Unlocking New Frontiers in Alzheimer’s Treatment with Christian Howell, CEO of Cognito Therapeutics

[00:00:02] Hey everybody, welcome back to the Outcomes Rocket. So excited to have you join us again. Today I have the privilege of hosting an outstanding leader in healthcare, a friend and a previous colleague, Christian Howell. He is the Chief Executive Officer at Cognito Therapeutics. He's a well-recognized healthcare leader with over 20 years of experience across startup and corporate landscapes, managing P&L from early stage to mature markets.

[00:00:31] He's just done an incredible job overall, had a great time with him during my tenure at Medtronic where our paths crossed. And now him and his company are transforming the field of Alzheimer's. He started his career early as an officer of the U.S. Navy, but I want to open it up to him to share a little bit more. Christian, thanks so much for joining us.

[00:00:53] Well, thanks, man. Thanks for having me. Yeah, it's great. Couldn't be more, one, couldn't be more excited to join and two, couldn't, I don't know if it's the right way to say it, but couldn't be more proud of what you've kind of done since our time together at Medtronic. So you just absolutely crushed it, built a name for yourself. I'm very honored to have the chance to sit and talk with you. So it's great.

[00:01:12] Oh, man. Appreciate that, man. Coming from you, it means a lot. So you guys are building some really great things and I want to uncover all that today. What sparked your interest, first of all, in healthcare and entrepreneurship and how did it lead you to Cognito Therapeutics?

[00:01:28] Yeah, it's a really good question. I'll try to do the background in just a couple of minutes, but you mentioned my background in the Navy and that was really an eye opener for me, just this idea of service-based leadership. And so when I was finishing my time in the Navy, I was looking at ways where I could find a balance between sort of doing well and doing good.

[00:01:46] And a friend of mine turned to turn me on to medical devices and the opportunity to be in the operating room and helping physicians and surgeons. It just seemed incredibly cool to me.

[00:01:55] And so I was recruited out of the military, got right into medical devices. I spent probably 18 years in medical devices in an array of roles. And then my last job was this unbelievable experience where I got to work for Omar Ishrac, who was the CEO of Medtronic.

[00:02:08] And he was trying to sort of revolutionize Medtronic into this organization, not $30 billion based on volume, but $30 billion based on value.

[00:02:18] And he sort of charged me to say like, okay, let's go figure out from a commercial context, how do we do this? How do we partner with health systems? How do we build business models that can do this?

[00:02:26] And it really taught me one, a couple of things. One, you know, I came from the military and I thought the Navy was a mission-driven organization.

[00:02:34] I've never seen a more mission-driven organization than Medtronic. And that's a great, great thing because it's guided them to some spectacular place.

[00:02:41] But too, it taught me this important result of like data and focus on outcomes and focus on costs.

[00:02:46] And so then I had the opportunity when Omar went to Intel to lean into this idea of real-world data and real-world evidence.

[00:02:53] I joined a company called ATN and I was the GM of their medical device and diagnostic business, really trying to take really robust real-world data, like stuff that you see in the EMR, stuff you see in registries and claims data.

[00:03:05] And could you do scientific analysis against it to create evidence in which important decisions could be made, right?

[00:03:10] Because that was a real important part of value-based healthcare was like, how are we looking at the data to determine who should get what intervention and what?

[00:03:17] And I love that job, like working with med device companies, working with the FDA, working with payers.

[00:03:23] And one of my clients was Cognito.

[00:03:25] And so I spent some time and I like couldn't get my head around the idea that there was this sort of novel, unbelievably interesting technology that was having this impact or potential impact on patients.

[00:03:38] And then a mentor of mine, a guy by the name of Rick Coates, who was the chief scientific and medical officer at Medtronic Joint Cognito's board.

[00:03:45] And he sort of reached out and said, like, I think there's a real here, here.

[00:03:49] And so I joined as the chief commercial officer.

[00:03:51] And then just probably six, eight weeks ago, I was asked to step into the CEO role, which has been awesome.

[00:03:56] I mean, it's just been incredible to start thinking about like cultural pillars and impact to patients and the things that we can do.

[00:04:03] So it's been great.

[00:04:04] That's awesome, Christian.

[00:04:04] Well, congratulations on a well-earned role here.

