Episode Transcript
[00:00:00] Speaker A: We think we've identified really the toxic target within the amyloid field to neutralize and pursue in the interest of patient benefit.
[00:00:20] Speaker B: Dan, thank you so much for taking the time to have this conversation. I'm really excited to be speaking with you today.
[00:00:24] Speaker A: Brandon, thank you for making the time and inviting me here. Excited to share the Acumen story with you and help address any questions you might have on the company, our programs, and what we're seeking to accomplish in the Neurosciences space.
[00:00:39] Speaker B: Totally. So for the audience, Dan is the founder and CEO of Acumen, doing some tremendous research in Alzheimer's disease. Dan has 20 plus years of neuroscience investing and company building. And I'm excited today to kind of jump into the story of Acumen and why he decided to kind of place a bic, a bicycle, a big bet on this program. But Dan, we'd love for you to maybe just kick us off with a kind of sketch of your career to date and the path to kind of landing here and kind of going all in on Acumen.
[00:01:09] Speaker A: Sure. Thanks. Brandon, you alluded to the background. I've spent about 25 years as an entrepreneurial leader in the life sciences space that's been principally focused on working with and building CNS related companies, initially after my MBA as an investor looking at a broad set of opportunities across companies and founders looking to advance impactful products to treat unmet needs in the neurosciences space, central nervous system space. And I've been involved with roughly 25 companies over that 25 years. And what's kind of distinct and interesting about Acumen is my involvement started not technically as a founder, but rather as a seed investor and has since grown to be in this chief executive role for the last six years plus.
But it has been a big investment of time and it's been hugely rewarding in terms of building the company and the people that we've brought into the organization and the progress we've made with what advancing the science and advancing our program, which I know we're going to go into on greater detail, which is around a product candidate called Subvertug, which we think has really interesting profile for early Alzheimer's disease. Sure.
[00:02:25] Speaker B: And having been on the investor side and seeing 25 companies, you probably had many opportunities to kind of jump into the game. What happened that you decided this was the time, this was the company.
[00:02:38] Speaker A: Thank you, Brandon. So a lot involving yourself in 25 companies in the neurosciences space, which is by definition one of the hardest areas of medicine and science to operate in. And I sort of learn on the job. And those 25 companies are probably the result of roughly 5,000 opportunities over that period of time. And so not everything is investment worthy. But acumen stands out really from the earliest days. I mean, the experience there was to identify some early science that was in the Alzheimer's space that had supportive intellectual property, their patents, and some early data. And it looked like that really served as the cornerstone of advancing potentially a more successful, more fruitful way to treat Alzheimer's disease. And we'll get more into that. But I think the most compelling thing in the early days for acumen were the makings of really an understanding of disease biology that kind of answered some of the unanswered questions around.
You know, people have heard about amyloid is associated with the disease, and we think we've identified really the toxic target within the amyloid field to neutralize and pursue in the interest of patient benefit.
[00:04:02] Speaker B: And yeah, maybe take me back to that first seed investment.
Very little data, certainly no human data.
What was so compelling at that point. And maybe that's a great narrative arc to kind of take us to some of the great early results you have.
[00:04:18] Speaker A: It is. Well, some of even going back, it's 20 years ago now, the controversy around the involvement of amyloid in Alzheimer's pathology.
There had been a history of observations that patients could die with a lot of amyloid plaque in their brain and yet not have exhibited any of the symptomology of memory or cognitive deficits. And so there's been the notion that plaques are a neurotoxic has been susceptible to a lot of. A lot of scrutiny, a lot of questions for a period of time.
And we know that. So not to go too deep into the biology, but we know that the a beta peptide, which is the principal constituent of a beta plaque, is a normally occurring, physiological relevant peptide that's actually produced in high frequency just in human beings and across a bunch of different species.
