There's not much metering. Kasper Roet's confidence in his company's technology can counter neurological disorders like ALS. If his long-standing and hands-on commitment to neuro research is any indication that confidence is well placed. I'm Ben Comer and I'm Matt Pillar and this is the Business of Biotech JPMorgan 2025 edition, and we're here in San Francisco at the law offices of Alston & Bird with Dr Roet, founder and. Ceo of QurAlis, to explore the why behind his optimism. Dr Roet, thanks for being here.
Matt Pillar:My pleasure. Thanks for inviting me.
Kasper Roet:It's our pleasure, dr Root, and I noticed you rolled the R on the first pronunciation and then rolled right back into the straight.
Ben Comer:American. Yeah, you know, I tried it and I thought it sounded a little funny coming out of my mouth. I need to practice it some more before I pull it back out.
Kasper Roet:I give you kudos for even trying. I appreciate that. So you've got a very diverse and hands-on background in pretty much everything that you've done hands-on background in pretty much everything that you've done. And I'm curious about the beginnings of your career. Before you got into life sciences, you started your career in IT. Is that correct?
Matt Pillar:That is correct.
Kasper Roet:So tell us a little bit about that and where, when and why the pivot from IT into life sciences occurred.
Matt Pillar:My IT life comes from the fact that I have a passion for computers. I started that as a very young child and when the internet boom started in the 1990s, I was one of the few people that knew how to assemble computers, take them apart, program them, build Wi-Fi networks. And so when I was finishing my bachelor degree at the University of Amsterdam, me and two friends were asked to help with small companies and student houses to set up their IT infrastructure so that everyone could get access to the internet. So I kind of rolled that into a company and that became actually an IT company that first built infrastructure, then built web applications and then also placed IT specialists at other companies to solve their problems. I had never anticipated being an entrepreneur before that. It was kind of a natural evolution to become an entrepreneur, and when I realized how great it was to actually be able to create your own visions into reality, I was caught and I knew I wanted to be an entrepreneur.
Kasper Roet:But I also knew.
Matt Pillar:I didn't actually want to be an IT entrepreneur it's my passion. I've always been on biology and I really wanted to develop medicine so that we could actually have a world hopefully a future world where we don't suffer from diseases anymore.
Kasper Roet:Yeah Well, let me just say that I think you made the right choice because your personality lends itself to medicine. I covered IT for like 20 years and the IT space. The people that I interviewed in the IT space not nearly as chill. As you are right, there's bigger egos in the IT space than there are in the life sciences, and so I think you made the right decision. Based on what I know about you so far, Good.
Matt Pillar:What was your first computer? My first computer. You know like I had a Commodore 64, but I actually had like a games computer before that. I don't think I must have explored it with a Comm computer anymore, but I think that well, I guess I'm an Atari before the Commodore. That's like evolved and you took all this apart. Yes, I always tried to make them a little faster and crank up their memory a little bit so I could play better games. That was really the big motivator, yeah.
Kasper Roet:What was your foray when you decided that you wanted to pursue something in the life sciences medicine related? What was your first foray into that field?
Matt Pillar:My first foray. You know, I started actually with artificial intelligence in my university track. But I come from the fields of a small farm town. Actually, the first lake that was dried out the big lake in the Netherlands was where I grew up and I had a microscope and I caught little bugs in the field and I was just taking them apart to see how they work. And that was really a passion for me, and not just thinking the box, but understanding biology and understanding nature. And so I was doing this artificial intelligence. But I realized a lot of people are probably better at programming and I realized I should just do what I'm really good at and I decided to study medical biology again at the University of Amsterdam and I loved it the moment I started that I was just in love with it. And then after that I enrolled in this IT company.