[00:04:08] And it's going to be an exciting ride for the company, knowing the type of leadership and the strategy that you could bring to the organization.

[00:04:15] For everybody really kind of tuning into our program today, you know, I think it's worth level setting on Alzheimer's, you know?

[00:04:23] So can you paint a picture of the current Alzheimer's treatment landscape and its limitations?

[00:04:28] Yeah.

[00:04:29] Let's just talk about Alzheimer's broadly, right?

[00:04:30] Because this is, to me, it is this unbelievably scary disease, right?

[00:04:35] I mean, we've all had friends or loved ones or folks that we touch with.

[00:04:37] I mean, we're at a point now where one in three people are dying with Alzheimer's disease.

[00:04:42] So it's really unlikely that you don't know someone in your life that's impacted.

[00:04:45] And I actually think of it as really one of the most cruel diseases.

[00:04:48] Not only is it cruel in that it starts to take function away from us, but we all know it takes memory and cognition away from our loved ones.

[00:04:55] And unfortunately, there's really no disease modifying therapy for the vast majority of patients, right?

[00:05:02] So there are about 6 million people in the United States with Alzheimer's disease.

[00:05:07] There are about 10 million people in the United States with what is called mild cognitive impairment, which is how the disease progresses.

[00:05:14] About 8 million of that 10 are undiagnosed.

[00:05:16] So we haven't been able to understand really without the appropriate biomarkers and measures to who has the likelihood of progressing Alzheimer's.

[00:05:24] And when they do progress, can we get to them early so that when they get to later stages where the disease really starts to take our loved ones from us, you know, we can lean into it.

[00:05:33] And, you know, that's the other thing is this is a plus one disease, right?

[00:05:37] So you have the person that's suffering from Alzheimer's disease, then you have the loved one that's having to care for them.

[00:05:42] So the United States loses about $400 million a year or billion dollars a year in workforce leaving to take care of Alzheimer's.

[00:05:50] That number is going to be a trillion dollars in 10 years.

[00:05:53] So it's massive.

[00:05:54] So the landscape, the current landscape is up until just the last couple of years, there really hasn't been anything in the world of disease modification.

[00:06:01] There have been a couple of monoclonal antibodies that have come to the market,

[00:06:05] which have been able to show some efficacy in slowing the progression of the disease by removing what's called amyloid plaque.

[00:06:12] There have been some concerns, not just around the efficacy and the cost of those drugs.

[00:06:16] I mean, everyone could probably remember the news around Adjahelm, but there's also been real concern about the safety of those drugs, right?

[00:06:22] That there's a risk of something called ARIA, which is a type of brain hemorrhage or brain bleed that they're dealing with.

[00:06:28] And then unfortunately, they can only really address about 8% of the population.

[00:06:32] So Cognito took a very different perspective to this.

[00:06:35] Maybe I'll just touch on our science.

[00:06:37] Yeah, let's do that.

[00:06:39] We're really the marriage of two sciences.

[00:06:41] There was a gentleman by the name of Ed Boyden, who was a neuroscientist out of MIT that was advancing a science called optogenetics,

[00:06:48] which was the idea of using light therapy to target specific regions of the brain.

[00:06:52] And then there was a neuroscientist by the name of Li Wei Tsai, who was pioneering the work in what's called 40 hertz gamma stimulation,

[00:06:59] which was if you could stimulate the neurons of the brain to oscillate at a particular frequency,

[00:07:04] which is 40 hertz, which is what our brains are sort of in top condition, the way our neurons communicate,

[00:07:09] that specific genes and proteins were expressed that were unbelievably important to preserving brain structure and volume.

[00:07:16] So not looking at it through the lens of amyloid, but looking at it through broader brain health and myelin preservation and structural preservation.

[00:07:25] And so what that allows us to do is it allows us to take that therapy and put it in a modality like a medical device.

[00:07:32] So it's a headset that patients wear.

[00:07:33] They wear it for an hour a day.

[00:07:36] It gives them, in our studies thus far, it's been very, very safe.

[00:07:40] We expect to be very, very cost effective.

[00:07:42] And we can address a very large portion of the population.

[00:07:46] We're doing everything we can to collect the evidence necessary to get this to market so that we can make it available to patients.