So the acumen scientists, these were researchers at Northwestern and University of Southern California, they had started to develop experimental methods using soluble aggregates of this amyloid beta peptide, or what I refer to as a beta oligomers. And those are not plaques and they're not monomers, but they're somewhere in the middle. And as it turns out, in their experiments, they demonstrated that these oligomers had a propensity to bind to neurons, brain cells that are involved in the circuitry and the function of the brain. And they did this right at the synapse, which is really the connective junction between neurons and the Thing that the mediators of circuit function, things like memory and cognitive processes. And so that acute toxicity that again was done like you said, not with clinical data, but in preclinical work, really became of interest to myself. And fortunately I was working with strong technical experts at the time that helped at least confirm the possibility, the plausibility that these might be really distinct targets to address Alzheimer's disease. And it was a combination of the non clinical evidence.
There actually at the time was some human derived evidence to support the notion that These oligomers were 70 fold elevated in Alzheimer's patients and again could help explain the discrepancy between plaque and plaque burden, which was not directly correlated to memory symptoms and cognitive decline.
So that became kind of as an early stage venture looking for high potential opportunities.
Myself and partners backed that opportunity in the early 2000s and shortly thereafter after that seed investment, actually the company was successful, securing a partnership with Merck and company. So all of a sudden we've got a multinational pharmaceutical company that is learning the underpinnings of the original acumen science. They're putting it in a pharma discovery platform with lots of researchers doing additional experimentation and discovery, which ultimately produced what we call AC193, which is a humanized monoclonal antibody that has high selectivity or preference for hitting these soluble aggregates or oligomers, which we think are the real toxins as opposed to plaques.
So yeah, so we put some at risk money on the front end of this opportunity. Merck invested about eight years, a lot of money and then consistent with the way the big pharmas operate, they made a portfolio prioritization decision somewhere in 2010, 2011, whereby they took a different path in their efforts to address Alzheimer's needs. And as a consequence of that decision, re acumen were able to reacquire exclusive rights to the program.
And thankfully we have since then had the benefit of raising capital and putting a team and expertise and moving the program forward. So yeah, it's kind of a fascinating history just given the way this field has evolved and for Alzheimer's research in general. I think if you go back to Those early days, 2010 and 20 to 2020, a tremendous amount of progress has been made as a consequence of some failed experiments, some development of better tools and better methodologies for identifying patients that would be amenable to different interventions. And so we kind of sit here, we'll talk more about subvertug. But I think generally, I think it's important to emphasize the success and the progress that the field has in fact made and that patients, you know, folks that, that may, you know, have either diagnosed Alzheimer's or have the possibility of being diagnosed as Alzheimer's should have more hope and, you know, optimism associated with, you know, what options and what future holds for them.
[00:09:45] Speaker B: Yeah, and that's a great tee up for a few different ways that we might take this conversation. But maybe just to start, the simplistic viewpoint in my mind is a distinction you're making between these plaques and these beta oligomers.
Maybe kind of like for the audience, like, help us sound like, what, what is a plaque? What is a beta oligomer? They both have amyloid in the beginning, so they sound the same.
[00:10:08] Speaker A: Right.
[00:10:10] Speaker B: Help us understand like kind of what is there.
[00:10:12] Speaker A: Yeah, well, I mean, one way to think about so. So the plaques are the pathological hallmark of the disease. Right. So it used to be before we had non invasive imaging means of identifying and quantifying plaques in humans, living humans, Alzheimer's diagnosis was really a post mortem assessment looking at human tissue and staining and looking at plaques. And what Lois ALZHEIMER Back in 1906 found was that his patient had this profound an abundance of these plaques throughout the brain. And so those are larger aggregates of principally this a beta peptide, but some other protein aggregates.
And as I mentioned, they're just sort of an end stage, if you will, of this bulky aggregation process that for a variety of reasons is not cleared effectively from the brain and just accumulates over roughly 25 years.
What's different with the oligomers is the oligomers are smaller, they are diffuse, so they have a degree of mobility and they're. At least a couple decades of research now have shown that they do have, as I mentioned, sort of a propensity to bind to neurons directly within the synapse. So they're more potent toxins and they're more directly associated with the like the onset and the propagation of the symptomology and the neurogenera processes versus plaque.
