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Ideagen Radio
Catalyze Impact Ep. 6 - Innovating Alzheimer's Treatment: Christian Howell on Non-Invasive Neurotherapies and Cognito's Breakthrough Advances
What if restoring brain health could be as simple as wearing a headset for an hour a day? Join us for a groundbreaking conversation with Christian Howell, CEO of Cognito Therapeutics, as we uncover the innovative technologies transforming Alzheimer's treatment. With roots in the pioneering work of MIT neuroscientists Dr. Li-Huei Tsai and Dr. Ed Boyden and supported by venture capitalist Gerald Chan, Cognito Therapeutics is leading the charge in non-invasive therapies. Learn how their Spectris technology uses 40 Hertz gamma stimulation to offer a significant breakthrough in neuroplasticity and cognitive preservation.
Discover the collaborative spirit driving the future of neuro therapies as we discuss Christian Howell's strategic vision for advancing brain health. Highlighting the significant strides from the Overture phase two trial to the anticipated Hope phase three trial, we explore how these partnerships with academic powerhouses like MIT and regulatory support from the FDA and CMS are crucial for ensuring both the safety and efficacy of new treatments. With a patient-centric approach, Christian and his team are dedicated to making treatment seamless in daily life, transitioning patients from skepticism to empowerment without compromising on safety.
Christian shares his leadership philosophy, drawing inspiration from Medtronic's founder, Earl Bakken, to challenge societal biases toward traditional pharmaceutical approaches. By advocating for physics-based therapies, Cognito aims to revolutionize neurotechnology and establish non-invasive treatments as primary or complementary options for neurodegenerative diseases. With a focus on empowering language and fostering an open dialogue about cognitive health, this episode offers a compelling vision for a future where brain health is as accessible and manageable as any other chronic condition.
#Cognito #Catalyzeimpact #ideagenglobal
Learn more about Cognito Therapeutics here: https://www.cognitotx.com/
View more episodes of The Catalyze Impact Podcast here: https://www.ideagenglobal.com/podcast
Welcome to the Catalyze Impact podcast on IdeaGen TV Today. I am thrilled to have with us Christian Howell, ceo of Cognito Therapeutics. Christian welcome, george. Thanks so much for having me. You know, christian, there's a lot of things that are inspiring in the world today, but I've got to say I'm really inspired by the work that you're doing and I'm ecstatic that our global audience will be able to hear more directly from you on exactly what that is. So, as we launch right into this interview, I'd like to ask you what inspired the founding of Cognito Therapeutics and how has your mission evolved over time?
Speaker 2:Yeah, you know, we are really lucky that there are kind of three key members of our founding. The first are two pioneering neuroscientists out of MIT Dr Li-Wei Tsai, who was pioneering this work of 40 hertz gamma stimulation stimulating the neurons of the brain to oscillate at a frequency to promote a biological change that is incredibly important for the preservation of brain health and brain structure. And then Dr Ed Boyden, who had been pioneering the work of optogenetics, which is using light therapy to target specific cells and genes in the brain to promote a biological effect. And so the two of them got together and said what, if we combine these therapies, would we have the ability to very effectively, very safely and very accurately target regions of the brain to promote brain health? And so they got together and they formed Cognito.
Speaker 2:And then the third member of that team was really Gerald Chan, and so Gerald is a venture capitalist and a philanthropist in Boston, leads Morningside Ventures, and they went to him. Originally he's been an enormous supporter of promoting brain health and solutions in neurodegenerative disease and he seeded the company and the company really exploded from there. I came in as CEO in August of last year and our mission really is how can we transform brain health and our initial focus is in Alzheimer's disease. But we are firm believers that an active brain is a healthy brain and if we can promote activity in the brain to drive biological expression that's important for health, then we will be able to support the brain's defense against other neurodegenerative conditions including Parkinson's and multiple sclerosis and others.
Speaker 1:That's just remarkable, and the journey is one that is so, so, just inspiring. And so, as we look at the various ways you're doing what you're doing, there's something called spectrous. Various ways you're doing what you're doing, there's something called spectrics. And how does spectrous work and what makes it a breakthrough, a literal breakthrough in Alzheimer's treatment?
