Anthony DePasqua, CEO of EnClear Therapies, sits down with Neil to discuss the company’s technology in development to remove toxic proteins from cerebrospinal spinal fluid to treat patients with ALS and other neurodegenerative conditions.
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Full Transcript
Danny Levine (Producer)
Now we've got Anthony DePasqua, who's CEO of EnClear Therapies on the show today. What is EnClear Therapies?
Neil Littman (Host)
Yeah. EnClear is actually a portfolio company of Bioverge. They are developing a device that is able to filter the cerebral spinal fluid from patients suffering from a, their lead indication is ALS, but it's really a platform technology that can be potentially broadly applied to a variety of different neurodegenerative diseases. So, so they're, they are working under the clearance hypothesis to filter out what are believed to be the toxic proteins that cause the underlying condition for ALS.
Danny Levine (Producer)
It seems this as a bit, it navigates to what's been done with blood. It known yet that there's a therapeutic benefit for this approach?
Neil Littman (Host)
Well, early evidence is pointing in that direction. This is still a relatively novel approach. To my knowledge, there are no approved therapies that have implemented this Clarence hypothesis. However, there, the technology has been around for decades now, largely in the academic setting, there are a number of commercial players that are pursuing this approach. I think there's a lot of evidence pointing to, if we can remove the toxic proteins that are thought to cause the disease in this case, LLS, but same holds true for Alzheimer's or Parkinson's that patients would significantly benefit that the disease could, in some cases be halted from progressing could potentially be reversed in some cases we don't know how far I, I'm not sure there's a lot of evidence around that, but I think they're there. The scientific hypothesis I think is pretty strong and has been supported from early, certainly lab data in cells, but also know preclinical animal model data as well.
Danny Levine (Producer)
If the technology does work, is there an expectation how broadly applicable it might be?
Neil Littman (Host)
Well, I think that's one of the things that we really liked that bio verge about what and Claire is doing. Is that an ALS in particular? There are no real, no, no great treatment options exist today. It is a true unmet medical need. So what, and Claire is pursuing, right? If it works is a total paradigm shift in game changer for patients with ALS and in many ways the, the technology that they're developing could be applied to other diseases as well, such as Alzheimer's or Parkinson's or other neurodegenerative diseases. If thesis holds true and the technology works as we all hope it will then yeah. I mean, there are huge benefits that can be seen from, from patients suffering from these devastating diseases.
Danny Levine (Producer)
If you're all set,
Neil Littman (Host)
I'm all set. Let's do it. Tony, thank you so much for joining us. I'm excited to have you on the show today.
Anthony DePasqua (Guest)
Thanks for having me. I'm looking forward to it.
Neil Littman (Host)
Today we're going to talk about EnClear therapies, the neurodegenerative condition. ALS, we're gonna talk about your technology for removing toxic proteins from the CSF, but I'd love to start with ALS Tony for listeners, not familiar with the condition. What is ALS.
Anthony DePasqua (Guest)
ALS is a pretty devastating disease that folks have been looking at for over a hundred years. A lot of folks know it from the ice bucket challenge. Even before that is Lou Gehrig's disease, the famous baseball player who had it many years ago, and it strikes people pretty much in their prime and they, in the middle of their lives, it starts with someone having difficulty walking, eating, and speech, disruption, weakness in your legs. Unfortunately it takes about a year to get diagnosed. You move from your primary care to a neurologist, to a specialist, and then you receive this ALS diagnosis. You're told, unfortunately, your life expectancy is now two to five years. You're going to be in a wheelchair and about in less than a year. Unfortunately there's no real therapeutic options for you. It's really about management of your life for these final years as your body, your, your neurological system, the degrades very rapidly around you.
Danny Levine (Producer)
And.
Neil Littman (Host)
Tony, is this a, is this a genetic disease, or does this manifest if it sounds like it manifests later in life or do we know the underlying cause of the disease?
Anthony DePasqua (Guest)
Well, so as the underlying biology becomes more understood and genetic mutations become more evident and understood, it just becomes ALS is a much more complicated disease than originally thought as many of these neurodegenerative diseases are. There are most certainly genetic components to this disease, C nine orf 72 is the largest genetic mutation for ALS patients, but there's also a spar, a large sporadic group where there is less genetic component there. Folks are just now starting to understand the biologic underpinnings of that portion of the disease.