Now what the field is talking about now is that, you know, we do have, there's correlation data between plaque reduction because we now have these imaging agents that allow us to look at a human living with, with Alzheimer's disease, look at their brain and look at the level of plaque they have. And if we're able to drive the level of plaque as measured by that PET scan down below a particular threshold that has correlated with a clinical benefit, we at Acumen think that, you know, that's, it's sort of A secondary effect of reducing amyloid in totality inclusive of oligomers that, that, that produces that, that clinical benefit. And what's exciting about the, our Phase 2 study for Suburb Tug is, you know, we are going more directly at these oligomers. We do have a little bit of an effect on reduction of that amyloid signal on a PET scan. But we think because we're going more directly at these toxic species, we think we're going to have an improved safety and clinical benefit for patients.
[00:12:54] Speaker B: Yeah, I'm too curious to ask here. You've been the lucky beneficiary of I think, how the story with anti amyloid plaques have kind of played out over the last little while.
I don't know about lucky or prescient is maybe the, the better term.
[00:13:12] Speaker A: Yeah, no, I mean, I think that, you know, for, for those that have been persistent in this space, they've been able to, to advance on the learnings and, and the new tools, you know, to, to progress the field. I think that we are, you know, and there's a lot of debate right now. I think there's an acceptance that plaques plaque reduction is, is a validated clinical strategy for Alzheimer's disease. I think what we want to do and I think our altitude AD phase two study will help inform is unlock greater safety and efficacy with higher, you know, coverage of these toxic species. So it is, you know, that we are in a moment of progress. We have two approved treatments in the US as the first disease modifying treatments in Alzheimer's disease. We just feel like there, that's something to build upon and really it is like, I think like you suggest, Brandon, like it's a progression whereby, you know, there's a. The tide has come in a little bit, but we want to like crest the wave and really like take it to the next level because we are a little more focused on something that could be even more beneficial to patients.
Yeah.
[00:14:22] Speaker B: So tell me about some of the early results.
Phase one had some interesting data and you're currently in phase two. Tell me about it all.
[00:14:30] Speaker A: Yeah, so, you know, everything was hypothetical before we got into the clinic and we have been fortunate to attract a really talented and experienced team around this program. Right. So as I mentioned, I've been involved with Acuan for an extended period of time. In roughly 2018, we were able to bring into the company some former Eli Lilly drug developers, folks that had been involved in early and late phase development efforts with a prior, one of Lily's agents. So there was a great familiarity with the oligomer hypothesis there was working knowledge of kind of how to innovate in clinical design and clinical execution.
And that really allowed me to go to, you know, kind of my investors and partners and get the money to move the program forward. Now what that meant was, you know, we took Sibernotug into a phase one study, a first in human study that was exclusively in Alzheimer's patients. So sometimes in drug development you'll do a phase one, which is principally a safety study in healthy volunteers.
But we felt that in order to inform the safety profile in particular and potentially establish target engagement, it would be more beneficial and justified to go into a patient population in both the single ascending dose portion and the multiple ascending dose portion. And in that study, I mean, the results exceeded our expectations to a great degree. We were, the first order of outcome is safety and we had a compelling safety profile.
One of the safety concerns with any of these amyloid targeted agents is something called the amyloid related imaging abnormality, which can be a swelling or a leakage in the brain. And you know, it's a significant concern, particularly where there's, you know, where you could have a, you know, there are asymptomatic cases and then symptomatic cases. And some of the symptomatic cases can be pretty grave. And as you might have heard reported elsewhere, both of the approved agents have had deaths in their studies that are attributed to the agents. And that's, that's, that's a concern. And, and suboptimal in our early phase study, which was relatively small, right. There were only in total about 48 subjects that were exposed to Suburban Tug. And we only had five cases of Aria, excuse me, six cases of Aria.
Five of those were asymptomatic and one was very mildly symptomatic. So that helped.
And we were pushing doses that with other agents had, you know, produced really dramatic symptomatic areas. So we know we've got this nice safety margin.
And what was, you know, so that's, that's a, you know, part of the building block for the target, the product profile. The other element that was really important in early phase, and this applies generally in CNS drug development, is you really like to have a target engagement assay in your early phase study so that you know that your agent is actually having a pharmacokinetic, pharmacodynamic effect on your intended target.