Matt Pillar:But I went back and did a master's in neuroscience and there I was working in one of the former gene therapy labs in the Netherlands. The lab of Joost Verhagen was really pushing gene therapy technologies forward. Because I wanted to translate. At that moment I already knew I wanted to make medicine and gene therapy is actually an ultimate medicine and that kind of got me the exposure in the neuroscience space, because that is where Yoast was working to make gene therapies for spinal cord repair, for paralyzed people, and so I did my master's internship there. I did a master's internship in UCSD with Mark Trushinsky, a big gene therapy scientist there, and then I came back to do a PhD. But again I wanted to do something that was really translational. So I started a gene therapy PhD project which was a collaboration between the University of Amsterdam, the Free University, a&t, which was Amsterdam Molecular Therapeutics, which later became Unicure, quite a successful gene therapy company. At that time they actually brought the first gene therapy into the Western markets for Klaipera, and so I was there at that time while they were doing that and I was also collaborating with Galapagos. They were part of the project. Basically it was called the Center Nolten Project, again to bring gene therapies to spinal cord repair. Basically it was called the sensor nolten project, again to bring gene therapies to spinal cord repair.
Matt Pillar:And so the institute where I worked, the nebulous institute for neuroscience, was actually, um, the. The director there started the dutch brain bank and the dutch brain bank is one of I think one of the best brain banks in the world, because usually within two hours after a donor passes away, the body is brought to the hospital and we're following an autopsy protocol to take out brain and spinal cord and process that in a certain way, depending on the disease. And I started to work there and became an autopsy coordinator, which meant that in the middle of the night I would get a phone call someone has passed away. Can you please organize the autopsy? So I would call the families, I would call the undertaker, I would call the neuropathologist, the section assistant, we would all go to the hospital, we would receive the body, we would then look at it and I could see the impact that all these neurodegenerative diseases have on patients talking to their family, looking at their bodies, looking at their brains, looking at their spinal cords, taking it apart and sometimes bringing the tissues back to the institute where, sometimes in the middle of the night, researchers would come to try to find out things that were happening in those diseases.
Matt Pillar:And that really caught me into the broader neurodegenerative space. And so, yeah, that is what really started to motivate me, just the incredible impact that those diseases have on those patients, both on them obviously they've passed away at that point but also on their families at that point, but also on their families and I decided I do and really specialize in development of therapies for neurodegenerative diseases.
Ben Comer:How did that really hands-on experience at the Netherlands Brain Bank influence your career and where you are now? Because that strikes me as unique. Not everyone in the industry has that degree of you know handling a brain that works in neuroscience.
Matt Pillar:Yeah, I can tell you it's really helpful right now because we're working on an autopsy program for our current trial and I understand how it works, what it means to have tissue, how it's processed you know I'm the CEO, but it's good to have that type of understanding. And you know my company is now collaborating with the Dutch Brain Bank. We just started a program also for Fragile X. We wanted to get tissue from Fragile X patients and the tissue that we got from these patients we've been able to study and really confirm a genetic target for Fragile X. I mean that has really helped me to appreciate the tissue and really confirm a genetic target for Fragile X. I mean that has really helped me to appreciate the tissue.
Matt Pillar:One of the other things that I really took away from that is how often patients are misdiagnosed, because clinicians misdiagnose patients based on clinical symptoms. But once you open up someone's body and you look actually on how the disease looks inside the body, very often we saw that the clinical diagnosis was not correct. But a clinical diagnosis often stands and so when you get tissue from a donor, the clinical diagnosis is the diagnosis. You have to really read through that to see if the pathological diagnosis is the same, because otherwise you're actually drawing the wrong conclusions on the materials that you use. And that's a very practical point where my experience there has really given me caution on interpretation of data from material from donors, and I think it's helping us do better things in Curalis, yeah, and I think it's helping us do better things in Curalis.
Kasper Roet:Yeah, so we kind of fast-forwarded to Curalis. There were a couple of stops between the Dutch Brain Bank and your founding of Curalis.