[00:07:52] Well, that's really exciting, Christian.

[00:07:54] Thanks for the context there.

[00:07:55] And it's called Spectrus AD.

[00:07:58] Yeah.

[00:07:59] Yes.

[00:08:00] Spectrus is the technology.

[00:08:01] The Spectrus is what we think about as that combination of optogenetics and 40 hertz.

[00:08:06] And then what we're doing is in our first lead product, we're directing it toward Alzheimer's.

[00:08:11] So our Overture study and our HOPE study are in mild to moderate Alzheimer's patients.

[00:08:15] But the therapy isn't limited to its impact on just Alzheimer's patients.

[00:08:22] In the future, we'll be able to leverage the therapy to other neurodegenerative conditions.

[00:08:26] We hope to be able to leverage it to broader aging, to even metabolic health.

[00:08:30] So we're kind of a tweeter.

[00:08:33] We're a therapeutic company, but our therapy is delivered through a medical device.

[00:08:38] And I've loved listening to some of your podcasts because I know you guys are talking about this, right?

[00:08:42] The idea of devices driving biological change.

[00:08:45] And I think it's the next frontier.

[00:08:47] I think we're so conditioned to devices kind of holding something open or a tool and a drug driving a biological change.

[00:08:57] But really what we're learning through neurostimulation and neuromodulation and others is that that stimulation can drive biological change.

[00:09:04] And I just think it makes for an incredibly interesting frontier in healthcare over the next 10 to 20 years.

[00:09:10] It really does.

[00:09:11] It's fascinating and exciting.

[00:09:13] And I love that you call it the new frontier because it's really nobody has figured it out.

[00:09:19] And with only 8% sort of addressable market, that leaves a huge opportunity.

[00:09:26] I'm shocked by the one third stack.

[00:09:29] That's crazy.

[00:09:30] I didn't know it was that high.

[00:09:31] 33% of us will die of this disease.

[00:09:34] You mentioned overture.

[00:09:35] Can you tell us a little bit more about the clinical trials and the results and really why this study could be very significant?

[00:09:45] Yeah.

[00:09:45] You know, overture, our phase two really provided us the jumping off point to go into a much larger phase three pivotal trial.

[00:09:53] So what overture taught us is across 73 patients at about five sites in the United States, what we learned was that over a six month period, we did a randomized sham controlled.

[00:10:07] So we had an active and a sham group.

[00:10:09] And what we saw was in the active group, in the group that received Spectrus, we saw a 77% slowing in what we call function.

[00:10:20] Right.

[00:10:21] So we're slowing the progression of Alzheimer's as it is measured by what we call the activities of daily living.

[00:10:26] We saw a 76% slowing in the loss of cognition, which is measured through the MMSC or the mini metal state exam.

[00:10:34] And then we also saw a 69% preservation in myelin.

[00:10:38] So one of the things that you're seeing is you're seeing brain volume loss in these patients with Alzheimer's disease, white matter converting to gray matter.

[00:10:46] And so what we've been able to do is we've been able to show that we can preserve on that.

[00:10:50] The other two really interesting things that we saw in overture was that one, we had no serious adverse events.

[00:10:57] So it showed to be enormously safe.

[00:10:58] And then the other thing we showed is once, you know, the technology, patients sit with it for an hour a day, every day.

[00:11:04] And one of the things we saw is that when patients finally develop the behavior, when they integrate it into their activities of daily living, right?

[00:11:12] I sit down, I have breakfast and I sit with Spectrus for the hour is that the adherence was very, very high.

[00:11:17] So the adherence was greater than 80%.

[00:11:18] That means that patients were sitting with it with the time that we wanted, the number of times per week.

[00:11:23] So overture was so, I don't want to call it eye-opening, but we'll call it sort of so exciting for us that when we then designed Hope, we did not want to deviate much from overture, right?

[00:11:35] If we could replicate what we learned and saw in overture in Hope, that we are on the precipice of something just unbelievable.

[00:11:43] So we did that just on a larger scale.

[00:11:44] So Hope will be 670 patients enrolled across 60 sites in the United States.

[00:11:50] We currently have about 530 patients enrolled.

[00:11:56] So we're almost 75% enrolled.