And in our study we leveraged some of kind of some non clinical work and an assay that Merck had, had, had developed and translated into a for human use assay. And that allowed us to measure subrna TUG actually bound to oligomers. So and with that we could, we, we demonstrated a dose response which informed that we really were covering our, our target. So we had therapeutic coverage of our target. And in fact we, we didn't need to go in the next study to go to higher doses to get more target engagement. We kind of hit a ceiling which, you know, for an early phase study saves you time and money for your dose strategy in phase two.
So that, that, that was really helpful. And then, you know, we had sort of the standard clinical measures as well as both imaging and fluid bio. Fluid biomarker assessments.
And what was interesting there at the higher doses, we did see a reduction in the amyloid PET signal.
And this is only after in the multiple ascending dose portion of the study there were only three administrations of the, of the drug. Right, three doses. And even with three doses we saw a reduction in the order of 20 to 25% of this of the amyloid, the PET scan.
So having the oligomer target engagement, the imaging biomarker pharmacodynamic effect was really encouraging. And then kind of the secondary element on the biomarker story is that we looked at cerebral spinal fluid. So you can look at, take cerebral spinal fluid from a lumbar puncture and evaluate different analytes that are in that fluid. And these are amyloid related, some of them are tau related, some of them are inflammatory, and some of them are synaptic. And I won't go into great detail, but we saw consistent results in terms of our effects on amyloid on phosphorylated tau, which is actually better, more correlated with disease progression and cognitive symptoms and then also inflammatory and synaptic markers. So again, when you put all of these things together, it really holds, holds. You know, we had this hypothesis about the, about Subaru tug and its target. And then, you know, we yielded these phase one results which has been, you know, really supportive about, you know, sort of the momentum we carried into phase two.
[00:20:15] Speaker B: Yeah, My understanding is now you have a FDA fast track designation as a tailwind.
[00:20:20] Speaker A: We do, yeah. Fast, Fast track designation. And you know, the, the phase, we can talk quickly about the phase two design. So, you know, we have these very informed dose levels for phase two.
So we have sort of this, what I would characterize as a high dose at 50 milligrams per kilogram and then a mid dose which is 35 milligrams per kilogram. And then we have placebo which is Standard.
So patients have, you know, two out of three chances of being on drug. And we think both of these dose levels have the possibility of being efficacious. And we'll be interested to see whether there's a differential, you know, whether there's a difference between those two doses in terms of the safety or the safety efficacy or, you know, pet reduction or biomarker effects. But it's.
Yeah, the phase one really was, you know, helped underpin the value proposition of participating in this altitude 80 phase 2 study, which has gone really well. I mean, you know, we, the phase one inpatients is a hard study to recruit. You really, you know, the value proposition there is advancing the science, supporting research.
You know, those participants, you know, we're grateful for their willingness to join the study. And research is important. I mean, it's the only way the field can advance. And I think, fortunately, as I described the study design and then the results, it was certainly a worthy endeavor for phase two. It's really more, you know, this is intended to be an efficacy proof of concept study.
And so there the motivation for folks to join knowing they have a two out of three chances of being on drug.
And then we also have an open label extension where after the blinded control period, everybody is eligible to go on active treatment.
[00:22:16] Speaker B: Yeah, I'd love to talk a little bit more about that. So Alzheimer's research, famously hard, famously competitive.
How else have you thought about designing this phase two in order to really stand out beyond the open label and the kind of ARM design?
[00:22:33] Speaker A: We've really put forward the phase one data so that we're, you know, mechanistically on track for proving out this oligomer hypothesis.
You know, we've tried to make it convenient for participants and for sites to, you know, the protocol is a fairly streamlined protocol. So I know we've got a lot of good feedback from sites that this is the study they wanted to be.
They wanted to be in. And I think that's also been relayed to participants that this is a really interesting science, really interesting and promising drug candidate. And, you know, it's, it's. It, you know, it has been some, you know, it's resonated. I think there's, you know, there's greater awareness generally in the population that Alzheimer's is not as, you know, that there should be hope and motivation to participate in research or go on treatment and, you know, not have the nihilism that persisted for, you know, for a couple of decades.
