it even a bigger burden to show up with the right kind of parameters that can help that payor make the decision earlier or together with us, as opposed to just showing up and telling them how great our devices without being able to contextualize this is the episode or this is the value-based arrangement that might make sense. And I think that that’s what is just very tough to do in the in the pure digital therapeutic space, unless you have a pretty well designed clinical trial where you can show that at least really good effectiveness, if not some efficacy. I think that’s what it that’s really what it’s going to take to kind of get get over this kind of that threshold to even get evaluated at scale.
Fred Goldstein 21:02
Let me ask you, Sean, was I incorrect in saying this was actually digital therapeutic? Because it’s actually a product, it would look be looked at much more like, say, an implant device or something like that?
Sean Gregory 21:12
Yeah, exactly. Right. So in the way we’re going through the FDA is is narrowly around the device, I think that you could absolutely see the device situated in maybe a care management program that had some care management level, app or digital type of experience. But I think that’s, you know, narrowly today, in order to be covered by CMS, we would have to be a device that operates independent of a digital therapeutic. And so today, if you were to see digital therapeutics being used by payers, you know, they’re they’re deciding to pay for it. above what, you know, what might maybe CMS would pay, let’s say, or Medicare Advantage by paying.
Fred Goldstein 21:59
And earlier on, you also mentioned, one of the big issues you have with obviously, medications and things like that, or even implants, you’re always looking for side effects or poor outcomes, etc. What sort of experiences have you seen in the study so far?
Sean Gregory 22:14
I mean, this is one of the most remarkable things that really excited me about the about the opportunity here. And that is, you know, in over 40,000 sessions, we’ve had no adverse events, no reportable adverse events to the FDA, and and we’re FDA breakthrough designated at the moment, we just had some safety data that I think is being reported at a conference coming up soon, we do have some side effects, people tend to have, let’s say, some dry eyes, you know, a lot of people that are photosensitive, or just having that kind of light stimulation for an hour, might report some dry eyes, sometimes there’s a little bit of dizziness for a few minutes, there could be a little bit of tinnitus, from the you know, in the from ear, and then maybe some mild headaches. And so we think those are pretty good trade-offs, especially comparatively in the space, but they’re not at a rate that is really alarming from a safety profile perspective. And I think that, that’s great for our audio-visual stimulation. But if you also think a little more broadly about the nonimplantable neural mod, whether it’s deep TMS or others, that’s kind of the same profile, there doesn’t seem to be I think, maybe headaches or have a little bit more density in some of those treatments. But there doesn’t seem to be really an adverse safety issue here.
Fred Goldstein 23:38
And when you said designated as a breakthrough, so what does that mean?
Sean Gregory 23:41
We were able to submit some earlier studies that gave us some designation by the FDA that there’s a unique potential here. And it also allowed us to have a, I guess, you’d maybe call it like a more structured approach to the next round of submission for the full for the full approval. You go through a process of being able to agree upon endpoints and things like that. And I think that we’ve, hopefully, we’ve designed the HOPE study to be able to deliver the evidence in that format. And then it also I believe, gives us some flexibility to do some real-world studies. So we’ve got some small real-world pilots happening in certain places as well. It was really based on the safety profile of the device.
Fred Goldstein 24:31
Got it? And, you know, obviously Alzheimer’s, one neurodegenerative disease, there are other sort of around that. Some have varying ranges or distance from Alzheimer’s. Are there other areas you’re looking at?
Sean Gregory 24:44
Certainly in in Parkinson’s, it looks like there’s some there’s some evidence is evidence being done broadly in neuroscience. There is a finding in our animal preclinical work have some improvements in myelination and if so, certainly that is a mechanism, a well known mechanism in MS. And so would there be an opportunity there. There’s, there’s a signal in and around traumatic brain injury, where, you know, again, kind of in the recovery of that, there’s some gamma issues, gamma oscillation issues. And so I think there’s certainly an opportunity to build on some of this science, the most exciting thing for us is to be focused on mild to moderate AD and MCI as a, as a precursor state. But really, trying to also add to the body of evidence around either in preclinical or in small scale studies, you know, what some of these adjacent indications might be. And that’s just, I mean, that, to me, is really exciting to think that the about the potential extensibility in some of those other morbidities,
Fred Goldstein 25:53
and these neurodegenerative disorders are just unbelievable. So it’d be nice to be able to see some things come through that could actually assist.
Sean Gregory 26:02
I absolutely agree. And I think we might sound a little corny, but our our phase three study for mild to moderate ad is is the name of the codename is HOPE. And I think that that’s the messaging where, in this particular sort of devastating disease, is there a little bit of hope, early on in the stages where the disease modification might slow the rate of progression, and provide a little bit of hope to patients and families. And I think for our MCI study, we’ve codenamed it, Tempus, which is Latin for time. And what we think that what we think might happen in MCI is, you know, there might be a little bit of an advanced disease progression and or is there some arresting of progression? And that just grants individuals and their families back, you know, a lot of time, a precious time, particularly at those life stages?
Fred Goldstein 26:57
Well, that’s fantastic. You know, Sean, I know you got a few more hoops you got to jump through to get this product done. But I want to thank you for coming on PopHealth Week and discussing it with us.
Sean Gregory 27:07
Fred, had a great time. Thanks so much for having me.
Fred Goldstein 27:09
And back to you, Gregg.
Gregg Masters 27:10
And that is the last word on today’s broadcast. I want to thank Dr. Sean Gregory, Vice President Health Economics and Market Access for Cognito Therapeutics for his time and insights today do follow Dr. Gregory and Cognito Therapeutics work on Twitter via @DrSeanGregory and @CognitoTX, respectively, and on the web via www.Cognitotx.com. And finally, if you’re enjoying our work at PopHealth Week, please like the show on the podcast platform of your choice. Share with your colleagues and do consider subscribing to keep up with new episodes as they’re posted. We stream live on health care now radio weekdays at 5:30 am 1:30 pm and 9:30 pm. Eastern and for you left coasters 2:30 am 10:30 am and 6:30 pm. Pacific for PopHealth Week, my co-host Fred Goldstein. This is Gregg Masters saying please stay safe everyone. Bye now.