[00:11:58] So that speaks, we'll be one of the largest.

[00:12:00] Yeah, thank you.

[00:12:01] I mean, we'll be one of the largest neurotech clinical trials ever conducted.

[00:12:07] And yeah, so, and again, it'll be 12 months instead of six, but the same randomized, shame-controlled model.

[00:12:15] One of the things we did with overture is we did what was called a OLE, which is an open label extension, meaning we moved the patients.

[00:12:21] We kept the patients on the active that wanted to stay on the active and we moved the sham to the active and we showed durability.

[00:12:26] So patients staying on it continue to see a positive treatment effect and we'll do the same with Hope.

[00:12:31] So yeah, we couldn't be more excited.

[00:12:33] So, you know, I love that.

[00:12:34] Watch this space.

[00:12:35] Watch this space for, you know, call it mid-26 when we think we get readout because I think we're the next disease-modifying readout in Alzheimer's.

[00:12:45] And if we see what we saw in overture, I think we're going to see the market really kind of turn on its ear on a physics-based approach rather than a biochemical-based approach.

[00:12:55] That's phenomenal.

[00:12:56] Like, I'm just, I love to hear about the significant reductions in that, you know, functional and cognitive decline.

[00:13:04] Brain atrophy is the other thing.

[00:13:06] Like, it's almost like an exercise.

[00:13:08] Like, you're exercising and if you could catch it early enough, and tell me if I'm thinking about this wrong, catch it early enough, you potentially increase somebody's functionality.

[00:13:19] Yeah, I mean, I don't think you increase it, but what you do is you absolutely slow the decline, right?

[00:13:24] So, for me, I think it's a fair, I think the way you just described it is a fair way to think about it, which is we know in cardiovascular health, if we can stimulate our heart rate to a certain rate, we know that there are great metabolic things that happen.

[00:13:36] And our ability to do that, there are restrictions on our ability to stimulate our heart rate, right?

[00:13:41] The same is true for our brain waves.

[00:13:43] So, when we get neurogyronic conditions, our ability to have our neurons oscillate at 40 hertz is limited.

[00:13:50] But if we can stimulate them to oscillate at 40 hertz, then what we learn is the genes and proteins and peptides that are released and evoked during those oscillations are incredibly important.

[00:14:02] So, you're right, it is sort of that way.

[00:14:04] It is this kind of sense of really stimulating the brain to start to produce the biological mechanisms that are necessary to preserve brain health.

[00:14:14] And that, like, you know, you can tell I get super jazzed up because I just think that's so unbelievably cool.

[00:14:20] Like Star Trek.

[00:14:21] Right, and the idea of doing it in a non-invasive way, right?

[00:14:24] This idea that we're not talking about patients having to be in the clinic, this is at home and it's safe.

[00:14:30] Like that, you know, it's one of the things I actually think sometimes we get from investors, which is, seems a little too good to be true.

[00:14:37] And I just think that one of the things that we're, there are very few truly novel sciences left in the market.

[00:14:45] We're seeing these, we've seen these with gene editing and CRISPR and mRNA and others.

[00:14:48] And this is just, this is a truly novel science that we've not seen before.

[00:14:54] And I have this sort of unbelievably large responsibility to steward that to market.

[00:15:01] And so I don't take that lightly.

[00:15:03] And I think that taking it full circle and the idea of kind of keep my true north being service and service-based leadership, like here's an opportunity, right?

[00:15:11] What more important population to be in service to than our mothers and fathers and aunts and uncles and brothers and sisters and all these people that have been so impactful in our lives.

[00:15:22] We get to be in service to them, to let them age gracefully with this disease.

[00:15:25] I love that.

[00:15:26] So great.

[00:15:27] I love the vision for it.

[00:15:29] And look, at the beginning of our chat, Christian, you mentioned, you alluded to kind of, this is just one indication.

[00:15:35] So like for Spectrus AD, like how do you envision this technology transforming Alzheimer's treatments, but also impacting patient lives in other ways?

[00:15:45] Yeah.

[00:15:46] I mean, I think, look, it is really important to know that our eyes are sort of clearly on the Alzheimer's ball right now, just because it's so enormous.

[00:15:55] It's such an enormous opportunity.