I think one of the other innovative aspects, and this is Maybe operational, but I think it also kind of speaks to what's ahead, is that there's been a tremendous amount of work and advancement in the blood based biomarker space. And so that's even less invasive than doing a PET scan for amyloid or tau.
And in our phase 2 study for the altitude AD study, we are using a plasma phosphotau 217 happens to be the analyte that has a high correlation with the amyloid PET signal. So you can basically predict on a blood test what is likely to be demonstrated on a PET scan. And in our study we used that as kind of screening visit one and established a threshold where if you're below a particular threshold, you're probably not going to meet the PET scan requirements. And so you don't get exposed, you basically screen fail because you're not really eligible for the study. On the other hand, if you are eligible, you quickly go in to get a confirmatory PET scan. And what we found was, and some of this data has already been kind of presented or messaged like we've had at least greater than 50% reduction in the negative amyloid PET scans as a consequence of doing this early Asthma P Tau 217 screen.
So and that's really where the field is headed.
[00:24:59] Speaker B: Right.
[00:24:59] Speaker A: Like I think we're going to have a much better ability to identify patients at earlier stages of disease that are more likely to progress.
And that is just going to bring a ton of economies and you know, presumably open up access for, you know, novel treatment and, and interventions that should, you know, serve the lives of these patients.
Yeah.
[00:25:24] Speaker B: You know, like it's remarkable to think about the kind of arc from cerebral spinal fluid through to just a blood draw.
[00:25:32] Speaker A: Well, no, I mean, and you know, cause we mentioned a couple of these, like it's really pathological, you know, you know, postmortem staining. And then we got the PET ligand so we, we could do, you know, PET scanning. And now we're in the era of blood based biomarkers. And that also happens at a time where we have these very high sensitivity instruments that allow us to multiplex a whole host of not only genotypic information, but proteomic information.
And so I think there is in the not too distant future, much more greater precision medicine in Alzheimer's. And that's where, you know, we see, you know, amyloid interventions are going to be kind of the cornerstone of treatment. We think submarine tug is going to be kind of at the, at the, you know, sort of the top of the List as we continue to progress, you know, options in that space. And then it'll be, what, what else, you know, what other agents, what other mechanisms can be brought to bear? And it'll be, you know, combination approaches that are likely to produce, you know, the most robust outcome for patients.
[00:26:42] Speaker B: What if, if you could take your acumen hat off for a moment. What, what other modalities or approaches are you most excited about or are you most, you know, actively watching?
[00:26:52] Speaker A: You know, I, you know, I'm encouraged by the diversity of approaches that are being pursued. Right. I think, you know, it is, this is not, I mean, it's a heterogeneous disease. I think we have to, we, we have to continue to advance the, the diagnostic sensitivities and capabilities and then exploit both novel drug targets, but potentially other forms of intervention. And then there's also this temporal aspect of, like, when do you intervene? Right? Like what, you know, like, if, you, if, you know, you have elevated amyloid levels and you're 45 or 50 years old, you know, you know, maybe it would be appropriate to, you know, go on some regimen of some, you know, some treatment piece to continue to push off, you know, the onset. So I, I think, you know, there's a lot of work to do, and I think, you know, that, you know, it. We, we need multiple shots on goal. And I do think the diversity of, of, of approaches that are out there, not all of them are going to work. I think we're going to continue to learn, you know, that's kind of the, the state of play in some of these other high profile targets like Tao and TR Modes of addressing the disease biology. We haven't, you know, those haven't kind of gotten quite to the clinical validation that people would hope, but I think there's still promise in pursuing those types of approaches.
[00:28:11] Speaker B: Yeah, Dan, you make it sound so easy, and surely and clearly history would suggest it's not. So what makes this particularly difficult?
[00:28:22] Speaker A: Yeah, I mean, the complexity and the technical degree of difficulty is all I can say is you're right on the mark. And yet, like, if we dwell on, on those elements that we will not make progress. That's, I think, the only way I can respond to that.