Matt Pillar:Yeah, again, I knew I wanted to develop medicine and I realized I know how a lot of companies worked. I worked as a computer specialist in a computer company as a side job. I was a telephone marketer for a while. I worked at an investment bank, and so I kind of knew a lot of different sectors.
Kasper Roet:Worked in a bar. Had no idea how you make a truck.
Matt Pillar:And it's like I want to start a company developing therapeutics, I really need to understand how to make a truck. And so in the Netherlands one of the big R&D organizations at that moment was J&J, who had their Janssen vaccine site there which was formerly Crucell but was acquired by J&J just before that time that I graduated with my PhD and I applied there and got a job, first as an assay potency development team leader and that kind of progressed into becoming a technical integrator and there I learned how you get something from research all the way to the clinic, because I worked together with Formulation, phil and ThinHash upstream processing, downstream processing, clinical assays, qc assays, r&d, cmc, and there, a couple of years in, I really understood how you can actually make a drug and how the pharmaceutical business works and what type of experts you need and all of that. And while I was doing that C9-472 was discovered big ALS gene.
Matt Pillar:My PhD program was spinal cord repair, gene therapies. So neuromuscular ALS is a neuromuscular disease and so it's the same tissues. But I thought we cannot treat ALS because we don't understand the disease.
Kasper Roet:But while I was at JMJ, a big ALS gene was discovered and then rapidly, 300 ALS genes were discovered.
Matt Pillar:And I'm a big data person, probably because of my passion for computers, and so I started looking at that and I thought this is incredible. We have the genetics of the disease. I could see pathways emerge. I could see this is incredible. We have the genetics of the disease, I could see pathways emerge. I could see disease mechanisms emerge. And so in my hobby time I took published data sets from post-mortem tissues, again connected to my work at the Dutch Brain man, looked at all the transcriptional profiles and the whole genome way to identify hub genes. That would explain why the disease actually develops and how it would potentially treat it.
Matt Pillar:I also realized we need a translational model so that we can test therapeutics and test hypotheses and did the same with all of the animal models that were published, all of the transcription data sets from all of the different ALS models that were published.
Matt Pillar:So I built this whole meta-analysis of human and animal post-mortem tissue to see if I could find things that were conserved between the two model systems Zero overlap.
Matt Pillar:I was incredibly frustrated because we have the genetics, we know what's gone wrong in patients, we can probably develop therapeutics, but we have no way to test it. How do we test this? And then I discovered Kevin Hagen's work, who was at Harvard and had taken skin cells from a patient, together with this collaborator at Mass General Hospital, james Berry, and he had used the Yamanaka protocols to turn drugs into stem cells. And he's a developmental biologist by training and knew how to make motor neurons from stem cells, and so he was able to create motor neurons from patients, and so the same neurons that are dying in a patient's spinal cord it would recreate from a skin cell and study. And so I thought this is phenomenal. That must translate. If we can see what has gone wrong in a patient's own cells, in the cells that are dying in their disease, and we can test potential therapeutics, then it must be translating again back to patients and so I decided to quit my job at J&J.
Matt Pillar:I looked up Kevin. I was collaborating with Clifford Wolfe, another professor, the head of the neurobiology center at Children's Hospital, and I said can I please work with you Because I want to learn this technology stem cell technology which was super controversial at that time. They liked my industry background. They had a collaboration with GSK. I had no one in their labs who actually knew how to work with pharma companies, so it kind of like was a good match. And then for three years I worked together with them learned everything.
Matt Pillar:I wanted to know about these neuronal model systems. And then I decided I'm done, I'm going to start my company. And so I told Kevin and my plan was to go back to Europe to do that. So I told Kevin. I'm like thank you so much, it's been incredibly great experience. I'm going to start an ALS company. And I talked to him about that before and he said, oh, maybe we can do something together. And I never really took him serious. He was a hard professor. But then he said, well, let's do that together.