Speaker 2:Yeah, it's a great question, and so I'm going to go back to this idea of an active brain as a healthy brain. And so, you know, oftentimes in therapeutic development, what we see is therapies developed in order to target specific elements of a disease, and then what we also see are therapeutics that are developed that boost systems within the body in order to better defend itself against the disease, and in many ways, I think we fall in that latter camp. So, going back to the work of Li Wei and Ed, what we know is that our brain, at various points, is oscillating at various levels. When we're sleeping, when we're active, when we're deep in thought, and when the brain is most active and most productive, it oscillates at a frequency we call gamma, which is around 40 Hertz, and what that's telling us is that's the frequency in which the neurons are firing, neuroplasticity is occurring, and for the brain to be able to operate at 40 Hertz, there needs to be specific genes and proteins and peptides expressed that preserve that level of function and that level of brain structure and health. And what we know in a neurodegenerative brain is that ability to oscillate at that gamma level is dramatically suppressed.
Speaker 2:And so what we've learned is, by using this non-invasive neurostimulation called Spectris, we are able to stimulate the neurons of the brain to oscillate at 40 hertz by delivering 40 hertz gamma stimulation through an audio visual method.
Speaker 2:And what we are seeing is sort of real breakthrough, and we're very fortunate not just the term breakthrough, meaning something we've not seen before, but an actual designation from the Center for Devices and Radiological Health for our technology, meaning that there hasn't been other technologies like this. We have a breakthrough designation and work very closely with our colleagues at the FDA to make sure that we bring a safe and effective therapy to market Just very quickly. The way that the therapy is delivered is we use flashing light and sound. So patients wear a headset that has LED lights around the goggles and a pulse tone through a headphone. They wear it for an hour a day, every day, and what we've seen in our both the preclinical work out of MIT and the clinical research we've done to date is really an unbelievable impact on the preservation of cognition, on the preservation of function and the preservation of brain structure, measured through white matter and myelin. So that's made us enormously confident as we've gone forward into much more substantive clinical research.
Speaker 1:That is just, you know, again, incredible to hear and so, taking that just a step further, christian, how does Cognito ensure the basic efficacy and safety of this non-invasive therapy.
Speaker 2:We sort of are, you know, in the world of the life sciences. We're a little bit of a tweener right. In some contexts we look very much like a medical technology or a medical device, but the therapeutic impact we're driving is much more akin to that of a biopharmaceutical. What we're doing differently is, rather than using chemistry to drive biology, we're using physics to drive biology, and what we sort of realized is that it's unbelievably important for us to build a very robust pre-clinical and clinical portfolio so that when we go to regulators and we go to payers and, more importantly, when we go to patients and physicians, there is a very substantive evidence portfolio that they can look at and feel comfortable that not only is this technology unbelievably safe, but this technology is also unbelievably efficacious.
Speaker 2:And you know, I think the most telling data point we have to date is our phase two trial that we did called overture, and it was a randomized, sham, controlled six-month study.
Speaker 2:And what we found was, in the preservation of cognition, measured through the mini mental state exam, we showed a 70 percent preservation compared to the sham.
Speaker 2:In the measure of function which we use, the ADCS, adl, which is a measure of activities of daily living, we showed a 76% preservation of brain structure, which is measured through you know which we're measuring myelin through MRI.
Speaker 2:What we saw was a 70% preservation of brain structure. So those are really best in class and it gave us that proof of concept study, gave us enormous confidence to move forward into a much more robust phase three which we are currently enrolling. We have about 600 patients as of today, in the early part of the year, enrolled in what will ultimately be a 670 patient 12 month randomized-controlled trial that we're really excited that we'll have an opportunity to provide top-line readout sometime in the middle of 26. So you know, there is oftentimes said that the evidentiary burden for pharmaceuticals is in the pre-market space and there is an evidentiary burden for medical devices in the pre-market space and there is an evidentiary burden for medical devices in the post-market and we've really taken a disposition that we have an evidentiary burden across our entire product lifecycle. So we have invested very much, like a biopharmaceutical, in the amount of preclinical research that we've done.