It is difficult, I think, because I've been involved in the field, you know, for a number of years. I, I have seen, you know, you know, people, you know, the, the absence of perseverance doesn't get you where you want to go. I mean, you know, we, it is, I think, having the resolve and being driven by the science. Right. Like I think I have, at least in my experience at Acumen, I've routinely looked for some disqualifying outcome result or something that says this is not, you know, this is no longer worth the investment of time and effort.
And time and again, I've kind of been taken aback that things happen and data are produced, and we'll see.
This phase two study is obviously a big and still uncertain outcome, but I'm hopeful that we can take a big, giant step forward for the field and really buttress this notion that amyloid is not monolithic, that there are differentiated targets, and these monoclonals have different differential effects. In. In patients.
Yeah. You know, in.
[00:29:57] Speaker B: In speaking with a lot of clinics that do research in this space, I hear a lot about patient recruitment potentially being difficult just given, you know, the. The population that we're just talking about here. I'd love to hear, you know, how you think about that and the ways that you've kind of maybe designed around it.
[00:30:14] Speaker A: Yeah. So, you know, we really, you know, it was interesting. We launched the Phase two study in the second quarter of last year, and this is a pretty. A sizable study. I don't think I mentioned it's, you know, 540 patients. Right. Which is, you know, and our first study was 62.
So for a small organization like Acumen, that's a. That's a, you know, order of magnitude larger undertaking.
We.
And this was also at a time when the first couple agents were being approved. So I think it wasn't clear at the outset what the rate of adoption and whether patients would be willing to participate in research.
You know, and, you know, given that there were a couple approved agents, what we found was there, at least in our experience, there was enough awareness, enough experience at the site level and a willingness on the part of patients to come into our study. Kind of, as we talked about, I think a challenge for the field, and this is no surprise, is access to research. Access to treatment in certain populations and demographics is still a challenge. And so we had a pretty ambitious campaign to try to ensure diversity in our phase two study, and we'll see how that reads out. But I know that is still an area of high priority for us at Acumen, you know, to. To ensure, you know, an equity orientation on ensuring people are participating. You know, that's. Yeah. For. For multiple reasons, as. As I'm sure you can appreciate.
Sure. Yeah.
[00:31:50] Speaker B: I mean, our kind of internal discussion around this has been that it's good science.
[00:31:58] Speaker A: Yeah, Fair enough. Right? Yeah, totally. Spotlight but it's, but it's, you know that it's not unique to all of you know, all of us need to fig, you know, keep working to crack that nut. Because I think it's not, you know. Yeah. And that is, it's multifactorial too. Like I think it's not, there's not like a one size solution for remedying that, that, that issue in research.
[00:32:23] Speaker B: Sure, absolutely.
I looked at it.
Know why so many patients in a phase two? I don't often see a step up like that. What, what, what's behind that?
[00:32:35] Speaker A: Yeah, yeah. So we, I mean like, I mean simply I think we wanted to make sure that we had adequate power to get to this proof of concept to validate the oligomer hypothesis or at least you know, bring clarity to the, the risk benefit profile of of submarine tug. And we do. This has been conducted in a fashion that would make it registration eligible. That's not. We would be filing for approval on this study but we think it would be supportive evidence that could be filed on in conjunction with a confirmatory phase 3 study which would be slightly larger but basically the same design, maybe probably only one active dose but very similar kind of protocol and, and methodology. I, I'm certainly would use the 217 screen again.
Right.
But yeah, so yeah, it's really having the resources and not wanting to be, I mean you know, part, some of my experience. I've seen a lot of companies try to get by, you know, sort of try to get by with some incremental smaller studies but in this disease it just doesn't, you know, you can convince you you don't want to under power your study and just miss and then be kind of left in a, a little bit of a lurch.
[00:33:57] Speaker B: Should, should more sponsors be doing a, a straight to kind of like a, a registration ready like phase two? Like, like how do you think about that?
[00:34:07] Speaker A: I know our, our strategy is guided based on the, the experience on the team which you know has that direct, you know, FDA interaction. We did have a, you know we have fasttrack designation. We had a.