Neil Littman (Host)
I think that's a good segue into what you're developing it EnClear. That's really a technology to remove what are thought to be the toxic proteins from the cerebral spinal fluid. Could you, could you talk about at a high level, the clearance hypothesis in general, maybe it's origins, if I'm not mistaken. I think that clearance hypothesis and this concept of removing toxic proteins from the CSF was started actually in with Alzheimer's. Could you talk just about the hypothesis in general and then we can dive into what's unique about enclaves approach?
Anthony DePasqua (Guest)
Sure, sure. And, and it's worth noting that folks have actually been looking at your cerebral spinal fluid CSF as a toxic component of neurological disease for 40 plus years now. There's been good evidence along the way to support that there is components here that are toxic by nature. The company itself started by looking at an actual genetic mutation, the C nine orf 72 genetic mutation, which we found there are proteins developed as part of that mutation that don't exist in the human popular normal human population. We tested those on human cells and saw that those were very toxic in the academic world has found that they're very toxic. That started us down this path we've since then moved into the sporadic population as well, and found other toxic proteins that are present in your CSF and cause human neuronal deaths. So, it's been an ongoing academic affair, but also more recently at end Clare therapies.
Anthony DePasqua (Guest)
We have started to look at these components of CSF finding that they are in fact toxic and, and starting to use our system to remove those that toxicity. The, and this has been looked at actually not just an ALS, as you said, in Alzheimer's and Parkinson's disease, frontal temporal dementia and PSP as well. So, so many neurological diseases are now looking at the CSF as a possible gateway for a toxicity associated with the disease and B ways of therapeutically approaching, treating patients with diseases.
Neil Littman (Host)
Tony, I want to dive into something you mentioned. I mean, this has been pursued largely the world of academia for, as you mentioned, 40 plus years. Some of this technology obviously is now in the commercial sector looking to be developed. I, I think the, the story of how enclaves technology in particular came about is it's really interesting. Can, could you describe about the origin of the initial technology, how and where it was developed, and then we can talk about the path forward from here.
Anthony DePasqua (Guest)
Yeah, absolutely. And, and it is kind of a, an interesting intersection of medical device and biotech, one of the founders of a ALS, another ALS biotech company and some of their scientific group were looking at new and novel ways of getting a therapeutic drug molecule past the blood-brain barrier, which is a very difficult thing for many therapeutics to get past this gateway, to the brain basically. They came up with this idea of research relating CSF mechanically to move the molecule around as they needed, but in doing so, they also noted, well, we know about these other proteins that have been shown to be toxic. If we're research relating CSF to deliver something, can we re circulate CSF to remove something? That's the idea of end clear therapies happen right there. At that point, actually, that's where I get involved, because that was a very biotech centric company.
Anthony DePasqua (Guest)
They said, well, this is a very medical device oriented therapeutic. I had a relationship with a number of the founders there and scientific group there. They called me in who has a med tech background to see if this was something we could spin off and build as a system, which we have since done.
Neil Littman (Host)
So, as you think about the developing the technology from a regulatory perspective, how is this going to be regulated? This is going to be regulated as a medical device. This is a drug device combination.
Anthony DePasqua (Guest)
It really becomes a dependent on what we're using this system for, from a therapeutic standpoint of removing these toxic proteins. We've been in conversations with the FDA and we're currently with their device group there and going through the device pathway. That seems it's going to, it's a PMA pathway there, but that seems pretty solid and clear. Now, if we use the system for a clinical diagnostic of gaining access to, looking at other components of CSF, or by delivering therapeutic of other nature than it might, then it becomes drug device combo and moves into another area of the FDA.
Neil Littman (Host)
Interesting. As you think about developing this as a drug device combo and using this I guess what I would say is a platform technology, w w where are you for this to you? W w when do you actually anticipate being in the clinic with w with the technology, with the device?
