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An Insider’s Perspective on the Near Future of Alzheimer’s Care · StartUp Health NOW Podcast

• 0:00
  Welcome back to Startup Health Now, the podcast where we celebrate the entrepreneurs and the innovators who are transforming health. I'm Logan Plaster. My guest this week is Dr.
• 0:09
  Laura Nycenbaum, the executive director of drug discovery at ADDF, the Alzheimer's Drug Discovery Foundation.
• 0:16
  I was recently in attendance at AAIC, the largest Alzheimer's conference in the world, and one of the themes I heard again and again from founders was that we are at a tipping point in Alzheimer's innovation, that our ability to predict and to detect and then treat Alzheimer's disease is growing faster than ever.
• 0:34
  Were those the perspectives of a few highly optimistic entrepreneurs? To answer that question and to get an insider's perspective on the near future of Alzheimer's care, I dialed up Dr.
• 0:44
  Nycenbaum, who has spent decades working on Alzheimer's biomarkers and therapeutics.
• 0:50
  In our conversation, Nycenbaum talks about new tests and therapeutics that are coming online and pulls back the curtain for how ADDF supports startups. Let's get into it. [upbeat music] Dr.
• 1:03
  Laura Nycenbaum from ADDF, uh, great to have you with me, and thanks for taking a little bit of time. Yeah, wonderful to be here. Wonderful to speak with you.
• 1:12
  You know, we just launched our-- la-launched our Alzheimer's moonshot with, uh, with help from the Gates Foundatio-- the Gates Ventures and ADDF.
• 1:20
  And so it's been important to us to get to know some of the leaders, uh, behind these organizations, um, and a-a-and your name rose to the top.
• 1:29
  So it's important for me to understand some of the science and some of the, the work that you're doing that's so important.
• 1:34
  So why don't you give us a little background of how you came to ADDF and specifically got working on Alzheimer's? Yeah. It's a, uh... It actually starts, uh, quite a ways back.
• 1:47
  Um, I actually was raised by two counseling psychologists, and so I've always been fascinated by the brain, trying to understand what's going on when people are thinking and feeling.
• 1:58
  And so I, um, really started out trying to follow that interest and got into science and the brain study and neuroscience.
• 2:08
  Ultimately ended up as, um, a, uh, professor at University of Connecticut, and was fascinated by trying to understand the development of the brain.
• 2:19
  But for me, what I wanted to really understand was how could I take that to some type of translational health impact. And so that brought me into, um, joining a pharmaceutical company, Eli Lilly and Company.
• 2:34
  And while I was there, um, I had a great experience, um, leading a lab, um, developing molecules that we could bring into the clinic to help in various different diseases, including Alzheimer's disease, and then ultimately, um, taking a step closer to clinical and started on, uh, understanding biomarkers and ultimately clinical development for diseases such as Alzheimer's.
• 3:04
  And this was really important to me because I wanted to be able to impact human health.
• 3:10
  And after my time at, um, Lilly, I then went on to join Biogen, where I participated in, um, leading the biomarker strategy for the development of their Alzheimer's, uh, disease anti-amyloid therapy, aducanumab.
• 3:26
  And so after that twenty-five years of really being in the trenches and focused on some very specific drug development, I wanted to be able to look more broadly across the entire field, and that's where my connections with ADDF really started.
• 3:43
  So I was, uh, in dialogue with the, um, co-founder How- Dr. Howard Fillit and Mark Roithmayr, the CEO.
• 3:53
  And, um, this looked to be such an amazing opportunity to be able to come in and catalyze not just one or two drugs, but the entire field of Alzheimer's disease research.
• 4:06
  So that's how I, uh, got connected with ADDF, and, um, it's been a, a great experience as I've been here the past two years. Wonderful. I wanna wind back to something you said about your desire for translational impact.
• 4:22
  Uh, what I'm gathering is you wanted to take the academic world, uh, work that you were doing, and you wanted to impact real patient lives. And so I wanna ask you for a second about that challenge.
• 4:33
  I was just talking to another founder who described the exact same thing, where his team had amazing research and it wasn't reaching patients decade after decade.
• 4:43
  So could-- Just talk to me a little bit about some of the inherent challenges of bringing academic work into the lives of real patients. Yeah.
• 4:52
  Uh, that is a great question because we know that academia is a great, um, area and fosters innovation.
• 5:03
  But then taking that science and translating it into something that can actually impact human health, um, has a number of challenges.
• 5:13
  So trying to understand, um, what those barriers are, um, and how we can help bridge those is something that, you know, we have been able to do at ADDF and, quite frankly, in collaboration with the Startup Health.
• 5:29
  So when you look at, um, coming up with an idea of, um, a particular target and designing molecules that could then, um, be able to be used to, um, modify whatever that target or mechanism is,
• 5:49
  that's important, but we then have to bring that into human clinical trials.