Speaker 1:And to hear how you're going about this is really what's profound Christian. And so, as you look at other areas and other potential applications for Cognito's technology beyond Alzheimer's, what would those be? What are some of the other areas over the horizon that you're considering?
Speaker 2:Yeah, it's an unbelievable I'm spoiled, candidly, as the leader not just of the company and the incredible scientists and employees that we have, but also sort is a healthy brain. And promoting this type of brain health and conditioning the brain to better defend itself against neurodegenerative conditions not only allows us to address the challenges that you know seven million Americans are facing as it relates in Alzheimer's. There are somewhere between 10 and 12 million people in the United States with mild cognitive impairment, and 8 to 10 million of those have not even been diagnosed yet disease that I think we're going to have a really unique opportunity to provide a safe, effective, cost-effective at-home therapy for them.
Speaker 2:And then, if we think about the brain's ability to defend itself against other neurodegenerative conditions, things like multiple sclerosis, parkinson's Lewy body are all areas that we're really interested in exploring and then what we also know is that a healthy brain has the ability to key systems like the glymphatic system, which are very important for neuroinflammation, and so things like traumatic brain injury and concussion are also things that are better resolved and served with an active and healthy brain. So there's also cardiometabolic diseases. So you know, companies of our size a mentor of mine used to say don't die of starvation, they die of indigestion, and so we really want to strike a balance between sort of recognizing the responsibility we have as an organization to bring this therapy to as many patients as possible, but also making sure that we do the job that's directly in front of us, which is delivering a very high quality study, working with the regulators to make sure that we are demonstrating our safety and our efficacy, and then initially driving this to patients in the Alzheimer's space, starting with those that are mild and moderate.
Speaker 1:You know it's just startling. You know, listening to you in a very positive way, obviously, to hear, first of all, your excitement, but also, you know, the excitement based on what you see is the future and the opportunity to help so many, so many people across the world really, and that's really what we're talking about here so many people across the world, really.
Speaker 2:And that's really what we're talking about here. Yeah, I mean it's.
Speaker 2:You know, you can see in the background a chapter of my career at one point was in the Navy and what it centered for me. You know, my dad was also a veteran and sort of gave me this idea of a life of service. And so at the organization, you know, at Cognito, we really are North Star of the patients and and the patients families, candidly, because these diseases are plus one, they're not just impacting our mothers and fathers and brothers and sisters, but they're also impacting our, you know, their husbands and wives and their families, and so we really work hard to make sure that we keep the patient front and center for us and acknowledging that that at some point will be patients beyond just Alzheimer's patients.
Speaker 1:You know and that again is what's so incredibly exciting You're entering phase three. Could you, christian, talk a little bit you've mentioned it, but talk a little bit more about the Orbiture phase two trial and what key findings you came across and, ultimately, the impacts it had on your patients?
Speaker 2:Sure, you know it's interesting. You know we talked a little bit about the impact of cognition and to function into brain volume out of Overture were so significant that we really worked hard to not change what we were doing when we went into Hope. And so you know, we had 74 patients in the Overture trial. We moved that number to 670. We were at five sites across the United States for Overture. We've now moved that to more than 60 sites across the United States. We were six months within Overture. We've now moved that to 12 months.
Speaker 2:What is exciting about the Overture is we did what was called an open label extension, which is giving patients the opportunity that were on the active therapy to remain on the active therapy and for those that were on the sham therapy to move on the active therapy and for those that were on the sham therapy to move to active.
Speaker 2:And we looked at those patients for an additional 12 months and, excitingly, we learned two things. The first thing we learned is that for the active group we were able to show durability, so this preservation of cognition and function and brain volume remained. The other thing we were able to show is that we were able to arrest the decline of the sham group, and so they could also then benefit from the preservation that the active group had seen over the course of 12 months. That was unbelievably exciting for us to show and again thinking, putting patient-centric to show that we not only you know could be perceived as like a durable treatment where patients can continue to integrate this as a part of their daily activities, but also that we can continue to impact those that had experienced even more decline. We'll be doing the same as a part of our hope study, so we're really excited to be able to continue to deliver that evidence to physicians and thought leaders and subject matter experts and patients so they understand just how efficacious this device is.