Matt Pillar:And let's do it here. Let me introduce you to some people who might be interested in being part of that, and that actually led to the creation of Curalis, and both Kevin and Clifford became co-founders, together with myself and the CEO of another company that Kevin started, jonathan Fleming, who used to be a managing partner at Oxford Biosciences. He decided to be part of that as well, and we created Curalis to develop precision therapeutics for ATLAS based on the insight derived from these patient-derived disease models, and so the first two big discoveries that were made are now in the clinic. Those are our first clinical programs.
Ben Comer:I had just a follow-up on J&J. Is Curalis, a member of J-Labs, part of the incubator there? Yes, and what sort of benefits come along with that? What's your experience with that program?
Matt Pillar:I think J&J has J-Labs to get close access to new and exciting technologies.
Kasper Roet:So you know Q-State started.
Matt Pillar:So the company where Jonathan worked was called Q-State and Q-State was founded out of Q-State. So Q-State was kind of helping get Q-State established. The first office that I had was basically a closet in Q-State. It's like a little room in the middle of the building without any windows. My wife bought me a plant. The plant was the real employee of the office, but you know, we were raising a little bit of seed money and then someone advised me to apply for a golden ticket with Amgen to get access to Lab Central.
Matt Pillar:Lab Central is one of the maybe the foremost bio-incubator space in the world. It's like in the middle of Kendall Square, 700 Main Street, started by Johannes Brughaaf, and I won Kira was one won the MJ Golden Ticket. They have a ticket like this, big like a piece of cardboard, but it gave me access to LabCentral and I actually didn't know what it was until I got there. Jlab is a sponsor of LabCentral and so our office that we got at LabCentral was right next to JLab's office and so suddenly we had this and then we became a JLab member. You know we applied and we want that as well, but what you then get is a very close vicinity to a large pharmaceutical company and the people that are interested in new technologies. We were bringing precision therapies based on central technology, which is a very new technology. At that time J&J was very interested in that. The other company that was right next to that was Roche. They also had an office right next to us, and so that is one of these amazing things that you have in Kendall Square. It's just close to all of these companies, and we won another golden ticket from Pfizer, got another year of extension at LabCentral. But it's really the proximity of small companies to large companies which makes Cambridge and Massachusetts such an exciting environment. Basically, labcentral is kind of the pinnacle of all of that, because that's where it all kind of comes together in a very close density. Where's the company located now?
Matt Pillar:So at some point when we were starting to close our Series A, it was time for us to get more space. I wanted to stay in Kendall because I liked the buzz, but my team set Casper to commute to Kendall. It's really painful for us. We live outside of the city. It takes us half an hour just to be in Cambridge and half an hour back if it's a good day, so I can get a little bit further away. So I said, fine, we're going to stay in Cambridge. So we are now behind the ILLWAC station in West Cambridge. There's a little biotech hub there as well. Gsk sits there, ucb sits there, a-side sits there A bunch of little companies. It's actually quite a nice, a little small company.
Kasper Roet:Our friends at Alston and Byrd set us up with some amazing space to record during JPM week. The firm's national healthcare and life sciences practice has more than 100 attorneys actively involved in the healthcare industry across the full spectrum of legal disciplines. The signature strength of this practice is its ability to master complex representations that draw on the coordinated expertise of its regulatory compliance, public policy, transactional corporate governance, securities, FDA, biotech, IP, government investigations, investigations and litigation practice areas. Alston and Bird represents life sciences companies and their partners in corporate stages ranging from private to newly public to well-established, and in a variety of stages of product development, from preclinical to post-approval commercial launch. Learn more at Alstoncom and tell them you learned about them.
Kasper Roet:On the business of biotech, I want to talk a little bit about the regulatory scene in the space that you're in. You just mentioned your clinical programs and we'll get into that a little bit more deeply later on in the conversation. But being in a space that's not super well charted from a regulatory standpoint, what's been your experience with the regulators as you've moved those programs into the clinic?