• 5:55
  And we know that taking that first stepFrom the lab into human trials is what we call the first valley of death, and that's where having the funding, having the know-how of, um, being able to actually design the right studies, the right, um, clinical trials, knowing that you need to use biomarkers to be able to establish target engagement and show pharmacodynamic changes.
• 6:26
  That's really one of the first hurdles that many investigators, academic investigators reach.
• 6:33
  Um, once they've been able to take those molecules through the early phase of clinical trials, um, they then oftentimes reach a second valley of death, where they're going from the first, um, human trials into the much larger studies, where those larger studies need to show the effectiveness, um, the efficacy of the drug.
• 6:57
  And again, many of these investigators face hurdles around both know-how and funding- Yeah... to be able to, um, enable those types of studies. Yeah, very interesting.
• 7:10
  I- if you would, pull back the curtain for us and give us a bit of an inside look at how you help companies through, whether it's through the, the DXA, the, the Diagnostics Accelerator, uh, and also s- more broadly, your venture philanthropy model, kinda how it works.
• 7:27
  Yeah. So ADDF, um, really takes a very unique approach.
• 7:31
  So we are interested in, um, being able to provide funding to innovators who may not be able to receive funding, um, from either for-profit companies or even, um, if the ideas are seen to be too risky.
• 7:51
  So venture philanthropy, um, is a unique approach where on the one hand we have the philanthropy non-profit dollars. They are being able to be used to enable much more risky endeavors.
• 8:07
  And if any of the, um, studies or companies are successful in advancing their approaches, whether that might yield, uh, licensing or even, um, uh, acquisition from a, uh, a for-profit entity, any of the funds that we would receive back from our investments would get funneled right back into, uh, further scientific research.
• 8:36
  So we really would view any return on investment that we make, um, as serendipity. Got it.
• 8:44
  Um, I think what all of our viewers and listeners really wanna know is what are the promising innovations coming out of your program? So you're designed to, to, you know, bring academic work to life in the real world.
• 8:57
  You're designed to support these amazing new innovations in Alzheimer's, so what are some of those companies that you're excited about? What should people feel optimistic about right now in this field? Yeah.
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  So, um, you know, as, um, we know at ADDF, we really fund, uh, a broad swath of the research.
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  So we have our biomarker and diagnostics work, so primarily funded through the Diagnostics Accelerator, and that's where we're trying to enable companies to advance, um, diagnostics and biomarkers into accessible and, uh, commercialized products.
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  And these can be important for being able to identify the right patients and also to help advance the research.
• 9:47
  So here, um, out of the Diagnostic Accelerator, we're very excited about some of the blood biomarkers that are recently, um, coming to light. So,
• 9:59
  um, we've been, um, really excited about, uh, some of the plasma p-tau assays that have recently been shown to be very, um, accurate.
• 10:11
  And so one of our, um, in, uh, investments in Altpath, which is a company that has a plasma p-tau217 antibody, um, has recently, uh, been licensed for their antibody by Roche Diagnostics, which is of course one of, um, really the most well-known diagnostic companies.
• 10:35
  So very excited about Altpath.
• 10:38
  Um, we also then are interested in digital biomarkers, um, and the reason that digital is so important is that can help identify those individuals who might go on to develop symptoms and progress for Alzheimer's disease.
• 10:55
  Um, another interesting company there is Altoida.
• 11:00
  Um, and then if we look at some of our, um, therapeutic companies, we are very excited, um, about the fact that, um, for Alzheimer's disease, in addition to some of the, um, drugs that are now coming to market focused on amyloid, so the anti-amyloid antibodies, we think that it's going to be key to be able to target some of the real drivers for the development of Alzheimer's disease.
• 11:32
  And so we focus on what we call the biology of aging- Hmm... which indicates that there are really some key risk factors that dev- that go into developing Alzheimer's disease.
• 11:45
  So these include things such as inflammation, mitochondrial dysfunction, senolytics.
• 11:52
  Um, and so in this regard, we're very excited about the potential for some of our, um, companiesThat are developing these therapeutics, such as, um, Koya or, um, Lexeo, some of these companies that are focused on novel mechanisms.
• 12:14
  And we see the potential of bringing these into combination, um, with things such as the anti-amyloid antibodies.
• 12:24
  So we're very excited about advancing these novel therapies, and then coupling the biomarkers to be able to then identify which patient should be treated with which type of mechanism.
• 12:42
  Yeah. So in this way, leading to more of a precision medicine approach. Yeah.
• 12:47
  Uh, speaking of combination therapies, one of the things that has fascinated me about meeting the, the new members of the Alzheimer's Moonshot is how many of them have really unique strategies and technologies for early detection of Alzheimer's which immediately makes you think, how do these things all come together in a complementary way?
• 13:08
  You just mentioned blood biomarkers, but one company's doing voice biomarkers. One's doing eye movement tracking, eye color analysis.
• 13:18
  I, I, I wonder if you could comment on how these things, you could see these things potentially coming together and being, uh, the whole is greater than the sum of its parts.