[00:15:56] And we think that, but I have a responsibility to also look and say like, what are all the other places that this can be done?

[00:16:01] And fortunately, we have this sort of wonderful relationship with our founders who are constantly and continually looking at new disease states and new conditions and new areas where this might be able to be better.

[00:16:14] So in many ways, that is a wonderful sort of guiding force for us that we get to look and say, not work our way backwards, not sort of say like, hey, we have this hammer and let's go walk around and look for nails on where it can be used.

[00:16:29] It's where is the biological change coming in which disease states or conditions is that most impactful?

[00:16:37] How do we measure that?

[00:16:38] And then how do we design a modality to deliver that effectively to the patients?

[00:16:43] And that part to me, I think is going to be really interesting in the years to come.

[00:16:47] That Spectrus AD is an at-home headset that doesn't mean that Spectrus MS or PD or Spectrus for wellness or Spectrus for metabolic health, that we don't think about other modalities at the time.

[00:17:01] So the world's really open for us on that.

[00:17:03] But we are laser focused right now on getting hope because we just think it gives us so much tailwind to be successful.

[00:17:11] A hundred percent.

[00:17:12] No, I love that.

[00:17:13] And certainly exciting to sort of think ahead, but the big opportunities in front of us with Alzheimer's.

[00:17:18] Look, I love this discussion, Christian.

[00:17:20] We could talk about this forever.

[00:17:22] Maybe we do a part two.

[00:17:23] I want to thank you for being with us on the podcast.

[00:17:26] As a closing here, I wanted to just kind of leave you the opportunity to give our listeners a closing thought

[00:17:34] and where they can learn more about Spectrus AD, Cognito Therapeutics, and the work that you and the team are doing.

[00:17:40] Yeah.

[00:17:41] So you can certainly go to our website, which is cognitotx.com.

[00:17:45] There's been some really wonderful publications put out.

[00:17:47] There was just a nature paper published last week.

[00:17:50] So I think if you just Google nature and Cognito Therapeutics, you will see it.

[00:17:54] It's a wonderful.

[00:17:55] And the beginning part of it, I think, is through the lens of the patient, which I think is unbelievably cool.

[00:18:01] And you get to sort of see what their interaction has been with the therapy.

[00:18:04] I think if I were to leave just with a thought, which is the one thing that I have sort of learned as I've come across throughout my career,

[00:18:14] is this idea of sort of curiosity, right?

[00:18:18] This idea of like entering rooms with being the person with the most to learn, being inquisitive, being asked a question.

[00:18:24] Because I think about this, right?

[00:18:25] I think a lot of us would have said, oh, we think that resolving a neurodegenerative condition must be solved through a biochemical solution.

[00:18:33] And I think what we're seeing is that it's not necessarily true.

[00:18:35] We've learned that in other spaces, that drug therapy might have been the first to place.

[00:18:39] But then as biomedical technology has come in, that it can provide an equal, even greater solution.

[00:18:46] I think here's an opportunity in this space with neurodegenerative disease to say, let's be open-minded to a physics-based intervention.

[00:18:52] Let's be curious for that, because I think that's what puts us above in this space,

[00:18:56] is really engaging in these conversations as curious as we can.

[00:19:00] A mind at work is a great thing.

[00:19:01] I love that, Christian.

[00:19:02] What a great way to close us out here.

[00:19:05] And certainly the paradigm shifting technology you guys are building is just super promising.

[00:19:11] Thank you for being with us, folks.

[00:19:13] By the way, that nature study, as well as all the different ways to get in touch with Christian and the company,

[00:19:19] we'll include those in the show notes.

[00:19:20] So make sure you check those out.

[00:19:22] Thank you all for tuning in.

[00:19:24] If something today resonated, whether you're an investor, whether you're a potential partner,

[00:19:29] curious about the study, definitely reach out.

[00:19:32] And Christian, just want to say thank you for the amazing work that you and the team are up to.

[00:19:37] Thanks, man.

[00:19:37] I appreciate you inviting me.

[00:19:38] I adore what you guys are doing.

[00:19:39] So I'm super excited.

[00:19:41] Thanks, Christian.

[00:19:41] Appreciate you.

[00:19:42] All right, buddy.

[00:19:43] Be well.

[00:19:43] Talk to you soon.