Matt Pillar:Yeah, our experience with the regulators overall has been good, but we've noticed that the FDA has a kind of on the genetic medicines where our programs kind of fall, specifically the RNA therapeutics, and the FDA has a very conservative approach to that, very much focused on risk, much less focused on benefit, and so that has basically driven us to start our clinical work outside of the United States. So Curalis is running programs. We have now three programs. They're running in six different countries in Canada, the UK, belgium, netherlands, ireland and Germany and not in the US. And then we found out that a lot of other companies are doing the exact same thing. And when I started to talk around and like are we the only people that think that we shouldn't start in the US, we actually found out that almost every company that we talked to has that opinion because it creates just a regulatory risk and a hurdle. And why would you take that, basically, if you don't have to? And so we've brought together a consortium of companies it's now 11 companies with we as a kind of the founding members of Curalis Stokes Therapeutics, avivity, bio, ultragenyx and we brought together other companies to really try to catalyze changes and work with the FDA to see if we can build more of a risk-benefit approach into the regulatory pathway.
Matt Pillar:So I think the SEA in particular has done a lot of really good things on the back end.
Matt Pillar:Trying to get to certain endpoints biomarkers and Alzheimer's has been a remarkable step forward there, with amyloid in ALS, where we are currently with our programs, a big step forward because of neurofilament for the SOD1 population.
Matt Pillar:So I think there's been a big development and evolution in a positive way. On getting trucks maybe faster through the development pipeline and maybe faster to an accelerated approval. But on the front end there's been a very rigid system and so we think that there should be improvements there. So we've made that from the consortium. We've made a case to the FDA went to the Rare Disease Hub Day which was organized in October. I presented there, stoke presented there, avidity presented there. There were a number of other companies that were presenting there as well, and we made it clear that we'd like to work with the FDA because they made this important step on creating a Rare Disease Hub to see if there could be ways in which we can also smooth this process, because at this moment American innovation is basically leaving the United States and it's not benefiting American patients and that is kind of our broking system.
Ben Comer:Is it your feeling that the regulators have been open to listening and collaborating with you? Do you feel like you've been able to move the needle as a company?
Matt Pillar:Yes, I think you know there are differences also in the way CBER and CEDAR operate, but Peter Marks was there, patricia Capazzoni was there and I was able to connect with both of them and you don't have commitments, they're right there on the spot.
Matt Pillar:But there was definitely a positive attitude and an understanding that this wasn't the first time that they heard about it, like other companies have, but this is the first time that I think the companies have kind of united and I know the large pharmaceutical companies have the exact same few points because I talked to all of them, because we're all working together.
Matt Pillar:But there's definitely an understanding and there was an appreciation and a willingness, I think, to make improvements, and so the FDA has then put out a call to get written feedback and then recently also put out a call for all of the nucleotide therapies on what could be an improvement for the regulatory framework and, again on behalf of the consortium, we have provided that and that was just submitted like two days ago, and so it all takes time, but I think there is a. There is definitely uh, there are things moving in a hopefully in a positive direction. But obviously Rob Caleb stepped down, so we're going to get a new commissioner Patricia just announced to step down, so we also have to see what who's going to be there to work with. So hopefully that will not create too much chaos, that we can continue to move, yeah.
Kasper Roet:I was going to ask where you feel I mean, it sounds like there's a concerted effort that, uh, I guess to continue to apply not not pressure but influence, um, and I was gonna ask where, where perhaps you feel as though influence is is limited or metered, like where more work needs to be done, but it sounds like that's kind of tbD, depending on some administrative positioning.
Matt Pillar:I think so. Yeah, I mean I knew Rob was going to leave, but the KHS departure, I think, was a surprise to everyone, and so now we're going to have to see what we should work with. But I think the reason why it's so important is that this is the time of genetic medicine, this is the time of RNA therapeutics. You can see a lot of different companies active in this space. The genetic insights into disease the thing that got me interested to develop therapies for ALS, because the genetics gives us a real handle on how to treat this disease. The best way to do that is probably through genetic medicine, because the two kind of link very nicely together. But you have to have a different approach to that than you have for small molecules or antibodies, and so there's a real need, I think, for us to all evolve rapidly with these new technologies and also from a regulatory side, and so we will continue to communicate that very strongly to the FDA and whoever will be the new leaders of CEDAR and the FDA themselves, because there's no time to lose.