Anthony DePasqua (Guest)
Yeah, so for our ALS CSF toxicity therapeutic, we are less than a year from the, from our first clinical trials. We're taking a pathway it's called an early feasibility study. It's on the device side. Basically it allows us to go to a very small patient population and test out the device. Most certainly we've already gone through, we'll have already finished up our safety testing and making sure that this is not going to harm anybody, but really it's an early safety human test to show that a, that we can recirculate CSF safely in humans, but also B that we can target it and remove the proteins that we're, that we want to. We're about a year away from that one's the furthest along.
Neil Littman (Host)
And then that's very exciting. And, assuming obviously there's a lot of risks that go along with clinical trials, but assuming the device, does what you think it does and what early evidence has shown that it can do. What, what does this mean for patients suffering from ALS? How does this change the treatment paradigm?
Anthony DePasqua (Guest)
Well, so we look at this as a huge paradigm shift for this patient population. If we move forward, there's still, an efficacy trial that will, we'll go into motion for the commercial release of the product. Once that happens, there's, this is an opportunity to halt the progression of ALS in a patient population that, saving them three months is a huge thing. We think we can do much better than that. And, and we can do it in a way that's relatively low invasive for them where they're not unlike kidney dialysis type methodology. They're coming into a, a service center that's local to them. So they don't have to travel. They're having their CSF cleansed for all intents and purposes. They get to go home and continue with their lives. We think we can impact this patient population by a extending their lives in a real meaningful way, but be doing it in a non-invasive way where they can stay close to home, live their lives, their quality of lives as long as possible.
Neil Littman (Host)
And, and how would this actually be delivered at the patient bedside? What would you need to have, surgeons to deliver this type of treatment or occurred, nurse practitioners, for example, deliver this, or can you talk about some of the, the training that would need to take place to deliver this type of therapies across, across the nation and then really at some point across the world?
Anthony DePasqua (Guest)
Yeah. The way the system works is that the patient is implanted with a couple of catheters in subcutaneous port, so that the catheters are pretty standard catheters that are implanted in other patient populations, from everything from hydrocephalus, which is having a pressure in your brain to deep brain stimulators, to delivering drugs in your, in your back for pain relief. The subcutaneous ports are just like chemo ports that are placed for patients receiving chemotherapy. They're underneath the skin at that point. A neurosurgeon would do that in an outpatient setting. Pretty standardized procedure, that's low invasive, minimally invasive, and a patient can go home the same day. After that, the research insulation and cleaning of the CSF can happen and what we hope infusion centers, which are locally based. Usually there's a tech that w that could run this, that portion of it for the patient, an RN, most certainly, but a tech could certainly handle the research relation portion.
Neil Littman (Host)
Great. And, and have you, is it too early, have you had any discussions with payers, have you thought about how this type of product would be reimbursed?
Anthony DePasqua (Guest)
Yeah, so we have had some early discussions with payers we're really very early in the process, but we know that takes a long time. At the end of the day, there's good reimbursement protocols for patient population, such as this that are desperately in need of therapeutics. There's a relatively clear but long pathway for fair and reasonable reimbursement for what we're providing.
Neil Littman (Host)
As we think about the, the platform technology. It sounds like, a L S excuse me, is the beachhead, if you will, for the platform, there's certainly a dire need from the patient perspective of no real available treatment options today, as you think about the platform technology, it sounds like this could potentially be used for other neurological conditions as well. Could you, could you talk about that?
Anthony DePasqua (Guest)
Yeah. W absolutely. That we actually look at this from a platform technology that has three verticals coming off of it. One is this therapeutic CSF toxicity vertical in which we think we can treat any number of neurological diseases, where there are toxic proteins present in CSF that are known to cause the neuro, the neural neuronal deficits such as Parkinson's or even all simers are in that category. And, and so we'll continue to move those programs forward, but we also believe that there are two other verticals, one of which is this delivery mechanism where we're able to deliver other therapeutics, pass the blood-brain barrier into the deep brain tissue and spine tissue that they need to go in are quite frankly unable to go with the current technology. That goes across many different disease states, not just neurodegenerative, but all the way to oncology and a number of others.