Technically we had an end of phase two meeting with the agency after the phase one study. So the Lex address for terminology is a little complicated but it was really to ensure that the phase two study could be eligible for submission as a pivotal. So we think that you know, we are also sensitive to the fact there are a couple agents. I mean we want to move this as expeditiously as possible and I do think you know, given the competitive landscape and the need and demand for better treatment options. It just made sense to do this kind of at scale and on a path towards a submission. There is, I mean, we don't speak.
I think that there are outcome scenarios for altitude AD that would almost require us to go to the agency and see what, you know, accelerated or rolling type of review might, might be warranted, particularly given the state of, you know, sort of the, the safety profile of these current agents and, and, and, or the, the inconvenience of, you know, bi weekly dosing.
You know, there's, you know, and we know this population is growing, right? Like this is just, you know, there's 7 million Americans with early Alzheimer's disease. That number is going to double or triple in the next 10 to 15 years.
And so how do we adequately open up treatment options for that population?
So we'll see if we could get an outcome in altitude AD that would behoove us to go visit with regulators and see if there was something innovative that they would be open to, to open up access and maybe bring Sabor tug forward ahead of a confirmatory phase three, which is our dated plan. I mean that just to be perfectly clear. Yeah, yeah.
[00:36:09] Speaker B: There's nothing, there's nothing new you're saying here.
[00:36:11] Speaker A: Yes.
Yeah.
[00:36:14] Speaker B: When are we expecting to learn more about this?
I don't know if you've said so.
[00:36:19] Speaker A: Phase two, we started first patient was dose in May of 24.
We have publicly guided that we will complete enrollment in the first half of 2025. So that's a really big milestone for us again with a small company enrolling a sizable phase two.
Stay tuned.
The enrollment has gone extremely well, far better than what we had budgeted for, which is fantastic. And then the study is designed to read out. The primary endpoint is an assessment of a composite score called the IDRS at 18 months, which is kind of standard design for a cognitive clinical outcome. And then we'll of course be looking at all of the aspects of safety. But then the biomarkers, both imaging and fluid biomarkers. So if you do that kind of math, I think we should be reading out the study before the end of next year.
[00:37:13] Speaker B: Yeah, really exciting.
[00:37:17] Speaker A: Sorry, finish the thought. No, that's it. Yeah, it is very exciting. I mean it's. Well, there's a little bit of a, you know, incubation period. We got, you know, like it was 11 wait. But we're staring down. The completion of the enrollment is sort of imminent, which is exciting. And then, and then we become more date certain on you Know, when are we going to read, study out? Yeah.
[00:37:36] Speaker B: Fantastic. Help me, help me think a little bit about the future. How are you hoping for the future of care in this space to evolve our patients? If I'm a patient or a caregiver listening to this show right now, um, what, what should I be thinking about in terms of how care is going to evolve?
[00:37:55] Speaker A: Yeah, so. So, Brandon, I think also. Well, maybe let's start with just awareness and acceptance because I think we're going to be. And there's, there's some, you know, when I think about care, I'm, I'm going to sort of take it to holistically that, that we as a society recognize that, you know, people are going to be, you know, will continue to be susceptible to Alzheimer's disease, that, that managing, assisting and otherwise facilitating the lives of these people is going to be something that is sort of a shared experience in some ways that we, you know, need to, you take a degree of responsibility for, for that sort of people living their best lives. I think in, in terms of, you know, treatments and care from a clinic, you know, clinical medicine standpoint, my hope is it becomes, you know, safe and efficacious and more convenient. Right. And that's, you know, notions particularly like right now in, in our space, you know, the objective of having a subcutaneous formulation is something that may be, you know, a more convenient way to get your treatment.
And that's something that we're working on. We do, we do have a phase one study of a, of a subcutaneous dosing of subronitide that we'll read out in the first quarter. And we think that's going to be an important aspect of, like I said, you know, care generally, but opening up access and, but I, you know, I just, I want to just re. Emphasize this notion that we are. The tools are going to be there for more precise identification of patients and hopefully the treatment options, you know, given the diversity of stuff that's in the pipeline, including, you know, submarine tug. But other things, even in, with different modalities or mechanisms will also advance. And we'll just be in a better state of addressing this area of what today is a very large area of unmet need that we can address it in an effective way and give people more, better quality years of living than the absence of treatments, which, if you're like me, you've seen firsthand the ravages of Alzheimer's disease or neurodegeneration. And, you know, it's devastating to see what, you know, the end state consequences of the absence of being able to address this insidious disease.