Ben Comer:Basically, yeah, you're an admitted optimist. How realistic do you think interagency collaboration is and greater harmonization?
Matt Pillar:Well, I think you know, harmonization can be good, but harmonization can also be bad. It depends on you know which who's harmonizing.
Kasper Roet:What part of harmony are we discussing here?
Matt Pillar:But you know there are a lot of things I don't completely understand. I know that the EMA and the FDA are connecting Health Canada, the NHRA, but there's a lot of also higher level conversations. The experiences that we've had with Q-RALIS is that regulators in different countries have a different way of looking at things, and so I think that's fine. And you know, maybe it's good that I'm a big believer in group thinking and the diversity of opinions. It's also good if they communicate a lot so that they can learn from each other.
Matt Pillar:But I'm mostly an optimist because I believe that everyone wants the same thing. Like everyone has family members who have been sick or who have passed away, or you're afraid of family members or friends getting sick or passing away, we all want medicine. We all want to have treatments for diseases. I've met so many people now that have ALS or have passed away from ALS, or have family members or friends that have the disease, and that's just one disease, right, it's the same in oncology, it's the same in epilepsy, you name it. Everyone wants treatments and so if you use that, then we should all be able to find common grounds to do the right things and to make a framework that supports therapy development. So I'm very optimistic because I think it's common sense. I don't know why anyone wouldn't want to do that.
Ben Comer:Well, and I think ALS has one of the more active patient advocacy communities. That wasn't the original ice bucket challenge around ALS. Does that help you in your role at Ecuralis?
Matt Pillar:Yes, the Ice Bucket Challenge was really created by Pete Frates and the ALS Association has really lifted that, I think, to a global awareness. It has been incredibly important for ALS because I think most people had not even heard of the disease before the Ice Bucket Challenge. Now everyone knows about the disease. It has also brought a lot of money to the foundation and to other organizations, and one of my fellowships when I was working at Harvard was from the ALS Association. So you know, in a way, the research that has also led to the creation of Q-RALIS is, I think, directly supported by money from the Icebreaker Challenge, Milton Safenov-Richfield. So, yes, I think that type of awareness and that action has been incredibly important and that action has been incredibly important.
Kasper Roet:You referenced this, I guess the risk of the exodus of clinical activity and innovation away from the FDA because there are lower barriers and other perhaps lower barriers and other regulatory jurisdictions. That's to say, you didn't even mention Australia, which has been one of the major sort of siphons of clinical activity away from the US. What would you call on the space to do, like you've been like, admirably active in calling for and influencing change? What would you call on the rest of the space to do, like? What levers might they have to push and pull to join the effort? Do you see enough activity going on in the greater landscape.
Matt Pillar:Once you start doing these things, you notice how many other companies are doing that.
Matt Pillar:I think the weakness is that companies advocate for themselves a lot and don't unite enough to have a united message. Because if one company goes and is lobbying for, in this case, the FDA to look at its own processes, it feels like that company is just trying to help themselves and no one likes that, because that just feels kind of like it doesn't feel good. It's like you're trying to skew the system in your own benefit, but that's not what we're trying to do. There's definitely something not working in the system and the fixing that will benefit everyone, and so we've done a lot of background conversations also with companies that maybe don't want to publicly be part of a consortium, but that we have the same message so that the same message is being heard over and over and over again.
Matt Pillar:So because, in the end, if you give 10 different messages to someone, they can't remember any of this. Right? I think someone remembers maybe three things very well. So you want to make sure that you have your priorities straight as a whole biotech sector and then you you give the same message that, even if it is not part of our consortium, but an independent message, and so that is something that we've been doing also with the consortium, and talked to all of the large pharma companies that are active in the ALS space, and we're all aligned, so it's important that we work in that manner.