• 13:28
  Uh, h- what does that look like in the future? Yeah. That's so important because, um, we know that we are going to need to be able to look at the pathology, um, that helps to define Alzheimer's disease.
• 13:44
  So we need to be able to see the pathology in the brain, or at least detect pathology in the brain. This is where blood tests, um, are really going to be critical.
• 13:55
  But we also need to be able to assess, um, the clinical symptoms.
• 14:01
  So this is where digital, speech, eye tracking can help identify those individuals who not only have the pathology associated with Alzheimer's disease, which can develop up to two decades before symptoms actually start to appear, and then therefore, which of those individuals should go on to get treated with drugs, either from a preventative perspective or once they start to develop symptoms.
• 14:34
  So it's really looking at the full spectrum and the full individual. It can't just be one piece of the puzzle- Right... for us to be able to truly understand what's going on for individuals. Yeah, that makes sense.
• 14:50
  I wanna pull back from the micro to the macro.
• 14:53
  W- we've been talking a lot with the Alzheimer's Moonshot about being in an inflection point, and for, there was a long time when people were laboring in this field, and maybe they had some ideas about early detection, but it wasn't particularly useful 'cause there wasn't, there weren't therapies and treatments.
• 15:09
  Mm-hmm. Uh, but now that seems to be shifting, and so given your vantage point, uh, imagine we're at a cocktail party and I just ask you, "Hey, where is Alzheimer's innovation at today?" Um, how optimistic are you?
• 15:23
  Are we at an inflection point? Give it to me at that high level. Yeah. What I would say is we are at an amazing point in Alzheimer's reachur- research and care.
• 15:35
  You know, I started at Lilly in 1998 and, you know, they were o- even then working on, um, Alzheimer's drugs and had been working on Alzheimer's drugs for quite a while.
• 15:50
  For so many years, the field was faced with trial after trial of not showing positive results, and just in the last few years, there's been that first demonstration of some efficacy for these drugs.
• 16:09
  And coupled with that, we've had this huge innovation curve from a biomarkers and diagnostics perspective.
• 16:18
  Uh, you know, we never would've imagined that we would be able to detect, um, in blood the fact that there was amyloid in the brain.
• 16:28
  And so I see this as an amazing point where we're starting to really take off in that innovation phase, and I'm incredibly enthusiastic, optimistic.
• 16:44
  Um, even, you know, from a prevention perspective, we now know that there are actual lifestyle modifications that can, um, through rigorous means of double-blind placebo-controlled trials, demonstrate that we can reduce the likelihood of going on to show cognitive decline.
• 17:08
  So across a number of spectrums, I think we're at a point where we can start to harvest all of this amazing research that's been conducting over the past, uh, couple of decades, quite frankly. I love it.
• 17:22
  I appreciate that positive perspective, um, and knowing that you, given what you know, you see us at this amazing inflection point.
• 17:31
  Um, but in contrast to that, we've got all these startups who are working in Alzheimer's, and succeeding as a startup, even with an amazing idea, even at that inflection point in the market, is incredibly hard, and you see it through the diagnostics accelerator.
• 17:46
  So maybe as a final question, I could have you turn your focus towards the founders that we work with and that you work with, and share a little bit of the advice, um, that you think they need in order to survive and thrive, leap the valley of death, and be able to bring their essential creations to market.Yeah, that's a wonderful question, and so important.
• 18:10
  You know, as I've, uh, become more familiar with the biotech and startup space, what I've realized is it's so important, one, to really, um, you know, uh,
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  have that innovative idea and pursue it, um, with great, um,
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  gusto and, uh, perseverance, and to then, um, be sure to take advantage of the incredible network around, um, all of the innovators.
• 18:45
  I think StartUp Health is, you know, the, the perfect opportunity to do this because there are so many people that have gone through this process, either as startups, um, themselves and founders, or through the great network of mentors and collaborators that have had that experience over the, you know, the years, the decades.
• 19:11
  So being able to capitalize on that, um, and learn from each other is just so important. Um, I think that the field is at a point where there is optimism.
• 19:26
  There's, um, you know, as we see some more success, I think that there will be more money coming into the space. Um, yes, it is not, you know, uh, it is still a challenge, but utilize those networks.
• 19:44
  Um, and, uh, there are, um, different, you know, fields and players who want to see success here, and I think we're beginning to see that. I love that. The word that comes to mind is momentum.
• 19:59
  W- the momentum is building. Absolutely. Build on it. Recognize it. Build on it. Dr. Nissenbaum, thank you for taking time with me today.
• 20:06
  You know, the work that we're doing with this Alzheimer's moonshot wouldn't be possible without the support from ADDF and the decades of work that you've done, uh, in this field, laying the groundwork, and, uh, we're just happy to be able to support in any way that we can these amazing founders.
• 20:22
  So thanks for taking time with me today and giving us a, a view from, uh, from your work. Thank you, Logan. It was my pleasure. All right. Take care. Be well. [upbeat music] Thanks for listening to StartUp Health NOW.
• 20:36
  We'll be back again with another episode next week. [upbeat music]