Speaker 2:One other element I would add is we had no serious adverse events, and so, in a space where, you know, we are trying to pioneer new medicines and new neuromedicines and there are challenges between efficacy and safety in some of those therapies, we're enormously fortunate that that is not something that we are challenged with. That the device is unbelievably safe and in the UX research that we've had with patients that have come out of the study, we've heard that it's also incredibly usable. We had adherence over 80% in our phase two, which means that patients are using it consistently. We're seeing even better than that in our HOPE study, so we're unbelievably excited that not only is this a safe and efficacious therapy, but it's something that is easily integrated into patients' daily lives.
Speaker 1:That's just, you know, incredible as well to hear and again, I think your enthusiasm is really what's clearly contagious, and that optimism that so many folks will be able to take part potentially in this game. Changing, you know, treatment is just, it's just incredible.
Speaker 2:I will be completely honest Of all the jobs I've had in my entire lives and you really look for something to be purpose-driven this is one that's as easy to get out of bed in the morning or spend the extra hour, because it does feel like this sense of responsibility of stewarding this unbelievable therapy.
Speaker 1:Yeah, yeah, it's just remarkable. And so, in terms of collaboration, what types of collaborative efforts are in place with, for example, academic institutions or other healthcare organizations that can help to further your critical research?
Speaker 2:Yeah, you know, I think about partnership really in a couple of lenses, so one. We have a very robust network of academic sites that we've worked with both in the development of our clinical research and our preclinical research, and the lead in that has been the unbelievable partners that we have at MIT, and so they continue to be enormously explorative in a preclinical space around the possibilities of this and in many ways help guide and direct the therapy areas that we think we can move into From a. You know, I am lucky throughout the day. You know I no longer say that I'm the dumbest person in every room, I just say that I'm the person who has the most to learn in every room I go to, because we have an unbelievably robust both scientific advisory board, medical advisory board. The board of directors is a organization of our size that is as well guided by internationally recognized scientific minds and medical minds that are really making sure that we are unbelievably fluent in the technology and that we're unbelievably fluent in the needs of the patient.
Speaker 2:The third group and I really don't say this, I mean this generally is I think of organizations like the FDA and CMS and even commercial payers as our partners in this. I am an enormous believer that under Jeff Shuren's leadership and under Michelle Tarver's leadership and under Rob Califf's leadership at the FDA, they have really tried to drive an ecosystem where companies in our position can engage the FDA designation, whether it's programs like early payer feedback. There are programs like TAP where they can help early stage companies design, trial design. I just think you know, for a long time I think there was this disposition toward the FDA and CMS of only go to them when you need to, and we have taken a completely different approach on that and we really do think of our review team and the FDA and the guidance that they give as partners, and I'll continue to think of them when I think of partners.
Speaker 2:I think the same with CMS, as they sort of help us think through coverage and reimbursement and how to navigate those pathways as efficiently as possible so we can get this to patients. So I really am incredibly fortunate that I have academic centers, I have thought leaders, I have government organizations that are tremendous partners. And then I would also say is I'm looking now to build very robust partnerships with health systems, to think about how, given the dexterity of the therapy, given the idea that it can be impactful, not just Alzheimer's, but Parkinson's and multiple sclerosis and cardiometabolic health and concussion and epilepsy. You know how do I explore those inside the walls of large health systems. So there's an economy of scale and sharing. So that's also a lot of work we'll be doing here in the next 12 to 18 months.
Speaker 1:You know it's. It's also incumbent upon me to you know, chat with you a little bit about your leadership principles. You alluded to the Navy and your service to our nation, which we're deeply grateful for, and so I'd like to ask you, christian, what leadership principles guide your decision-making as CEO of Cognito?