Ben Comer:Basically, yeah, maybe we can turn it back to Kira Alice's development and clinical assets right now. Could you give us a sense of where you are and maybe what your next big milestones or goals are with your clinical programs?
Matt Pillar:Yes, I'd be very happy to and just maybe want to also explain where your clinical programs come from. So the first big discovery that was made using patient stem cells, which were then generated into neurons, was that there's a loss of a potassium channel called KD7.2. The loss of that potassium channel leads to neuronal death in these stem cell models and so if you activate that potassium channel you can protect against that. We found out it's misplaced. It's pre-mRNA includes a skeptic exon which turns it into a protein which is rapidly degraded again, leading to neuronal death. But you can protect against that with a KD7 opener.
Matt Pillar:So that is something that we have now brought to the clinic and that program is currently at the end of its phase one. We've actually run three studies, four studies in parallel a MAD study, a multiple ascending dose study to look at tolerability of course incredibly important. We've also run a healthy volunteer study to look at biomarkers that predict survival for ALS but also for epilepsy, to look at biomarkers that predict efficacy in epilepsy, because the potassium channels are very important for epilepsy. We ran a PK study to look at the three different formulations, to see which formulations would be best for these different indications, and we've also ran a patient study to see how this compound works in patients.
Matt Pillar:Most of that data is reading now to the end of this quarter, and so this is an incredibly important quarter for us, and so we're very excited about looking at the results. Then we have the second big discovery that was made, again from my co-founder was the loss of our staph-2 micro tubules, stabilizing protein essential for the innervation of your muscle, so your motor neurons protect from your spinal cord all the way to your muscles, for instance in your hands and in your feet.
Matt Pillar:That innervation is lost when there's a loss of staph in tube. What Kevin discovered is that it's driven by a mis-splicing event, and when we realized that it was just after SpingRoss.
Matt Pillar:It was approved for spinal muscular atrophy, a splice correction ASO targeting motor neurons in the spinal cords of estimated patients, showing remarkable effects in those patients. Really transforming therapy that is marketed by BioChip has helped so many different patients. We thought we can do that also for restoring staph in two levels and bringing staph in two levels back to normal, which again is lost in almost every ALS patient. At this moment we're running a dose range finding trial in six different countries where patients are dose-free for D-glu that have injections into their spinal cord with an ASO, an incisor oligonucleotide that restores these staph name levels, and we are now basically expanding on two different dose levels to see which of these dose levels is going to be effective for following patients for an extended period of time. We're looking at biomarkers that predict efficacy, neurofilament and compact muscle action potential, which measures this innervation, and we're going to read that out in the first half of next year.
Ben Comer:And what phase are you in on your clinical trials with those two?
Matt Pillar:So I would say that it's now in a phase two phase, but with these programs you kind of adapt from phase one to phase two. With the KV7, we're at the end of phase one and we're planning to start phase two trials at the end of the year.
Ben Comer:With the KV7 opener, which prevents the potassium channel from shutting down, which then prevents the neuronal death? Does that have to be administered very early on after diagnosis of ALS, or when do you have to catch the patient to?
Matt Pillar:prevent that from closing.
Ben Comer:Yeah, that's a great question.
Kasper Roet:So ALS is a progressive neurodegenerative disease.
Matt Pillar:So ALS is a progressive neurodegenerative disease and so other than, for instance, parkinson's, where if you have symptoms you've lost almost all of your dopaminergic neurons, so there's not a lot to actually protect it.