Yeah, absolutely.
[00:40:27] Speaker B: And you know, I think, I think, I'm sure that's sitting in your shoes.
Simultaneously thrilled at the amount of attention and effort being applied, but also acutely aware of what that means in terms of competition.
[00:40:46] Speaker A: Yeah, that's right. I mean it's now, I mean it's becoming a business. It hadn't been a business up until the script approval. So now this space has gone commercial and you can see the dynamic in the room has changed because the behaviors and some of the people attending the meetings and the messages and it's been kind of fascinating to observe.
I'm incredibly proud of the team that we have at Acumen. I mean it's a mission driven group with a ton of expertise and insights into kind of how we're different and why we think we can be even more successful. So that competition is a motivating factor for all of us to just to know, to follow the science and get the job done.
So it's really exciting time.
[00:41:42] Speaker B: Yeah, for sure.
Maybe. Last question for you. Here is the magic wand question. If you could change anything, you had a magic wand, you could change anything about how research is currently being done in the space, what would you change?
Why?
[00:41:59] Speaker A: Well, I think one of the, one of the rate limiters in the neurodegenerative space generally this applies to certainly for Alzheimer's, but also Parkinson's is if we could have validated biomarkers that allow for, you know, convincing early trial results, that allow for whether a regulatory or an informed go no go decision. Because, you know, look, the, this, what we've undertaken in altitude AD, you know, this is an 18 month outcome with 540 subjects. So that's a. You asked the question why so big? And partly because we want to be successful, but partly. And that's because doing a either shorter time point or smaller study, you know, may not get the answer. It just may, you know, put people into something that is inconclusive. A failed study. Right. Which nobody really wants.
So my, the one thing that I would change and it's a little bit about the science and the technology and then ultimately it could be about the regulatory, you know, the regulatory environment. You know, can we advance innovative treatments on, you know, some biomarker measure that doesn't require, you know, 500 plus patients and 18 months to figure it out? And look, I think we're headed in that direction.
We're not there today, but I think in the next five and certainly 10 years.
That's how we'll be doing interrogating new approaches in this disease population.
[00:43:37] Speaker B: It's amazing how often there's a flavor of answer to this question, and it's amazing.
It's amazing how often it comes up that it's in the form of endpoints, biomarkers, just like different ways to measure to make the science more effective.
[00:43:56] Speaker A: Yeah, I mean. I mean, I'm not surprised to hear that, because it is like, you know, I mean, that's why people got out of it. It's tough, you know, and you can't. There's no fast fail. Right. Like it is. It's like you kind of need to do the Folsom experiment, you know, or study to get an informed result. And I think that's.
There's a whole host of things to think about, conceptually, about why we won't be, you know, running these types of larger studies, you know, in several years out where we have, you know, whether it's machine learning and other elements of AI and biomarker, you know, fluid biomarker multiplex, highly sensitive instruments that inform, you know, biological effects in a smaller population or sooner, and possibly even more sensitive, you know, neurophysiological measurements, whether it's, you know, brain, you know, EEG or other assessments of, you know, brain vitality, health or function. I mean, I think all of those things should be part of the future possibilities.
[00:45:07] Speaker B: Absolutely.
Well, Dan, I think that's a brilliant note to end on. I appreciate you taking the time to have this conversation and just share more with me in the audience.
[00:45:16] Speaker A: Brandon, thanks for your time. Great conversation. I really enjoyed it.
Good list of questions. Hopefully there's enough content there for your audience to be curious about our story and about acumen. And know the key takeaway is that we are in a, you know, in a progressive, successful mode, and people should be hopeful about the future and. And treating Alzheimer's disease.
[00:45:39] Speaker B: Absolutely.