Speaker 2:Yeah, you know, I was incredibly fortunate that in my in a previous role, I had the opportunity to work very closely with Omar Israq, who was the CEO of Medtronic, and I had worked, you know, obviously, in the Navy, where we had a very clear mission for what we were trying to achieve. And, if possible, I think it might have been even clearer at Medtronic. And when Omar was retiring and Jeff Martha, who I have an enormous amount of admiration for, came in, I asked Omar, what is the piece of advice that you're going to give to Jeff? And I thought I was going to get this broad, publicly traded company, this is the way you need to think about the markets piece. And what he said to me was Christian, it's quite simple, which is fidelity to the mission.
Speaker 2:And Earl Bakken, when he started Medtronic, was very thoughtful in the way that he built the mission. And the mission not only is aspirational but it's also strategic for us. And so I really took that to heart and, as a CEO of Cognito, wanted to make sure that we built a mission that not only was something our employees and our investors and outside the company could look at and say. That resonates with me this idea of restoring brain health, of focusing on patients, was going to be something that resonated, but that it also gave real clarity to my organization on where we would go. So if it's outside of that mission, it really allows us to say, okay, we know what we're directed to, let's stay focused on the mission.
Speaker 2:And then the other piece I would just two other pieces I would say is one if there is a North Star within our company, the North Star is the patient, and so we are constantly putting the patient front of mind and thinking about their experience, thinking about their needs, thinking about their challenges. We really we talk a lot about it. One of our core cultural pillars is in service to others. And then the last piece I would just say is you know, I love that quote which is in God, we trust all others bring data. Which is in God, we trust all others bring data.
Speaker 2:And so I think, as a leader, one of the things that I can do is give confidence to my team that the way that I'm going to make decisions is empirical, that there is an objectivity, not a subjectivity. And I think the way that you do that is you ground that in data, and you ground that you know data should lead into evidence and evidence should lead into decision. And I think what it does, is it just? It provides an enormous amount of clarity for the team. Knowing I've got a North Star, I know the mission I'm trying to achieve and I know how decisions are made, and I think that sort of framework has allowed the employees to really put themselves in a position where they're just constantly overachieving, which is unbelievable for us and as somebody that's fortunate enough to lead the company.
Speaker 1:Christian. That's incredible background and I love the nexus with the CEO, medtronic. I mean, I think having that mentorship, and from a leadership standpoint, especially from visionary leaders, is something that is priceless and I'm sure is something that you recognize in your role. Now You're adopting a lot of those lessons.
Speaker 2:And so you know, please. No, I was just gonna say I completely agree, right, I think I think we all read the books and I think we all watch, but it's amazing how much you have the opportunity when you can put yourself in a position to learn firsthand. Um and I, I was just incredibly fortunate, like with omar or with jeff or the other leaders that I worked with at medtronic who went and became CEOs of companies. You know that I don't know. I just think always being a constant learner, being a mind at work, like always trying to understand what resonates what doesn't, it has served me incredibly well thus far in my career.
Speaker 1:And you can see that and you can see that, and I'd like to ask you you know, with that leadership come hurdles, and so what is the biggest hurdle that you've had to overcome in terms of getting the non-invasive neurostimulation therapies widely adopted?
Speaker 2:adopted? It's a great question. Quickly, I think what they are is. We have an inclination, I think as a society, that in the context of medicine that chemistry drives biology. So what I should be looking for is pharmaceutical or biochemical-like therapies to drive biological change, and in many cases that's right.
Speaker 2:But we have learned in that particular systems of the body that physics is actually a better way to drive biology. And the central nervous system is a key system for using physics-based interventions like ours, like pulse ultrasound, like TMS or transmagnetic stimulation. And we've seen this in other spaces. You know, for years the you know standard of care in atrial fibrillation was drug therapy and then what we learned is either using cryo or RF ablation became a much more effective therapeutic approach for specific patients. So I think we've learned this in other spaces and we're seeing this around different neural stimulation and I think getting people comfortable and shifting their perspective that oftentimes physics can drive biology is really the biggest one. And then I think the next great frontier is just getting patients and physicians comfortable with new therapies.