Anthony DePasqua (Guest)
We continue to work with partners to advance that technology forward. On top of that, there's never really been a good access for CSF or clinical biomarkers for taking regular samples, for getting good re testing results for the biology within the CSF on an ongoing basis. We provide a platform that you can get live data on a regular basis.
Neil Littman (Host)
Tony, I mean, those are all, I think, really fascinating areas to pursue. As you think about prioritizing, is there one of those three pillars that you're prioritizing or driving hard at, or are you pursuing all of those in parallel?
Anthony DePasqua (Guest)
We are most certainly focused almost a hundred percent on the ALS therapeutic pillar and as our, a, our lead program, but also our it drives the platform forward in the most meaningful way, but that being said, we have some ongoing partnerships in the delivery side that will continue to manage this as we go.
Neil Littman (Host)
Antonio, on the ALS therapeutic side, could you talk about some of the preclinical data that you've seen that you're excited about? I believe you've completed some large animal models. Can you talk about what you've seen coming out of those studies?
Anthony DePasqua (Guest)
Yes, absolutely. The way we take our science, very, our preclinical work very seriously. And, and so we've walked up from the bench with cell models to small animals, to large animals and admittedly there's no good large animal model for ALS. We've, we've had to get creative with cell models as well as small animal models, but we've seen on the bench, the toxicity of these proteins, we are targeting toxicity of ALS CSF. We're proving out that, yes, this, that the things we want to clean are toxic, and yes, we can clean them. On the small animal, we wanted to make sure that weren't adding any toxicity by doing what were the mechanisms that we're using in doing what we're doing. So, so we've had a good success in our small animal studies. In the large animals, most recently we've shown that we can research violate CSF on long on a long-term basis, extremely safely, and in doing so, we've actually also recently shown that we can take down indogenous levels of TDP 43 and actually Tao as well, several isoforms of tau.
Anthony DePasqua (Guest)
We're really pleased with all of these studies leading up to our human studies that we've shown that we're onto something from a toxicity standpoint, that we're not creating any toxicity by doing what we're doing and that we're, we've got a safe mechanism. That's, that's pretty efficient at reducing these proteins from, from animal model.
Neil Littman (Host)
As you think about moving forward with development, what do you see as the key risks in developing the technology as you move through, finalizing, ind enabling studies or preclinical studies I should say, and moving into first in human clinical studies.
Anthony DePasqua (Guest)
Yep. Yeah, just to be clear, we're on the ALS therapy where it'll be an IDE submission on the device side. We see this in three, the risks in three buckets, we still have our cell and biology work to complete, although we have good initial data where we continue to generate data for that IDE submission, we have more large animal work to do as well. Although everything is positive, whenever you're doing those studies, there's a small risk. There's some product development, validation, and verification going on as we speak. Although it's going very well, there's always a risk that something comes up in those tests as well. Along with that, although we've brought FDA along from the very beginning, there's always a risk that they come back and ask us for something that, that they hadn't asked for in the past or that we hadn't seen. I see it as a, mostly tactical risks, but certainly there's a lot going on at once and there's still still a bunch of, for us to do.
Neil Littman (Host)
Sure. Then, as you think about moving into the clinic, you talked about this, but could you explain a little more about what types of studies that you will need to complete in order to garner FDA approval for this device where there'll be further studies beyond that the, the first in-human trial that you had mentioned?
Anthony DePasqua (Guest)
I have. Absolutely. This, as I said, this first early feasibility study is like a phase one safety study for a farm pharmacological therapy. It will study the safety of the mechanism, the device, and then that we are reducing the protein mode that we say we're going to reduce. Once we get through that, we have some more, actually we go back to preclinical work for to update anything that we've learned from that EFS study, which it will be 10 or less patients, and really is there to educate us all, not just on the safety of the system, but also the mechanics of the biology and some of the questions we have on regeneration of the proteins, how the proteins may come out of the tissue may not how often we may need to treat patients. Some of those questions will start to be answered and inform us as to future product design.
Anthony DePasqua (Guest)
We'll do a little more of the product design in the middle, and then we have to go back for a pivotal trial on efficacy trial for FDA approval.
Neil Littman (Host)
Any idea how many patients that efficacy trial would require.