Matt Pillar:Still, in ALS, when people have developed symptoms, they still have a lot of their motor neurons and so over time there's motor neurons that are still healthy, there's motor neurons that are sick and there's motor neurons that have died, and so obviously at the end of the disease a lot of neurons have died, but at the beginning not. So in essence you can treat anywhere and have an impact on the disease. But in reality the earlier you treat, the bigger impact you will have on preventing loss of function. So the earlier you treat, the bigger impact you will have on preventing loss of function. So the earlier you treat, the better you are at picking up effects of a potential therapeutic. And so early treatment I think, has become kind of a norm for all neurodegenerative diseases, not because the therapies don't work if you treat later, but just because that's where you have the biggest impact on the disease.
Kasper Roet:We're going to run short on time here, so just a few more questions and then we'll chat. I talked too much, no, no, no, you're doing great, terrific responses. It's been a super meaningful conversation. I like the global aspect of it, but in keeping with progress at Curalis, you mentioned that you were one of the fortunate companies to have a presentation at JPMorgan. There are so many biotechs here who don't have opportunities to present at the conference. They're here for the ancillary activity. How did that go?
Matt Pillar:It was a great honor to be invited as a private company to present at the JPMorgan conference. I thought it was a great success.
Kasper Roet:I didn't anticipate that you would tell me oh, it was awful man, I mean it, just it spiraled yeah.
Matt Pillar:Oh, we got some good questions back also because there have been failures in the AOS space and how do we look at that?
Matt Pillar:And yeah, I don't want to go too deep into it, but the traditional approach of companies has just been looking at mechanisms that may play a role in disease and then having a compound, or usually a small molecule, that acts on that mechanism and then hoping that it does something. We're following it really from a genetic approach. So we actually have. We're the leading company in the development of therapeutics for ALS because we have three programs in development on genetic targets the. The last one, on 13, is partnered with eli still pre-clinical, but it's this genetic approach that we know works, and so I've been trying to educate that to people and uh, and so this was a question that we got also at the JP Morgan conference. Just want to give you a little bit more information on that at Baltimore.
Kasper Roet:Yeah Well, I was going to ask you and hopefully this will answer the question, because we spoke like a week or so ago. Two weeks ago, we had the opportunity to chit chat with you about what we're going to talk about today and I remember you saying specifically like we know it works, we have the tools, and you said now we just need to do it. So hopefully that question is going to be answered. What's going on right now in terms of all right we're going to go from we know it works, now we just need to do it?
Matt Pillar:Yeah, so the first gene that was discovered for ALS is SOD1. And that was discovered in 1993. It was approved in 2023. So it took 30 years to get through an approval. At this moment, if we understand what is going wrong in the genetics of a disease, we can be in the clinic four years later with a genetic medicine. The path from a genetic discovery to a development candidate, to an IND, to a POC, is a scalable path with these genetic medicines, specifically for RNA therapeutics, and so that is very powerful, because genetics makes us understand why someone gets sick not for every disease, but for a lot of diseases.
Kasper Roet:We understand the genetics.
Matt Pillar:We have now the technology to build that into a medicine relatively quickly in a very reproducible manner, and so we have now done. At Curalis. We've made four development candidates. We know exactly how long that takes. We know exactly how to do these AD&D enabling studies. We've done that multiple times as well, and we now have also learned how to actually run POC programs.
Matt Pillar:That's not just for ALS right, but there's many other diseases where that can be done. And again that comes back again on why we need also a regulatory framework that fits with that, because I think as a humanity you heard me say this in the beginning no one wants to be sick. No one wants their friends and family members to be sick. We have an opportunity to make really meaningful therapeutics for many different people in a very fast way relatively to the past and in a very high probability for the success type of matter. But so we need to do it, yeah.
Ben Comer:That's Curalis. Founder and CEO of Casper Root. I'm Ben Fommer, very nice.
Kasper Roet:And I'm Matt Feller. You did a much better job.
Ben Comer:Oh, thank you, and you just listened to the Business of Biotech from JPM 2025. Listen and subscribe wherever you listen to podcasts or take our video cast in at Bioprocess Online and Life Science Leader. Thanks for listening and see you next week.