Speaker 2:Right, we have to make sure as the life science companies that we are to that earlier point about bringing substantive evidence to the market, and I really think companies need to be thinking about their evidence strategy across their entire product lifecycle preclinical, clinical, post-market coverage and reimbursement, health economics. I think we think about that far too episodically and what I've really tried to do is get the organization to be thinking about our evidence strategy in a more holistic perspective. But I think one, staying committed and prioritizing evidence, and then two, you know, helping and making sure that we are changing perspective around physics and chemistry those have been the challenges to date. But you know, in the world of challenges those certainly aren't insurmountable. So we're sort of keen to take them on.
Speaker 1:That's right, christian. That's the approach that I think is so powerful and embedded within your methodology. And so, as we approach the conclusion of this interview, what is Cognito's long-term vision? What's your vision for neurotechnology and neurodegenerative disease treatment?
Speaker 2:Yeah, it's a great question. I mean I think we are the first and on the cusp of a truly innovative health technology, and what I mean by that is I believe that there are ways that this therapy can be used as a primary therapeutic in Alzheimer's disease, in multiple sclerosis and Parkinson's disease. I believe that there's an opportunity for it to be used in combination. You know we talked about cancer therapeutics that address the disease and therapeutics that address the disease and therapeutics that boost the system.
Speaker 2:Because of our approach, we have the ability to work with an array of other therapies safely and even promote their efficacy. And then there is this really interesting path around preservation and performance and thinking about ways that specters could be used proactively by patients or by older adults to drive cognitive performance. And then there's even this really interesting lens of general performance and that we know that our brains are operating at peak performance when they're oscillating at 40 hertz. Is there a future where we'll use this very safe intervention to drive performance in other areas? So I think about it really from the perspective of are we one of the first truly high dexterity health technologies, and that technology is directed to impact health when there is disease and when there is an opportunity to condition ourselves to either prevent the progression of disease or get our brains working at peak performance.
Speaker 1:You know and you can see it, and you can hear it and you can understand it. We're at the cusp of something that is truly, you know, profound, and we're also grateful to you and Cognito for all the work you're doing and certainly wishing you great success in this phase. Three, 600 participants in the trials I mean it's incredible. Christian, what is your final call to action from this interview for our global audience?
Speaker 2:Yeah, maybe I'll do two right. One might be a little provocative, but I think it's important, and then the other goes to what we talked about. The first one is I'd ask everyone to be sensitive and thoughtful about language. One of the things what I've tried you've not heard me say in the course of this conversation is the term dementia, and that was on purpose, because I believe that there is a stigmatism and the data shows this about dementia, and what I think it can cause is people to be reluctant to address the issues, so they aren't labeled with that, and so we know what's important for our parents and for our families is that we're highly attuned to our cognitive performance and if that cognitive performance becomes impaired, that we go and we seek out help. And I think, if we can use different language around that and there's some wonderful work being done by different groups Mike Zendel's work comes to mind with changing the D word, but it's something that I you know, it's a call to action for the group, which is let's create an environment where as many certainly Americans or people around the world are comfortable embracing some of the challenges that they might be feeling and we put no headwind in front of them that might make them reluctant to address it.
Speaker 2:And then the other is let's really be explorative and understand that we're at a new you know, brain health has kind of come to the forefront.
Speaker 2:We have we've done an unbelievable job as a culture addressing other chronic conditions, whether it be cardiovascular disease, obesity, cancer, but what it has, what has created, is we are now aging into concerns around neurodegenerative disease and I think that same sort of pioneering, open-minded, explorative spirit that we took into those other spaces we need to do with this and we're hoping that we're sort of one, the first of many approaches that look at this, as you know, from as many different angles as we can and really trying to find ways that we can drive benefit. So those are sort of my two last call to action. And, george, I can't thank you enough for giving me the opportunity to share this with your audience and I just you know I couldn't be more excited about our future and our impact to patients. So any opportunity I can have to share that enthusiasm and share what we're doing, I am enormously thankful and to your group and to idea Jen and you.
Speaker 1:Christian Howell, CEO of Cognito Therapeutics changing the world. Thank you for all you're doing and, most importantly, thank you for your leadership, Christian. We really appreciate it. Thanks.
Speaker 2:George, I appreciate the time.
Speaker 1:Thank you.