Anthony DePasqua (Guest)
Well, we're still in early development of that since we haven't gotten through our early feasibility study, but that could be anywhere from 40 to 80 patients. This is a a fast moving, progressing disease in small patient population. It won't be thousands of patients, but it'll certainly be around a hundred or less.
Neil Littman (Host)
So, so Tony, I don't want to put you on the spot here, but in an ideal world, assuming that things go relatively, according to plan, which they never do in the world of science and biology and clinical development. When would you anticipate would be the earliest that the, the product could actually be on the market,
Anthony DePasqua (Guest)
If ever if everything goes as planned in the next five years, we'll have a product on the market.
Neil Littman (Host)
As we talked about earlier, I mean, that that's incredibly exciting for a patient suffering from this devastating disease. So, Tony, I want to thank you for joining us today. If people want to learn more or getting in contact with you or what's the best way for them to learn more and read to,
Anthony DePasqua (Guest)
Yeah. Please check us out on the internet, on our website, we have a contact page and we'll happily respond to there.
Neil Littman (Host)
Excellent. Well, Tony, thank you so much for joining us on the show today.
Anthony DePasqua (Guest)
Thanks for having me.
Danny Levine (Producer)
Well now, what did you think?
Neil Littman (Host)
Yeah, I think that was a great conversation with Tony. I think we, we, learned a lot about the clearance hypothesis, how their technology is actually able to remove some of the toxic protein, some of the, specific proteins that they're targeting, w why this hypothesis makes sense. You heard Tony talk about how this has actually been in development, not their technology specifically, but thesis has been around for 40 plus years. So it's not new. I think what is new is that this is now being applied in the commercial sending, and that, is really driving this forward to, move into first in human clinical trials in the relatively near future, which I think is really exciting, especially given that this is a really devastating disease with no really viable treatment options today.
Danny Levine (Producer)
Neurodegenerative diseases have been fairly intractable to therapeutic approaches. Does that elevate the case for this type of a different approach?
Neil Littman (Host)
I think so. I mean, I think that is one of the things that really attracted Alice to EnClear to begin with is that we know that pharmacological interventions have a, let's just say extremely high failure rate when it comes to neurodegenerative diseases. So is there a different approach? I think what Ann Claire is doing is, is somewhat orthogonal to, more traditional pharmacological approaches. There is a lot of scientific evidence supporting the rationale for this approach. It's still pretty early in the development timelines, right? They're not quite in clinical trials yet, but there's enough scientific rationale and evidence to support that this approach makes a lot of sense. Given the high failure rate with, on the drug side of the equation, yeah. This is definitely a shot on goal that is worth taking. Particularly if you think about it from the patient perspective, we've gotta be pursuing all avenues to try to get new therapies in the hands of patients and in the hands of clinicians for these types of devastating diseases that are really, unmet medical needs.
Neil Littman (Host)
At this point,
Danny Levine (Producer)
The drug failures in this area would suggest that drug developers may not be pursuing the right targets for these diseases. How well is the case that removing these toxic proteins would provide benefit?
Neil Littman (Host)
Well, again, I think early evidence shows that they, that this approach can provide evidence. Again, it's in a variety of different disease settings, right? It's ALS I think there's some early evidence in Parkinson's disease Alzheimer's as well. I think the scientific rationale is there. The early scientific evidence is supportive of the rationale, but again, it is still early days, all the technology needs to be born out in clinical trials. But I think the rationale is sound. Again, given the high failure rate we've seen with drugs, that these approaches are certainly worth pursuing.
Danny Levine (Producer)
This. If successful will be a real novel approach to treating these conditions, how much of an obstacle is it to get doctors to adopt this type of new technology?
Neil Littman (Host)
Well, that's a really interesting question, Danny. I, I don't think it would be that big of an obstacle given there are no alternative options out there. This isn't like it would be a me too, type therapy or device, right. This would be a game changing, paradigm shifting type of technology for patients that have no other options. So, our sense and my, and my sense is that this would be readily adopted as soon as it's proven to be safe and effective.
Danny Levine (Producer)
Well nail until next time.
Neil Littman (Host)
Thank you, Danny.
Danny Levine (Producer)
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